ArticleJournal of diabetes research2016
Metformin Protects H9C2 Cardiomyocytes from High-Glucose and Hypoxia/Reoxygenation Injury via Inhibition of Reactive Oxygen Species Generation and Inflammatory Responses: Role of AMPK and JNK.
Article in Journal of diabetes research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Renal Complications after Percutaneous Coronary Interventions on Concurrent Metformin Therapy: A Systematic Review with Meta-Analysis.Clinical medicine & research · 2023Pooled it
- Kaempferol attenuates LPS-induced inflammatory responses in H9c2 cells through involvement of the IL-6/JAK2/STAT3 pathway.Molecular biology reports · 2026Article
- 3D Bioprinted Fat-Myocardium Model Unravels the Role of Adipocyte Hypertrophy in Atrial Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Imeglimin Alleviates High-Glucose-Induced Bioenergetic and Oxidative Stress Thereby Enhancing Intercellular Adhesion in H9c2 Cardiomyoblasts.International journal of molecular sciences · 2025Article
- Isoform-specific roles of AMP-activated protein kinase in cardiac physiology and pathophysiology.Frontiers in cardiovascular medicine · 2025Review
- Molecular Basis of Cardiomyopathies in Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Pterostilbene Reverses Epigenetic Silencing of Nrf2 and Enhances Antioxidant Response in Endothelial Cells in Hyperglycemic Microenvironment.Nutrients · 2024Article
- OiScience · 2024Article
- Novel insights into the role of mitochondria in diabetic cardiomyopathy: molecular mechanisms and potential treatments.Cell stress & chaperones · 2023Review
- Role of gibberellins, neem leaf extract, and serine in improving wheat growth and grain yield under drought-triggered oxidative stress.Physiology and molecular biology of plants : an international journal of functional plant biology · 2023Article
- Metformin mitigates SASP secretion and LPS-triggered hyper-inflammation in Doxorubicin-induced senescent endothelial cells.Frontiers in aging · 2023Article
- Metformin Acutely Mitigates Oxidative Stress in Human Atrial Tissue: A Pilot Study in Overweight Non-Diabetic Cardiac Patients.Life (Basel, Switzerland) · 2022Article
- Bioactive Peptides and Exercise Modulate the AMPK/SIRT1/PGC-1α/FOXO3 Pathway as a Therapeutic Approach for Hypertensive Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Metformin: A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia.Pharmaceuticals (Basel, Switzerland) · 2022Review
- LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion InjuryFrontiers in cell and developmental biology · 2022Article
- Ginkgolide B Protects Against Ischemic StrokeFrontiers in pharmacology · 2022Article
- Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence.Biomolecules · 2021Review
- LncRNA-Fendrr protects against the ubiquitination and degradation of NLRC4 protein through HERC2 to regulate the pyroptosis of microglia.Molecular medicine (Cambridge, Mass.) · 2021Article
- Metformin protects high glucose‑cultured cardiomyocytes from oxidative stress by promoting NDUFA13 expression and mitochondrial biogenesis via the AMPK signaling pathway.Molecular medicine reports · 2020Article
- Inhibitory Action of Antidiabetic Drugs on the Free Radical Production by the Rod Outer Segment Ectopic Aerobic Metabolism.Antioxidants (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is a first-line drug for the management of type 2 diabetes. Recent studies suggested cardioprotective effects of metformin against ischemia/reperfusion injury. However, it remains elusive whether metformin provides direct protection against hypoxia/reoxygenation (H/R) injury in cardiomyocytes under normal or hyperglycemic conditions. This study in H9C2 rat cardiomyoblasts was designed to determine cell viability under H/R and high-glucose (HG, 33 mM) conditions and the effects of cotreatment with various concentrations of metformin (0, 1, 5, and 10 mM). We further elucidated molecular mechanisms underlying metformin-induced cytoprotection, especially the possible involvement of AMP-activated protein kinase (AMPK) and Jun NH(2)-terminal kinase (JNK). Results indicated that 5 mM metformin improved cell viability, mitochondrial integrity, and respiratory chain activity under HG and/or H/R (P < 0.05). The beneficial effects were associated with reduced levels of reactive oxygen species generation and proinflammatory cytokines (TNF-α, IL-1α, and IL-6) (P < 0.05). Metformin enhanced phosphorylation level of AMPK and suppressed HG + H/R induced JNK activation. Inhibitor of AMPK (compound C) or activator of JNK (anisomycin) abolished the cytoprotective effects of metformin. In conclusion, our study demonstrated for the first time that metformin possessed direct cytoprotective effects against HG and H/R injury in cardiac cells via signaling mechanisms involving activation of AMPK and concomitant inhibition of JNK.
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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.