袖状胃切除术后小肠和下丘脑营养感受对肝脏葡萄糖输出的调节

项目名称： 袖状胃切除术后小肠和下丘脑营养感受对肝脏葡萄糖输出的调节

项目编号： No.81471020

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王可新

作者单位： 山东大学

项目金额： 65万元

中文摘要： 袖状胃切除术能迅速、持久地缓解糖尿病，但其机制尚不明确。本课题组前期研究发现，袖状胃切除术后糖尿病的迅速改善与肝脏葡萄糖输出减少密切相关，而小肠和下丘脑通过其营养感受机制分别激活肠-脑-肝轴和脑-肝轴对肝脏葡萄糖输出进行调节，小肠和下丘脑的营养感受机制受损与糖尿病形成有关。因此，本课题组推测：袖状胃切除术后，小肠和下丘脑的营养感受机制得以修复，通过激活肠-脑-肝轴和脑-肝轴对肝脏葡萄糖输出进行调节，进而改善糖代谢。本课题组拟以高脂喂养联合STZ诱导的糖尿病Wistar大鼠为动物模型，建立袖状胃切除术手术模型，通过小肠灌注、侧脑室灌注、基础胰岛素-正葡萄糖钳夹等技术研究袖状胃切除术后近端小肠、远端小肠和下丘脑的营养感受对肝脏葡萄糖输出的调节。本研究旨在探讨小肠和下丘脑营养感受机制对肝脏葡萄糖输出中的调节作用，进一步揭示袖状胃切除术缓解糖尿病的机制。

中文关键词： 2型糖尿病；袖状胃切除术；营养感受；肝脏葡萄糖输出；下丘脑

英文摘要： Sleeve gastrectomy surgery induces rapid and durable remission of diabetes. However, the exact mechanisms remain ambiguous. Our previous studies have confirmed that the rapid improvement of diabetes after sleeve gastrectomy is tightly associated with reduced hepatic glucose production, which is physiologically regulated by nutrient sensing in small intestine and hypothalamus through activating the gut-brain-liver axis and brain-liver. The development of diabetes is associated with the impaired nutrient sensing in small intestine and hypothalamus. Based on the above research, we speculate that the impaired nutrient sensing in small intestine and hypothalamus is repaired after sleeve gastrectomy. The repaired nutrient sensing regulates hepatic glucose production and alleviates diabetes. The present study is initiated to confirm the repairment and regulation of hepatic glucose production by nutrient sensing in the proximal intestine, distal intestine and hypothalamus, using basal insulin-euglycemic clamp test, gut infusion and lateral ventricle infusion techniques on STZ-induced type 2 diabetes Wistar rats after sleeve gastrectomy. This study aims to discuss the regulation of hepatic glucose production by small intestine and hypothalamus nutrient sensing after sleeve gastrectomy, and to further reveal the mechanisms of diabetes remission after sleeve gastrectomy.

英文关键词： type 2 diabetes;sleeve gastrectomy;nutrient sensing;hepatic glucose production;hypothalamus