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

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