血管内皮胰岛素抵抗（IR）是糖尿病心脑血管事件发病的关键始动环节，但高糖（HG）引起血管内皮IR机制尚未完全阐明。我们前期研究发现PPARγ能以配体依赖-PPRE非依赖方式转录阻抑NF-κB通路对抗高（血）糖诱导血管IR。另有研究表明，PPARγ1K77位点SUMO-1化参与了PPARγ1功能的负性调控，但PPARγ1K77SUMO-1化是否能以配体非依赖-PPRE依赖方式调控高（血）糖诱导血管IR，至今国内外尚未见报道。本项目紧紧围绕拟解决的关键科学问题 "PPARγ1 K77位点SUMO-1化以配体非依赖-PPRE依赖的转录阻抑途径调控高糖诱导血管内皮IR"，应用细胞生物学、分子生物学，生物信息学和模式动物结合的方法研究PPARγ-1 SUMO化修饰在高（血）糖诱导血管内皮IR的作用及机制。本研究可揭示高（血）糖诱导血管内皮IR又一新机制,为IR相关疾病治疗提供新的防治策略和分子靶点。

Endothelial insulin resistance（IR）is an initial and critical state in many cardiocerebrovascular events induced by diabetes. However, the underlying mechanism which endothelial IR is induced by high glucose(HG) or hyperglycemia is unfully to be clarified to date. Our previous studies have shown that PPARγantagonize endothelial IR induced by HG or hyperglycemia in a manner of ligand-dependent and PPRE-independent transrepression to NF-κB pathway. Other studies have revealed that the sumoylation of PPARγ1 at a lysine 77 site is involved in a negative regulation of PPARγ1 function. There is no any report worldwide to date whether PPARγ1K77SUMO-1 regulates endothelial IR induced by HG or hyperglycemia by a way of a ligand-independent and PPRE-dependent transrepression. As a result, this project will be tightly surrounding the key scientific issiu that 'PPARγ1K77SUMO-1 regulates endothelial IR induced by HG or hyperglycemia by a way of a ligand-independent and PPRE-dependent transrepression' to be studied.The study will offer a novel mechanism uderlying endothelial IR induced by HG or hyperglycemia and offer a preventional/ therapeutic strategy and potential targets for IR and its relate metabolic disease.