Activation of protein kinase C by a tumor-promoting phorbol ester in pancreatic islets

Abstract

Rat pancreatic islet homogenates display protein kinase C activity. This phospholipid-dependent and calcium-sensitive enzyme is activated by diacylglycerol or the tumor-promoting phorbol ester 12- O-tetradecanoylphorbol-13-acetate (TPA). In the presence of TPA, the K a for Ca 2+ is close to 5 μM. TPA does not affect phosphoinositide turnover but stimulates [ 32P]- and [ 3H]choline-labelling of phosphatidylcholine in intact islets. Exogenous phospholipase C stimulates insulin release, in a sustained and glucose-independent fashion. The secretory response to phospholipase C persists in media deprived of CaCl 2. It is proposed that protein kinase C participates in the coupling of stimulus recognition to insulin release evoked by TPA, phospholipase C and, possibly, those secretatogues causing phosphoinositide breakdown in pancreatic islets.