ArticlePloS one2013
Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Trial
- Metabolic Dysregulation in Laminopathies: Implications for Heart Failure and Cardiac Health.Current heart failure reports · 2026Review
- PGC-1α activity and mitochondrial dysfunction in preterm infants.Frontiers in physiology · 2022Review
- Skeletal muscle mitochondrial respiration in a model of age-related osteoarthritis is impaired after dietary rapamycin.Experimental gerontology · 2021Article
- Comparative analysis of long non‑coding RNA expression profiles induced by resveratrol and metformin treatment for hepatic insulin resistance.International journal of molecular medicine · 2021Article
- Suppression of Pyruvate Dehydrogenase Kinase by Dichloroacetate in Cancer and Skeletal Muscle Cells Is Isoform Specific and Partially Independent of HIF-1α.International journal of molecular sciences · 2021Article
- Inducible deletion of skeletal muscle AMPKα reveals that AMPK is required for nucleotide balance but dispensable for muscle glucose uptake and fat oxidation during exercise.Molecular metabolism · 2020Article
- Exercise-Pharmacology Interactions: Metformin, Statins, and Healthspan.Physiology (Bethesda, Md.) · 2020Review
- Benefits of Metformin in Attenuating the Hallmarks of Aging.Cell metabolism · 2020Review
- Taming expectations of metformin as a treatment to extend healthspan.GeroScience · 2019Review
- Metformin adapts its cellular effects to bioenergetic status in a model of metabolic dysfunction.Scientific reports · 2018Article
- Metformin Exerts Beneficial Effects in Hemorrhagic Shock in An AMPKα1-Independent Manner.Shock (Augusta, Ga.) · 2018Article
- Swim Training Modulates Skeletal Muscle Energy Metabolism, Oxidative Stress, and Mitochondrial Cholesterol Content in Amyotrophic Lateral Sclerosis Mice.Oxidative medicine and cellular longevity · 2018Article
- Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target.The Journal of pharmacology and experimental therapeutics · 2017Review
- Metformin Attenuates Cognitive Impairments in Hypoxia-Ischemia Neonatal Rats via Improving Remyelination.Cellular and molecular neurobiology · 2017Article
- Metformin ameliorates gender-and age-dependent hemodynamic instability and myocardial injury in murine hemorrhagic shock.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice.Aging and disease · 2017Article
- Beneficial effects of combined resveratrol and metformin therapy in treating diet-induced insulin resistance.Physiological reports · 2016Article
- Cardioprotective actions of Notch1 against myocardial infarction via LKB1-dependent AMPK signaling pathway.Biochemical pharmacology · 2016Article
- Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice.Behavioural brain research · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for diabetic muscles. The molecular mechanism behind the effect of metformin is not fully clarified but inhibition of complex I in the mitochondria and also activation of the 5'AMP activated protein kinase (AMPK) has been reported in muscle. Furthermore, both AMPK activation and metformin treatment have been associated with stimulation of mitochondrial function and biogenesis. However, a causal relationship in skeletal muscle has not been investigated. We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead α(2) (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued the respiration defect compared to the WT mice. Metformin did not influence protein activities or expressions in either WT or AMPK KD mice.We conclude that two weeks of in vivo metformin treatment enhances mitochondrial respiration in the mitochondrial deficient AMPK KD but not WT mice. The improvement seems to be unrelated to AMPK, and does not involve changes in key mitochondrial proteins.
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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.