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Cell Metab. 2012 Aug 8;16(2):265-73. doi: 10.1016/j.cmet.2012.07.005.

Thioredoxin-interacting protein mediates ER stress-induced β cell death through initiation of the inflammasome.

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  • 1Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

Recent clinical and experimental evidence suggests that endoplasmic reticulum (ER) stress contributes to the life-and-death decisions of β cells during the progression of type 1 and type 2 diabetes. Although crosstalk between inflammation and ER stress has been suggested to play a significant role in β cell dysfunction and death, a key molecule connecting ER stress to inflammation has not been identified. Here we report that thioredoxin-interacting protein (TXNIP) is a critical signaling node that links ER stress and inflammation. TXNIP is induced by ER stress through the PERK and IRE1 pathways, induces IL-1β mRNA transcription, activates IL-1β production by the NLRP3 inflammasome, and mediates ER stress-mediated β cell death. Collectively, our results suggest that TXNIP is a potential therapeutic target for diabetes and ER stress-related human diseases such as Wolfram syndrome.

Copyright © 2012 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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