改善胰岛素抵抗是治疗2型糖尿病的关键。miR-29过表达与2型糖尿病发生发展有密切关系，但机制尚未清楚。课题组前期研究证明异槲皮苷可调控PI3K/AKT信号通路基因、蛋白表达，改善胰岛素抵抗；并下调胰岛素抵抗细胞miR-29的表达；生物信息学预测miR-29与PIK3R1/PTEN-3’UTR碱基序列互补配对。目前异槲皮苷调控miR-29改善胰岛素抵抗的机制尚未见有报道。我们提出假说：异槲皮苷通过介导miR-29调控靶基因PIK3RI、PTEN，改善胰岛素抵抗。本课题拟从分子、细胞、组织及动物水平等多层次明确异槲皮苷调控miR-29作用；探讨异槲皮苷介导miR-29调控PIK3R1、PTEN靶基因机制；确定miR-29的靶基因是PIK3R1、PTEN。本研究将通过miRNA调控靶基因这一新观点探讨异槲皮苷介导miR-29调控靶基因改善胰岛素抵抗的作用机制，为2型糖尿病的预防与治疗提供新思路

Improving insulin resistance plays a key role on therapy type 2 diabetes mellitus. Overexpression is related to the development and progression of type 2 diabetes mellitus, which the mechanisms are still unclear. At our prophase studies, we confirmed that isoquercitrin ameliorated insulin resistance by regulation the expression of gene and protein on PI3K/AKT signaling pathway, and downregulation miR-29 expression. Through the target genes prediction and related bioinformatics analysis, the data provided PIK3R1 and PTEN genes contained the binding site of miR-29 in 3’UTR.At present, the mechanisms of isoquercitrin improving insulin resistance by regulating miR-29 had not been reported. We proposed a hypothesis that isoquercitrin ameliorate insulin resistance by miR-29-mediated regulation the target genes PIK3R1 and PTEN. We will perform the experiments from various aspects, such as molecular, cell, tissue and animal, and so on, to identify the effect of isoquercitrin regulation on miR-29;to explore the mechanism of isoquercitrin regulation target genes PIK3R1,PTEN by miR-29-mediated,and to determine the target genes of miR-29 are PIK3R1 and PTEN. Our researchs will utilize a innovation views which miRNA regulate the target gene to study the mechanisms of isoquercitrin improving insulin resistance on regulation target genes via miR-29 mediated. It will provide a new ways for prevention and therapy type 2 diabetes mellitus.