INSULIN-STIMULATED GLUT4 TRANSLOCATION IS MEDIATED BY A DIVERGENT INTRACELLULAR SIGNALING PATHWAY

Insulin stimulates glucose transport largely by mediating translocatio n of the insulin-sensitive glucose transporter (GLUT4) from an intrace llular compartment to the plasma membrane. Using single cell microinje ction of 3T3-L1 adipocytes, coupled with immunofluorescence detection of GLUT4 proteins, we have determined that inhibition of endogenous p2 1(ras) or injection of oncogenic p21(ras) has no effect on insulin-sti mulated GLUT4 translocation. On the other hand, micro injection of ant i-phosphotyrosine antibodies or inhibition of endogenous phosphatidyli nositol 3-kinase by microinjection of a GST-p85 SH2 fusion protein mar kedly inhibits this biologic effect of insulin. These data suggest tha t the p21(ras)/mitogen-activated protein kinase pathway is not involve d in this metabolic effect of insulin, whereas tyrosine phosphorylatio n and stimulation of phosphatidylinositol 3-kinase activity are critic al components of this signaling pathway.