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十二指肠-空肠旁路术可减轻链脲佐菌素诱导的糖尿病大鼠胰岛的进行性衰竭。

Duodenal-jejunal bypass attenuates progressive failure of pancreatic islets in streptozotocin-induced diabetic rats.

作者信息

Wang Tingfeng, Zhang Peng, Zhang Xiong, Cao Ting, Zheng Chengzhu, Yu Bo

机构信息

Center for Metabolic and Bariatric Surgery, Fudan University Pudong Medical Center, Shanghai, China.

Center for Metabolic and Bariatric Surgery, Fudan University Pudong Medical Center, Shanghai, China; Center for Medical Research and Innovation, Fudan University Pudong Medical Center, Shanghai, China.

出版信息

Surg Obes Relat Dis. 2017 Feb;13(2):250-260. doi: 10.1016/j.soard.2016.08.500. Epub 2016 Aug 31.

Abstract

BACKGROUND

Preservation of pancreatic beta cell function has been increasingly appealing in the treatment of type 2 diabetes. Evidence is still limited on how bariatric surgery affects pancreatic beta cell apoptosis.

SETTING

University medical center.

OBJECTIVE

The study aimed to investigate the effect of a major component of Roux-en-Y gastric bypass, duodenal-jejunal bypass, on protecting pancreatic beta cells from progressive loss.

METHODS

Forty-five normal Sprague-Dawley rats were randomly assigned into 3 groups: duodenal-jejunal bypass (DJB) group (n = 16) and sham (S) group (n = 17), based upon the procedure received, and a control (C) group (n = 12) without any procedure performed, to eliminate potential traumatic effects from surgery. Ten days after surgery, streptozotocin (STZ, 45 mg/kg weight) was injected intraperitoneally into each animal, including the control animals, to selectively induce pancreatic beta cell apoptosis. Weight, food intake, plasma glucose level, and the results of an oral glucose tolerance test were measured before surgery, pre-STZ injection, and up to 4 weeks after STZ injection. Plasma insulin and glucagon-like peptide-1 levels were also assayed during oral glucose tolerance test. At the end, pancreatic tissues were sliced and stained for beta cell analysis.

RESULTS

There were no significant differences in weight among all groups at any time points measured, despite rats in the S and C groups consuming more food than those in the DJB group as measured on day 10 (P<.05) and day 20 (P<.01) after STZ injection. Animals undergoing DJB did not experience symptoms typical of uncompensated diabetes, including hyperphagia and progressive weight loss. After STZ injection, fasting plasma glucose levels in the DJB group were significantly lower than those in the C and S groups (P<.001). When challenged by glucose load, DJB rats also had a better glycemic excursion (P<.01) and incretin response compared with C and S rats (P<.05). In addition, pancreatic beta cell size and mass was better preserved in DJB rats (P< .001).

CONCLUSION

DJB is able to protect pancreatic beta cells from apoptosis, which leads to better glycemic control and delayed onset of diabetes. These results imply the necessity of including a DJB component when designing bariatric procedure to achieve a better long-term outcome.

摘要

背景

在2型糖尿病的治疗中,保留胰腺β细胞功能越来越受到关注。关于减肥手术如何影响胰腺β细胞凋亡的证据仍然有限。

地点

大学医学中心。

目的

本研究旨在探讨Roux-en-Y胃旁路手术的主要组成部分十二指肠-空肠旁路术对保护胰腺β细胞免于渐进性丧失的作用。

方法

45只正常的Sprague-Dawley大鼠根据接受的手术方式随机分为3组:十二指肠-空肠旁路术(DJB)组(n = 16)和假手术(S)组(n = 17),以及未进行任何手术的对照组(C)组(n = 12),以消除手术可能带来的创伤性影响。术后10天,对每只动物(包括对照动物)腹腔注射链脲佐菌素(STZ,45 mg/kg体重),以选择性诱导胰腺β细胞凋亡。在手术前、注射STZ前以及注射STZ后长达4周的时间内,测量体重、食物摄入量、血浆葡萄糖水平以及口服葡萄糖耐量试验结果。在口服葡萄糖耐量试验期间还检测了血浆胰岛素和胰高血糖素样肽-1水平。最后,将胰腺组织切片并进行β细胞分析染色。

结果

在测量的任何时间点,所有组的体重均无显著差异,尽管在注射STZ后第10天(P<0.05)和第20天(P<0.01)测量时,S组和C组的大鼠比DJB组的大鼠消耗更多食物。接受DJB手术的动物未出现未代偿性糖尿病的典型症状,包括食欲亢进和体重逐渐减轻。注射STZ后,DJB组的空腹血浆葡萄糖水平显著低于C组和S组(P<0.001)。当受到葡萄糖负荷挑战时,与C组和S组大鼠相比,DJB大鼠的血糖波动也更好(P<0.01),肠促胰岛素反应也更好(P<0.05)。此外,DJB大鼠的胰腺β细胞大小和数量得到了更好的保留(P<0.001)。

结论

DJB能够保护胰腺β细胞免于凋亡,从而实现更好的血糖控制并延迟糖尿病的发生。这些结果表明,在设计减肥手术时,有必要纳入DJB部分以获得更好的长期效果。

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