Mitev V
Mol Med (Sofia). 1996;1(2):4-8.
Insulin is a key hormone regulating glucose homeostasis and has many cellular effects on metabolism, growth, and differentiation. Insulin action is mediated through a specific cell-surface receptor. The first step following insulin binding consists in receptor autophosphorylation and stimulation of its tyrosine kinase activity. Among the multiple substrates, the insulin receptor substrate-1 (IRS-1) is the major cytoplasmic substrate for insulin. IRS-1 binds several Src homology 2 (SH2) proteins through its multiple tyrosine phosphorylation sites: phosphatidylinositol 3-kinase (PI 3-kinase), the Ras guanine-nucleotide-releasing complex Grb2-SOS, the tyrosine phosphatase Syp, and the adapter protein Nck. IRS-1 is essential for many, but not all of the insulin's biological responses. Recently, a primary alternative substrate, i.e. IRS-2, was purified and cloned. Numerous biochemical abnormalities of the insulin signaling system lead to insulin resistance. No doubt, the recent data about the molecular mechanisms of insulin action will provide new insights into the pathophysiology and therapy of diabetes and other insulin resistant states.
胰岛素是调节葡萄糖稳态的关键激素，对代谢、生长和分化具有多种细胞效应。胰岛素的作用是通过特定的细胞表面受体介导的。胰岛素结合后的第一步是受体自身磷酸化并刺激其酪氨酸激酶活性。在多个底物中，胰岛素受体底物-1（IRS-1）是胰岛素的主要细胞质底物。IRS-1通过其多个酪氨酸磷酸化位点结合几种Src同源2（SH2）蛋白：磷脂酰肌醇3激酶（PI 3激酶）、Ras鸟嘌呤核苷酸释放复合物Grb2-SOS、酪氨酸磷酸酶Syp和衔接蛋白Nck。IRS-1对许多但并非所有胰岛素的生物学反应都是必不可少的。最近，一种主要的替代底物，即IRS-2，被纯化并克隆。胰岛素信号系统的许多生化异常会导致胰岛素抵抗。毫无疑问，最近关于胰岛素作用分子机制的数据将为糖尿病和其他胰岛素抵抗状态的病理生理学和治疗提供新的见解。
