脂肪因子Chemerin在骨骼肌胰岛素抵抗发生中的作用及其机制

项目名称： 脂肪因子Chemerin在骨骼肌胰岛素抵抗发生中的作用及其机制

项目编号： No.30871002

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 沈伟利

作者单位： 上海交通大学

项目金额： 31万元

中文摘要： 线粒体功能障碍可能是导致2型糖尿病骨骼肌胰岛素抵抗发生的重要原因，多种脂肪因子参与其中的调控。Chemerin是新近发现的脂肪因子，我们在高游离脂肪酸诱导的C2C12骨骼肌胰岛素抵抗的细胞模型中发现，Chemerin受体( CMKLR1)的表达与骨骼肌线粒体功能密切相关，提出Chemerin可能参与调控骨骼肌胰岛素抵抗。本项目拟从细胞和动物的整体水平上阐明1）Chemerin对骨骼肌细胞糖脂代谢的影响； 2) Chemerin通过调节骨骼肌线粒体的功能和生成而影响骨骼肌细胞的糖脂代谢；３)Chemerin-CMKLR1 通路与骨骼肌胰岛素信号通路的交互关系；4)在整体动物模型上，观察给予外源性脂肪因子Chemerin负荷情况下，胰岛素抵抗和糖、脂代谢的改变。以进一步阐明Chemerin－线粒体－胰岛素抵抗之间的关系，为确立胰岛素抵抗治疗的药物靶点开辟新的视角。

中文关键词： 骨骼肌;胰岛素抵抗;线粒体; Chemerin.

英文摘要： Mitochondrial dysfunction in skeletal muscle has been implicated in the development of type 2 diabetes. Many of adipokines are involved in progression to diabetes. Chemerin- a new adipokine, we demonstrate that the expression of chemerin receptor is associated with skeletal muscle mitochondrial function in an cellular model that palmitate induced insulin resistance; and suggest that Chemerin may be involved in modulating skeletal muscle insulin resistance. We will test this hypothesis using two different models: C2C12 myotubes, treated with palmitate, i.e., an in vitro system; and the chronic chemerin-induced rat model, i.e., an in vivo system. The following specific aims are proposed: 1) Effect of Chemerin on skeletal muscle glucose and lipoid metabolism; 2) Determine if chemerin improve skeletal muscle glucose and lipoid metabolism by enhancing mitochondrial biogenesis and function; 3) Crosstalk between Chemerin-CMKLR1 pathway and insulin signaling pathway in skeletal muscles; 4) A euglycemic-hyperinsulinemic clamp technique was applied to study of insulin sensitivity and glucose and lipid metabolism in chemerin-treated rats. To clarify the relationship among Chemerin-mitochondrion insulin resistance. Activation of the chemerin pathway may be a promising target for thetreatment of insulin resistance.

英文关键词： skeletal muscle; mitochondrion;insulin resistance; chemerin.