Endothelin-1 and endothelin-3 stimulate insulin release by isolated rat pancreatic islets

Endothelins (ETs) are potent vasoconstrictive peptides released from the en dothelium and other tissues, which act on target cells by receptorial calci um-mediated mechanisms. ET-1 levels are increased in diabetes, and observat ions suggest the involvement of ETs in the pathogenesis of diabetic angiopa thy. However, it is not possible to exclude that ETs might also influence i nsulin secretion or function. In vivo infusion of ET-1 in rats induces hypo glycaemia and hyperinsulinemia and in vitro incubation with ET-1 stimulates insulin release by mouse islets. Therefore, ETs might be involved in a cir culus vitiosus, resulting in hyperinsulinemia and diabetic angiopathy. The purpose of our study was to verify the effect of ET-1 on rat islets, in bot h the presence and absence of physiological glucose concentration. Moreover , we tested the effect of another isoform of endothelins, ET-3, and verifie d the involvement of extracellular calcium in such events. Islets were incu bated with increasing ET-1 or ET-3, with or without glucose 5.6 mM. Other s amples were prepared using calcium-free medium. Incubation in medium contai ning ET-1 and ET-3, in the presence of glucose and calcium, induced an incr ease in insulin release. When ET-1 and ET-3 were incubated without glucose and calcium, insulin release was not modified. Our studies demonstrate that : 1) ET-3, like ET-1, stimulates insulin release by rat isolated islets; 2) direct insulin stimulating effect on islets of both ET-1 and ET-3 is evide nt with physiological glucose concentrations and is calcium mediated. These results support the hypothesis of ET involvement in the regulation of insu lin secretion. (C) 2000, Editrice Kurtis.