Diabetes regulates fructose absorption through thioredoxin-interacting protein
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 f...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-10-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/18313 |
| _version_ | 1811199792538189824 |
|---|---|
| author | James R Dotimas Austin W Lee Angela B Schmider Shannon H Carroll Anu Shah Julide Bilen Kayla R Elliott Ronald B Myers Roy J Soberman Jun Yoshioka Richard T Lee |
| author_facet | James R Dotimas Austin W Lee Angela B Schmider Shannon H Carroll Anu Shah Julide Bilen Kayla R Elliott Ronald B Myers Roy J Soberman Jun Yoshioka Richard T Lee |
| author_sort | James R Dotimas |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:53:18Z |
| format | Article |
| id | doaj.art-feec9b69db374cbf80e078c2f6484bd5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:53:18Z |
| publishDate | 2016-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-feec9b69db374cbf80e078c2f6484bd52022-12-22T03:52:52ZengeLife Sciences Publications LtdeLife2050-084X2016-10-01510.7554/eLife.18313Diabetes regulates fructose absorption through thioredoxin-interacting proteinJames R Dotimas0Austin W Lee1Angela B Schmider2Shannon H Carroll3Anu Shah4Julide Bilen5Kayla R Elliott6Ronald B Myers7Roy J Soberman8Jun Yoshioka9Richard T Lee10https://orcid.org/0000-0003-4687-1381Department 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 StatesDepartment 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 StatesNephrology Division, Department of Medicine, Massachusetts General Hospital, Charlestown, United StatesDepartment 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 StatesDepartment 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 StatesDepartment 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 StatesDepartment 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 StatesDepartment 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 StatesNephrology Division, Department of Medicine, Massachusetts General Hospital, Charlestown, United States; Molecular Imaging Core, Massachusetts General Hospital, Charlestown, United StatesDepartment 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 StatesDepartment 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 StatesMetabolic 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.https://elifesciences.org/articles/18313fructosediabetesmetabolismTxnipGLUT2GLUT5 |
| spellingShingle | James R Dotimas Austin W Lee Angela B Schmider Shannon H Carroll Anu Shah Julide Bilen Kayla R Elliott Ronald B Myers Roy J Soberman Jun Yoshioka Richard T Lee Diabetes regulates fructose absorption through thioredoxin-interacting protein eLife fructose diabetes metabolism Txnip GLUT2 GLUT5 |
| title | Diabetes regulates fructose absorption through thioredoxin-interacting protein |
| title_full | Diabetes regulates fructose absorption through thioredoxin-interacting protein |
| title_fullStr | Diabetes regulates fructose absorption through thioredoxin-interacting protein |
| title_full_unstemmed | Diabetes regulates fructose absorption through thioredoxin-interacting protein |
| title_short | Diabetes regulates fructose absorption through thioredoxin-interacting protein |
| title_sort | diabetes regulates fructose absorption through thioredoxin interacting protein |
| topic | fructose diabetes metabolism Txnip GLUT2 GLUT5 |
| url | https://elifesciences.org/articles/18313 |
| work_keys_str_mv | AT jamesrdotimas diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT austinwlee diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT angelabschmider diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT shannonhcarroll diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT anushah diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT julidebilen diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT kaylarelliott diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT ronaldbmyers diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT royjsoberman diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT junyoshioka diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein AT richardtlee diabetesregulatesfructoseabsorptionthroughthioredoxininteractingprotein |