ArticleInternational journal of cardiology2009
Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation.
Article in International journal of cardiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01410604. Cited by 73 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.
Inflammatory Mediators in Obese Adolescents With Insulin Resistance Following Metformin Treatment: Controlled Randomized Clinical Trial
Who cites it
73 citing papers in PubMed, 158 citations in OpenAlex.
- Differential effect of concomitant antidiabetic agents on carotid atherosclerosis: a subgroup analysis of the PROLOGUE study.Heart and vessels · 2019Trial
- Article
- The Gut Microbiota-Related Antihyperglycemic Effect of Metformin.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Chemotherapy-Induced Peripheral Neuropathy: A Recent Update on Pathophysiology and Treatment.Life (Basel, Switzerland) · 2024Review
- Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS.The Journal of clinical endocrinology and metabolism · 2023 · on this mapArticle
- Anti-inflammatory therapy of atherosclerosis: focusing on IKKβ.Journal of inflammation (London, England) · 2023Review
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- Endothelial AMPKα1/PRKAA1 exacerbates inflammation in HFD-fed mice.British journal of pharmacology · 2022Article
- A Novel Pyrazolo[3,4-Molecules and cells · 2022Article
- Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients.Frontiers in molecular biosciences · 2022Review
- Effects of antidiabetic agents on Alzheimer's disease biomarkers in experimentally induced hyperglycemic rat model by streptozocin.PloS one · 2022Article
- AICAR decreases acute lung injury by phosphorylating AMPK and upregulating heme oxygenase-1.The European respiratory journal · 2021Article
- Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated fromBiomolecules · 2021Article
- Metformin acts to suppress β-hydroxybutyric acid-mediated inflammatory responses through activation of AMPK signaling in bovine hepatocytes.Journal of animal science · 2021Article
- The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus.International journal of molecular sciences · 2021Review
- Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System.Biomedicines · 2021Review
- Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Neuroinflammatory Triangle Presenting Novel Pharmacological Targets for Ischemic Brain Injury.Frontiers in immunology · 2021Review
- Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function.Theranostics · 2021Review
- A new aspect of an old friend: the beneficial effect of metformin on anti-tumor immunity.BMB reports · 2020Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetformin has been reported to reduce cardiovascular complications in diabetic patients. The purpose of the present study was to investigate the anti-inflammatory effects of metformin on endothelial cells and the related molecular mechanisms.
methodsHuman umbilical vein endothelial cells (HUVEC) were used for the experiments. The effects of metformin on TNF-alpha-induced IL-6 production were investigated. Modulation of AMPK and related signal transduction pathways were also performed.
resultsTNF-alpha increased IL-6 secretion by HUVEC in a dose-dependent manner but inhibitors of NF-kappaB abolished the TNF-alpha-induced IL-6 production. Pre-treatment with metformin (100-1000 micromol/L) also inhibited TNF-alpha-induced IL-6 production, phosphorylation of IkappaB kinase (IKK) alpha/beta and IkappaB-alpha degradation. Metformin increased phosphorylation of AMP-activated kinase (AMPK) but wortmannin, a PI3K inhibitor, negated its effects on AMPK phosphorylation and TNF-alpha-induced IkappaB-alpha degradation. AICAR, a direct AMPK activator, had inhibitory effects on TNF-alpha-induced IL-6 production, similar to that of metformin. Transfection of siRNA against alpha1-AMPK eradicated the inhibitory effects of metformin on TNF-alpha-induced IL-6, implying the essential role of AMPK.
conclusionsMetformin had anti-inflammatory effects on endothelial cells and inhibited TNF-alpha-induced IKKalpha/beta phosphorylation, IkappaB-alpha degradation and IL-6 production in HUVEC. This effect was related to PI3K-dependent AMPK phosphorylation.
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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 Socratic graph.