近年来，肠道被发现作为机体抵抗能量过剩和代谢失衡的第一道防线而备受关注，但其信号在“肠-脑-肝”之间的转导及脂糖代谢的调节机制，目前并不清楚。nesfatin-1是一个与肥胖和能量代谢有关的肽类激素， 新近发现nesfatin-1在胃肠道内分泌细胞中有大量的分泌，提示胃肠道nesfatin-1有可能参与机体的代谢调控过程。课题组前期实验发现肠源Nesfatin-1信号能改善机体肝胰岛素抵抗。因此本项目拟将十二指肠导管植入灌流术、中枢第三脑室微量给药系统和扩展胰岛素钳夹术相结合,并利用3-3H葡萄糖、2-脱氧-3H葡萄糖和14C乳酸盐三种示踪技术及分子生物学方法，探讨肠nesfatin-1信号变化对机体糖动力学的影响。在此基础上，全面评价nesfatin-1对机体脂糖代谢的可能信号转导通路及分子机制。本课题的实施有助于全面解读肠源肽类激素及“肠-脑-肝”轴信号转导的调节机制具有极为重要的意义

Recently, the gut was the first of defense against excess energy and metabolic abnormality caused a lot of attention. But, it is unknown whether the gut derived peptide hormone is mediated through a gut-brain - liver neuronal network to control glucose homeostasis in vivo. Nesfatin-1, as a peptide hormone, associated with obesity and energy metabolism. Recently discovered, nesfatin-1 has a lot of secretion in gastrointestinal endocrine cells. It is indicate that gastrointestinal tract nesfatin-1 may be involved metabolic regulation。Our preliminary experimental research found that intestinal Nesfatin-1 signals can improve peripheral insulin resistance. In this study, the effects of nesfatin-1 on glucose kinetics will be assessed by association intraduodenal infusions and euglycemic-hyperinsulinemic clamp studies based on three tracer-dilution methodologies as well as molecular biology methods. On that basis, the possible signal transduction pathway and molecular mechanism of nesfatin-1 on lipid and glucose metabolism will be also comprehensive assessed. This project will highlight a previously unappreciated role of duodenal nesfatin-1 signaling and "gut brain liver" axis signal in regulation mechanism of signal transduction。