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GLP-1R Responsiveness Predicts Individual Gastric Bypass Efficacy on Glucose Tolerance in Rats
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, a...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900539/ https://www.ncbi.nlm.nih.gov/pubmed/24186863 http://dx.doi.org/10.2337/db13-0511 |
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author | Habegger, Kirk M. Heppner, Kristy M. Amburgy, Sarah E. Ottaway, Nickki Holland, Jenna Raver, Christine Bartley, Erin Müller, Timo D. Pfluger, Paul T. Berger, Jose Toure, Mouhamadoul Benoit, Stephen C. DiMarchi, Richard D. Perez-Tilve, Diego D’Alessio, David A. Seeley, Randy J. Tschöp, Matthias H. |
author_facet | Habegger, Kirk M. Heppner, Kristy M. Amburgy, Sarah E. Ottaway, Nickki Holland, Jenna Raver, Christine Bartley, Erin Müller, Timo D. Pfluger, Paul T. Berger, Jose Toure, Mouhamadoul Benoit, Stephen C. DiMarchi, Richard D. Perez-Tilve, Diego D’Alessio, David A. Seeley, Randy J. Tschöp, Matthias H. |
author_sort | Habegger, Kirk M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3900539 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-39005392015-02-01 GLP-1R Responsiveness Predicts Individual Gastric Bypass Efficacy on Glucose Tolerance in Rats Habegger, Kirk M. Heppner, Kristy M. Amburgy, Sarah E. Ottaway, Nickki Holland, Jenna Raver, Christine Bartley, Erin Müller, Timo D. Pfluger, Paul T. Berger, Jose Toure, Mouhamadoul Benoit, Stephen C. DiMarchi, Richard D. Perez-Tilve, Diego D’Alessio, David A. Seeley, Randy J. Tschöp, Matthias H. Diabetes Metabolism 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. American Diabetes Association 2014-02 2014-01-16 /pmc/articles/PMC3900539/ /pubmed/24186863 http://dx.doi.org/10.2337/db13-0511 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Metabolism Habegger, Kirk M. Heppner, Kristy M. Amburgy, Sarah E. Ottaway, Nickki Holland, Jenna Raver, Christine Bartley, Erin Müller, Timo D. Pfluger, Paul T. Berger, Jose Toure, Mouhamadoul Benoit, Stephen C. DiMarchi, Richard D. Perez-Tilve, Diego D’Alessio, David A. Seeley, Randy J. Tschöp, Matthias H. GLP-1R Responsiveness Predicts Individual Gastric Bypass Efficacy on Glucose Tolerance in Rats |
title | GLP-1R Responsiveness Predicts Individual Gastric Bypass Efficacy on Glucose Tolerance in Rats |
title_full | GLP-1R Responsiveness Predicts Individual Gastric Bypass Efficacy on Glucose Tolerance in Rats |
title_fullStr | GLP-1R Responsiveness Predicts Individual Gastric Bypass Efficacy on Glucose Tolerance in Rats |
title_full_unstemmed | GLP-1R Responsiveness Predicts Individual Gastric Bypass Efficacy on Glucose Tolerance in Rats |
title_short | GLP-1R Responsiveness Predicts Individual Gastric Bypass Efficacy on Glucose Tolerance in Rats |
title_sort | glp-1r responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900539/ https://www.ncbi.nlm.nih.gov/pubmed/24186863 http://dx.doi.org/10.2337/db13-0511 |
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