中枢CART信号调控NPY诱导外周胰岛素抵抗形成的作用及机制研究

项目名称： 中枢CART信号调控NPY诱导外周胰岛素抵抗形成的作用及机制研究

项目编号： No.81500647

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 隆敏

作者单位： 中国人民解放军第三军医大学

项目金额： 18万元

中文摘要： 近年，中枢神经系统对外周胰岛素抵抗（IR）的调控备受关注。课题组前期发现食欲促进递质—神经肽Y（NPY）可诱导IR形成，但其调控机制不明。项目基于中枢NPY与可卡因-苯丙胺转录调节肽（CART）表达位置紧密关联的解剖学特性，以及课题组进一步实验发现（CART刺激体外培养脑片NPY释放），推测中枢CART信号可能通过调控NPY诱导外周IR形成。拟于体外诱导分化3T3-L1/C2C12细胞、原代神经细胞、脑片以及大鼠体内，双向调节CART（激动剂与重组慢病毒注射、si-与sh-RNA），阐明CART对NPY及外周IR的潜在影响；解析中枢CART/NPY信号对IR的关键调控；寻找CART与NPY间的信号级联途径（预实验提示可能与ERK1,2磷酸化相关）；从而揭示中枢CART/NPY信号与外周IR关联，探索其信号级联机制，旨在深入理解IR乃至代谢紊乱形成机理，为其干预提供新的策略与依据。

中文关键词： 糖尿病；胰岛素抵抗；可卡因-苯丙胺转录调节肽；神经肽Y

英文摘要： In recent years, the regulation of central nervous system on peripheral insulin resistance (IR) becomes a research hotspot in diabetic field.Our previous research indicated neuropeptide Y (NPY) expressing in energy modulation center contribute to the peripheral IR, but the mechanism is still not clear. Accumulating evidence suggested that there is close location between cocaine amphetamine transcriptional regulatory peptides (CART) and NPY expressed in central nervous system. Moreover, our result indicated CART stimulated hypothalamus NPY expression. Our hypothesis is central CART contributes IR by modulating NPY expression. In this project, CART gene will be over expressed or silenced (activator/ recombinant lentiviral particles and si/sh RNA) in vivo and in vitro experiments. Primary nerve cells and IR rats’ brain slices will be incubated by CART, NPY expression and ERK signaling pathway will be measured. CART will be used to intervene the differentiated 3T3-L1 cells or C2C12 cells, and the effect of CART and NPY on carbohydrate metabolism in adipocytes will be detected. The aim of this project is to elucidate the modulation of CART on NPY induced peripheral tissue IR, and find a new therapeutic strategy for IR.

英文关键词： diabetes mellitus;insulin resistance;cocaine amphetamine regulatory transcriptional;neuropeptide Y