菩人丹对OLETF大鼠脂肪组织胰岛素信号转导通路及网络节点的调控作用研究

胰岛素抵抗是2型糖尿病（T2DM）的核心病理机制之一，糖、脂毒性加剧了胰岛素抵抗的发展进程，脂肪组织是胰岛素抵抗的主要靶组织之一，与肥胖、脂代谢紊乱关系密切。本研究拟在前期菩人丹降糖、减肥、调脂、降低胰岛素抵抗指数等研究的基础上，选取OLETF大鼠睾周脂肪组织为研究对象，针对脂肪组织胰岛素信号转导网络节点及信号通路，采用"点-线-面"循序渐进的研究模式，以IR/IRS、PI3K亚基、AKT亚基三个关键节点为研究靶标，结合PI3K、Ras-MAPK、CAP/Cbl/TC10信号通路中核心蛋白的磷酸化以及中、下游调控因子的表达变化，研究脂肪组织胰岛素抵抗的本质，探究菩人丹对胰岛素信号转导通路直接和间接的调控作用，揭示菩人丹改善脂肪组织胰岛素抵抗的作用机制，为"养阴清热、活血化瘀、祛痰化湿"之菩人丹改善肥胖T2DM胰岛素抵抗提供实验依据。

Insulin resistance contributes to the pathogenesis of type 2 diabetes mellitus, which can be aggravated by gluco- and lipo- toxicity. Adipose tissues play a very important role in insulin resistance. Based on former experimental and the clinical researches, which confirmed PRD's significant hypoglycemic, anti-hyperlipidemia and weight-reducing effects, we will study the regulation effect of PRD on the insulin signaling pathway in adipose tissue of OLETF rats in this research. IR/IRS, PI3K subunits and AKT subunits are the critical nodes in the insulin signaling network, and they play a key role in insulin signal transduction pathways, including PI3K, Ras-MAPK, and CAP/Cbl/TC10 pathway. These pathways are connected with each other by the cross-talk, and subsequently form a complicated signal transduction network. By investigating the activation of these three signaling pathways and the phosphorylation of their downstream and intermediate effectors, we can indicate PRD's direct or indirect regulation effect on the insulin signaling network, and elucidated the mechanisms of reducing insulin resistance by PRD. In this research, we are trying to reveal the essence of insulin resistance in adipose tissues, and explore the scientific connotation of PRD's anti-diabetes effect. In order to provide experimental evidence for prevention and treatment of insulin resistance by "heat-clearing and yin-nourishing, eliminating the stagnant and activating the blood, eliminating damp and dissolving phlegm" of PRD.