Enhanced Glucose Control Following Vertical Sleeve Gastrectomy Does Not Require a β-Cell Glucagon-Like Peptide 1 Receptor

Diabetes
Jonathan D DourosDavid A D'Alessio

Abstract

Bariatric surgeries, including vertical sleeve gastrectomy (VSG), resolve diabetes in 40-50% of patients. Studies examining the molecular mechanisms underlying this effect have centered on the role of the insulinotropic glucagon-like peptide 1 (GLP-1), in great part because of the ∼10-fold rise in its circulating levels after surgery. However, there is currently debate over the role of direct β-cell signaling by GLP-1 to mediate improved glucose tolerance following surgery. In order to assess the importance of β-cell GLP-1 receptor (GLP-1R) for improving glucose control after VSG, a mouse model of this procedure was developed and combined with a genetically modified mouse line allowing an inducible, β-cell-specific Glp1r knockdown (Glp1rβ-cell-ko). Mice with VSG lost ∼20% of body weight over 30 days compared with sham-operated controls and had a ∼60% improvement in glucose tolerance. Isolated islets from VSG mice had significantly greater insulin responses to glucose than controls. Glp1r knockdown in β-cells caused glucose intolerance in diet-induced obese mice compared with obese controls, but VSG improved glycemic profiles to similar levels during oral and intraperitoneal glucose challenges in Glp1rβ-cell-ko and Glp1rWT mice....Continue Reading

References

Jul 1, 1963·The Journal of Clinical Investigation·R H UNGERL L MADISON
Oct 14, 2004·JAMA : the Journal of the American Medical Association·Henry BuchwaldKaren Schoelles
Feb 25, 2010·Endocrinology·Andrew C ShinHans-Rudolf Berthoud
Sep 1, 2011·Nature Neuroscience·Sander NieuwenhuisEric-Jan Wagenmakers
Apr 27, 2012·American Journal of Physiology. Endocrinology and Metabolism·N B JørgensenJ J Holst
Jan 31, 2013·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·C DirksenJ L Madsen
May 21, 2013·Cell Metabolism·Jonathan E Campbell, Daniel J Drucker
Sep 24, 2013·The Journal of Clinical Endocrinology and Metabolism·M NannipieriE Ferrannini
Dec 26, 2013·American Journal of Physiology. Endocrinology and Metabolism·Adam P ChambersDarleen A Sandoval
Mar 29, 2014·Nature·Karen K RyanRandy J Seeley
Apr 1, 2014·The New England Journal of Medicine·Philip R SchauerUNKNOWN STAMPEDE Investigators
Apr 26, 2014·The Journal of Clinical Investigation·Stephanie SisleyRandy J Seeley
Jun 22, 2014·Reviews in Endocrine & Metabolic Disorders·Marzieh Salehi, David A D'Alessio
Feb 5, 2015·Cell Metabolism·Ronald W AlfaSeung K Kim
Dec 8, 2015·Nature Medicine·Jonathan E CampbellDaniel J Drucker
Sep 28, 2016·Physiological Reports·Bethany A CarboneauMaureen Gannon

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Citations

Feb 6, 2019·JCI Insight·Megan E CapozziJonathan E Campbell
Mar 16, 2019·The Journal of Endocrinology·Peixin LiHu Huang
Mar 19, 2019·Journal of Neuroendocrinology·Darleen A Sandoval
May 18, 2019·Endocrinology·Jonathan D Douros, Jonathan E Campbell
Dec 27, 2019·Journal of Diabetes Science and Technology·Mercedes BurnsideMartin de Bock
Jun 27, 2019·Endocrine Reviews·Jonathan D DourosDavid A D'Alessio
Oct 18, 2019·JCI Insight·Ki-Suk KimDarleen A Sandoval
Aug 26, 2019·Journal of Molecular Biology·Alejandra TomasColin Leech
Feb 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Lili DingWendong Huang
Mar 19, 2020·Cell Metabolism·Ruth E GimenoRandy J Seeley

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Methods Mentioned

BETA
gastric bypass
ELISA
AlphaLISA
transgenic

Software Mentioned

GraphPad Prism

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