Molecular mechanisms of insulin signal transduction and diabetes mellitus

胰岛素是一种独特的降低血糖水平的激素，尽管有几种激素可以提高血糖浓度。然而，引起血糖水平快速下降的GLUT4易位不仅由inuslin触发，还包括其他生长因子PDGF和EGF。利用PDGF受体的突变体，我们得出结论，这些生长因子激活的PI3-激酶主要传递GLUT4易位的信号。这些发现促进了GLUT4易位的分子机制的阐明。我们接下来研究了GTPGammaS的靶分子，因为GTPGammaS的治疗触发了GLUT4的易位。我们建立了在我们的细胞系统中稳定表达正常突变的ras、rab、rad蛋白的克隆，并检测了过表达的G蛋白对胰岛素刺激的GLUT4转位的影响。结果表明，Rab、ras、Rho和rad可能不参与GLUT4易位的胰岛素信号转导途径。我们最近的研究结果表明，一类三聚体G蛋白可能参与了GTP-GammaS刺激的GLUT4转位，但该信号转导途径不依赖于胰岛素信号转导途径。

Insulin is a unique hormone to decrease blood glucose level, althou there are several hormones which have abilities to increase the conctration of blood glucose. However the GLUT4 translocation which causes rapid decrease of blood glucose level is not triggered only by inuslin but also other growth factors, PDGF and EGF.Using the mutants of PDGF receptor, we concluded that the PI 3-kinase activated by these growth factors is mainly transmitted the signal of the GLUT4 translocation. These findings promoted the elucidation of the molecular mechanisms of GLUT4 translocation.We next examined the target molecule of GTPgammaS, because the treatment of GTPgammaS tiggered the GLUT4 translocation. We established the clones in which normal on mutant ras, rab, rad proteins are stablely expressed in our cell system, and we examined the effect of the over-expressed G-proteins on the insulin-stimulated GLUT4 translocation. The results indicated that rab, ras, rho and rad is probably not involved in the insulin signaling pathway of GLUT4 translocation. Our recent results suggested that a kind of trimeric G proteins may be involved the GTPgammaS-stimulated GLUT4 translocation, butthis signaling pathway is independent from the insulin signaling pathway.