Hanyang Med Rev.  2012 Nov;32(4):171-178. 10.7599/hmr.2012.32.4.171.

Endocrine Diseases in Diabetes Mellitus

• Park Y

• KMID: 2168206
• DOI: http://doi.org/10.7599/hmr.2012.32.4.171

Abstract

The endocrine pancreas secretes several hormones including insulin and glucagon and dysfunction of them may lead to diabetes mellitus. The integrated regulation of systemic glucose balance prevents the devastating consequences of hypoglycemia and hyperglycemia. This remarkable homeostatic feat is accomplished primarily by hormones, but also by neurotransmitters and substrate effects, and it reflects the interplay of plasma glucose-lowering and glucose-raising factors. Moreover, endocrine diseases frequently co-associate with diabetes mellitus. There have also been several reports on changes in growth hormone (GH) in nutrient excess or deprivation. GH is released into the general circulation where it interacts with multiple peripheral tissues through its receptor, GH receptor, to regulate growth and metabolic function. In humans, GH levels decrease in states of nutrient excess such as obesity, and increase in response to nutrient deprivation such as fasting. Considering that GH regulates metabolism of carbohydrate, lipid, and protein, clarifying the mechanisms by which metabolic changes alter GH synthesis and secretion will increase our knowledge on the pathophysiology and treatment of metabolic diseases. In this review, the effect of nutrient excess and nutrient deficiency on GH axis function in humans will be summarized, with particular emphasis on studies exploring the direct effects of systemic signals, including insulin-like growth factor 1 (IGF-1) and insulin, on somatotrope function. Moreover, there will be a discussion over the overlap syndrome consisting of multiple endocrine neoplasm (MEN) and polyglandular autoimmune diseases (PGA).

Keyword

Diabetes Mellitus; Growth Hormone; Obesity; Fasting; Nutritional Physiological Phenomena

MeSH Terms

Autoimmune Diseases
Diabetes Mellitus
Endocrine System Diseases
Fasting
Glucagon
Glucose
Growth Hormone
Humans
Hyperglycemia
Hypoglycemia
Insulin
Islets of Langerhans
Metabolic Diseases
Neurotransmitter Agents
Nutritional Physiological Phenomena
Obesity
Plasma
Axis, Cervical Vertebra
Glucagon
Glucose
Growth Hormone
Insulin
Neurotransmitter Agents

Reference

1. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia. 2003. 46:3–19.

2. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. 2003. 26:1902–1912.

3. Frohman LA, Kineman RD, Kamegai J, Park S, Teixeira LT, Coschigano KT, et al. Secretagogues and the somatotrope: signaling and proliferation. Recent Prog Horm Res. 2000. 55:269–290.

4. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005. 85:495–522.

5. Luque RM, Huang ZH, Shah B, Mazzone T, Kineman RD. Effects of leptin replacement on hypothalamic-pituitary growth hormone axis function and circulating ghrelin levels in ob/ob mice. Am J Physiol Endocrinol Metab. 2007. 292:E891–E899.

6. Mezey E, Hunyady B, Mitra S, Hayes E, Liu Q, Schaeffer J, et al. Cell specific expression of the sst2A and sst5 somatostatin receptors in the rat anterior pituitary. Endocrinology. 1998. 139:414–419.

7. Scacchi M, Pincelli AI, Cavagnini F. Growth hormone in obesity. Int J Obes Relat Metab Disord. 1999. 23:260–271.

8. Lanzi R, Luzi L, Caumo A, Andreotti AC, Manzoni MF, Malighetti ME, et al. Elevated insulin levels contribute to the reduced growth hormone (GH) response to GH-releasing hormone in obese subjects. Metabolism. 1999. 48:1152–1156.

9. De Marinis L, Bianchi A, Mancini A, Gentilella R, Perrelli M, Giampietro A, et al. Growth hormone secretion and leptin in morbid obesity before and after biliopancreatic diversion: relationships with insulin and body composition. J Clin Endocrinol Metab. 2004. 89:174–180.

10. Cattaneo L, De Gennaro Colonna, Zoli M, Muller E, Cocchi D. Characterization of the hypothalamo-pituitary-IGF-I axis in rats made obese by overfeeding. J Endocrinol. 1996. 148:347–353.

11. Luque RM, Kineman RD. Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function. Endocrinology. 2006. 147:2754–2763.

12. Ghigo E, Procopio M, Maccario M, Bellone J, Arvat E, Campana S, et al. Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity? Horm Metab Res. 1993. 25:305–308.

13. Yeagley D, Guo S, Unterman T, Quinn PG. Gene- and activation-specific mechanisms for insulin inhibition of basal and glucocorticoid-induced insulin-like growth factor binding protein-1 and phosphoenolpyruvate carboxykinase transcription. Roles of forkhead and insulin response sequences. J Biol Chem. 2001. 276:33705–33710.

14. Maccario M, Tassone F, Gianotti L, Lanfranco F, Grottoli S, Arvat E, et al. Effects of recombinant human insulin-like growth factor I administration on the growth hormone (gh) response to GH-releasing hormone in obesity. J Clin Endocrinol Metab. 2001. 86:167–171.

15. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001. 50:707–709.

