Enhancement by adenosine of insulin-induced activation of phosphoinositide3-kinase and protein kinase B in rat adipocytes

The role of adenosine receptor in regulation of insulin-induced activation of phosphoinositide S-kinase (PI 3-kinase) and protein kinase B was studied in isolated rat adipocytes. Rat adipocytes are known to spontaneously rele ase adenosine, which in turn binds and stimulates the adenosine A, receptor s on the cells. In the present study, we observed that degradation of this adenosine by adenosine deaminase attenuated markedly the insulin-induced ac cumulation of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3), a product of PI 3-kinase. p-Aminophenylacetyl xanthine amine congener (PAPA -XAC), an inhibitor of the adenosine A(1) receptor, also inhibited the insu lin-induced PtdIns(3,4,5)P-3 accumulation, When extracellular adenosine was inactivated by adenosine deaminase, phenylisopropyladenosine, an adenosine A(1) receptor agonist, potentiated the insulin-induced accumulation of Ptd Ins(3,4,5)P-3, Insulin-induced activation of protein kinase B, the activity of which is controlled by the lipid products of PI 3-kinase, was also pote ntiated by adenosine. Prostaglandin E-2, another activator of a pertussis t oxin-sensitive GTP-binding protein in these cells, potentiated the insulin actions. Thus, the receptors coupling to the GTP-binding protein were found to positively regulate the production of PtdIns(3,4,5)P-3, a putative seco nd messenger for insulin actions, in physiological target cells of insulin.