作为2型糖尿病主要特征之一，胰岛素抵抗的发生发展与GLUT4转运障碍密切相关。二甲双胍是2型糖尿病患者的一线核心用药。研究显示，二甲双胍能够可以提高脂肪细胞GLUT4贮存囊泡（GSVs）向胞膜的转运效率，改善胰岛素抵抗。进一步研究证实，二甲双胍主要是经由AMPK信号途径发挥作用，但其具体分子机制尚未完全阐明。v-SNARE蛋白家族(VAMP2、VAMP3、VAMP4、VAMP7、VAMP8)介导GSVs向细胞膜的转运，并且在GSVs胞吐及胞吞过程中具有重要作用。本项目拟从3T3-L1脂肪细胞及2型糖尿病脂肪细胞入手，明确究竟哪些v-SNAREs成员参与了二甲双胍对GLUT4转运的调控，并进一步明确二甲双胍激活的AMPK信号通路与v-SNAREs的关系。该研究有助于深入阐明二甲双胍改善脂肪细胞胰岛素抵抗的机制，并为进一步探索改善胰岛素抵抗的药物新靶点提供信息。

As one of the major pathological features, the development of insulin resistance is associated with the abnormal translocation of glucose transporter4 (GLUT4). Metformine is the first-line oral therapy of type 2 diabetes . Metformine can increase the efficiency of GLUT4 storage vesicle (GSVs)translocation and improve insulin resistance.It is suggested that metformin acts by sitmulating the activation of AMPK. However the precise molecular mechanisms of the effects of metformine are still not elucidated. V-SNARE protein families(VAMP2, VAMP3, VAMP4, VAMP7 and VAMP8) mediate the translocation of the GSVs and play an crucial role in the exocytosis and endocytosis of GSVs. We speculate that metformine might increased the GLUT4 translocation by regulating some v-SNAREs.In the current study, we investigated the roles of v-SNAREs in the effect of metformine on GLUT4 translocation, and its relationship with the AMPK activation in 3T3-L1 adipocyte and primary adipocytes of type 2 diabetes. It will help us to elucidate the mechanisms of how metformine improve insulin reisitance, and will help us to find the new target of improving the insulin resistance.