Comprehensive Physiology Wiley Online Library

Thyroid Hormone Regulation of Islet Cell Hormone Metabolic Actions

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Molecular Actions of Thyroid Hormone
2 Thyroid Hormone Regulation of Growth and Development
3 Extrahypothalamic Thyrotropin‐Releasing Hormone
4 Metabolic Actions of Islet Cell Hormones
4.1 Insulin
4.2 Glucagon
4.3 Amylin
4.4 Calcitonin Gene‐Related Peptide
4.5 Somatostatin
4.6 Pancreatic Polypeptide
5 Thyroid Hormone Regulation of Insulin Metabolic Actions
5.1 Euthyroidism
5.2 Hyperthyroidism
5.3 Hypothyroidism
6 Thyroid Hormone Regulation of Glucagon Metabolic Actions
6.1 Hyperthyroidism
6.2 Hypothyroidism
7 Thyroid Hormone Regulation of Somatostatin Metabolic Actions
7.1 Hyperthyroidism
7.2 Hypothyroidism
8 Thyroid Hormone Regulation of Pancreatic Polypeptide Metabolic Actions
9 Summary and Conclusions
Figure 1. Figure 1.

Rat liver nuclear T3 binding as a function of plasma T3 levels.

[Reprinted with permission from Oppenheimer 202, with permission. Copyright © 1987 American Association for the Advancement of Science.]
Figure 2. Figure 2.

Isoforms of the rat thyroid receptor and related proteins. The amino acid sequences are deduced from rat cDNAs. Numbering of the amino acid residues is indicated above each isoform. The percent of amino acid identity in the DNA‐binding domain is also indicated (numbered from the first cysteine residue). Identical patterns indicate 100% identity. Similar patterns (horizontal lines) indicate highly similar sequences in the TRβ and TRα1 isoforms. Human TRα2 has two fewer amino acids in its unique carboxyl terminus.

[From Lazar 147 with permission.]
Figure 3. Figure 3.

Functional domains of the thyroid hormone receptor. The amino acid numbering for TRβ1 is illustrated

[From Lazar 147 with permission.]
Figure 4. Figure 4.

Organization of the human amylin gene. A. Schematic representation of the amylin genomic clone LDhIAP‐M1. EcoR1 restriction endonuclease sites are represented as R. Exons are indicated as open boxes, and the sequenced region is indicated by a thick bar. The location and orientation of Alu repetitive sequence elements are indicated by arrows. B. Relationship between hIAPP mRNA and gene. The region of the mRNA encoded by each exon is indicated: 5′‐UT and 3′‐UT represent the 5′‐ and 3′‐untranslated regions of the mRNA, and SP denotes the signal peptide.

[From Nishi et al. 194 with permission.]
Figure 5. Figure 5.

Schematic representation of the structural organization of the human α‐calcitonin/CGRP gene. Two different mRNAs may be produced from the alternative processing of the single primary transcript and the use of two polyadenylation sites: one coding for the calcitonin precursor and the other for the CGRP precursor. Posttranslational modifications include intramolecular disulfide bridge formation at the N terminus and amidation of the C‐terminal residue. CT, calcitonin; KC, katacalcin; CGRP, calcitonin gene‐related peptide.

[From Wimalawansa, 300 with permission.]
Figure 6. Figure 6.

Schematic diagram summarizing the processing of mammalian preprosomatostatin. Note that the “central peptide” shown with a dashed line is only hypothetical and has not yet been found in tissue.

[From Patel and Tannenbaum 216 with permission.]
Figure 7. Figure 7.

Ink sequence containing three potential nuclear hormone‐receptor half‐sites. The consensus sequence is a half‐site for RAR, TR, and VDR. The Ink sequence corresponds to −1037 to −1006 of the human insulin gene as cloned in plasmid phins300. Also shown are response elements in the bovine and rat growth hormone (bGH and rGH, respectively) genes and TREpal (an artificial response element), which contain two receptor half‐sites arranged as a palindrome with zero spacing, and which mediate responses to both retinoic acid and T3, and direct‐repeat retinoic acid response elements with 2 base pair spacing (DR‐2), which are located in the mouse CRBI (mCRBI) and the mouse CRABPII (mCRABPII). The black dots below each sequence denote variations from the consensus half‐site sequence.

[From Clark et al. 47 with permission.]
Figure 8. Figure 8.

Effect of thyroid hormone status on GLUT1 and GLUT4 glucose transporters in rat epididymal adipocyte total cellular membranes. A total cellular membrane fraction was prepared from adipocytes of euthyroid (E), hypothyroid (h), and hyperthyroid (H) rats as described. Membrane proteins (100 μg/lane) were subjected to SDS‐PAGE and blotted onto nitrocellulose. GLUT1 and GLUT4 glucose transporters were identified with an antiserum against a C‐terminal peptide of GLUT1 and GLUT4 glucose transporters, respectively. Typical autoradiographs are shown.

[From Matthei et al. 169 with permission of the Journal of Endocrinology Ltd.]
Figure 9. Figure 9.

Effect of hyperthyroidism on GLUT4 glucose transporters in rat epididymal adipocyte plasma membranes. Columns represent mean numbers of gold particles per square micrometer (μm2) of cell surface; bars denote SEM calculated on normalized counts from five experiments. Group T vs. group C GLUT4, p < .01; α2, p < .3. T, triiodothyronine‐treated; C, controls; GLUT4, glucose transporter isoform; α2, Na/K‐ATPase isoform.

[From Voldstedlund et al. 284, with permission.]
Figure 10. Figure 10.

Mean (± SEM) concentrations of glucose, insulin, C‐peptide, and rates of insulin secretion during a hyperglycemic clamp in hyperthyroid patients and control subjects.

[From O'Meara et al. 201 with permission.]
Figure 11. Figure 11.

Plasma glucose and counterregulatory hormones before and after insulin administration in hyperthyroid and control women. The significance values between the two groups obtained by ANOVA were as follows: glucose, F = 7.1, p < .01; glucagon, F = 99.5, p < .001; epinephrine, f = 0.2, p > .1; norepinephrine,f = 557.7, p > .001; growth hormone, F = 18.1, p < 0.001; ACTH, F = 23.5, p < .001; and cortisol, F = 1.5, p > .1. Separating the fall in plasma glucose (0–20 min) from the plasma glucose recovery 20‐120 mm), the corresponding ANOVA F values were 2.1 (p > .1) and 14.8 (p < .001), respectively.

[From Moghetti et al. 175 with permission.]


Figure 1.

Rat liver nuclear T3 binding as a function of plasma T3 levels.

[Reprinted with permission from Oppenheimer 202, with permission. Copyright © 1987 American Association for the Advancement of Science.]


Figure 2.

Isoforms of the rat thyroid receptor and related proteins. The amino acid sequences are deduced from rat cDNAs. Numbering of the amino acid residues is indicated above each isoform. The percent of amino acid identity in the DNA‐binding domain is also indicated (numbered from the first cysteine residue). Identical patterns indicate 100% identity. Similar patterns (horizontal lines) indicate highly similar sequences in the TRβ and TRα1 isoforms. Human TRα2 has two fewer amino acids in its unique carboxyl terminus.

[From Lazar 147 with permission.]


Figure 3.

Functional domains of the thyroid hormone receptor. The amino acid numbering for TRβ1 is illustrated

[From Lazar 147 with permission.]


Figure 4.

Organization of the human amylin gene. A. Schematic representation of the amylin genomic clone LDhIAP‐M1. EcoR1 restriction endonuclease sites are represented as R. Exons are indicated as open boxes, and the sequenced region is indicated by a thick bar. The location and orientation of Alu repetitive sequence elements are indicated by arrows. B. Relationship between hIAPP mRNA and gene. The region of the mRNA encoded by each exon is indicated: 5′‐UT and 3′‐UT represent the 5′‐ and 3′‐untranslated regions of the mRNA, and SP denotes the signal peptide.

[From Nishi et al. 194 with permission.]


Figure 5.

Schematic representation of the structural organization of the human α‐calcitonin/CGRP gene. Two different mRNAs may be produced from the alternative processing of the single primary transcript and the use of two polyadenylation sites: one coding for the calcitonin precursor and the other for the CGRP precursor. Posttranslational modifications include intramolecular disulfide bridge formation at the N terminus and amidation of the C‐terminal residue. CT, calcitonin; KC, katacalcin; CGRP, calcitonin gene‐related peptide.

[From Wimalawansa, 300 with permission.]


Figure 6.

Schematic diagram summarizing the processing of mammalian preprosomatostatin. Note that the “central peptide” shown with a dashed line is only hypothetical and has not yet been found in tissue.

[From Patel and Tannenbaum 216 with permission.]


Figure 7.

Ink sequence containing three potential nuclear hormone‐receptor half‐sites. The consensus sequence is a half‐site for RAR, TR, and VDR. The Ink sequence corresponds to −1037 to −1006 of the human insulin gene as cloned in plasmid phins300. Also shown are response elements in the bovine and rat growth hormone (bGH and rGH, respectively) genes and TREpal (an artificial response element), which contain two receptor half‐sites arranged as a palindrome with zero spacing, and which mediate responses to both retinoic acid and T3, and direct‐repeat retinoic acid response elements with 2 base pair spacing (DR‐2), which are located in the mouse CRBI (mCRBI) and the mouse CRABPII (mCRABPII). The black dots below each sequence denote variations from the consensus half‐site sequence.

[From Clark et al. 47 with permission.]


Figure 8.

Effect of thyroid hormone status on GLUT1 and GLUT4 glucose transporters in rat epididymal adipocyte total cellular membranes. A total cellular membrane fraction was prepared from adipocytes of euthyroid (E), hypothyroid (h), and hyperthyroid (H) rats as described. Membrane proteins (100 μg/lane) were subjected to SDS‐PAGE and blotted onto nitrocellulose. GLUT1 and GLUT4 glucose transporters were identified with an antiserum against a C‐terminal peptide of GLUT1 and GLUT4 glucose transporters, respectively. Typical autoradiographs are shown.

[From Matthei et al. 169 with permission of the Journal of Endocrinology Ltd.]


Figure 9.

