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Endocrine Function after Bariatric Surgery

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ABSTRACT

Obesity increases the risks of metabolic disorders including type 2 diabetes mellitus (T2DM). Bariatric surgery is the most successful therapeutic option that causes sustained weight loss and improvements in obesity comorbidities. Roux‐en‐Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are two of the most frequently performed bariatric surgeries. Despite their different anatomical rearrangement, they have remarkably similar success in both weight loss and T2DM remission. Interestingly, they also both cause a wide range of endocrine changes. Many of these endocrine changes are reflected specifically within the intestine and are implicated as mechanisms for the metabolic success of surgery. However, while most of the work shows that these hormonal changes are associated with the metabolic changes after surgery, causation has been difficult to ascertain. Here, we review the endocrine changes after RYGB and VSG and explore their mechanistic role in the success of bariatric surgery. Further, we explore important changes in gastrointestinal function and the role of these changes in the increase in postprandial endocrine responses after bariatric surgery. © 2017 American Physiological Society. Compr Physiol 7:783‐798, 2017.

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Figure 1. Figure 1. Changes in GI tract anatomy after RYGB and VSG. In RYGB, small gastric pouch is made and is anastomosed to the jejunum. The stomach and duodenum remain in the peritoneal cavity, and the distal end of the duodenum is anastomosed about 1 m distal to the pouch‐intestine juncture. Therefore, ingested foods bypass 95% of stomach and the majority of the upper intestinal tract. In VSG, 80% of the stomach along the greater curvature is removed.
Figure 2. Figure 2. Hormonal responses to a meal after RYGB and VSG and their hypothesized role in body weight and glucose regulation. RYGB and VSG cause many similar postprandial hormonal changes. For example, both surgeries increase total bile acids, FGF19, insulin, GLP‐1, PYY, and at least acutely after surgery, glucagon. However, while VSG reduces ghrelin and GIP, consistent changes in ghrelin are not seen after RYGB. RYGB additionally increases obestatin, motilin, GIP, and neurotensin. Based on the known physiological role of these hormones, we hypothesize that they could play a role in regulating either body weight (dashed lines), or glucose homeostasis (solid lines), or both.
Figure 3. Figure 3. Preproglucagon‐derived peptides expression and processing. Preproglucagon genes are predominantly found in the enteroendocrine L‐cells, pancreatic α‐cells, and within the nucleus of the solitary tract (NTS) in the hindbrain. Once the preproglucagon gene is translated into the proglucagon peptide, it is processed into several different peptides by tissue‐specific posttranslational modification. In pancreatic α‐cells, prohormone convertase 2 (Pcsk2) predominantly cleaves proglucagon to glicentin‐related pancreatic polypeptide (GRPP), glucagon, intervening peptide 1 (IP1), and major proglucagon fragment. Meanwhile in the enteroendocrine L‐cells and in the brain, Pcsk1 cleaves proglucagon into GRPP, oxyntomodulin (OXM), glucagon‐like peptide‐1 (GLP‐1), GLP‐2, and IP2.
Figure 4. Figure 4. Bile acid production and signaling. Bile acids are initially synthesized in the liver from cholesterol. These primary bile acids, cholic acid (CA), and chenodeoxycholic acid (CDCA) are usually stored in the gallbladder. When a meal is ingested, the primary bile acids flow into the small intestine to help with fat digestion. In the small intestine, some primary bile acids are processed into the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), by intestinal microbiota. These primary and secondary bile acids are reabsorbed by passive diffusion and active transport in the distal small intestine and consequently circulate back to the liver through the portal vein. The primary and secondary bile acids can be conjugated with taurine or glycine in the liver. This process is called enterohepatic circulation of bile acids. In addition to acting as a detergent, bile acids activate a G protein‐coupled receptor called TGR5, which, within the intestine, stimulates GLP‐1 secretion. In parallel, bile acids can activate a nuclear receptor transcription factor called FXR, which, in the intestine, stimulates the release of fibroblast growth factor 19 (FGF19). Both the RYGB and VSG increase total bile acids secretion but whether this is necessary for the increase in FGF19 and GLP‐1 increases are still unclear. However, genetic KO models suggest that both receptors are necessary for at least some surgical outcome.
Figure 5. Figure 5. Changes in digestive processes after RYGB and VSG. In both RYGB and VSG, there is a surgical restructuring of the stomach, which reduces peristalsis but increases gastric emptying rate (GER). While it remains unknown how these surgeries alter digestive enzyme content, there is limited macronutrient malabsorption after VSG and only fat malabsorption, as opposed to normal carbohydrate and protein absorption, is seen with RYGB. In addition, glucose absorption seems to be increased by both RYGB and VSG. Lastly, the increased GER likely contributes to the increased delivery of nutrients to the distal enteroendocrine cells (EEC) and this may contribute to the increase in gut peptide secretions.
Figure 6. Figure 6. The gut‐morphological changes after RYGB and VSG. The invasive surgical processes after RYGB and VSG cause different gut‐morphological changes. After RYGB, there are increases in villus height within the enterocytes and crypt cell proliferation and maturation within the Roux and common limb. Increased enteroendocrine cell (EEC) number and density in the Roux limb and common limb may contribute the increased gut peptide secretion. On the other hand, VSG has no impact on intestinal growth and crypt maturation, but does seem to cause villus height elongation and increased L‐cells numbers.


Figure 1. Changes in GI tract anatomy after RYGB and VSG. In RYGB, small gastric pouch is made and is anastomosed to the jejunum. The stomach and duodenum remain in the peritoneal cavity, and the distal end of the duodenum is anastomosed about 1 m distal to the pouch‐intestine juncture. Therefore, ingested foods bypass 95% of stomach and the majority of the upper intestinal tract. In VSG, 80% of the stomach along the greater curvature is removed.


Figure 2. Hormonal responses to a meal after RYGB and VSG and their hypothesized role in body weight and glucose regulation. RYGB and VSG cause many similar postprandial hormonal changes. For example, both surgeries increase total bile acids, FGF19, insulin, GLP‐1, PYY, and at least acutely after surgery, glucagon. However, while VSG reduces ghrelin and GIP, consistent changes in ghrelin are not seen after RYGB. RYGB additionally increases obestatin, motilin, GIP, and neurotensin. Based on the known physiological role of these hormones, we hypothesize that they could play a role in regulating either body weight (dashed lines), or glucose homeostasis (solid lines), or both.


