最近研究表明，肝脏来源的分泌蛋白hepatokine在糖尿病及代谢综合征的病理生理过程中发挥重要作用。申请者在前期工作中首次报道在肥胖以及过营养状态下，hepatokine LECT2在肝脏中呈高表达，并且LECT2的上调能引起骨骼肌的胰岛素抵抗，但目前LECT2在肝脏中的调节及其机制并不完全清楚。本项目拟选用2型糖尿病患者，C57BL/6J小鼠及H4IIEC3肝细胞为主要研究对象，通过相关性分析、RT-PCR、Western blot、ELISA，尾静脉高压注射质粒DNA等方法，从人群水平、整体水平、细胞水平及分子水平探讨二甲双胍等AMPK激动剂对LECT2的表达及分泌的调控；并进一步使用启动子克隆，报道基因构建，SiRNA，质粒转染，ChIP等研究手段，确定调节LECT2表达的转录因子。本研究的开展，可望阐明LECT2在肝脏中调控的机制，从而为糖尿病的防治提供新思路新靶点。

Recent researches have indicated that liver-derived secretory protein hepatokines play an important role in the pathophysiology of type 2 diabetes and metabolic syndrome. We have previously found and reported that on the condition of obesity and over-nutrition, the over-produced hepatokine LECT2 from the liver induces skeletal muscle insulin resistance. However, the mechanism of its regulation in the liver is not clear. In this project, we will perform correlation and regression analysis, RT-PCR, Western blot, ELISA, mouse tail-vein hydrodynamic injection experiments and so on to examine the function of AMPK agonists such as metformin on the expression and secretion of LECT2 from molecular biology level to clinical level. And we will determine the transcription factor of LECT2 in the liver by promoter assay, SiRNA experiment, plasmid transfection experiment and ChIP assay. This project will elucidate the regulation mechanism of hepatokine LECT2 in liver, and provide new opportunities and targets for the prevention and treatment of type 2 diabetes.