MASTOPARAN STIMULATES INSULIN-SECRETION FROM PANCREATIC BETA-CELLS BYEFFECTS AT A LATE-STAGE IN THE SECRETORY PATHWAY

Mastoparan (MP) is a component of wasp venom which stimulates secretio n from a number of cell types. We have used intact and electrically pe rmeabilised 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 extracellula r Ca2+. MP also stimulated ATP electrically permeabilised islets in wh ich intracellular Ca2+ was clamped at a substimulatory concentration ( 50 nM). MP-induced insulin secretion was not inhibited by down-regulat ion of islet protein kinase C, nor by the protein kinase inhibitor sta urosporine, nor by the cyclic AMP antagonist Rp-adenosine 3',5'-cyclic phosphorothioate. However, MP-induced secretion from permeabilised is lets was inhibited by the presence of guanosine 5'-O-2-thiodiphosphate . These results suggest that MP stimulates insulin secretion by a mech anism that is independent of changes in cytoSoliC Ca2+ or protein kina se activation, but which is dependent, at least in part, upon activati on of a GTP-binding protein at a late stage in the secretory process.