摘要：SummaryTxNIP (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 β cells, its regulation in liver cells has been less investigated. In the current study, we aim at providing a better understanding ofTxnipregulation in hepatocytes in response to physiological stimuli and in the context of hyperglycemia indb/dbmice. 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.Graphical abstractDisplay OmittedHighlights•TxNIP is considered as a potential candidate drug target for type 2 diabetes•We provide better understanding ofTxnipregulation and function in liver•HepaticTxnipis up-regulated by both ChREBP and FoxO1 transcription factors•We suggest a role for TxNIP in the physiological adaptation to nutrient restrictionMolecular Physiology ; Molecular Biology ; Endocrinology
