DIFFERENTIAL REQUIREMENT FOR P21(RAS) ACTIVATION IN THE METABOLIC SIGNALING BY INSULIN

To evaluate the role of the ''Ras pathway'' in mediating metabolic sig naling by insulin, we employed lovastatin to inhibit isoprenilation of Ras proteins in Rat-1 fibroblasts transfected with human insulin rece ptors (HIRc cells) and in differentiated 3T3-L1 adipocytes, Lovastatin blocked an ability of insulin to activate p21(ras) and mitogen-activa ted protein kinase, Lovastatin also significantly (p < 0.01) reduced i nsulin effects on thymidine incorporation and glucose incorporation in to glycogen, Nevertheless, an effect of insulin on glucose uptake rema ined unaffected, It appears that in contrast to its mitogenic action a nd to its effect on glycogenesis, an effect of insulin on glucose upta ke does not require p21(ras) activation.