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

描述（由申请人提供）：肠促胰岛素GLP-1是一种有效的葡萄糖介导的胰岛素分泌剂。2型糖尿病（DM2）患者肠促胰岛素对胰岛素分泌的作用减弱，但给予GLP-1能够恢复DM患者的细胞对葡萄糖的敏感性。胃旁路手术（GBP）后经历DM2缓解的患者餐后GLP-1释放迅速（在数周内），持续（数年），放大，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

DESCRIPTION (provided by applicant): 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 t 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.