Ghrelin signalling in β-cells regulates insulin secretion and blood glucose

Diabetes, Obesity and Metabolism

Volumn 16, Issue , 2014, Pages 111-117

  Yada, T ^a   Damdindorj, B ^a   Rita, R S ^a   Kurashina, T ^a   Ando, A ^a   Taguchi, M ^a   Koizumi, M ^a   Sone, H ^a,b   Nakata, M ^a   Kakei, M ^a   Dezaki, K ^a  

^a JICHI MEDICAL UNIVERSITY   (Japan)

^b Niigata Women's College   (Japan)

Author keywords

Ca2+; cAMP; Diabetes; Ghrelin; Ghrelin knockout; GHS R; Insulin release; Islet; Kv channel; Paracrine; cell

Indexed keywords

CALCIUM ION; CYCLIC AMP; GHRELIN; GLUCOSE; GUANINE NUCLEOTIDE BINDING PROTEIN; GHRELIN RECEPTOR; GHRL PROTEIN, HUMAN; GLUCOSE BLOOD LEVEL; INSULIN;

ACTION POTENTIAL; CELL ISOLATION; DRUG TARGETING; GLUCOSE BLOOD LEVEL; GLUCOSE INTOLERANCE; HUMAN; INSULIN BLOOD LEVEL; INSULIN RELEASE; LIPID DIET; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PARACRINE SIGNALING; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; BIOLOGICAL MODEL; FEEDBACK SYSTEM; FOOD INTAKE; GENETICS; KNOCKOUT MOUSE; METABOLISM; PANCREAS ISLET; SECRETION (PROCESS);

ANIMALS; APPETITE REGULATION; BLOOD GLUCOSE; FEEDBACK, PHYSIOLOGICAL; GHRELIN; HUMANS; INSULIN; INSULIN-SECRETING CELLS; ISLETS OF LANGERHANS; MICE, KNOCKOUT; MODELS, BIOLOGICAL; RECEPTORS, GHRELIN; SIGNAL TRANSDUCTION;

EID: 84908510168     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12344     Document Type: Review

References (43)

1. Kojima M, Hosoda H, Date Y et al. Ghrelin is a growth-hormone-releasing peptide from stomach. Nature 1999; 402: 656-660.
2. Howard AD, Feighner SD, Cully DF et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996; 273: 974-977.
3. Ariyasu H, Takaya K, Tagami T et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001; 86: 4753-4758.
4. Nakazato M, Murakami N, Date Y et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409: 194-198.
5. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407: 908-913.
6. Kojima M, Kangawa K. Drug insight: the functions of ghrelin and its potential as a multitherapeutic hormone. Nat Clin Pract Endocrinol Metab 2006; 2: 80-88.
7. Tschop M, Weyer C, Tataranni PA et al. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707-709.
8. Ariyasu H, Takaya K, Hosoda H et al. Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin. Endocrinology 2002; 143: 3341-3350.
9. Shiiya T, Nakazato M, Mizuta M et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002; 87: 240-244.
10. Ikezaki A, Hosoda H, Ito K et al. Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. Diabetes 2002; 51: 3408-3411.
11. Poykko SM, Kellokoski E, Horkko S et al. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 2003; 52: 2546-2553.
12. Broglio F, Benso A, Castiglioni C et al. The endocrine response to ghrelin as a function of gender in humans in young and elderly subjects. J Clin Endocrinol Metab 2003; 88: 1537-1542.
13. 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.
14. Broglio F, Arvat E, Benso A et al. Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans. J Clin Endocrinol Metab 2002; 87: 3783-3790.
15. 2+ signaling in β-cells: implication in the glycemic control in rodents. Diabetes 2004; 53: 3142-3151.
16. 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.
17. Tong J, Davis HW, Summer S et al. Acute administration of unacylated ghrelin has no effect on basal or stimulated insulin secretion in healthy humans. Diabetes 2014; 63: 2309-2319.
18. 2+ signaling and insulin release in islet β-cells: novel signal transduction of ghrelin. Diabetes 2007; 56: 2319-2327.
19. 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.
20. 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.
21. 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.
22. Shiau YS, Huang PT, Liou HH et al. Structural basis of binding and inhibition of novel tarantula toxins in mammalian voltage-dependent potassium channels. Chem Res Toxicol 2003; 16: 1217-1225.
23. Dezaki K, Boldbataar D, Sone H et al. Ghrelin attenuates cAMP-PKA signaling to evoke insulinostatic cascade in islet β-cells. Diabetes 2011; 60: 2315-2324.
24. Damdindorj B, Dezaki K, Kurashina T et al. Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells. FEBS Lett 2012; 586: 2555-2562.
25. Date Y, Nakazato M, Hashiguchi S et al. Ghrelin is present in pancreatic α-cells of humans and rats and stimulates insulin secretion. Diabetes 2002; 51: 124-129.
26. 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.
27. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 2008; 132: 387-396.
28. An W, Li Y, Xu G et al. Modulation of ghrelin O-acyltransferase expression in pancreatic islets. Cell Physiol Biochem 2010; 26: 707-716.
29. 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.
30. 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.
31. 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.
32. Wierup N, Sundler F. Ultrastructure of islet ghrelin cells in the human fetus. Cell Tissue Res 2005; 319: 423-428.
33. Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L. Ghrelin cells replace insulin-producing β cells in two mouse models of pancreas development. Proc Natl Acad Sci U S A 2004; 101: 2924-2929.
34. Asakawa A, Inui A, Kaga T et al. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003; 52: 947-952.
35. Sun Y, Ahmed S, Smith RG. Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 2003; 23: 7973-7981.
36. Wortley KE, Anderson KD, Garcia K et al. Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci U S A 2004; 101: 8227-8232.
37. Wortley KE, del Rincon JP, Murray JD et al. Absence of ghrelin protects against early-onset obesity. J Clin Invest 2005; 115: 3573-3578.
38. De Smet B, Depoortere I, Moechars D et al. Energy homeostasis and gastric emptying in ghrelin knockout mice. J Pharmacol Exp Ther 2006; 316: 431-439.
39. Gauna C, Delhanty PJ, Hofland LJ et al. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 2005; 90: 1055-1060.
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. Doi A, Shono T, Nishi M et al. IA-2β, 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.
42. Zhang CY, Baffy G, Perret P et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, β cell dysfunction, and type 2 diabetes. Cell 2001; 105: 745-755.
43. Kohno D, Nakata M, Maekawa F et al. Leptin suppresses ghrelin-induced activation of neuropeptide Y neurons in the arcuate nucleus via phosphatidylinositol 3-kinase- and phosphodiesterase 3-mediated pathway. Endocrinology 2007; 148: 2251-2263.