TC10 and insulin-stimulated glucose transport

Insulin stimulates glucose uptake in insulin-responsive tissues by means of the translocation of the glucose transporter GLUT4 from intracellular sites to the plasma membrane. Two pathways are required, one involving activation of a phosphatidylinositol 3-kinase (PI 3-kinase) and downstream protein kinases, and one involving activation of the Rho-family GTPase TC10. TC10 activation by insulin is catalyzed by the exchange factor C3G, which is translocated to lipid rafts along with its binding partner CrkII as a consequence of Cbl tyrosine phosphorylation by the insulin receptor. This activation of TC10 is dependent on localization of TC10 in the lipid raft subdomains of the plasma membrane. We describe experimental approaches using the insulin-responsive cell line 3T3-L1 adipocytes to study the role of TC10 in insulin-stimulated glucose transport.