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Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training

Christian K. Roberts, Andrea L. Hevener, R. James Barnard

10.1002/cphy.c110062

Source: Volume 3, Issue 1, January 2013

Published online: January 2013

Full Article on Wiley Online Library



Abstract

Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Regardless of the true definition, based on current population estimates, nearly 100 million have MS. It is often characterized by insulin resistance, which some have suggested is a major underpinning link between physical inactivity and MS. The purpose of this review is to: (i) provide an overview of the history, causes and clinical aspects of MS, (ii) review the molecular mechanisms of insulin action and the causes of insulin resistance, and (iii) discuss the epidemiological and intervention data on the effects of exercise on MS and insulin sensitivity. © 2013 American Physiological Society. Compr Physiol 3:1‐58, 2013.

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Figure 1. Figure 1.

Graph depicting the hyperbolic relation between insulin secretion and insulin sensitivity. Insulin secretion rises as insulin sensitivity falls when an individual goes from a state of exercise training/being physically active (point A) to detraining/sedentary (point B) and vice versa, that is, bidirectionality of the two arrows from B to A when undergoing exercise training/increasing physical activity levels. A failure of insulin secretion to compensate for a fall in insulin sensitivity is noted when both insulin secretion and insulin sensitivity decline from points B to C, leading to elevated fasting glucose and prediabetes (impaired glucose tolerance). A progressive decline in both insulin secretion and insulin sensitivity to point D indicates type 2 diabetes. Adapted from reference (9) with permission.
Figure 2. Figure 2.

Schematic of the insulin receptor and critical sites of tyrosine phosphorylation. CR, cysteine‐rich region; JM, juxtamembrane; KD, kinase domain; CT, C‐terminal domain; Y: tyrosine residue.
Figure 3. Figure 3.

Schematic of insulin signal transduction through canonical IRS1/PI3K pathway and through abbreviations: Cbl/CAP/TC10 pathway associated with lipid rafts in the plasma membrane. Akt or PKB, protein kinase B; APS, adapter protein with a PH and SH2 domain; CAP, c‐Cbl‐associated protein; Cbl, proto‐oncogene; GLUT4, insulin responsive glucose transporter highly expressed in myocytes and adipocytes; IRS, insulin receptor substrate; PDK1, phosphoinositide‐dependent kinase 1; PIP3, phosphatidylinositol (3,4,5)‐trisphosphate; PKC, protein kinase C; TC10, small Ras‐related GTPase, member of the Rho family.
Figure 4. Figure 4.

Schematic illustrating mechanisms promoting inflammation that is now recognized as an important underpinning contributing in the pathogenesis of insulin resistance via impairment of insulin signal transduction. Abbreviations: AP‐1, adaptor protein 1; IKK, I kappa B kinase; IKKkinase; IκB‐α, inhibitor of kappa B; IL, interleukin; IRAK, interleukin receptor‐associated kinase; JAK, janus kinase; JNK, c‐Jun N‐terminal kinase. Originally identified kinase family that binds and phosphorylates c‐Jun on Ser‐63 and Ser‐73 within its transcriptional activation domain. MAPK2, mitogen‐activated protein kinase 2; MAPK3, mitogen‐activated protein kinase 3; NF‐κB, nuclear factor κ B (nuclear factor kappa‐light‐chain‐enhancer of activated B cells); RIP, receptor‐interacting serine/threonine‐protein kinase; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; TLR, toll‐like receptor; TRADD, tumor necrosis factor receptor type 1‐associated DEATH domain protein (adaptor protein); TRAF, TNF receptor associated factors.
Figure 5. Figure 5.

Schematic of adipose tissue‐secreted factors that act on muscle and liver to promote insulin resistance.
Figure 6. Figure 6.

The role of macrophages in the development of obesity. (A) Increased abundance of F4/80 positive macrophages in visceral perigonadal adipose tissue obtained from obese mice. (a) Lean female, (b) Ay/+ female, (c) Lep o/ob female, (d) lean male, (e) diet‐induced obesity, and (f) Lep ob/ob male mice. F4/80 positive cells are small, dispersed and rarely aggregated in adipose tissue from lean animals (a and d), but found frequently in clusters “crowning” adipocytes in adipose tissue from high‐fat fed and genetically obese mice (c, e, and f). Reprinted, with permission, from reference (685). (B) Schematic overview of the effects of adipose macrophage infiltration on the development of tissue inflammation and insulin resistance. Classically activated macrophages in adipose tissue from obese humans and rodents are shown to secrete insulin resistance producing proinflammatory cytokines and chemokines. Reprinted, with permission, from reference (686).
Figure 7. Figure 7.

Prevalence of metabolic syndrome according to cardiorespiratory fitness quintiles in more than 7000 women enrolled in the Aerobics Center Longitudinal Study from 1979 to 2000. Number of subjects in each quintile is I: 796; II: 1173; III: 1241; IV: 1754; and V: 2140. Adapted from reference (190) with permission.
Figure 8. Figure 8.

(A) Age and smoking adjusted prevalence of metabolic syndrome in men according to level of muscular strength and cardiorespiratory fitness. Q1 represents the lowest and Q4 the highest muscular strength quartile. (B) Incidence of MS across muscular strength categories by age groups. Incidence rates per 1000 man‐years are shown labeled with bars. The number of subjects for each age group is 20‐39: 1239; 40‐49: 1249; and 50+: 745. Q1 represents the lowest and Q4 the highest muscular strength quartile. The linear trend p values for the age groups 20‐39, 40‐49, and 50+ are less < 0.001, 0.01, and 0.05, respectively. Adapted from references (321,322) with permission.
Figure 9. Figure 9.

Impact of fitness on relative risk for all‐cause and cardiovascular disease (CVD) mortality associated with metabolic syndrome before and after the inclusion of cardiorespiratory fitness (CRF) as a covariate in more than 19,000 men 20‐83 years of age from Aerobics Center Longitudinal Study. Error bars represent 95% confidence intervals and demonstrate that after inclusion of CRF as a covariate, all‐cause and CVD mortality were no longer statistically significant. Adapted from reference (339) with permission.
Figure 10. Figure 10.

All‐cause (A) and cardiovascular disease (B) mortality death rates per 10,000 mean‐years of follow‐up in “healthy” and subjects with metabolic syndrome (MS), adjusted for age and year of examination more than 19,000 men 20‐83 years of age from Aerobics Center Longitudinal Study. The theoretical contributions of fitness and MS are depicted by brackets. Adapted from reference (339) with permission.
Figure 11. Figure 11.

Relative risk (RR) of (A) all‐cause and (B) cardiovascular disease (CVD) mortality in more than 19,000 men from Aerobics Center Longitudinal Study, adjusted for age, examination year, smoking, alcohol consumption, possible existence of CVD, and parental history of premature CVD. Second and forth bars within a body mass index category refer to cardiorespiratory fitness (CRF)‐adjusted RR's. Data, with permission, from reference (340).
Figure 12. Figure 12.

Adjusted cases of metabolic syndrome (MS) based on minutes per week of leisure time physical activity in fit and unfit men after an average 4‐year follow‐up (375). Copyright 2002 American Diabetes Association. From Diabetes Care®, Vol. 25, 2002; 1612‐1618. Reprinted by permission of the American Diabetes Association.
Figure 13. Figure 13.

Schematic diagram of future directions to determine mechanisms by which aerobic training (AT) and resistance training (RT) increase insulin sensitivity. Although there is preliminary evidence, more research is needed to clearly identify the mechanisms that are involved, as denoted by the question marks linking AT and RT to enhance insulin signaling.
Figure 14. Figure 14.

Insulin sensitivity and physical activity measured by accelerometer by quartiles of average number of counts/min and quartiles of percent time sedentary in the insulin sensitivity and cardiovascular risk study. M/I is the unit measurement of insulin sensitivity (μmol.min−1kgFFM−1nmol/L−1) (41). Copyright 2008 American Diabetes Association. From Diabetes Care®, Vol. 57, 2008; 2613‐2618. Reprinted by permission of the American Diabetes Association.
Figure 15. Figure 15.

Effects of training and age on area under the curve for (A) glucose and (B) insulin during an oral glucose tolerance test. Adapted, with permission, from reference (579).
Figure 16. Figure 16.

Effects of chronic training (dashed line), inactivity (solid line) for 10 days and one single bout (dotted line) of aerobic exercise on (A) blood glucose and (B) insulin during an oral glucose tolerance test in well‐trained subjects. Adapted, with permission, from reference (263).


Figure 1.

Graph depicting the hyperbolic relation between insulin secretion and insulin sensitivity. Insulin secretion rises as insulin sensitivity falls when an individual goes from a state of exercise training/being physically active (point A) to detraining/sedentary (point B) and vice versa, that is, bidirectionality of the two arrows from B to A when undergoing exercise training/increasing physical activity levels. A failure of insulin secretion to compensate for a fall in insulin sensitivity is noted when both insulin secretion and insulin sensitivity decline from points B to C, leading to elevated fasting glucose and prediabetes (impaired glucose tolerance). A progressive decline in both insulin secretion and insulin sensitivity to point D indicates type 2 diabetes. Adapted from reference (9) with permission.



Figure 2.

Schematic of the insulin receptor and critical sites of tyrosine phosphorylation. CR, cysteine‐rich region; JM, juxtamembrane; KD, kinase domain; CT, C‐terminal domain; Y: tyrosine residue.



Figure 3.

Schematic of insulin signal transduction through canonical IRS1/PI3K pathway and through abbreviations: Cbl/CAP/TC10 pathway associated with lipid rafts in the plasma membrane. Akt or PKB, protein kinase B; APS, adapter protein with a PH and SH2 domain; CAP, c‐Cbl‐associated protein; Cbl, proto‐oncogene; GLUT4, insulin responsive glucose transporter highly expressed in myocytes and adipocytes; IRS, insulin receptor substrate; PDK1, phosphoinositide‐dependent kinase 1; PIP3, phosphatidylinositol (3,4,5)‐trisphosphate; PKC, protein kinase C; TC10, small Ras‐related GTPase, member of the Rho family.



Figure 4.

Schematic illustrating mechanisms promoting inflammation that is now recognized as an important underpinning contributing in the pathogenesis of insulin resistance via impairment of insulin signal transduction. Abbreviations: AP‐1, adaptor protein 1; IKK, I kappa B kinase; IKKkinase; IκB‐α, inhibitor of kappa B; IL, interleukin; IRAK, interleukin receptor‐associated kinase; JAK, janus kinase; JNK, c‐Jun N‐terminal kinase. Originally identified kinase family that binds and phosphorylates c‐Jun on Ser‐63 and Ser‐73 within its transcriptional activation domain. MAPK2, mitogen‐activated protein kinase 2; MAPK3, mitogen‐activated protein kinase 3; NF‐κB, nuclear factor κ B (nuclear factor kappa‐light‐chain‐enhancer of activated B cells); RIP, receptor‐interacting serine/threonine‐protein kinase; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; TLR, toll‐like receptor; TRADD, tumor necrosis factor receptor type 1‐associated DEATH domain protein (adaptor protein); TRAF, TNF receptor associated factors.



Figure 5.

Schematic of adipose tissue‐secreted factors that act on muscle and liver to promote insulin resistance.



Figure 6.

The role of macrophages in the development of obesity. (A) Increased abundance of F4/80 positive macrophages in visceral perigonadal adipose tissue obtained from obese mice. (a) Lean female, (b) Ay/+ female, (c) Lep o/ob female, (d) lean male, (e) diet‐induced obesity, and (f) Lep ob/ob male mice. F4/80 positive cells are small, dispersed and rarely aggregated in adipose tissue from lean animals (a and d), but found frequently in clusters “crowning” adipocytes in adipose tissue from high‐fat fed and genetically obese mice (c, e, and f). Reprinted, with permission, from reference (685). (B) Schematic overview of the effects of adipose macrophage infiltration on the development of tissue inflammation and insulin resistance. Classically activated macrophages in adipose tissue from obese humans and rodents are shown to secrete insulin resistance producing proinflammatory cytokines and chemokines. Reprinted, with permission, from reference (686).



Figure 7.

Prevalence of metabolic syndrome according to cardiorespiratory fitness quintiles in more than 7000 women enrolled in the Aerobics Center Longitudinal Study from 1979 to 2000. Number of subjects in each quintile is I: 796; II: 1173; III: 1241; IV: 1754; and V: 2140. Adapted from reference (190) with permission.



Figure 8.

(A) Age and smoking adjusted prevalence of metabolic syndrome in men according to level of muscular strength and cardiorespiratory fitness. Q1 represents the lowest and Q4 the highest muscular strength quartile. (B) Incidence of MS across muscular strength categories by age groups. Incidence rates per 1000 man‐years are shown labeled with bars. The number of subjects for each age group is 20‐39: 1239; 40‐49: 1249; and 50+: 745. Q1 represents the lowest and Q4 the highest muscular strength quartile. The linear trend p values for the age groups 20‐39, 40‐49, and 50+ are less < 0.001, 0.01, and 0.05, respectively. Adapted from references (321,322) with permission.



Figure 9.

Impact of fitness on relative risk for all‐cause and cardiovascular disease (CVD) mortality associated with metabolic syndrome before and after the inclusion of cardiorespiratory fitness (CRF) as a covariate in more than 19,000 men 20‐83 years of age from Aerobics Center Longitudinal Study. Error bars represent 95% confidence intervals and demonstrate that after inclusion of CRF as a covariate, all‐cause and CVD mortality were no longer statistically significant. Adapted from reference (339) with permission.



Figure 10.

All‐cause (A) and cardiovascular disease (B) mortality death rates per 10,000 mean‐years of follow‐up in “healthy” and subjects with metabolic syndrome (MS), adjusted for age and year of examination more than 19,000 men 20‐83 years of age from Aerobics Center Longitudinal Study. The theoretical contributions of fitness and MS are depicted by brackets. Adapted from reference (339) with permission.



Figure 11.

Relative risk (RR) of (A) all‐cause and (B) cardiovascular disease (CVD) mortality in more than 19,000 men from Aerobics Center Longitudinal Study, adjusted for age, examination year, smoking, alcohol consumption, possible existence of CVD, and parental history of premature CVD. Second and forth bars within a body mass index category refer to cardiorespiratory fitness (CRF)‐adjusted RR's. Data, with permission, from reference (340).



Figure 12.

Adjusted cases of metabolic syndrome (MS) based on minutes per week of leisure time physical activity in fit and unfit men after an average 4‐year follow‐up (375). Copyright 2002 American Diabetes Association. From Diabetes Care®, Vol. 25, 2002; 1612‐1618. Reprinted by permission of the American Diabetes Association.



Figure 13.

Schematic diagram of future directions to determine mechanisms by which aerobic training (AT) and resistance training (RT) increase insulin sensitivity. Although there is preliminary evidence, more research is needed to clearly identify the mechanisms that are involved, as denoted by the question marks linking AT and RT to enhance insulin signaling.



Figure 14.

Insulin sensitivity and physical activity measured by accelerometer by quartiles of average number of counts/min and quartiles of percent time sedentary in the insulin sensitivity and cardiovascular risk study. M/I is the unit measurement of insulin sensitivity (μmol.min−1kgFFM−1nmol/L−1) (41). Copyright 2008 American Diabetes Association. From Diabetes Care®, Vol. 57, 2008; 2613‐2618. Reprinted by permission of the American Diabetes Association.



Figure 15.

Effects of training and age on area under the curve for (A) glucose and (B) insulin during an oral glucose tolerance test. Adapted, with permission, from reference (579).



Figure 16.

Effects of chronic training (dashed line), inactivity (solid line) for 10 days and one single bout (dotted line) of aerobic exercise on (A) blood glucose and (B) insulin during an oral glucose tolerance test in well‐trained subjects. Adapted, with permission, from reference (263).

