ArticleScientific reports2020
The importance of the AMPK gamma 1 subunit in metformin suppression of liver glucose production.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- AMPK γ-Subunit Isoform Switching Governs Temozolomide Resistance and Survival in Glioblastoma.Cells · 2026Article
- VCPIP1 drives diabetic cardiomyopathy by deubiquitinating AMPKγ1 and preventing AMPKα-γ subunit assembly in cardiomyocytes.Signal transduction and targeted therapy · 2026Article
- Overview of Metformin and Neurodegeneration: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Role of the AMP-Activated Protein Kinase in the Pathogenesis of Polycystic Ovary Syndrome.Indian journal of clinical biochemistry : IJCB · 2024Review
- Biguanides and glucagon like peptide 1 receptor agonists in the amelioration of post liver transplant weight gain; a scoping review of the mechanism of action, safety and efficacy.Gastroenterology and hepatology from bed to bench · 2024Article
- Refeeding-associated AMPKNature aging · 2023Article
- Honokiol acts as an AMPK complex agonist therapeutic in non-alcoholic fatty liver disease and metabolic syndrome.Chinese medicine · 2023Article
- Roles of AMPK and Its Downstream Signals in Pain Regulation.Life (Basel, Switzerland) · 2021Review
- Multifaceted Role of AMPK in Viral Infections.Cells · 2021Review
- Alterations of Gut Microbiota by Overnutrition Impact Gluconeogenic Gene Expression and Insulin Signaling.International journal of molecular sciences · 2021Review
- Anti-flavivirus Properties of Lipid-Lowering Drugs.Frontiers in physiology · 2021Review
- Metformin and Systemic Metabolism.Trends in pharmacological sciences · 2020Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Metformin has been used to treat patients with type 2 diabetes for over 60 years, however, its mechanism of action is still not completely understood. Our previous reports showed that high-fat-diet (HFD)-fed mice with liver-specific knockout of both AMPK catalytic α1 and α2 subunits exhibited significantly higher fasting blood glucose levels and produced more glucose than floxed AMPK catalytic α1 and α2 mice after long-term metformin treatment, and that metformin promotes the formation of the functional AMPK αβγ heterotrimeric complex. We tested the importance of each regulatory γ subunit isoform to metformin action in this current study. We found that depletion of γ1, but not γ2 or γ3, drastically reduced metformin activation of AMPK. HFD-fed mice with depletion of the γ1 subunit are resistant to metformin suppression of liver glucose production. Furthermore, we determined the role of each regulatory cystathionine-β-synthase (CBS) domain in the γ1 subunit in metformin action and found that deletion of either CBS1 or CBS4 negated metformin's effect on AMPKα phosphorylation at T172 and suppression of glucose production in hepatocytes. Our data indicate that the γ1 subunit is required for metformin's control of glucose metabolism in hepatocytes. Furthermore, in humans and animal models, metformin treatment leads to the loss of body weight, we found that the decrease in body weight gain in mice treated with metformin is not directly attributable to increased energy expenditure.
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