title: Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption.
abstract: Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.
authors.affiliation: *Department of Pharmacology and Physiology, New Jersey Medical School, and Department of Biological Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA.
authors.forename: Chirag
authors.initials: C
authors.lastname: Patel
authors.affiliation: *Department of Pharmacology and Physiology, New Jersey Medical School, and Department of Biological Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA.
authors.forename: Veronique
authors.initials: V
authors.lastname: Douard
authors.affiliation: *Department of Pharmacology and Physiology, New Jersey Medical School, and Department of Biological Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA.
authors.forename: Shiyan
authors.initials: S
authors.lastname: Yu
authors.affiliation: *Department of Pharmacology and Physiology, New Jersey Medical School, and Department of Biological Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Gao
authors.affiliation: *Department of Pharmacology and Physiology, New Jersey Medical School, and Department of Biological Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA ferraris@njms.rutgers.edu.
authors.forename: Ronaldo P
authors.initials: RP
authors.lastname: Ferraris
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D005631:Fructokinases / Q000235:genetics / Q000378:metabolism; D005632:Fructose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D051296:Glucose Transporter Type 5; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D005631:Fructokinases; D005632:Fructose; D051246:Glucose Transport Proteins, Facilitative; D051296:Glucose Transporter Type 5; D051269:Sodium-Glucose Transporter 1; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C465351:Slc2a5 protein, mouse; C495675:Slc5a1 protein, mouse; C021475:ketohexokinase
keywords: GLUT5; Rab11a; ketohexokinase; sugar