GLUCOSE-STIMULATED INSULIN-SECRETION IS NOT DEPENDENT ON ACTIVATION OF PROTEIN KINASE-A

The involvement of cyclic AMP-dependent protein kinase A (PKA) in the exocytotic release of insulin from rat pancreatic islets was investigated using the Rp isomer of adenosine 3′,5′-cyclic phosphorothioate (Rp-cAMPS). Preincubation of electrically permeabilised islets with Rp-cAMPS (1mM, 1h, 4°C) inhibited cAMP-induced phosphorylation of islet proteins of apparent molecular weights in the range 20-90kDa, but did not affect basal (50nM Ca2+) nor Ca2+-stimulated (10μM) protein phosphorylation. Similarly, Rp-cAMPS (500μM) inhibited both cAMP- (100μM) and 8BrcAMP-induced (100μM) insulin secretion from electrically permeabilised islets without affecting Ca2+-stimulated (10μM) insulin release. In intact islets, Rp-cAMPS (500μM) inhibited forskolin (1μM, 10μM) potentiation of insulin secretion, but did not significantly impair the insulin secretory response to a range of glucose concentrations (2-20mM). These results suggest that cAMP-induced activation of PKA is not essential for either basal or glucose-stimulated insulin secretion from rat islets. © 1990 Academic Press, Inc.