16. St-Pierre DH, Bastard JP, Coderre L, Brochu M, Karelis AD, Lavoie ME, et al. Association of acylated ghrelin profiles with chronic inflammatory markers in overweight and obese postmenopausal women: a MONET study. Eur J Endocrinol. 2007. 157:419–426.

17. Childs GV, Akhter N, Haney A, Syed M, Odle A, Cozart M, et al. The somatotrope as a metabolic sensor: deletion of leptin receptors causes obesity. Endocrinology. 2011. 152:69–81.

18. Penalva A, Burguera B, Casabiell X, Tresguerres JA, Dieguez C, Casanueva FF. Activation of cholinergic neurotransmission by pyridostigmine reverses the inhibitory effect of hyperglycemia on growth hormone (GH) releasing hormone-induced GH secretion in man: does acute hyperglycemia act through hypothalamic release of somatostatin. Neuroendocrinology. 1989. 49:551–554.

19. Renier G, Serri O. Effects of acute and prolonged glucose excess on growth hormone release by cultured rat anterior pituitary cells. Neuroendocrinology. 1991. 54:521–525.

20. Norrelund H. The metabolic role of growth hormone in humans with particular reference to fasting. Growth Horm IGF Res. 2005. 15:95–122.

21. Scacchi M, Ida Pincelli A, Cavagnini F. Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. Front Neuroendocrinol. 2003. 24:200–224.

22. Henry BA, Rao A, Tilbrook AJ, Clarke IJ. Chronic food-restriction alters the expression of somatostatin and growth hormone-releasing hormone in the ovariectomised ewe. J Endocrinol. 2001. 170:R1–R5.

23. Sugihara H, Emoto N, Shibasaki T, Minami S, Wakabayashi I. Increased pituitary growth hormone-releasing factor (GRF) receptor messenger ribonucleic acid expression in food-deprived rats. Brain Res. 1996. 742:355–358.

24. Tannenbaum GS, Painson JC, Lengyel AM, Brazeau P. Paradoxical enhancement of pituitary growth hormone (GH) responsiveness to GH-releasing factor in the face of high somatostatin tone. Endocrinology. 1989. 124:1380–1388.

25. Itoh M. Immunoreactive somatostatin in the hypothalamus and other regions of the rat brain: effects of insulin, glucose, alpha- or beta-blocker and L-dopa. Endocrinol Jpn. 1979. 26:41–58.

26. Sato M, Frohman LA. Differential effects of central and peripheral administration of growth hormone (GH) and insulin-like growth factor on hypothalamic GH-releasing hormone and somatostatin gene expression in GH-deficient dwarf rats. Endocrinology. 1993. 133:793–799.

27. Melmed S, Yamashita S, Yamasaki H, Fagin J, Namba H, Yamamoto H, et al. IGF-I receptor signalling: lessons from the somatotroph. Recent Prog Horm Res. 1996. 51:189–215.

28. Ganda OP, Bachman ES. Porte D, Sherwin RS, Baron A, Ellenberg M, Rifkin H, editors. Diabetes secondary to endocrinopathies. Ellenberg and Rifkin's diabetes mellitus. 6th ed. New York: McGraw-Hill;2003–2425.

29. Melmed S. Medical progress: Acromegaly. N Engl J Med. 2006. 355:2558–2573.

30. Lebovitz HE. Jameson JL, De Groot LJ, editors. Hyperglycemia secondary to nondiabetic conditions and therapies. Endocrinology. 2010. Philadelphia: Elsevier;808–821.

31. Colao A. Pituitary tumours: the prolactinoma. Best Pract Res Clin Endocrinol Metab. 2009. 23:575–596.

32. Bertagna X, Guignat L, Groussin L, Bertherat J. Cushing’s disease. Best Pract Res Clin Endocrinol Metab. 2009. 23:607–623.

33. Jeong IK, Kim SH, Chung JH, Min YK, Lee MS, Lee MK, et al. The change of insulin sensitivity and insulin secretion according to glucose metabolism status in patients with cushing's syndrome. J Korean Soc Endocrinol. 2003. 18:392–403.

34. Kim MS, Yoon CY, Cho YM, Jung HS, Shin CS, Park KS, et al. Changes in plasma leptin levels relating to short-term thyroid manipulation in rats. J Korean Soc Endocrinol. 2002. 17:197–205.

35. Lee DH, Chung MY, Chang YJ, Park SS, Choi EJ, Kang HC, et al. Changes in insulin sensitivity and insulin secretory function in hyperthyroid patients. J Korean Soc Endocrinol. 1994. 9:108–114.

36. Marx SJ, Wells SA. Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors. Multiple endocrine neoplasia. Williams textbook of endocrinology. 2011. 12ed. Philadelphia: Elsevier;1728–1767.

37. Sung HY, Chun YJ, Lee H, Kwon BJ, Park KW, Lee JM, et al. A case of familial multiple endocrine neoplasia with MEN1 gene mutation. J Korean Endocr Soc. 2006. 21:560–566.

38. Park YS. Loss of function of the autoimmune regulator (AIRE) gene and development of poyendocrinopathy. J Korean Soc Endocrinol. 2003. 18:439–449.