References
 1. Executive summary of The Third Report of The National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285: 2486‐2497, 2001.
 2.Physical Activity Guideline Advisory Committee Report. Washington, DC: U.S. Department of Health and Human Services, 2008.
 3. Abdul‐Ghani MA, Matsuda M, Balas B, DeFronzo RA. Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 30: 89‐94, 2007.
 4. Abdul‐Ghani MA, Williams K, DeFronzo RA, Stern M. What is the best predictor of future type 2 diabetes? Diabetes Care 30: 1544‐1548, 2007.
 5. Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, Minnemann T, Shulman GI, Kahn BB. Adipose‐selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 409: 729‐733, 2001.
 6. Abumrad NA, el‐Maghrabi MR, Amri EZ, Lopez E, Grimaldi PA. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long‐chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. J Biol Chem 268: 17665‐17668, 1993.
 7. Abumrad NA, Perkins RC, Park JH, Park CR. Mechanism of long chain fatty acid permeation in the isolated adipocyte. J Biol Chem 256: 9183‐9191, 1981.
 8. Adams JM,II, Pratipanawatr T, Berria R, Wang E, DeFronzo RA, Sullards MC, Mandarino LJ. Ceramide content is increased in skeletal muscle from obese insulin‐resistant humans. Diabetes 53: 25‐31, 2004.
 9. Ader M, Bergman RN. Insulin sensitivity in the intact organism. Baillieres Clin Endocrinol Metab 1: 879‐910, 1987.
 10. Aguirre V, Uchida T, Yenush L, Davis R, White MF. The c‐Jun NH(2)‐terminal kinase promotes insulin resistance during association with insulin receptor substrate‐1 and phosphorylation of Ser(307). J Biol Chem 275: 9047‐9054, 2000.
 11. Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF. Phosphorylation of Ser307 in insulin receptor substrate‐1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem 277: 1531‐1537, 2002.
 12. Ahima RS, Kelly J, Elmquist JK, Flier JS. Distinct physiologic and neuronal responses to decreased leptin and mild hyperleptinemia. Endocrinology 140: 4923‐4931, 1999.
 13. Ahmad F, Azevedo JL, Cortright R, Dohm GL, Goldstein BJ. Alterations in skeletal muscle protein‐tyrosine phosphatase activity and expression in insulin‐resistant human obesity and diabetes. J Clin Invest 100: 449‐458, 1997.
 14. Ahmad F, Considine RV, Bauer TL, Ohannesian JP, Marco CC, Goldstein BJ. Improved sensitivity to insulin in obese subjects following weight loss is accompanied by reduced protein‐tyrosine phosphatases in adipose tissue. Metabolism 46: 1140‐1145, 1997.
 15. Ahmadi N, Eshaghian S, Huizenga R, Sosnin K, Ebrahimi R, Siegel R. Effects of intense exercise and moderate caloric restriction on cardiovascular risk factors and inflammation. Am J Med 124: 978‐982, 2011.
 16. Al‐Khalili L, Bouzakri K, Glund S, Lonnqvist F, Koistinen HA, Krook A. Signaling specificity of interleukin‐6 action on glucose and lipid metabolism in skeletal muscle. Mol Endocrinol 20: 3364‐3375, 2006.
 17. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC, Jr. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and international association for the Study of Obesity. Circulation 120: 1640‐1645, 2009.
 18. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15: 539‐553, 1998.
 19. Amati F, Dubé JJ, Alvarez‐Carnero E, Edreira MM, Chomentowski P, Coen PM, Switzer GE, Bickel PE, Stefanovic‐Racic M, Toledo FGS, Goodpaster BH. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance. Diabetes 60: 2588‐2597, 2011.
 20. Andersen JL, Schjerling P, Andersen LL, Dela F. Resistance training and insulin action in humans: Effects of de‐training. J Physiol (Lond) 551: 1049‐1058, 2003.
 21. Andersen JN, Mortensen OH, Peters GH, Drake PG, Iversen LF, Olsen OH, Jansen PG, Andersen HS, Tonks NK, Moller NP. Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol Cell Biol 21: 7117‐7136, 2001.
 22. Anderssen SA, Carroll S, Urdal P, Holme I. Combined diet and exercise intervention reverses the metabolic syndrome in middle‐aged males: Results from the Oslo Diet and Exercise Study. Scand J Med Sci Sports 17: 687‐695, 2007.
 23. Andersson N, Strandberg L, Nilsson S, Adamovic S, Karlsson MK, Ljunggren O, Mellstrom D, Lane NE, Zmuda JM, Nielsen C, Orwoll E, Lorentzon M, Ohlsson C, Jansson JO. A variant near the interleukin‐6 gene is associated with fat mass in Caucasian men. Int J Obes (Lond) 34: 1011‐1019, 2010.
 24. Aquilante CL, Kosmiski LA, Knutsen SD, Zineh I. Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults. Metabolism 57: 494‐501, 2008.
 25. Araki E, Lipes MA, Patti ME, Bruning JC, Haag BL, II, Johnson RS, Kahn CR. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS‐1 gene. Nature 372: 186‐190, 1994.
 26. Araujo EP, De Souza CT, Gasparetti AL, Ueno M, Boschero AC, Saad MJA, Velloso LA. Short‐term in vivo inhibition of insulin receptor substrate‐1 expression leads to insulin resistance, hyperinsulinemia, and increased adiposity. Endocrinology 146: 1428‐1437, 2005.
 27. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J‐i, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose‐specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257: 79‐83, 1999.
 28. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw‐Boris A, Poli G, Olefsky J, Karin M. IKK‐beta links inflammation to obesity‐induced insulin resistance. Nat Med 11: 191‐198, 2005.
 29. Arner P, Pettersson A, Mitchell PJ, Dunbar JD, Kharitonenkov A, Ryden M. FGF21 attenuates lipolysis in human adipocytes ‐ a possible link to improved insulin sensitivity. FEBS Lett 582: 1725‐1730, 2008.
 30. Aron‐Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A, Aissat A, Guerre‐Millo M, Clement K. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab 94: 4619‐4623, 2009.
 31. Aronson D, Sella R, Sheikh‐Ahmad M, Kerner A, Avizohar O, Rispler S, Bartha P, Markiewicz W, Levy Y, Brook GJ. The association between cardiorespiratory fitness and C‐reactive protein in subjects with the metabolic syndrome. J Am Coll Cardiol 44: 2003‐2007, 2004.
 32. Aronson D, Sheikh‐Ahmad M, Avizohar O, Kerner A, Sella R, Bartha P, Markiewicz W, Levy Y, Brook GJ. C‐Reactive protein is inversely related to physical fitness in middle‐aged subjects. Atherosclerosis 176: 173‐179, 2004.
 33. Atlantis E, Martin SA, Haren MT, Taylor AW, Wittert GA. Inverse associations between muscle mass, strength, and the metabolic syndrome. Metabolism 58: 1013‐1022, 2009.
 34. Avorn J, Monette J, Lacour A, Bohn RL, Monane M, Mogun H, LeLorier J. Persistence of use of lipid‐lowering medications: A cross‐national study. JAMA 279: 1458‐1462, 1998.
 35. Ay L, Kopp H‐P, Brix J‐M, Ay C, Quehenberger P, Schernthaner G‐H, Pabinger I, Schernthaner G. Thrombin generation in morbid obesity: Significant reduction after weight loss. J Thromb Haemost 8: 759‐765, 2010.
 36. Babraj J, Vollaard N, Keast C, Guppy F, Cottrell G, Timmons J. Extremely short duration high intensity interval training substantially improves insulin action in young healthy males. BMC Endocrine Disorders 9: 3, 2009.
 37. Bacchi E, Negri C, Zanolin ME, Milanese C, Faccioli N, Trombetta M, Zoppini G, Cevese A, Bonadonna RC, Schena F, Bonora E, Lanza M, and Moghetti P. Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects. Diabetes Care 35: 676‐682, 2012.
 38. Bae SS, Cho H, Mu J, Birnbaum MJ. Isoform‐specific regulation of insulin‐dependent glucose uptake by Akt/protein kinase B. J Biol Chem 278: 49530‐49536, 2003.
 39. Baldo A, Sniderman A, St Luce S, Zhang X, Cianflone K. Signal transduction pathway of acylation stimulating protein: Involvement of protein kinase C. J Lipid Res 36: 1415‐1426, 1995.
 40. Balducci S, Zanuso S, Nicolucci A, De Feo P, Cavallo S, Cardelli P, Fallucca S, Alessi E, Fallucca F, Pugliese G. Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: A randomized controlled trial: The Italian Diabetes and Exercise Study (IDES). Arch Intern Med 170: 1794‐1803, 2010.
 41. Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 16: 442‐443, 1999.
 42. Balkau B, Mhamdi L, Oppert JM, Nolan J, Golay A, Porcellati F, Laakso M, Ferrannini E. Physical activity and insulin sensitivity: The RISC study. Diabetes 57: 2613‐2618, 2008.
 43. Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM. Increased p85/55/50 expression and decreased phosphotidylinositol 3‐kinase activity in insulin‐resistant human skeletal muscle. Diabetes 54: 2351‐2359, 2005.
 44. Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, Scherer PE, Steppan CM, Ahima RS, Obici S, Rossetti L, Lazar MA. Regulation of fasted blood glucose by resistin. Science 303: 1195‐1198, 2004.
 45. Banks EA, Brozinick JT, Jr., Yaspelkis BB, III, Kang HY, Ivy JL. Muscle glucose transport, GLUT‐4 content, and degree of exercise training in obese Zucker rats. Am J Physiol 263: E1010‐E1015, 1992.
 46. Barakat HA, Carpenter JW, McLendon VD, Khazanie P, Leggett N, Heath J, Marks R. Influence of obesity, impaired glucose tolerance, and NIDDM on LDL structure and composition. Possible link between hyperinsulinemia and atherosclerosis. Diabetes 39: 1527‐1533, 1990.
 47. Barbieri M, Rizzo MR, Papa M, Boccardi V, Esposito A, White MF, Paolisso G. The IRS2 Gly1057Asp variant is associated with human longevity. J Gerontol A Biol Sci Med Sci 65: 282‐286, 2009.
 48. Barnard RJ. Prostate cancer prevention by nutritional means to alleviate metabolic syndrome. Am J Clin Nutr 86: s889‐s893, 2007.
 49. Barnard RJ, Faria DJ, Menges JE, Martin DA. Effects of a high‐fat, sucrose diet on serum insulin and related atherosclerotic risk factors in rats. Atherosclerosis 100: 229‐236, 1993.
 50. Barnard RJ, Roberts CK, Varon SM, Berger JJ. Diet‐induced insulin resistance precedes other aspects of the metabolic syndrome. J Appl Physiol 84: 1311‐1315, 1998.
 51. Barnard RJ, Wen SJ. Exercise and diet in the prevention and control of the metabolic syndrome. Sports Med 18: 218‐228, 1994.
 52. Barnard RJ, Youngren JF, Martin DA. Diet, not aging, causes skeletal muscle insulin resistance. Gerontology 41: 205‐211, 1995.
 53. Barnard RJ, Youngren JF, Scheck SH. Reversibility of diet‐induced skeletal muscle insulin resistance. Diabetes Research 32: 213‐221, 1997.
 54. Baron AD. Hemodynamic actions of insulin. Am J Physiol 267: E187‐E202, 1994.
 55. Barwell N, Malkova D, Moran C, Cleland S, Packard C, Zammit V, Gill J. Exercise training has greater effects on insulin sensitivity in daughters of patients with type 2 diabetes than in women with no family history of diabetes. Diabetologia 51: 1912‐1919, 2008.
 56. Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, Vidal H, Hainque B. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 85: 3338‐3342, 2000.
 57. Baumann CA, Ribon V, Kanzaki M, Thurmond DC, Mora S, Shigematsu S, Bickel PE, Pessin JE, Saltiel AR. CAP defines a second signalling pathway required for insulin‐stimulated glucose transport. Nature 407: 202‐207, 2000.
 58. Befroy DE, Petersen KF, Dufour S, Mason GF, de Graaf RA, Rothman DL, Shulman GI. Impaired mitochondrial substrate oxidation in muscle of insulin‐resistant offspring of type 2 diabetic patients. Diabetes 56: 1376‐1381, 2007.
 59. Benetos A, Thomas F, Pannier B, Bean K, Jego B, Guize L. All‐cause and cardiovascular mortality using the different definitions of metabolic syndrome. Am J Cardiol 102: 188‐191, 2008.
 60. Benner JS, Glynn RJ, Mogun H, Neumann PJ, Weinstein MC, Avorn J. Long‐term persistence in use of statin therapy in elderly patients. JAMA 288: 455‐461, 2002.
 61. Benrick A, Jirholt P, Wernstedt I, Gustafsson M, Scheller J, Eriksson AL, Boren J, Hedner T, Ohlsson C, Hard T, Rose‐John S, Jansson JO. A non‐conservative polymorphism in the IL‐6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population. Regul Pept 146: 189‐196, 2008.
 62. Bento JL, Palmer ND, Mychaleckyj JC, Lange LA, Langefeld CD, Rich SS, Freedman BI, Bowden DW. Association of protein tyrosine phosphatase 1B gene polymorphisms with type 2 diabetes. Diabetes 53: 3007‐3012, 2004.
 63. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte‐secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7: 947‐953, 2001.
 64. Berglund ED, Li CY, Bina HA, Lynes SE, Michael MD, Shanafelt AB, Kharitonenkov A, Wasserman DH. Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. Endocrinology 150: 4084‐4093, 2009.
 65. Bergman RN. Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal‐model approach. Diabetes 38: 1512‐1527, 1989.
 66. Bezaire V, Bruce CR, Heigenhauser GJ, Tandon NN, Glatz JF, Luiken JJ, Bonen A, Spriet LL. Identification of fatty acid translocase on human skeletal muscle mitochondrial membranes: Essential role in fatty acid oxidation. Am J Physiol Endocrinol Metab 290: E509‐E515, 2006.
 67. Bjorbaek C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS. Identification of SOCS‐3 as a potential mediator of central leptin resistance. Mol Cell 1: 619‐625, 1998.
 68. Bjorbak C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, Myers MG, Jr. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem 275: 40649‐40657, 2000.
 69. Bjorntorp P. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10: 493‐496, 1990.
 70. Björntorp P, Fahlén M, Grimby G, Gustafson A, Holm J, Renström P, Scherstén T. Carbohydrate and lipid metabolism in middle‐aged, physically well‐trained men. Metabolism 21: 1037‐1044, 1972.
 71. Blüher M. Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes 117: 241‐250, 2009.
 72. Bo S, Ciccone G, Baldi C, Benini L, Dusio F, Forastiere G, Lucia C, Nuti C, Durazzo M, Cassader M, Gentile L, Pagano G. Effectiveness of a lifestyle intervention on metabolic syndrome. A randomized controlled trial. J Gen Intern Med 22: 1695‐1703, 2007.
 73. Bonen A, Dyck DJ, Ibrahimi A, Abumrad NA. Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36. Am J PhysiolAm J Physiol 276: E642‐E649, 1999.
 74. Bonen A, Luiken JJ, Arumugam Y, Glatz JF, Tandon NN. Acute regulation of fatty acid uptake involves the cellular redistribution of fatty acid translocase. J Biol Chem 275: 14501‐14508, 2000.
 75. Booth FW, Laye MJ. Lack of adequate appreciation of physical exercise's complexities can pre‐empt appropriate design and interpretation in scientific discovery. J Physiol 587: 5527‐5539, 2009.
 76. Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Comprehensive Physiology. John Wiley & Sons, Inc., 2011.
 77. Bouchard C, An P, Rice T, Skinner JS, Wilmore JH, Gagnon J, Perusse L, Leon AS, Rao DC. Familial aggregation of VO2 max response to exercise training: Results from the HERITAGE Family Study. J Appl Physiol 87: 1003‐1008, 1999.
 78. Boule NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Effects of exercise training on glucose homeostasis: The heritage family study. Diabetes Care 28: 108‐114, 2005.
 79. Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, Walder K, Segal D. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 148: 4687‐4694, 2007.
 80. Bozaoglu K, Segal D, Shields KA, Cummings N, Curran JE, Comuzzie AG, Mahaney MC, Rainwater DL, VandeBerg JL, MacCluer JW, Collier G, Blangero J, Walder K, Jowett JB. Chemerin is associated with metabolic syndrome phenotypes in a Mexican‐American population. J Clin Endocrinol Metab 94: 3085‐3088, 2009.
 81. Braun B, Zimmermann MB, Kretchmer N. Effects of exercise intensity on insulin sensitivity in women with non‐insulin‐dependent diabetes mellitus. J Appl Physiol 78: 300‐306, 1995.
 82. Brouwer BG, Visseren FLJ, and van der Graaf Y. The effect of leisure‐time physical activity on the presence of metabolic syndrome in patients with manifest arterial disease. The SMART study. Am Heart J 154: 1146‐1152, 2007.
 83. Brozinick JT, Jr., Etgen GJ, Jr., Yaspelkis BB, III, Ivy JL. Glucose uptake and GLUT‐4 protein distribution in skeletal muscle of the obese Zucker rat. Am J Physiol 267: R236‐R243, 1994.
 84. Brozinick JT, Jr., McCoid SC, Reynolds TH, Nardone NA, Hargrove DM, Stevenson RW, Cushman SW, Gibbs EM. GLUT4 overexpression in db/db mice dose‐dependently ameliorates diabetes but is not a lifelong cure. Diabetes 50: 593‐600, 2001.
 85. Bruce CR, Carey AL, Hawley JA, Febbraio MA. Intramuscular heat shock protein 72 and heme oxygenase‐1 mRNA are reduced in patients with type 2 diabetes. Diabetes 52: 2338‐2345, 2003.
 86. Bruce CR, Hawley JA. Improvements in insulin resistance with aerobic exercise training: A lipocentric approach. Med Sci Sports Exerc 36: 1196‐1201, 2004.
 87. Bruce CR, Hoy AJ, Turner N, Watt MJ, Allen TL, Carpenter K, Cooney GJ, Febbraio MA, Kraegen EW. Overexpression of carnitine palmitoyltransferase‐1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high‐fat diet–induced insulin resistance. Diabetes 58: 550‐558, 2009.
 88. Bruce CR, Thrush AB, Mertz VA, Bezaire V, Chabowski A, Heigenhauser GJ, Dyck DJ. Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am J Physiol Endocrinol Metab 291: E99‐E107, 2006.
 89. Bryant NJ, Govers R, James DE. Regulated transport of the glucose transporter GLUT4. Nat Rev Mol Cell Biol 3: 267‐277, 2002.
 90. Burgomaster KA, Hughes SC, Heigenhauser GJF, Bradwell SN, Gibala MJ. Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans. J Appl Physiol 98: 1985‐1990, 2005.
 91. Burguera B, Proctor D, Dietz N, Guo Z, Joyner M, Jensen MD. Leg free fatty acid kinetics during exercise in men and women. Am J Physiol Endocrinol Metab 278: E113‐E117, 2000.
 92. Burstein R, Polychronakos C, Toews CJ, MacDougall JD, Guyda HJ, Posner BI. Acute reversal of the enhanced insulin action in trained athletes. Association with insulin receptor changes. Diabetes 34: 756‐760, 1985.
 93. Busch AK, Gurisik E, Cordery DV, Sudlow M, Denyer GS, Laybutt DR, Hughes WE, Biden TJ. Increased fatty acid desaturation and enhanced expression of stearoyl coenzyme A desaturase protects pancreatic beta‐cells from lipoapoptosis. Diabetes 54: 2917‐2924, 2005.
 94. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. Local and systemic insulin resistance resulting from hepatic activation of IKK‐beta and NF‐kappaB. Nat Med 11: 183‐190, 2005.
 95. Camhi SM, Stefanick ML, Katzmarzyk PT, Young DR. Metabolic syndrome and changes in body fat from a low‐fat diet and/or exercise randomized controlled trial. Obesity 18: 548‐554, 2009.
 96. Campbell SE, Tandon NN, Woldegiorgis G, Luiken JJ, Glatz JF, Bonen A. A novel function for fatty acid translocase (FAT)/CD36: Involvement in long chain fatty acid transfer into the mitochondria. J Biol Chem 279: 36235‐36241, 2004.
 97. Camus JP. Gout, diabetes, hyperlipemia: A metabolic trisyndrome. Rev Rhum Mal Osteoartic 33: 10‐14, 1966.
 98. Caranti DA, de Mello MT, Prado WL, Tock L, Siqueira KO, de Piano A, Lofrano MC, Cristofalo DMJ, Lederman H, Tufik S, Dâmaso AR. Short‐ and long‐term beneficial effects of a multidisciplinary therapy for the control of metabolic syndrome in obese adolescents. Metabolism 56: 1293‐1300, 2007.
 99. Carey A, Kingwell B. Novel pharmacological approaches to combat obesity and insulin resistance: Targeting skeletal muscle with ‘exercise mimetics’. Diabetologia 52: 2015‐2026, 2009.
 100. Carey A, Petersen E, Bruce C, Southgate R, Pilegaard H, Hawley J, Pedersen B, Febbraio M. Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: Effect of interleukin‐6 infusion. Diabetologia 49: 1000‐1007, 2006.
 101. Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, Prelovsek O, Hohnen‐Behrens C, Watt MJ, James DE, Kemp BE, Pedersen BK, Febbraio MA. Interleukin‐6 increases insulin‐stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP‐activated protein kinase. Diabetes 55: 2688‐2697, 2006.
 102. Carnethon MR, Gidding SS, Nehgme R, Sidney S, Jacobs DR, Jr, Liu K. Cardiorespiratory fitness in young adulthood and the development of cardiovascular disease risk factors. JAMA 290: 3092‐3100, 2003.
 103. Carroll S, Cooke CB, Butterly RJ. Metabolic clustering, physical activity and fitness in nonsmoking, middle‐aged men. Med Sci Sports Exerc 32: 2079‐2086, 2000.
 104. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin‐induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 72: 3666‐3670, 1975.
 105. Castaneda F, Layne JE, Castaneda C. Skeletal muscle sodium glucose co‐transporters in older adults with type 2 diabetes undergoing resistance training. Int J Med Sci 3: 84‐91, 2006.
 106. Catalán V, Gómez‐Ambrosi J, Rodríguez A, Ramírez B, Silva C, Rotellar F, Gil M, Cienfuegos J, Salvador J, Frühbeck G. Increased adipose tissue expression of lipocalin‐2 in obesity is related to inflammation and matrix metalloproteinase‐2 and metalloproteinase‐9 activities in humans. J Mol Med 87: 803‐813, 2009.
 107. Cauza E, Hanusch‐Enserer U, Strasser B, Kostner K, Dunky A, Haber P. Strength and endurance training lead to different post exercise glucose profiles in diabetic participants using a continuous subcutaneous glucose monitoring system. Eur J Clin Invest 35: 745‐751, 2005.
