title: Reassessment of GLUT7 and GLUT9 as Putative Fructose and Glucose Transporters.
abstract: Although increased dietary fructose consumption is associated with metabolic impairments, the mechanisms and regulation of intestinal fructose absorption are poorly understood. GLUT5 is considered to be the main intestinal fructose transporter. Other GLUT family members, such as GLUT7 and GLUT9 are also expressed in the intestine and were shown to transport fructose and glucose. A conserved isoleucine-containing motif (NXI) was proposed to be essential for fructose transport capacity of GLUT7 and GLUT9 but also of GLUT2 and GLUT5. In assessing whether human GLUT2, GLUT5, GLUT7, and GLUT9 are indeed fructose transporters, we expressed these proteins in Xenopus laevis oocytes. Stably transfected NIH-3T3 fibroblasts were used as second expression system. In proving the role of the NXI motif, variants p.I322V of GLUT2 and p.I296V of GLUT5 were tested as well. Sugar transport was measured by radiotracer flux assays or by metabolomics analysis of cell extracts by GC-MS. Fructose and glucose uptakes by GLUT7 were not increased in both expression systems. In search for the physiological substrate of GLUT7, cells overexpressing the protein were exposed to various metabolite mixtures, but we failed to identify a substrate. Although urate transport by GLUT9 could be shown, neither fructose nor glucose transport was detectable. Fructose uptake was decreased by the GLUT2 p.I322V variant, but remained unaffected in the p.I296V GLUT5 variant. Thus, our work does not find evidence that GLUT7 or GLUT9 transport fructose or glucose or that the isoleucine residue determines fructose specificity. Rather, the physiological substrate of GLUT7 awaits to be discovered.
authors.affiliation: Pediatric Nutritional Medicine, Klinikum rechts der Isar (MRI), Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München, Fachgebiet Pädiatrische Ernährungsmedizin, Gregor-Mendel-Str. 2, 85354, Freising, Germany.|ZIEL-Institute for Food and Health, Freising, Germany.
authors.forename: Karolin
authors.initials: K
authors.lastname: Ebert
authors.affiliation: Pediatric Nutritional Medicine, Klinikum rechts der Isar (MRI), Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München, Fachgebiet Pädiatrische Ernährungsmedizin, Gregor-Mendel-Str. 2, 85354, Freising, Germany.|ZIEL-Institute for Food and Health, Freising, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Ludwig
authors.affiliation: Chair of Nutritional Physiology, Technische Universität München, Freising, Germany.|ZIEL-Institute for Food and Health, Freising, Germany.
authors.forename: Kerstin Elisabeth
authors.initials: KE
authors.lastname: Geillinger
authors.affiliation: Pediatric Nutritional Medicine, Klinikum rechts der Isar (MRI), Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München, Fachgebiet Pädiatrische Ernährungsmedizin, Gregor-Mendel-Str. 2, 85354, Freising, Germany.|ZIEL-Institute for Food and Health, Freising, Germany.
authors.forename: Gina Catalina
authors.initials: GC
authors.lastname: Schoberth
authors.affiliation: Pediatric Nutritional Medicine, Klinikum rechts der Isar (MRI), Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München, Fachgebiet Pädiatrische Ernährungsmedizin, Gregor-Mendel-Str. 2, 85354, Freising, Germany.|ZIEL-Institute for Food and Health, Freising, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Essenwanger
authors.affiliation: Chair of Nutritional Physiology, Technische Universität München, Freising, Germany.|ZIEL-Institute for Food and Health, Freising, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Stolz
authors.affiliation: Chair of Nutritional Physiology, Technische Universität München, Freising, Germany.|ZIEL-Institute for Food and Health, Freising, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.affiliation: Pediatric Nutritional Medicine, Klinikum rechts der Isar (MRI), Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München, Fachgebiet Pädiatrische Ernährungsmedizin, Gregor-Mendel-Str. 2, 85354, Freising, Germany. heiko.witt@tum.de.|ZIEL-Institute for Food and Health, Freising, Germany. heiko.witt@tum.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Witt
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D005632:Fructose / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D009865:Oocytes / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D009004:Monosaccharide Transport Proteins; C487892:SLC2A7 protein, human; C411811:SLC2A9 protein, human; D005632:Fructose; D005947:Glucose
keywords: Fructose transport; GLUT5; GLUT7; GLUT9; Intestine