Effect of hyperthyroidism on GLUT4 glucose transporters in rat epididymal adipocyte plasma membranes. Columns represent mean numbers of gold particles per square micrometer (μm2) of cell surface; bars denote SEM calculated on normalized counts from five experiments. Group T vs. group C GLUT4, p < .01; α2, p < .3. T, triiodothyronine‐treated; C, controls; GLUT4, glucose transporter isoform; α2, Na/K‐ATPase isoform.

[From Voldstedlund et al. 284, with permission.]


Figure 10.

Mean (± SEM) concentrations of glucose, insulin, C‐peptide, and rates of insulin secretion during a hyperglycemic clamp in hyperthyroid patients and control subjects.

[From O'Meara et al. 201 with permission.]


Figure 11.

Plasma glucose and counterregulatory hormones before and after insulin administration in hyperthyroid and control women. The significance values between the two groups obtained by ANOVA were as follows: glucose, F = 7.1, p < .01; glucagon, F = 99.5, p < .001; epinephrine, f = 0.2, p > .1; norepinephrine,f = 557.7, p > .001; growth hormone, F = 18.1, p < 0.001; ACTH, F = 23.5, p < .001; and cortisol, F = 1.5, p > .1. Separating the fall in plasma glucose (0–20 min) from the plasma glucose recovery 20‐120 mm), the corresponding ANOVA F values were 2.1 (p > .1) and 14.8 (p < .001), respectively.

