ArticleAmerican journal of translational research2019
Metformin mitigates autoimmune insulitis by inhibiting Th1 and Th17 responses while promoting Treg production.
Article in American journal of translational research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- Metabolic switch: lymphocytes and the onset of T-cell-mediated autoimmunity.Cellular & molecular immunology · 2026Review
- The Neuroimmune Duality of CD4⁺ T Cells: Drivers of Damage and Repair in the Brain.Molecular neurobiology · 2026Review
- Review
- Modulating Th17/Treg Balance in Alzheimer's Disease: Therapeutic Insights from Natural Compounds and Immunometabolism.Brain sciences · 2026Review
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Metformin Promotes Acquisition of Immune Tolerance in Allergen-Specific Immunotherapy.Allergy, asthma & immunology research · 2026Article
- Commentary: Increased circulating Th17 cells and altered CD4 T cell maturation and differentiation in active tuberculosis with type 2 diabetes: a pilot study.Frontiers in immunology · 2026Article
- Immunometabolic reprogramming in sepsis: mechanisms, clinical endotypes, and therapeutic opportunities.Frontiers in immunology · 2026Review
- The effect of metformin treatment during primary influenza infection on heterologous challenge in young and aged mice.Frontiers in aging · 2026Article
- Metformin as a Metabolic Adjuvant to Amoxicillin: A Hypothesis on Synergistic Antibacterial Action.Advanced pharmaceutical bulletin · 2025Article
- Metabolic regulation of Th17 and Treg cell balance by the mTOR signaling.Metabolism open · 2025Review
- AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia.The Journal of clinical investigation · 2025Article
- The Possible Role of Metformin and Fibroblast Growth Factor-21 in Multiple Sclerosis Neuropathology: Birds of a Feather Flock Together.The European journal of neuroscience · 2025Review
- Metformin prevents diabetes development in type 1 diabetes models via suppression of mTOR and STAT3 signaling in immune cells.Scientific reports · 2025Article
- Sweet regulation - The emerging immunoregulatory roles of hexoses.Journal of advanced research · 2025Review
- Review
- The role of autophagy in the pathogenesis and treatment of multiple sclerosis.Autophagy reports · 2025Review
- Review
- Metformin Restrains the Proliferation of CD4+ T Lymphocytes by Inducing Cell Cycle Arrest in Normo- and Hyperglycemic Conditions.Biomolecules · 2024Article
- Reprogramming of Lipid Metabolism Mediates Crosstalk, Remodeling, and Intervention of Microenvironment Components in Breast Cancer.International journal of biological sciences · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes mellitus (T1DM) is still one of the major threats on global public health. This autoimmune condition is mainly caused by the imbalance of auto-reactive inflammatory effector T cells (Teffs) and protective regulatory T cells (Tregs). Therefore, inhibiting the development of Teffs and/or promoting Tregs provides a therapeutic strategy for preventing the development of T1DM. Pathways of energy metabolism have been shown to play a pivotal role in dictating the activation, differentiation and immune function of T cells. Studies have shown that inhibition of glycolysis suppresses the development of Th1 and Th17 cells, but promotes Treg production. AMP-activated protein kinase (AMPK) is a master sensor and regulator of cellular energy metabolism in mammals, which has also been demonstrated to interfere with T cell differentiation and effector function through inhibiting mammalian target of rapamycin (mTOR) and subsequent inhibition of glycolysis, and enhancement of lipid oxidation. In this study, we found that AMPK activator metformin suppresses T cell proliferation and inhibits the differentiation of Th1 and Th17 cells while promoting the development of Tregs in vitro in a dose-dependent manner. Treatment of NOD mice with metformin significantly mitigated autoimmune insulitis and substantially decreased the number of pro-inflammatory IFN-γ+ as well as IL17+ CD4 T cells in the spleens of NOD mice. However, a significantly increased percentage of regulatory IL-10+ and Foxp3+ CD4 T cells were seen. We provided a novel potential therapeutic method--by regulating T cell metabolism through targeting AMPK, to reduce the severity of autoimmune insulitis.
Indexed as
Identifiers
31105845PMC6511786W2946361401What OpenQuestion holds
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.