Covalent binding of thioredoxin to TXNIP is required for diet-induced insulin resistance in the liver.

ABSTRACT: Hepatic insulin resistance is an important pathophysiology in type 2 diabetes, and the mechanisms by which high-caloric diets induce insulin resistance are unclear. Among vertebrate animals, mammals have retained a unique molecular change that allows an intracellular arrestin domain-containing protein called Thioredoxin-Interacting Protein (TXNIP) to bind covalently to thioredoxin, allowing TXNIP to "sense" oxidative stress. Here, we show that a single cysteine in TXNIP mediates the development of hepatic insulin resistance in the setting of a high-fat diet (HFD). Mice with an exchange of TXNIP Cysteine 247 for Serine (C247S) showed improved whole-body and hepatic insulin sensitivity compared with WT controls following an 8-week HFD. HFD-fed TXNIP C247S mouse livers also showed improved in

SUBMITTER: Dagdeviren S 

PROVIDER: S-EPMC12180993 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature