胃旁路术后下丘脑POMC/CART神经元和NPY/AgRP神经元对肝脏葡萄糖输出的调控研究

胃旁路术能迅速、持久地改善糖代谢，但是作用机制不明。本课题组前期研究发现，胃旁路术后糖代谢的迅速改善与肝脏葡萄糖产生减少密切相关，而下丘脑POMC/CART和NPY/AgRP神经元对肝脏葡萄糖产生具有重要的调节作用,神经元兴奋性和表达异常与糖尿病形成有关。因此，本课题组推测：胃旁路术后，POMC/CART和NPY/AgRP神经元兴奋性和表达异常恢复，由葡萄糖、LCFAs等营养物质和GLP-1、PYY等肠道激素、胰岛素和脂肪因子Leptin介导的神经元调节肝脏葡萄糖输出的功能恢复，进而改善了糖代谢。本课题拟以高脂饮食联合STZ诱导的糖尿病Wistar大鼠为动物模型，建立胃旁路术的手术模型十二指肠空肠旁路术（DJB），通过脑室灌注、玻璃微电极细胞外记录和基础胰岛素-正葡萄糖钳夹等技术，研究胃旁路术后POMC/CART神经元和NPY/AgRP神经元兴奋性和表达的变化及其对肝脏葡萄糖输出的调节。

Gastric bypass induces rapid and sustained improvement of glucose metabolism, but the mechanism is undefined. Our previous studies have found that the rapid improvement of diabetes after gastric bypass is associated with reduced hepatic glucose production(HGP), and hypothalamic POMC/CART neurons and NPY/AgRP neurons regulate normal HGP, abnormal firing rate and expression of the neurons induced by glucose, LCFAs, GLP-1, PYY and leptin contribute to diabetes. Based on these, our group speculates that, after gastric bypass, firing rate and expression of POMC/CART neurons and NPY/AgRP neurons recover, thereby the function of the neurons regulating HGP recover, and improve glucose metabolism. Our group intend to use high-fat diet combined STZ-induced diabetic Wistar rats as animal model, duodenal jejunal bypass (DJB) as surgical model of gastric bypass to study the role of hypothalamic POMC/CART neurons and NPY/AgRP neurons in the regulation of HGP after gastric bypass by the intraventricular perfusion, extracellular glass microelectrodes recording and pancreatic-euglycemic clamp techniques.