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A Single Dose of Oral Metformin Reduces the Post-Prandial Glucose Response Through a Transient Modulation of Apical Sodium-Glucose Co-Transporter

40 Pages Posted: 11 Oct 2019 Sneak Peek Status: Review Complete

See all articles by Lorea Zubiaga

Lorea Zubiaga

University of Lille - European Genomic Institute for Diabetes

Olivier Briand

University of Lille - European Genomic Institute for Diabetes

Florent Auger

University of Lille - Preclinical Imaging Core Facility

Veronique Touche

University of Lille - European Genomic Institute for Diabetes

Thomas Hubert

University of Lille - European Genomic Institute for Diabetes

Julien Thévenet

University of Lille - European Genomic Institute for Diabetes

Camille Marciniak

University of Lille - European Genomic Institute for Diabetes

Audrey Quenon

University of Lille - European Genomic Institute for Diabetes

Caroline Bonner

University of Lille - European Genomic Institute for Diabetes

Violeta Raverdy

University of Lille - European Genomic Institute for Diabetes

Mehdi Daoudi

University of Lille - European Genomic Institute for Diabetes

Julie Kerr-Conte

University of Lille - European Genomic Institute for Diabetes

Gianni Pasquetti

University of Lille - European Genomic Institute for Diabetes

Hermann Koepsell

University of Würzburg - Institute of Anatomy and Cell Biology

Daniela Zdzieblo

University of Würzburg - Institute of Anatomy and Cell Biology

Markus Müehlemanns

University of Würzburg - Institute of Anatomy and Cell Biology

Bernard Thorens

University of Lausanne - Center for Integrative Genomics

Nathalie Delzenne

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Laure Bindels

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Benoit Deprez

University of Lille - European Genomic Institute for Diabetes

Marie C. Vatyghem

University of Lille - European Genomic Institute for Diabetes

Blandine Laferrère

Columbia University - New York Nutrition Obesity Research Center

Bart Staels

University of Lille - European Genomic Institute for Diabetes

Huglo Damien

University of Lille - Preclinical Imaging Core Facility

Sophie Lestavel

University of Lille - European Genomic Institute for Diabetes

Francois Pattou

University of Lille - European Genomic Institute for Diabetes

More...

Abstract

Metformin (MET) is the most prescribed antidiabetic drug but its mechanism of action remains elusive. Recent clinical data point to the gut as MET primary target. In the present study we explored the effect of MET in the gut transport machinery. Using “in vitro” human enterocytes (Caco-2/TC7 cells) we showed that MET transiently reduced the apical density of sodium-glucose transporter 1 (SGLT1) and decreased the absorption of α-Methyl-D-1-glucopyranoside in an AMPK-independent manner, without changes in the post-translational signals. Administered 1hour before a glucose challenge in different animal models, MET reduced the postprandial glucose response (PGR). MET also reduced the urinary appearance of 2-(18F)-fluoro-2-deoxy-D-glucose after the intraluminal administration of the radiotracer. MET effect reducing PGR was maintained in glucose transporter type 2 (GLUT2)-KO mice but abrogated in (SGLT1)-KO animals. In conclusion, we unveiled the reversible effect of MET on SGLT1 trafficking, resulting in a transient decrease of the intestinal glucose absorption.

Keywords: metformin, sodium-glucose transporter 1 (SGLT1), Caco-2/TC7 intestinal human cells, intestinal glucose absorption

Suggested Citation

Zubiaga, Lorea and Briand, Olivier and Auger, Florent and Touche, Veronique and Hubert, Thomas and Thévenet, Julien and Marciniak, Camille and Quenon, Audrey and Bonner, Caroline and Raverdy, Violeta and Daoudi, Mehdi and Kerr-Conte, Julie and Pasquetti, Gianni and Koepsell, Hermann and Zdzieblo, Daniela and Müehlemanns, Markus and Thorens, Bernard and Delzenne, Nathalie and Bindels, Laure and Deprez, Benoit and Vatyghem, Marie C. and Laferrère, Blandine and Staels, Bart and Damien, Huglo and Lestavel, Sophie and Pattou, Francois, A Single Dose of Oral Metformin Reduces the Post-Prandial Glucose Response Through a Transient Modulation of Apical Sodium-Glucose Co-Transporter (October 8, 2019). CELL-REPORTS-D-19-03694. Available at SSRN: https://ssrn.com/abstract=3466339 or http://dx.doi.org/10.2139/ssrn.3466339
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Lorea Zubiaga

University of Lille - European Genomic Institute for Diabetes

France

Olivier Briand

University of Lille - European Genomic Institute for Diabetes

France

Florent Auger

University of Lille - Preclinical Imaging Core Facility

France

Veronique Touche

University of Lille - European Genomic Institute for Diabetes

France

Thomas Hubert

University of Lille - European Genomic Institute for Diabetes

France

Julien Thévenet

University of Lille - European Genomic Institute for Diabetes

France

Camille Marciniak

University of Lille - European Genomic Institute for Diabetes

France

Audrey Quenon

University of Lille - European Genomic Institute for Diabetes

France

Caroline Bonner

University of Lille - European Genomic Institute for Diabetes

France

Violeta Raverdy

University of Lille - European Genomic Institute for Diabetes

France

Mehdi Daoudi

University of Lille - European Genomic Institute for Diabetes

France

Julie Kerr-Conte

University of Lille - European Genomic Institute for Diabetes

France

Gianni Pasquetti

University of Lille - European Genomic Institute for Diabetes

France

Hermann Koepsell

University of Würzburg - Institute of Anatomy and Cell Biology

Germany

Daniela Zdzieblo

University of Würzburg - Institute of Anatomy and Cell Biology

Germany

Markus Müehlemanns

University of Würzburg - Institute of Anatomy and Cell Biology

Germany

Bernard Thorens

University of Lausanne - Center for Integrative Genomics

Switzerland

Nathalie Delzenne

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group ( email )

Belgium

Laure Bindels

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Belgium

Benoit Deprez

University of Lille - European Genomic Institute for Diabetes

France

Marie C. Vatyghem

University of Lille - European Genomic Institute for Diabetes

France

Blandine Laferrère

Columbia University - New York Nutrition Obesity Research Center

United States

Bart Staels

University of Lille - European Genomic Institute for Diabetes

France

Huglo Damien

University of Lille - Preclinical Imaging Core Facility

France

Sophie Lestavel

University of Lille - European Genomic Institute for Diabetes

France

Francois Pattou (Contact Author)

University of Lille - European Genomic Institute for Diabetes ( email )

France

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