ArticleMolecular endocrinology (Baltimore, Md.)2015
New Insight Into Metformin Action: Regulation of ChREBP and FOXO1 Activities in Endothelial Cells.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- Sugar Shockwaves: How the Fructose-Glucose-ChREBP Pathway Hijacks Liver Metabolism.Life (Basel, Switzerland) · 2026Review
- Unraveling the role of ChREBP in lung adenocarcinoma: Expression, regulatory networks, and potential functional impact.PloS one · 2026Article
- Metformin Inhibits Inflammation by Targeting the NLRP3 Inflammasome: Linking NF-κB/NEK7/AMPK Signaling to Mitochondrial Function.Journal of inflammation research · 2026Review
- Effect of metformin in a novel experimental model of peripheral artery disease.Clinical science (London, England : 1979) · 2025Article
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on β-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study.International journal of molecular sciences · 2025Article
- Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes.Circulation research · 2024Article
- Rutin attenuates ensartinib-induced hepatotoxicity by non-transcriptional regulation of TXNIP.Cell biology and toxicology · 2024Article
- Metformin alleviates bevacizumab-induced vascular endothelial injury in mice through growth differentiation factor 15 upregulation.Iranian journal of basic medical sciences · 2024Article
- The role of ChREBP in carbohydrate sensing and NAFLD development.Nature reviews. Endocrinology · 2023Review
- Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis of insulin resistance, beta-cell glucotoxicity, and diabetic vascular complications.Frontiers in endocrinology · 2023Article
- TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients.Medicine and pharmacy reports · 2022Review
- Article
- Phenothiazine Inhibits Neuroinflammation and Inflammasome Activation Independent of Hypothermia After Ischemic Stroke.Molecular neurobiology · 2021Article
- Effect of Sleeve Gastrectomy on Plasma Thioredoxin-Interacting Protein (TXNIP).Obesity surgery · 2021Article
- PHLPP1/Nrf2-Mdm2 axis induces renal apoptosis via influencing nucleo-cytoplasmic shuttling of FoxO1 during diabetic nephropathy.Molecular and cellular biochemistry · 2021Article
- Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook.International journal of molecular sciences · 2021Review
- The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target.International journal of molecular sciences · 2021Review
- Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function.Theranostics · 2021Review
- Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells.Cell metabolism · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.