Figure 3. Preproglucagon‐derived peptides expression and processing. Preproglucagon genes are predominantly found in the enteroendocrine L‐cells, pancreatic α‐cells, and within the nucleus of the solitary tract (NTS) in the hindbrain. Once the preproglucagon gene is translated into the proglucagon peptide, it is processed into several different peptides by tissue‐specific posttranslational modification. In pancreatic α‐cells, prohormone convertase 2 (Pcsk2) predominantly cleaves proglucagon to glicentin‐related pancreatic polypeptide (GRPP), glucagon, intervening peptide 1 (IP1), and major proglucagon fragment. Meanwhile in the enteroendocrine L‐cells and in the brain, Pcsk1 cleaves proglucagon into GRPP, oxyntomodulin (OXM), glucagon‐like peptide‐1 (GLP‐1), GLP‐2, and IP2.


Figure 4. Bile acid production and signaling. Bile acids are initially synthesized in the liver from cholesterol. These primary bile acids, cholic acid (CA), and chenodeoxycholic acid (CDCA) are usually stored in the gallbladder. When a meal is ingested, the primary bile acids flow into the small intestine to help with fat digestion. In the small intestine, some primary bile acids are processed into the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), by intestinal microbiota. These primary and secondary bile acids are reabsorbed by passive diffusion and active transport in the distal small intestine and consequently circulate back to the liver through the portal vein. The primary and secondary bile acids can be conjugated with taurine or glycine in the liver. This process is called enterohepatic circulation of bile acids. In addition to acting as a detergent, bile acids activate a G protein‐coupled receptor called TGR5, which, within the intestine, stimulates GLP‐1 secretion. In parallel, bile acids can activate a nuclear receptor transcription factor called FXR, which, in the intestine, stimulates the release of fibroblast growth factor 19 (FGF19). Both the RYGB and VSG increase total bile acids secretion but whether this is necessary for the increase in FGF19 and GLP‐1 increases are still unclear. However, genetic KO models suggest that both receptors are necessary for at least some surgical outcome.


Figure 5. Changes in digestive processes after RYGB and VSG. In both RYGB and VSG, there is a surgical restructuring of the stomach, which reduces peristalsis but increases gastric emptying rate (GER). While it remains unknown how these surgeries alter digestive enzyme content, there is limited macronutrient malabsorption after VSG and only fat malabsorption, as opposed to normal carbohydrate and protein absorption, is seen with RYGB. In addition, glucose absorption seems to be increased by both RYGB and VSG. Lastly, the increased GER likely contributes to the increased delivery of nutrients to the distal enteroendocrine cells (EEC) and this may contribute to the increase in gut peptide secretions.


Figure 6. The gut‐morphological changes after RYGB and VSG. The invasive surgical processes after RYGB and VSG cause different gut‐morphological changes. After RYGB, there are increases in villus height within the enterocytes and crypt cell proliferation and maturation within the Roux and common limb. Increased enteroendocrine cell (EEC) number and density in the Roux limb and common limb may contribute the increased gut peptide secretion. On the other hand, VSG has no impact on intestinal growth and crypt maturation, but does seem to cause villus height elongation and increased L‐cells numbers.
References
 1.Abbott CR, Small CJ, Kennedy AR, Neary NM, Sajedi A, Ghatei MA, Bloom SR. Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246 attenuates the effect of endogenous and exogenous peptide YY(3‐36) on food intake. Brain Res 1043: 139‐144, 2005. 10.1016/j.brainres.2005.02.065.
 2.Arble DM, Sandoval DA, Seeley RJ. Mechanisms underlying weight loss and metabolic improvements in rodent models of bariatric surgery. Diabetologia 58: 211‐220, 2015. 10.1007/s00125‐014‐3433‐3.
 3.Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujimiya M, Niijima A, Fujino MA, Kasuga M. Ghrelin is an appetite‐stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 120: 337‐345, 2001.
 4.Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. Gut hormone PYY(3‐36) physiologically inhibits food intake. Nature 418: 650‐654, 2002. 10.1038/nature02666.
 5.Belgaumkar AP, Vincent RP, Carswell KA, Hughes RD, Alaghband‐Zadeh J, Mitry RR, le Roux CW, Patel AG. Changes in bile acid profile after laparoscopic sleeve gastrectomy are associated with improvements in metabolic profile and fatty liver disease. Obes Surg 26: 1195‐1202, 2016. 10.1007/s11695‐015‐1878‐1.
 6.Bojsen‐Moller KN, Dirksen C, Jorgensen NB, Jacobsen SH, Serup AK, Albers PH, Hansen DL, Worm D, Naver L, Kristiansen VB, Wojtaszewski JF, Kiens B, Holst JJ, Richter EA, Madsbad S. Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux‐en‐Y gastric bypass. Diabetes 63: 1725‐1737, 2014. 10.2337/db13‐1307.
 7.Borg CM, le Roux CW, Ghatei MA, Bloom SR, Patel AG, Aylwin SJ. Progressive rise in gut hormone levels after Roux‐en‐Y gastric bypass suggests gut adaptation and explains altered satiety. Br J Surg 93: 210‐215, 2006. 10.1002/bjs.5227.
 8.Bose M, Teixeira J, Olivan B, Bawa B, Arias S, Machineni S, Pi‐Sunyer FX, Scherer PE, Laferrere B. Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery. J Diabetes 2: 47‐55, 2010. 10.1111/j.1753‐0407.2009.00064.x.
 9.Boyle CN, Lutz TA. Amylinergic control of food intake in lean and obese rodents. Physiol Behav 105: 129‐137, 2011. 10.1016/j.physbeh.2011.02.015.
 10.Braun M, Ramracheya R, Rorsman P. Autocrine regulation of insulin secretion. Diabetes Obes Metab 14 (Suppl 3): 143‐151, 2012. 10.1111/j.1463‐1326.2012.01642.x.
 11.Bryant EJ, King NA, Falken Y, Hellstrom PM, Holst JJ, Blundell JE, Naslund E. Relationships among tonic and episodic aspects of motivation to eat, gut peptides, and weight before and after bariatric surgery. Surg Obes Relat Dis 9: 802‐808, 2013. 10.1016/j.soard.2012.09.011.
 12.Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab 17: 819‐837, 2013. 10.1016/j.cmet.2013.04.008.
 13.Canales BK, Schafer AL, Shoback DM, Carpenter TO. Gastric bypass in obese rats causes bone loss, vitamin D deficiency, metabolic acidosis, and elevated peptide YY. Surg Obes Relat Dis 10: 878‐884, 2014. 10.1016/j.soard.2014.01.021.