 108. Cha BS, Ciaraldi TP, Park KS, Carter L, Mudaliar SR, Henry RR. Impaired fatty acid metabolism in type 2 diabetic skeletal muscle cells is reversed by PPARgamma agonists. Am J Physiol Endocrinol Metab 289: E151‐E159, 2005.
 109. Chadt A, Leicht K, Deshmukh A, Jiang LQ, Scherneck S, Bernhardt U, Dreja T, Vogel H, Schmolz K, Kluge R, Zierath JR, Hultschig C, Hoeben RC, Schurmann A, Joost HG, Al‐Hasani H. Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet‐induced obesity. Nat Genet 40: 1354‐1359, 2008.
 110. Chaika OV, Chaika N, Volle DJ, Hayashi H, Ebina Y, Wang L‐M, Pierce JH, Lewis RE. Mutation of tyrosine 960 within the insulin receptor juxtamembrane domain impairs glucose transport but does not inhibit ligand‐mediated phosphorylation of insulin receptor substrate‐2 in 3T3‐L1 adipocytes. J Biol Chem 274: 12075‐12080, 1999.
 111. Chang L, Chiang SH, Saltiel AR. Insulin signaling and the regulation of glucose transport. Mol Med 10: 65‐71, 2004.
 112. Chavey C, Lazennec G, Lagarrigue S, Clapé C, Iankova I, Teyssier J, Annicotte J‐S, Schmidt J, Mataki C, Yamamoto H, Sanches R, Guma A, Stich V, Vitkova M, Jardin‐Watelet B, Renard E, Strieter R, Tuthill A, Hotamisligil GS, Vidal‐Puig A, Zorzano A, Langin D, Fajas L. CXC ligand 5 is an adipose‐tissue derived factor that links obesity to insulin resistance. Cell Metabolism 9: 339‐349, 2009.
 113. Chen AK, Roberts CK, Barnard RJ. Effect of a short‐term diet and exercise intervention on metabolic syndrome in overweight children. Metabolism 55: 871‐878, 2006.
 114. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP. Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell 84: 491‐495, 1996.
 115. Chiang S‐H, Baumann CA, Kanzaki M, Thurmond DC, Watson RT, Neudauer CL, Macara IG, Pessin JE, Saltiel AR. Insulin‐stimulated GLUT4 translocation requires the CAP‐dependent activation of TC10. Nature 410: 944‐948, 2001.
 116. Cho ER, Shin A, Kim J, Jee SH, Sung J. Leisure‐time physical activity is associated with a reduced risk for metabolic syndrome. Ann Epidemiol 19: 784‐792, 2009.
 117. Cho YM, Youn BS, Chung SS, Kim KW, Lee HK, Yu KY, Park HJ, Shin HD, Park KS. Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans. Diabetologia 47: 559‐565, 2004.
 118. Choi CS, Savage DB, Abu‐Elheiga L, Liu Z‐X, Kim S, Kulkarni A, Distefano A, Hwang Y‐J, Reznick RM, Codella R, Zhang D, Cline GW, Wakil SJ, Shulman GI. Continuous fat oxidation in acetyl–CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Proc Nat Acad Sci U S A 104: 16480‐16485, 2007.
 119. Christ‐Roberts CY, Pratipanawatr T, Pratipanawatr W, Berria R, Belfort R, Kashyap S, Mandarino LJ. Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Metabolism 53: 1233‐1242, 2004.
 120. Chung J, Nguyen A‐K, Henstridge DC, Holmes AG, Chan MHS, Mesa JL, Lancaster GI, Southgate RJ, Bruce CR, Duffy SJ, Horvath I, Mestril R, Watt MJ, Hooper PL, Kingwell BA, Vigh L, Hevener A, Febbraio MA. HSP72 protects against obesity‐induced insulin resistance. Proc Nat Acad Sci U S A 105: 1739‐1744, 2008.
 121. Chung SS, Choi HH, Kim KW, Cho YM, Lee HK, Park KS. Regulation of human resistin gene expression in cell systems: An important role of stimulatory protein 1 interaction with a common promoter polymorphic site. Diabetologia 48: 1150‐1158, 2005.
 122. Church TS, Blair SN. When will we treat physical activity as a legitimate medical therapy … even though it does not come in a pill? Br J Sports Med 43: 80‐81, 2009.
 123. Churilla JR, Fitzhugh EC. Relationship between leisure‐time physical activity and metabolic syndrome using varying definitions: 1999‐2004 NHANES. Diab Vasc Dis Res 6: 100‐109, 2009.
 124. Cianflone K, Xia Z, Chen LY. Critical review of acylation‐stimulating protein physiology in humans and rodents. Biochim Biophys Acta 1609: 127‐143, 2003.
 125. Cipolletta D, Kolodin D, Benoist C, Mathis D. Tissular T(regs): A unique population of adipose‐tissue‐resident Foxp3+CD4+ T cells that impacts organismal metabolism. Semin Immunol 23: 431‐437, 2011.
 126. Clevenger CM, Parker Jones P, Tanaka H, Seals DR, DeSouza CA. Decline in insulin action with age in endurance‐trained humans. J Appl Physiol 93: 2105‐2111, 2002.
 127. Coe NR, Bernlohr DA. Physiological properties and functions of intracellular fatty acid‐binding proteins. Biochim Biophys Acta 1391: 287‐306, 1998.
 128. Coker RH, Hays NP, Williams RH, Brown AD, Freeling SA, Kortebein PM, Sullivan DH, Starling RD, Evans WJ. Exercise‐induced changes in insulin action and glycogen metabolism in elderly adults. Med Sci Sports Exerc 38: 433‐438, 2006.
 129. Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacob HJ, Black AEK, Maas D, Takahashi M, Kihara S, Tanaka S, Matsuzawa Y, Blangero J, Cohen D, Kissebah A. The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 86: 4321‐4325, 2001.
 130. Copps KD, Hancer NJ, Opare‐Ado L, Qiu W, Walsh C, White MF. Irs1 serine 307 promotes insulin sensitivity in mice. Cell Metab 11: 84‐92, 2010.
 131. Cortez‐Cooper MY, DeVan AE, Anton MM, Farrar RP, Beckwith KA, Todd JS, Tanaka H. Effects of high intensity resistance training on arterial stiffness and wave reflection in women. Am J Hypertens 18: 930‐934, 2005.
 132. Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y, Moller DE, Kharitonenkov A. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149: 6018‐6027, 2008.
 133. Cox JH, Cortright RN, Dohm GL, Houmard JA. Effect of aging on response to exercise training in humans: Skeletal muscle GLUT‐4 and insulin sensitivity. J Appl Physiol 86: 2019‐2025, 1999.
 134. Craig BW, Everhart J, Brown R. The influence of high‐resistance training on glucose tolerance in young and elderly subjects. Mech Ageing Dev 49: 147‐157, 1989.
 135. Crimmins NA, Martin LJ. Polymorphisms in adiponectin receptor genes ADIPOR1 and ADIPOR2 and insulin resistance. Obesity Reviews 8: 419‐423, 2007.
 136. Crowe S, Wu LE, Economou C, Turpin SM, Matzaris M, Hoehn KL, Hevener AL, James DE, Duh EJ, Watt MJ. Pigment epithelium‐derived factor contributes to insulin resistance in obesity. Cell Metab 10: 40‐47, 2009.
 137. Cuff DJ, Meneilly GS, Martin A, Ignaszewski A, Tildesley HD, Frohlich JJ. Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Diabetes Care 26: 2977‐2982, 2003.
 138. Czech MP. The nature and regulation of the insulin receptor: Structure and function. Annu Rev Physiol 47: 357‐381, 1985.
 139. D'Aiuto F SW, Netuveli G, Donos N, Hingorani AD, Deanfield J, Tsakos G. Association of the metabolic syndrome with severe periodontitis in a large U.S. population‐based syrvey. J Clin Endocrinol Metab 93: 3989‐3994, 2008.
 140. D'Alessandris C, Lauro R, Presta I, Sesti G. C‐reactive protein induces phosphorylation of insulin receptor substrate‐1 on Ser307 and Ser612 in L6 myocytes, thereby impairing the insulin signalling pathway that promotes glucose transport. Diabetologia 50: 840‐849, 2007.
 141. da Luz G, Frederico MJ, da Silva S, Vitto MF, Cesconetto PA, de Pinho RA, Pauli JR, Silva AS, Cintra DE, Ropelle ER, De Souza CT. Endurance exercise training ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue in obese rats. Eur J Appl Physiol 111: 2015‐2023, 2011.
 142. Daray LA, Henagan TM, Zanovec M, Earnest CP, Johnson LG, Winchester J, Tuuri G, Stewart LK. Endurance and resistance training lowers C‐reactive protein in young, healthy females. Appl Physiol Nutr Metab 36: 660‐670, 2011.
 143. Davidson LE, Hudson R, Kilpatrick K, Kuk JL, McMillan K, Janiszewski PM, Lee S, Lam M, Ross R. Effects of exercise modality on insulin resistance and functional limitation in older adults: A randomized controlled trial. Arch Intern Med 169: 122‐131, 2009.
 144. Davis JE, Gabler NK, Walker‐Daniels J, Spurlock ME. Tlr‐4 deficiency selectively protects against obesity induced by diets high in saturated fat. Obesity (Silver Spring) 16: 1248‐1255, 2008.
 145. de Kloet AD, Krause EG, Kim D‐H, Sakai RR, Seeley RJ, Woods SC. The effect of angiotensin‐converting enzyme inhibition using captopril on energy balance and glucose homeostasis. Endocrinology 150: 4114‐4123, 2009.
 146. de Zeeuw D, Bakker SJ. Does the metabolic syndrome add to the diagnosis and treatment of cardiovascular disease? Nat Clin Pract Cardiovasc Med 5 (Suppl 1): S10‐S14, 2008.
 147. DeFronzo RA. Lilly lecture 1987. The triumvirate: Beta‐cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37: 667‐687, 1988.
 148. Defronzo RA, Ferrannini E. Insulin resistance: A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diabetes Care 14: 173‐194, 1991.
 149. DeFronzo RA, Sherwin RS, Kraemer N. Effect of physical training on insulin action in obesity. Diabetes 36: 1379‐1385, 1987.
 150. Dela F, Handberg A, Mikines KJ, Vinten J, Galbo H. GLUT 4 and insulin receptor binding and kinase activity in trained human muscle. J Physiol 469: 615‐624, 1993.
 151. Dela F, Kjaer M. Resistance training, insulin sensitivity and muscle function in the elderly. Essays Biochem 42: 75‐88, 2006.
 152. Dela F, Larsen JJ, Mikines KJ, Ploug T, Petersen LN, Galbo H. Insulin‐stimulated muscle glucose clearance in patients with NIDDM. Effects of one‐legged physical training. Diabetes 44: 1010‐1020, 1995.
 153. Dela F, Mikines KJ, von Linstow M, Secher NH, Galbo H. Effect of training on insulin‐mediated glucose uptake in human muscle. Am J Physiol 263: E1134‐E1143, 1992.
 154. Dela F, Ploug T, Handberg A, Petersen LN, Larsen JJ, Mikines KJ, Galbo H. Physical training increases muscle GLUT4 protein and mRNA in patients with NIDDM. Diabetes 43: 862‐865, 1994.
 155. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 444: 881‐887, 2006.
 156. Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodes‐Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: Contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 28: 1039‐1049, 2008.
 157. Devaraj S, Dasu MR, Singh U, Rao LV, Jialal I. C‐reactive protein stimulates superoxide anion release and tissue factor activity in vivo. Atherosclerosis 203: 67‐74, 2009.
 158. Devaraj S, Singh U, Jialal I. Human C‐reactive protein and the metabolic syndrome. Curr Opin Lipidol 20: 182‐189, 2009.
 159. Di Paola R, Frittitta L, Miscio G, Bozzali M, Baratta R, Centra M, Spampinato D, Santagati MG, Ercolino T, Cisternino C, Soccio T, Mastroianno S, Tassi V, Almgren P, Pizzuti A, Vigneri R, Trischitta V. A variation in 3′ UTR of hPTP1B increases specific gene expression and associates with insulin resistance. Am J Hum Genet 70: 806‐812, 2002.
 160. DiPietro L, Dziura J, Yeckel CW, Neufer PD. Exercise and improved insulin sensitivity in older women: Evidence of the enduring benefits of higher intensity training. J Appl Physiol 100: 142‐149, 2006.
 161. Dobbins RL, Szczepaniak LS, Bentley B, Esser V, Myhill J, McGarry JD. Prolonged inhibition of muscle carnitine palmitoyltransferase‐1 promotes intramyocellular lipid accumulation and insulin resistance in rats. Diabetes 50: 123‐130, 2001.
 162. Dobrzyn A, Gorski J. Ceramides and sphingomyelins in skeletal muscles of the rat: Content and composition. Effect of prolonged exercise. Am J Physiol Endocrinol Metab 282: E277‐E285, 2002.
 163. Donges CE, Duffield R, Drinkwater EJ. Effects of resistance or aerobic exercise training on interleukin‐6, C‐reactive protein, and body composition. Med Sci Sports Exerc 42: 304‐313, 2010.
 164. Dostalova I, Haluzikova D, Haluzik M. Fibroblast growth factor 21: A novel metabolic regulator with potential therapeutic properties in obesity/type 2 diabetes mellitus. Physiol Res 58: 1‐7, 2009.
 165. Dube JJ, Amati F, Stefanovic‐Racic M, Toledo FGS, Sauers SE, Goodpaster BH. Exercise‐induced alterations in intramyocellular lipids and insulin resistance: The athlete's paradox revisited. Am J Physiol Endocrinol Metab 294: E882‐E888, 2008.
 166. DuBose KD, Eisenmann JC, Donnelly JE. Aerobic fitness attenuates the metabolic syndrome score in normal‐weight, at‐risk‐for‐overweight, and overweight children. Pediatrics 120: e1262‐e1268, 2007.
 167. Dudek RW, Dohm GL, Holman GD, Cushman SW, Wilson CM. Glucose transporter localization in rat skeletal muscle. Autoradiographic study using ATB‐(2‐3H]BMPA photolabel. FEBS Lett 339: 205‐208, 1994.
 168. Duffaut C, Galitzky J, Lafontan M, Bouloumie A. Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun 384: 482‐485, 2009.
 169. Duffaut C, Zakaroff‐Girard A, Bourlier V, Decaunes P, Maumus M, Chiotasso P, Sengenes C, Lafontan M, Galitzky J, Bouloumie A. Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol 29: 1608‐1614, 2009.
 170. Duncan GE, Perri MG, Theriaque DW, Hutson AD, Eckel RH, Stacpoole PW. Exercise training, without weight loss, increases insulin sensitivity and postheparin plasma lipase activity in previously sedentary adults. Diabetes Care 26: 557‐562, 2003.
 171. Dunstan DW, Daly RM, Owen N, Jolley D, De Courten M, Shaw J, Zimmet P. High‐intensity resistance training improves glycemic control in older patients with type 2 diabetes. Diabetes Care 25: 1729‐1736, 2002.
 172. Ebeling P, Bourey R, Koranyi L, Tuominen JA, Groop LC, Henriksson J, Mueckler M, Sovijarvi A, Koivisto VA. Mechanism of enhanced insulin sensitivity in athletes. Increased blood flow, muscle glucose transport protein (GLUT‐4) concentration, and glycogen synthase activity. J Clin Invest 92: 1623‐1631, 1993.
 173. Egawa K, Maegawa H, Shimizu S, Morino K, Nishio Y, Bryer‐Ash M, Cheung AT, Kolls JK, Kikkawa R, Kashiwagi A. Protein‐tyrosine phosphatase‐1B negatively regulates insulin signaling in L6 myocytes and fao hepatoma cells. J Biol Chem 276: 10207‐10211, 2001.
 174. Ehses JA, Lacraz G, Giroix M‐H, Schmidlin F, Coulaud J, Kassis N, Irminger J‐C, Kergoat M, Portha B, Homo‐Delarche F, Donath MY. IL‐1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. Proc Nat Acad Sci U S A 106: 13998‐14003, 2009.
 175. Ekelund U, Brage Sr, Franks PW, Hennings S, Emms S, Wareham NJ. Physical activity energy expenditure predicts progression toward the metabolic syndrome independently of aerobic fitness in middle‐aged healthy Caucasians. Diabetes Care 28: 1195‐1200, 2005.
 176. Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms‐Hagen J, Chan C‐C, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase‐1B gene. Science 283: 1544‐1548, 1999.
 177. Elias CF, Aschkenasi C, Lee C, Kelly J, Ahima RS, Bjorbaek C, Flier JS, Saper CB, Elmquist JK. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23: 775‐786, 1999.
 178. Ellis L, Morgan DO, Koshland DE, Jr., Clauser E, Moe GR, Bollag G, Roth RA, Rutter WJ. Linking functional domains of the human insulin receptor with the bacterial aspartate receptor. Proc Natl Acad Sci U S A 83: 8137‐8141, 1986.
 179. Elmquist JK, Elias CF, Saper CB. From lesions to leptin: Hypothalamic control of food intake and body weight. Neuron 22: 221‐232, 1999.
 180. Eriksson J, Taimela S, Koivisto VA. Exercise and the metabolic syndrome. Diabetologia 40: 125‐135, 1997.
 181. Ernst MC, Issa M, Goralski KB, Sinal CJ. Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes. Endocrinology 151: 1998‐2007, 2010.
 182. Ervin RB. Prevalence of Metabolic Syndrome Among Adults 20 Years of Age and Over, by Sex, Age, Race and Ethnicity, and Body Mass Index: United States, 2003‐2006. National Health Statistics Report. Hyattsville, MD, 2009.
 183. Evans EM, Van Pelt RE, Binder EF, Williams DB, Ehsani AA, Kohrt WM. Effects of HRT and exercise training on insulin action, glucose tolerance, and body composition in older women. J Appl Physiol 90: 2033‐2040, 2001.
 184. Fagerholm S, Ortegren U, Karlsson M, Ruishalme I, Stralfors P. Rapid insulin‐dependent endocytosis of the insulin receptor by caveolae in primary adipocytes. PLoS ONE 4: e5985, 2009.
 185. Falasca M, Hughes WE, Dominguez V, Sala G, Fostira F, Fang MQ, Cazzolli R, Shepherd PR, James DE, Maffucci T. The role of phosphoinositide 3‐kinase C2α in insulin signaling. J Biol Chem 282: 28226‐28236, 2007.
 186. Famulla S, Lamers D, Hartwig S, Passlack W, Horrighs A, Cramer A, Lehr S, Sell H, Eckel J. Pigment epithelium‐derived factor is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells. Int J Obes (Lond) 35: 762‐772, 2010.
 187. Farese RV, Sajan MP, Standaert ML. Atypical protein kinase C in insulin action and insulin resistance. Biochem Soc Trans 33: 350‐353, 2005.
 188. Farese RV, Sajan MP, Yang H, Li P, Mastorides S, Gower WR, Jr., Nimal S, Choi CS, Kim S, Shulman GI, Kahn CR, Braun U, Leitges M. Muscle‐specific knockout of PKC‐lambda impairs glucose transport and induces metabolic and diabetic syndromes. J Clin Invest 117: 2289‐2301, 2007.
 189. Farrell SW, Cheng YJ, Blair SN. Prevalence of the metabolic syndrome across cardiorespiratory fitness levels in women. Obes Res 12: 824‐830, 2004.
 190. Febbraio MA, Koukoulas I. HSP72 gene expression progressively increases in human skeletal muscle during prolonged, exhaustive exercise. J Appl Physiol 89: 1055‐1060, 2000.
 191. Febbraio MA, Steensberg A, Walsh R, Koukoulas I, van Hall G, Saltin B, Pedersen BK. Reduced glycogen availability is associated with an elevation in HSP72 in contracting human skeletal muscle. J Physiol 538: 911‐917, 2002.
 192. Fenicchia LM, Kanaley JA, Azevedo JL, Jr., Miller CS, Weinstock RS, Carhart RL, Ploutz‐Snyder LL. Influence of resistance exercise training on glucose control in women with type 2 diabetes. Metabolism 53: 284‐289, 2004.
 193. Ferder L, Inserra F, Martinez‐Maldonado M. Inflammation and the metabolic syndrome: Role of angiotensin II and oxidative stress. Curr Hypertens Rep 8: 191‐198, 2006.
 194. Ferrannini E, Haffner SM, Mitchell BD, Stern MP. Hyperinsulinaemia: The key feature of a cardiovascular and metabolic syndrome. Diabetologia 34: 416‐422, 1991.
 195. Ferrara CM, Goldberg AP, Ortmeyer HK, Ryan AS. Effects of aerobic and resistive exercise training on glucose disposal and skeletal muscle metabolism in older men. J Gerontol A Biol Sci Med Sci 61: 480‐487, 2006.
 196. Festa A, D'Agostino R, Jr., Howard G, Mykkanen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: The Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102: 42‐47, 2000.
 197. Finley CE, LaMonte MJ, Waslien CI, Barlow CE, Blair SN, Nichaman MZ. Cardiorespiratory fitness, macronutrient intake, and the metabolic syndrome: The Aerobics Center Longitudinal Study. J Am Diet Assoc 106: 673‐679, 2006.
 198. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 31: 289‐294, 2008.
 199. Flores MB, Fernandes MF, Ropelle ER, Faria MC, Ueno M, Velloso LA, Saad MJ, Carvalheira JB. Exercise improves insulin and leptin sensitivity in hypothalamus of Wistar rats. Diabetes 55: 2554‐2561, 2006.
 200. Flynn MG, McFarlin BK. Toll‐like receptor 4: Link to the anti‐inflammatory effects of exercise? Exerc Sport Sci Rev 34: 176‐181, 2006.
 201. Ford ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care 28: 2745‐2749, 2005.
 202. Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the metabolic syndrome among U.S. Adults. Diabetes Care 27: 2444‐2449, 2004.
 203. Ford ES, Kohl HW, Mokdad AH, Ajani UA. Sedentary behavior, physical activity, and the metabolic syndrome among U.S. adults[ast][ast]. Obesity 13: 608‐614, 2005.
 204. Ford ES, Li C, Sattar N. Metabolic syndrome and incident diabetes: Current state of the evidence. Diabetes Care 31: 1898‐1904, 2008.
 205. Foster DW. Insulin resistance–a secret killer? N Engl J Med 320: 733‐734, 1989.
 206. Franks PW, Ekelund U, Brage Sr, Wong M‐Y, Wareham NJ. Does the association of habitual physical activity with the metabolic syndrome differ by level of cardiorespiratory fitness? Diabetes Care 27: 1187‐1193, 2004.
 207. Fresno M, Alvarez R, Cuesta N. Toll‐like receptors, inflammation, metabolism and obesity. Arch Physiol Biochem 117: 151‐164, 2011.
 208. Friedman JE, Dohm GL, Leggett‐Frazier N, Elton CW, Tapscott EB, Pories WP, Caro JF. Restoration of insulin responsiveness in skeletal muscle of morbidly obese patients after weight loss. Effect on muscle glucose transport and glucose transporter GLUT4. J Clin Invest 89: 701‐705, 1992.
 209. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 395: 763‐770, 1998.
 210. Frøsig C, Jørgensen SB, Hardie DG, Richter EA, Wojtaszewski JFP. 5′‐AMP‐activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle. Am J Physiol Endocrinol Metab 286: E411‐E417, 2004.
 211. Frosig C, Rose AJ, Treebak JT, Kiens B, Richter EA, Wojtaszewski JF. Effects of endurance exercise training on insulin signaling in human skeletal muscle: Interactions at the level of phosphatidylinositol 3‐kinase, Akt, and AS160. Diabetes 56: 2093‐2102, 2007.
 212. Fruebis J, Tsao T‐S, Javorschi S, Ebbets‐Reed D, Erickson MRS, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30‐kDa adipocyte complement‐related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Nat Acad Sci U S A 98: 2005‐2010, 2001.
