Baumann C A, Saltiel A R
Department of Cell Biology, Parke-Davis Pharmaceutical Research and the Department of Physiology, University of Michigan, Ann Arbor, USA.
Bioessays. 2001 Mar;23(3):215-22. doi: 10.1002/1521-1878(200103)23:3<215::AID-BIES1031>3.0.CO;2-S.
Insulin resistance is thought to be the primary defect in the pathophysiology of type 2 diabetes. Thus, understanding the cellular mechanisms of insulin action may contribute significantly to developing new treatments for this disease. Although the effects of insulin on glucose and lipid metabolism are well documented, gaps remain in our understanding of the precise molecular mechanisms of signal transduction for the hormone. One potential clue to understanding the unique cellular effects of insulin may lie in the compartmentalization of signaling molecules and metabolic enzymes. We review this evidence, and speculate on how PI-3 kinase-independent and -dependent signaling pathways both diverge from the insulin receptor and converge at discrete targets to insure the specificity of insulin action.
胰岛素抵抗被认为是2型糖尿病病理生理学中的主要缺陷。因此,了解胰岛素作用的细胞机制可能对开发这种疾病的新疗法有重大贡献。尽管胰岛素对葡萄糖和脂质代谢的影响已有充分记录,但我们对该激素信号转导的确切分子机制的理解仍存在空白。理解胰岛素独特细胞效应的一个潜在线索可能在于信号分子和代谢酶的区室化。我们回顾了这一证据,并推测了PI-3激酶非依赖性和依赖性信号通路如何既从胰岛素受体发散又在离散靶点汇聚,以确保胰岛素作用的特异性。