vinexinβ基因对高脂饮食诱导糖尿病小鼠的表型影响及机制研究

2型糖尿病的核心发病机制是胰岛素抵抗，胰岛素抵抗的机制主要是各种因素导致的胰岛素信号通路受损。遗传因素，肥胖，炎症反应的激活，内质网应激反应，氧化应激反应等等是导致胰岛素抵抗的关键因素。vinexin是一种衔接蛋白，参与调节生长因子诱导的信号通路中。早有研究证实其家族蛋白CAP以不依赖PI3K/AKT 的方式参与调节胰岛素信号通路，并且有研究证实vinexin在胰岛周围的а细胞中大量表达。同时我们课题组证实，与lean 小鼠相比，2型糖尿病模型ob/ob小鼠各组织中vinexin的表达发生了明显的变化。因此我们提出vinexin基因参与到2型糖尿病的发生发展过程中。本课题拟通过vinexin基因敲除小鼠给予高脂饮食喂养建立2型糖尿病模型的方法及细胞实验深入研究Vinexin基因对2型糖尿病的糖脂代谢、炎症反应及胰岛素信号通路的影响，并探讨其分子机制，为2型糖尿病的治疗提供可能的分子靶点。

The core pathogenesis of type 2 diabetes is insulin resistance, the essence of which is impaired insulin signaling pathway. Genetic factors, obesity, and the activation of the inflammatory response, endoplasmic reticulum stress response, and oxidative stress are the key factors leading to insulin resistance. Vinexin is an adapter protein involved in the regulation of growth factor-induced signaling pathways. Early studies have confirmed its family protein CAP regulated the insulin signal pathway by non-PI3K/AKT pathway. And studies discovered vinexin was largely expressed around the islets. Our research group confirmed that the expression of Vinexin in the tissues of T2DM model mice significant changed compared with lean mice. Then we suggest vinexin may participate in the process of the development of T2DM. The topics proposed to research the role of Vinexin genes in glucose and lipid metabolism, inflammatory response and insulin signal pathway of T2DM, and further explore the possible molecular mechanisms, which may become a new molecular target for the therapy of type 2 diabetes.