title: Diabetes regulates fructose absorption through thioredoxin-interacting protein.
abstract: Metabolic studies suggest that the absorptive capacity of the small intestine for fructose is limited, though the molecular mechanisms controlling this process remain unknown. Here we demonstrate that thioredoxin-interacting protein (Txnip), which regulates glucose homeostasis in mammals, binds to fructose transporters and promotes fructose absorption by the small intestine. Deletion ofTxnipin mice reduced fructose transport into the peripheral bloodstream and liver, as well as the severity of adverse metabolic outcomes resulting from long-term fructose consumption. We also demonstrate that fructose consumption induces expression of Txnip in the small intestine. Diabetic mice had increased expression of Txnip in the small intestine as well as enhanced fructose uptake and transport into the hepatic portal circulation. The deletion ofTxnipin mice abolished the diabetes-induced increase in fructose absorption. Our results indicate that Txnip is a critical regulator of fructose metabolism and suggest that a diabetic state can promote fructose uptake.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Dotimas
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: Austin W
authors.initials: AW
authors.lastname: Lee
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Charlestown, United States.
authors.forename: Angela B
authors.initials: AB
authors.lastname: Schmider
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: Shannon H
authors.initials: SH
authors.lastname: Carroll
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: Anu
authors.initials: A
authors.lastname: Shah
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: Julide
authors.initials: J
authors.lastname: Bilen
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: Kayla R
authors.initials: KR
authors.lastname: Elliott
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Myers
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Charlestown, United States.|Molecular Imaging Core, Massachusetts General Hospital, Charlestown, United States.
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Soberman
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshioka
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
authors.forename: Richard T
authors.identifier: 0000-0003-4687-1381
authors.initials: RT
authors.lastname: Lee
mesh_terms: D000327:Adsorption; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004195:Disease Models, Animal; D005632:Fructose / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C445672:Txnip protein, mouse; D005632:Fructose; D013879:Thioredoxins
keywords: GLUT2; GLUT5; Txnip; biochemistry; cell biology; diabetes; fructose; metabolism; mouse