Contribution of Endogenous Glucagon-Like Peptide 1 to Glucose Metabolism After Roux-en-Y Gastric Bypass

  1. Adrian Vella1
  1. 1Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN
  2. 2Department of Information Engineering, University of Padua, Padua, Italy
  3. 3Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
  4. 4Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, MN
  1. Corresponding author: Adrian Vella, vella.adrian{at}
  1. M.S. and J.H.L. contributed equally to this study.


The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the β-cell response to glucose (ϕTotal, 13 ± 1 vs. 11 ± 1 × 10−9 min−1, P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.


  • Received June 18, 2013.
  • Accepted September 22, 2013.

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  1. Diabetes vol. 63 no. 2 483-493
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