糖尿病（DM）已成为影响国民经济的重大公共卫生问题之一，实现DM精准防控有着重大的科学意义。DM的发生发展与体内氧化应激体系之间存在紧密联系，对氧磷酶1（Paraoxonase1，PON1）是体内广泛存在的抗氧化酶，其抗氧化活性的降低可导致胰岛素抵抗进而促进糖尿病的发生。空间结构是蛋白质准确发挥功能活性的基本保障，而糖基化作为一种重要的翻译后修饰是调节蛋白质空间结构的途径之一。本项目拟建立生物样本中蛋白质糖基化修饰快速分型和精确定量分析平台，对健康人群、糖尿病高危人群、糖尿病患者人群的PON1的糖基化修饰状态进行表征，并鉴定糖链精细结构。同时对人群样本中PON1活性进行测定，分析糖基化修饰状态与活性的相关性。进一步对PON1参与的胰岛素抵抗调控通路中的关键信号分子和蛋白质进行定量分析，系统阐释PON1糖基化修饰在糖尿病发病/干预分子网络中的关键作用，为实现糖尿病精准防控奠定理论依据。

The prevalence of diabetes mellitus is high in patients, however, the cure rate is low. And more than 90% of diabetes mellitus belong to type 2 diabetes(T2DM). T2DM has been one of critical health issues which affected the national economy. Therefore, it has great scientific value to realize precise control. There is inseparable relationship between T2DM and oxidative stress. Paraoxonase1 is a ubiquitous enzyme in body. It is said that the decreasing antioxidant activity of PON1 results in insulin resistance. It is essential to have fit space structure when the protein serves its function. Glycosylation, which is an important post-translation modification, is one of the ways to alter the space structure of protein. In this project a platform is planned to be established to class the glycosylation of protein rapidly and to quantitative analyze glycosylation accurately. With this platform the character the glycosylation of PON1 of the health control group, high risk group and the diabetes mellitus group will be analyzed, and the refined structure of oligosaccharides will be identified. Meanwhile the population PON1 activity will be measured. And then, the relatedness between glycosylation character of PON1 and PON activity will be analyzed. Further the key signaling molecules and protein in the regulating pathway of insulin resistance in which PON1 is involved in will be quantitative analyzed. It will assist to systematically elucidate the key role of PON1 glycosylation on onset of T2DM/intervention molecular network, which will establish theoretical base for the realization of precise control of T2DM.