New Insight Into Metformin Action: Regulation of ChREBP and FOXO1 Activities in Endothelial Cells

摘要: Metformin has been considered a potential adjunctive therapy in treating poorly controlled type 1 diabetes with obesity and insulin resistance, owing to its potent effects on improving sensitivity. However, the underlying mechanism of metformin's vascular protective remains obscure. Thioredoxin-interacting protein (TXNIP), key regulator cellular redox state induced by high-glucose concentration, decreases thioredoxin reductase activity mediates apoptosis oxidative stress. Here we report that high glucose-induced endothelial dysfunction is associated induction TXNIP expression primary human aortic cells exposed conditions, whereas metformin treatment suppresses high-glucose-induced at mRNA levels. We further show high-glucose-stimulated nuclear entry rate two transcription factors, carbohydrate response element-binding (ChREBP) forkhead box O1 (FOXO1), as well their recruitment promoter. An AMP-activated kinase inhibitor partially compromised these effects. Our data suggest resulting from concentrations expression. down-regulates inactivating ChREBP FOXO1 cells, through activation.