抄録
Ghrelin, isolated from the human and rat stomach, is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). We have reported that GHS-R was expressed in rat pancreatic islets and that ghrelin suppressed glucose-induced insulin release via activation of voltage-dependent delayed rectifier K+ channels and attenuation of glucose-induced action potentials, leading to suppression of glucose-induced Ca2+ signaling in β-cells. In this study, we aimed to determine the involvement of cyclic AMP productions, another major signalling pathway for insulin release, in the ghrelin-induced suppression of insulin release. Both GHS-R blockade and anti-ghrelin antiserum markedly enhanced 8.3 mM glucose-induced insulin release in rat perfused pancreas and isolated islets. GHS-R blockade and anti-ghrelin antiserum also enhanced 8.3 mM glucose-induced cyclic AMP productions in rat islets. Conversely, exogenous ghrelin (10 nM) suppressed insulin release and cyclic AMP productions. In the presence of either dibtyryl cyclic AMP or adenylate cyclase inhibitor MDL12330A, ghrelin failed to attenuate glucose-induced insulin release. This study suggests that ghrelin suppresses glucose-induced cyclic AMP production as well as cytosolic Ca2+ response. These abilities of ghrelin to impede cyclic AMP and Ca2+ signaling routes at least partly account for the inhibition of glucose-induced insulin release. [J Physiol Sci. 2006;56 Suppl:S68]
