Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.
Diabetes. 2013 Sep;62(9):3044-52. doi: 10.2337/db13-0022. Epub 2013 May 6.
β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)-specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.
β 细胞功能在接受 Roux-en-Y 胃旁路 (RYGB) 手术后的口服葡萄糖刺激下会在 2 型糖尿病患者中得到改善。这与胰高血糖素样肽 1 (GLP-1) 的过度分泌有关，但因果关系尚未确定。本研究旨在使用 exendin(9-39) (Ex-9)，一种 GLP-1 受体 (GLP-1R) 特异性拮抗剂，研究 GLP-1 在改善 RYGB 后 β 细胞功能和葡萄糖耐量以及调节胰高血糖素释放中的作用。在手术前、手术后 1 周和 3 个月，检查了 9 例 2 型糖尿病患者。每次就诊均包括两天的实验，允许进行随机输注盐水或 Ex-9 的餐试。RYGB 后，葡萄糖耐量改善，β 细胞葡萄糖敏感性 (β-GS) 增加一倍，GLP-1 反应大大增加，胰高血糖素分泌增强。GLP-1R 阻断在手术前不会影响 β 细胞功能或餐引起的胰高血糖素释放，但会损害葡萄糖耐量。RYGB 后，β-GS 降至术前水平，胰高血糖素分泌增加，Ex-9 输注会损害葡萄糖耐量。因此，GLP-1 在 RYGB 后的过度作用对改善 2 型糖尿病患者的 β 细胞功能、控制胰高血糖素释放和葡萄糖耐量非常重要。
