ArticleThe Journal of biological chemistry2012
Metformin regulates glucose transporter 4 (GLUT4) translocation through AMP-activated protein kinase (AMPK)-mediated Cbl/CAP signaling in 3T3-L1 preadipocyte cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Pooled it
- Exploring the therapeutic response to sodium-glucose cotransporter-2 inhibition in INSR-related insulin resistance monogenic diabetes: case-based analysis and narrative review.Acta diabetologica · 2026Article
- Metabolomic Insights on Obesity and Diabetes from Feeding Diets Varying in Carbohydrate-Fat Ratios in Zucker Diabetic Fatty (ZDF) and Lean Zucker (ZInternational journal of molecular sciences · 2026Article
- Novel combination therapy with phenformin enhances the effects of lenvatinib in hepatocellular carcinoma via AMPK-mediated PDGFRβ degradation.Cancer cell international · 2025Article
- Immunometabolic alterations induced by GBD surgery and adjunct pharmacotherapy with metformin, orlistat, statins, and ACE inhibitors.Molecular biology reports · 2025Article
- Metformin Beyond Diabetes: A Precision Gerotherapeutic and Immunometabolic Adjuvant for Aging and Cancer.Cancers · 2025Review
- Severe Insulin Resistance Syndromes: Clinical Spectrum and Management.International journal of molecular sciences · 2025Review
- New Perspectives on the Molecular Action of Metformin in the Context of Cellular Transduction and Adipogenesis.International journal of molecular sciences · 2025Review
- Fungal Depsidones Stimulate AKT-Dependent Glucose Uptake in 3T3-L1 Adipocytes.Journal of natural products · 2024Article
- Metformin Restrains the Proliferation of CD4+ T Lymphocytes by Inducing Cell Cycle Arrest in Normo- and Hyperglycemic Conditions.Biomolecules · 2024Article
- Alpha-lipoic Acid Prevents Bone Loss in Type 2 Diabetes and Postmenopausal Osteoporosis Coexisting Conditions by Modulating the YAP/Glut4 Pathway.Cell biochemistry and biophysics · 2024Article
- Glycolipids Derived from the Korean Endemic PlantPlants (Basel, Switzerland) · 2024Article
- 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
- Research advances in the therapy of metabolic syndrome.Frontiers in pharmacology · 2024Review
- Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells.Exploration of targeted anti-tumor therapy · 2024Article
- Article
- Antihyperglycemic Properties of Extracts and Isolated Compounds from AustralianMolecules (Basel, Switzerland) · 2023Article
- SIRT3/GLUT4 signaling activation by metformin protect against cisplatin-induced ototoxicity in vitro.Archives of toxicology · 2023Article
- The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK.Nutrients · 2023Article
- Glucose Uptake Is Increased by Estradiol Dipropionate in L6 Skeletal Muscle Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is a leading oral anti-diabetes mellitus medication and is known to stimulate GLUT4 translocation. However, the mechanism by which metformin acts is still largely unknown. Here, we showed that short time treatment with metformin rapidly increased phosphorylation of Cbl in an AMP-activated protein kinase (AMPK)-dependent fashion in 3T3-L1 preadipocytes. Metformin also increased phosphorylation of Src in an AMPK-dependent manner. Src inhibition blocked metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK-Src-Cbl axis pathway. In addition, long term treatment with metformin stimulated the expression of Cbl-associated protein (CAP) mRNA and protein. Long term treatment with metformin stimulated phosphorylation of c-Jun N-terminal kinase (JNK) and its downstream molecule c-Jun, which is a critical molecule for CAP transcription. Knockdown of AMPK and JNK blocked metformin-induced expression of CAP, implying that metformin stimulates AMPK-JNK-CAP axis pathway. Moreover, AMPK knockdown attenuated metformin-induced Cbl/CAP multicomplex formation, which is critical for GLUT4 translocation. A colorimetric absorbance assay demonstrated that metformin-induced translocation of GLUT4 was suppressed in CAP or Cbl knockdown cells. Furthermore, the promoter activity of CAP was increased by metformin in an AMPK/JNK-dependent fashion. In summary, these results demonstrate that metformin modulates GLUT4 translocation by regulating Cbl and CAP signals via AMPK.
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