The role of calcium in mediating phorbol ester- and insulin-stimulated adipocyte lipogenesis

The roles of protein kinase C, calcium and calmodulin in mediating insulin-stimulated lipogenesis by rat adipocytes were investigated using the protein kinase C activator, phorbol myristate acetate (PMA); the protein kinase C inhibitors, H7 and polymixin B; the calcium ionophore, A23187; the calcium channel blocker, verapamil; and the calmodulin inhibitor, calmidazolium. PMA caused a concentration-dependent, parallel left shift of the insulin-lipogenesis dose response curve. Both PMA- and insulin-stimulated lipogenesis were inhibited by H7 and polymixin B. A23187 enhanced the stimulatory action of both insulin and PMA was not inhibited by H7. The stimulatory effects of insulin in PMA were inhibited by verapamil and calmidazolium. These data indicate that insulin receptor-lipogenesis coupling in rat adipocytes is mediated by protein kinase C-elicited calcium influx and activation of calmodulin.