[From Moghetti et al. 175 with permission.]
References
 1. Abrams, M. I., and D. R. Gilligan. Carbohydrate metabolism in human hypothyroidism induced by total ablation of the thyroid gland. II. The blood sugar response to insulin. Am. J. Med. Sci. 188: 796–800, 1934.
 2. Achmadi, J., and Y. Terashima. The effect of propylthiouracilinduced low thyroid function on secretion response and action of insulin in sheep. Domest. Anim. Endocrinol. 12: 157–166, 1995.
 3. Adrian, T. E., H. S. Besterman, C. N. Mallinson, C. Caralotis, and S. R. Bloom. Impaired pancreatic polypeptide release in patients with chronic pancreatitis and steatorrhea. Gut 20: 98–101, 1979.
 4. Adrian, T. E., S. R. Bloom, M. G. Bryant, J. M. Polak, P. H. Heitz, and A. J. Barnes. Distribution and release of human pancreatic polypeptide. Gut 17: 940–944, 1976.
 5. Adrian, T. E., L. O. Uttenthal, S. J. Williams, and S. R. Bloom. Secretion of pancreatic polypeptide in patients with pancreatic endocrine tumors. N. Engl. J. Med. 315: 287–291, 1986.
 6. Ahren, B.. Hyperthyroidism and glucose intolerance. Acta Med. Scand. 220: 5–14, 1986.
 7. Alevizaki, M., A. Shiraishi, F. V. Rasool, G. J. Ferrier, I. Macintyre, and S. Legon. The calcitonin‐like sequence of the ã CGRP gene. FEBS Lett. 206: 47–52, 1986.
 8. Allen, F. M.. Experimental studies in diabetes. Series II. The intestinal pancreatic function in relation to body mass and metabolism. 10. The influence of the thyroid upon diabetes. J. Metab. Res. 1: 619–665, 1922.
 9. Amara, S. G., J. L. Arriza, S. E. Leff, L. W. Swanson, R. M. Evans, and M. G. Rosenfeld. Expression in brain of a messenger RNA encoding a novel neuropeptide homologous to calcitonin generelated peptide. Science 229: 1094–1097, 1985.
 10. Amara, S. G., V. Jonas, M. G. Rosenfeld, E. S. Ong, and R. M. Evans. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature 298: 240–244, 1982.
 11. Amherdt, M., Y. C. Patel, and L. Orci. Selective binding of somatostatin‐14 and somatostatin‐28 to islet cells revealed by quantitative electron microscopic autoradiography. J. Clin. Invest. 80: 1455–1458, 1987.
 12. Andersen, O. O., T. Friis, and G. Rosselin. Glucose tolerance and insulin secretion in hyperthyroidism. Acta Endocrinol. 84: 576–587, 1977.
 13. Anderson, W. T.. Studies on blood sugar and glycosuria in exophthalmic goitre. Acta Med. Scand. 54: 1, 1933.
 14. Andreani, D., F. Fallucca, G. Tamburrano, M. Iavicoli, and G. Menzinger. Insulin, glucagon, and growth hormone in primary adult myxoedema. Diabetologia 10: 7–12, 1974.
 15. Andreani, D., G. Menzinger, F. Fallucca, G. Alberti, G. Tamburrano, and C. Cassano. Insulin levels in thyrotoxicosis and primary myxoedema: response to intravenous glucose and glucagon. Diabetologia 6: 1–7, 1970.
 16. Andrus, E. C.. Hyperthyroidism and diabetes mellitus. Bull. Johns Hopkins Hosp. 50: 383–393, 1932.
 17. Baetens, D., F. Malaisse‐Lagae, A. Perrelet, and L. Orci. Endocrine pancreas: three dimensional reconstruction shows two types of islets of Langerhans. Science 206: 1323–1325, 1979.
 18. Bailey, C. J., I. M. Lord, and T. W. Atkins. The insulin receptor and diabetes. In: Recent Advances in Diabetes, edited by M. Nattrass, and J. Santiago. Edinburgh: Churchill Livingstone, p. 27, 1993.
 19. Baldini, M., A. Catania, A. Orsatti, M. G. Manfredi, P. Motta, and L. Cantalamessa. Inhibitory effect of somatostatin on abnormal GH response to TRH in primary hypothyroidism. Exp. Clin. Endocrinol. 99: 80–83, 1992.
 20. Baniahmad, A., I. Ha, D. Reinberg, S. Tsai, M. J. Tsai, and B. W. O'Malley. Interaction of human thyroid hormone receptor ä with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc. Natl. Acad. Sci. USA 90: 8832–8836, 1993.
 21. Baniahmad, A., C. Steiner, A. C. Kohne, and R. Renkawitz. Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site. Cell 61: 505–514, 1990.
 22. Baniahmad, A., S. Y. Tsai, B. W. O'Malley, and M. J. Tsai. Kindred S thyroid hormone receptor is an active and constitutive silencer and repressor for thyroid hormone and retinoic acid responses. Proc. Natl. Acad. Sci. USA 89: 10633–10637, 1992.
 23. Barzilai, N., E. Karnieli, D. Barzilai, and P. Cohen. Correlation between glucose disposal and amino acids levels in hyperthyroidism. Horm. Metab. Res. 25: 382–385, 1993.
 24. Beer, S. F., J. H. Parr, R. C. Temple, and C. N. Hales. The effect of thyroid disease on proinsulin and C‐peptide levels. Clin. Endocrinol. 30: 378–383, 1989.
 25. Bell, G. I., and T. Reisine. Molecular biology of somatostatin receptors. Trends Neurosci. 16: 34–38, 1993.
 26. Benvenga, S., F. Trimarchi, and A. Facchiano. Homology of calcitonin with the amyloid‐related proteins. J. Endocrinol. Invest. 17: 119–122, 1994.
 27. Bernal, J., and J. Nunez. Thyroid hormones and brain development. Eur. J. Endocrinol. 133: 390–398, 1995.
 28. Bodansky, A.. Effect of thyroidectomy upon the reaction of sheep to insulin. Proc. Soc. Exp. Biol. Med. 21: 46, 1923.
 29. Boden, G., X. Chen, J. Rosner, and M. Barton. Effects of a 48‐h fat infusion on insulin secretion and glucose utilization. Diabetes 44: 1239–1242, 1995.
 30. Bottazzo, G. F., A. G. Cudworth, D. J. Moul, D. Doniach, and H. Festenstein. Evidence for a primary autoimmune type of diabetes mellitus. Br. Med. J. 2: 1253–1255, 1978.
 31. Bradley, D. J., H. C. Towle, and W. S. Young III. Spatial and temporal expression of α‐ and ã‐thyroid hormone receptor mRNAs, including the ã2 subtype, in the developing mammalian nervous system. J. Neurosci. 12: 2288–2302, 1992.
 32. Brent, G. A., D. D. Moore, and P. R. Larsen. Thyroid hormone regulation of gene expression. Annu. Rev. Physiol. 53: 17–35, 1991.
 33. Brent, G. A., G. R. Williams, and J. W. Harney. Effects of varying the position of thyroid hormone response elements within the rat growth hormone promoter: implications for positive and negative regulations by 3,5,3′‐triiodothyronine. Mol. Endocrinol. 5: 542–548, 1991.
 34. Britton, S. W., and W. K. Myers. The thyroid gland and the sensitivity of animals to insulin. Am. J. Physiol. 84: 132–140, 1928.
 35. Brown, J. G., and D. J. Millward. Dose response of protein turnover in rat skeletal muscle to triiodothyronine treatment. Biochem. Biophys. Acta 757: 182–190, 1983.
 36. Brown, M. J., and A. H. Morice. Clinical pharmacology of vasodilator peptides. J. Cardiovasc. Pharmacol. 10 (Suppl 12): S82–S87, 1987.
 37. Bruno, J. F., Y. Xu, J. Song, and M. Berelowitz. Tissue distribution of somatostatin receptor subtype messenger ribonucleic acid in the rat. Endocrinol. 133: 2561–2567, 1993.
 38. Burn, J. H. and H. P. Marks. On the relation of thyroidectomy to the effect of insulin on the blood sugar of rabbits. J. Physiol. 59: 8, 1924.
 39. Cameron, G. R.. The influence of thyroid feeding on the islets of Langerhans in the guinea‐pig. J. Pathol. Bacteriol. 29: 177, 1929.
 40. Canter, W. J., W. S. Van Der Weijden Benjamin, and F. H. Faas. Effect of a protein‐free diet on muscle protein turnover and antigen conservation in euthyroid and hyperthyroid rats. Biochem. J. 217: 471–476, 1984.
 41. Cavagnini, F., M. Peracchi, U. Raggi, R. Bana, A. E. Pontiroli, A. Malinverni, and M. Pinto. Impairment of growth hormone and insulin secretion in hyperthyroidism. Eur. J. Clin. Invest. 4: 71–77, 1974.
 42. Cavallo‐Perrin, P., A. Bruno, L. Boine, M. Cassader, G. Lenti, and G. Pagano. Insulin resistance in Graves disease: a quantitative invivo evaluation. Eur. J. Clin. Invest. 18: 607–613, 1988.
 43. Cech, J. M. and J. M Amatruda. The effect of triiodothyronine on insulin binding and action in rat adipocytes. Horm. Metab. Res. 15: 530–532, 1983.
 44. Cheek, D. B., and J. E. Graystone. Insulin and growth hormone: regulators of growth with particular reference to muscle. Kidney Int. 14: 317–322, 1978.
 45. Chilson, O. P. and J. Sacks. Effect of hyperthyroidism on distribution of adenosine phosphates and glycogen in liver. Proc. Soc. Exp. Biol. Med. 101: 331–332, 1959.
 46. Chin, S. Y., J. M. Hall, S. D. Brain, and I. K. Morton. Vasodilator responses to calcitonin gene‐related peptide (CGRP) and amylin in the rat perfused kidney are mediated via CGRPI receptors. J. Pharmacol. Exp. Ther. 269: 989–992, 1994.
 47. Clark, A. R., M. E. Wilson, N. J. London, R. F. James, and K. Docherty. Identification and characterization of a functional retinoic acid/thyroid hormone‐response element upstream of the human insulin gene enhancer. Biochem. J. 309: 863–870, 1995.
 48. Cohen, A. M.. Interrelation of insulin activity and thyroid function. Am. J. Physiol. 188: 287–294, 1957.
 49. Cohen, P., N. Barzilai, D. Barzilai, and E. Karnieli. Correlation between insulin clearance and insulin responsiveness: studies in normal, obese, hyperthyroid and Cushing's syndrome patients. Metabolism 35: 744–749, 1986.
 50. Cooper, G.J.S.. Amylin compared with calcitonin gene‐related peptide: structure, biology, and relevance to metabolic disease. Endocrine Rev. 15: 163–201, 1994.
 51. Cooper, G.J.S., B. Leighton, G. D. Dimitriadis, M. Parry‐Billings, J. M. Kowalchuk, K. Howland, J. B. Rothbard, A. C. Willis, and K.B.M. Reid. Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. Proc. Natl. Acad. Sci. USA 85: 7763–7766, 1988.
 52. Cooper, G.J.S., B. Leighton, A. C. Willis, and A. J. Day. The amylin superfamily: a novel grouping of biologically active polypeptides related to the insulin A‐chain. Prog. Growth Factor Res. 1: 99–105, 1989.
 53. Cooper, G.J.S., A. C. Willis, A. Clark, R. C. Turner, R. B. Sim, and K.B.M. Reid. Purification and characterization of a peptide from amyloid‐rich pancreases of type 2 diabetic patients. Proc. Natl. Acad. Sci. USA 84: 8628–8632, 1987.
