Effect of trifluoperazine on the action of insulin in rat adipocytes

Abstract

Trifluoperazine (TFP), a potent inhibitor of calmodulin action, at a concentration of 12 microM decreased the stimulating effects of insulin on 1) fat cell pyruvate dehydrogenase (PDH) activation, 2) generation/action of PDH activator by adipocyte plasma membranes, and 3) insulin-induced loss of insulin receptors, without altering spermine-induced activation of fat cell PDH or preventing insulin stimulation of glucose oxidation. In addition to these effects on insulin action, TFP abolished several biological actions of the insulin-generated PDH stimulator from liver particulate fractions. These actions include fat cell PDH activation and decrease in receptors. These data indicate that TFP inhibits both membrane-associated and intracellular components of insulin action. The results suggest involvement of calcium-binding protein (calmodulin) and/or phospholipid dependent-calcium activated protein kinase C in some of the actions of insulin in fat cells. The insulin effect on glucose oxidation appears to be less dependent on these mediators.