Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells

Marouan Zarrouk, David K. Finlay, Marc Foretz, Benoit Viollet, Doreen A. Cantrell (Lead / Corresponding author)

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    The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK.
    Original languageEnglish
    Article numbere106710
    Number of pages7
    JournalPLoS ONE
    Issue number9
    Publication statusPublished - 2 Sept 2014


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