铁过载可促进2型糖尿病的发生发展，但其机理尚不清楚。文献报道，胰岛素受体或受体底物酪氨酸发生硝化，会影响其磷酸化，导致胰岛素抵抗；我们发现，铁过载可显著促进组织蛋白质酪氨酸的硝化水平。由于2型糖尿病的特征之一是胰岛素抵抗，因此，我们推测铁催化胰岛素信号蛋白酪氨酸硝化，引起胰岛素抵抗，是铁过载促进2型糖尿病的主要原因之一。本课题拟在整体动物、细胞和无细胞体系上，通过调控一氧化氮生成，采用免疫沉淀、免疫印迹、HPLC-MS/MS及其他生化技术，研究铁过载对胰岛素敏感组织和细胞中胰岛素信号蛋白的硝化情况，及硝化对蛋白功能的影响。从蛋白质酪氨酸硝化的角度，阐明铁过载促进2型糖尿病发生发展的分子机理。此外，通过这个新靶点，探讨兼有铁络合和抗氧化活性及辅助治疗糖尿病的黄芩苷抑制2型糖尿病的分子机理。研究结果可为防治2型糖尿病及研发相关药物提供科学依据和新的作用靶点，具有重要的科学意义和潜在的应用前景。

Excessive iron may promote the progress of type 2 diabetes, however, the mechanism is still unclear. It has been reported that insulin receptor (IR) and insulin rceptor substrate (IRS) were nitrated in type 2 diabetes and subsequently the tyrosine phosphorylation was interfered, leading to insulin resistance. In our previous study, we found that iron overload significantly promoted protein tyrosine nitration in animal tissues. Since one of the pathognomonic feature of type 2 diabetes is insulin resistance, we hypothesis that one of the mechanism of iron promoting type 2 diabetes, may due to iron catalyzing the nitration of tyrosine residues of insulin signaling proteins. In this project, by using immuno precipitation, western blotting, immunofluorescence, HPLC-MS/MS and other biochemical analysis, we will study the effects of iron overload on site selection of tyrosine nitration of insulin signaling proteins under different nitric oxide producing conditions, and the changes of insulin signaling protein function in mouse liver, muscle and adipose tissues and cells, as well as cell free system. These results will elucidate the mechanism of excessive iron on promoting type 2 diabetes. Meanwhile, this project will also study the inhibitory effect of baicalin, which is adjunctive therapy medicine for diabetes and posseses both iron chelation and antioxidant activity, on protein tyrosine nitration, these results will provide rationality for developping new adjunctive therapy medicine for type 2 diabetes.