Molecular mechanisms of insulin signal transduction and diabetes mellitus

点击翻译按钮获取中文摘要

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.