 213. Fruman DA, Cantley LC, Carpenter CL. Structural organization and alternative splicing of the murine phosphoinositide 3‐kinase p85 alpha gene. Genomics 37: 113‐121, 1996.
 214. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Visfatin: A protein secreted by visceral fat that mimics the effects of insulin. Science 307: 426‐430, 2005.
 215. Furuhashi M, Tuncman G, Gorgun CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS. Treatment of diabetes and atherosclerosis by inhibiting fatty‐acid‐binding protein aP2. Nature 447: 959‐965, 2007.
 216. Gaidhu MP, Perry RL, Noor F, Ceddia RB. Disruption of AMPKalpha1 signaling prevents AICAR‐induced inhibition of AS160/TBC1D4 phosphorylation and glucose uptake in primary rat adipocytes. Mol Endocrinol 24: 1434‐1440, 2010.
 217. Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: A meta‐analysis. Am J Med 119: 812‐819, 2006.
 218. Galluzzo A, Amato MC, Giordano C. Insulin resistance and polycystic ovary syndrome. Nutr Metab Cardiovasc Dis 18: 511‐518, 2008.
 219. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, Montori VM. Metabolic syndrome and risk of incident cardiovascular events and death: A systematic review and meta‐analysis of longitudinal studies. J Am Coll Cardiol 49: 403‐414, 2007.
 220. Garvey WT, Maianu L, Hancock JA, Golichowski AM, Baron A. Gene expression of GLUT4 in skeletal muscle from insulin‐resistant patients with obesity, IGT, GDM, and NIDDM. Diabetes 41: 465‐475, 1992.
 221. Garvey WT, Maianu L, Zhu JH, Brechtel‐Hook G, Wallace P, Baron AD. Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. J Clin Invest 101: 2377‐2386, 1998.
 222. Geering B, Cutillas PR, Vanhaesebroeck B. Regulation of class IA PI3Ks: Is there a role for monomeric PI3K subunits? Biochem Soc Trans 035: 199‐203, 2007.
 223. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti‐inflammatory effects of exercise: Mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 11: 607‐615, 2011.
 224. Goldfine AB, Silver R, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci 1: 36‐43, 2008.
 225. Goldstein BJ, Mahadev K, Wu X, Zhu L, Motoshima H. Role of insulin‐induced reactive oxygen species in the insulin signaling pathway. Antioxid Redox Signal 7: 1021‐1031, 2005.
 226. Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: Evidence for a paradox in endurance‐trained athletes. J Clin Endocrinol Metab 86: 5755‐5761, 2001.
 227. Goodpaster BH, Katsiaras A, Kelley DE. Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes 52: 2191‐2197, 2003.
 228. Goodyear LJ. The exercise pill ‐ too good to be true? N Engl J Med 359: 1842‐1844, 2008.
 229. Goossens GH. The role of adipose tissue dysfunction in the pathogenesis of obesity‐related insulin resistance. Physiol Behav 94: 206‐218, 2008.
 230. Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, Muruganandan S, Sinal CJ. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 282: 28175‐28188, 2007.
 231. Gordon BA, Benson AC, Bird SR, Fraser SF. Resistance training improves metabolic health in type 2 diabetes: A systematic review. Diabetes Res Clin Pract 83: 157‐175, 2009.
 232. Gordon S, Martinez FO. Alternative activation of macrophages: Mechanism and functions. Immunity 32: 593‐604, 2010.
 233. Gotto AM, Jr., Blackburn GL, Dailey GE, III, Garber AJ, Grundy SM, Sobel BE, Weir MR. The metabolic syndrome: A call to action. Coron Artery Dis 17: 77‐80, 2006.
 234. Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson P‐A, Smith U, Kahn BB. Retinol‐binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 354: 2552‐2563, 2006.
 235. Gregor MF, Hotamisligil GS. Thematic review series: Adipocyte biology. Adipocyte stress: The endoplasmic reticulum and metabolic disease. J Lipid Res 48: 1905‐1914, 2007.
 236. Gregor MF, Yang L, Fabbrini E, Mohammed BS, Eagon JC, Hotamisligil GS, Klein S. Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Diabetes 58: 693‐700, 2009.
 237. Grimditch GK, Barnard RJ, Hendricks L, Weitzman D. Peripheral insulin sensitivity as modified by diet and exercise training. Am J Clin Nutr 48: 38‐43, 1988.
 238. Grimditch GK, Barnard RJ, Sternlicht E, Whitson RH, Kaplan SA. Effect of diet on insulin binding and glucose transport in rat sarcolemmal vesicles. Am J Physiol 252: E420‐E425, 1987.
 239. Grundy SM. Point: The metabolic syndrome still lives. Clin Chem 51: 1352‐1354, 2005.
 240. Grundy SM, Brewer HB, Jr, Cleeman JI, Smith SC, Jr, Lenfant C, and for the Conference Participants. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation 109: 433‐438, 2004.
 241. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Jr., Spertus JA, Costa F. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112: 2735‐2752, 2005.
 242. Gum RJ, Gaede LL, Koterski SL, Heindel M, Clampit JE, Zinker BA, Trevillyan JM, Ulrich RG, Jirousek MR, Rondinone CM. Reduction of protein tyrosine phosphatase 1B increases insulin‐dependent signaling in ob/ob mice. Diabetes 52: 21‐28, 2003.
 243. Guo S, Copps KD, Dong X, Park S, Cheng Z, Pocai A, Rossetti L, Sajan M, Farese RV, White MF. The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic nutrient homeostasis. Mol Cell Biol 29: 5070‐5083, 2009.
 244. Gupte AA, Bomhoff GL, Swerdlow RH, Geiger PC. Heat treatment improves glucose tolerance and prevents skeletal muscle insulin resistance in rats fed a high‐fat diet. Diabetes 58: 567‐578, 2009.
 245. Gupte AA, Bomhoff GL, Touchberry CD, Geiger PC. Acute heat treatment improves insulin‐stimulated glucose uptake in aged skeletal muscle. J Appl Physiol 110: 451‐457, 2011.
 246. Gustafson TA, He W, Craparo A, Schaub CD, O'Neill TJ. Phosphotyrosine‐dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non‐SH2 domain. Mol Cell Biol 15: 2500‐2508, 1995.
 247. Gustavsson J, Parpal S, Karlsson M, Ramsing C, Thorn H, Borg M, Lindroth M, Peterson KH, Magnusson KE, Stralfors P. Localization of the insulin receptor in caveolae of adipocyte plasma membrane. FASEB J 13: 1961‐1971, 1999.
 248. Haffner SM, Katz MS, Dunn JF. Increased upper body and overall adiposity is associated with decreased sex hormone binding globulin in postmenopausal women. Int J Obes (Lond) 15: 471‐478, 1991.
 249. Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP. Prospective analysis of the insulin‐resistance syndrome (syndrome X). Diabetes 41: 715‐722, 1992.
 250. Haider DG, Mittermayer F, Schaller G, Artwohl M, Baumgartner‐Parzer SM, Prager G, Roden M, Wolzt M. Free fatty acids normalize a rosiglitazone‐induced visfatin release. Am J Physiol Endocrinol Metab 291: E885‐E890, 2006.
 251. Halldin M, Rosell M, de Faire U, Hellénius ML. The metabolic syndrome: Prevalence and association to leisure‐time and work‐related physical activity in 60‐year‐old men and women. Nutr Metab Cardiovasc Dis 17: 349‐357, 2007.
 252. Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, Omatsu T, Nakajima T, Sarui H, Shimazaki M, Kato T, Okuda J, Ida K. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 143: 722‐728, 2005.
 253. Han DH, Hancock CR, Jung SR, Higashida K, Kim SH, Holloszy JO. Deficiency of the mitochondrial electron transport chain in muscle does not cause insulin resistance. PLoS ONE 6: e19739, 2011.
 254. Hansel B, Giral P, Nobecourt E, Chantepie S, Bruckert E, Chapman MJ, Kontush A. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high‐density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab 89: 4963‐4971, 2004.
 255. Hansen PA, Gulve EA, Marshall BA, Gao J, Pessin J, Holloszy JO, Mueckler M. Skeletal muscle glucose transport and metabolism are enhanced in transgenic mice overexpressing the Glut4 glucose transporter. J Biol Chem 270: 1679‐1684, 1995.
 256. Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, Yamauchi T, Otabe S, Okada T, Eto K, Kadowaki H, Hagura R, Akanuma Y, Yazaki Y, Nagai R, Taniyama M, Matsubara K, Yoda M, Nakano Y, Kimura S, Tomita M, Ito C, Froguel P, Kadowaki T. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51: 536‐540, 2002.
 257. Hassinen M, Lakka TA, Savonen K, Litmanen H, Kiviaho L, Laaksonen DE, Komulainen P, Rauramaa R. Cardiorespiratory fitness as a feature of metabolic syndrome in older men and women. Diabetes Care 31: 1242‐1247, 2008.
 258. Haunerland NH, Spener F. Fatty acid‐binding proteins–insights from genetic manipulations. Prog Lipid Res 43: 328‐349, 2004.
 259. Hawley JA, Holloszy JO. Exercise: It's the real thing! Nutr Rev 67: 172‐178, 2009.
 260. Healy GN, Dunstan DW, Salmon J, Cerin E, Shaw JE, Zimmet PZ, Owen N. Objectively measured light‐intensity physical activity is independently associated with 2‐h plasma glucose. Diabetes Care 30: 1384‐1389, 2007.
 261. Heath GW, Gavin JR, III,, Hinderliter JM, Hagberg JM, Bloomfield SA, Holloszy JO. Effects of exercise and lack of exercise on glucose tolerance and insulin sensitivity. J Appl Physiol 55: 512‐517, 1983.
 262. Heffernan KS, Jae SY, Vieira VJ, Iwamoto GA, Wilund KR, Woods JA, Fernhall B. C‐reactive protein and cardiac vagal activity following resistance exercise training in young African‐American and white men. Am J Physiol Regul Integr Comp Physiol 296: R1098‐R1105, 2009.
 263. Hein TW, Singh U, Vasquez‐Vivar J, Devaraj S, Kuo L, Jialal I. Human C‐reactive protein induces endothelial dysfunction and uncoupling of eNOS in vivo. Atherosclerosis 206: 61‐68, 2009.
 264. Heitmeier MR, Arnush M, Scarim AL, Corbett JA. Pancreatic beta‐cell damage mediated by beta‐cell production of interleukin‐1. A novel mechanism for virus‐induced diabetes. J Biol Chem 276: 11151‐11158, 2001.
 265. Helge JW, Dobrzyn A, Saltin B, Gorski J. Exercise and training effects on ceramide metabolism in human skeletal muscle. Exp Physiol 89: 119‐127, 2004.
 266. Helledie T, Antonius M, Sorensen RV, Hertzel AV, Bernlohr DA, Kolvraa S, Kristiansen K, Mandrup S. Lipid‐binding proteins modulate ligand‐dependent trans‐activation by peroxisome proliferator‐activated receptors and localize to the nucleus as well as the cytoplasm. J Lipid Res 41: 1740‐1751, 2000.
 267. Hevener AL, Olefsky JM, Reichart D, Nguyen MT, Bandyopadyhay G, Leung HY, Watt MJ, Benner C, Febbraio MA, Nguyen AK, Folian B, Subramaniam S, Gonzalez FJ, Glass CK, Ricote M. Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest 117: 1658‐1669, 2007.
 268. Higaki Y, Wojtaszewski JF, Hirshman MF, Withers DJ, Towery H, White MF, Goodyear LJ. Insulin receptor substrate‐2 is not necessary for insulin‐ and exercise‐stimulated glucose transport in skeletal muscle. J Biol Chem 274: 20791‐20795, 1999.
 269. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature 420: 333‐336, 2002.
 270. Hojman P, Dethlefsen C, Brandt C, Hansen J, Pedersen L, Pedersen BK. Exercise‐induced muscle‐derived cytokines inhibit mammary cancer cell growth. Am J Physiol Endocrinol Metab 301: E504‐E510, 2011.
 271. Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, Liu Y, Narra K, Hoehn KL, Knotts TA, Siesky A, Nelson DH, Karathanasis SK, Fontenot GK, Birnbaum MJ, Summers SA. Inhibition of ceramide synthesis ameliorates glucocorticoid‐, saturated‐fat‐, and obesity‐induced insulin resistance. Cell Metab 5: 167‐179, 2007.
 272. Holland WL, Summers SA. Sphingolipids, insulin resistance, and metabolic disease: New insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev 29: 381‐402, 2008.
 273. Hollenbeck CB, Haskell W, Rosenthal M, Reaven GM. Effect of habitual physical activity on regulation of insulin‐stimulated glucose disposal in older males. J Am Geriatr Soc 33: 273‐277, 1985.
 274. Holloway GP, Chou CJ, Lally J, Stellingwerff T, Maher AC, Gavrilova O, Haluzik M, Alkhateeb H, Reitman ML, Bonen A. Increasing skeletal muscle fatty acid transport protein 1 (FATP1) targets fatty acids to oxidation and does not predispose mice to diet‐induced insulin resistance. Diabetologia 54: 1457‐1467, 2011.
 275. Holme I, Tonstad S, Sogaard A, Larsen P, Haheim L. Leisure time physical activity in middle age predicts the metabolic syndrome in old age: Results of a 28‐year follow‐up of men in the Oslo study. BMC Public Health 7: 154, 2007.
 276. Holten MK, Zacho M, Gaster M, Juel C, Wojtaszewski JFP, Dela F. Strength training increases insulin‐mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes. Diabetes 53: 294‐305, 2004.
 277. Hood MS, Little JP, Tarnopolsky MA, Myslik F, Gibala MJ. Low‐volume interval training improves muscle oxidative capacity in sedentary adults. Med Sci Sports Exerc 43: 1849‐1856, 2011.
 278. Hopps E, Canino B, Caimi G. Effects of exercise on inflammation markers in type 2 diabetic subjects. Acta diabetologica 48: 183‐189, 2011.
 279. Hori H, Sasaoka T, Ishihara H, Wada T, Murakami S, Ishiki M, Kobayashi M. Association of SH2‐containing inositol phosphatase 2 with the insulin resistance of diabetic db/db mice. Diabetes 51: 2387‐2394, 2002.
 280. Hotamisligil GS. The role of TNF‐alpha and TNF receptors in obesity and insulin resistance. J Internal Medicine 245: 621‐625, 1999.
 281. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140: 900‐917, 2010.
 282. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor‐alpha in human obesity and insulin resistance. J Clin Invest 95: 2409‐2415, 1995.
 283. Hotamisligil GS, Budavari A, Murray D, Spiegelman BM. Reduced tyrosine kinase activity of the insulin receptor in obesity‐diabetes. Central role of tumor necrosis factor‐alpha. J Clin Invest 94: 1543‐1549, 1994.
 284. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS‐1‐mediated inhibition of insulin receptor tyrosine kinase activity in TNF‐alpha‐ and obesity‐induced insulin resistance. Science 271: 665‐668, 1996.
 285. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor‐α: Direct role in obesity‐linked insulin resistance. Science 259: 87‐91, 1993.
 286. Houmard JA, Egan PC, Neufer PD, Friedman JE, Wheeler WS, Israel RG, Dohm GL. Elevated skeletal muscle glucose transporter levels in exercise‐trained middle‐aged men. J Physiol Endocrinol Metab 261: E437‐E443, 1991.
 287. Houmard JA, Hortobagyi T, Neufer PD, Johns RA, Fraser DD, Israel RG, Dohm GL. Training cessation does not alter GLUT‐4 protein levels in human skeletal muscle. J Appl Physiol 74: 776‐781, 1993.
 288. Houmard JA, Shaw CD, Hickey MS, Tanner CJ. Effect of short‐term exercise training on insulin‐stimulated PI 3‐ kinase activity in human skeletal muscle. Am J Physiol 277: E1055‐E1060, 1999.
 289. Houmard JA, Shinebarger MH, Dolan PL, Leggett‐Frazier N, Bruner RK, McCammon MR, Israel RG, Dohm GL. Exercise training increases GLUT‐4 protein concentration in previously sedentary middle‐aged men. Am J Physiol 264: E896‐E901, 1993.
 290. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol 96: 101‐106, 2004.
 291. Houmard JA, Tyndall GL, Midyette JB, Hickey MS, Dolan PL, Gavigan KE, Weidner ML, Dohm GL. Effect of reduced training and training cessation on insulin action and muscle GLUT‐4. J Appl Physiol 81: 1162‐1168, 1996.
 292. Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bjorbaek C, Flier JS. Enhanced leptin sensitivity and attenuation of diet‐induced obesity in mice with haploinsufficiency of Socs3. Nat Med 10: 734‐738, 2004.
 293. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose‐specific gene dysregulated in obesity. J Biol Chem 271: 10697‐10703, 1996.
 294. Huang CJ, Lin CY, Haataja L, Gurlo T, Butler AE, Rizza RA, Butler PC. High expression rates of human islet amyloid polypeptide induce endoplasmic reticulum stress mediated beta‐cell apoptosis, a characteristic of humans with type 2 but not type 1 diabetes. Diabetes 56: 2016‐2027, 2007.
 295. Hubbard S, Wei L, Ellis l, Hendrickson W. Crystal structure of the tyrosine kinase domain of the human insulin receptor. Nature 372: 746‐754, 1994.
 296. Hubbard SR. Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog. EMBO J 16: 5572‐5581, 1997.
 297. Huber J, Kiefer FW, Zeyda M, Ludvik B, Silberhumer GR, Prager G, Zlabinger GJ, Stulnig TM. CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity. J Clin Endocrinol Metab 93: 3215‐3221, 2008.
 298. Huber K. Plasminogen activator inhibitor type‐1 (part two): Role for failure of thrombolytic therapy. PAI‐1 resistance as a potential benefit for new fibrinolytic agents. J Thromb Thrombolysis 11: 195‐202, 2001.
 299. Hughes VA, Fiatarone MA, Fielding RA, Kahn BB, Ferrara CM, Shepherd P, Fisher EC, Wolfe RR, Elahi D, Evans WJ. Exercise increases muscle GLUT‐4 levels and insulin action in subjects with impaired glucose tolerance. Am J Physiol 264: E855‐E862, 1993.
 300. Hung J, McQuillan BM, Thompson PL, Beilby JP. Circulating adiponectin levels associate with inflammatory markers, insulin resistance and metabolic syndrome independent of obesity. Int J Obes (Lond) 32: 772‐779, 2008.
 301. Hurley BF, Hagberg JM, Goldberg AP, Seals DR, Ehsani AA, Brennan RE, Holloszy JO. Resistive training can reduce coronary risk factors without altering VO2max or percent body fat. Med Sci Sports Exerc 20: 150‐154, 1988.
 302. Ibanez J, Izquierdo M, Arguelles I, Forga L, Larrion JL, Garcia‐Unciti M, Idoate F, Gorostiaga EM. Twice‐weekly progressive resistance training decreases abdominal fat and improves insulin sensitivity in older men with type 2 diabetes. Diabetes Care 28: 662‐667, 2005.
 303. IDF. Worldwide definition of the metabolic syndrome. http://www.idf.org, 2005.
 304. Ilanne‐Parikka P, Eriksson JG, Lindström J, Peltonen M, Aunola S, Hämäläinen H, Keinänen‐Kiukaanniemi S, Laakso M, Valle TT, Lahtela J, Uusitupa M, Tuomilehto J. Effect of lifestyle intervention on the occurrence of metabolic syndrome and its components in the Finnish diabetes prevention study. Diabetes Care 31: 805‐807, 2008.
 305. Ilanne‐Parikka P, Laaksonen DE, Eriksson JG, Lakka TA, Lindstr J, Peltonen M, Aunola S, Keinänen‐Kiukaanniemi S, Uusitupa M, Tuomilehto J. Leisure‐time physical activity and the metabolic syndrome in the Finnish diabetes prevention study. Diabetes Care 33: 1610‐1617, 2010.
 306. Irwin ML, Ainsworth BE, Mayer‐Davis EJ, Addy CL, Pate RR, Durstine JL. Physical activity and the metabolic syndrome in a tri‐ethnic sample of women. Obes Res 10: 1030‐1037, 2002.
 307. Ishihara H, Sasaoka T, Kagawa S, Murakami S, Fukui K, Kawagishi Y, Yamazaki K, Sato A, Iwata M, Urakaze M, Ishiki M, Wada T, Yaguchi S, Tsuneki H, Kimura I, Kobayashi M. Association of the polymorphisms in the 5′‐untranslated region of PTEN gene with type 2 diabetes in a Japanese population. FEBS Lett 554: 450‐454, 2003.
 308. Ishii T, Yamakita T, Sato T, Tanaka S, Fujii S. Resistance training improves insulin sensitivity in NIDDM subjects without altering maximal oxygen uptake. Diabetes Care 21: 1353‐1355, 1998.
 309. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24: 683‐689, 2001.
 310. Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid‐induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB‐α. Diabetes 51: 2005‐2011, 2002.
 311. Izumiya Y, Bina HA, Ouchi N, Akasaki Y, Kharitonenkov A, Walsh K. FGF21 is an Akt‐regulated myokine. FEBS Lett 582: 3805‐3810, 2008.
 312. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 288: 462‐467, 2002.
 313. Jacob S, Machann J, Rett K, Brechtel K, Volk A, Renn W, Maerker E, Matthaei S, Schick F, Claussen C‐D, Haring H‐U. Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of tpe 2 diabetic subjects. Diabetes 48: 1113‐1119, 1999.
 314. JeBailey L, Rudich A, Huang X, Ciano‐Oliveira CD, Kapus A, Klip A. Skeletal muscle cells and adipocytes differ in their reliance on TC10 and Rac for insulin‐induced actin remodeling. Mol Endocrinol 18: 359‐372, 2004.
 315. Jeppesen J, Mogensen M, Prats C, Sahlin K, Madsen K, Kiens B. FAT/CD36 is localized in sarcolemma and in vesicle‐like structures in subsarcolemma regions but not in mitochondria. J Lipid Res 51: 1504‐1512, 2010.
 316. Johnson JL, Slentz CA, Houmard JA, Samsa GP, Duscha BD, Aiken LB, McCartney JS, Tanner CJ, Kraus WE. Exercise training amount and intensity effects on metabolic syndrome (from Studies of a Targeted Risk Reduction Intervention through Defined Exercise). Am J Cardiol 100: 1759‐1766, 2007.
 317. Joost HG, Thorens B. The extended GLUT‐family of sugar/polyol transport facilitators: Nomenclature, sequence characteristics, and potential function of its novel members (review). Mol Membr Biol 18: 247‐256, 2001.
 318. Jung HS, Park KH, Cho YM, Chung SS, Cho HJ, Cho SY, Kim SJ, Kim SY, Lee HK, Park KS. Resistin is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovasc Res 69: 76‐85, 2006.
 319. Jurca R, Lamonte MJ, Barlow CE, Kampert JB, Church TS, Blair SN. Association of muscular strength with incidence of metabolic syndrome in men. Med Sci Sports Exerc 37: 1849‐1855, 2005.
