title: Islet β-cell ghrelin signaling for inhibition of insulin secretion.
abstract: Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach, where circulating ghrelin is produced predominantly. In addition to its unique role in regulating growth-hormone release, mealtime hunger, lipid metabolism, and the cardiovascular system, ghrelin is involved in the regulation of glucose metabolism. Ghrelin is expressed in pancreatic islets and released into pancreatic microcirculations. Ghrelin inhibits insulin release in mice, rats, and humans. Pharmacological and genetic blockades of islet-derived ghrelin markedly augment glucose-induced insulin release. The signal transduction mechanisms of ghrelin in islet β-cells are very unique, being distinct from those utilized for growth-hormone release. Ghrelin attenuates the glucose-induced cAMP production and PKA activation, which drives activation of Kv channels and suppression of the glucose-induced [Ca(2+)](i) increase and insulin release in β-cells. Insulinostatic function of the ghrelin-GHS-R system in islets is a potential therapeutic target for type 2 diabetes.
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Japan. dezaki@jichi.ac.jp
authors.forename: Katsuya
authors.initials: K
authors.lastname: Dezaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D007328:Insulin; D007329:Insulin Antagonists; D009842:Oligopeptides; D054440:Receptors, Ghrelin; D000242:Cyclic AMP; D005947:Glucose