 54. Cote, G. J., and R. F. Gagel. Dexamethasone differentially affects the level of calcitonin and calcitonin gene‐related peptide mRNAs expressed in a human medullary thyroid carcinoma cell line. J. Biol. Chem. 261: 15524–15528, 1986.
 55. Czech, M. P., C. C. Malbon, K. Kerman, W. Gitomer, and P. F. Pilch. Effect of thyroid status on insulin action in rat adipocytes and skeletal muscle. J. Clin. Invest. 66: 574–582, 1980.
 56. Dainiak, N., R. Hoffman, L. A. Maffei, and B. G. Forget. Potentiation of human erythropoiesis in vitro by thyroid hormone. Nature 272: 260–262, 1978.
 57. D'Alessio, D. A., C. Sieber, C. Beglinger, and J. W. Ensinck. A physiologic role for somatostatin‐28 as a regulator of insulin secretion. J. Clin. Invest. 84: 857–862, 1989.
 58. Davidson, M. B.. The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly. Metabolism 28: 688–705, 1979.
 59. De Bodo, R. C. and N. Altszuler. Insulin hypersensitivity and physiological insulin antagonists. Physiol. Rev. 38: 389–445, 1958.
 60. Defronzo, R. A., and E. Ferrannini. Insulin actions in vivo: protein metabolism. In: International Textbook of Diabetes Mellitus, edited by K.G.G.M. Alberti, R. A. De Fronzo, H. Kean, and P. Zimmet. Chichester: John Wiley and Sons, Ltd., p. 467–512, 1992.
 61. Deruyter, H., K. D. Burman, L. Wartofsky, and S. J. Taylor. Effects of thyroid hormones on the insulin receptor in rat liver membranes. Endocrinology 110: 1922–1925, 1982.
 62. Diaz, G. B., A. A. Paladini, M. E. Garcia, and J. J. Gagliardino. Changes induced by hypothyroidism in insulin secretion and in the properties of islet plasma membranes. Arch. Int. Physiol. Biochem. Biophys. 101: 263–269, 1993.
 63. Dimitriadis, G., B. Baker, H. Marsh, L. Mandarino, R. Rizza, R. Bergman, M. Haymond, and J. Gerich. Effect of thyroid hormone excess on action, secretion and metabolism of insulin in humans. Am. J. Physiol. 248: E593–E601, 1985.
 64. Doar, J. W., T. C. Stamp, V. Wynne, and T. K. Audhya. Effects of oral and intravenous glucose loading in thyrotoxicosis: studies of plasma glucose, free fatty acid, plasma insulin and blood pyruvate levels. Diabetes 18: 633–639, 1969.
 65. Donnerer, J., R. Schuligoi, C. Stein, and R. Amann. Upregulation, release, and axonal transport of substance P and calcitonin generelated peptide in adjuvant inflammation and regulatory function of nerve growth factor. Regul. Pept. 46: 150–154, 1993.
 66. Dow, D. S. and C. E. Allen. Steady‐state oxidation of glucose in hyperthyroid and hypothyroid rats. Can. J. Biochem. Physiol. 39: 981–990, 1961.
 67.Dumontpallier. Goître exophthalmique et glycosurie chez la měme malade. C. R. Soc. Biol. 4: 116, 1867.
 68. Eaton, R. P., R. C. Allen, D. S. Schade, K. M. Erickson, and J. Standefer. Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. J. Clin. Endocrinol. Metab. 51: 520–528, 1980.
 69. Ebiou, J. C., M. Bulant, P. Nicholas, and S. Aratan‐Spire. Pattern of thyrotropin‐releasing hormone secretion from the adult and neonatal rat pancreas: comparison with insulin secretion. Endocrinology 130: 1371–1379, 1992.
 70. Elgee, N. J. and R. H. Williams. Effects of thyroid function on insulin‐I131 degradation. Am. J. Physiol. 180: 13–15, 1955.
 71. Elrick, H., C. J. Hlad, and Y. Arai. Influence of thyroid function on carbohydrate metabolism and a new method for assessing response to insulin. J. Clin. Endocrinol. Metab. 21: 387–400, 1961.
 72. Farrant, R.. Hyperthyroidism: its experimental production in animals. Br. Med. J. 2: 1363, 1913.
 73. Federspil, G., M. Zaccaria, D. Casara, N. Sicolo, and C. Scandellari. Plasma insulin response to glibornuride in thyrotoxicosis. Diabete Metab. 2: 27–31, 1976.
 74. Ferrannini, E., and R. A. Defronzo. Insulin actions in vivo: glucose metabolism. In: International Textbook of Diabetes Mellitus, edited by K.G.G.M. Alberti, R.A. De Fronzo, H. Kean, and P. Zimmet. Chichester: John Wiley and Sons, Ltd., p. 409–438, 1992.
 75. Fondell, J. D., A. L. Roy, and R. G. Roeder. Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. Genes Dev. 7: 1400–1410, 1992.
 76. Forman, B. M., and H. H. Samuels. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol. Endocrinol. 4: 1293–1301, 1990.
 77. Forman, B. M., C. R. Yang, M. Au, J. Casanova, J. Ghysdael, and H. H. Samuels. A domain containing leucine‐zipper‐like motifs mediates novel in vivo interactions between the thyroid hormone and retinoic acid receptors. Mol. Endocrinol. 8: 1610–1626, 1989.
 78. Forman, B. M., C. Yang, F. Stanley, J. Casanova, and H. H. Samuels. C‐erbA protooncogenes mediate thyroid hormone‐dependent and independent regulation of the rat growth hormone and prolactin genes. Mol. Endocrinol. 2: 902–911, 1988.
 79. Foss, M. C., G.M.G.F. Paccola, M.J.A. Saad, W. P. Pimenta, C. E. Piccinato, and N. lazigi. Peripheral glucose metabolism in human hyperthyroidism. J. Clin. Endocrinol. Metab. 70: 1167–1172, 1990.
 80. Foster, D. P., and W. L. Lowrie. Diabetes mellitus associated with hyperthyroidism. Endocrinology 23: 681–691, 1938.
 81. Friedman, G. A., and J. Gottesman. The thyroid factor in pancreatic diabetes. Proc. N.Y. Pathol. Soc. 22: 211, 1923.
 82. Girgis, S. I., C. Lynch, C. J. Hillyard, J. C. Stevenson, P. A. Hill, D. W. Macdonald, and I. Macintyre. Calcitonin gene peptides: the diagnostic value of measurement in medullary thyroid carcinoma. Henry Ford Hosp. Med. J. 35: 118–119, 1987.
 83. Giustina, A., and W. B. Wehrenberg. Influence of thyroid hormones on the regulation of growth hormone secretion. Eur. J. Endocrinol. 133: 646–653, 1995.
 84. Glaser, B., A. I. Vinik, A. A. Sive, and J. C. Floyd, Jr.. Plasma human pancreatic polypeptide responses to administered secretin (effects of surgical vagotomy, cholinergic blockade and chronic pancreatitis). J. Clin. Endocrinol. Metab. 50: 1094–1099, 1980.
 85. Goldblat, M. W.. Insulin and the thyroidectomized rabbit. J. Physiol. 86: 46–59, 1936.
 86. Goodman, E. C., and L. L. Iversen. Calcitonin gene‐related peptide: novel neuropeptide. Life Sci. 38: 2169–2178, 1986.
 87. Gordon, A. S., and E. D. Zanjani. Humoral control of hemopoiesis. Adv. Int. Med. 18: 39–58, 1972.
 88. Greenberg, G. R., R. F. McCloy, T. E. Adrian, V. S. Chadwick, J. H. Baron, and S. R. Bloom. Inhibition of pancreatic and gallbladder functions by pancreatic polypeptide in man. Lancet 2: 1280–1283, 1978.
 89. Griffiths, W. J.. Insulin resistance and diagnosis of thyroid disease. Q. J. Med. 8: 23–40, 1939.
 90. Haber, R. S., F. Ismail‐Beigi, and J. N. Loeb. Time course of Na, K transport and other metabolic responses to thyroid hormone in clone 9 cells. Endocrinology 123: 238–247, 1988.
 91. Hagg, S. A., and S. A. Adibi. Leucine metabolism in thyrotoxicosis: plasma aminogram and 3‐methyl‐histidne excretion before and after treatment. Metabolism 34: 813–816, 1985.
 92. Hales, C. N., and D. E. Hyams. Plasma concentrations of glucose, nonesterified fatty acids and insulin during oral glucose tolerance tests in thyrotoxicosis. Lancet 2: 69–71, 1964.
 93. Halmi, N. S., H. Albert, D. J. Doughman, D. K. Granner, and B. N. Spirtos. Improved intravenous glucose tolerance in thyroidectomized or hypophysectomized rats treated with triiodothyronine. Endocrinology 64: 618–620, 1959.
 94. Hardeveld, C., and A.A.H. Van Kassenarr. Influence of experimental hyperthyroidism on skeletal muscle metabolism in the rat. Acta Endocrinol. 85: 71–83, 1977.
 95. Harris, P. E., M. Walker, F. Clark, P. D. Home, and K. G. Alberti. Forearm muscle metabolism in primary hypothyroidism. Eur. J. Clin. Invest. 23: 585–588, 1993.
 96. Heise, E., H. G. Joost, and A. Hasselblatt. Insulin binding and response to insulin of adipocytes from thyroxine‐treated rats. Endocrinology 110: 955–960, 1982.
 97. Heitz, P., J. M. Polak, and S. R. Bloom. Identification of the Dl cell as the source of human pancreatic polypeptide. Gut 17: 755–758, 1976.
 98. Herring, P. T.. The action of thyroid upon the growth of the body and organs of the white rat. Q. J. Exp. Physiol. 11: 231, 1917.
 99. Hess, W. N.. Islets of Langerhans in the pancreas of white rats. Anat. Rec. 84: 526, 1922.
 100. Hickman, P. E.. The effect of endogenous somatostatin upon human thyrotrophin (TSH) secretion. Horm. Metab. Res. 24: 73–77, 1992.
 101. Himms‐Hagen, J.. Sympathetic regulation of metabolism. Pharmacol. Rev. 19: 367–461, 1967.
 102. Hirata, Y., Y. Takagi, S. Takata, Y. Fukuda, H. Yoshimi, and T. Fujita. Calcitonin gene‐related peptide receptor in cultured vascular smooth muscle and endothelial cells. Biochem. Biophys. Res. Commun. 151: 1113–1121, 1988.
 103. Hoch, F. L.. Metabolic effects of thyroid hormones. In: Handbook of Physiology, Vol. 3, Endocrinology, Section 7, Thyroid, edited by M. A. Greer, and D. H. Solomon. Washington, DC: American Physiological Society, p. 391, 1974.
 104. Hodin, R. A., M. A. Lazar, and W. W. Chin. Differential and tissuespecific regulation of multiple rat c‐erbA messenger RNA species by thyroid hormone J. Clin. Invest. 85: 101–105, 1990.
 105. Hodin, R. A., M. A. Lazar, B. I. Wintman, D. S. Darling, R. J. Koenig, P. R. Larsen, D. D. Moore, and W. W. Chin. Identification of a thyroid hormone receptor that is pituitary‐specific. Science 244: 76–79, 1989.
 106. Hokfelt, T., S. Efendic, C. Hellerstrom, O. Johansson, R. Luft, and A. Arimura. Cellular localization of somatostatin in the endocrinelike cells and neurons of the rat with special reference to the Alcells of the pancreatic islets and to the hypothalamus. Acta Endocrinol. [Copenh.] 80 (Suppl 200): 5–41, 1975.
