title: Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells.
abstract: We studied interactive effects of insulinotropic GLP-1 and insulinostatic ghrelin on rat pancreatic islets. GLP-1 potentiated glucose-induced insulin release and cAMP production in isolated islets and [Ca(2+)](i) increases in single β-cells, and these potentiations were attenuated by ghrelin. Ghrelin suppressed [Ca(2+)](i) responses to an adenylate cyclase activator forskolin. Moreover, GLP-1-induced insulin release and cAMP production were markedly enhanced by [D-lys(3)]-GHRP-6, a ghrelin receptor antagonist, in isolated islets. These results indicate that both exogenous and endogenous islet-derived ghrelin counteracts glucose-dependent GLP-1 action to increase cAMP production, [Ca(2+)](i) and insulin release in islet β-cells, positioning ghrelin as a modulator of insulinotropic GLP-1.
authors: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan.
authors: Boldbaatar
authors: B
authors: Damdindorj
authors: Katsuya
authors: K
authors: Dezaki
authors: Tomoyuki
authors: T
authors: Kurashina
authors: Hideyuki
authors: H
authors: Sone
authors: Rauza
authors: R
authors: Rita
authors: Masafumi
authors: M
authors: Kakei
authors: Toshihiko
authors: T
authors: Yada
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology*; D007515:Islets of Langerhans / Q000166:cytology*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D054439:Ghrelin; D007328:Insulin; D005576:Colforsin; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005947:Glucose; D002118:Calcium