GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- 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
Published Date
- February 2014
Published In
Volume / Issue
- 63 / 2
Start / End Page
- 505 - 513
PubMed ID
- 24186863
Pubmed Central ID
- PMC3900539
Electronic International Standard Serial Number (EISSN)
- 1939-327X
Digital Object Identifier (DOI)
- 10.2337/db13-0511
Language
- eng
Conference Location
- United States