W2476 ameliorates β-cell dysfunction and exerts therapeutic effects in mouse models of diabetes via modulation of the thioredoxin-interacting protein signaling pathway.

ABSTRACT: Recent evidence shows that high glucose levels recruit carbohydrate response element-binding protein, which binds the promoter of thioredoxin-interacting protein (txnip), thereby regulating its expression in β-cells. Overexpression of txnip not only induces β-cell apoptosis but also reduces insulin production. Thus, the discovery of compounds that either inhibit TXNIP activity or suppress its expression was the focus of the present study. INS-1E cells stably transfected with either a txnip proximal glucose response element connected to a luciferase reporter plasmid (BG73) or full-length txnip promoter connected to a luciferase reporter plasmid (CL108) were used in primary and secondary high-throughput screening campaigns, respectively. From 256 000 synthetic compounds, a small molecule com

SUBMITTER: Li T 

PROVIDER: S-EPMC5519249 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature