Mid to Distal Small Bowel Resection with the Preservation of the Terminal Ileum Improves Glucose Homeostasis in Diabetic Rats by Activating the Hindgut-Dependent Mechanism
Mid to Distal Small Bowel Resection with the Preservation of the Terminal Ileum Improves Glucose Homeostasis in Diabetic Rats by Activating the Hindgut-Dependent Mechanism
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DOI：
10.1007/s11605-014-2507-3
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发表时间：
2014-06-01
影响因子：
3.2
通讯作者：
Yuan, Lianwen
中科院分区：
文献类型：
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作者：
Duan, Jinyuan;Zhou, Jianping;Yuan, Lianwen
本研究的目的是建立一种新的手术模型来验证“后肠假说”，从而研究肠道在葡萄糖稳态中的作用和减肥手术的作用机制。给Sprague-Dawley大鼠高脂高糖饮食，并给予链脲佐菌素（STZ） 25 mg/kg。脂糖喂养/ stz治疗的大鼠随机分为保留回肠末端的中至远端小肠切除术（DBRPI）和假手术（仅进行肠操作的正式切腹）组。术后观察大鼠12周。主要结局指标为体重、食物摄入、非空腹血糖、口服葡萄糖耐量试验（OGTT）、胰岛素耐量试验（ITT）、空腹和葡萄糖诱导胰岛素水平、胰高血糖素样肽-1 （GLP-1）、肽YY （PYY）、血清胆汁酸和血脂。DBRPI组和假手术组术后的体重和食物摄入量没有差异。与假对照组相比，DBRPI组在术后4周和12周的非空腹血糖、口服葡萄糖耐量和胰岛素耐量均有改善。DBRPI引起术后12周血清胰岛素、PYY和GLP-1水平升高；此外，DBRPI导致12周时血清甘油三酯、总胆汁酸、总胆红素和直接胆红素水平升高，游离脂肪酸水平降低。本研究为后肠在减肥手术后糖尿病改善中的关键作用提供了强有力的证据。此外，这些发现证实了DBRPI是一种简单有效的手术模型，可以在减肥手术的背景下检验“后肠假说”和重点研究胆肠肝循环。
The aim of this study was to develop a novel surgical model to test the "hindgut hypothesis" and thereby study the role of the gut in glucose homeostasis and the mechanism of action of bariatric surgery.Sprague-Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid to distal small bowel resection with the preservation of the terminal ileum (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation only) groups. Rats were observed for 12 weeks after the operation. The main outcome measures were weight, food intake, non-fasting glucose, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum bile acids, and lipid profile.The DBRPI and sham groups exhibited no difference in weight and food intake after surgery. When compared to the sham controls, the DBRPI group displayed an improvement in non-fasting glucose, oral glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks postoperation; furthermore, DBRPI resulted in higher serum levels of triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and lower free fatty acid level at 12 weeks.This study provides strong evidences for the key role of hindgut in the amelioration of diabetes after bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and effective surgical model for testing the "hindgut hypothesis" and focused study of biliary enterohepatic recycling in the context of bariatric operations.