ArticleThe Journal of biological chemistry2013
Metformin increases mitochondrial energy formation in L6 muscle cell cultures.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials.BMC medicine · 2022Pooled it
- Novel effects of reverse transcriptase inhibitor supplementation in skeletal muscle of old mice.Physiological genomics · 2025Article
- Effects of long-term metformin administration associated with high-intensity interval training on physical performance, glycogen concentration, GLUT-4 content, and NMR-based metabolomics in healthy rats.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Article
- Metformin: A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area.International journal of molecular sciences · 2021Review
- Skeletal muscle mitochondrial respiration in a model of age-related osteoarthritis is impaired after dietary rapamycin.Experimental gerontology · 2021Article
- Differential effects of metformin on reductive activity and energy production in pituitary tumor cells compared to myogenic precursors.Endocrine · 2020Article
- Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells.Scientific reports · 2020Article
- How treatments with endocrine and metabolic drugs influence pituitary cell function.Endocrine connections · 2020Review
- Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis.Oxidative medicine and cellular longevity · 2019Article
- Article
- Effects of Rhizome Extract of Dioscorea batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes.Molecules (Basel, Switzerland) · 2018Article
- Metformin adapts its cellular effects to bioenergetic status in a model of metabolic dysfunction.Scientific reports · 2018Article
- Metformin Attenuates Cognitive Impairments in Hypoxia-Ischemia Neonatal Rats via Improving Remyelination.Cellular and molecular neurobiology · 2017Article
- Metformin prevents ischaemic ventricular fibrillation in metabolically normal pigs.Diabetologia · 2017Article
- Metformin Promotes Apoptosis but Suppresses Autophagy in Glucose-Deprived H4IIE Hepatocellular Carcinoma Cells.Diabetes & metabolism journal · 2015Article
- Effects of metformin, buformin, and phenformin on the post-initiation stage of chemically induced mammary carcinogenesis in the rat.Cancer prevention research (Philadelphia, Pa.) · 2015Article
- Metformin as a cellular protector; a synoptic view of modern evidences.Journal of nephropharmacology · 2015Review
- Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart.British journal of pharmacology · 2014Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A popular hypothesis for the action of metformin, the widely used anti-diabetes drug, is the inhibition of mitochondrial respiration, specifically at complex I. This is consistent with metformin stimulation of glucose uptake by muscle and inhibition of gluconeogenesis by liver. Yet, mitochondrial inhibition is inconsistent with metformin stimulation of fatty acid oxidation in both tissues. In this study, we measured mitochondrial energy production in intact cells adapting an in vivo technique of phosphocreatine (PCr) formation following energy interruption ("PCr recovery") to cell cultures. Metformin increased PCr recovery from either dinitrophenol (DNP) or azide in L6 cells. We found that metformin alone had no effect on cell viability as measured by total ATP concentration, trypan blue exclusion, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction. However, treatments with low concentrations of DNP or azide reversibly decreased ATP concentration. Metformin increased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction during recovery from either agent. Viability measured by trypan blue exclusion indicated that cells were intact under these conditions. We also found that metformin increased free AMP and, to a smaller extent, free ADP concentrations in cells, an action that was duplicated by a structurally unrelated AMP deaminase inhibitor. We conclude that, in intact cells, metformin can lead to a stimulation of energy formation, rather than an inhibition.
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What OpenQuestion holds
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.