Wortmannin converts insulin but not oxytocin from an antilipolytic to a lipolytic agent in the presence of forskolin.

Insulin is an important regulator of glucose transport and lipolysis in adipocytes. The present studies compared the effects of insulin in rat adipocytes with the effects of oxytocin and peroxovanadate, which mimic some effects of insulin. The antilipolytic effects of peroxovanadate and oxytocin were unaffected by 500 nmol/L wortmannin, which blocked the antilipolytic action of insulin. However, wortmannin, which is a relatively specific inhibitor of phosphatidylinositol 3-kinase, did block most of the stimulation of glucose metabolism by peroxovanadate while having little effect on that due to oxytocin. Under appropriate conditions, it was also possible to demonstrate a lipolytic action of insulin, especially with low (0.1 to 1 nmol/L) concentrations of insulin after exposure of adipocytes to 50 nmol/L wortmannin. The data provide additional support for the hypothesis that oxytocin and peroxovanadate affect adipose tissue metabolism by mechanisms distinctly different from those involved in insulin action.