Duodenal-Jejunal Exclusion Improves Glucose Tolerance in the Diabetic, Goto-Kakizaki Rat by a GLP-1 Receptor-Mediated Mechanism
Duodenal-Jejunal Exclusion Improves Glucose Tolerance in the Diabetic, Goto-Kakizaki Rat by a GLP-1 Receptor-Mediated Mechanism
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DOI：
10.1007/s11605-009-0912-9
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发表时间：
2009-10-01
影响因子：
3.2
通讯作者：
Tso, Patrick
中科院分区：
文献类型：
--
作者：
Kindel, Tammy L.;Yoder, Stephanie M.;Tso, Patrick
背景胃转流术可快速缓解2型糖尿病。没有因果关系的证据表明特定的肠道激素变化与术后葡萄糖稳态的改善有关。我们假设，手术增加血糖调节因子GLP-1可以改善糖尿病GK大鼠的葡萄糖耐量。我们比较了两个程序，增加远端小肠刺激，回肠间置（IT），和回肠空肠exclusion（DJE.Methods DJE，IT，WE Sham，或IT Sham在GK大鼠。在第4周和第6周检测葡萄糖耐量，后者使用和不使用Exendin-[9-39]（GLP-1受体拮抗剂）。结果尽管体重分布相似，但WE和IT后4周的OGTT显著改善，WE和IT后血浆GLP-1水平显著升高，DJE后空肠中段和回肠的肠道GLP-1水平升高。Exendin-[9-39]可抑制DJE后葡萄糖耐量的改善。结论WE可增加GLP-1的分泌，改善葡萄糖耐量，这种作用可被GLP-1受体拮抗剂逆转。这项研究提供了直接的证据表明，胃旁路样手术后葡萄糖耐量的改善是由增强的GLP-1作用介导的。
Background Gastric bypass results in the rapid resolution of type 2 diabetes. No causal evidence exists to link specific gut hormone changes with improvements in glucose homeostasis post-operatively. We hypothesized that surgical augmentation of the glucoregulatory factor GLP-1 would improve glucose tolerance in diabetic GK rats. We compared two procedures that increase distal small bowel stimulation, ileal interposition (IT), and duodenal-jejunal exclusion (DJE).Methods DJE, IT, WE Sham, or IT Sham were performed in GK rats. Glucose tolerance was tested at 4 and 6 weeks, the latter with and without Exendin-[9-39], a GLP-1 receptor antagonist. Small bowel segments were harvested for GLP-1 protein content 2 weeks after WE or Sham surgery.Results Despite similar weight profiles, a significant improvement in the OGTT was noted at 4 weeks after WE and IT. Plasma GLP-1 levels were significantly elevated after WE and IT. Intestinal GLP-1 was increased in the mid-jejunum and ileum after DJE. Exendin-[9-39] abolished the improvement in glucose tolerance after DJE.Conclusions WE increased GLP-1 secretion and improved glucose tolerance, an effect that was reversed by GLP-1 receptor antagonism. This study provides direct evidence that improvement of glucose tolerance following a gastric bypass-like surgery is mediated by enhanced GLP-1 action.