HGF-Met轴在胰岛素抵抗中的作用及分子机制研究

项目名称： HGF-Met轴在胰岛素抵抗中的作用及分子机制研究

项目编号： No.81200587

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 荆亚莉

作者单位： 南京大学

项目金额： 23万元

中文摘要： 改善胰岛素抵抗在2型糖尿病治疗中起着重要的作用。最新研究显示HGF-Met轴通过调节肝糖原的摄取及输出参与糖代谢。我们前期研究发现药物可通过作用于PI3K-AKt信号通路来改善胰岛素抵抗。预实验结果提示，HGF及其受体Met在胰岛素抵抗模型肝脏中的表达不同于正常对照组，我们还发现在脂肪酸诱导的胰岛素抵抗细胞模型中，经重组HGF治疗后，磷酸化AKt活性增加，IRS-1的丝氨酸位点磷酸化减弱。因此，我们推断HGF及其受体Met结合后，通过调节PI3K-AKt活性从而改善胰岛素抵抗。本项目将在此基础上，从分子、细胞、整体水平进一步明确HGF-Met轴与胰岛素抵抗的关系，探讨HGF-Met轴通过PI3K-AKt信号通路改善胰岛素抵抗的分子机制。本项目的开展可加深对胰岛素抵抗的理解，从而为改善胰岛素抵抗提供新的思路和理论依据。

中文关键词： HGF；MET；胰岛素抵抗；脂代谢；糖代谢

英文摘要： Improving insulin resistance plays an important role in the treatment of type 2 diabetes. Recent studies showed that HGF-Met axis regulated metabolism by stimulating hepatic glucose uptake and suppressing hepatic glucose output. Our previous researches revealed that some drugs could improve insulin resistance through PI3K-Akt signaling pathway. Preliminary experiments suggested that the expression of HGF and its receptor Met in insulin resistance model liver was significantly different from the normal control group, and on free fatty acid-induced insulin resistance cell model, after treatment with recombinant human HGF, the activity of phosphorylated AKt was significantly increased, and phosphorylation of serine residues in insulin receptor substrate-1 (IRS-1) was decreased. Therefore, we concluded that HGF binding to its receptor Met may up-regulate activity of PI3K-AKt to improve insulin resistance. Based on the above researches, this study will further clarify the relationship between HGF-Met axis and insulin resistance，and explore the molecular mechanism of HGF-Met axis in improving insulin resistance through PI3K-Akt pathway. We expect our findings will provide novel insights into the molecular mechanism of insulin resistance, and could eventually contribute to the improvement of insulin resistance.

英文关键词： HGF；MET；Insulin resistance；Lipid metabolism；Glucose metabolism