肠-脑-肝轴对2型糖尿病大鼠胃旁路术后早期肝胰岛素敏感性的调控研究

胃旁路术能迅速、持久地缓解 2 型糖尿病，但其作用机制不明。研究发现胃旁路术后早期糖尿病的改善与肝胰岛素敏感性升高密切相关。本课题组结合前期研究分析认为：肠-脑-肝轴对胃旁路术后早期肝胰岛素敏感性的调控具有重要的作用。为了验证上述假说，本课题组拟以非肥胖性2型糖尿病Goto-kakizaki大鼠为动物模型，实施胃旁路术，进行如下研究：（1）食物信号对小肠的刺激在胃旁路术后早期肝胰岛素敏感性改善中的作用；（2）小肠迷走神经在胃旁路术后早期肝胰岛素敏感性改善中的作用；（3）下丘脑摄食能量代谢中枢在胃旁路术后早期的改变及在肝胰岛素敏感性改善中的作用；（4）肝迷走神经在胃旁路术后早期肝胰岛素敏感性改善中的作用。本课题旨在阐述肠-脑-肝轴在胃旁路术后早期2型糖尿病缓解中的作用和机制，为2型糖尿病的治疗提供新的理念。

Gastric bypass induces rapid and durable remission of type 2 diabetes, but the mechanism is undefined. Previous studies have found that early improvement in glucose homeostasis after gastric bypass is closely related with increased hepatic insulin sensitivity. Based on previous studies, our group speculate that gut -brain-liver axis plays an important role in the regulation of hepatic insulin sensitivity early after gastric bypass. .In order to prove this hypothesis, we perform gastric bypass on non-obese diabetic Goto-kakizaki rats and conduct following studies: (1) the role of contact of small intestine with digested nutrients in the regulation of hepatic insulin sensitivity early after surgery;(2) the role of intestinal afferent vagus nerve in the regulation of hepatic insulin sensitivity early after surgery; (3) changes of hypothalamic neurons regulating energy homeostasis and balance early after surgery and the role in the regulation of hepatic insulin sensitivity; (4) the role of hepatic efferent vagus nerve in the regulation of hepatic insulin sensitivity early after surgery..This study aims to elucidate the role of gut-brain-liver axis in regulating hepatic insulin sensitivity early after gastric bypass in type 2 diabetic rats, and provides novel targets for management of type 2 diabetes.