回肠旁路术引起代谢改善中肠激素 GLP-1 的作用。
The role of the gut hormone GLP-1 in the metabolic improvements caused by ileal transposition.
机构信息
Department of Surgery, University Hospital/University of Cincinnati, Cincinnati, Ohio 45267, USA.
出版信息
J Surg Res. 2012 Nov;178(1):33-9. doi: 10.1016/j.jss.2011.04.044. Epub 2011 May 18.
BACKGROUND
Bariatric surgery alters the gastrointestinal hormonal milieu leading to improved glucose homeostasis, though the mechanism leading to these changes is poorly understood. Ileal transposition (IT) is a procedure that is neither restrictive nor malabsorptive but nevertheless produces profound improvements in glucose regulation. Ileal transposition involves a short segment of distal ileum being transposed to the proximal jejunum in an isoperistaltic direction, thereby avoiding any gastric resection or intestinal bypass.
METHODS
Diet-induced obese rats underwent either ileal transposition (IT) or Sham procedures. The Sham operated rats were pair-fed to the IT surgical group to control for the effects of reduced food intake. Body composition data were recorded at specific time points, and glucose tolerance tests were performed at 5 and 6 wk, both in the presence and absence of Exendin 9-39, a known glucose-like peptide 1 (GLP-1) receptor antagonist. A subset of naïve rats were also maintained for comparison.
RESULTS
IT and Sham operated rats had no differences in food intake and body weight, however, IT rats had a significant decrease in their body fat composition (P < 0.05). No difference existed in glucose tolerance when exposed to an intraperitoneal glucose load, however, IT rats showed markedly improved glucose tolerance when submitted to an oral glucose tolerance test (P < 0.001). Blocking GLP-1 receptors reversed these important improvements in rats with IT surgery.
CONCLUSIONS
The present work recapitulates what is seen in rodents and humans that IT improves glucose tolerance and body composition. The present data provide compelling evidence that these improvements are a product of increased GLP-1 secretion that results from placing the key GLP-1 secreting cells closer to chyme coming from the stomach. Such data support the notion that rather than restriction or malabsorption, the underling molecular mechanisms that mediate the potent improvements produced by bariatric procedures involve increased activation of GLP-1 signaling.
背景
减重手术改变了胃肠道激素环境，导致葡萄糖内稳态改善，尽管导致这些变化的机制尚不清楚。回肠转位（IT）是一种既不限制也不吸收的手术，但它能显著改善血糖调节。回肠转位涉及将一小段远端回肠以等蠕动方向转位到近端空肠，从而避免任何胃切除术或肠旁路术。
方法
饮食诱导肥胖大鼠接受回肠转位（IT）或假手术。假手术组大鼠与 IT 手术组进行等热量喂养，以控制食物摄入量减少的影响。在特定时间点记录身体成分数据，并在存在和不存在 Exendin 9-39（一种已知的葡萄糖样肽 1（GLP-1）受体拮抗剂）的情况下进行 5 周和 6 周的葡萄糖耐量试验。还保留了一组天真大鼠进行比较。
结果
IT 和假手术组大鼠的食物摄入量和体重没有差异，但 IT 大鼠的体脂组成明显减少（P <0.05）。在接受腹腔内葡萄糖负荷时，葡萄糖耐量没有差异，但在口服葡萄糖耐量试验时，IT 大鼠的葡萄糖耐量明显改善（P <0.001）。阻断 GLP-1 受体可逆转 IT 手术后大鼠的这些重要改善。
结论
本工作再现了在啮齿动物和人类中观察到的 IT 改善葡萄糖耐量和体成分的情况。本数据提供了令人信服的证据，表明这些改善是 GLP-1 分泌增加的结果，这是由于将关键的 GLP-1 分泌细胞更接近来自胃的食糜。这些数据支持这样一种观点，即介导减重手术产生的强大改善的潜在分子机制不是限制或吸收不良，而是 GLP-1 信号的激活增加。
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