Abstract
Ghrelin is a peptide isolated from the human and rat stomach as an endogenous ligand for growth hormone secretagoue receptor (GHS-R). mRNAs for ghrelin and GHS-R are present in the pancreatic islets. We previously reported that both the glucose-induced insulin release and cytosolic Ca2+ responses to glucose were enhanced by GHS-R antagonist and suppressed by ghrelin in isolated pancreatic islets of the rats. This finding suggested that endogenous ghrelin in islets inhibits glucose-induced insulin release. To further clarify the physiological role of the endogenous ghrelin in insulin release, we employed perfusion system of the isolated rat pancreas that retains the intact microcirculation in islets. Both the first and second phases of glucose-induced insulin release were significantly increased by GHR-antagonist and antiserum against ghrelin, while they were reduced by exogenous ghrelin. However, effects of GHS-R antagonist, anti-ghrelin antiserum and ghrelin on glucose-induced insulin release were absolutely abolished in the rats that were pre-treated with pertussis toxin, a specific inhibitor of certain subtypes of GTP-binding proteins (Gi and Go). These results indicate that endogenous ghrelin inhibits glucose-induced insulin release under physiological conditions preserving microcirculation in islets and that ghrelin exerts the inhibitory effect via GHS-R and in a pertussis toxin-sensitive manner. [Jpn J Physiol 55 Suppl:S76 (2005)]
