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)

    Research output: Contribution to journalArticle

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    Abstract

    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
    Volume9
    Issue number9
    DOIs
    Publication statusPublished - 2 Sep 2014

    Fingerprint

    metformin
    AMP-activated protein kinase
    T-cells
    Adenine Nucleotides
    Metformin
    Adenosine
    Protein Kinases
    T-lymphocytes
    Phosphates
    T-Lymphocytes
    Adenosine Monophosphate
    immune response
    hypoglycemic agents
    Hypoxia-Inducible Factor 1
    Cell proliferation
    Cell growth
    Sirolimus
    cell differentiation
    Cell Differentiation
    cell growth

    Cite this

    Zarrouk, Marouan ; Finlay, David K. ; Foretz, Marc ; Viollet, Benoit ; Cantrell, Doreen A. / Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. In: PLoS ONE. 2014 ; Vol. 9, No. 9.
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    Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. / Zarrouk, Marouan; Finlay, David K.; Foretz, Marc; Viollet, Benoit; Cantrell, Doreen A. (Lead / Corresponding author).

    In: PLoS ONE, Vol. 9, No. 9, e106710, 02.09.2014.

    Research output: Contribution to journalArticle

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    AU - Cantrell, Doreen A.

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    AB - 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.

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