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Publication : Dual regulation of TxNIP by ChREBP and FoxO1 in liver.

First Author  Noblet B Year  2021
Journal  iScience Volume  24
Issue  3 Pages  102218
PubMed ID  33748706 Mgi Jnum  J:370377
Mgi Id  MGI:6717796 Doi  10.1016/j.isci.2021.102218
Citation  Noblet B, et al. (2021) Dual regulation of TxNIP by ChREBP and FoxO1 in liver. iScience 24(3):102218
abstractText  TxNIP (Thioredoxin-interacting protein) is considered as a potential drug target for type 2 diabetes. Although TxNIP expression is correlated with hyperglycemia and glucotoxicity in pancreatic beta cells, its regulation in liver cells has been less investigated. In the current study, we aim at providing a better understanding of Txnip regulation in hepatocytes in response to physiological stimuli and in the context of hyperglycemia in db/db mice. We focused on regulatory pathways governed by ChREBP (Carbohydrate Responsive Element Binding Protein) and FoxO1 (Forkhead box protein O1), transcription factors that play central roles in mediating the effects of glucose and fasting on gene expression, respectively. Studies using genetically modified mice reveal that hepatic TxNIP is up-regulated by both ChREBP and FoxO1 in liver cells and that its expression strongly correlates with fasting, suggesting a major role for this protein in the physiological adaptation to nutrient restriction.
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