ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Two weeks of metformin treatment induces AMPK-dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 83 citations in OpenAlex.
- DMH1 improves palmitic acid-Induced insulin resistance in cardiomyocytes via PP2A inhibition and AKT/AMPK signaling activation.Scientific reports · 2026Article
- Impact of Metformin Therapy on Vitamin B12 Levels in Patients With Type 2 Diabetes Mellitus.Endocrinology, diabetes & metabolism · 2025Article
- New Perspectives on the Molecular Action of Metformin in the Context of Cellular Transduction and Adipogenesis.International journal of molecular sciences · 2025Review
- Article
- Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise.Nature metabolism · 2024Article
- PAK4 phosphorylates and inhibits AMPKα to control glucose uptake.Nature communications · 2024Article
- Association of metabolic-dysfunction associated steatotic liver disease with polycystic ovary syndrome.iScience · 2024Review
- 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
- Review
- Redox state and altered pyruvate metabolism contribute to a dose-dependent metformin-induced lactate production of human myotubes.American journal of physiology. Cell physiology · 2023Article
- Metabolic Action of Metformin.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport.International journal of molecular sciences · 2022Review
- Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.PloS one · 2022Article
- PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle.Frontiers in endocrinology · 2022Article
- Metabolomic Approaches to Investigate the Effect of Metformin: An Overview.International journal of molecular sciences · 2021Review
- Vanillin modulates activities linked to dysmetabolism in psoas muscle of diabetic rats.Scientific reports · 2021Article
- Review
- The Current and Potential Therapeutic Use of Metformin-The Good Old Drug.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Comparison of Visceral Fat Reduction by Ipragliflozin and Metformin in Elderly Type 2 Diabetes Patients: Sub-Analysis of a Randomized-Controlled Study.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2021Article
- PGC-1α-Targeted Therapeutic Approaches to Enhance Muscle Recovery in Aging.International journal of environmental research and public health · 2020Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
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Abstract
Metformin-induced activation of the 5'-AMP-activated protein kinase (AMPK) has been associated with enhanced glucose uptake in skeletal muscle, but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent on AMPK signaling. Oral doses of metformin or saline treatment were given to muscle-specific kinase dead (KD) AMPKα2 mice and wild-type (WT) littermates either once or chronically for 2 wk. Soleus and extensor digitorum longus muscles were used for measurements of glucose transport and Western blot analyses. Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (∼45%, P < 0.01) but not of AMPK KD mice. Insulin signaling at the level of Akt protein expression or Thr(308) and Ser(473) phosphorylation was not changed by metformin treatment. Insulin signaling at the level of Akt and TBC1D4 protein expression as well as Akt Thr(308)/Ser(473) and TBC1D4 Thr(642)/Ser(711) phosphorylation were not changed by metformin treatment. Also, protein expressions of Rab4, GLUT4, and hexokinase II were unaltered after treatment. The acute metformin treatment did not affect glucose uptake in muscle of either of the genotypes. In conclusion, we provide novel evidence for a role of AMPK in potentiating the effect of insulin on glucose uptake in soleus muscle in response to chronic metformin treatment.
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Registered trials
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