 14.Cariou B, van Harmelen K, Duran‐Sandoval D, van Dijk TH, Grefhorst A, Abdelkarim M, Caron S, Torpier G, Fruchart JC, Gonzalez FJ, Kuipers F, Staels B. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem 281: 11039‐11049, 2006. 10.1074/jbc.M510258200.
 15.Cavin JB, Couvelard A, Lebtahi R, Ducroc R, Arapis K, Voitellier E, Cluzeaud F, Gillard L, Hourseau M, Mikail N, Ribeiro‐Parenti L, Kapel N, Marmuse JP, Bado A, Le Gall M. Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux‐en‐Y gastric bypass vs sleeve gastrectomy. Gastroenterology 150: 454‐464 e459, 2016. 10.1053/j.gastro.2015.10.009.
 16.Cejvan K, Coy DH, Efendic S. Intra‐islet somatostatin regulates glucagon release via type 2 somatostatin receptors in rats. Diabetes 52: 1176‐1181, 2003.
 17.Chambers AP, Jessen L, Ryan KK, Sisley S, Wilson‐Perez HE, Stefater MA, Gaitonde SG, Sorrell JE, Toure M, Berger J, D'Alessio DA, Woods SC, Seeley RJ, Sandoval DA. Weight‐independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 141: 950‐958, 2011. 10.1053/j.gastro.2011.05.050.
 18.Chambers AP, Kirchner H, Wilson‐Perez HE, Willency JA, Hale JE, Gaylinn BD, Thorner MO, Pfluger PT, Gutierrez JA, Tschop MH, Sandoval DA, Seeley RJ. The effects of vertical sleeve gastrectomy in rodents are ghrelin independent. Gastroenterology 144: 50‐52 e55, 2013. 10.1053/j.gastro.2012.09.009.
 19.Chambers AP, Smith EP, Begg DP, Grayson BE, Sisley S, Greer T, Sorrell J, Lemmen L, LaSance K, Woods SC, Seeley RJ, D'Alessio DA, Sandoval DA. Regulation of gastric emptying rate and its role in nutrient‐induced GLP‐1 secretion in rats after vertical sleeve gastrectomy. Am J Physiol Endocrinol Metab 306: E424‐E432, 2014. 10.1152/ajpendo.00469.2013.
 20.Chambers AP, Stefater MA, Wilson‐Perez HE, Jessen L, Sisley S, Ryan KK, Gaitonde S, Sorrell JE, Toure M, Berger J, D'Alessio DA, Sandoval DA, Seeley RJ, Woods SC. Similar effects of roux‐en‐Y gastric bypass and vertical sleeve gastrectomy on glucose regulation in rats. Physiol Behav 105: 120‐123, 2011. 10.1016/j.physbeh.2011.05.026.
 21.Chambers AP, Wilson‐Perez HE, McGrath S, Grayson BE, Ryan KK, D'Alessio DA, Woods SC, Sandoval DA, Seeley RJ. Effect of vertical sleeve gastrectomy on food selection and satiation in rats. Am J Physiol Endocrinol Metab 303: E1076‐E1084, 2012. 10.1152/ajpendo.00211.2012.
 22.Chelikani PK, Haver AC, Reidelberger RD. Intravenous infusion of peptide YY(3‐36) potently inhibits food intake in rats. Endocrinology 146: 879‐888, 2005. 10.1210/en.2004‐1138.
 23.Chen CY, Lee WJ, Asakawa A, Fujitsuka N, Chong K, Chen SC, Lee SD, Inui A. Insulin secretion and interleukin‐1beta dependent mechanisms in human diabetes remission after metabolic surgery. Curr Med Chem 20: 2374‐2388, 2013.
 24.Chiang JY. Bile acid metabolism and signaling. Compr Physiol 3: 1191‐1212, 2013. 10.1002/cphy.c120023.
 25.Claudel T, Staels B, Kuipers F. The Farnesoid X receptor: A molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 25: 2020‐2030, 2005. 10.1161/01.ATV.0000178994.21828.a7.
 26.Cummings BP, Bettaieb A, Graham JL, Stanhope KL, Kowala M, Haj FG, Chouinard ML, Havel PJ. Vertical sleeve gastrectomy improves glucose and lipid metabolism and delays diabetes onset in UCD‐T2DM rats. Endocrinology 153: 3620‐3632, 2012. 10.1210/en.2012‐1131.
 27.Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, Bloom SR. Oxyntomodulin inhibits food intake in the rat. Endocrinology 142: 4244‐4250, 2001. 10.1210/endo.142.10.8430.
 28.Dakin CL, Small CJ, Batterham RL, Neary NM, Cohen MA, Patterson M, Ghatei MA, Bloom SR. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 145: 2687‐2695, 2004. 10.1210/en.2003‐1338.
 29.Dawes LG, Muldoon JP, Greiner MA, Bertolotti M. Cholecystokinin increases bile acid synthesis with total parenteral nutrition but does not prevent stone formation. J Surg Res 67: 84‐89, 1997. 10.1006/jsre.1996.4953.
 30.Deacon CF, Wamberg S, Bie P, Hughes TE, Holst JJ. Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal‐induced incretin secretion in dogs. J Endocrinol 172: 355‐362, 2002.
 31.Delhanty PJ, Huisman M, Julien M, Mouchain K, Brune P, Themmen AP, Abribat T, van der Lely AJ. The acylated (AG) to unacylated (UAG) ghrelin ratio in esterase inhibitor‐treated blood is higher than previously described. Clin Endocrinol (Oxf) 82: 142‐146, 2015. 10.1111/cen.12489.
 32.Deloose E, Janssen P, Lannoo M, Van der Schueren B, Depoortere I, Tack J. Higher plasma motilin levels in obese patients decrease after Roux‐en‐Y gastric bypass surgery and regulate hunger. Gut 65: 1110‐1118, 2016. 10.1136/gutjnl‐2015‐309242.
 33.Dimitriadis E, Daskalakis M, Kampa M, Peppe A, Papadakis JA, Melissas J. Alterations in gut hormones after laparoscopic sleeve gastrectomy: A prospective clinical and laboratory investigational study. Ann Surg 257: 647‐654, 2013. 10.1097/SLA.0b013e31826e1846.
 34.Ding L, Sousa KM, Jin L, Dong B, Kim BW, Ramirez R, Xiao Z, Gu Y, Yang Q, Wang J, Yu D, Pigazzi A, Schones D, Yang L, Moore D, Wang Z, Huang W. Vertical sleeve gastrectomy activates GPBAR‐1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology, 2016. 10.1002/hep.28689.