 107. Holst, J.. Glycosuria and diabetes in exophthalmic goitre. Acta Med. Scand. 55: 302, 1921.
 108. Hoovers, J. M., E. Redecker, F. Speleman, J. W. Hoppener, S. Bhola, J. Bliek, N. Van Roy, N. J. Leschot, A. Westerveld, and M. Mannens. High resolution chromosomal localization of the human calcitonin/CGRP/IAPP gene family members. Genomics 15: 525–529, 1993.
 109. Hoppener, J. W., P. H. Steenbergh, J. Zandberg, G. J. Adema, A. H. Geurts Van Kessel, C. J. Lips, and H. S. Jansz. A third CALC (pseudo)gene on chromosome 11. FEBS Lett. 233: 57–63, 1988.
 110. Houssay, B. A.. Thyroid and metathyroid diabetes. Endocrinology 35: 158–172, 1944.
 111. Houssay, B. A.. The thyroid and diabetes. Vitam. Horm. 4: 187–206, 1946.
 112. Houssay, B. A.. The action of the thyroid on diabetes. Recent Prog. Horm. Res. 2: 277–291, 1948.
 113. Houssay, B. A., V. G. Foglia, and C. Martinez. The influence of the thyroid on alloxan and pancreatic diabetes in the rat. Endocrinology. 39: 361–369, 1946.
 114. Howden, C. W., C. Logue, K. Gavin, L. Collie, and P. C. Rubin. Haemodynamic effects of intravenous human calcitonin generelated peptide in man. Clin. Sci. 74: 413–418, 1988.
 115. Ikeda, M.. Plasma insulin levels in endocrine diseases. II. Plasma insulin levels in patients with hyperthyroidism. Folia Endocrinol. Jpn. 47: 291–297, 1971.
 116. Ikeda, M., K. Fujiyama, T. Hoshino, Y. Tanaka, T. Takeuchi, H. Mashiba, and M. Tominaga. Acute effect of thyroid hormone on insulin secretion in rats. Biochem. Pharmacol. 40: 1769–1771, 1990.
 117. Ikeriji, K., T. Yamada, and H. Ogura. Age‐related glucose tolerance in hyperthyroid patients. Diabetes 27: 543–549, 1978.
 118. Imura, H., Y. Seino, M. Ikeda, T. Taminato, Y. Miyamoto, and Y. Goto. Impaired plasma insulin response to arginine in hyperthyroidism. Important role of rise of blood glucose in 2nd phase of insulin release induced by arginine. Diabetes 25: 961–968, 1976.
 119. Ismail‐Beigi, F.. Regulation of Na+K+‐ATPase expression by thyroid hormone. Semin. Nephrol. 12: 44–48, 1992.
 120. James, W. D.. Glycosuria from taking thyroid extract. Br. J. Dermatol. 6: 177, 1894.
 121. Janney, N. W., and V. I. Isaacson. The blood sugar in thyroid and other endocrine diseases. The significance of hypoglycemia and the delayed blood sugar curve. Arch. Intern. Med. 22: 160, 1918.
 122. John, H. J.. Carbohydrate metabolism in hyperthyroidism. Endocrinology 11: 497–581, 1927.
 123. John, H. J.. Hyperthyroidism showing carbohydrate metabolism disturbances. JAMA 99: 620–627, 1932.
 124. Johnson, M. D., M. E. Gray, and M. T. Stahlman. Calcitonin generelated peptide in human fetal lung and in neonatal lung disease. J. Histochem. Cytochem. 36: 199–204, 1988.
 125. Jolin, T., G. Morreale de Escobar, and F. Escobar del Rey. Differential effects in the rat of thyroidectomy, propylthiouracil and other goitrogens on plasma insulin and thyroid weight. Endocrinology 87: 99–110, 1970.
 126. Jolfn. T. and A. Montes. The different effects of thyroidectomy, KC104 and propylthiouracil on insulin secretion and glucose uptake in the rat. Endocrinology 94: 1502–1507, 1974.
 127. Joseph, P. K., and K. Subrahmanyam. Effect of growth hormone, insulin, thyroxine and cortisone on renal gluconeogenesis. Arch. Biochem. Biophys. 127: 288–291, 1968.
 128. Joslin, E. P., and F. H. Lahey. Diabetes and hyperthyroidism. Am. J. Med. Sci. 176: 1–22, 1928.
 129. Joslin, E. P. and F. H. Lahey. Diabetes and hyperthyroidism. Ann. Surg. 100: 629–637, 1934.
 130. Kabadi, U. M., and A. B. Eisenstein. Glucose intolerance in hyperthyroidism: role of glucagon. J. Clin. Endocrinol. Metab. 50: 392–396, 1980.
 131. Kabadi, U. M. and B. N. Premachandra. Lowering of T3 and rise in reverse T3 induced by hyperglucagonemia: altered thyroid hormone metabolism, not altered release of thyroid hormones. Horm. Metab. Res. 19: 486–489, 1987.
 132. Katsilambros, N., R. Ziegler, H. Schatz, M. Hinz, V. Maier, and E. F. Pfeiffer. Intravenous glucose tolerance and insulin secretion in the rat after thyroidectomy. Horm. Metab. Res. 4: 377–379, 1972.
 133. Katz, D., and M. A. Lazar. Dominant negative activity of an endogenous thyroid hormone receptor variant (α2) is due to competition for binding sites on target genes. J. Biol. Chem. 268: 20904–20910, 1993.
 134. Kelley, M. J., R. H. Snider, K. L. Becker, and B. E. Johnson. Small cell lung carcinoma cell lines express mRNA for calcitonin and alpha‐ and beta‐calcitonin gene‐related peptides. Cancer Lett. 81: 19–25, 1994.
 135. Kinash, B., and R. E. Haist. The influence of the thyroid gland on the islets of Langerhans and the pancreas. Can. J. Biochem. Physiol. 33: 380–384, 1955.
 136. Kissebah, A. H.. Insulin actions in vivo: insulin and lipoprotein metabolism. In: International Textbook of Diabetes Mellitus, edited by K.G.G.M. Alberti, R. A. De Fronzo, H. Kean, and P. Zimmet. Chichester: John Wiley and Sons, Ltd., p. 439–458, 1992.
 137. Klaushofer, K., F. Varga, H. Glantschnig, N. Fratzl‐Zelman, E. Czerwenka, H. J. Leis, K. Koller, and M. Peterlik. The regulatory role of thyroid hormones in bone cell growth and differentiation. J. Nutr. 125 (Suppl 7): 1996S–2003S, 1995.
 138. Klein, R. M., and J. C. McKenzie. The role of cell renewal in the ontogeny of the intestine. II. Regulation of cell proliferation in adult, fetal, and neonatal intestine. J. Pediatr. Gastroenterol. Nutr. 2: 204–228, 1983.
 139. Kliewer, S. A., K. Umesono, D. J. Mangelsdorf, and R. M. Evans. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone, and vitamin D3 signaling. Nature 355: 446–449, 1992.
 140. Koenig, R. J., M. A. Lazar, R. A. Hodin, G. A. Brent, P. R. Larsen, and W. W. Chin. Inhibition of thyroid hormone action by a nonhormone binding c‐erbA protein generated by alternative mRNA splicing. Nature 337: 659–661, 1989.
 141. Kojima, M.. Studies on the endocrine glands. The relations between the pancreas and thyroid and parathyroid glands. Q. J. Exp. Physiol. 11: 255–318, 1917.
 142. Kuriyama, S.. The influence of thyroid feeding upon carbohydrate metabolism. Am. J. Physiol. 43: 481–496, 1917.
 143. Kurokawa, R., V. C. Yu, A. Naar, S. Kyakumoto, Z. Han, S. Silverman, M. G. Rosenfeld, and C. K. Glass. Differential orientations of the DNA‐binding domain and carboxy‐terminal dimerization interface regulate binding site selection by nuclear receptor heterodimers. Genes Dev. 7: 1423–1435, 1993.
 144. Lam, K.S.L., R.T.T. Yeung, P.W.M. Ho, and S. K. Lam. Glucose intolerance in thyrotoxicosis: roles of insulin, glucagon and somatostatin. Acta Endocrinol. [Copenh.] 114: 228–234, 1987.
 145. Lamberg, B. A.. Glucose metabolism in thyroid disease. Acta Med. Scand. 178: 351–362, 1965.
 146. Lauder, J. M.. Hormonal and humoral influences on brain development. Psychoneuroendocrinology 8: 121–155, 1983.
 147. Lazar, M. A.. Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr. Rev. 14: 184–193, 1993.
 148. Lazar, M. A., R. A. Hodin, and W. W. Chin. Human carboxylterminal variant of α‐type c‐erbA inhibits trans‐activation by thyroid hormone receptors without binding thyroid hormone. Proc. Natl. Acad. Sci. USA 86: 7771–7774, 1989.
 149. Lebovitz, H. E., and G. S. Eisenbarth. Hormonal regulation of cartilage growth and metabolism. Vitam. Horm. 33: 575–648, 1975.
 150. Lefebvre, P. J.. Biosynthesis, secretion and action of glucagon. In: International Textbook of Diabetes Mellitus, edited by K.G.G.M., Alberti, R. A. De Fronzo, H. Kean, and P. Zimmet. Chichester: John Wiley and Sons, Ltd., p. 333–340, 1992.
 151. Lenzen, S.. Dose‐response studies on the inhibitory effect of thyroid hormones on insulin secretion in the rat. Metabolism 27: 81–88, 1978.
 152. Lenzen, S., and C. J. Bailey. Thyroid hormones, gonadal and adrenocortical steroids and the function of the islets of Langerhans. Endocr. Rev. 5: 411–434, 1984.
 153. Lenzen, S., and A. Hasselblatt. The effect of thyroxine treatment on the dynamics of insulin release from the isolated perfused rat pancreas. Naunyn Schmiedebergs. Arch. Pharmacol. 282: 317–321, 1974.
 154. Lenzen, S., H. G. Joost, and A. Hasselblatt. The inhibition of insulin secretion from the perfused rat pancreas after thyroxine treatment. Diabetologia 12: 495–500, 1976.
 155. Lenzen, S., H. G. Joost, and A. Hasselblatt. Thyroid function and insulin secretion from the perfused pancreas in the rat. Endocrinology 99: 125–129, 1976.
 156. Lenzen, S., and G. Klöppel. Insulin secretion and the morphological and metabolic characteristics of pancreatic islets of hyperthyroid ob/ob mice. Endocrinology 103: 1546–1555, 1978.
 157. Lenzen, S., and H. Kücking. Inhibition of insulin secretion by L‐thyroxine and D‐thyroxine treatment in rats under the influence of drugs affecting the adrenergic nervous system. Acta Endocrinol. 100: 527–533, 1982.
 158. Lenzen, S., U. Panten, and A. Hasselblatt. Thyroxine treatment and insulin secretion in the rat. Diabetologia 11: 49–55, 1975.
 159. Levin, J.. The effects of hormones on the absorptive, metabolic and digestive functions of the small intestine. J. Endocrinol. 45: 315–348, 1969.
 160. Levitt, N. S., A. I. Vinik, A. A. Sive, S. Vantonder, and A. Lund. Impaired pancreatic polypeptide responses to insulin‐induced hypoglycemia in diabetic autonomic neuropathy. J. Clin. Endocrinol. Metab. 50: 445–449, 1980.
 161. Levy, A., M. C. Matovelle, S. L. Lightman, and W. S. Young III. The effects of pituitary stalk transsection, hypophysectomy and thyroid hormone status on insulin‐like growth factor 2‐, growth hormone releasing hormone‐, and somatostatin mRNA prevalence in rat brain. Brain Res. 579: 1–7, 1992.
