Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass

Abstract

Aims/hypothesis: Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones, including GLP-1, is altered. Methods: Eleven severely obese glucose-tolerant individuals underwent three hyperglycaemic clamps with arginine bolus and co-infusion of either GLP-1, glucose-dependent insulinotropic polypeptide (GIP) or saline before, and at 1 week and 3 months after RYGB. In addition, an OGTT was performed before and 3 months after surgery. Results: After RYGB, insulin sensitivity improved at 1 week and 3 months, while insulin stimulation and glucagon suppression in response to the clamp with saline co-infusion were largely unaltered. The influence of i.v. GLP-1 and GIP on insulin and glucagon secretion was also unchanged postoperatively. In response to the postoperative OGTT at 3 months, insulin and GLP-1, but not GIP, secretion increased. Furthermore, the glucose profile during the OGTT was altered, with a substantial reduction in 2 h plasma glucose and a paradoxical hypersecretion of glucagon. Conclusions/interpretation: After RYGB, insulin hypersecretion is linked to the oral, but not the i.v., route of administration and is associated with exaggerated release and preserved insulinotropic action of GLP-1, while both the secretion and action of GIP are unchanged. The results highlight the importance of increased GLP-1 secretion for improving postoperative glucose metabolism. Trial registration: ClinicalTrials.gov NCT01559779. © 2013 Springer-Verlag Berlin Heidelberg.