Studies on the molecular basis of insulin actions

与伦敦的M.Waterfield教授合作，我们发现与IRS-1相关的磷酸肌肽3-激酶介导胰岛素对葡萄糖转运（葡萄糖转运体的易位）和膜褶皱的刺激作用。我们还发现一个与IRS-1结合的接头蛋白Nck，在体外结合了两个116kDa和130kDa的蛋白。我们在沃特菲尔德教授的实验室分析了这两种蛋白质的氨基酸序列，并克隆了这两种蛋白质的cDNA。与巴斯大学的G.Holman教授合作，我们发现wortmannin，一种磷酸肌肽3-激酶抑制剂，抑制胰岛素对3T3-L1脂肪细胞中葡萄糖转运（GLUT4从细胞质溶胶转运到质膜）的刺激作用。此外，我们分析了在wortmannin和胰岛素存在下GLUT4的动力学，得出wortmannin抑制胰岛素对3T3-L1脂肪细胞中GULT4胞吐作用的刺激作用，而不是内吞作用。

In collaboration with Professor M.Waterfield in London, we found phosphoinositide 3-kinases associated with IRS-1 mediate the stimulatory effect of insulin on the glucose transport (translocation of glucose transporters) and membrane ruffling. We also found that an adaptor protein Nck, which binds to IRS-1, associates two proteins of 116kDa and 130kDa in vitro. The amino acid sequence of these proteins was analyzed in Professor Waterfield's laboratory and we cloned the cDNA of these two proteins.In collaboration with Professor G.Holman in Bath, we found that wortmannin, an inhibitor of phosphoinositide 3-kinase, inhibits the stimulatory effect of insulin on glucose transport (translocation of GLUT4 from cytosols to plasma membranes) in 3T3-L1 adipocytes. Furthermore, we analyzed the kinetics of GLUT4 in the presence of wortmannin and insulin and concluded that wortmannin inhibited the stimulatory effect of insulin on the exocytosis, but not the endocytosis, of GULT4 in 3T3-L1 adipocytes.