Study on the mechanism of insulin stimulation of glucose transport

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In the present study, we calrified that insulin stimulated guanine nucleotide exchange on Rab4 in rat adipocytes. This insulin action was markedly attenuated with phosphatidylinositol (PI) 3-kinase inhibitors, wortmannin or LY294002, suggesting that Pl 3-kinase may be an essential signaling component for insulin activation of Rab4. Additionally, we investigated the interaction of Rab4 with syntaxin4, a t-SNARE protein implicated in the insulin-induced exocytic fusion of the GLUT4-containing vesicle with the plasma membrane. Rab4 and syntaxin4 were co-immunoprecipitated from the homogenate of rat adipocytes. The interaction of the two proteins were attenuated by pretreatment of the cells with insulin but enhanced with GTPgammaS.GTP-binding proteins regulate both exocytotic and endocytotic steps of GLUT4-containing vesicles in rat adipocytes. Furthermore, we demonstrated that protein kinase Cgamma may be the upstream regulator of the insulin action on Rab4.We also clarified that dynamin is a regulatory GTPase of GLUT4 endocytosis by using mutant dynamin expressed in CHO cells.