Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans

Diabetes

Volumn 59, Issue 9, 2010, Pages 2145-2151

  Tong, Jenny ^a   Prigeon, Ronald L ^b   Davis, Harold W ^a   Bidlingmaier, Martin ^c   Kahn, Steven E ^d   Cummings, David E ^d   Tschöp, Matthias H ^a   D'Alessio, David ^a,e  

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF MARYLAND   (United States)

^c LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^e VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADRENALIN; GHRELIN; GLUCAGON; GLUCOSE; GROWTH HORMONE; HYDROCORTISONE; INSULIN; NORADRENALIN; GLUCOSE BLOOD LEVEL;

ADRENALIN BLOOD LEVEL; ADULT; ARTICLE; CLINICAL ARTICLE; CONTINUOUS INFUSION; CONTROLLED STUDY; DRUG DOSE COMPARISON; FEMALE; GLUCAGON BLOOD LEVEL; GLUCOSE BLOOD LEVEL; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE; GROWTH HORMONE BLOOD LEVEL; HORMONE ACTION; HUMAN; HUMAN EXPERIMENT; HYDROCORTISONE BLOOD LEVEL; INSULIN BLOOD LEVEL; INSULIN RELEASE; INTRAVENOUS GLUCOSE TOLERANCE TEST; MALE; NORADRENALIN BLOOD LEVEL; NORMAL HUMAN; PRIORITY JOURNAL; ADOLESCENT; ANTAGONISTS AND INHIBITORS; BLOOD; DRUG EFFECTS; GLUCOSE TOLERANCE TEST; METABOLISM; MIDDLE AGED; REFERENCE VALUE; SECRETION (PROCESS); YOUNG ADULT;

ADOLESCENT; ADULT; BLOOD GLUCOSE; FEMALE; GHRELIN; GLUCOSE; GLUCOSE TOLERANCE TEST; GROWTH HORMONE; HUMANS; HYDROCORTISONE; INSULIN; MALE; MIDDLE AGED; REFERENCE VALUES; YOUNG ADULT;

EID: 77956357163     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db10-0504     Document Type: Article

References (49)

1. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000;407:908-913
2. Cummings DE. Ghrelin and the short- and long-term regulation of appetite and body weight. Physiol Behav 2006;89:71-84
3. Castaneda TR, Tong J, Datta R, Culler M, Tschop MH. Ghrelin in the regulation of body weight and metabolism. Front Neuroendocrinol 2010;31:44-60
4. Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology 1984;114:1537-1545
5. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-660
6. Arvat E, Di Vito L, Broglio F, Papotti M, Muccioli G, Dieguez C, Casanueva FF, Deghenghi R, Camanni F, Ghigo E. Preliminary evidence that Ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans. J Endocrinol Invest 2000;23:493-495
7. Tschop M, Wawarta R, Riepl RL, Friedrich S, Bidlingmaier M, Landgraf R, Folwaczny C. Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest 2001;24:RC19-21
8. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50:1714-1719
9. Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, Heiman ML, Lehnert P, Fichter M, Tschop M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol 2001;145:669-673
10. Shimizu Y, Nagaya N, Isobe T, Imazu M, Okumura H, Hosoda H, Kojima M, Kangawa K, Kohno N. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res 2003;9:774-778
11. Nagaya N, Uematsu M, Kojima M, Date Y, Nakazato M, Okumura H, Hosoda H, Shimizu W, Yamagishi M, Oya H, Koh H, Yutani C, Kangawa K. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001;104:2034-2038
12. Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, van der Lely AJ, Deghenghi R, Ghigo E. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 2001;86:5083-5086
13. Sun Y, Asnicar M, Smith RG. Central and peripheral roles of ghrelin on glucose homeostasis. Neuroendocrinology 2007;86:215-228
14. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong SS, Chaung LY, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJ, Dean DC, Melillo DG, Patchett AA, Nargund R, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LH. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996;273:974-977 (Pubitemid 26275178)
15. Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD. Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 1997;48:23-29 (Pubitemid 27298124)
16. Dezaki K, Hosoda H, Kakei M, Hashiguchi S, Watanabe M, Kangawa K, Yada T. Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2 signaling in beta-cells: implication in the glycemic control in rodents. Diabetes 2004;53:3142-3151
17. Date Y, Nakazato M, Hashiguchi S, Dezaki K, Mondal MS, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S. Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 2002;51:124-129
18. Volante M, Allia E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, Muccioli G, Ghigo E, Papotti M. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 2002;87:1300-1308
19. Colombo M, Gregersen S, Xiao J, Hermansen K. Effects of ghrelin and other neuropeptides (CART, MCH, orexin A and B, and GLP-1) on the release of insulin from isolated rat islets. Pancreas 2003;27:161-166
20. Wierup N, Svensson H, Mulder H, Sundler F. The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept 2002;107:63-69
21. Wierup N, Yang S, McEvilly RJ, Mulder H, Sundler F. Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. J Histochem Cytochem 2004;52:301-310
22. Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L. Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci U S A 2004;101:2924-2929
23. Egido EM, Rodriguez-Gallardo J, Silvestre RA, Marco J. Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol 2002;146:241-244
24. Reimer MK, Pacini G, Ahren B. Dose-dependent inhibition by ghrelin of insulin secretion in the mouse. Endocrinology 2003;144:916-921
25. Salehi A, Dornonville de la Cour C, Hakanson R, Lundquist I. Effects of ghrelin on insulin and glucagon secretion: a study of isolated pancreatic islets and intact mice. Regul Pept 2004;118:143-150
26. Dezaki K, Sone H, Koizumi M, Nakata M, Kakei M, Nagai H, Hosoda H, Kangawa K, Yada T. Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance. Diabetes 2006;55:3486-3493
27. Sun Y, Asnicar M, Saha PK, Chan L, Smith RG. Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice. Cell Metab 2006;3:379-386
28. Akamizu T, Takaya K, Irako T, Hosoda H, Teramukai S, Matsuyama A, Tada H, Miura K, Shimizu A, Fukushima M, Yokode M, Tanaka K, Kangawa K. Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects. Eur J Endocrinol 2004;150:447-455
29. Lucidi P, Murdolo G, Di Loreto C, Parlanti N, De Cicco A, Fatone C, Taglioni C, Fanelli C, Broglio F, Ghigo E, Bolli GB, Santeusanio F, De Feo P. Metabolic and endocrine effects of physiological increments in plasma ghrelin concentrations. Nutr Metab Cardiovasc Dis 2005;15:410-417
30. Elder DA, Prigeon RL, Wadwa RP, Dolan LM, D'Alessio DA. Beta-cell function, insulin sensitivity, and glucose tolerance in obese diabetic and nondiabetic adolescents and young adults. J Clin Endocrinol Metab 2006;91:185-191
31. Kahn SE, Montgomery B, Howell W, Ligueros-Saylan M, Hsu CH, Devineni D, McLeod JF, Horowitz A, Foley JE. Importance of early phase insulin secretion to intravenous glucose tolerance in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 2001;86:5824-5829
32. Damjanovic SS, Lalic NM, Pesko PM, Petakov MS, Jotic A, Miljic D, Lalic KS, Lukic L, Djurovic M, Djukic VB. Acute effects of ghrelin on insulin secretion and glucose disposal rate in gastrectomized patients. J Clin Endocrinol Metab 2006;91:2574-2581
33. Tamagawa T, Henquin JC. Epinephrine modifications of insulin release and of 86Rb or 45Ca2 fluxes in rat islets. Am J Physiol 1983;244:E245-E252
34. Sherwin RS, Sacca L. Effect of epinephrine on glucose metabolism in humans: contribution of the liver. Am J Physiol 1984;247:E157-E165
35. Barseghian G, Levine R. Effect of corticosterone on insulin and glucagon secretion by the isolated perfused rat pancreas. Endocrinology 1980;106:547-552
36. Kalhan SC, Adam PA. Inhibitory effect of prednisone on insulin secretion in man: model for duplication of blood glucose concentration. J Clin Endocrinol Metab 1975;41:600-610
37. Bratusch-Marrain PR, Smith D, DeFronzo RA. The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 1982;55:973-982 (Pubitemid 13054363)
38. Rizza RA, Mandarino LJ, Gerich JE. Effects of growth hormone on insulin action in man. Mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization. Diabetes 1982;31:663-669
39. Dezaki K, Kakei M, Yada T. Ghrelin uses Galphai2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet β-cells: novel signal transduction of ghrelin. Diabetes 2007;56:2319-2327
40. Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002;87:2988
41. Andralojc KM, Mercalli A, Nowak KW, Albarello L, Calcagno R, Luzi L, Bonifacio E, Doglioni C, Piemonti L. Ghrelin-producing epsilon cells in the developing and adult human pancreas. Diabetologia 2009;52:486-493
42. Obici S, Zhang BB, Karkanias G, Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 2002;8:1376-1382
43. Obici S, Feng Z, Karkanias G, Baskin DG, Rossetti L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci 2002;5:566-572
44. Pocai A, Morgan K, Buettner C, Gutierrez-Juarez R, Obici S, Rossetti L. Central leptin acutely reverses diet-induced hepatic insulin resistance. Diabetes 2005;54:3182-3189
45. Gronemeyer H. Control of transcription activation by steroid hormone receptors. FASEB J 1992;6:2524-2529
46. Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 2001;280:R1483-R1487
47. Vestergaard ET, Gormsen LC, Jessen N, Lund S, Hansen TK, Moller N, Jorgensen JO. Ghrelin infusion in humans induces acute insulin resistance and lipolysis independent of growth hormone signaling. Diabetes 2008;57:3205-3210
48. Ahima RS. Ghrelin - a new player in glucose homeostasis? Cell Metab 2006;3:301-302
49. van der Lely AJ. Ghrelin and new metabolic frontiers. Horm Res 71 Suppl 2009;1:129-133