ArticleCell reports2019
Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 2 of them syntheses that pooled it.
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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
239 citing papers in PubMed, 2 syntheses or guidelines pooled it, 411 citations in OpenAlex.
- Food-derived dihydromyricetin and metabolic dysfunction-associated steatotic liver disease: a preclinical systematic review and meta-analysis.Frontiers in nutrition · 2026Pooled it
- The Effect of Metformin on Bladder Cancer Incidence and Outcomes: A Systematic Review and Meta-Analysis.Bladder cancer (Amsterdam, Netherlands) · 2022Pooled it
- Repeated application of passive mechanical stress produces selective metabolic and extracellular matrix adaptations in human skeletal muscle but does not prevent disuse-induced atrophy.Function (Oxford, England) · 2026Trial
- Multiparameter MRI assessment of metformin and exercise effects on skeletal muscle in prediabetes: a randomized controlled trial.European radiology experimental · 2025Trial
- Glucose-induced histone lactylation confers metformin resistance in colorectal cancer stem cells.Nature communications · 2026Article
- The coordinated actions of metformin in the intestine and liver improves hyperglycemia.Cell reports · 2026Article
- The mTOR/AMPK signaling axis in placental dysfunction and preeclampsia: mechanisms and therapeutic targeting with metformin.Molecular biology reports · 2026Review
- Article
- The zinc-nitric oxide axis in acute brain injury: Convergent oxidative-nitrative stress, peroxynitrite signaling, and therapeutic targets.Redox biology · 2026Review
- Metformin inhibits PDGFβ signaling to suppress hyaluronan and cytokine production in thyroid eye disease.Experimental eye research · 2026Article
- Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy.FEBS open bio · 2026Article
- Metformin beyond Glycemic Control: New Mechanistic Insights and Expanding Therapeutic Horizons.Diabetes & metabolism journal · 2026Review
- Metformin treatment impairs the adenine nucleotide translocator activity and energy metabolism in human clear cell renal carcinoma cells.Scientific reports · 2026Article
- Mitochondrial Functional Capacity Is Impaired in Angiotensin II-Infused Mice and Not Recovered by Metformin.Biomedicines · 2026Article
- Headache associated with adverse cognitive trajectories in Chinese aging cohort: a group-based trajectory modeling study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- The Interaction Between Mitophagy Dysregulation and the Diabetic Bladder Microenvironment.Journal of diabetes · 2026Review
- Male obesity causes adipose mitochondrial dysfunction in FNature communications · 2026Article
- Multimodal Therapeutic Strategies for the Management of Sarcopenia and Frailty in Chronic Obstructive Pulmonary Disease: A Narrative Review.Nutrients · 2026Review
- Diabetes management in maternally inherited diabetes and deafness (MIDD): A review and a proposed treatment algorithm.Diabetes, obesity & metabolism · 2026Review
- Molecular mechanisms of metformin action: From metabolic effects to lifespan extension and healthspan promotion.Journal of medical biochemistry · 2026Article
179 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Impaired mitochondrial respiratory activity contributes to the development of insulin resistance in type 2 diabetes. Metformin, a first-line antidiabetic drug, functions mainly by improving patients' hyperglycemia and insulin resistance. However, its mechanism of action is still not well understood. We show here that pharmacological metformin concentration increases mitochondrial respiration, membrane potential, and ATP levels in hepatocytes and a clinically relevant metformin dose increases liver mitochondrial density and complex 1 activity along with improved hyperglycemia in high-fat- diet (HFD)-fed mice. Metformin, functioning through 5' AMP-activated protein kinase (AMPK), promotes mitochondrial fission to improve mitochondrial respiration and restore the mitochondrial life cycle. Furthermore, HFD-fed-mice with liver-specific knockout of AMPKα1/2 subunits exhibit higher blood glucose levels when treated with metformin. Our results demonstrate that activation of AMPK by metformin improves mitochondrial respiration and hyperglycemia in obesity. We also found that supra-pharmacological metformin concentrations reduce adenine nucleotides, resulting in the halt of mitochondrial respiration. These findings suggest a mechanism for metformin's anti-tumor effects.
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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.