Department of Investigative Medicine, Imperial Weight Centre, Imperial College London, London W6 8RF, United Kingdom.
Endocrinology. 2012 Aug;153(8):3613-9. doi: 10.1210/en.2011-2145. Epub 2012 Jun 6.
Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes.
胃旁路手术可在不减轻体重的情况下缓解 2 型糖尿病。我们的假设是,解剖结构改变导致的胆汁流量变化可能部分解释了手术的代谢结果。我们前瞻性地研究了 12 例接受胃旁路手术和 6 例接受胃带手术的患者,研究时间为 6 周。检测了血浆成纤维细胞生长因子(FGF)19(由回肠末端吸收胆汁酸刺激产生)和血浆胆汁酸。在犬和啮齿动物模型中,我们研究了改变胆汁流量后的肠激素反应变化。与胃带术相比,胃旁路术后 FGF19 和总血浆胆汁酸水平升高。在犬模型中,食物和胆汁本身都能刺激饱腹感肠激素反应。然而,当两者结合时,反应会加倍。在大鼠中,将内源性胆汁引流到回肠末端会导致饱腹感肠激素反应增强、食物摄入量减少和体重下降。总之,胃旁路术后,胆汁流量发生改变,导致血浆胆汁酸、FGF19、肠促胰岛素和饱腹感肠激素浓度增加。阐明胃旁路手术的作用机制可能为 2 型糖尿病的治疗提供新的方法。