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 ghrelin and GHS-R were expressed in 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, which leads to suppression of glucose-induced Ca2+ signaling in β-cells. In this study, we employed ghrelin knockout (Ghr-KO) mice and explored physiological role of ghrelin in the regulation of insulin release. Glucose-induced, but not KCl-induced, insulin release from isolated islets of Ghr-KO mice was significantly greater than that of wild-type control mice, while insulin content was unaltered. Ghr-KO mice displayed increased insulin and decreased glucose responses in glucose tolerance tests. In contrast, no significant differences in insulin tolerance tests were observed between Ghr-KO and wild-type mice. These findings reveal that the islet-originated ghrelin serves as a physiological downregulator of glucose-induced insulin release. [J Physiol Sci. 2007;57 Suppl:S125]