 35.Dirksen C, Damgaard M, Bojsen‐Moller KN, Jorgensen NB, Kielgast U, Jacobsen SH, Naver LS, Worm D, Holst JJ, Madsbad S, Hansen DL, Madsen JL. Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux‐en‐Y gastric bypass. Neurogastroenterol Motil 25: 346‐e255, 2013. 10.1111/nmo.12087.
 36.Dirksen C, Jorgensen NB, Bojsen‐Moller KN, Kielgast U, Jacobsen SH, Clausen TR, Worm D, Hartmann B, Rehfeld JF, Damgaard M, Madsen JL, Madsbad S, Holst JJ, Hansen DL. Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux‐en‐Y gastric bypass. Int J Obes (Lond) 37: 1452‐1459, 2013. 10.1038/ijo.2013.15.
 37.Dixon JB, le Roux CW, Rubino F, Zimmet P. Bariatric surgery for type 2 diabetes. Lancet 379: 2300‐2311, 2012. 10.1016/S0140‐6736(12)60401‐2.
 38.Drucker DJ, Erlich P, Asa SL, Brubaker PL. Induction of intestinal epithelial proliferation by glucagon‐like peptide 2. Proc Natl Acad Sci U S A 93: 7911‐7916, 1996.
 39.Eickhoff H, Louro TM, Matafome PN, Vasconcelos F, Seica RM, Castro ESF. Amelioration of glycemic control by sleeve gastrectomy and gastric bypass in a lean animal model of type 2 diabetes: Restoration of gut hormone profile. Obes Surg 25: 7‐18, 2015. 10.1007/s11695‐014‐1309‐8.
 40.Falken Y, Hellstrom PM, Holst JJ, Naslund E. Changes in glucose homeostasis after Roux‐en‐Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: Role of gut peptides. J Clin Endocrinol Metab 96: 2227‐2235, 2011. 10.1210/jc.2010‐2876.
 41.Fehmann HC, Goke R, Goke B. Cell and molecular biology of the incretin hormones glucagon‐like peptide‐I and glucose‐dependent insulin releasing polypeptide. Endocr Rev 16: 390‐410, 1995. 10.1210/edrv‐16‐3‐390.
 42.Fiorucci S, Mencarelli A, Palladino G, Cipriani S. Bile‐acid‐activated receptors: Targeting TGR5 and farnesoid‐X‐receptor in lipid and glucose disorders. Trends Pharmacol Sci 30: 570‐580, 2009. 10.1016/j.tips.2009.08.001.
 43.Fukami A, Seino Y, Ozaki N, Yamamoto M, Sugiyama C, Sakamoto‐Miura E, Himeno T, Takagishi Y, Tsunekawa S, Ali S, Drucker DJ, Murata Y, Seino Y, Oiso Y, Hayashi Y. Ectopic expression of GIP in pancreatic beta‐cells maintains enhanced insulin secretion in mice with complete absence of proglucagon‐derived peptides. Diabetes 62: 510‐518, 2013. 10.2337/db12‐0294.
 44.Gerhard GS, Styer AM, Wood GC, Roesch SL, Petrick AT, Gabrielsen J, Strodel WE, Still CD, Argyropoulos G. A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux‐en‐Y gastric bypass. Diabetes Care 36: 1859‐1864, 2013. 10.2337/dc12‐2255.
 45.Grong E, Graeslie H, Munkvold B, Arbo IB, Kulseng BE, Waldum HL, Marvik R. Gastrin secretion after bariatric surgery‐response to a protein‐rich mixed meal following Roux‐En‐Y gastric bypass and sleeve gastrectomy: A pilot study in normoglycemic women. Obes Surg 26: 1448‐1456, 2016. 10.1007/s11695‐015‐1985‐z.
 46.Grunddal KV, Ratner CF, Svendsen B, Sommer F, Engelstoft MS, Madsen AN, Pedersen J, Nohr MK, Egerod KL, Nawrocki AR, Kowalski T, Howard AD, Poulsen SS, Offermanns S, Backhed F, Holst JJ, Holst B, Schwartz TW. Neurotensin is coexpressed, coreleased, and acts together with GLP‐1 and PYY in enteroendocrine control of metabolism. Endocrinology 157: 176‐194, 2016. 10.1210/en.2015‐1600.
 47.Guijarro A, Suzuki S, Chen C, Kirchner H, Middleton FA, Nadtochiy S, Brookes PS, Niijima A, Inui A, Meguid MM. Characterization of weight loss and weight regain mechanisms after Roux‐en‐Y gastric bypass in rats. Am J Physiol Regul Integr Comp Physiol 293: R1474‐1489, 2007. 10.1152/ajpregu.00171.2007.
 48.Hansen CF, Bueter M, Theis N, Lutz T, Paulsen S, Dalboge LS, Vrang N, Jelsing J. Hypertrophy dependent doubling of L‐cells in Roux‐en‐Y gastric bypass operated rats. PLoS One 8: e65696, 2013. 10.1371/journal.pone.0065696.
 49.Hao Z, Townsend RL, Mumphrey MB, Patterson LM, Ye J, Berthoud HR. Vagal innervation of intestine contributes to weight loss After Roux‐en‐Y gastric bypass surgery in rats. Obes Surg 24: 2145‐2151, 2014. 10.1007/s11695‐014‐1338‐3.
 50.Hartmann B, Thulesen J, Hare KJ, Kissow H, Orskov C, Poulsen SS, Holst JJ. Immunoneutralization of endogenous glucagon‐like peptide‐2 reduces adaptive intestinal growth in diabetic rats. Regul Pept 105: 173‐179, 2002.
 51.Honey RN, Weir GC. Acetylcholine stimulates insulin, glucagon, and somatostatin release in the perfused chicken pancreas. Endocrinology 107: 1065‐1068, 1980. 10.1210/endo‐107‐4‐1065.
 52.Hort Y, Baker E, Sutherland GR, Shine J, Herzog H. Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1. Genomics 26: 77‐83, 1995.
 53.Iida A, Seino Y, Fukami A, Maekawa R, Yabe D, Shimizu S, Kinoshita K, Takagi Y, Izumoto T, Ogata H, Ishikawa K, Ozaki N, Tsunekawa S, Hamada Y, Oiso Y, Arima H, Hayashi Y. Endogenous GIP ameliorates impairment of insulin secretion in proglucagon‐deficient mice under moderate beta cell damage induced by streptozotocin. Diabetologia 59: 1533‐1541, 2016. 10.1007/s00125‐016‐3935‐2.
