Long term change of GLP-1 insulinotropic effect after GBP surgery

7-摘要 肠促胰岛素GLP-1是一种有效的葡萄糖介导的胰岛素促分泌素。 2型糖尿病（DM 2）患者的肠促胰岛素对胰岛素分泌的影响减弱 但GLP-1的给药能够恢复DM患者的葡萄糖敏感性。 胃旁路手术（GBP）后经历DM 2缓解的患者， 快速（数周内）和持续（数年）的餐后GLP-1过度释放， 肠促胰岛素对胰岛素分泌的作用正常化。体外和/或啮齿动物 研究表明，GLP-1可以刺激细胞生长和分化。是否 GBP后持续增强GLP-1释放导致更大的细胞功能 未知在本提案中，我们将研究1）内源性GLP-1在 通过使用exendin 9-39（GLP-1）， 1受体拮抗剂; 2）葡萄糖输注后最大细胞反应的变化 GBP后给予精氨酸; 3）胰岛素敏感性和身体组成， GBP前和GBP后2年内的重度肥胖和DM 2患者; 4） GBP后DM 2缓解的决定因素。了解DM 2的机制 GBP后的缓解或缺乏将有助于确定结果的预测因素， 开发治疗严重肥胖和2型糖尿病的替代药物。

7- Abstract The intestinal incretin GLP-1 is a potent glucose-mediated insulin secretagogue. Patients with type 2 diabetes (DM2) have a blunted incretin effect on insulin secretion but the administration of GLP-1 is able to restore ¿-cell sensitivity to glucose in DM. Patients who experienced DM2 remission after gastric bypass surgery (GBP) have rapid (within weeks), and sustained (years), exaggerated post-prandial GLP-1 release, with normalization of the incretin effect on insulin secretion. In vitro and/or rodent studies show that GLP-1 can stimulate ¿-cell growth and differentiation. Whether the sustained enhanced GLP-1 release after GBP results in greater ¿-cell function is unknown. In this proposal we will examine 1) The role of endogenous GLP-1 in the recovery of ¿-cell function in response to oral glucose, by using exendin 9-39, a GLP- 1 receptor antagonist; 2) The change of maximal ¿-cell response to glucose infusion and arginine administration after GBP; 3) Insulin sensitivity and body composition, in patients with severe obesity and DM2, before and up to 2 years after GBP; 4) Determinants of DM2 remission after GBP. Understanding the mechanisms of DM2 remission, or lack of, after GBP will help identify predictors of outcome as well as develop medical alternatives for the treatment of severe obesity and DM2.