English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/216970
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Absence of TXNIP in humans leads to lactic acidosis and low serum methionine linked to deficient respiration on pyruvate

Authorskatsu-Jiménez, Yurika; Vázquez-Calvo, Carmela; Maffezzini, Camilla; Halldin, María; Peng, Xiaoxiao; Freyer, Xiaoxiao; Wredenberg,Anna; Giménez-Cassina, Alfredo; Wedell, Anna; Arner, Elias S.J
Issue Date21-Jan-2019
CitationDiabetes 68: 709-723 (2019)
AbstractThioredoxin-interacting protein (TXNIP) is an a-arrestin that can bind to and inhibit the antioxidant protein thioredoxin (TXN). TXNIP expression is induced by glucose and promotes b-cell apoptosis in the pancreas, and deletion of its gene in mouse models protects against diabetes. TXNIP is currently studied as a potential new target for antidiabetic drug therapy. In this study, we describe a family with a mutation in the TXNIP gene leading to nondetectable expression of TXNIP protein. Symptoms of affected family members include lactic acidosis and low serum methionine levels. Using patient-derived TXNIP-deficient fibroblasts and myoblasts, we show that oxidative phosphorylation is impaired in these cells when given glucose and pyruvate but normalized with malate. Isolated mitochondria from these cells appear to have normal respiratory function. The cells also display a transcriptional pattern suggestive of a high basal activation of the Nrf2 transcription factor. We conclude that a complete lack of TXNIP in human is nonlethal and leads to specific metabolic distortions that are, at least in part, linked to a deficient respiration on pyruvate. The results give important insights into the impact of TXNIP in humans and thus help to further advance the development of antidiabetic drugs targeting this protein.
Publisher version (URL)http://dx.doi.org/10.2337/db18-0557
Identifiersdoi: 10.2337/db18-0557
issn: 1939-327X
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
Giménez-CassinaA_AbsenceofTXNIPinHumans.pdf1,7 MBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.