 54.Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM, Fujimiya M. Ghrelin, appetite, and gastric motility: The emerging role of the stomach as an endocrine organ. FASEB J 18: 439‐456, 2004. 10.1096/fj.03‐0641rev.
 55.Jacobsen SH, Olesen SC, Dirksen C, Jorgensen NB, Bojsen‐Moller KN, Kielgast U, Worm D, Almdal T, Naver LS, Hvolris LE, Rehfeld JF, Wulff BS, Clausen TR, Hansen DL, Holst JJ, Madsbad S. Changes in gastrointestinal hormone responses, insulin sensitivity, and beta‐cell function within 2 weeks after gastric bypass in non‐diabetic subjects. Obes Surg 22: 1084‐1096, 2012. 10.1007/s11695‐012‐0621‐4.
 56.Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM. Gut‐expressed gustducin and taste receptors regulate secretion of glucagon‐like peptide‐1. Proc Natl Acad Sci U S A 104: 15069‐15074, 2007. 10.1073/pnas.0706890104.
 57.Jarhult J, Farnebo LO, Hamberger B, Holst J, Schwartz TW. The relation between catecholamines, glucagon and pancreatic polypeptide during hypoglycaemia in man. Acta Endocrinol (Copenh) 98: 402‐406, 1981
 58.Jeon TI, Zhu B, Larson JL, Osborne TF. SREBP‐2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice. J Clin Invest 118: 3693‐3700, 2008. 10.1172/JCI36461.
 59.Jimenez A, Casamitjana R, Viaplana‐Masclans J, Lacy A, Vidal J. GLP‐1 action and glucose tolerance in subjects with remission of type 2 diabetes after gastric bypass surgery. Diabetes Care 36: 2062‐2069, 2013. 10.2337/dc12‐1535.
 60.Jorgensen NB, Dirksen C, Bojsen‐Moller KN, Jacobsen SH, Worm D, Hansen DL, Kristiansen VB, Naver L, Madsbad S, Holst JJ. Exaggerated glucagon‐like peptide 1 response is important for improved beta‐cell function and glucose tolerance after Roux‐en‐Y gastric bypass in patients with type 2 diabetes. Diabetes 62: 3044‐3052, 2013. 10.2337/db13‐0022.
 61.Kars M, Yang L, Gregor MF, Mohammed BS, Pietka TA, Finck BN, Patterson BW, Horton JD, Mittendorfer B, Hotamisligil GS, Klein S. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes 59: 1899‐1905, 2010. 10.2337/db10‐0308.
 62.Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon‐like peptide‐1 secretion through TGR5 in a murine enteroendocrine cell line STC‐1. Biochem Biophys Res Commun 329: 386‐390, 2005. 10.1016/j.bbrc.2005.01.139.
 63.Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M, Fukusumi S, Habata Y, Itoh T, Shintani Y, Hinuma S, Fujisawa Y, Fujino M. A G protein‐coupled receptor responsive to bile acids. J Biol Chem 278: 9435‐9440, 2003. 10.1074/jbc.M209706200.
 64.Kim KS, Egan JM, Jang HJ. Denatonium induces secretion of glucagon‐like peptide‐1 through activation of bitter taste receptor pathways. Diabetologia 57: 2117‐2125, 2014. 10.1007/s00125‐014‐3326‐5.
 65.Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino‐Powell K, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ. FGF19 as a postprandial, insulin‐independent activator of hepatic protein and glycogen synthesis. Science 331: 1621‐1624, 2011. 10.1126/science.1198363.
 66.Kohli R, Bradley D, Setchell KD, Eagon JC, Abumrad N, Klein S. Weight loss induced by Roux‐en‐Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. J Clin Endocrinol Metab 98: E708‐712, 2013. 10.1210/jc.2012‐3736.
 67.Kojima M, Kangawa K. Ghrelin: Structure and function. Physiol Rev 85: 495‐522, 2005. 10.1152/physrev.00012.2004.
 68.Korner J, Inabnet W, Febres G, Conwell IM, McMahon DJ, Salas R, Taveras C, Schrope B, Bessler M. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux‐en‐Y gastric bypass. Int J Obes (Lond) 33: 786‐795, 2009. 10.1038/ijo.2009.79.
 69.Krarup T, Saurbrey N, Moody AJ, Kuhl C, Madsbad S. Effect of porcine gastric inhibitory polypeptide on beta‐cell function in type I and type II diabetes mellitus. Metabolism 36: 677‐682, 1987.
 70.Kumar S, Lau R, Hall C, Palaia T, Brathwaite CE, Ragolia L. Bile acid elevation after Roux‐en‐Y gastric bypass is associated with cardio‐protective effect in Zucker Diabetic Fatty rats. Int J Surg 24: 70‐74, 2015. 10.1016/j.ijsu.2015.11.010.
 71.Laferrere B, Swerdlow N, Bawa B, Arias S, Bose M, Olivan B, Teixeira J, McGinty J, Rother KI. Rise of oxyntomodulin in response to oral glucose after gastric bypass surgery in patients with type 2 diabetes. J Clin Endocrinol Metab 95: 4072‐4076, 2010. 10.1210/jc.2009‐2767.
 72.Laferrere B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, Lee H, Yapp K, Olivan B. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab 93: 2479‐2485, 2008. 10.1210/jc.2007‐2851.
 73.le Roux CW, Borg C, Wallis K, Vincent RP, Bueter M, Goodlad R, Ghatei MA, Patel A, Bloom SR, Aylwin SJ. Gut hypertrophy after gastric bypass is associated with increased glucagon‐like peptide 2 and intestinal crypt cell proliferation. Ann Surg 252: 50‐56, 2010. 10.1097/SLA.0b013e3181d3d21f.
 74.le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, Lonroth H, Fandriks L, Ghatei MA, Bloom SR, Olbers T. Gut hormones as mediators of appetite and weight loss after Roux‐en‐Y gastric bypass. Ann Surg 246: 780‐785, 2007. 10.1097/SLA.0b013e3180caa3e3.
 75.Lee WJ, Chen CY, Chong K, Lee YC, Chen SC, Lee SD. Changes in postprandial gut hormones after metabolic surgery: A comparison of gastric bypass and sleeve gastrectomy. Surg Obes Relat Dis 7: 683‐690, 2011. 10.1016/j.soard.2011.07.009.
 76.Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev 89: 147‐191, 2009. 10.1152/physrev.00010.2008.
 77.Liou AP, Paziuk M, Luevano JM, Jr., Machineni S, Turnbaugh PJ, Kaplan LM. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med 5: 178ra141, 2013. 10.1126/scitranslmed.3005687.
 78.Lo CM, King A, Samuelson LC, Kindel TL, Rider T, Jandacek RJ, Raybould HE, Woods SC, Tso P. Cholecystokinin knockout mice are resistant to high‐fat diet‐induced obesity. Gastroenterology 138: 1997‐2005, 2010. 10.1053/j.gastro.2010.01.044.
 79.Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 6: 507‐515, 2000.
 80.Lutz TA. Amylinergic control of food intake. Physiol Behav 89: 465‐471, 2006. 10.1016/j.physbeh.2006.04.001.
 81.Ma K, Saha PK, Chan L, Moore DD. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest 116: 1102‐1109, 2006. 10.1172/JCI25604.
 82.Magkos F, Bradley D, Eagon JC, Patterson BW, Klein S. Effect of Roux‐en‐Y gastric bypass and laparoscopic adjustable gastric banding on gastrointestinal metabolism of ingested glucose. Am J Clin Nutr 103: 61‐65, 2016. 10.3945/ajcn.115.116111.
 83.Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B. Identification of a nuclear receptor for bile acids. Science 284: 1362‐1365, 1999.
 84.Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K. Identification of membrane‐type receptor for bile acids (M‐BAR). Biochem Biophys Res Commun 298: 714‐719, 2002.
 85.Masuda Y, Tanaka T, Inomata N, Ohnuma N, Tanaka S, Itoh Z, Hosoda H, Kojima M, Kangawa K. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 276: 905‐908, 2000. 10.1006/bbrc.2000.3568.
 86.McGavigan AK, Garibay D, Henseler ZM, Chen J, Bettaieb A, Haj FG, Ley RE, Chouinard ML, Cummings BP. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut, 2015. 10.1136/gutjnl‐2015‐309871.
 87.Mokadem M, Zechner JF, Uchida A, Aguirre V. Leptin is required for glucose homeostasis after Roux‐en‐Y gastric bypass in mice. PLoS One 10: e0139960, 2015. 10.1371/journal.pone.0139960.
 88.Mumphrey MB, Hao Z, Townsend RL, Patterson LM, Berthoud HR. Sleeve gastrectomy does not cause hypertrophy and reprogramming of intestinal glucose metabolism in rats. Obes Surg 25: 1468‐1473, 2015. 10.1007/s11695‐014‐1547‐9.
 89.Mumphrey MB, Patterson LM, Zheng H, Berthoud HR. Roux‐en‐Y gastric bypass surgery increases number but not density of CCK‐, GLP‐1‐, 5‐HT‐, and neurotensin‐expressing enteroendocrine cells in rats. Neurogastroenterol Motil 25: e70‐79, 2013. 10.1111/nmo.12034.
 90.Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature 444: 854‐859, 2006. 10.1038/nature05484.
 91.Myronovych A, Kirby M, Ryan KK, Zhang W, Jha P, Setchell KD, Dexheimer PJ, Aronow B, Seeley RJ, Kohli R. Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight‐loss‐independent manner. Obesity (Silver Spring) 22: 390‐400, 2014. 10.1002/oby.20548.
 92.Myronovych A, Salazar‐Gonzalez RM, Ryan KK, Miles L, Zhang W, Jha P, Wang L, Setchell KD, Seeley RJ, Kohli R. The role of small heterodimer partner in nonalcoholic fatty liver disease improvement after sleeve gastrectomy in mice. Obesity (Silver Spring) 22: 2301‐2311, 2014. 10.1002/oby.20890.
 93.Nannipieri M, Baldi S, Mari A, Colligiani D, Guarino D, Camastra S, Barsotti E, Berta R, Moriconi D, Bellini R, Anselmino M, Ferrannini E. Roux‐en‐Y gastric bypass and sleeve gastrectomy: Mechanisms of diabetes remission and role of gut hormones. J Clin Endocrinol Metab 98: 4391‐4399, 2013. 10.1210/jc.2013‐2538.
 94.Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon‐like peptide 1 [7‐36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type‐2 diabetes mellitus. J Clin Invest 91: 301‐307, 1993. 10.1172/JCI116186.
 95.Nausheen S, Shah IH, Pezeshki A, Sigalet DL, Chelikani PK. Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats. Am J Physiol Endocrinol Metab 305: E507‐518, 2013. 10.1152/ajpendo.00130.2013.
 96.Nguyen NQ, Debreceni TL, Bambrick JE, Bellon M, Wishart J, Standfield S, Rayner CK, Horowitz M. Rapid gastric and intestinal transit is a major determinant of changes in blood glucose, intestinal hormones, glucose absorption and postprandial symptoms after gastric bypass. Obesity (Silver Spring) 22: 2003‐2009, 2014. 10.1002/oby.20791.
 97.Nguyen NQ, Debreceni TL, Bambrick JE, Chia B, Deane AM, Wittert G, Rayner CK, Horowitz M, Young RL. Upregulation of intestinal glucose transporters after Roux‐en‐Y gastric bypass to prevent carbohydrate malabsorption. Obesity (Silver Spring) 22: 2164‐2171, 2014. 10.1002/oby.20829.
 98.Nies VJ, Sancar G, Liu W, van Zutphen T, Struik D, Yu RT, Atkins AR, Evans RM, Jonker JW, Downes MR. Fibroblast growth factor signaling in metabolic regulation. Front Endocrinol (Lausanne) 6: 193, 2015. 10.3389/fendo.2015.00193.
 99.Odstrcil EA, Martinez JG, Santa Ana CA, Xue B, Schneider RE, Steffer KJ, Porter JL, Asplin J, Kuhn JA, Fordtran JS. The contribution of malabsorption to the reduction in net energy absorption after long‐limb Roux‐en‐Y gastric bypass. Am J Clin Nutr 92: 704‐713, 2010. 10.3945/ajcn.2010.29870.
 100.Ogawa A, Harris V, McCorkle SK, Unger RH, Luskey KL. Amylin secretion from the rat pancreas and its selective loss after streptozotocin treatment. J Clin Invest 85: 973‐976, 1990. 10.1172/JCI114528.
 101.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 type 2 diabetes. Science 313: 1137‐1140, 2006. 10.1126/science.1128294.
 102.Papamargaritis D, le Roux CW, Sioka E, Koukoulis G, Tzovaras G, Zacharoulis D. Changes in gut hormone profile and glucose homeostasis after laparoscopic sleeve gastrectomy. Surg Obes Relat Dis 9: 192‐201, 2013. 10.1016/j.soard.2012.08.007.
 103.Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM. Bile acids: Natural ligands for an orphan nuclear receptor. Science 284: 1365‐1368, 1999.
