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 Ca²⁺ 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 CaCl₂. 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.