胰岛素信号通路、炎症信号通路与泛素-蛋白酶体系统的交互作用

胰岛素抵抗是肥胖和2型糖尿病的主要表征。胰岛素信号通路根据是否需要胰岛素受体底物（insulin receptor substrate, IRS）介导可分为IRS介导和非IRS介导的信号通路，其中以IRS介导的信号通路为主。肥胖可增强炎性细胞因子表达并活化IKKβ/NF κB和JNK等炎症信号通路，抑制IRS酪氨酸磷酸化，从而阻止胰岛素的信号转导，降低胰岛素的敏感性，表现为胰岛素抵抗。泛素 蛋白酶体系统作为机体蛋白降解的主要途径，与胰岛素和炎症信号通路联系密切，一方面胰岛素信号通路的阻断可活化泛素依赖的蛋白降解，另一方面，泛素依赖的蛋白降解系统也可直接降解胰岛素和炎症信号通路的关键蛋白，影响胰岛素的作用。本文拟综述肥胖时，胰岛素信号通路、炎症相关信号通路和泛素 蛋白酶体系统之间的交互作用，在分子水平上探讨胰岛素抵抗的发生机制。

Cross-talk among Insulin Signals,Inflammatory Signals and Ubiquitin-proteasome System

The insulin resistance is a major common characterization for obesity and type 2 diabetes. In obesity patients, the expression of inflammatory cytokines are increased and associated inflammatory signaling pathways are activated, which lead to a chronic low-grade inflammatory state and the sensitivity decrease of target tissues to insulin. Ubiquitin-proteasome system as the main way of protein degradation is closely linked with insulin and inflammatory signaling pathways. On one hand, the blocking of insulin signaling pathway can activate the ubiquitin-depended protein degradation; on the other hand, the ubiquitin-depended proteasome system can also directly degrade the key proteins of insulin and inflammatory signaling pathways, affecting the insulin action. This paper intends to analyze the cross-talk among the insulin signal pathway, inflammation signal pathway and ubiquitin-proteasome system in the state of obesity, and to understand the pathogenesis of insulin resistance at the molecular level.