Cortistatin hyperpolarizes pancreatic beta cell membrane and reduces glucose-stimulated insulin secretion

Results Using insulin and glucagon secretion protocols with fresh islets isolated from C57BL6 mice, we observed that CORT reduced the glucose-stimulated insulin secretion (GSIS) in a similar magnitude from that of SST (p<0.01), an effect mediated by SST-R5 receptor. Glucagon secretion in response to 0.5 mM glucose was completely abrogated in the presence of CORT (p<0.001), as well as for SST. Beta cell function were further investigated and we observed that the reduction in insulin secretion was paralleled by a decrease in the glucose-induced calcium levels observed by fura-2 calcium imaging (p<0.001). As opposed to the effects on SST, the effect of CORT in beta cell calcium load was blocked by specific SST-R5 receptor antagonist, suggesting a higher affinity of CORT for this receptor. In addition, CORT reduced beta cell membrane potential and abolished action potential firings in perforated patch clamp experiments (p<0.001). CORT also diminished calcium currents in whole cell patch clamp experiments.