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Elife. 2016 Oct 11;5. pii: e18313. doi: 10.7554/eLife.18313.

Diabetes regulates fructose absorption through thioredoxin-interacting protein.

Author information

1
Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.
2
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
3
Nephrology Division, Department of Medicine, Massachusetts General Hospital, Charlestown, United States.
4
Molecular Imaging Core, Massachusetts General Hospital, Charlestown, United States.

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 of Txnip in 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 of Txnip in 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.

KEYWORDS:

GLUT2; GLUT5; Txnip; biochemistry; cell biology; diabetes; fructose; metabolism; mouse

PMID:
27725089
PMCID:
PMC5059142
DOI:
10.7554/eLife.18313
[Indexed for MEDLINE]
Free PMC Article

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