Figure 2.

Regulation and signaling of β-cell TXNIP. β-Cell TXNIP expression is strongly induced by glucose and is increased in diabetes as well as in response to ER stress, and this induction is conferred at the transcriptional level by ChREBP and at the posttranscriptional level by a decrease in miR-17 and is modulated by a number of additional factors. TXNIP in turn inhibits thioredoxin function and promotes oxidative stress and β-cell death. In addition, by modulating the expression of distinct microRNAs (miR-204 and miR-124a) and with that the expression of their target genes (MafA and FoxA2) TXNIP inhibits insulin transcription while inducing IAPP transcription. These detrimental effects are further magnified by the fact that TXNIP promotes its own expression, again via ChREBP.