 320. Jurca R, Lamonte MJ, Church TS, Earnest CP, Fitzgerald SJ, Barlow CE, Jordan AN, Kampert JB, Blair SN. Associations of muscle strength and fitness with metabolic syndrome in men. Med Sci Sports Exerc 36: 1301‐1307, 2004.
 321. Kaburagi Y, Yamamoto‐Honda R, Tobe K, Ueki K, Yachi M, Akanuma Y, Stephens R, Kaplan D, Yazaki Y, Kadowaki T. The role of the NPXY motif in the insulin receptor in tyrosine phosphorylation of insulin receptor substrate‐1 and Shc. Endocrinology 136: 3437‐3443, 1995.
 322. Kaczocha M, Vivieca S, Sun J, Glaser ST, Deutsch DG. Fatty acid binding proteins transport N‐acylethanolamines to nuclear receptors and are targets of endocannabinoid transport inhibitors. J Biol Chem 287: 3415‐3424, 2011.
 323. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 26: 439‐451, 2005.
 324. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116: 1784‐1792, 2006.
 325. Kagawa S, Soeda Y, Ishihara H, Oya T, Sasahara M, Yaguchi S, Oshita R, Wada T, Tsuneki H, Sasaoka T. Impact of transgenic overexpression of SH2‐containing inositol 5′‐phosphatase 2 on glucose metabolism and insulin signaling in mice. Endocrinology 149: 642‐650, 2008.
 326. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: Time for a critical appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 28: 2289‐2304, 2005.
 327. Kalmijn S, Foley D, White L, Burchfiel CM, Curb JD, Petrovitch H, Ross GW, Havlik RJ, Launer LJ. Metabolic cardiovascular syndrome and risk of dementia in japanese‐ american elderly men: The honolulu‐asia aging study. Arterioscler Thromb Vasc Biol 20: 2255‐2260, 2000.
 328. Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, Ohtsuka‐Kowatari N, Kumagai K, Sakamoto K, Kobayashi M, Yamauchi T, Ueki K, Oishi Y, Nishimura S, Manabe I, Hashimoto H, Ohnishi Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Nagai R, Kadowaki T. Overexpression of monocyte chemoattractant protein‐1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 281: 26602‐26614, 2006.
 329. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M. MCP‐1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116: 1494‐1505, 2006.
 330. Kane S, Sano H, Liu SC, Asara JM, Lane WS, Garner CC, Lienhard GE. A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase‐activating protein (GAP) domain. J Biol Chem 277: 22115‐22118, 2002.
 331. Kanzaki M, Mora S, Hwang JB, Saltiel AR, Pessin JE. Atypical protein kinase C (PKCzeta/lambda) is a convergent downstream target of the insulin‐stimulated phosphatidylinositol 3‐kinase and TC10 signaling pathways. J Cell Biol 164: 279‐290, 2004.
 332. Kanzaki M, Watson RT, Khan AH, Pessin JE. Insulin stimulates actin comet tails on intracellular GLUT4‐containing compartments in differentiated 3T3L1 adipocytes. J Biol Chem 276: 49331‐49336, 2001.
 333. Kaplan NM. The deadly quartet. Upper‐body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 149: 1514‐1520, 1989.
 334. Karlsson HK, Zierath JR, Kane S, Krook A, Lienhard GE, Wallberg‐Henriksson H. Insulin‐stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects. Diabetes 54: 1692‐1697, 2005.
 335. Kasapis C, Thompson PD. The effects of physical activity on serum C‐reactive protein and inflammatory markers: A systematic review. J Am Coll Cardiol 45: 1563‐1569, 2005.
 336. Katz EB, Stenbit AE, Hatton K, DePinho R, Charron MJ. Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature 377: 151‐155, 1995.
 337. Katzmarzyk PT, Church TS, Blair SN. Cardiorespiratory fitness attenuates the effects of the metabolic syndrome on all‐cause and cardiovascular disease mortality in men. Arch Intern Med 164: 1092‐1097, 2004.
 338. Katzmarzyk PT, Church TS, Janssen I, Ross R, Blair SN. Metabolic syndrome, obesity, and mortality. Diabetes Care 28: 391‐397, 2005.
 339. Katzmarzyk PT, Janssen I, Ross R, Church TS, Blair SN. The importance of waist circumference in the definition of metabolic syndrome: Prospective analyses of mortality in men. Diabetes Care 29: 404‐409, 2006.
 340. Katzmarzyk PT, Leon AS, Wilmore JH, Skinner JS, Rao DC, Rankinen T, Bouchard C. Targeting the metabolic syndrome with exercise: Evidence from the HERITAGE Family Study. Med Sci Sports Exerc 35: 1703‐1709, 2003.
 341. Kaur J, Adya R, Tan BK, Chen J, Randeva HS. Identification of chemerin receptor (ChemR23) in human endothelial cells: Chemerin‐induced endothelial angiogenesis. Biochem Biophys Res Commun 391: 1762‐1768, 2010.
 342. Kavanaugh WM, Williams LT. An alternative to SH2 domains for binding tyrosine‐phosphorylated proteins. Science 266: 1862‐1865, 1994.
 343. Kawamoto R, Kohara K, Tabara Y, Miki T. An association between metabolic syndrome and the estimated glomerular filtration rate. Intern Med 47: 1399‐1406, 2008.
 344. Kawanishi N, Yano H, Yokogawa Y, Suzuki K. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high‐fat‐diet‐induced obese mice. Exerc Immunol Rev 16: 105‐118, 2010.
 345. Keaney JF, Jr., Larson MG, Vasan RS, Wilson PWF, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ. Obesity and systemic oxidative stress: Clinical correlates of oxidative stress in The Framingham Study. Arterioscler Thromb Vasc Biol 23: 434‐439, 2003.
 346. Kelly KR, Blaszczak A, Haus JM, Patrick‐Melin A, Fealy CE, Solomon TPJ, Kalinski MI, Kirwan JP. A 7‐d exercise program increases high–molecular weight adiponectin in obese adults. Med Sci Sports Exerc 44: 69‐74, 2012.
 347. Kemmler W, Von Stengel S, Engelke K, Kalender WA. Exercise decreases the risk of metabolic syndrome in elderly females. Med Sci Sports Exerc 41: 297‐305, 2009.
 348. Khan AH, Capilla E, Hou JC, Watson RT, Smith JR, Pessin JE. Entry of newly synthesized GLUT4 into the insulin‐responsive storage compartment is dependent upon both the amino terminus and the large cytoplasmic loop. J Biol Chem 279: 37505‐37511, 2004.
 349. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA, Gromada J, Brozinick JT, Hawkins ED, Wroblewski VJ, Li DS, Mehrbod F, Jaskunas SR, Shanafelt AB. FGF‐21 as a novel metabolic regulator. J Clin Invest 115: 1627‐1635, 2005.
 350. Kiens B, Kristiansen S, Jensen P, Richter EA, Turcotte LP. Membrane associated fatty acid binding protein (FABPpm) in human skeletal muscle is increased by endurance training. Biochem Biophys Res Commun 231: 463‐465, 1997.
 351. Kim JY, Hickner RC, Cortright RL, Dohm GL, Houmard JA. Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab 279: E1039‐E1044, 2000.
 352. King DS, Dalsky GP, Clutter WE, Young DA, Staten MA, Cryer PE, Holloszy JO. Effects of exercise and lack of exercise on insulin sensitivity and responsiveness. J Appl Physiol 64: 1942‐1946, 1988.
 353. King DS, Dalsky GP, Staten MA, Clutter WE, Van Houten DR, Holloszy JO. Insulin action and secretion in endurance‐trained and untrained humans. J Appl Physiol 63: 2247‐2252, 1987.
 354. Kirchgessner TG, Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Tumor necrosis factor‐alpha contributes to obesity‐related hyperleptinemia by regulating leptin release from adipocytes. J Clin Invest 100: 2777‐2782, 1997.
 355. Kirwan JP, del Aguila LF, Hernandez JM, Williamson DL, O'Gorman DJ, Lewis R, Krishnan RK. Regular exercise enhances insulin activation of IRS‐1‐associated PI3‐ kinase in human skeletal muscle. J Appl Physiol 88: 797‐803, 2000.
 356. Kirwan JP, Solomon TP, Wojta DM, Staten MA, Holloszy JO. Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 297: E151‐E156, 2009.
 357. Klaman LD, Boss O, Peroni OD, Kim JK, Martino JL, Zabolotny JM, Moghal N, Lubkin M, Kim Y‐B, Sharpe AH, Stricker‐Krongrad A, Shulman GI, Neel BG, Kahn BB. Increased energy expenditure, decreased adiposity, and tissue‐specific insulin sensitivity in protein‐tyrosine phosphatase 1B‐deficient mice. Mol Cell Biol 20: 5479‐5489, 2000.
 358. Klein BE, Klein R, Lee KE. Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in beaver dam. Diabetes Care 25: 1790‐1794, 2002.
 359. Klimcakova E, Polak J, Moro C, Hejnova J, Majercik M, Viguerie N, Berlan M, Langin D, Stich V. Dynamic strength training improves insulin sensitivity without altering plasma levels and gene expression of adipokines in subcutaneous adipose tissue in obese men. J Clin Endocrinol Metab 91: 5107‐5112, 2006.
 360. Klover PJ, Zimmers TA, Koniaris LG, Mooney RA. Chronic exposure to interleukin‐6 causes hepatic insulin resistance in mice. Diabetes 52: 2784‐2789, 2003.
 361. Knudsen SH, Hansen LS, Pedersen M, Dejgaard T, Hansen J, Hall GV, Thomsen C, Solomon TPJ, Pedersen BK, and Krogh‐Madsen R. Changes in insulin sensitivity precede changes in body composition during 14 days of step reduction combined with overfeeding in healthy young men. J Appl Physiol 113: 7‐15, 2012.
 362. Koren S, Fantus IG. Inhibition of the protein tyrosine phosphatase PTP1B: Potential therapy for obesity, insulin resistance and type‐2 diabetes mellitus. Best Pract Res Clin Endocrinol Metab 21: 621‐640, 2007.
 363. Kotani K, Ogawa W, Matsumoto M, Kitamura T, Sakaue H, Hino Y, Miyake K, Sano W, Akimoto K, Ohno S, Kasuga M. Requirement of atypical protein kinase clambda for insulin stimulation of glucose uptake but not for Akt activation in 3T3‐L1 adipocytes. Mol Cell Biol 18: 6971‐6982, 1998.
 364. Kovacikova M, Sengenes C, Kovacova Z, Siklova‐Vitkova M, Klimcakova E, Polak J, Rossmeislova L, Bajzova M, Hejnova J, Hnevkovska Z, Bouloumie A, Langin D, Stich V. Dietary intervention‐induced weight loss decreases macrophage content in adipose tissue of obese women. Int J Obes (Lond) 35: 91‐98, 2010.
 365. Krabbe K, Nielsen A, Krogh‐Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, Fischer C, Lindegaard B, Petersen A, Taudorf S, Secher N, Pilegaard H, Bruunsgaard H, Pedersen B. Brain‐derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia 50: 431‐438, 2007.
 366. Kramer HF, Witczak CA, Taylor EB, Fujii N, Hirshman MF, Goodyear LJ. AS160 regulates insulin‐ and contraction‐stimulated glucose uptake in mouse skeletal muscle. J Biol Chem 281: 31478‐31485, 2006.
 367. Kressel G, Trunz B, Bub A, Hülsmann O, Wolters M, Lichtinghagen R, Stichtenoth DO, Hahn A. Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk. Atherosclerosis 202: 263‐271, 2009.
 368. Krisan AD, Collins DE, Crain AM, Kwong CC, Singh MK, Bernard JR, Yaspelkis BB, III. Resistance training enhances components of the insulin signaling cascade in normal and high‐fat‐fed rodent skeletal muscle. J Appl Physiol 96: 1691‐1700, 2004.
 369. Kriska AM, Pereira MA, Hanson RL, de Courten MP, Zimmet PZ, Alberti KG, Chitson P, Bennett PH, Narayan KM, Knowler WC. Association of physical activity and serum insulin concentrations in two populations at high risk for type 2 diabetes but differing by BMI. Diabetes Care 24: 1175‐1180, 2001.
 370. Krogh‐Madsen R, Thyfault JP, Broholm C, Mortensen OH, Olsen RH, Mounier R, Plomgaard P, van Hall G, Booth FW, Pedersen BK. A 2‐wk reduction of ambulatory activity attenuates peripheral insulin sensitivity. J Appl Physiol 108: 1034‐1040, 2010.
 371. Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: A 1H NMR spectroscopy study. Diabetologia 42: 113‐116, 1999.
 372. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Froguel P, Nagai R, Kimura S, Kadowaki T, Noda T. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 277: 25863‐25866, 2002.
 373. Kurlawalla‐Martinez C, Stiles B, Wang Y, Devaskar SU, Kahn BB, Wu H. Insulin hypersensitivity and resistance to streptozotocin‐induced diabetes in mice lacking PTEN in adipose tissue. Mol Cell Biol 25: 2498‐2510, 2005.
 374. Laaksonen DE, Lakka HM, Salonen JT, Niskanen LK, Rauramaa R, Lakka TA. Low levels of leisure‐time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care 25: 1612‐1618, 2002.
 375. Lacraz G, Giroix M‐H, Kassis N, Coulaud J, Galinier A, Noll C, Cornut M, Schmidlin F, Paul J‐L, Janel N, Irminger J‐C, Kergoat M, Portha B, Donath MY, Ehses JA, Homo‐Delarche F. Islet endothelial activation and oxidative stress gene expression is reduced by IL‐1Ra treatment in the type 2 diabetic GK rat. PLoS One 4: e6963, 2009.
 376. Lagathu C, Bastard JP, Auclair M, Maachi M, Capeau J, Caron M. Chronic interleukin‐6 (IL‐6) treatment increased IL‐6 secretion and induced insulin resistance in adipocyte: Prevention by rosiglitazone. Biochem Biophys Res Commun 311: 372‐379, 2003.
 377. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The metabolic syndrome and total and cardiovascular disease mortality in middle‐aged men. JAMA 288: 2709‐2716, 2002.
 378. Lakka TA, Laaksonen DE, Lakka HM, Mannikko N, Niskanen LK, Rauramaa R, Salonen JT. Sedentary lifestyle, poor cardiorespiratory fitness, and the metabolic syndrome. Med Sci Sports Exerc 35: 1279‐1286, 2003.
 379. LaMonte MJ, Barlow CE, Jurca R, Kampert JB, Church TS, Blair SN. Cardiorespiratory fitness is inversely associated with the incidence of metabolic syndrome: A prospective study of men and women. Circulation 112: 505‐512, 2005.
 380. Landin K, Tengborn L, Smith U. Elevated fibrinogen and plasminogen activator inhibitor (PAI‐1) In hypertension are related to metabolic risk factors for cardiovascular disease. J Intern Med 227: 273‐278, 1990.
 381. Landsberg L. Body fat distribution and cardiovascular risk: A tale of 2 sites. Arch Intern Med 168: 1607‐1608, 2008.
 382. Lang CH, Silvis C, Deshpande N, Nystrom G, Frost RA. Endotoxin stimulates in vivo expression of inflammatory cytokines tumor necrosis factor alpha, interleukin‐1beta, ‐6, and high‐mobility‐group protein‐1 in skeletal muscle. Shock 19: 538‐546, 2003.
 383. Larance M, Ramm G, James DE. The GLUT4 code. Mol Endocrinol 22: 226‐233, 2008.
 384. Larsen J, Andersen M, Kragstrup J, Gram LF. High persistence of statin use in a Danish population: Compliance study 1993–1998. Br J Clin Pharmacol 53: 375‐378, 2002.
 385. Laybutt DR, Preston AM, Akerfeldt MC, Kench JG, Busch AK, Biankin AV, Biden TJ. Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia 50: 752‐763, 2007.
 386. Lazar DF, Saltiel AR. Lipid phosphatases as drug discovery targets for type 2 diabetes. Nat Rev Drug Discov 5: 333‐342, 2006.
 387. LeBlanc J, Nadeau A, Boulay M, Rousseau‐Migneron S. Effects of physical training and adiposity on glucose metabolism and 125I‐insulin binding. J Appl Physiol 46: 235‐239, 1979.
 388. LeBlanc J, Nadeau A, Richard D, Tremblay A. Studies on the sparing effect of exercise on insulin requirements in human subjects. Metabolism 30: 1119‐1124, 1981.
 389. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM. Abnormal splicing of the leptin receptor in diabetic mice. Nature 379: 632‐635, 1996.
 390. Lee J, Kim S‐U, Kang H‐S. Low cardio/respiratory fitness as an independent predictor of metabolic syndrome in Korean young men. Eur J Appl Physiol 108: 633‐639, 2010.
 391. Lee J, O'Hare T, Pilch PF, Shoelson SE. Insulin receptor autophosphorylation occurs asymmetrically. J Biol Chem 268: 4092‐4098, 1993.
 392. Lee J, Pilch PF. The insulin receptor: Structure, function, and signaling. Am J Physiol 266: C319‐C334, 1994.
 393. Lee JM, Kim JH, Son HS, Hong EG, Yu JM, Han KA, Min KW, Chang SA. Valsartan increases circulating adiponectin levels without changing HOMA‐IR in patients with type 2 diabetes mellitus and hypertension. J Int Med Res 38: 234‐241, 2010.
 394. Leiter LA, Lewanczuk RZ. Of the renin‐angiotensin system and reactive oxygen species Type 2 diabetes and angiotensin II inhibition. Am J Hypertens 18: 121‐128, 2005.
 395. Lemieux I, Pascot A, Prud'homme D, Almeras N, Bogaty P, Nadeau A, Bergeron J, Despres JP. Elevated C‐reactive protein: Another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol 21: 961‐967, 2001.
 396. Levin BE, Dunn‐Meynell AA, Banks WA. Obesity‐prone rats have normal blood‐brain barrier transport but defective central leptin signaling before obesity onset. Am J Physiol Regul Integr Comp Physiol 286: R143‐R150, 2004.
 397. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943‐1947, 1997.
 398. Liao Y, Kwon S, Shaughnessy S, Wallace P, Hutto A, Jenkins AJ, Klein RL, Garvey WT. Critical evaluation of adult treatment panel III criteria in identifying insulin resistance with dyslipidemia. Diabetes Care 27: 978‐983, 2004.
 399. Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE. The lipopolysaccharide‐activated toll‐like receptor (TLR)‐4 induces synthesis of the closely related receptor TLR‐2 in adipocytes. J Biol Chem 275: 24255‐24263, 2000.
 400. Little JP, Gillen JB, Percival ME, Safdar A, Tarnopolsky MA, Punthakee Z, Jung ME, Gibala MJ. Low‐volume high‐intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J Appl Physiol 111: 1554‐1560, 2011.
 401. Little JP, Safdar A, Wilkin GP, Tarnopolsky MA, Gibala MJ. A practical model of low‐volume high‐intensity interval training induces mitochondrial biogenesis in human skeletal muscle: Potential mechanisms. J Physiol 588: 1011‐1022, 2010.
 402. Liu G, Hou JC, Watson RT, Pessin JE. Initial entry of IRAP into the insulin‐responsive storage compartment occurs prior to basal or insulin‐stimulated plasma membrane recycling. Am J Physiol Endocrinol Metab 289: E746‐E752, 2005.
 403. Liu J, Kimura A, Baumann CA, Saltiel AR. APS facilitates c‐Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3‐L1 adipocytes. Mol Cell Biol 22: 3599‐3609, 2002.
 404. Loh K, Deng H, Fukushima A, Cai X, Boivin B, Galic S, Bruce C, Shields BJ, Skiba B, Ooms LM, Stepto N, Wu B, Mitchell CA, Tonks NK, Watt MJ, Febbraio MA, Crack PJ, Andrikopoulos S, Tiganis T. Reactive oxygen species enhance insulin sensitivity. Cell metabolism 10: 260‐272, 2009.
 405. Lohmann D, Liebold F, Heilmann W, Senger H, Pohl A. Diminished insulin response in highly trained athletes. Metabolism 27: 521‐524, 1978.
 406. Luiken JJ, Arumugam Y, Dyck DJ, Bell RC, Pelsers MM, Turcotte LP, Tandon NN, Glatz JF, Bonen A. Increased rates of fatty acid uptake and plasmalemmal fatty acid transporters in obese Zucker rats. J Biol Chem 276: 40567‐40573, 2001.
 407. Luiken JJ, Dyck DJ, Han XX, Tandon NN, Arumugam Y, Glatz JF, Bonen A. Insulin induces the translocation of the fatty acid transporter FAT/CD36 to the plasma membrane. Am J Physiol Endocrinol Metab 282: E491‐E495, 2002.
 408. Luotola K, Paakkonen R, Alanne M, Lanki T, Moilanen L, Surakka I, Pietila A, Kahonen M, Nieminen MS, Kesaniemi YA, Peters A, Jula A, Perola M, Salomaa V, and for the Health AIRGENE Study Groups. Association of variation in the interleukin‐1 gene family with diabetes and glucose homeostasis. J Clin Endocrinol Metab 94: 4575‐4583, 2009.
 409. Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL, McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 53: 336‐346, 2004.
 410. MacDougall JD, Hicks AL, MacDonald JR, McKelvie RS, Green HJ, Smith KM. Muscle performance and enzymatic adaptations to sprint interval training. J Appl Physiol 84: 2138‐2142, 1998.
 411. Maeda K, Cao H, Kono K, Gorgun CZ, Furuhashi M, Uysal KT, Cao Q, Atsumi G, Malone H, Krishnan B, Minokoshi Y, Kahn BB, Parker RA, Hotamisligil GS. Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab 1: 107‐119, 2005.
 412. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet‐induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8: 731‐737, 2002.
 413. Maedler K, Dharmadhikari G, Schumann DM, Størling J. Interleukin‐1 beta targeted therapy for type 2 diabetes. Expert Opin Biol Ther 9: 1177‐1188, 2009.
 414. Maedler K, Sergeev P, Ehses JA, Mathe Z, Bosco D, Berney T, Dayer J‐M, Reinecke M, Halban PA, Donath MY. Leptin modulates β cell expression of IL‐1 receptor antagonist and release of IL‐1β in human islets. Proc Nat Acad Sci U S A 101: 8138‐8143, 2004.
 415. Magnussen CG, Koskinen J, Chen W, Thomson R, Schmidt MD, Srinivasan SR, Kivimaki M, Mattsson N, Kahonen M, Laitinen T, Taittonen L, Ronnemaa T, Viikari JSA, Berenson GS, Juonala M, Raitakari OT. Pediatric metabolic syndrome predicts adulthood metabolic syndrome, subclinical atherosclerosis, and type 2 diabetes mellitus but is no better than body mass index alone: The Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study. Circulation 122: 1604‐1611, 2010.
 416. Mahadev K, Wu X, Zilbering A, Zhu L, Lawrence JT, Goldstein BJ. Hydrogen peroxide generated during cellular insulin stimulation is integral to activation of the distal insulin signaling cascade in 3T3‐L1 adipocytes. J Biol Chem 276: 48662‐48669, 2001.
 417. Mahadev K, Zilbering A, Zhu L, Goldstein BJ. Insulin‐stimulated hydrogen peroxide reversibly inhibits protein‐tyrosine phosphatase 1b in vivo and enhances the early insulin action cascade. J Biol Chem 276: 21938‐21942, 2001.
 418. Mao X, Kikani CK, Riojas RA, Langlais P, Wang L, Ramos FJ, Fang Q, Christ‐Roberts CY, Hong JY, Kim R‐Y, Liu F, Dong LQ. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat Cell Biol 8: 516‐523, 2006.
