Russell's viper venom stimulates insulin secretion from rat islets of Langerhans

Burmese Russell's viper venom (RVV) caused a dose- and temperature-dependent stimulation of insulin secretion from islets of Langerhans isolated from rat pancreas by collagenase digestion. RVV stimulated both basal and glucose-induced insulin secretion at concentrations which did not compromise islet cell viability as assessed by exclusion of trypan blue dye. The effects of RVV on insulin secretion could not be attributed to the activation of protein kinase C (PKC), since down-regulation of PKC by prolonged exposure to a tumour-promoting phorbol ester did not abolish subsequent secretory responses to RVV. However, RVV-induced insulin secretion was inhibited in the absence of extracellular Ca2+, and RVV did not stimulate insulin secretion from Ca(2+)-clamped electrically permeabilized islets at either substimulatory (50 nmol/l) or stimulatory (10 mumol/l) concentrations of Ca2+, suggesting that changes in cytosolic Ca2+ are important in the stimulation of insulin secretion by RVV. The phospholipase A2 (PLA2) inhibitor quinacrine caused a dose-dependent inhibition of RVV-induced insulin secretion, suggesting that the activation of PLA2, perhaps in response to Ca2+ influx, may be partially responsible for RVV-induced insulin secretion.