EFFECTS OF OVEREXPRESSING WILD-TYPE AND MUTANT PDGF RECEPTORS ON TRANSLOCATION OF GLUT4 IN TRANSFECTED RAT ADIPOSE-CELLS

Activation of phosphatidylinositol 3-kinase (PI3K) by insulin is neces sary for the effect of insulin to recruit GLUT4 to the cell surface in insulin target cells. In adipose cells, stimulation of endogenous PDG F receptors (PDGF-R) results in increased PI3K activity without causin g recruitment of GLUT4. We overexpressed wild-type or mutant forms of the PDGF-R in rat adipose cells and examined their effects on PDGF- an d insulin-stimulated recruitment of co-transfected epitope-tagged GLUT 4. Control cells expressing only tagged GLUT4 had a 3-fold increase in cell surface GLUT4 upon insulin stimulation but no response to PDGF. Cells overexpressing wild-type PDGF-R maintained insulin responsivenes s and, in addition, acquired the ability to recruit GLUT4 in response to PDGF. Surprisingly, overexpression of F740/ F751 (mutant PDGF-R una ble to directly activate PI3K) led to similar results. Nevertheless, w ortmannin (an inhibitor of PI3K) blocked effects of both PDGF and insu lin to recruit GLUT4. Our data suggest that overexpression of PDGF-R m ediates positive effects on GLUT4 translocation by a wortmannin sensit ive pathway not dependent on direct interaction of the PDGF-R with PI3 K. (C) 1996 Academic Press, Inc.