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

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.

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。

胃旁路术能迅速、持久地缓解2型糖尿病，但其作用机制尚未完全阐明。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，本课题组以非肥胖性2型糖尿病Goto-kakizaki 大鼠以及高质饮食联合链脲佐菌素诱导的糖尿病Wistar大鼠为动物模型，实施十二指肠空肠旁路术（DJB）及袖状胃切除术（SG），探究胃旁路术后早期糖尿病大鼠肝脏胰岛素敏感性的变化及其相关机制，并进一步明确下丘脑摄食能量代谢中枢和迷走神经在其中的作用。研究结果表明，炎症反应、脂质生成、内质网应激、胰岛素信号通路变化等机制均参与胃旁路术后肝脏胰岛素敏感性的升高，下丘脑作为能量代谢调节中枢发挥重要作用，但上述作用不完全依赖于迷走神经。本研究进一步阐释了胃旁路术治疗2型糖尿病的机制，为2型糖尿病的治疗提供新的靶点和理念。