 419. Massiera F, Bloch‐Faure M, Ceiler D, Murakami K, Fukamizu A, Gasc JM, Quignard‐Boulange A, Negrel R, Ailhaud G, Seydoux J, Meneton P, Teboul M. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J 15: 2727‐2729, 2001.
 420. Matsubara Y, Kano K, Kondo D, Mugishima H, Matsumoto T. Differences in adipocytokines and fatty acid composition between two adipocyte fractions of small and large cells in high‐fat diet‐induced obese mice. Ann Nutr Metabol 54: 258‐267, 2009.
 421. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp. Diabetes Care 22: 1462‐1470, 1999.
 422. Matsumoto M, Ogawa W, Akimoto K, Inoue H, Miyake K, Furukawa K, Hayashi Y, Iguchi H, Matsuki Y, Hiramatsu R, Shimano H, Yamada N, Ohno S, Kasuga M, Noda T. PKClambda in liver mediates insulin‐induced SREBP‐1c expression and determines both hepatic lipid content and overall insulin sensitivity. J Clin Invest 112: 935‐944, 2003.
 423. Matthews VB, Allen TL, Risis S, Chan MH, Henstridge DC, Watson N, Zaffino LA, Babb JR, Boon J, Meikle PJ, Jowett JB, Watt MJ, Jansson JO, Bruce CR, Febbraio MA. Interleukin‐6‐deficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia 53: 2431‐2441, 2010.
 424. Matthews VB, Astrom MB, Chan MH, Bruce CR, Krabbe KS, Prelovsek O, Akerstrom T, Yfanti C, Broholm C, Mortensen OH, Penkowa M, Hojman P, Zankari A, Watt MJ, Bruunsgaard H, Pedersen BK, Febbraio MA. Brain‐derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP‐activated protein kinase. Diabetologia 52: 1409‐1418, 2009.
 425. Mauvais‐Jarvis F, Ueki K, Fruman DA, Hirshman MF, Sakamoto K, Goodyear LJ, Iannacone M, Accili D, Cantley LC, Kahn CR. Reduced expression of the murine p85alpha subunit of phosphoinositide 3‐kinase improves insulin signaling and ameliorates diabetes. J Clin Invest 109: 141‐149, 2002.
 426. Mayer‐Davis EJ, D'Agostino R, Jr., Karter AJ, Haffner SM, Rewers MJ, Saad M, Bergman RN, Intensity and amount of physical activity in relation to insulin sensitivity: The Insulin Resistance Atherosclerosis Study. JAMA 279: 669‐674, 1998.
 427. McGettrick AJ, Feener EP, Kahn CR. Human insulin receptor substrate‐1 (IRS‐1) polymorphism G972R causes IRS‐1 to associate with the insulin receptor and inhibit receptor autophosphorylation. J Biol Chem 280: 6441‐6446, 2005.
 428. Mendez‐Hernandez P, Flores Y, Siani C, Lamure M, Dosamantes‐Carrasco LD, Halley‐Castillo E, Huitron G, Talavera J, Gallegos‐Carrillo K, Salmeron J. Physical activity and risk of metabolic syndrome in an urban Mexican cohort. BMC Public Health 9: 276, 2009.
 429. Menzaghi C, Trischitta V, Doria A. Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes 56: 1198‐1209, 2007.
 430. Metcalfe RS, Babraj JA, Fawkner SG, Vollaard NB. Towards the minimal amount of exercise for improving metabolic health: Beneficial effects of reduced‐exertion high‐intensity interval training. Eur J Appl Physiol, 2011.
 431. Mikines KJ. The influence of physical activity and inactivity on insulin action and secretion in man. Acta Physiol Scand Suppl 609: 1‐43, 1992.
 432. Mikines KJ, Dela F, Tronier B, Galbo H. Effect of 7 days of bed rest on dose‐response relation between plasma glucose and insulin secretion. Am J Physiol 257: E43‐E48, 1989.
 433. Mikines KJ, Richter EA, Dela F, Galbo H. Seven days of bed rest decrease insulin action on glucose uptake in leg and whole body. J Appl Physiol 70: 1245‐1254, 1991.
 434. Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H. Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am J Physiol 254: E248‐E259, 1988.
 435. Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H. Effect of training on the dose‐response relationship for insulin action in men. J Appl Physiol 66: 695‐703, 1989.
 436. Mikines KJ, Sonne B, Tronier B, Galbo H. Effects of acute exercise and detraining on insulin action in trained men. J Appl Physiol 66: 704‐711, 1989a.
 437. Mikines KJ, Sonne B, Tronier B, Galbo H. Effects of training and detraining on dose‐response relationship between glucose and insulin secretion. Am J Physiol 256: E588‐E596, 1989b.
 438. Mikus CR, Oberlin DJ, Libla J, Boyle LJ, Thyfault JP. Glycaemic control is improved by 7 days of aerobic exercise training in patients with type 2 diabetes. Diabetologia 55: 1417‐1423, 2012.
 439. Mikus CR, Oberlin DJ, Libla JL, Taylor AM, Booth FW, Thyfault JP. Lowering physical activity impairs glycemic control in healthy volunteers. Med Sci Sports Exerc 44: 225‐231, 2012.
 440. Miller JP, Pratley RE, Goldberg AP, Gordon P, Rubin M, Treuth MS, Ryan AS, Hurley BF. Strength training increases insulin action in healthy 50‐ to 65‐yr‐old men. J Appl Physiol 77: 1122‐1127, 1994.
 441. Miller WJ, Sherman WM, Ivy JL. Effect of strength training on glucose tolerance and post‐glucose insulin response. Med Sci Sports Exerc 16: 539‐543, 1984.
 442. Mills PJ, Hong S, Redwine L, Carter SM, Chiu A, Ziegler MG, Dimsdale JE, Maisel AS. Physical fitness attenuates leukocyte‐endothelial adhesion in response to acute exercise. J Appl Physiol 101: 785‐788, 2006.
 443. Min J, Okada S, Kanzaki M, Elmendorf JS, Coker KJ, Ceresa BP, Syu LJ, Noda Y, Saltiel AR, Pessin JE. Synip: A novel insulin‐regulated syntaxin 4‐binding protein mediating GLUT4 translocation in adipocytes. Mol Cell 3: 751‐760, 1999.
 444. Min L, Leung YM, Tomas A, Watson RT, Gaisano HY, Halban PA, Pessin JE, Hou JC. Dynamin is functionally coupled to insulin granule exocytosis. J Biol Chem 282: 33530‐33536, 2007.
 445. Minoura H, Takeshita S, Kimura C, Hirosumi J, Takakura S, Kawamura I, Seki J, Manda T, Mutoh S. Mechanism by which a novel non‐thiazolidinedione peroxisome proliferator‐activated receptor gamma agonist, FK614, ameliorates insulin resistance in Zucker fatty rats. Diabetes Obes Metab 9: 369‐378, 2007.
 446. Misra A, Alappan NK, Vikram NK, Goel K, Gupta N, Mittal K, Bhatt S, Luthra K. Effect of supervised progressive resistance‐exercise training protocol on insulin sensitivity, glycemia, lipids, and body composition in Asian Indians with type 2 diabetes. Diabetes Care 31: 1282‐1287, 2008.
 447. Moller DE. Potential role of TNF‐[alpha] in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 11: 212‐217, 2000.
 448. Monzavi R, Dreimane D, Geffner ME, Braun S, Conrad B, Klier M, Kaufman FR. Improvement in risk factors for metabolic syndrome and insulin resistance in overweight youth who are treated with lifestyle intervention. Pediatrics 117: e1111‐e1118, 2006.
 449. Moore JB. Non‐alcoholic fatty liver disease: The hepatic consequence of obesity and the metabolic syndrome. Proc Nutr Soc 69: 211‐220, 2010.
 450. Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM. Erralpha and Gabpa/b specify PGC‐1alpha‐dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci U S A 101: 6570‐6575, 2004.
 451. Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H, Yoshimura A. Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet‐induced obesity. Nat Med 10: 739‐743, 2004.
 452. Morris MJ, Chen H, Watts R, Shulkes A, Cameron‐Smith D. Brain neuropeptide Y and CCK and peripheral adipokine receptors: Temporal response in obesity induced by palatable diet. Int J Obes (Lond) 32: 249‐258, 2008.
 453. Morrison JA, Ford ES, Steinberger J. The pediatric metabolic syndrome. Minerva Med 99: 269‐287, 2008.
 454. Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, Rinfret S, Schiffrin EL, Eisenberg MJ. The metabolic syndrome and cardiovascular risk: A systematic review and meta‐analysis. J Am Coll Cardiol 56: 1113‐1132, 2010.
 455. Murata Y, Tsuruzoe K, Kawashima J, Furukawa N, Kondo T, Motoshima H, Igata M, Taketa K, Sasaki K, Kishikawa H, Kahn CR, Toyonaga T, Araki E. IRS‐1 transgenic mice show increased epididymal fat mass and insulin resistance. Biochem Biophys Res Commun 364: 301‐307, 2007.
 456. Murray I, Havel PJ, Sniderman AD, Cianflone K. Reduced body weight, adipose tissue, and leptin levels despite increased energy intake in female mice lacking acylation‐stimulating protein. Endocrinology 141: 1041‐1049, 2000.
 457. Murray I, Sniderman AD, Cianflone K. Enhanced triglyceride clearance with intraperitoneal human acylation stimulating protein in C57BL/6 mice. Am J Physiol 277: E474‐E480, 1999.
 458. Muscari A, Bozzoli C, Puddu GM, Rovinetti C, Fiorentini GP, Roversi RA, Puddu P. Correlations between serum lipids and complement components in adults without demonstrated atherosclerotic disease. Atherosclerosis 81: 111‐118, 1990.
 459. Muse ED, Obici S, Bhanot S, Monia BP, McKay RA, Rajala MW, Scherer PE, Rossetti L. Role of resistin in diet‐induced hepatic insulin resistance. J Clin Invest 114: 232‐239, 2004.
 460. Myers MG, Jr., Grammer TC, Brooks J, Glasheen EM, Wang LM, Sun XJ, Blenis J, Pierce JH, White MF. The pleckstrin homology domain in insulin receptor substrate‐1 sensitizes insulin signaling. J Biol Chem 270: 11715‐11718, 1995.
 461. Nassis GP, Papantakou K, Skenderi K, Triandafillopoulou M, Kavouras SA, Yannakoulia M, Chrousos GP, Sidossis LS. Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls. Metabolism 54: 1472‐1479, 2005.
 462. Nieto‐Vazquez I, Fernández‐Veledo S, de Alvaro C, Rondinone CM, Valverde AM, Lorenzo M. Protein–tyrosine phosphatase 1B–deficient myocytes show increased insulin sensitivity and protection against tumor necrosis factor‐α–induced insulin resistance. Diabetes 56: 404‐413, 2007.
 463. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15: 914‐920, 2009.
 464. Niu W, Bilan PJ, Yu J, Gao J, Boguslavsky S, Schertzer JD, Chu G, Yao Z, Klip A. PKCepsilon regulates contraction‐stimulated GLUT4 traffic in skeletal muscle cells. J Cell Physiol 226: 173‐180, 2011.
 465. Nollen EAA, Morimoto RI. Chaperoning signaling pathways: Molecular chaperones as stress‐sensing ‘heat shock’ proteins. J Cell Sci 115: 2809‐2816, 2002.
 466. Norheim F, Raastad T, Thiede B, Rustan AC, Drevon CA, Haugen F. Proteomic identification of secreted proteins from human skeletal muscle cells and expression in response to strength training. Am J Physiol Endocrinol Metab 301: E1013‐E1021, 2011.
 467. Norquay LD, D'Aquino KE, Opare‐Addo LM, Kuznetsova A, Haas M, Bluestone JA, White MF. Insulin receptor substrate‐2 in beta‐cells decreases diabetes in nonobese diabetic mice. Endocrinology 150: 4531‐4540, 2009.
 468. O'Neill TJ, Craparo A, Gustafson TA. Characterization of an interaction between insulin receptor substrate 1 and the insulin receptor by using the two‐hybrid system. Mol Cell Biol 14: 6433‐6442, 1994.
 469. Odegaard JI, Ricardo‐Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A. Macrophage‐specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447: 1116‐1120, 2007.
 470. Ofei F, Hurel S, Newkirk J, Sopwith M, Taylor R. Effects of an engineered human anti‐TNF‐alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45: 881‐885, 1996.
 471. Ohman MK, Wright AP, Wickenheiser KJ, Luo W, Russo HM, Eitzman DT. Monocyte chemoattractant protein‐1 deficiency protects against visceral fat‐induced atherosclerosis. Arterioscler Thromb Vasc Biol 30: 1151‐1158, 2010.
 472. Ohmori R, Momiyama Y, Kato R, Taniguchi H, Ogura M, Ayaori M, Nakamura H, Ohsuzu F. Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease. J Am Coll Cardiol 46: 379‐380, 2005.
 473. Ohmura K, Ishimori N, Ohmura Y, Tokuhara S, Nozawa A, Horii S, Andoh Y, Fujii S, Iwabuchi K, Onoe K, Tsutsui H. Natural killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet‐induced obese mice. Arterioscler Thromb Vasc Biol 30: 193‐199, 2010.
 474. Okura T, Nakata Y, Ohkawara K, Numao S, Katayama Y, Matsuo T, Tanaka K. Effects of aerobic exercise on metabolic syndrome improvement in response to weight reduction[ast][ast]. Obesity 15: 2478‐2484, 2007.
 475. Old LJ. Tumor necrosis factor (TNF). Science 230: 630‐632, 1985.
 476. Olsen RH, Krogh‐Madsen R, Thomsen C, Booth FW, Pedersen BK. Metabolic responses to reduced daily steps in healthy nonexercising men. JAMA 299: 1261‐1263, 2008.
 477. Olson TP, Dengel DR, Leon AS, Schmitz KH. Changes in inflammatory biomarkers following one‐year of moderate resistance training in overweight women. Int J Obes (Lond) 31: 996‐1003, 2007.
 478. Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S, and for the Diabetes Prevention Program Research Group. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: The diabetes prevention program randomized trial. Ann Intern Med 142: 611‐619, 2005.
 479. Osawa H, Yamada K, Onuma H, Murakami A, Ochi M, Kawata H, Nishimiya T, Niiya T, Shimizu I, Nishida W, Hashiramoto M, Kanatsuka A, Fujii Y, Ohashi J, Makino H. The G/G genotype of a resistin single‐nucleotide polymorphism at ‐420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3. Am J Hum Genet 75: 678‐686, 2004.
 480. Oshida Y, Yamanouchi K, Hayamizu S, Nagasawa J, Ohsawa I, Sato Y. Effects of training and training cessation on insulin action. Int J Sports Med 12: 484‐486, 1991.
 481. Oshida Y, Yamanouchi K, Hayamizu S, Sato Y. Long‐term mild jogging increases insulin action despite no influence on body mass index or VO2 max. J Appl Physiol 66: 2206‐2210, 1989.
 482. Oshima Y, Ouchi N, Sato K, Izumiya Y, Pimentel DR, Walsh K. Follistatin‐like 1 is an Akt‐regulated cardioprotective factor that is secreted by the heart. Circulation 117: 3099‐3108, 2008.
 483. Ostergard T, Andersen JL, Nyholm B, Lund S, Nair KS, Saltin B, Schmitz O. Impact of exercise training on insulin sensitivity, physical fitness, and muscle oxidative capacity in first‐degree relatives of type 2 diabetic patients. Am J Physiol Endocrinol Metab 290: E998‐E1005, 2006.
 484. Ouchi N, Oshima Y, Ohashi K, Higuchi A, Ikegami C, Izumiya Y, Walsh K. Follistatin‐like 1, a secreted muscle protein, promotes endothelial cell function and revascularization in ischemic tissue through a nitric‐oxide synthase‐dependent mechanism. J Biol Chem 283: 32802‐32811, 2008.
 485. Owyang AM, Maedler K, Gross L, Yin J, Esposito L, Shu L, Jadhav J, Domsgen E, Bergemann J, Lee S, Kantak S. XOMA 052, an anti‐IL‐1{beta} monoclonal antibody, improves glucose control and {beta}‐cell function in the diet‐induced obesity mouse model. Endocrinology 151: 2515‐2527, 2010.
 486. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306: 457‐461, 2004.
 487. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Gorgun CZ, Hotamisligil GS. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of tType 2 diabetes. Science 313: 1137‐1140, 2006.
 488. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: Prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988‐1994. Arch Intern Med 163: 427‐436, 2003.
 489. Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 300: 472‐476, 2003.
 490. Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, Landaker EJ, Goldfine AB, Mun E, DeFronzo R, Finlayson J, Kahn CR, Mandarino LJ. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 100: 8466‐8471, 2003.
 491. Pearce LR, Komander D, Alessi DR. The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol 11: 9‐22, 2010.
 492. Pedersen BK, Febbraio M. Muscle‐derived interleukin‐6–A possible link between skeletal muscle, adipose tissue, liver, and brain. Brain Behav Immun 19: 371‐376, 2005.
 493. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: Focus on muscle‐derived interleukin‐6. Physiol Rev 88: 1379‐1406, 2008.
 494. Pedersen BK, Steensberg A, Keller P, Keller C, Fischer C, Hiscock N, van Hall G, Plomgaard P, Febbraio MA. Muscle‐derived interleukin‐6: Lipolytic, anti‐inflammatory and immune regulatory effects. Pflügers Arch 446: 9‐16, 2003.
 495. Pederson TM, Kramer DL, Rondinone CM. Serine/threonine phosphorylation of IRS‐1 triggers its degradation: Possible regulation by tyrosine phosphorylation. Diabetes 50: 24‐31, 2001.
 496. Peeters RA, Veerkamp JH, Geurts van Kessel A, Kanda T, Ono T. Cloning of the cDNA encoding human skeletal‐muscle fatty‐acid‐binding protein, its peptide sequence and chromosomal localization. Biochem J 276 (Pt 1): 203‐207, 1991.
 497. Pellmé F, Smith U, Funahashi T, Matsuzawa Y, Brekke H, Wiklund O, Taskinen M‐R, Jansson P‐A. Circulating adiponectin levels are reduced in nonobese but insulin‐resistant first‐degree relatives of type 2 diabetic patients. Diabetes 52: 1182‐1186, 2003.
 498. Perseghin G, Price TB, Petersen KF, Roden M, Cline GW, Gerow K, Rothman DL, Shulman GI. Increased glucose transport‐phosphorylation and muscle glycogen synthesis after exercise training in insulin‐resistant subjects. N Engl J Med 335: 1357‐1362, 1996.
 499. Perseghin G, Scifo P, De Cobelli F, Pagliato E, Battezzati A, Arcelloni C, Vanzulli A, Testolin G, Pozza G, Del Maschio A, Luzi L. Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: A 1H‐13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 48: 1600‐1606, 1999.
 500. Pessin JE, Saltiel AR. Signaling pathways in insulin action: Molecular targets of insulin resistance. J Clin Invest 106: 165‐169, 2000.
 501. Pessin JE, Thurmond DC, Elmendorf JS, Coker KJ, Okada S. Molecular basis of insulin‐stimulated GLUT4 vesicle trafficking. Location! Location! Location! J Biol Chem 274: 2593‐2596, 1999.
 502. Petersen AMW, Pedersen BK. The anti‐inflammatory effect of exercise. J Appl Physiol 98: 1154‐1162, 2005.
 503. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin‐resistant offspring of patients with type 2 diabetes. N Engl J Med 350: 664‐671, 2004.
 504. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291: 1730‐1737, 2004.
 505. Pitsavos C, Panagiotakos DB, Chrysohoou C, Kavouras S, Stefanadis C. The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: The ATTICA study. Eur J Cardiovasc Prev Rehabil 12: 151‐158, 2005.
 506. Poehlman ET, Dvorak RV, DeNino WF, Brochu M, Ades PA. Effects of resistance training and endurance training on insulin sensitivity in nonobese, young women: A controlled randomized trial. J Clin Endocrinol Metab 85: 2463‐2468, 2000.
 507. Polak J, Moro C, Klimcakova E, Hejnova J, Majercik M, Viguerie N, Langin D, Lafontan M, Stich V, Berlan M. Dynamic strength training improves insulin sensitivity and functional balance between adrenergic alpha 2A and beta pathways in subcutaneous adipose tissue of obese subjects. Diabetologia 48: 2631‐2640, 2005.
 508. Poltorak A, Smirnova I, He X, Liu M‐Y, Van Huffel C, Birdwell D, Alejos E, Silva M, Du X, Thompson P, Chan EKL, Ledesma J, Roe B, Clifton S, Vogel SN, Beutler B. Genetic and physical mapping of the Lps locus: Identification of the toll‐4 receptor as a candidate gene in the critical region. Blood Cells Mol Dis 24: 340‐355, 1998.
 509. Pomeroy C, Mitchell J, Eckert E, Raymond N, Crosby R, Dalmasso AP. Effect of body weight and caloric restriction on serum complement proteins, including factor D/adipsin: Studies in anorexia nervosa and obesity. Clin Exp Immunol 108: 507‐515, 1997.
 510. Potashnik R, Bloch‐Damti A, Bashan N, Rudich A. IRS1 degradation and increased serine phosphorylation cannot predict the degree of metabolic insulin resistance induced by oxidative stress. Diabetologia 46: 639‐648, 2003.
 511. Previs SF, Withers DJ, Ren J‐M, White MF, Shulman GI. Contrasting effects of IRS‐1 versus IRS‐2 gene disruption on carbohydrate and lipid metabolism in vivo. J Biol Chem 275: 38990‐38994, 2000.
 512. Prodi E, Obici S. Minireview: The brain as a molecular target for diabetic therapy. Endocrinology 147: 2664‐2669, 2006.
 513. Qi L, Zhang C, van Dam RM, Hu FB. Interleukin‐6 genetic variability and adiposity: Associations in two prospective cohorts and systematic review in 26,944 individuals. J Clin Endocrinol Metab 92: 3618‐3625, 2007.
 514. Quinn LS, Anderson BG, Strait‐Bodey L, Stroud AM, Argiles JM. Oversecretion of interleukin‐15 from skeletal muscle reduces adiposity. Am J Physiol Endocrinol Metab 296: E191‐E202, 2009.
 515. Rabe B, Chalaris A, May U, Waetzig GH, Seegert D, Williams AS, Jones SA, Rose‐John S, Scheller J. Transgenic blockade of interleukin 6 transsignaling abrogates inflammation. Blood 111: 1021‐1028, 2008.
 516. Rajala MW, Qi Y, Patel HR, Takahashi N, Banerjee R, Pajvani UB, Sinha MK, Gingerich RL, Scherer PE, Ahima RS. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes 53: 1671‐1679, 2004.
 517. Rana JS, Nasir K, Santos RD, Roguin A, Orakzai SH, Carvalho JA, Meneghello R, Blumenthal RS. Increased level of cardiorespiratory fitness blunts the inflammatory response in metabolic syndrome. Int J Cardiol 110: 224‐230, 2006.
 518. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty‐acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1: 785‐789, 1963.
 519. Rangwala SM, Rich AS, Rhoades B, Shapiro JS, Obici S, Rossetti L, Lazar MA. Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 53: 1937‐1941, 2004.
 520. Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H. Evidence for a release of BDNF from the brain during exercise. Exp Physiol 94: 1062‐106, 2009.