 162. Liljenquist, J. E., G. L. Meuller, A. D. Cherrington, U. Keller, J‐L. Chiasson, J. M. Perry, W. W. Lacy, and P. Rabinowitz. Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man. J. Clin. Invest. 59: 369–374, 1977.
 163. MacCullum, W. G.. On the relation of the islands of Langerhans to glycosuria. Bull. Johns Hopkins Hosp. 20: 265–268, 1909.
 164. Malaisse, W. J., F. Malaisse‐Lagae, and E. F. McCraw. Effects of thyroid function upon insulin secretion. Diabetes 16: 643–646, 1967.
 165. Malaisse‐Lagae, F., Y. Stefan, J. Cox, A. Perrelet, and L. Orci. Identification of a lobe in the adult human pancreas rich in pancreatic polypeptide. Diabetologia 17: 361–365, 1979.
 166. Maracek, R. L., and J. M. Feldman. Effect of hyperthyroidism on insulin and glucose dynamics in rabbits. Endocrinology 92: 1604–1611, 1973.
 167. Marks, H. P.. Effect of thyroid feeding on sugar tolerance. J. Physiol. 60: 402–410, 1925.
 168. Marliss, E. B., T. T. Aoki, R. H. Unger, J. S. Soeldner, and G. F. Cahill, Jr.. Glucagon levels and metabolic effects in prolonged fasted man. J. Clin. Invest. 49: 2256–2270, 1970.
 169. Matthaei, S., B. Trost, A. Hamann, C. Kausch, H. Benecke, H. Greten, W. Hoppner, and H. H. Klein. Effect of in vivo thyroid hormone status on insulin signaling and GLUT1 and GLUT4 glucose transport systems in rat adipocytes. J. Endocrinol. 144: 347–357, 1995.
 170. McCulloch, A. J., R. Nosadini, A. Pernet, M. Priniewska, D. B. Cook, F. Clark, D. G. Johnston, and K.G.G.M. Alberti. Glucose turnover and indices of recycling in thyrotoxicosis and primary thyroid failure. Clin. Sci. 64: 41–47, 1983.
 171. Menahan, L. A., and O. Wieland. The role of thyroid function in the metabolism of perfused rat liver with particular reference to gluconeogenesis. Eur. J. Biochem. 10: 188–194, 1969.
 172. Messmer, B., F. G. Zimmerman, and H. J. Lenz. Regulation of exocrine pancreatic secretion by cerebral TRH and CGRP: role of VIP, muscarinic, and adrenergic pathways. Am. J. Physiol. 264: G237–G242, 1993.
 173. Minvielle, S., S. Giscard‐Dartevelle, R. Cohen, J. Taboulet, F. Labye, A. Jullienne, P. Rivaille, G. Milhaud, M. S. Moukhtar, and F. Lasmoles. A novel calcitonin carboxyl‐terminal peptide produced in medullary thyroid carcinoma by alternative RNA processing of the calcitonin/calcitonin gene‐related peptide gene. J. Biol. Chem. 266: 24627–24631, 1991.
 174. Mirsky, I. A., and R. H. Broh‐Kahn. The effect of experimental hyperthyroidism on carbohydrate metabolism. Am. J. Physiol. 117: 6–12, 1936.
 175. Moghetti, P., R. Castello, F. Tosi, M. G. Zenti, C. Magnani, A. Bolner, L. Perobelli, and M. Muggeo. Glucose counterregulatory response to acute hypoglycemia in hyperthyroid human subjects. J. Clin. Endocrinol. Metab. 78: 169–173, 1994.
 176. Molander, D. W., and A. Kirschbaum. Hyperglycemia and glucosuria following thyroid administration in alloxan treated rats. J. Lab. Clin. Med. 34: 492–496, 1949.
 177. Montminy, M. R., G. A. Gonzalez, and K. H. Yamamoto. Characteristics of the cAMP response unit. Recent Prog. Horm. Res. 46: 219–229, 1990.
 178. Morley, J. E.. Extrahypothalamic thyrotropin releasing hormone (TRH)—its distribution and functions. Life Sci. 25: 1539–1550, 1979.
 179. Morrison, W. L., J. N. Gibson, R. T. Jung, and M. R. Rennie. Skeletal muscle and whole body protein turnover in thyroid disease. Eur. J. Clin. Invest. 18: 62–68, 1988.
 180. Moussavi, R., E. Meisami, and P. S. Timiras. Compensatory cell proliferation and growth in the rat heart after postnatal hypothyroidism. Am. J. Physiol. 248: E381–E387, 1985.
 181. Müller, M. J., K. J. Acheson, E. Jequier, and A. G. Burger. Effect of thyroid hormones on oxidative and nonoxidative glucose metabolism in humans. Am. J. Physiol. 255: E146–E152, 1988.
 182. Müller, M. J., A. G. Burger, E. Ferrannini, E. Jequier, and K. J. Acheson. Glucoregulatory function of thyroid hormones: role of pancreatic hormones. Am. J. Physiol. 256: E101–E110, 1989.
 183. Müller, M. J., P. E. Mitchinson, U. Paschen, and H. J. Seitz. Glucoregulatory function of glucagon in hypo‐, eu‐, and hyperthyroid miniature pigs. Diabetologia 31: 368–374, 1988.
 184. Müller, M. J., J. Möring, U. Paschen, and H. J. Seitz. Glucoregulatory function of thyroid hormones: evidence for an insulinindependent effect. Exp. Clin. Endocrinol. 93: 313–320, 1989.
 185. Müller, M. J., and H. J. Seitz. In vivo turnover in hypo‐ and hyperthyroid starved rat. Pflügers Arch. 386: 47–52, 1980.
 186. Müller, M. J., and H. J. Seitz. Thyroid hormone action on intermediary metabolism. Klin. Wochenschr. 62: 11–18, 1984.
 187. Müller, M. J., P. Ulrich, and H. Seitz. Thyroid hormone regulation of glucose homeostasis in the miniature pig. Endocrinology 112: 2025–2031, 1983.
 188. Murray, M. B., and C. C. Towle. Identification of nuclear factors that enhance binding of the thyroid hormone receptor to a thyroid hormone response element. Mol. Endocrinol. 3: 1434–1442, 1989.
 189. Nadal‐Ginard, B., and V. Mahdavi. Molecular basis of cardiac performance: plasticity of the myocardium generated through protein isoform switches. J. Clin. Invest. 84: 1963–1700, 1989.
 190. Nakagawa, T., B. D. Nelkin, S. B. Baylin, and A. De Bustros. Transcriptional and posttranscription modulation of calcitonin gene expression by sodium n‐butyrate in cultured medullary thyroid carcinoma. Cancer Res. 48: 2096–2100, 1988.
 191. Nakazato, M., J. Asai, M. Miyazato, S. Matsukura, K. Kangawa, and H. Matsuo. Isolation and identification of islet amyloid polypeptide in normal human pancreas. Regul. Pept. 31: 179–186, 1990.
 192. Neal, W. B., L. R. Dragstedt, G. R. Rogers, and G. McKeague. Effect of destruction of thyroid glands by radioactive iodine on pancreatic diabetes in dog. Am. J. Physiol. 168: 29–32, 1952.
 193. Nilsson, A., C. Ohlsson, O. G. Isaksson, A. Lindahl, and J. Isgaard. Hormonal regulation of longitudinal bone growth. Eur. J. Clin. Nutr. 48 (Suppl 1): S150–S158, 1994.
 194. Nishi, M., T. Sanke, S. Seino, R. L. Eddy, Y. S. Fan, M. G. Byers, T. B. Shows, G. I. Bell, and D. F. Steiner. Human islet amyloid polypeptide gene: complete nucleotide sequence, chromosomal localization, and evolutionary history. Mol. Endocrinol. 3: 1775–1781, 1989.
 195. O'Donnell, A. L., and R. J. Koenig. Mutational analysis identifies a new functional domain of the thyroid hormone receptor. Mol. Endocrinol. 4: 715–720, 1990.
 196. Ohlsen, P. M., S. Danowski, C. Vidalon, U. Ahmad, S. Nolan, and T. Stephan. Glucose tolerance, insulin, and growth hormone in thyrotoxicosis and myxedema. Endocr. Res. Commun. 1: 435–448, 1974.
 197. Okajima, F., and M. Ui. Adrenergic modulation of insulin secretion in vivo dependent on thyroid states. Am. J. Physiol. 234: E196–E201, 1978.
 198. Okajima, F., and M. Ui. Metabolism of glucose in hyper‐ and hypothyroid rats in vivo. Biochem. J. 182: 565–575, 1979.
 199. Okajima, F., and M. Ui. Metabolism of glucose in hyper‐ and hypothyroid rats in vivo. Minor role of endogenous insulin in thyroiddependent changes in glucose turnover. Biochem. J. 182: 577–584, 1979.
 200. Okajima, F., and M. Ui. Metabolism of glucose in hyper‐ and hypothyroid rats in vivo. Relation of catecholamine actions to thyroid activity in controlling glucose turnover. Biochem. J. 182: 585–592, 1979.
 201. O'Meara, N. M., J. D. Blackman, J. Sturis, and K. S. Polonsky. Alterations in the kinetics of C‐peptide and insulin secretion in hyperthyroidism. J. Clin. Endocrinol. Metab. 76: 79–84, 1993.
 202. Oppenheimer, J. H.. Thyroid hormone action at the cellular level. Science 203: 971–979, 1979.
 203. Oppenheimer, J. H., D. Koerner, H. L. Schwartz, and M. L. Surks. Specific nuclear triiodothyronine binding sites in rat liver and kidney. J. Clin. Endocrinol. Metab. 35: 330–333, 1972.
 204. Oppenheimer, J. H., and H. L. Schwartz. Molecular basis of thyroid hormone‐dependent brain development. Endocr. Rev. 18: 462–475, 1997.
 205. Oppenheimer, J. H., H. L. Schwartz, C. N. Mariash, W. B. Kinlaw, N. C. Wong, and H. C. Freake. Advances in our understanding of thyroid hormone action at the cellular level. Endocr. Rev. 8: 288–308, 1987.
 206. Oppenheimer, J. H., H. L. Schwartz, M. I. Surks, D. Koerner, and W. H. Dillman. Nuclear receptors and the initiation of thyroid hormone action. Recent Prog. Horm. Res. 32: 529–565, 1976.
 207. Orsetti, A., F. Collard, and C. Jaffiol. Abnormalities of carbohydrate metabolism in experimental and clinical hyperthyroidism: studies on plasma insulin and on the A‐ and B‐chains of insulin. Acta Diabetol. Lat. 11: 486–492, 1974.
 208. Ortved, A. O., T. Friis, and B. Ottesen. Glucose tolerance and insulin secretion in hyperthyroidism. Acta Endocrinol. 84: 576–587, 1977.
 209. Osei, K., J. M. Falko, T. M. O'Dorisio, and D. R. Adam. Decreased serum C‐peptide/insulin molar ratios after oral glucose ingestion in hyperthyroid patients. Diabetes Care 7: 471–475, 1984.
 210. Owyang, C., S. R. Achem‐Karam, and A. I. Vinik. Pancreatic polypeptide and intestinal migrating motor complex in humans. Gastroenterology 84: 10–17, 1983.
 211. Pan, M. G., T. Florio, and P. J. C. Stork. G protein activation of a hormone‐stimulated phosphatase in human tumor cells. Science 256: 1215–1217, 1992.
 212. Panetta, R., M. T. Greenwood, A. Warszynska, L. L. Demchyshyn, R. Day, H. B. Niznik, C. B. Srikant, and Y. C. Patel. Molecular cloning, functional characterization, and chromosomal localization of a novel human somatostatin receptor (SSTR5) with preferential affinity for SS‐28. Mol. Pharmacol. 45: 417–427, 1994.
