Diabetologia

, Volume 56, Issue 12, pp 2679–2687

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

  • Carsten Dirksen
  • Kirstine N. Bojsen-Møller
  • Nils B. Jørgensen
  • Siv H. Jacobsen
  • Viggo B. Kristiansen
  • Lars S. Naver
  • Dorte L. Hansen
  • Dorte Worm
  • Jens J. Holst
  • Sten Madsbad
Article

DOI: 10.1007/s00125-013-3055-1

Cite this article as:
Dirksen, C., Bojsen-Møller, K.N., Jørgensen, N.B. et al. Diabetologia (2013) 56: 2679. doi:10.1007/s00125-013-3055-1

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.

Keywords

Bariatric surgery Glucagon Glucagon-like peptide-1 Glucose-dependent insulinotropic polypeptide Insulin Insulin resistance Insulin secretion rate Obesity 

Abbreviations

AGRarg

Acute glucagon response to arginine

AIRarg

Acute insulin response to arginine

AIRglu

Acute insulin response to glucose

DI

Disposition index

GIP

Glucose-dependent insulinotropic polypeptide

GLP

Glucagon-like peptide

iAUC

Incremental AUC

IGI

Insulinogenic index

ISR

Insulin secretion rate

OGIS

Oral glucose insulin sensitivity

RYGB

Roux-en-Y gastric bypass

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Carsten Dirksen
    • 1
    • 2
  • Kirstine N. Bojsen-Møller
    • 1
    • 2
  • Nils B. Jørgensen
    • 1
    • 2
    • 3
  • Siv H. Jacobsen
    • 1
    • 2
  • Viggo B. Kristiansen
    • 4
  • Lars S. Naver
    • 4
  • Dorte L. Hansen
    • 1
  • Dorte Worm
    • 1
  • Jens J. Holst
    • 2
    • 3
  • Sten Madsbad
    • 1
  1. 1.Department of EndocrinologyHvidovre HospitalHvidovreDenmark
  2. 2.NNF Center for Basic Metabolic Research, the Panum InstituteUniversity of CopenhagenCopenhagen NDenmark
  3. 3.Department of Biomedical SciencesUniversity of CopenhagenCopenhagen NDenmark
  4. 4.Department of Surgical GastroenterologyHvidovre HospitalHvidovreDenmark

Personalised recommendations