A role for protein kinase B beta/Akt2 in insulin-stimulated GLUT4 translocation in adipocytes

Insulin stimulates glucose uptake into muscle and fat cells by promoting th e translocation of glucose transporter 4 (GLUT4) to the cell surface. Phosp hatidylinositide 3-kinase (PI3K) has been implicated in this process. Howev er, the involvement of protein kinase B (PKB)/Akt, a downstream target of P I3K in regulation of GLUT4 translocation, has been controversial. Here we r eport that microinjection of a PKB substrate peptide or an antibody to PKB inhibited insulin-stimulated GLUT4 translocation to the plasma membrane by 66 or 56%, respectively. We further examined the activation of PKB isoforms following treatment of cells with insulin or platelet-derived growth facto r (PDGF) and found that PKB beta is preferentially expressed in both rat an d 3T3-L1 adipocytes, whereas PKB alpha expression is down-regulated in 3T3- L1 adipocytes. A switch in growth factor response was also observed when 3T 3-L1 fibroblasts were differentiated into adipocytes. While PDGF was more e fficacious than insulin in stimulating PKB phosphorylation in fibroblasts, PDGF did not stimulate PKB beta phosphorylation to any significant extent i n adipocytes, as assessed by several methods. Moreover, insulin, but not PD GF, stimulated the translocation of PKB beta to the plasma membrane and hig h-density microsome fractions of 3T3-L1 adipocytes. These results support a role for PKB beta in insulin-stimulated glucose transport in adipocytes.