Thioredoxin-interacting protein stimulates its own expression via a positive feedback loop

Academic Article


  • Thioredoxin-interacting protein (TXNIP) has emerged as a key regulator of important cellular processes including redox state, inflammation, and apoptosis and plays a particularly critical role in pancreatic β-cell biology and diabetes development. High glucose and diabetes induce TXNIP expression, whereas inhibition of TXNIP expression or TXNIP deficiency protects against pancreatic β-cell apoptosis and diabetes. We now have discovered that TXNIP stimulates its own expression by promoting dephosphorylation and nuclear translocation of its transcription factor, carbohydrate response element-binding protein (ChREBP), resulting in a positive feedback loop as well as regulation of other ChREBP target genes playing important roles in glucose and lipid metabolism. Considering the detrimental effects of elevated TXNIP in β-cell biology, this novel pathway sheds new light onto the vicious cycle of increased TXNIP, leading to even more TXNIP expression, oxidative stress, inflammation, β-cell apoptosis, and diabetes progression. Moreover, the results demonstrate, for the first time, that TXNIP modulates ChREBP activity and thereby uncover a previously unappreciated link between TXNIP signaling and cell metabolism. © 2014 by the Endocrine Society.
  • Digital Object Identifier (doi)

    Author List

  • Chen J; Jing G; Xu G; Shalev A
  • Start Page

  • 674
  • End Page

  • 680
  • Volume

  • 28
  • Issue

  • 5