Abstract
Ghrelin, isolated from the human and rat stomach, is the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R). Both ghrelin and GHS-R are also present in the pancreas. This present study explored a possible physiological function of ghrelin in the regulation of insulin and glucose metabolism. Systemic administration of ghrelin increased blood glucose concentrations in a GH-independent manner in fasted mice. In the glucose tolerance test (GTT), ghrelin increased glucose levels further and decreased insulin levels. Conversely, administration of GHS-R antagonists lowered fasting glucose concentrations, markedly attenuated increases in glucose levels and enhanced increases in insulin levels during GTT. In isolated rat pancreatic islets, glucose-induced insulin release was reduced by ghrelin, while it was enhanced by GHS-R antagonists and anti-ghrelin antiserum. Cytosolic Ca2+ responses to glucose were enhanced by GHS-R antagonist in islets and suppressed by ghrelin in single β-cells. These findings suggest that endogenous ghrelin in islets reacts with GHS-Rs on β-cells and inhibits glucose-induced insulin release, thereby upwardly regulating blood glucose levels both in the basal state and upon glucose challenge. [Jpn J Physiol 54 Suppl:S74 (2004)]
