ArticleDiabetes2015
Methotrexate promotes glucose uptake and lipid oxidation in skeletal muscle via AMPK activation.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review.Cells · 2021Pooled it
- Pooled it
- From Joints to Arteries: How Rheumatoid Arthritis Therapies Influence Atherosclerotic Cardiovascular Disease Risk.Journal of the American Heart Association · 2026Review
- Recent advances in methotrexate pharmacology and potential therapeutic uses in age-related cardiometabolic and neurodegenerative diseases.Pharmacological reviews · 2026Review
- CXCL2 is a modifiable driver of sarcopenic inflammation attenuated by exercise in older women: Integrated transcriptomic and experimental evidence.Journal of sport and health science · 2026Article
- Metabolic and Anthropometric Alterations in Juvenile Idiopathic Arthritis: A Focus on Cardiometabolic Risk and Non-Invasive Evaluation Methods.Metabolites · 2026Review
- Importance of the electrophoresis and pulse energy for siRNA-mediated gene silencing by electroporation in differentiated primary human myotubes.Biomedical engineering online · 2024Article
- Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus.Journal of cachexia, sarcopenia and muscle · 2023Article
- Drug dosage modifications in 24 million in-patient prescriptions covering eight years: A Danish population-wide study of polypharmacy.PLOS digital health · 2023Article
- Immunometabolism at the Heart of Cardiovascular Disease.JACC. Basic to translational science · 2023Review
- A cellular overview of immunometabolism in systemic lupus erythematosus.Oxford open immunology · 2023Review
- Research progress of AMP-activated protein kinase and cardiac aging.Open life sciences · 2023Review
- AICAR Improves Outcomes of Metabolic Syndrome and Type 2 Diabetes Induced by High-Fat Diet in C57Bl/6 Male Mice.International journal of molecular sciences · 2022Article
- ATIC-Associated De Novo Purine Synthesis Is Critically Involved in Proliferative Arterial Disease.Circulation · 2022Article
- AICAR promotes endothelium-independent vasorelaxation by activating AMP-activated protein kinase via increased ZMP and decreased ATP/ADP ratio in aortic smooth muscle.Journal of basic and clinical physiology and pharmacology · 2022Article
- B7-H4 Polymorphism Influences the Prevalence of Diabetes Mellitus and Pro-Atherogenic Dyslipidemia in Patients with Psoriasis.Journal of clinical medicine · 2022Article
- Diabetes-Modifying Antirheumatic Drugs: The Roles of DMARDs as Glucose-Lowering Agents.Medicina (Kaunas, Lithuania) · 2022Review
- Emerging Glycation-Based Therapeutics-Glyoxalase 1 Inducers and Glyoxalase 1 Inhibitors.International journal of molecular sciences · 2022Review
- Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies.The Journal of clinical investigation · 2022Review
- Phosphorylation of NaThe Journal of membrane biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Methotrexate (MTX) is a widely used anticancer and antirheumatic drug that has been postulated to protect against metabolic risk factors associated with type 2 diabetes, although the mechanism remains unknown. MTX inhibits 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC) and thereby slows the metabolism of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl-5'-monophosphate (ZMP) and its precursor AICAR, which is a pharmacological AMPK activator. We explored whether MTX promotes AMPK activation in cultured myotubes and isolated skeletal muscle. We found MTX markedly reduced the threshold for AICAR-induced AMPK activation and potentiated glucose uptake and lipid oxidation. Gene silencing of the MTX target ATIC activated AMPK and stimulated lipid oxidation in cultured myotubes. Furthermore, MTX activated AMPK in wild-type HEK-293 cells. These effects were abolished in skeletal muscle lacking the muscle-specific, ZMP-sensitive AMPK-γ3 subunit and in HEK-293 cells expressing a ZMP-insensitive mutant AMPK-γ2 subunit. Collectively, our findings underscore a role for AMPK as a direct molecular link between MTX and energy metabolism in skeletal muscle. Cotherapy with AICAR and MTX could represent a novel strategy to treat metabolic disorders and overcome current limitations of AICAR monotherapy.
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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.