A role for kinesin in insulin-stimulated GLUT4 glucose transporter translocation in 3T3-L1 adipocytes

Insulin regulates glucose uptake in adipocytes and muscle by stimulating th e movement of sequestered glucose transporter 4 (GLUT4) proteins from intra cellular membranes to the cell surface. Here we report that optimal insulin -mediated GLUT4 translocation is dependent upon both microtubule and actin- based cytoskeletal structures in cultured adipocytes, Depolymerization of m icrotubules and F-actin in 3T3-L1 adipocytes causes the dispersion of perin uclear GLUT4-containing membranes and abolishes insulin action on GLUT4 mov ements to the plasma membrane. Furthermore, heterologous expression in 3T3- L1 adipocytes of the microtubule-binding protein hTau40, which impairs kine sin motors that move toward the plus ends of microtubules, markedly delayed the appearance of GLUT4 at the plasma membrane in response to insulin, The hTau40 protein had no detectable effect on microtubule structure or perinu clear GLUT4 localization under these conditions. These results are consiste nt with the hypothesis that both the actin and microtubule-based cytoskelet on, as well as a kinesin motor, direct the translocation of GLUT4 to the pl asma membrane in response to insulin.