Mastoparan stimulates insulin secretion from pancreatic beta-cells by effects at a late stage in the secretory pathway

Abstract

Mastoparan (MP) is a component of wasp venom which stimulates secretion from a number of cell types. We have used intact and electrically permeabilised islets of Langerhans to investigate the mechanisms through which MP stimulates insulin secretion from pancreatic beta-cells. MP caused a temperature-dependent and dose-related stimulation of insulin secretion from intact islets at a substimulatory concentration (2 mM) of glucose, which was not dependent upon the presence of extracellular Ca2+. MP also stimulated ATP-independent insulin secretion from electrically permeabilised islets in which intracellular Ca2+ was clamped at a substimulatory concentration (50 nM). MP-induced insulin secretion was not inhibited by down-regulation of islet protein kinase C, nor by the protein kinase inhibitor staurosporine, nor by the cyclic AMP antagonist Rp-adenosine 3',5'-cyclic phosphorothioate. However, MP-induced secretion from permeabilised islets was inhibited by the presence of guanosine 5'-O-2-thiodiphosphate. These results suggest that MP stimulates insulin secretion by a mechanism that is independent of changes in cytosolic Ca2+ or protein kinase activation, but which is dependent, at least in part, upon activation of a GTP-binding protein at a late stage in the secretory process.