ArticleThe Journal of biological chemistry2015
Metformin activates AMP-activated protein kinase by promoting formation of the αβγ heterotrimeric complex.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- mTOR Inhibitors in Castration-Resistant Prostate Cancer: A Systematic Review.Targeted oncology · 2017Pooled it
- Enhancing the Efficacy of Metformin in Neoadjuvant Therapy for Breast Cancer: A Meta-Analysis Based on Randomized Clinical Trials.Cancer control : journal of the Moffitt Cancer CenterPooled it
- Extracellular Matrix-MYCAF Signatures Correlate with Resistance to Neoadjuvant aPD-L1 Immune Checkpoint Inhibition with Durvalumab + Metformin in HPV+ HNSCC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Metformin in Diabetes and Beyond: Therapeutic Mechanisms, Lactic Acidosis, Organ-Specific Effects, and Nanotechnology-Based Delivery Strategies.Current medical science · 2026Review
- Targeting GSTZ1 Sensitizes KRASG12C-Mutant Lung Cancer Cells by Overcoming Glutathione and Glycolysis Pathway Rewiring.Cancer research communications · 2026Article
- Metformin beyond Glycemic Control: New Mechanistic Insights and Expanding Therapeutic Horizons.Diabetes & metabolism journal · 2026Review
- Metformin drives HIF-1α-mediated dual metabolic reprogramming to enhance γδ T cell therapy in triple-negative breast cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Metformin-A Type 2 Diabetes Mellitus Drug-And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Piperine-induced AMPK activation and cell cycle arrest: insights from molecular simulations and experimental validation in breast cancer.Medical oncology (Northwood, London, England) · 2026Article
- Promoting Autophagy Mitigates Stress-Induced Remodeling in Patient iPSC-CMs with the Phospholamban R9C Mutation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metformin Protects Against Persistent Atrial Fibrillation in an Equine Model.Circulation. Arrhythmia and electrophysiology · 2025Article
- Targeting Lipophagy in Liver Diseases: Impact on Oxidative Stress and Steatohepatitis.Antioxidants (Basel, Switzerland) · 2025Review
- Targeting negative phosphorylation to activate AMPK.Endocrine connections · 2025Article
- Therapeutic effects of metformin on cocaine conditioned place preference and locomotion.Behavioral neuroscience · 2025Article
- AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia.The Journal of clinical investigation · 2025Article
- Autophagy in adult stem cell homeostasis, aging, and disease therapy.Cell regeneration (London, England) · 2025Review
- Unraveling the Ties: Type 2 Diabetes and Parkinson's Disease - A Nano-Based Targeted Drug Delivery Approach.Current diabetes reviews · 2025Review
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- AMPK in Intestinal Health and Disease: A Multifaceted Therapeutic Target for Metabolic and Inflammatory Disorders.Drug design, development and therapy · 2025Review
- STARD7 maintains intestinal epithelial mitochondria architecture, barrier integrity, and protection from colitis.JCI insight · 2024Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Metformin is the most widely prescribed oral anti-diabetic agent. Recently, we have shown that low metformin concentrations found in the portal vein suppress glucose production in hepatocytes through activation of AMPK. Moreover, low concentrations of metformin were found to activate AMPK by increasing the phosphorylation of AMPKα at Thr-172. However, the mechanism underlying the increase in AMPKα phosphorylation at Thr-172 and activation by metformin remains unknown. In the current study, we find that low concentrations of metformin promote the formation of the AMPK αβγ complex, resulting in an increase in net phosphorylation of the AMPK α catalytic subunit at Thr-172 by augmenting phosphorylation by LKB1 and antagonizing dephosphorylation by PP2C.
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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.