title: Intestinal invalidation of the glucose transporter GLUT2 delays tissue distribution of glucose and reveals an unexpected role in gut homeostasis.
abstract: Intestinal glucose absorption is orchestrated by specialized glucose transporters such as SGLT1 and GLUT2. However, the role of GLUT2 in the regulation of glucose absorption remains to be fully elucidated.
  
  
  
  We wanted to evaluate the role of GLUT2 on glucose absorption and glucose homeostasis after intestinal-specific deletion of GLUT2 in mice (GLUT2ΔIECmice).
  
  
  
  As anticipated, intestinal GLUT2 deletion provoked glucose malabsorption as visualized by the delay in the distribution of oral sugar in tissues. Consequences of intestinal GLUT2 deletion in GLUT2ΔIECmice were limiting body weight gain despite normal food intake, improving glucose tolerance, and increasing ketone body production. These features were reminiscent of calorie restriction. Other adaptations to intestinal GLUT2 deletion were reduced microvillus length and altered gut microbiota composition, which was associated with improved inflammatory status. Moreover, a reduced density of glucagon-like peptide-1 (GLP-1) positive cells was compensated by increased GLP-1 content per L-cell, suggesting a preserved enteroendocrine function in GLUT2ΔIECmice.
  
  
  
  Intestinal GLUT2 modulates glucose absorption and constitutes a control step for the distribution of dietary sugar to tissues. Consequently, metabolic and gut homeostasis are improved in the absence of functional GLUT2 in the intestine, thus mimicking calorie restriction.
authors.affiliation: INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Cités, UPD Univ Paris 05, CNRS, IHU ICAN, Paris, France.
authors.forename: Charlotte C
authors.initials: CC
authors.lastname: Schmitt
authors.affiliation: INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Cités, UPD Univ Paris 05, CNRS, IHU ICAN, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Aranias
authors.affiliation: Plateforme imagerie du vivant, Centre de Recherche Cardiovasculaire de Paris, INSERM U970, Université Paris Descartes-Sorbonne Paris cité, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.affiliation: INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Cités, UPD Univ Paris 05, CNRS, IHU ICAN, Paris, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Chateau
authors.affiliation: INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Cités, UPD Univ Paris 05, CNRS, IHU ICAN, Paris, France.
authors.forename: Maude
authors.initials: M
authors.lastname: Le Gall
authors.affiliation: EA4065, Faculté de pharmacie, Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
authors.forename: Anne-Judith
authors.initials: AJ
authors.lastname: Waligora-Dupriet
authors.affiliation: INSERM UMR-1073, Gastroenterology Department, Rouen University Hospital, Rouen, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Melchior
authors.affiliation: INSERM U1016 and CNRS UMR8104, Institut Cochin, Laboratoire d'Excellence INFLAMEX, Paris, France.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Rouxel
authors.affiliation: Service de Coprologie Fonctionnelle, Hopital La Pitié Salpêtrière, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kapel
authors.affiliation: INSERM UMR-1073, Gastroenterology Department, Rouen University Hospital, Rouen, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gourcerol
authors.affiliation: Plateforme imagerie du vivant, Centre de Recherche Cardiovasculaire de Paris, INSERM U970, Université Paris Descartes-Sorbonne Paris cité, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
authors.affiliation: INSERM U1016 and CNRS UMR8104, Institut Cochin, Laboratoire d'Excellence INFLAMEX, Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Lehuen
authors.affiliation: INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Cités, UPD Univ Paris 05, CNRS, IHU ICAN, Paris, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Brot-Laroche
authors.affiliation: INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Cités, UPD Univ Paris 05, CNRS, IHU ICAN, Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Leturque
authors.affiliation: INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Cités, UPD Univ Paris 05, CNRS, IHU ICAN, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Serradas
authors.affiliation: INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Cités, UPD Univ Paris 05, CNRS, IHU ICAN, Paris, France. Electronic address: alexandra.grosfeld@crc.jussieu.fr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Grosfeld
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006706:Homeostasis; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001786:Blood Glucose; D051246:Glucose Transport Proteins, Facilitative; D051273:Glucose Transporter Type 2; C495682:Slc2a2 protein, mouse; D051269:Sodium-Glucose Transporter 1; D052216:Glucagon-Like Peptide 1; D005947:Glucose
keywords: 2FDG, 2-deoxy-2-[18F]fluoro-d-glucose; DPP-IV, dipeptidyl-peptidase IV; GLP-1; GLP-1, glucagon-like peptide-1; GLUT1-7, glucose transporter 1–7; Glucose homeostasis; IEC, intestinal epithelial cells; IL, interleukin; IPGTT, intraperitoneal glucose tolerance test; ITT, insulin tolerance test; Intestinal adaptation; Malabsorption; Microbiota; OGTT, oral glucose tolerance test; PET-CT, Positron Emission Tomography-Computed Tomography; SGLT1, sodium-glucose transporter 1