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GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.

Publication ,  Journal Article
Habegger, KM; Heppner, KM; Amburgy, SE; Ottaway, N; Holland, J; Raver, C; Bartley, E; Müller, TD; Pfluger, PT; Berger, J; Toure, M; Benoit, SC ...
Published in: Diabetes
February 2014

Several bariatric operations are currently used to treat obesity and obesity-related comorbidities. These vary in efficacy, but most are more effective than current pharmaceutical treatments. Roux-en-Y gastric bypass (RYGB) produces substantial body weight (BW) loss and enhanced glucose tolerance, and is associated with increased secretion of the gut hormone glucagon-like peptide 1 (GLP-1). Given the success of GLP-1-based agents in lowering blood glucose levels and BW, we hypothesized that an individual sensitivity to GLP-1 receptor agonism could predict metabolic benefits of surgeries associated with increased GLP-1 secretion. One hundred ninety-seven high-fat diet-induced obese male Long-Evans rats were monitored for BW loss during exendin-4 (Ex4) administration. Stable populations of responders and nonresponders were identified based on Ex4-induced BW loss and GLP-1-induced improvements in glucose tolerance. Subpopulations of Ex4 extreme responders and nonresponders underwent RYGB surgery. After RYGB, responders and nonresponders showed similar BW loss compared with sham, but nonresponders retained impaired glucose tolerance. These data indicate that the GLP-1 response tests may predict some but not all of the improvements observed after RYGB. These findings present an opportunity to optimize the use of bariatric surgery based on an improved understanding of GLP-1 biology and suggest an opportunity for a more personalized therapeutic approach to the metabolic syndrome.

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Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

February 2014

Volume

63

Issue

2

Start / End Page

505 / 513

Location

United States

Related Subject Headings

  • Weight Loss
  • Venoms
  • Receptors, Glucagon
  • Rats, Long-Evans
  • Rats
  • Peptides
  • Obesity
  • Male
  • Glucose Tolerance Test
  • Glucagon-Like Peptide-1 Receptor
 

Citation

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Habegger, K. M., Heppner, K. M., Amburgy, S. E., Ottaway, N., Holland, J., Raver, C., … Tschöp, M. H. (2014). GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats. Diabetes, 63(2), 505–513. https://doi.org/10.2337/db13-0511
Habegger, Kirk M., Kristy M. Heppner, Sarah E. Amburgy, Nickki Ottaway, Jenna Holland, Christine Raver, Erin Bartley, et al. “GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.Diabetes 63, no. 2 (February 2014): 505–13. https://doi.org/10.2337/db13-0511.
Habegger KM, Heppner KM, Amburgy SE, Ottaway N, Holland J, Raver C, et al. GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats. Diabetes. 2014 Feb;63(2):505–13.
Habegger, Kirk M., et al. “GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.Diabetes, vol. 63, no. 2, Feb. 2014, pp. 505–13. Pubmed, doi:10.2337/db13-0511.
Habegger KM, Heppner KM, Amburgy SE, Ottaway N, Holland J, Raver C, Bartley E, Müller TD, Pfluger PT, Berger J, Toure M, Benoit SC, Dimarchi RD, Perez-Tilve D, D’Alessio DA, Seeley RJ, Tschöp MH. GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats. Diabetes. 2014 Feb;63(2):505–513.

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

February 2014

Volume

63

Issue

2

Start / End Page

505 / 513

Location

United States

Related Subject Headings

  • Weight Loss
  • Venoms
  • Receptors, Glucagon
  • Rats, Long-Evans
  • Rats
  • Peptides
  • Obesity
  • Male
  • Glucose Tolerance Test
  • Glucagon-Like Peptide-1 Receptor