 213. Papapetrou, P. D., D. A. Koutras, and B. Malamos. Lactate, pyruvate and thyroid function. J. Endocrinol. 47: 519–520, 1970.
 214. Patel, Y. C.. General aspects of the biology and function of somatostatin. In: Somatostatin: Basic and Clinical Aspects of Neuroscience Series, Vol. 4, edited by C. Weil, E. E. Muller, and M. O. Thorner. Berlin: Springer‐Verlag, p. 1–16, 1992.
 215. Patel, Y. C., M. T. Greenwood, A. Warszynska, R. Panetta, and C. B. Srikant. All five cloned human somatostatin receptors (hSSTR1–5) are functionally coupled to adenyl cyclase. Biochem. Biophys. Res. Comm. 198: 605–612, 1994.
 216. Patel, Y. C., and G. S. Tannenbaum, eds. Somatostatin: basic and clinical aspects. Metabolism 39 (Suppl 2): 1–191, 1990.
 217. Patel, Y. C., T. Wheatley, and C. Ning. Multiple forms of immunoreactive somatostatin: comparison of distribution in neural and nonneural tissues and portal plasma of the rat. Endocrinology 109: 1943–1949, 1981.
 218. Perez, G., B. Ungaro, A. Covelli, G. Morrone, G. Lombardi, F. Scopacasa, and R. Rossi. Altered glucoregulatory response to physiological infusion of epinephrine and glucagon in hyperthyroidism. J. Clin. Endocrinol. Metab. 51: 972–977, 1980.
 219. Perlman, L. V.. Familial incidence of diabetes in hyperthyroidism. Ann. Intern. Med. 55: 796–799, 1961.
 220. Peterman, J. B., W. Born, J. Y. Chang, and J. A. Fischer. Identification in the human nervous system, pituitary, and thyroid of a novel calcitonin gene‐related peptide, and partial amino acid sequence in the spinal cord. J. Biol. Chem. 262: 542–545, 1987.
 221. Petty, K. J.. Tissue‐ and cell‐specific distribution of nuclear proteins that interact with the human ã‐thyroid hormone receptor. Thyroid 3 (Suppl): T119 (abstract), 1993.
 222. Piatnek‐Leunissen, D., and R. E. Olson. Cardiac failure in the dog as a consequence of exogenous hyperthyroidism. Circ. Res. 20: 242–252, 1967.
 223. Picon, L., and C. Levacher. Thyroid hormones and adipose tissue development. J. Physiol. 75: 539–543, 1979.
 224. Polak, J. M., S. Bloom, T. E. Adrian, and P. Heitz. Pancreatic polypeptide in insulinomas, VIPomas and glucagonomas. Lancet I: 326–330, 1976.
 225. Raue, F., E. Blind, and A. Grauer. PDN‐21 (katacalcin) and chromogranin A: tumor markers for medullary thyroid carcinoma. Henry Ford Hosp. Med. J. 40: 296–298, 1992.
 226. Regan, J. F., and R. M. Wilder. Hyperthyroidism and diabetes. Arch. Intern. Med. 65: 1116–1122, 1940.
 227. Reichlin, S.. Somatostatin. N. Engl. J. Med. 309: 1495–1501, 1983.
 228. Reichlin, S.. Somatostatin: Basic and Clinical Status. New York: Plenum Press, 1987.
 229. Renauld, A., L. L. Andrade, R. C. Sverdlik, and R. R. Rodriguez. Serum insulin response to glucose infusion in hyperthyroid dogs. Horm. Metab. Res. 6: 400–403, 1974.
 230. Renauld, A., J.E.B. Pinto, R. C. Sverdlik, and V. G. Foglia. Studies on the effect of hyperthyroidism on the insulin response to hyperglycemia in the dog. Horm. Metab. Res. 3: 247–251, 1971.
 231. Renauld, A., J.E.B. Pinto, R. C. Sverdlik, and V. G. Foglia. Studies on the effect of thyroidectomy on the insulin response to hyperglycemia in the dog. Acta Physiol. Lat. Am. 23: 29–36, 1973.
 232. Renauld, A., R. C. Sverdlik, and L. L. Andrade. Effects of hypothyroidism on serum immunoreactive insulin, free fatty acids and blood sugar in the dog as tested for oral glucose. Horm. Metab. Res. 6: 137–141, 1974.
 233. Renauld, A., R. C. Sverdlik, L. L. Andrade, and R. R. Rodriguez. Studies on the effect of thyroxine replacement therapy on the increased insulin response to hyperglycemia in the thyroidectomized dog. Horm. Metab. Res. 4: 373–376, 1972.
 234. Renauld, A., R. C. Sverdlik, and D. Garrido. Blood sugar, serum insulin and serum free fatty acid responses to slow graded glucose in thyroxine‐treated dogs. Acta Diabetol. Lat. 17: 189–197, 1980.
 235. Renauld, A., R. C., Sverdlik, and D. Garrido. Blood sugar, serum insulin and serum fatty acid responses to graded glucose pulses in hypothyroid dogs. Acta Diabetol. Lat. 19: 97–105, 1982.
 236. Renauld, A., R. C. Sverdlik, and R. R. Rodriguez. Blood concentration of glucose, insulin and free fatty acids in shortly thyroxinetreated dogs: effects of alpha‐blockade and isoproterenol. Horm. Metab. Res. 14: 101, 1982.
 237. Rentoumis, A., V.K.K. Chatterjee, L. D. Madison, S. Datta, G. D. Gallagher, L. J. Degroot, and J. L. Jameson. Negative and positive transcriptional regulation by thyroid hormone receptor isoforms. Mol. Endocrinol. 4: 1522–1531, 1990.
 238. Ribeiro, R. C., J. W. Apriletti, B. L. West, R. L. Wagner, R. J. Fletterick, F. Schaufele, and J. D. Baxter. The molecular biology of thyroid hormone action. Ann. New York Acad. Sci. 758: 366–389, 1995.
 239. Rohdenburg, G. L.. Thyroid diabetes. Endocrinology 4: 63–70, 1920.
 240. Rohrer, L., F. Raulf, C. Bruns, R. Buettner, F. Hofstaedter, and R. Schule. Cloning and characterization of a fourth human somatostatin receptor. Proc. Natl. Acad. Sci. USA 90: 4196–4200, 1993.
 241. Romney, J. S., J. Chan, F. E. Carr, A. D. Mooradian, and N. C. Wong. Identification of the thyroid hormone‐responsive messenger RNA Spot 11 as apolipoprotein‐A1 messenger RNA and effects of the hormone on the promoter. Mol. Endocrinol. 6: 943–950, 1992.
 242. Roti, E., L. E. Braverman, G. Robuschi, M. Salvi, E. Garlini, L. D'Amato, D. Maestri, M. Montermini, E. Borciani, and A. Pezzarossa. Basal and glucose and arginine stimulated serum concentrations of insulin, C‐peptide and glucagon in hyperthyroid patients. Metabolism 35: 337–342, 1986.
 243. Rowe, A. W.. The metabolism of galactose. III. The influence of disturbed endocrine function. Am. J. Med. Sci. 190: 686–700, 1935.
 244. Sakurai, A., A. Nakai, and L. J. Degroot. Expression of three forms of thyroid hormone receptor in human tissues. Mol. Endocrinol. 3: 392–399, 1989.
 245. Sandler, M. P., R. P. Robinson, D. Rabin, W. W. Lacy, and N. N. Abumrad. The effect of thyroid hormones on gluconeogenesis and forearm metabolism in man. J. Clin. Endocrinol. Metab. 56: 479–485, 1983.
 246. Sap, J., A. Munoz, K. Damm, Y. Goldberg, J. Ghysdael, A. Leutz, H. Beug, and B. Vennstrom. The c‐erbA protein is a high‐affinity receptor for thyroid hormone. Nature 324: 635–640, 1986.
 247. Sato, K., D. C. Han, Y. Fujii, T. Tsushima, and K. Shizume. Thyroid hormone stimulates alkaline phosphatase activity in cultured rat osteoblastic cells (ROS 17/2.8) through 3,5,3′‐triiodo‐l‐thyronine nuclear receptors. Endocrinology 120: 1873–1881, 1987.
 248. Schwartz, H. L., K. A. Strait, N. C. Ling, and J. H. Oppenheimer. Quantitation of rat tissue thyroid hormone binding receptor isoforms by immunoprecipitation of nuclear triiodothyronine binding capacity. J. Biol. Chem. 267: 11794–11799, 1992.
 249. Scow, R. O., and J. Cornfield. Effect of thyroidectomy and food intake on oral and intravenous glucose tolerances in rats. Am. J. Physiol. 179: 39–42, 1954.
 250. Segal, J., and A. Gordon. The effect of 3,5,3′‐triiodo‐l‐thyronine on the kinetic parameters of sugar transport in cultured chick embryo heart cells. Endocrinology 101: 1468–1474, 1977.
 251. Seino, Y., Y. Goto, H. Kurahachi, H. Sakurai, M. Ikeda, S. Kadowaki, Y. Inoue, K. Mori, T. Taminato, and H. Imura. Alteration of plasma glucagon response to arginine after treatment in patients with diabetes mellitus, Cushing's syndrome and hypothyroidism. Horm. Metab. Res. 9: 28–32, 1977.
 252. Seino, Y., Y. Goto, T. Taminato, M. Ikeda, and H. Imura. Plasma insulin and glucagon responses to arginine in patients with thyroid dysfunction. J. Clin. Endocrinol. Metabol. 38: 1136–1140, 1974.
 253. Seino, Y., H. Kurahachi, Y. Goto, T. Taminato, M. Ikeda, and H. Imura. Comparative insulinogenic effects of glucose, arginine, and glucagon in patients with diabetes mellitus, endocrine disorders and liver disease. Acta Diabetol. Lat. 12: 89–99, 1975.
 254. Seltzer, H. S., E. W. Allen, A. L. Herron, and M. T. Brennan. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J. Clin. Invest. 46: 323–335, 1967.
 255. Setoft, L., and L. G. Heding. Hypersecretion of proinsulin in thyrotoxicosis. Diabetologia 21: 103–107, 1981.
 256. Shaw, J. H., and G. M. Cerchio. Hypoinsulinemia of hypothyroidism. Arch. Intern. Med. 132: 657–661, 1973.
 257. Shaw, J. H., G. S. Motto, E. Papagiannes, and G. A. Williams. Insulin metabolism in hypothyroidism. Diabetes 24: 922–925, 1975.
 258. Shima, K., N. Sawazaki, R. Tanaka, S. Morishita, S. Tarui, and M. Nishikawa. The pancreatic alpha and beta cell responses to l‐arginine and insulin‐induced hypoglycemia in hyperthyroidism. Acta Endocrinol. 83: 114–122, 1976.
 259. Shpiner, L. P.. Increased metabolism only one factor in the production and maintenance of the hyperglycemia and glycosuria in experimental hyperthyroidism. Am. J. Physiol. 92: 672–678, 1930.
 260. Shupnik, M. A., W. W. Chin, J. F. Habener, and E. C. Ridgeway. Transcriptional regulation of the thyrotropin subunit genes by thyroid hormone. J. Biol. Chem. 260: 2900–2903, 1985.
 261. Shupnik, M. A., and E. C. Ridgeway. Triiodothyronine rapidly decreases transcription of the thyrotropin subunit genes in thyrotropic tumor explants. Endocrinology 117: 1940–1946, 1985.
 262. Simonides, W. S., C. Van Hardeveld, and P. R. Larsen. Identification of sequences in the promoter of the fast isoform of sarcoplasmic reticulum Ca‐ATPase (SERCA1) required for transcriptional activation by thyroid hormone. Thyroid 2: 5102 (abstract), 1992.