 521. Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93: s64‐s73, 2008.
 522. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37: 1595‐1607, 1988.
 523. Reaven GM. Insulin resistance, cardiovascular disease, and the metabolic syndrome: How well do the emperor's clothes fit? Diabetes Care 27: 1011‐1012, 2004.
 524. Reaven GM. The metabolic syndrome: Requiescat in pace. Clin Chem 51: 931‐938, 2005.
 525. Reaven GM. The metabolic syndrome: Is this diagnosis necessary? Am J Clin Nutr 83: 1237‐1247, 2006.
 526. Reaven GM, Chen YD, Jeppesen J, Maheux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles. J Clin Invest 92: 141‐146, 1993.
 527. Reaven GM, Risser TE, Chen Y‐DI, Reaven EP. Characterizaiton of a model of dietary‐induced hypetriglyceridemia in young, nonobese rats. J Lipid Res 20: 371‐378, 1979.
 528. Reil TD, Barnard RJ, Kashyap VS, Roberts CK, Gelabert HA. Diet‐induced changes in endothelial dependent relaxation of the rat aorta. J Surg Res 85: 96‐100, 1999.
 529. Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111: 932‐939, 2005.
 530. Reinehr T, Kleber M, Toschke AM. Lifestyle intervention in obese children is associated with a decrease of the metabolic syndrome prevalence. Atherosclerosis 207: 174‐180, 2009.
 531. Ren JM. Overexpression of Glut4 protein in muscle increases basal and insulin‐stimulated whole body glucose disposal in conscious mice. J Clin Invest 95: 429‐432, 1995.
 532. Rennie KL, McCarthy N, Yazdgerdi S, Marmot M, Brunner E. Association of the metabolic syndrome with both vigorous and moderate physical activity. Int J Epidemiol 32: 600‐606, 2003.
 533. Ress C, Tschoner A, Engl J, Klaus A, Tilg H, Ebenbichler CF, Patsch JR, Kaser S. Effect of bariatric surgery on circulating chemerin levels. Eur J Clin Invest 40: 277‐280, 2010.
 534. Retnakaran R, Shen S, Hanley AJ, Vuksan V, Hamilton JK, Zinman B. Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test. Obesity 16: 1901‐1907, 2008.
 535. Rewers M, Zaccaro D, D'Agostino R, Haffner S, Saad MF, Selby JV, Bergman R, Savage P. Insulin sensitivity, insulinemia, and coronary artery disease: The Insulin Resistance Atherosclerosis Study. Diabetes Care 27: 781‐787, 2004.
 536. Reynolds IVTH, Supiano MA, Dengel DR. Resistance training enhances insulin‐mediated glucose disposal with minimal effect on the tumor necrosis factor‐alpha system in older hypertensives. Metabolism 53: 397‐402, 2004.
 537. Reynolds THIV, Supiano MA, Dengel DR. Regional differences in glucose clearance: Effects of insulin and resistance training on arm and leg glucose clearance in older hypertensive individuals. J Appl Physiol 102: 985‐991, 2007.
 538. Ribas V, Drew BG, Le JA, Soleymani T, Daraei P, Sitz D, Mohammad L, Henstridge DC, Febbraio MA, Hewitt SC, Korach KS, Bensinger SJ, Hevener AL. Myeloid‐specific estrogen receptor {alpha} deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development. Proc Nat Acad Sci U S A 108: 16457‐16462, 2011.
 539. Richards JC, Johnson TK, Kuzma JN, Lonac MC, Schweder MM, Voyles WF, Bell C. Short‐term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to beta‐adrenergic stimulation. J Physiol 588: 2961‐2972, 2010.
 540. Richter EA, Kiens B, Wojtaszewski JFP. Can exercise mimetics substitute for exercise? Cell Metabolism 8: 96‐98, 2008.
 541. Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, Kelley DE. Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes 54: 8‐14, 2005.
 542. Roberts CK, Ng C, Hama S, Eliseo AJ, Barnard RJ. Effect of a short‐term diet and exercise intervention on inflammatory/anti‐inflammatory properties of HDL in overweight/obese men with cardiovascular risk factors. J Appl Physiol 101: 1727‐1732, 2006.
 543. Roberts CK, Vaziri ND, Liang KH, Barnard RJ. Reversibility of chronic experimental syndrome X by diet. Hypertension 37: 1323‐1328, 2001.
 544. Roepstorff C, Steffensen CH, Madsen M, Stallknecht B, Kanstrup IL, Richter EA, Kiens B. Gender differences in substrate utilization during submaximal exercise in endurance‐trained subjects. Am J Physiol Endocrinol Metab 282: E435‐E447, 2002.
 545. Rogers MA, King DS, Hagberg JM, Ehsani AA, Holloszy JO. Effect of 10 days of physical inactivity on glucose tolerance in master athletes. J Appl Physiol 68: 1833‐1837, 1990.
 546. Roh SG, Song SH, Choi KC, Katoh K, Wittamer V, Parmentier M, Sasaki S. Chemerin–a new adipokine that modulates adipogenesis via its own receptor. Biochem Biophys Res Commun 362: 1013‐1018, 2007.
 547. Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: An update. Clin Endocrinol 64: 355‐365, 2006.
 548. Ropelle ER, Fernandes MF, Flores MB, Ueno M, Rocco S, Marin R, Cintra DE, Velloso LA, Franchini KG, Saad MJ, Carvalheira JB. Central exercise action increases the AMPK and mTOR response to leptin. PLoS One 3: e3856, 2008.
 549. Ropelle ER, Pauli JR, Prada PO, de Souza CT, Picardi PK, Faria MC, Cintra DE, Fernandes MF, Flores MB, Velloso LA, Saad MJ, Carvalheira JB. Reversal of diet‐induced insulin resistance with a single bout of exercise in the rat: The role of PTP1B and IRS‐1 serine phosphorylation. J Physiol 577: 997‐1007, 2006.
 550. Rose‐John S, Scheller J, Elson G, Jones SA. Interleukin‐6 biology is coordinated by membrane‐bound and soluble receptors: Role in inflammation and cancer. J Leukoc Biol 80: 227‐236, 2006.
 551. Rosen OM, Herrera R, Olowe Y, Petruzzelli LM, Cobb MH. Phosphorylation activates the insulin receptor tyrosine protein kinase. Proc Natl Acad Sci U S A 80: 3237‐3240, 1983.
 552. Ross A, Leveritt M. Long‐term metabolic and skeletal muscle adaptations to short‐sprint training: Implications for sprint training and tapering. Sports Med 31: 1063‐1082, 2001.
 553. Ross R, Aru J, Freeman J, Hudson R, Janssen I. Abdominal adiposity and insulin resistance in obese men. Am J Physiol Endocrinol Metab 282: E657‐E663, 2002.
 554. Rotter V, Nagaev I, Smith U. Interleukin‐6 (IL‐6) induces insulin resistance in 3T3‐L1 adipocytes and is, like IL‐8 and tumor necrosis factor‐alpha, overexpressed in human fat cells from insulin‐resistant subjects. J Biol Chem 278: 45777‐45784, 2003.
 555. Rui L, Aguirre V, Kim JK, Shulman GI, Lee A, Corbould A, Dunaif A, White MF. Insulin/IGF‐1 and TNF‐alpha stimulate phosphorylation of IRS‐1 at inhibitory Ser307 via distinct pathways. J Clin Invest 107: 181‐189, 2001.
 556. Russell AP. Lipotoxicity: The obese and endurance‐trained paradox. Int J Obes Relat Metab Disord 28: S66‐S71, 2004.
 557. Ryan AS, Hurlbut DE, Lott ME, Ivey FM, Fleg J, Hurley BF, Goldberg AP. Insulin action after resistive training in insulin resistant older men and women. J Am Geriatr Soc 49: 247‐253, 2001.
 558. Ryan AS, Pratley RE, Goldberg AP, Elahi D. Resistive training increases insulin action in postmenopausal women. J Gerontol A Biol Sci Med Sci 51: M199‐M205, 1996.
 559. Saberi M, Woods NB, de Luca C, Schenk S, Lu JC, Bandyopadhyay G, Verma IM, Olefsky JM. Hematopoietic cell‐specific deletion of toll‐like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high‐fat‐fed mice. Cell Metab 10: 419‐429, 2009.
 560. Sadagurski M, Norquay L, Farhang J, D'Aquino K, Copps K, White MF. Human IL6 enhances leptin action in mice. Diabetologia, 2009.
 561. Sajan MP, Standaert ML, Miura A, Kahn CR, Farese RV. Tissue‐specific differences in activation of atypical protein kinase C and protein kinase B in muscle, liver, and adipocytes of insulin receptor substrate‐1 knockout mice. Mol Endocrinol 18: 2513‐2521, 2004.
 562. Saleh J, Blevins JE, Havel PJ, Barrett JA, Gietzen DW, Cianflone K. Acylation stimulating protein (ASP) acute effects on postprandial lipemia and food intake in rodents. Int J Obes Relat Metab Disord 25: 705‐713, 2001.
 563. Saltevo J, Vanhala M, Kautiainen H, Kumpusalo E, Laakso M. Association of C‐reactive protein, interleukin‐1 receptor antagonist and adiponectin with the metabolic syndrome. Mediators Inflamm 2007: 93573, 2007.
 564. Saltiel AR, Pessin JE. Insulin signaling in microdomains of the plasma membrane. Traffic 4: 711‐716, 2003.
 565. Sano H, Kane S, Sano E, Miinea CP, Asara JM, Lane WS, Garner CW, Lienhard GE. Insulin‐stimulated phosphorylation of a Rab GTPase‐activating protein regulates GLUT4 translocation. J Biol Chem 278: 14599‐14602, 2003.
 566. Santos AC, Ebrahim S, Barros H. Alcohol intake, smoking, sleeping hours, physical activity and the metabolic syndrome. Preventive Medicine 44: 328‐334, 2007.
 567. Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Nat Acad Sci U S A 100: 7265‐7270, 2003.
 568. Sasaoka T, Wada T, Tsuneki H. Lipid phosphatases as a possible therapeutic target in cases of type 2 diabetes and obesity. Pharmacol Ther 112: 799‐809, 2006.
 569. Sato Y, Iguchi A, Sakamoto N. Biochemical determination of training effects using insulin clamp technique. Horm Metab Res 16: 483‐486, 1984.
 570. Satoh H, Nguyen MT, Miles PD, Imamura T, Usui I, Olefsky JM. Adenovirus‐mediated chronic “hyper‐resistinemia” leads to in vivo insulin resistance in normal rats. J Clin Invest 114: 224‐231, 2004.
 571. Sattar N, Gaw A, Scherbakova O, Ford I, O'Reilly DSJ, Haffner SM, Isles C, Macfarlane PW, Packard CJ, Cobbe SM, Shepherd J. Metabolic syndrome with and without C‐reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 108: 414‐419, 2003.
 572. Sauter NS, Schulthess FT, Galasso R, Castellani LW, Maedler K. The antiinflammatory cytokine interleukin‐1 receptor antagonist protects from high‐fat diet‐induced hyperglycemia. Endocrinology 149: 2208‐2218, 2008.
 573. Sawka‐Verhelle D, Filloux C, Tartare‐Deckert S, Mothe I, Obberghen E. Identification of stat 5B as a substrate of the insulin receptor. Eur J Biochem 250: 411‐417, 1997.
 574. Schaffer JE, Lodish HF. Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell 79: 427‐436, 1994.
 575. Scheck SH, Barnard RJ, Lawani LO, Youngren IF, Martin DA, Singh, R. Effects of NIDDM on the glucose transport system in human skeletal muscle. Diabetes Res 16: 111‐119, 1991.
 576. Schmitz‐Peiffer C. Protein kinase C and lipid‐induced insulin resistance in skeletal muscle. Ann N Y Acad Sci 967: 146‐157, 2002.
 577. Seals DR, Hagberg JM, Allen WK, Hurley BF, Dalsky GP, Ehsani AA, Holloszy JO. Glucose tolerance in young and older athletes and sedentary men. J Appl Physiol 56: 1521‐1525, 1984.
 578. Seals DR, Hagberg JM, Hurley BF, Ehsani AA, Holloszy JO. Effects of endurance training on glucose tolerance and plasma lipid levels in older men and women. JAMA 252: 645‐649, 1984.
 579. Sebastian D, Herrero L, Serra D, Asins G, Hegardt FG. CPT I overexpression protects L6E9 muscle cells from fatty acid‐induced insulin resistance. Am J Physiol Endocrinol Metab 292: E677‐E686, 2007.
 580. Seino S, Seino M, Nishi S, Bell GI. Structure of the human insulin receptor gene and characterization of its promoter. Proc Natl Acad Sci U S A 86: 114‐118, 1989.
 581. Seino Y, Ikeda U, Takahashi M, Hojo Y, Irokawa M, Kasahara T, Shimada K. Expression of monocyte chemoattractant protein‐1 in vascular tissue. Cytokine 7: 575‐579, 1995.
 582. Sell H, Laurencikiene J, Taube A, Eckardt K, Cramer A, Horrighs A, Arner P, Eckel J. Chemerin is a novel adipocyte‐derived factor inducing insulin resistance in primary human skeletal muscle cells. Diabetes 58: 2731‐2740, 2009.
 583. Senn JJ. Toll‐like receptor‐2 is essential for the development of palmitate‐induced insulin resistance in myotubes. J Biol Chem 281: 26865‐26875, 2006.
 584. Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin‐6 induces cellular insulin resistance in hepatocytes. Diabetes 51: 3391‐3399, 2002.
 585. Sethi JK, Xu H, Uysal KT, Wiesbrock SM, Scheja L, Hotamisligil GS. Characterisation of receptor‐specific TNF[alpha] functions in adipocyte cell lines lacking type 1 and 2 TNF receptors. FEBS Letters 469: 77‐82, 2000.
 586. Shaibi GQ, Cruz ML, Ball GD, Weigensberg MJ, Salem GJ, Crespo NC, Goran MI. Effects of resistance training on insulin sensitivity in overweight Latino sdolescent males. Med Sci Sports Exerc 38: 1208‐1215, 2006.
 587. Shanely RA, Nieman DC, Henson DA, Jin F, Knab AM, Sha W. Inflammation and oxidative stress are lower in physically fit and active adults. Scand J Med Sci Sports, 2011. DOI: 10.1111/j.1600‐0838.2011.01373.x.
 588. Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A. Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 27: 2450‐2457, 2004.
 589. Shima Y, Kitaoka K, Yoshiki Y, Maruhashi Y, Tsuyama T, Tomita K. Effect of heat shock preconditioning on ROS scavenging activity in rat skeletal muscle after downhill running. J Physiol Sci 58: 341‐348, 2008.
 590. Shisheva A. Phosphoinositides in insulin action on GLUT4 dynamics: Not just PtdIns(3,4,5)P3. Am J Physiol Endocrinol Metab 295: E536‐E544, 2008.
 591. Shojaee‐Moradie F, Baynes K, Pentecost C, Bell J, Thomas E, Jackson N, Stolinski M, Whyte M, Lovell D, Bowes S, Gibney J, Jones R, Umpleby A. Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism. Diabetologia 50: 404‐413, 2007.
 592. Short KR, Vittone JL, Bigelow ML, Proctor DN, Rizza RA, Coenen‐Schimke JM, Nair KS. Impact of aerobic exercise training on age‐related changes in insulin sensitivity and muscle oxidative capacity. Diabetes 52: 1888‐1896, 2003.
 593. Simoneau JA, Kelley DE. Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. J Appl Physiol 83: 166‐171, 1997.
 594. Simoneau JA, Veerkamp JH, Turcotte LP, Kelley DE. Markers of capacity to utilize fatty acids in human skeletal muscle: Relation to insulin resistance and obesity and effects of weight loss. FASEB J 13: 2051‐2060, 1999.
 595. Simons LA, Levis G, Simons J. Apparent discontinuation rates in patients prescribed lipid‐lowering drugs. Med J Aust 164: 208‐211, 1996.
 596. Singh U, Devaraj S, Jialal I. C‐reactive protein stimulates myeloperoxidase release from polymorphonuclear cells and monocytes: Implications for acute coronary syndromes. Clin Chem 55: 361‐364, 2009.
 597. Sleigh A, Raymond‐Barker P, Thackray K, Porter D, Hatunic M, Vottero A, Burren C, Mitchell C, McIntyre M, Brage S, Carpenter TA, Murgatroyd PR, Brindle KM, Kemp GJ, O'Rahilly S, Semple RK, Savage DB. Mitochondrial dysfunction in patients with primary congenital insulin resistance. J Clin Invest 121: 2457‐2461, 2011.
 598. Smith SR, Bai F, Charbonneau C, Janderova L, Argyropoulos G. A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. Diabetes 52: 1611‐1618, 2003.
 599. Smutok MA, Kokkinos PF, Farmer C, Dawson P, Shulman R, DeVane‐Bell J, Patterson J, Charabogos C, Goldberg AP, Hurley BF. Aerobic versus strength training for risk factor intervension in middle‐aged men at high risk for coronary heart disease. Metabolism 42 (2): 177‐184, 1993.
 600. Smutok MA, Reece C, Kokkinos PF, Farmer CM, Dawson PK, DeVane J, Patterson J, Goldberg AP, Hurley BF. Effects of exercise training modality on glucose tolerance in men with abnormal glucose regulation. Int J Sports Med 15: 283‐289, 1994.
 601. Staib JL, Tumer N, Powers SK. Increased temperature and protein oxidation lead to HSP72 mRNA and protein accumulation in the in vivo exercised rat heart. Exp Physiol 94: 71‐80, 2009.
 602. Standaert ML, Sajan MP, Miura A, Kanoh Y, Chen HC, Farese RV, Jr., and Farese RV. Insulin‐induced activation of atypical protein kinase C, but not protein kinase B, is maintained in diabetic (ob/ob and Goto‐Kakazaki) liver. Contrasting insulin signaling patterns in liver versus muscle define phenotypes of type 2 diabetic and high fat‐induced insulin‐resistant states. J Biol Chem 279: 24929‐24934, 2004.
 603. Steensberg A, Keller C, Starkie RL, Osada T, Febbraio MA, Pedersen BK. IL‐6 and TNF‐alpha expression in, and release from, contracting human skeletal muscle. Am J Physiol Endocrinol Metab 283: E1272‐E1278, 2002.
 604. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low‐density lipoprotein that increase its atherogenicity. N Engl J Med 320: 915‐924, 1989.
 605. Steinberg GR, Dyck DJ. Development of leptin resistance in rat soleus muscle in response to high‐fat diets. Am J Physiol Endocrinol Metab 279: E1374‐E1382, 2000.
 606. Steinberg GR, McAinch AJ, Chen MB, O'Brien PE, Dixon JB, Cameron‐Smith D, Kemp BE. The suppressor of cytokine signaling 3 inhibits leptin activation of AMP‐kinase in cultured skeletal muscle of obese humans. J Clin Endocrinol Metab 91: 3592‐3597, 2006.
 607. Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ. Leptin increases FA oxidation in lean but not obese human skeletal muscle: Evidence of peripheral leptin resistance. Am J Physiol Endocrinol Metab 283: E187‐E192, 2002.
 608. Steinberg GR, Smith AC, Wormald S, Malenfant P, Collier C, Dyck DJ. Endurance training partially reverses dietary‐induced leptin resistance in rodent skeletal muscle. Am J Physiol Endocrinol Metab 286: E57‐E63, 2004.
 609. Stenbit AE, Tsao TS, Li J, Burcelin R, Geenen DL, Factor SM, Houseknecht K, Katz EB, Charron MJ. GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat Med 3: 1096‐1101, 1997.
 610. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 409: 307‐312, 2001.
 611. Steppan CM, Brown EJ, Wright CM, Bhat S, Banerjee RR, Dai CY, Enders GH, Silberg DG, Wen X, Wu GD, Lazar MA. A family of tissue‐specific resistin‐like molecules. Proc Natl Acad Sci U S A 98: 502‐506, 2001.
 612. Steppan CM, Wang J, Whiteman EL, Birnbaum MJ, Lazar MA. Activation of SOCS‐3 by resistin. Mol Cell Biol 25: 1569‐1575, 2005.
 613. Stewart KJ, Bacher AC, Turner K, Lim JG, Hees PS, Shapiro EP, Tayback M, Ouyang P. Exercise and risk factors associated with metabolic syndrome in older adults. Am J Prev Med 28: 9‐18, 2005.
 614. Stiles B, Wang Y, Stahl A, Bassilian S, Lee WP, Kim Y‐J, Sherwin R, Devaskar S, Lesche R, Magnuson MA, Wu H. Live‐specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity. Proc Nat Acad Sci U S A 101: 2082‐2087, 2004.
 615. Stiles BL, Kuralwalla‐Martinez C, Guo W, Gregorian C, Wang Y, Tian J, Magnuson MA, Wu H. Selective deletion of pten in pancreatic {beta} cells leads to increased islet mass and resistance to STZ‐induced diabetes. Mol Cell Biol 26: 2772‐2781, 2006.
 616. Stone S, Abkevich V, Russell DL, Riley R, Timms K, Tran T, Trem D, Frank D, Jammulapati S, Neff CD, Iliev D, Gress R, He G, Frech GC, Adams TD, Skolnick MH, Lanchbury JS, Gutin A, Hunt SC, Shattuck D. TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition. Hum Mol Genet 15: 2709‐2720, 2006.
 617. Stuart CA, Shangraw RE, Prince MJ, Peters EJ, Wolfe RR. Bed‐rest‐induced insulin resistance occurs primarily in muscle. Metabolism 37: 802‐806, 1988.
 618. Summers SA. Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 45: 42‐72, 2006.
 619. Sun X, M M, MG M, EM G, JM B, CR K, and MF W. Expression and function of IRS‐1 in insulin signal transmission. J Biol Chem 267: 22662‐22672, 1992.
 620. Sun X, Rothenberg P, Kahn CR, Backer J, Araki E, Wilden P, Cahill D, Goldstein B, White MF. Structure of the insulin receptor substrate IRS‐1 defines a unique signal transduction protein. Nature 352: 73‐77, 1991.
 621. Suzuki T, Hirata K, Elkind MS, Jin Z, Rundek T, Miyake Y, Boden‐Albala B, Di Tullio MR, Sacco R, Homma S. Metabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: The Northern Manhattan Study (NOMAS). Am Heart J 156: 405‐410, 2008.
 622. Sweeney G, Somwar R, Ramlal T, Volchuk A, Ueyama A, Klip A. An inhibitor of p38 mitogen‐activated protein kinase prevents insulin‐stimulated glucose transport but not glucose transporter translocation in 3T3‐L1 adipocytes and L6 myotubes. J Biol Chem 274: 10071‐10078, 1999.
 623. Swift DL, Johannsen NM, Earnest CP, Blair SN, Church TS. Effect of exercise training modality on C‐reactive protein in type‐2 diabetes. Med Sci Sports Exerc, 2011.
 624. Szczypaczewska M, Nazar K, Kaciuba‐Uscilko H. Glucose tolerance and insulin response to glucose load in body builders. Int J Sports Med 10: 34‐37, 1989.
 625. Tabata I, Suzuki Y, Fukunaga T, Yokozeki T, Akima H, Funato K. Resistance training affects GLUT‐4 content in skeletal muscle of humans after 19 days of head‐down bed rest. J Appl Physiol 86: 909‐914, 1999.
 626. Takala TO, Nuutila P, Knuuti J, Luotolahti M, Yki‐Jarvinen H. Insulin action on heart and skeletal muscle glucose uptake in weight lifters and endurance athletes. Am J Physiol 276: E706‐E711, 1999.
 627. Tamemoto H. Insulin resistance and growth retardation in mice lacking insulin receptor substrate‐1. Nature 372: 182‐186, 1994.
 628. Tamura Y, Sugimoto M, Murayama T, Minami M, Nishikaze Y, Ariyasu H, Akamizu T, Kita T, Yokode M, Arai H. C‐C chemokine receptor 2 inhibitor improves diet‐induced development of insulin resistance and hepatic steatosis in mice. J Atheroscler Thromb 17: 219‐228, 2010.
 629. Tamura Y, Sugimoto M, Murayama T, Ueda Y, Kanamori H, Ono K, Ariyasu H, Akamizu T, Kita T, Yokode M, Arai H. Inhibition of CCR2 ameliorates insulin resistance and hepatic steatosis in db/db mice. Arterioscler Thromb Vasc Biol 28: 2195‐2201, 2008.
