ESSENTIAL ROLE OF PHOSPHATIDYLINOSITOL 3-KINASE IN INSULIN-INDUCED ACTIVATION AND PHOSPHORYLATION OF THE CGMP-INHIBITED CAMP-PHOSPHODIESTERASE IN RAT ADIPOCYTES - STUDIES USING THE SELECTIVE INHIBITOR WORTMANNIN

Incubation of rat adipocytes with wortmannin, a potent and selective p hosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, completely block ed the antilipolytic action of insulin (IC(50)approximate to 100 nM), the insulin-induced activation and phosphorylation of cGMP-inhibited c AMP phosphodiesterase (cGI-PDE) as well as the activation of the insul in-stimulated cGI-PDE kinase (IC(50)approximate to 10-30 nM). No direc t effects of the inhibitor on the insulin-stimulated cGI-PDE kinase, t he cGI-PDE and the hormone-sensitive lipase were observed. These data suggest that activation of PI 3-kinase upstream of the insulin-stimula ted cGI-PDE kinase in the antilipolytic insulin signalchain has an ess ential role for insulin-induced cGI-PDE activation/ phosphorylation an d anti-lipolysis.