 104.Patti ME, Houten SM, Bianco AC, Bernier R, Larsen PR, Holst JJ, Badman MK, Maratos‐Flier E, Mun EC, Pihlajamaki J, Auwerx J, Goldfine AB. Serum bile acids are higher in humans with prior gastric bypass: Potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring) 17: 1671‐1677, 2009. 10.1038/oby.2009.102.
 105.Peterli R, Steinert RE, Woelnerhanssen B, Peters T, Christoffel‐Courtin C, Gass M, Kern B, von Fluee M, Beglinger C. Metabolic and hormonal changes after laparoscopic Roux‐en‐Y gastric bypass and sleeve gastrectomy: A randomized, prospective trial. Obes Surg 22: 740‐748, 2012. 10.1007/s11695‐012‐0622‐3.
 106.Peterli R, Wolnerhanssen B, Peters T, Devaux N, Kern B, Christoffel‐Courtin C, Drewe J, von Flue M, Beglinger C. Improvement in glucose metabolism after bariatric surgery: Comparison of laparoscopic Roux‐en‐Y gastric bypass and laparoscopic sleeve gastrectomy: A prospective randomized trial. Ann Surg 250: 234‐241, 2009. 10.1097/SLA.0b013e3181ae32e3.
 107.Pournaras DJ, Glicksman C, Vincent RP, Kuganolipava S, Alaghband‐Zadeh J, Mahon D, Bekker JH, Ghatei MA, Bloom SR, Walters JR, Welbourn R, le Roux CW. The role of bile after Roux‐en‐Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology 153: 3613‐3619, 2012. 10.1210/en.2011‐2145.
 108.Ramracheya RD, McCulloch LJ, Clark A, Wiggins D, Johannessen H, Olsen MK, Cai X, Zhao CM, Chen D, Rorsman P. PYY‐dependent restoration of impaired insulin and glucagon secretion in type 2 diabetes following Roux‐En‐Y gastric bypass surgery. Cell Rep 15: 944‐950, 2016. 10.1016/j.celrep.2016.03.091.
 109.Reimann F, Tolhurst G, Gribble FM. G‐protein‐coupled receptors in intestinal chemosensation. Cell Metab 15: 421‐431, 2012. 10.1016/j.cmet.2011.12.019.
 110.Richardson CT, Walsh JH, Hicks MI, Fordtran JS. Studies on the mechanisms of food‐stimulated gastric acid secretion in normal human subjects. J Clin Invest 58: 623‐631, 1976. 10.1172/JCI108509.
 111.Rorsman P, Braun M. Regulation of insulin secretion in human pancreatic islets. Annu Rev Physiol 75: 155‐179, 2013. 10.1146/annurev‐physiol‐030212‐183754.
 112.Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, Anderson CM, Parkes DG, Baron AD. Leptin responsiveness restored by amylin agonism in diet‐induced obesity: Evidence from nonclinical and clinical studies. Proc Natl Acad Sci U S A 105: 7257‐7262, 2008. 10.1073/pnas.0706473105.
 113.Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva‐Datchary P, Myronovych A, Karns R, Wilson‐Perez HE, Sandoval DA, Kohli R, Backhed F, Seeley RJ. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 509: 183‐188, 2014. 10.1038/nature13135.
 114.Sachdev S, Wang Q, Billington C, Connett J, Ahmed L, Inabnet W, Chua S, Ikramuddin S, Korner J. FGF 19 and bile acids increase following Roux‐en‐Y gastric bypass but not after medical management in patients with type 2 diabetes. Obes Surg 26: 957‐965, 2016. 10.1007/s11695‐015‐1834‐0.
 115.Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science 341: 406‐410, 2013. 10.1126/science.1235103.
 116.Salehi M, Gastaldelli A, D'Alessio DA. Blockade of glucagon‐like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass. Gastroenterology 146: 669‐680 e662, 2014. 10.1053/j.gastro.2013.11.044.
 117.Salehi M, Prigeon RL, D'Alessio DA. Gastric bypass surgery enhances glucagon‐like peptide 1‐stimulated postprandial insulin secretion in humans. Diabetes 60: 2308‐2314, 2011. 10.2337/db11‐0203.
 118.Samat A, Malin SK, Huang H, Schauer PR, Kirwan JP, Kashyap SR. Ghrelin suppression is associated with weight loss and insulin action following gastric bypass surgery at 12 months in obese adults with type 2 diabetes. Diabetes Obes Metab 15: 963‐966, 2013. 10.1111/dom.12118.
 119.Sandoval DA, D'Alessio DA. Physiology of proglucagon peptides: Role of glucagon and GLP‐1 in health and disease. Physiol Rev 95: 513‐548, 2015. 10.1152/physrev.00013.2014.
 120.Santo MA, Riccioppo D, Pajecki D, Kawamoto F, de Cleva R, Antonangelo L, Marcal L, Cecconello I. Weight regain after gastric bypass: Influence of gut hormones. Obes Surg 26: 919‐925, 2016. 10.1007/s11695‐015‐1908‐z.
 121.Sato T, Nakamura Y, Shiimura Y, Ohgusu H, Kangawa K, Kojima M. Structure, regulation and function of ghrelin. J Biochem 151: 119‐128, 2012. 10.1093/jb/mvr134.
 122.Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 366: 1567‐1576, 2012. 10.1056/NEJMoa1200225.
 123.Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ. Oxyntomodulin from distal gut. Role in regulation of gastric and pancreatic functions. Dig Dis Sci 34: 1411‐1419, 1989.
 124.Schwartz MW, Woods SC, Porte D, Jr., Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 404: 661‐671, 2000. 10.1038/35007534.
 125.Shin AC, Zheng H, Townsend RL, Sigalet DL, Berthoud HR. Meal‐induced hormone responses in a rat model of Roux‐en‐Y gastric bypass surgery. Endocrinology 151: 1588‐1597, 2010. 10.1210/en.2009‐1332.
 126.Sonne DP, Samuel van Nierop F, Kulik W, Soeters MR, Vilsboll T, Knop FK. Postprandial plasma concentrations of individual bile acids and FGF‐19 in patients with type 2 diabetes. J Clin Endocrinol Metab: 101: 3002‐3009, 2016. 10.1210/jc.2016‐1607.
 127.Stefater MA, Perez‐Tilve D, Chambers AP, Wilson‐Perez HE, Sandoval DA, Berger J, Toure M, Tschop M, Woods SC, Seeley RJ. Sleeve gastrectomy induces loss of weight and fat mass in obese rats, but does not affect leptin sensitivity. Gastroenterology 138: 2426‐2436, 2436 e2421‐2423, 2010. 10.1053/j.gastro.2010.02.059.
