Insulin-Like, Antilipolytic Effect of 12-O-Tetradecanoyl Phorbol 13-Acetate in Rat White Adipocytes

Abstract

Previous experimental data documenting an insulin like-effect of 12-O-tetradecanoyl phorbol 13-acetate (TPA), a specific activator of protein kinase C, on glucose transport in adipocytes prompted us to test the hypothesis that TPA might display another insulin-like effect, i.e., antagonize catecholamine-induce lipolysis. TPA (100 nM) led to a decrease of both free fatty acid (41%) and glycerol (58%) release due to 1 microM norepinephrine stimulation in isolated rat adipocytes. TPA also diminished the antilipolytic effect of insulin (5 ng.ml-1) in the presence of 1 microM norepinephrine. Thus, the residual lipolysis with insulin was 25% for free fatty acids and 24% for glycerol release. In the presence of TPA, these values increased to 50% and 45%, respectively. TPA (100 nM) addition to isolated adipocytes induced protein kinase C translocation from the cytosol to the membrane fraction. In control cells, 94.7 +/- 2.9% of the enzyme was found in the cytosol, with the rest found in the membrane. At 10 min after TPA (100 nM) addition, the corresponding value was 43.6 +/- 17.4%, with the rest in the membrane (n = 6, P less than 0.05). These findings indicate that protein kinase C might be involved not only in the insulin action on glucose transport, but also in the mechanism of insulin's antilipolytic action.