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

Diabetologia. 2013 Dec;56(12):2679-87. doi: 10.1007/s00125-013-3055-1. Epub 2013 Sep 19.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Female
  • Gastric Bypass*
  • Gastric Inhibitory Polypeptide / metabolism*
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucose Clamp Technique / methods
  • Glucose Tolerance Test
  • Humans
  • Hyperglycemia / metabolism
  • Insulin / metabolism*
  • Insulin Resistance
  • Insulin Secretion
  • Male
  • Obesity, Morbid / metabolism*
  • Obesity, Morbid / physiopathology
  • Obesity, Morbid / surgery
  • Pancreas / metabolism*
  • Peptide Fragments / metabolism*
  • Postprandial Period
  • Treatment Outcome


  • Blood Glucose
  • Insulin
  • Peptide Fragments
  • gastric inhibitory polypeptide (1-39)
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon

Associated data

  • ClinicalTrials.gov/NCT01559779