Insulin-induced Adipocyte Differentiation

Abstract

Insulin is a potent adipogenic hormone that triggers an induction of a series of transcription factors governing differentiation of pre-adipocytes into mature adipo-cytes. However, the exact link between the insulin signaling cascade and the intrinsic cascade of adipogen-esis remains incompletely understood. Herein we demonstrate that inhibition of prenylation of p21 ras and Rho-A arrests insulin-stimulated adipogenesis. Inhibition of farnesylation of p21 ras also blocked the ability of insulin to activate mitogen-activated protein (MAP) ki-nase and cyclic AMP response element-binding (CREB) protein. Expression of two structurally different induc-ible constitutively active CREB constructs rescued insulin-stimulated adipocyte differentiation from the inhibitory influence of prenylation inhibitors. Constitu-tively active CREB constructs induced expression of PPAR2, fatty acid synthase, GLUT-4, and leptin both in control and prenylation inhibitors-treated cells. It appears that insulin-stimulated prenylation of the Ras family GTPases assures normal phosphorylation and activation of CREB that, in turn, triggers the intrinsic cascade of adipogenesis.