The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes
The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes
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DOI：
10.1097/01.sla.0000224726.61448.1b
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发表时间：
2006-11-01
影响因子：
9
通讯作者：
Marescaux, Jacques
中科院分区：
文献类型：
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作者：
Rubino, Francesco;Forgione, Antonello;Marescaux, Jacques
背景资料：大多数接受Roux-en-Y胃旁路术（RYGB）的患者2型糖尿病迅速消退。先前的研究表明，这不仅仅是胃限制和体重减轻的结果，这意味着重排的肠道是主要的介导者。然而，目前尚不清楚糖尿病的改善是因为营养物质向远端肠道的输送增强和后肠信号分泌增加，从而改善葡萄糖稳态，还是因为近端肠道被排除部分的信号改变。我们试图区分这两种mechanism.Methods：后藤Kakizaki（GK）2型糖尿病大鼠进行空肠-空肠旁路（DJB），胃保留RYGB，排除近端肠，或胃空肠吻合术（GJ），这创造了一个捷径摄取营养物质，而不绕过任何肠道。对照组为配对喂养（PF）假手术和未处理的GK大鼠。然后对经历过GJ的大鼠再次手术以排除近端肠;相反，在经历过DJB的大鼠中恢复了十二指肠通道。口服葡萄糖耐量（OGTT），食物摄入量，体重，和肠道营养吸收measured.Results：有没有差异，食物摄入量，体重，或营养吸收手术组之间。与所有对照组相比，DJB治疗组大鼠的口服葡萄糖耐量明显更好，表现为葡萄糖峰值和曲线下面积更低（两者均P < 0.001）。GJ并不影响葡萄糖稳态，但在再手术GJ大鼠排除十二指肠营养通道显着改善葡萄糖耐量。相反，恢复DJB大鼠的十二指肠通道重建受损glucose tolerance.Conclusions：这项研究表明，绕过近端肠的一小段直接改善2型糖尿病，独立的影响对食物摄入量，体重，吸收不良，或营养输送到后肠。这些研究结果表明，近端肠旁路术可以考虑用于糖尿病治疗，并且近端肠的潜在未发现因素可能有助于2型糖尿病的病理生理学。
Background Data: Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms.Methods: Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured.Results: There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance.Conclusions: This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.