• Home
  • Search Results
  • New Insight Into Metformin Action: Regulation of ChREBP and FOXO1 Activities in Endothelial Cells.

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

Molecular endocrinology (Baltimore, Md.) (2015-07-07)
Xiaoyu Li, Karen L Kover, Daniel P Heruth, Dara J Watkins, Wayne V Moore, Kathyrin Jackson, Mengwei Zang, Mark A Clements, Yun Yan
ABSTRACT

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

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
Sodium chloride, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
HEPES, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
Sigma-Aldrich
Streptozocin, ≥75% α-anomer basis, ≥98% (HPLC), powder
Sigma-Aldrich
Sodium chloride, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
D-Mannitol, ≥98%
Sigma-Aldrich
Sodium chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
Sodium chloride solution, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
Sodium chloride solution, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
HEPES buffer solution, 1 M in H2O
Sigma-Aldrich
Sodium chloride solution, 5 M
SAFC
Sodium chloride solution, 5 M
SAFC
HEPES
Sigma-Aldrich
Sodium pyrophosphate tetrabasic, ≥95%
Sigma-Aldrich
Sodium chloride, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%
Sigma-Aldrich
D-Mannitol, ACS reagent
Sigma-Aldrich
HEPES, BioUltra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
1,1-Dimethylbiguanide hydrochloride, 97%
Sigma-Aldrich
Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
D-Mannitol, meets EP, FCC, USP testing specifications
Sigma-Aldrich
Sodium chloride solution, 0.85%
Sigma-Aldrich
Sodium chloride solution, BioUltra, for molecular biology, ~5 M in H2O
Sigma-Aldrich
D-Mannitol, BioXtra, ≥98% (HPLC)
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis
Sigma-Aldrich
D-Mannitol, suitable for plant cell culture
Sigma-Aldrich
HEPES, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
SAFC
HEPES
Sigma-Aldrich
Sodium chloride, BioPerformance Certified, ≥99% (titration), suitable for insect cell culture, suitable for plant cell culture
Sigma-Aldrich
HEPES, BioXtra, suitable for mouse embryo cell culture, ≥99.5% (titration)
Sigma-Aldrich
D-Mannitol, BioUltra, ≥99.0% (sum of enantiomers, HPLC)