 630. Tan BK, Adya R, Farhatullah S, Lewandowski KC, O'Hare P, Lehnert H, Randeva HS. Omentin‐1, a novel adipokine, is decreased in overweight insulin‐resistant women with polycystic ovary syndrome: Ex vivo and in vivo regulation of omentin‐1 by insulin and glucose. Diabetes 57: 801‐808, 2008.
 631. Tan BK, Chen J, Farhatullah S, Adya R, Kaur J, Heutling D, Lewandowski KC, O'Hare JP, Lehnert H, Randeva HS. Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes 58: 1971‐1977, 2009.
 632. Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: Insights into insulin action. Nat Rev Mol Cell Biol 7: 85‐96, 2006.
 633. Tanner CJ, Koves TR, Cortright RL, Pories WJ, Kim Y‐B, Kahn BB, Dohm GL, Houmard JA. Effect of short‐term exercise training on insulin‐stimulated PI 3‐kinase activity in middle‐aged men. J Physiol Endocrinol Metab 282: E147‐E153, 2002.
 634. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor, OB‐R. Cell 83: 1263‐1271, 1995.
 635. Taylor EB, An D, Kramer HF, Yu H, Fujii NL, Roeckl KS, Bowles N, Hirshman MF, Xie J, Feener EP, Goodyear LJ. Discovery of TBC1D1 as an insulin‐, AICAR‐, and contraction‐stimulated signaling nexus in mouse skeletal muscle. J Biol Chem 283: 9787‐9796, 2008.
 636. Taylor L, Midgley AW, Chrismas B, Madden LA, Vince RV, McNaughton LR. The effect of acute hypoxia on heat shock protein 72 expression and oxidative stress in vivo. Eur J Appl Physiol 109: 849‐855, 2010.
 637. Thirone AC, Huang C, Klip A. Tissue‐specific roles of IRS proteins in insulin signaling and glucose transport. Trends Endocrinol Metab 17: 72‐78, 2006.
 638. Thomas TR, Warner SO, Dellsperger KC, Hinton PS, Whaley‐Connell AT, Rector RS, Liu Y, Linden MA, Chockalingam A, Thyfault JP, Huyette DR, Wang Z, Cox RH. Exercise and the metabolic syndrome with weight regain. J Appl Physiol 109: 3‐10, 2010.
 639. Thong FS, Bilan PJ, Klip A. The Rab GTPase‐activating protein AS160 integrates Akt, protein kinase C, and AMP‐activated protein kinase signals regulating GLUT4 traffic. Diabetes 56: 414‐423, 2007.
 640. Tjonna AE, Lee SJ, Rognmo O, Stolen TO, Bye A, Haram PM, Loennechen JP, Al‐Share QY, Skogvoll E, Slordahl SA, Kemi OJ, Najjar SM, Wisloff U. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: A pilot study. Circulation 118: 346‐354, 2008.
 641. Todd MK, Yaspelkis BB, III, Turcotte LP. Short‐term leptin treatment increases fatty acids uptake and oxidation in muscle of high fat‐fed rats. Metabolism 54: 1218‐1224, 2005.
 642. Tracey KJ, Wei H, Manogue KR, Fong Y, Hesse DG, Nguyen HT, Kuo GC, Beutler B, Cotran RS, Cerami A, Lowry SF. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 167: 1211‐1227, 1988.
 643. Treebak JT, Taylor EB, Witczak CA, An D, Toyoda T, Koh HJ, Xie J, Feener EP, Wojtaszewski JF, Hirshman MF, Goodyear LJ. Identification of a novel phosphorylation site on TBC1D4 regulated by AMP‐activated protein kinase in skeletal muscle. Am J Physiol Cell Physiol 298: C377‐C385, 2010.
 644. Tremblay A, Simoneau JA, and Bouchard C. Impact of exercise intensity on body fatness and skeletal muscle metabolism. Metabolism 43: 814‐818, 1994.
 645. Trujillo ME, Scherer PE. Adiponectin–journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Inter Med 257: 167‐175, 2005.
 646. Trujillo ME, Sullivan S, Harten I, Schneider SH, Greenberg AS, Fried SK. Interleukin‐6 regulates human adipose tissue lipid metabolism and leptin production in vitro. J Clin Endocrinol Metab 89: 5577‐5582, 2004.
 647. Tsigos C, Papanicolaou DA, Defensor R, Mitsiadis CS, Kyrou I, Chrousos GP. Dose effects of recombinant human interleukin‐6 on pituitary hormone secretion and energy expenditure. Neuroendocrinology 66: 54‐62, 1997.
 648. Tsimikas S, Willerson JT, Ridker PM. C‐reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 47: C19‐C31, 2006.
 649. Tsochatzis EA, Manolakopoulos S, Papatheodoridis GV, Archimandritis AJ. Insulin resistance and metabolic syndrome in chronic liver diseases: Old entities with new implications. Scand J Gastroenterol 44: 6‐14, 2009.
 650. Tsukumo DM, Carvalho‐Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, Araujo EP, Vassallo J, Curi R, Velloso LA, Saad MJ. Loss‐of‐function mutation in Toll‐like receptor 4 prevents diet‐induced obesity and insulin resistance. Diabetes 56: 1986‐1998, 2007.
 651. Turban S, Hajduch E. Protein kinase C isoforms: Mediators of reactive lipid metabolites in the development of insulin resistance. FEBS letters 585: 269‐274, 2011.
 652. Turcotte LP, Srivastava AK, Chiasson J‐L. Fasting increases plasma membrane fatty acid‐binding protein (FABPPM) in red skeletal muscle. Molecular and Cellular Biochemistry 166: 153‐158, 1997.
 653. Turcotte LP, Swenberger JR, Tucker MZ, Yee AJ. Training‐induced elevation in FABPPM is associated with increased palmitate use in contracting muscle. J Appl Physiol 87: 285‐293, 1999.
 654. Turcotte LP, Swenberger JR, Zavitz Tucker M, Yee AJ. Increased fatty acid uptake and altered fatty acid metabolism in insulin‐resistant muscle of obese Zucker rats. Diabetes 50: 1389‐1396, 2001.
 655. Ueki K, Yballe CM, Brachmann SM, Vicent D, Watt JM, Kahn CR, Cantley LC. Increased insulin sensitivity in mice lacking p85β subunit of phosphoinositide 3‐kinase. Proc Nat Acad Sci U S A 99: 419‐424, 2002.
 656. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity‐induced insulin resistance in mice lacking TNF‐[alpha] function. Nature 389: 610‐614, 1997.
 657. Vague J. La differentiation sexuelle‐facteur determinant des formes de l'obesite’. Presse Med 30, 1947.
 658. van der Heijden G‐J, Toffolo G, Manesso E, Sauer PJJ, Sunehag AL. Aerobic exercise increases peripheral and hepatic insulin sensitivity in sedentary adolescents. J Clin Endocrinol Metab 94: 4292‐4299, 2009.
 659. Van Der Heijden G‐J, Wang ZJ, Chu Z, Toffolo G, Manesso E, Sauer PJJ, Sunehag AL. Strength exercise improves muscle mass and hepatic insulin sensitivity in obese youth. Med Sci Sports Exerc 42: 1973‐1980, 2010.
 660. Van der Poll T, Romijn JA, Endert E, Borm JJ, Buller HR, Sauerwein HP. Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. Am J Physiol Endocrinol Metab 261: E457‐E465, 1991.
 661. Van Guilder GP, Hoetzer GL, Greiner JJ, Stauffer BL, DeSouza CA. Influence of metabolic syndrome on biomarkers of oxidative stress and inflammation in obese adults. Obesity 14: 2127‐2131, 2006.
 662. Van Harmelen V, Ariapart P, Hoffstedt J, Lundkvist I, Bringman S, Arner P. Increased adipose angiotensinogen gene expression in human obesity. Obesity 8: 337‐341, 2000.
 663. Van Zwieten PA. Endothelial dysfunction in hypertension. A critical evaluation. Blood Press Suppl 2: 67‐70, 1997.
 664. Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S, Boutin P, Vaxillaire M, Lepretre F, Dupont S, Hara K, Clement K, Bihain B, Kadowaki T, Froguel P. Single‐nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte‐secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 11: 2607‐2614, 2002.
 665. Vgontzas AN, Bixler EO, Chrousos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 9: 211‐224, 2005.
 666. Vistisen B, Roepstorff K, Roepstorff C, Bonen A, van Deurs B, Kiens B. Sarcolemmal FAT/CD36 in human skeletal muscle colocalizes with caveolin‐3 and is more abundant in type 1 than in type 2 fibers. J Lipid Res 45: 603‐609, 2004.
 667. Vukovich MD, Arciero PJ, Kohrt WM, Racette SB, Hansen PA, Holloszy JO. Changes in insulin action and GLUT‐4 with 6 days of inactivity in endurance runners. J Appl Physiol 80: 240‐244, 1996.
 668. Wadley GD, Tunstall RJ, Sanigorski A, Collier GR, Hargreaves M, Cameron‐Smith D. Differential effects of exercise on insulin‐signaling gene expression in human skeletal muscle. J Appl Physiol 90: 436‐440, 2001.
 669. Waki H, Tontonoz P. Endocrine functions of adipose tissue. Annu Rev Pathol 2: 31‐56, 2007.
 670. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F, Froguel P, Kimura S, Nagai R, Kadowaki T. Impaired multimerization of human adiponectin mutants associated with diabetes. J Biol Chem 278: 40352‐40363, 2003.
 671. Walz A, Strieter RM, Schnyder S. Neutrophil‐activating peptide ENA‐78. Adv Exp Med Biol 351: 129‐137, 1993.
 672. Wang J, Obici S, Morgan K, Barzilai N, Feng Z, Rossetti L. Overfeeding rapidly induces leptin and insulin resistance. Diabetes 50: 2786‐2791, 2001.
 673. Wang Y, Lam KSL, Kraegen EW, Sweeney G, Zhang J, Tso AWK, Chow W‐S, Wat NMS, Xu JY, Hoo RLC, Xu A. Lipocalin‐2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 53: 34‐41, 2007.
 674. Wang Y, Nishina PM, Naggert JK. Degradation of IRS1 leads to impaired glucose uptake in adipose tissue of the type 2 diabetes mouse model TALLYHO/Jng. J Endocrinol 203: 65‐74, 2009.
 675. Wang Y, Simar D, Fiatarone Singh MA. Adaptations to exercise training within skeletal muscle in adults with type 2 diabetes or impaired glucose tolerance: A systematic review. Diabetes Metab Res Rev 25: 13‐40, 2009.
 676. Wannamethee SG, Shaper AG, Alberti KG. Physical activity, metabolic factors, and the incidence of coronary heart disease and type 2 diabetes. Arch Intern Med 160: 2108‐2116, 2000.
 677. Wannamethee SG, Shaper AG, Lennon L, Morris RW. Metabolic syndrome vs Framingham Risk Score for prediction of coronary heart disease, stroke, and type 2 diabetes mellitus. Arch Intern Med 165: 2644‐2650, 2005.
 678. Wannamethee SG, Shaper AG, Whincup PH. Modifiable lifestyle factors and the metabolic syndrome in older men: Effects of lifestyle changes. J Am Geriatr Soc 54: 1909‐1914, 2006.
 679. Warden SJ, Fuchs RK. Are “exercise pills” the answer to the growing problem of physical inactivity? Br J Sports Med 42: 562‐563, 2008.
 680. Watson RT, Pessin JE. GLUT4 translocation: The last 200 nanometers. Cell Signal 19: 2209‐2217, 2007.
 681. Watson RT, Pessin JE. Transmembrane domain length determines intracellular membrane compartment localization of syntaxins 3, 4, and 5. Am J Physiol Cell Physiol 281: C215‐C223, 2001.
 682. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AW, Jr. CCR2 modulates inflammatory and metabolic effects of high‐fat feeding. J Clin Invest 116: 115‐124, 2006.
 683. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW, Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796‐1808, 2003.
 684. Wellen KE, Hotamisligil GS. Obesity‐induced inflammatory changes in adipose tissue. J Clin Invest 112: 1785‐1788, 2003.
 685. Whaley MH, Kampert JB, Kohl HW, III, Blair SN. Physical fitness and clustering of risk factors associated with the metabolic syndrome. Med Sci Sports Exerc 31: 287‐293, 1999.
 686. White MF. The IRS‐signalling system: A network of docking proteins that mediate insulin action. Mol Cell Biochem 182: 3‐11, 1998.
 687. White MF, Kahn CR. The insulin signaling system. J Biol Chem 269: 1‐4, 1994.
 688. Whiteman EL, Cho H, Birnbaum MJ. Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab 13: 444‐451, 2002.
 689. Whyte LJ, Gill JMR, Cathcart AJ. Effect of 2 weeks of sprint interval training on health‐related outcomes in sedentary overweight/obese men. Metabolism 59: 1421‐1428, 2010.
 690. Wickham EP, Stern M, Evans RK, Bryan DL, Moskowitz WB, Clore JN, Laver JH. Prevalence of the metabolic syndrome among obese adolescents enrolled in a multidisciplinary weight management program: Clinical correlates and response to treatment. Metab Syndr Relat Disord 7: 179‐186, 2009.
 691. Wijesekara N, Konrad D, Eweida M, Jefferies C, Liadis N, Giacca A, Crackower M, Suzuki A, Mak TW, Kahn CR, Klip A, Woo M. Muscle‐specific pten deletion protects against insulin resistance and diabetes. Mol Cell Biol 25: 1135‐1145, 2005.
 692. Wijndaele K, Duvigneaud N, Matton L, Duquet W, Thomis M, Beunen G, Lefevre J, Philippaerts RM. Muscular strength, aerobic fitness, and metabolic syndrome risk in Flemish adults. Med Sci Sports Exerc 39: 233‐240, 2007.
 693. Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie‐Rosett J, Sowers MR. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: Prevalence and correlates of 2 phenotypes among the US population (NHANES 1999‐2004). Arch Intern Med 168: 1617‐1624, 2008.
 694. Wilson FH, Hariri A, Farhi A, Zhao H, Petersen KF, Toka HR, Nelson‐Williams C, Raja KM, Kashgarian M, Shulman GI, Scheinman SJ, Lifton RP. A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science 306: 1190‐1194, 2004.
 695. Wilson PWF, D'Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 112: 3066‐3072, 2005.
 696. Winnick JJ, Sherman WM, Habash DL, Stout MB, Failla ML, Belury MA, Schuster DP. Short‐term aerobic exercise training in obese humans with type 2 diabetes mellitus improves whole‐body insulin sensitivity through gains in peripheral, not hepatic insulin sensitivity. J Clin Endocrinol Metab 93: 771‐778, 2008.
 697. Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner‐Weir S, White MF. Disruption of IRS‐2 causes type 2 diabetes in mice. Nature 391: 900‐904, 1998.
 698. Wojtaszewski JFP, Birk JB, Frosig C, Holten M, Pilegaard H, Dela F. 5′AMP activated protein kinase expression in human skeletal muscle: Effects of strength training and type 2 diabetes. J Physiol (Lond) 564: 563‐573, 2005.
 699. Wolfrum C, Borrmann CM, Borchers T, Spener F. Fatty acids and hypolipidemic drugs regulate peroxisome proliferator‐activated receptors alpha ‐ and gamma‐mediated gene expression via liver fatty acid binding protein: A signaling path to the nucleus. Proc Nat Acad Sci U S A 98: 2323‐2328, 2001.
 700. Wu J, Ruas JL, Estall JL, Rasbach KA, Choi JH, Ye L, Bostrom P, Tyra HM, Crawford RW, Campbell KP, Rutkowski DT, Kaufman RJ, Spiegelman BM. The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC‐1alpha/ATF6alpha complex. Cell metabolism 13: 160‐169, 2011.
 701. Wu X, Hoffstedt J, Deeb W, Singh R, Sedkova N, Zilbering A, Zhu L, Park PK, Arner P, Goldstein BJ. Depot‐specific variation in protein‐tyrosine phosphatase activities in human omental and subcutaneous adipose tissue: A pPotential contribution to differential insulin sensitivity. J Clin Endocrinol Metab 86: 5973‐5980, 2001.
 702. Wu Y, Ouyang JP, Wu K, Wang SS, Wen CY, Xia ZY. Rosiglitazone ameliorates abnormal expression and activity of protein tyrosine phosphatase 1B in the skeletal muscle of fat‐fed, streptozotocin‐treated diabetic rats. British Journal of Pharmacology 146: 234‐243, 2005.
 703. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity‐related insulin resistance. J Clin Invest 112: 1821‐1830, 2003.
 704. Xu J‐W, Morita I, Ikeda K, Miki T, Yamori Y. C‐reactive protein suppresses insulin signaling in endothelial cells: Role of Sspleen tyrosine knase. Mol Endocrinol 21: 564‐573, 2007.
 705. Yamada P, Amorin F, Moseley P, Schneider S. Heat shock protein 72 response to exercise in humans. Sports Medicine 38: 715, 2008.
 706. Yamauchi T, Kadowaki T. Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int J Obes (Lond) 32: S13‐S18, 2008.
 707. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423: 762‐769, 2003.
 708. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada‐Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y, Kamon J, Tsuchida A, Kumagai K, Kozono H, Hada Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Awazawa M, Takamoto I, Froguel P, Hara K, Tobe K, Nagai R, Ueki K, Kadowaki T. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13: 332‐339, 2007.
 709. Yan Q‐W, Yang Q, Mody N, Graham TE, Hsu C‐H, Xu Z, Houstis NE, Kahn BB, Rosen ED. The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes 56: 2533‐2540, 2007.
 710. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436: 356‐362, 2005.
 711. Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, Shuldiner AR, Fried SK, McLenithan JC, Gong DW. Identification of omentin as a novel depot‐specific adipokine in human adipose tissue: Possible role in modulating insulin action. Am J Physiol Endocrinol Metab 290: E1253‐E1261, 2006.
 712. Yfanti C, Nielsen AR, Åkerström T, Nielsen S, Rose AJ, Richter EA, Lykkesfeldt J, Fischer CP, Pedersen BK. Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training. J Physiol Endocrinol Metab 300: E761‐E770, 2011.
 713. Yki‐Jarvinen H, Koivisto VA. Effects of body composition on insulin sensitivity. Diabetes 32: 965‐969, 1983.
 714. Youngren JF, Keen S, Kulp JL, Tanner CJ, Houmard JA, Goldfine ID. Enhanced muscle insulin receptor autophosphorylation with short‐term aerobic exercise training. Am J Physiol Endocrinol Metab 280: E528‐E533, 2001.
 715. Youngren JF, Paik J, Barnard RJ. Impaired insulin‐receptor autophosphorylation is an early defect in fat‐fed, insulin‐resistant rats. J Appl Physiol 91: 2240‐2247, 2001.
 716. Yu M, Blomstrand E, Chibalin AV, Wallberg‐Henriksson H, Zierath JR, Krook A. Exercise‐associated differences in an array of proteins involved in signal transduction and glucose transport. J Appl Physiol 90: 29‐34, 2001.
 717. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li Z‐W, Karin M, Shoelson SE. Reversal of obesity‐ and diet‐induced insulin resistance with salicylates or targeted disruption of ikkbeta. Science 293: 1673‐1677, 2001.
 718. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C‐reactive protein in healthy subjects: Associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19: 972‐978, 1999.
 719. Yuen DY, Dwyer RM, Matthews VB, Zhang L, Drew BG, Neill B, Kingwell BA, Clark MG, Rattigan S, Febbraio MA. Interleukin‐6 attenuates insulin‐mediated increases in endothelial cell signaling but augments skeletal muscle insulin action via differential effects on tumor necrosis factor‐alpha expression. Diabetes 58: 1086‐1095, 2009.
 720. Zabolotny JM, Haj FG, Kim Y‐B, Kim H‐J, Shulman GI, Kim JK, Neel BG, Kahn BB. Transgenic overexpression of protein‐tyrosine phosphatase 1B in muscle causes insulin resistance, but overexpression with leukocyte antigen‐related phosphatase does not additively impair insulin action. J Biol Chem 279: 24844‐24851, 2004.
 721. Zachwieja JJ, Toffolo G, Cobelli C, Bier DM, Yarasheski KE. Resistance exercise and growth hormone administration in older men: effects on insulin sensitivity and secretion during a stable‐label intravenous glucose tolerance test. Metabolism 45: 254‐260, 1996.
 722. Zavaroni I, Sander S, Scott S, Reaven GM. Effect of fructose feeding on insulin secretion and insulin action in the rat. Metabolism 29: 970‐973, 1980.
 723. Zeigerer A, McBrayer MK, McGraw TE. Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis, is dependent on RabGAP AS160. Mol Biol Cell 15: 4406‐4415, 2004.
 724. Zhang B, Berger J, Hu E, Szalkowski D, White‐Carrington S, Spiegelman B, Moller D. Negative regulation of peroxisome proliferator‐activated receptor‐gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor‐alpha. Mol Endocrinol 10: 1457‐1466, 1996.
 725. Zhang J, Wu Y, Zhang Y, LeRoith D, Bernlohr DA, Chen X. The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Mol Endocrinol 22: 1416‐1426, 2008.
 726. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425‐432, 1994.
 727. Zhou B, Wong CF. A computational study of the phosphorylation mechanism of the insulin receptor tyrosine kinase. Jf Phys Chem A 113: 5144‐5150, 2009.
 728. Zhou QL, Park JG, Jiang ZY, Holik JJ, Mitra P, Semiz S, Guilherme A, Powelka AM, Tang X, Virbasius J, Czech MP. Analysis of insulin signalling by RNAi‐based gene silencing. Biochem Soc Trans 32: 817‐821, 2004.
 729. Zinker BA, Rondinone CM, Trevillyan JM, Gum RJ, Clampit JE, Waring JF, Xie N, Wilcox D, Jacobson P, Frost L, Kroeger PE, Reilly RM, Koterski S, Opgenorth TJ, Ulrich RG, Crosby S, Butler M, Murray SF, McKay RA, Bhanot S, Monia BP, Jirousek MR. PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Nat Acad Sci U S A 99: 11357‐11362, 2002.
 730. Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais‐Jarvis F, Lowell BB, Wojtaszewski JF, Hirshman MF, Virkamaki A, Goodyear LJ, Kahn CR, Kahn BB. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med 6: 924‐928, 2000.
 731. Zoppini G, Targher G, Zamboni C, Venturi C, Cacciatori V, Moghetti P, Muggeo M. Effects of moderate‐intensity exercise training on plasma biomarkers of inflammation and endothelial dysfunction in older patients with type 2 diabetes. Nutr Metab Cardiovasc Dis 16: 543‐549, 2006
 732. Zou C, Shao J. Role of adipocytokines in obesity‐associated insulin resistance. J Nutr Biochem 19: 277‐286, 2008.

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Article Title: Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
 

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Christian K. Roberts, Andrea L. Hevener, R. James Barnard. Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training. Compr Physiol 2013, 3: 1-58. doi: 10.1002/cphy.c110062