GLP-1 Action and Glucose Tolerance in Subjects With Remission of Type 2 Diabetes After Gastric Bypass Surgery

OBJECTIVE-Glucagon like peptide-1 (GLP-1) has been suggested as a major factor for the improved glucose tolerance ensuing after Roux-en-Y gastric bypass (RYGBP) surgery. We examined the effect of blocking endogenous GLP-1 action on glucose tolerance in subjects with sustained remission of type 2 diabetes mellitus (T2DM) present before RYGBP. RESEARCH DESIGN AND METHODS-Blood glucose, insulin, C-peptide, glucagon, GLP-1, and glucose-dependent insulinotropic peptide levels were measured after a meal challenge with either exendin-(9-39) (a GLP-1r antagonist) or saline infusion in eight subjects with sustained remission of T2DM after RYGBP and seven healthy controls. RESULTS Infusion of exendin-(9-39) resulted in marginal deterioration of the 2-h plasma glucose after meal intake in RYGBP subjects [saline 784 +/- 15.1 mg/dL compared with exendin(9-39) 116.5 +/- 22.3 mg/dL; P < 0.001]. Furthermore, glucose response to meal intake was similarly enlarged in the two study groups [percent change in the area under the curve of glucose exendin-(9-39) infusion versus saline infusion: controls 10.84 +/- 8.8% versus RYGBP 9.94 +/- 8.4%; P = 0.884]. In the RYGBP group, the blockade of the enlarged GLP-1 response to meal intake resulted in reduced insulin (P = 0.001) and C-peptide (P < 0.001), but no change in glucagon (P = 0.258) responses. CONCLUSIONS-The limited deterioration of glucose tolerance on blockade of GLP-1 action in our study suggests the resolution of T2DM after RYGBP may be explained by mechanisms beyond enhancement of GLP-1 action.