iScience (Apr 2023)
Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes
- Lorea Zubiaga,
- Olivier Briand,
- Florent Auger,
- Veronique Touche,
- Thomas Hubert,
- Julien Thevenet,
- Camille Marciniak,
- Audrey Quenon,
- Caroline Bonner,
- Simon Peschard,
- Violeta Raverdy,
- Mehdi Daoudi,
- Julie Kerr-Conte,
- Gianni Pasquetti,
- Hermann Koepsell,
- Daniela Zdzieblo,
- Markus Mühlemann,
- Bernard Thorens,
- Nathalie D. Delzenne,
- Laure B. Bindels,
- Benoit Deprez,
- Marie C. Vantyghem,
- Blandine Laferrère,
- Bart Staels,
- Damien Huglo,
- Sophie Lestavel,
- François Pattou
Affiliations
- Lorea Zubiaga
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Olivier Briand
- University of Lille, Inserm, Centre Hospitalier Universitaire de Lille, Institut Pasteur de Lille, U1011-EGID, 59000 Lille, France
- Florent Auger
- University of Lille, Preclinical Imaging Core Facility, 59000 Lille, France
- Veronique Touche
- University of Lille, Inserm, Centre Hospitalier Universitaire de Lille, Institut Pasteur de Lille, U1011-EGID, 59000 Lille, France
- Thomas Hubert
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Julien Thevenet
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Camille Marciniak
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Audrey Quenon
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Caroline Bonner
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France; Institut Pasteur de Lille, 59000 Lille, France
- Simon Peschard
- University of Lille, Inserm, Centre Hospitalier Universitaire de Lille, Institut Pasteur de Lille, U1011-EGID, 59000 Lille, France
- Violeta Raverdy
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Mehdi Daoudi
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Julie Kerr-Conte
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Gianni Pasquetti
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Hermann Koepsell
- Institute of Anatomy and Cell Biology, University of Würzburg, 97070 Würzburg, Germany
- Daniela Zdzieblo
- Institute of Anatomy and Cell Biology, University of Würzburg, 97070 Würzburg, Germany
- Markus Mühlemann
- Institute of Anatomy and Cell Biology, University of Würzburg, 97070 Würzburg, Germany
- Bernard Thorens
- University of Lausanne, Center for Integrative Genomics, Lausanne, Switzerland
- Nathalie D. Delzenne
- Université catholique de Louvain, Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Brussels, Belgium
- Laure B. Bindels
- Université catholique de Louvain, Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Brussels, Belgium
- Benoit Deprez
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1177, 59000 Lille, France
- Marie C. Vantyghem
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France
- Blandine Laferrère
- Department of Medicine, New York Nutrition Obesity Research Center, Columbia University College of Physicians and Surgeons, New York, NY, USA
- Bart Staels
- University of Lille, Inserm, Centre Hospitalier Universitaire de Lille, Institut Pasteur de Lille, U1011-EGID, 59000 Lille, France
- Damien Huglo
- University of Lille, Preclinical Imaging Core Facility, 59000 Lille, France
- Sophie Lestavel
- University of Lille, Inserm, Centre Hospitalier Universitaire de Lille, Institut Pasteur de Lille, U1011-EGID, 59000 Lille, France
- François Pattou
- University of Lille, Centre Hospitalier Universitaire de Lille, European Genomic Institute for Diabetes, Inserm UMR-1190, 59000 Lille, France; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 4
p. 106057
Abstract
Summary: Metformin (MET) is the most prescribed antidiabetic drug, but its mechanisms of action remain elusive. Recent data point to the gut as MET’s primary target. Here, we explored the effect of MET on the gut glucose transport machinery. Using human enterocytes (Caco-2/TC7 cells) in vitro, we showed that MET transiently reduced the apical density of sodium-glucose transporter 1 (SGLT1) and decreased the absorption of glucose, without changes in the mRNA levels of the transporter. Administered 1 h before a glucose challenge in rats (Wistar, GK), C57BL6 mice and mice pigs, oral MET reduced the post-prandial glucose response (PGR). This effect was abrogated in SGLT1-KO mice. MET also reduced the luminal clearance of 2-(18F)-fluoro-2-deoxy-D-glucose after oral administration in rats. In conclusion, oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of SGLT1 in enterocytes, which may contribute to the clinical effects of the drug.
