The ghrelin O-acyltransferase-ghrelin system: A novel regulator of glucose metabolism

Current Opinion in Endocrinology, Diabetes and Obesity

Volumn 18, Issue 1, 2011, Pages 50-55

  Heppner, Kristy M ^a   Tong, Jenny ^a   Kirchner, Henriette ^a   Nass, Ralf ^b   Tschöp, Matthias H ^a  

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

^b UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Des acyl ghrelin; ghrelin; ghrelin O acyltransferase; glucose; insulin

Indexed keywords

ADENYLATE KINASE; GHRELIN; GHRELIN O ACYLTRANSFERASE; INSULIN; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 2;

ACYLATION; ADIPOCYTE; ARTICLE; CELL STIMULATION; EMBRYO DEVELOPMENT; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; GLUCOSE TRANSPORT; HORMONAL REGULATION; HUMAN; INSULIN RELEASE; INSULIN SENSITIVITY; LIVER CELL; METABOLIC DISORDER; NONHUMAN; NUTRITIONAL STATUS; PANCREAS ISLET BETA CELL;

ACYLTRANSFERASES; ANIMALS; DIABETES MELLITUS, TYPE 2; ENERGY METABOLISM; GHRELIN; GLUCOSE; GROWTH AND DEVELOPMENT; HUMANS; INSULIN; SIGNAL TRANSDUCTION;

EID: 78650829752     PISSN: 1752296X     EISSN: None     Source Type: Journal    
DOI: 10.1097/MED.0b013e328341e1d3     Document Type: Article

References (63)

1. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402:656-660.
2. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407:908-913.
3. Hosoda H, Kojima M, Mizushima T, et al. Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by posttranslational processing. J Biol Chem 2003; 278:64-70.
4. Hosoda H, Kojima M, Matsuo H, Kangawa K. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 2000; 279:909-913.
5. Nishi Y, Hiejima H, Hosoda H, et al. Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin. Endocrinology 2005; 146:2255-2264.
6. Gutierrez JA, Solenberg PJ, Perkins DR, et al. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci U S A 2008; 105:6320-6325.
7. Yang J, Brown MS, Liang G, et al. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 2008; 132:387-396.
8. Bednarek MA, Feighner SD, Pong SS, et al. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem 2000; 43:4370-4376.
9. Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000; 141:4325-4328.
10. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409:194-198.
11. Liu J, Prudom CE, Nass R, et al. Novel ghrelin assays provide evidence for independent regulation of ghrelin acylation and secretion in healthy young men. J Clin Endocrinol Metab 2008; 93:1980-1987.
12. Kageyama H, Funahashi H, Hirayama M, et al. Morphological analysis of ghrelin and its receptor distribution in the rat pancreas. Regul Pept 2005; 126:67-71.
13. Dezaki K, Hosoda H, Kakei M, et al. 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.
14. Date Y, Nakazato M, Hashiguchi S, et al. Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 2002; 51:124-129.
15. Volante M, Allia E, Gugliotta P, et al. 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.
16. Qader SS, Hakanson R, Rehfeld JF, et al. Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas. Regul Pept 2008; 146:230-237.
17. 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.
18. Wierup N, Yang S, McEvilly RJ, et al.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.
19. Holst B, Cygankiewicz A, Jensen TH, et al. High constitutive signaling of the ghrelin receptor: identification of a potent inverse agonist. Mol Endocrinol 2003; 17:2201-2210.
20. Holst B, Holliday ND, Bach A, et al. Common structural basis for constitutive activity of the ghrelin receptor family. J Biol Chem 2004; 279:53806-53817.
21. Petersen PS, Woldbye DP, Madsen AN, et al. In vivo characterization of high basal signaling from the ghrelin receptor. Endocrinology 2009; 150:4920-4930.
22. Dezaki K, Sone H, Koizumi M, et al. Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance. Diabetes 2006; 55:3486-3493.
23. Lee HM, Wang G, Englander EW, et al. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 2002; 143:185-190.
24. Reimer MK, Pacini G, Ahren B. Dose-dependent inhibition by ghrelin of insulin secretion in the mouse. Endocrinology 2003; 144:916-921.
25. Cui C, Ohnuma H, Daimon M, et al. Ghrelin infused into the portal vein inhibits glucose-stimulated insulin secretion in Wistar rats. Peptides 2008; 29: 1241-1246.
26. Sun Y, Asnicar M, Saha PK, et al. Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice. Cell Metab 2006; 3:379-386.
27. Broglio F, Arvat E, Benso A, et al. 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.
28. Broglio F, Gottero C, Prodam F, et al. Nonacylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 2004; 89:3062-3065.
29. Lucidi P, Murdolo G, Di Loreto C, et al. Metabolic and endocrine effects of physiological increments in plasma ghrelin concentrations. Nutr Metab Cardiovasc Dis 2005; 15:410-417.
30. Tong J, Prigeon RL, Davis HW, et al. Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. Diabetes 2010; 59:2145-2151.
31. 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.
32. Doi A, Shono T, Nishi M, et al. IA-2beta, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion. Proc Natl Acad Sci U S A 2006; 103:885-890.
33. Wang Y, Nishi M, Doi A, et al. Ghrelin inhibits insulin secretion through the AMPK-UCP2 pathway in beta cells. FEBS Lett 2010; 584:1503-1508.
34. Barseghian G, Levine R. Effect of corticosterone on insulin and glucagon secretion by the isolated perfused rat pancreas. Endocrinology 1980; 106: 547-552.
35. Ni H, De Waele K, Walia P, Chanoine JP. In vitro and in vivo effect of acylated and unacylated ghrelin on neonatal glucose homeostasis. Pediatr Res 2010; 67:609-613.
36. Gauna C, Delhanty PJ, Hofland LJ, et al. Ghrelin stimulates, whereas desoctanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 2005; 90:1055-1060.
37. Murata M, Okimura Y, Iida K, et al. Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J Biol Chem 2002; 277: 5667-5674.
38. Patel AD, Stanley SA, Murphy KG, et al. Ghrelin stimulates insulin-induced glucose uptake in adipocytes. Regul Pept 2006; 134:17-22.
39. Chen Y, Cao CP, Li CR, et al. Ghrelin modulates insulin sensitivity and tau phosphorylation in high glucose-induced hippocampal neurons. Biol Pharm Bull 2010; 33:1165-1169.
40. Heijboer AC, van den Hoek AM, Parlevliet ET, et al. Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice. Diabetologia 2006; 49:732-738.
41. Barazzoni R, Zanetti M, Cattin MR, et al. Ghrelin enhances in vivo skeletal muscle but not liver AKT signaling in rats. Obesity (Silver Spring) 2007; 15:2614-2623.
42. Vestergaard ET, Djurhuus CB, Gjedsted J, et al. Acute effects of ghrelin administration on glucose and lipid metabolism. J Clin Endocrinol Metab 2008; 93:438-444.
43. 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.
44. Vestergaard ET, Gormsen LC, Jessen N, et al. Ghrelin infusion in humans induces acute insulin resistance and lipolysis independent of growth hormone signaling. Diabetes 2008; 57:3205-3210.
45. Damjanovic SS, Lalic NM, Pesko PM, et al. Acute effects of ghrelin on insulin secretion and glucose disposal rate in gastrectomized patients. J Clin Endocrinol Metab 2006; 91:2574-2581.
46. Nass R, Pezzoli SS, OliveriMC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med 2008; 149:601-611.
47. 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.
48. Pfluger PT, Kirchner H, Gunnel S, et al. Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. Am J Physiol Gastrointest Liver Physiol 2008; 294:G610-G618.
49. Kirchner H, Gutierrez JA, Solenberg PJ, et al. GOAT links dietary lipids with the endocrine control of energy balance. Nat Med 2009; 15:741-745.
50. Zhao TJ, Liang G, Li RL, et al. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc Natl Acad Sci U S A 2010; 107:7467-7472.
51. Wortley KE, del Rincon JP, Murray JD, et al. Absence of ghrelin protects against early-onset obesity. J Clin Invest 2005; 115:3573-3578.
52. Longo KA, Charoenthongtrakul S, Giuliana DJ, et al. Improved insulin sensitivity and metabolic flexibility in ghrelin receptor knockout mice. Regul Pept 2008; 150:55-61.
53. Sun Y, Butte NF, Garcia JM, Smith RG. Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance. Endocrinology 2008; 149:843-850.
54. Muccioli G, Pons N, Ghe C, et al. Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a nontype 1a growth hormone secretagogue receptor. Eur J Pharmacol 2004; 498:27-35.
55. Baldanzi G, Filigheddu N, Cutrupi S, et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 2002; 159:1029-1037.
56. Rodriguez A, Gomez-Ambrosi J, Catalan V, et al. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int J Obes (Lond) 2009; 33:541-552.
57. Inhoff T, Monnikes H, Noetzel S, et al. Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats. Peptides 2008; 29:2159-2168.
58. Kumar R, Salehi A, Rehfeld JF, et al. Proghrelin peptides: desacyl ghrelin is a powerful inhibitor of acylated ghrelin, likely to impair physiological effects of acyl ghrelin but not of obestatin. A study of pancreatic polypeptide secretion from mouse islets. Regul Pept 2010; 164:65-70.
59. Gauna C, Kiewiet RM, Janssen JA, et al. Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions. Am J Physiol Endocrinol Metab 2007; 293:E697-E704.
60. Gauna C, Meyler FM, Janssen JA, et al. Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity. J Clin Endocrinol Metab 2004; 89:5035-5042.
61. Giovambattista A, Gaillard RC, Spinedi E. Ghrelin gene-related peptides modulate rat white adiposity. Vitam Horm 2008; 77:171-205.
62. Zhang W, Chai B, Li JY, et al. Effect of des-acyl ghrelin on adiposity and glucose metabolism. Endocrinology 2008; 149:4710-4716.
63. Delhanty PJ, Sun Y, Visser JA, et al. Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice. PLoS One 2010; 5:e11749.