 263. Sive, A. A., A. I. Vinik, and N. Levitt. Adrenergic modulation of human pancreatic polypeptide (hPP) release. Gastroenterology 79: 665–672, 1980.
 264. Sive, A. A., A. I. Vinik, and S. V. Vantonder. Pancreatic polypeptide (PP) responses to oral and intravenous glucose in man. Am. J. Gastroenterol. 71: 183–185, 1979.
 265. Smith, P. H., and D. Porte. Neuropharmacology of the pancreatic islets. Annu. Rev. Pharmacol. Toxicol. 16: 269–285, 1976.
 266. Solomon, N., C.C.J. Carpenter, I. L. Bennett, and A. M. Harvey. Schmidt's syndrome (thyroid and adrenal insufficiency) and coexistent diabetes mellitus. Diabetes 14: 300, 1965.
 267. Steenbergh, P. H., J. W. Hoppener, J. Zandberg, C. J. Lips, and H. S. Jansz. A second human calcitonin/CGRP gene. FEBS Lett. 183: 403–407, 1985.
 268. Steenbergh, P. H., J. W. Hoppener, J. Zandberg, A. Visser, C. J. Lips, and H. S. Jansz. Structure and expression of the human calcitonin/CGRP genes. FEBS Lett. 209: 97–103, 1986.
 269. Stern, H.. The association of Graves' disease with glycosuria and diabetes mellitus. JAMA 39: 972–978, 1902.
 270. Szecowka, J., K. Tatemoto, G. Rajamaki, and S. Efendic. Effects of PYY and PP on endocrine pancreas. Acta Physiol. Scand. 119: 123–126, 1983.
 271. Tam, S. P., K. S. Lam, and G. Srivastava. Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism. Endocrinology 137: 418–424, 1996.
 272. Tatum, A. L.. Morphological studies in experimental cretinism. J. Exp. Med. 1: 636–652, 1913.
 273. Tauveron, I., S. Charrier, C. Champredon, Y. Bonnet, C. Berry, G. Bayle, J. Prugnaud, C. Obled, J. Grizard, and P. Thiéblot. Response of leucine metabolism to hyperinsulinemia under amino acid replacement in experimental hyperthyroidism. Am. J. Physiol. 269: E499–E507, 1995.
 274. Taylor, R., A. J. McCulloch, S. Zeuzem, P. Gray, F. Clark, and K. G. Alberti. Insulin secretion, adipocyte insulin binding and insulin sensitivity in thyrotoxicosis. Acta Endocrinol. 109: 96–103, 1985.
 275. Tomic‐Canic, M., I. Sunjevaric, I. M. Freedberg, and M. Blumenberg. Identification of the retinoic acid and thyroid hormone receptor‐responsive elements in the human K14 keratin gene. J. Invest. Dermatol. 99: 842–847, 1992.
 276. Umeda, Y., M. Takamiya, H. Yoshizaki, and M. Arisawa. Inhibition of mitogen‐stimulated T lymphocyte proliferation by calcitonin gene‐related peptide. Biochem. Biophys. Res. Commun. 154: 227–235, 1988.
 277. Umesono, K., K. K. Murakami, C. C. Thompson, and R. E. Evans. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 65: 1255–1266, 1991.
 278. Unger, R. H.. Alpha and beta cell interrelationship in health and disease. Metabolism 23: 581–593, 1974.
 279. Unger, R. H., A. Okneda, E. Aguilar‐Parada, and A. M. Eisentraut. The role of aminogenic glucagon secretion in blood glucose homeostasis. J. Clin. Invest. 48: 810–822, 1969.
 280. Unger R. H., and L. Orci. Glucagon secretion, alpha cell metabolism, and glucagon action. In: Endocrinology, 3rd ed, Vol. 2, edited by L. J. De Groot, M. Besser, H. G. Burger, J. L. Jameson, D. L. Loriaux, J. C. Marshall, W. D. Odell, J. T. Potts, Jr., and A. H. Rubenstein. Philadelphia: W. B. Saunders Co., p. 1337–1353, 1995.
 281. Valcavi, R., F. Valente, C. Dieguez, M. Zini, M. Procopio, I. Portioli, and E. Ghigo. Evidence against depletion of the growth hormone (GH)‐releasable pool in human primary hypothyroidism: studies with GH‐releasing hormone, pyridostigmine, and arginine. J. Clin. Endocrinol. Metab. 77: 616–620, 1993.
 282. Vince, F. P., B. J. Boucher, R. D. Cohen, and J. Godfrey. The response of plasma sugar, free fatty acids, 11‐hydroxycorticosteroids and growth hormone to insulin‐induced hypoglycaemia and vasopressin in primary myxedema. J. Endocrinol. 48: 389–400, 1970.
 283. Vinik, A. I., B. L. Pinstone, and R. Hoffenberg. Studies on free fatty acid metabolism and hyperthyroidism. Metabolism 19: 93–101, 1970.
 284. Voldstedlund, M., J. Tranum‐Jensen, A. Handberg, and J. Vinten. Quantity of Na/K‐ATPase and glucose transporters in the plasma membrane of rat adipocytes is reduced by in vivo triiodothyronine. Eur. J. Endocrinol. 133: 626–634, 1995.
 285. Vonderhaar, B. K.. Lactose synthetase activity in mouse mammary glands is controlled by thyroid hormones. J. Cell Biol. 82: 675–681, 1979.
 286. Wahren, J., S. Efendic, R. Luft, L. Hagenfeldt, O. Bjorkman, and P. Felig. Influence of somatostatin on splanchnic glucose metabolism in post‐absorptive and 60‐hour fasted humans. J. Clin. Invest. 59: 299–307, 1977.
 287. Wajchenberg, B. L., F. P. Cesar, C. E. Leme, R. Didio, and J. Kieffer. Plasma insulin disappearance curve after intravenous insulin injection in human hyperthyroidism. Clin. Endocrinol. 8: 233–236, 1978.
 288. Wajchenberg, B. L., F. P. Cesar, C. E. Leme, T. T. Souza, R. R. Pieroni, and E. Mattar. Effects of adrenergic stimulating and blocking agents on glucose‐induced insulin responses to human thyrotoxicosis. Metabolism 27: 1715–1720, 1977.
 289. Wajchenberg, B. L., F. P. Cesar, C. E. Leme, I. T. Souza, R. R. Pieroni, and E. Mattar. Carbohydrate metabolism in thyrotoxicosis—studies on insulin secretion before and after remission from hyperthyroid state. Horm. Metab. Res. 10: 294–299, 1978.
 290. Weinberger, C., C. C. Thompson, E. S. Ong, R. Lebo, D. J. Gruol, and R. M. Evans. The c‐erbA gene encodes a thyroid hormone receptor. Nature 324: 641–646, 1986.
 291. Weinstein, S. P., J. Watts, P. N. Graves, and R. S. Haber. Stimulation of glucose transport by thyroid hormone in ARL 15 cells: increased abundance of glucose transporter protein and messenger ribonucleic acid. Endocrinology 126: 1421–1429, 1990.
 292. Weinstein, S. P., J. Watts, and R. S. Haber. Thyroid hormone increases muscle/fat glucose transporter gene expression in rat skeletal muscle. Endocrinology 129: 455–464, 1991.
 293. Wennlund, A., P. Felig, L. Hagenfeldt, and J. Wahren. Hepatic glucose production and splanchnic glucose exchange in hyperthyroidism. J. Clin. Endocrinol. Metab. 65: 174–180, 1986.
 294. Westermark, P., C. Wernstedt, E. Wilander, D. W. Hayden, T. D. O'Brien, and K. H. Johnson. Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide‐like protein also present in normal islet cells. Proc. Natl. Acad. Sci. USA 84: 3881–3885, 1987.
 295. Westermark, P., C. Wernstedt, E. Wilander, and A. Sletten. A novel peptide in the calcitonin gene‐related peptide family as an amyloid fibril protein in the endocrine pancreas. Biochem. Biophys. Res. Commun. 140: 827–831, 1987.
 296. Westermark, P., E. Wilander, G. T. Westermark, and K. H. Johnson. Islet amyloid polypeptide‐like immunoreactivity in the islet ã‐cells of type 2 (non‐insulin‐dependent) diabetic and non‐diabetic individuals. Diabetologia 30: 887–892, 1987.
 297. Wilder R. M.. Hyperthyroidism, myxedema and diabetes. Arch. Intern. Med. 38: 736–760, 1926.
 298. Williams, G., and S. R. Bloom. Somatostatin and pancreatic polypeptide. In: International Textbook of Diabetes Mellitus, edited by K.G.G.M. Alberti, R. A. De Fronzo, H. Kean, and P. Zimmet. Chichester: John Wiley and Sons, Ltd., p. 341–356, 1992.
 299. Williams, E. D., B. J. Ponder, and R. K. Craig. Immunohistochemical study of calcitonin gene‐related peptide in human medullary thyroid carcinoma and C cell hyperplasia. Clin. Endocrinol. [Oxf.] 27: 107–114, 1987.
 300. Wimalawansa, S. J.. Calcitonin gene‐related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr. Rev. 17: 533–585, 1996.
 301. Wimalawansa, S. J., R. D. Gunasekera, and F. Zhang. Isolation, purification, and characterization of calcitonin gene‐related peptide receptor. Peptides 14: 691–699, 1993.
 302. Wolf, E., and A. B. Eisenstein. Portal vein blood insulin and glucagon are increased in experimental hyperthyroidism. Endocrinology 108: 2109–2113, 1981.
 303. Wolfson, H.. On the alleged antagonistic action of the intestinal secretions of the pancreas and the thyroid. Am. J. Physiol. 81: 453–459, 1927.
 304. Wondisford, F. E., H. J. Steinfelder, M. Nations, and S. Radovick. AP‐1 antagonizes thyroid hormone receptor action on the thyrotropin ã‐subunit gene. J. Biol. Chem. 268: 2749–2754, 1993.
 305. Yaffe, B. M., and H. H. Samuels. Hormonal regulation of the growth hormone gene. Relationship of the rate of transcription to the level of nuclear thyroid hormone‐receptor complexes. J. Biol. Chem. 259: 6284–6291, 1984.
 306. Yen, P. M., A. Sugawara, S. Refetoff, and W. W. Chin. New insights on the mechanisms of the dominant negative effect of mutant thyroid hormone receptor in generalized resistance to thyroid hormone. J. Clin. Invest. 90: 1825–1831, 1992.
 307. Zaidi, M., T. J. Chambers, R. E. Gaines Das, H. R. Morris, and I. Macintyre. A direct action of human calcitonin gene‐related peptide on isolated osteoclasts. J. Endocrinol. 115: 511–518, 1987.
 308. Zamrazil, V., J. Nedvídková, V. Felt, J. Němec, and J. Havelka. The influence of thyroid function on the diabetogenic action of triamcinolone in man. Horm. Metab. Res. 8: 282–286, 1976.
 309. Zeckwer, I. T.. Some atypical responses of rabbits to insulin. Am. J. Physiol. 106: 273–282, 1933.
 310. Zhang, X. K., and M. Pfahl. Regulation of retinoid and thyroid hormone action through homodimeric and heterodimeric receptors. Trends Endocrinol. Metab. 4: 156–162, 1993.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Bart L. Clarke, Leslie J. Degroot. Thyroid Hormone Regulation of Islet Cell Hormone Metabolic Actions. Compr Physiol 2011, Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism: 907-938. First published in print 2001. doi: 10.1002/cphy.cp070229