 128.Steinert RE, Peterli R, Keller S, Meyer‐Gerspach AC, Drewe J, Peters T, Beglinger C. Bile acids and gut peptide secretion after bariatric surgery: A 1‐year prospective randomized pilot trial. Obesity (Silver Spring) 21: E660‐E668, 2013. 10.1002/oby.20522.
 129.Svendsen B, Pedersen J, Albrechtsen NJ, Hartmann B, Torang S, Rehfeld JF, Poulsen SS, Holst JJ. An analysis of cosecretion and coexpression of gut hormones from male rat proximal and distal small intestine. Endocrinology 156: 847‐857, 2015. 10.1210/en.2014‐1710.
 130.Theodorakis MJ, Carlson O, Michopoulos S, Doyle ME, Juhaszova M, Petraki K, Egan JM. Human duodenal enteroendocrine cells: Source of both incretin peptides, GLP‐1 and GIP. Am J Physiol Endocrinol Metab 290: E550‐E559, 2006. 10.1152/ajpendo.00326.2004.
 131.Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K. Targeting bile‐acid signalling for metabolic diseases. Nat Rev Drug Discov 7: 678‐693, 2008. 10.1038/nrd2619.
 132.Tomlinson E, Fu L, John L, Hultgren B, Huang X, Renz M, Stephan JP, Tsai SP, Powell‐Braxton L, French D, Stewart TA. Transgenic mice expressing human fibroblast growth factor‐19 display increased metabolic rate and decreased adiposity. Endocrinology 143: 1741‐1747, 2002. 10.1210/endo.143.5.8850.
 133.Tong J, Davis HW, Gastaldelli A, D'Alessio D. Ghrelin impairs prandial glucose tolerance and insulin secretion in healthy humans despite increasing GLP‐1. J Clin Endocrinol Metab 101: 2405‐2414, 2016. 10.1210/jc.2015‐4154.
 134.Unger RH, Cherrington AD. Glucagonocentric restructuring of diabetes: A pathophysiologic and therapeutic makeover. J Clin Invest 122: 4‐12, 2012. 10.1172/JCI60016.
 135.Vetter ML, Wadden TA, Teff KL, Khan ZF, Carvajal R, Ritter S, Moore RH, Chittams JL, Iagnocco A, Murayama K, Korus G, Williams NN, Rickels MR. GLP‐1 plays a limited role in improved glycemia shortly after Roux‐en‐Y gastric bypass: A comparison with intensive lifestyle modification. Diabetes 64: 434‐446, 2015. 10.2337/db14‐0558.
 136.Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439: 484‐489, 2006. 10.1038/nature04330.
 137.Whitney EN, Rolfes SR. Understanding Nutrition. Belmont, California: West/Wadsworth; London: International Thomson Pub., 1999.
 138.Wilcox G. Insulin and insulin resistance. Clin Biochem Rev 26: 19‐39, 2005.
 139.Wilson‐Perez HE, Chambers AP, Ryan KK, Li B, Sandoval DA, Stoffers D, Drucker DJ, Perez‐Tilve D, Seeley RJ. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon‐like Peptide 1 receptor deficiency. Diabetes 62: 2380‐2385, 2013. 10.2337/db12‐1498.
 140.Wu JM, Yu HJ, Lai HS, Yang PJ, Lin MT, Lai F. Improvement of heart rate variability after decreased insulin resistance after sleeve gastrectomy for morbidly obesity patients. Surg Obes Relat Dis 11: 557‐563, 2015. 10.1016/j.soard.2014.09.011.
 141.Yan W, Polidori D, Yieh L, Di J, Wu X, Moreno V, Li L, Briscoe CP, Shankley N, Dohm GL, Pories WJ. Effects of meal size on the release of GLP‐1 and PYY after Roux‐en‐Y gastric bypass surgery in obese subjects with or without type 2 diabetes. Obes Surg 24: 1969‐1974, 2014. 10.1007/s11695‐014‐1316‐9.
 142.Yang J, Feng X, Zhong S, Wang Y, Liu J. Gastric bypass surgery may improve beta cell apoptosis with ghrelin overexpression in patients with BMI >/= 32.5 kg/m(2.). Obes Surg 24: 561‐571, 2014. 10.1007/s11695‐013‐1135‐4.
 143.Ye J, Hao Z, Mumphrey MB, Townsend RL, Patterson LM, Stylopoulos N, Munzberg H, Morrison CD, Drucker DJ, Berthoud HR. GLP‐1 receptor signaling is not required for reduced body weight after RYGB in rodents. Am J Physiol Regul Integr Comp Physiol 306: R352‐362, 2014. 10.1152/ajpregu.00491.2013.
 144.Yousseif A, Emmanuel J, Karra E, Millet Q, Elkalaawy M, Jenkinson AD, Hashemi M, Adamo M, Finer N, Fiennes AG, Withers DJ, Batterham RL. Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl‐ghrelin, peptide YY3‐36 and active GLP‐1 levels in non‐diabetic humans. Obes Surg 24: 241‐252, 2014. 10.1007/s11695‐013‐1066‐0.
 145.Yu H, Ni Y, Bao Y, Zhang P, Zhao A, Chen T, Xie G, Tu Y, Zhang L, Su M, Wei L, Jia W, Jia W. Chenodeoxycholic acid as a potential prognostic marker for Roux‐en‐Y gastric bypass in Chinese obese patients. J Clin Endocrinol Metab 100: 4222‐4230, 2015. 10.1210/jc.2015‐2884.
 146.Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE, Krajmalnik‐Brown R. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 106: 2365‐2370, 2009. 10.1073/pnas.0812600106.
 147.Zhang JH, Nolan JD, Kennie SL, Johnston IM, Dew T, Dixon PH, Williamson C, Walters JR. Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids. Am J Physiol Gastrointest Liver Physiol 304: G940‐G948, 2013. 10.1152/ajpgi.00398.2012.
 148.Zhang Y, Lee FY, Barrera G, Lee H, Vales C, Gonzalez FJ, Willson TM, Edwards PA. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A 103: 1006‐1011, 2006. 10.1073/pnas.0506982103.
 149.Zhang JV, Ren PG, Avsian‐Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJ. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 310: 996‐999, 2005. 10.1126/science.1117255.

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Ki‐Suk Kim, Darleen A. Sandoval. Endocrine Function after Bariatric Surgery. Compr Physiol 2017, 7: 783-798. doi: 10.1002/cphy.c160019