Ghrelin Inhibits Insulin Release by Regulating the Expression of Inwardly Rectifying Potassium Channel 6.2 in Islets

IntroductionThe objective is to investigate the influence of ghrelin administration on both the insulin secretion and the expression of ATP-sensitive K+ channels in islet.MethodsGhrelin and [D-Lys3] growth hormone releasing peptide-6 were administered via intraperitoneal injection in Wistar rats at the doses 10 and 10 μmol/kg/d for 2 weeks, respectively. Then glucose tolerance tests were performed and plasma insulin concentrations were measured. Islets were isolated for insulin release experiments. Single β cells were isolated for electrophysiological experiments. Determination of the Kir6.2 and SUR1 mRNA and protein expression levels in islets was performed by polymerase chain reaction and western blotting.ResultsIntraperitoneal administration of exogenous ghrelin significantly (P < 0.05) increased blood glucose concentrations, attenuated insulin responses during glucose tolerance tests, reduced insulin release from the isolated islets induced by 11.1 and 16.7 mmol/L glucose, hyperpolarized the resting membrane potential and increased the Kir6.2 mRNA and protein expression levels. In contrast, counteraction of ghrelin by intraperitoneal injection of [D-Lys3] growth hormone releasing peptide-6 significantly (P < 0.05) attenuated the aforementioned changes. SUR1 expression levels were not altered in this study.ConclusionsGhrelin via pancreatic growth hormone secretagogue receptor up-regulates the Kir6.2 expression in islet by hyperpolarizing the resting membrane potential which results in the inhibition of insulin release.