Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells.
Citation:
Zarrouk M, Finlay DK, Foretz M, Viollet B, Cantrell DA, Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells., PloS one, 9, 9, 2014, e106710Download Item:
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.
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http://people.tcd.ie/finlaydDescription:
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Author: FINLAY, DAVID
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Journal ArticleCollections
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PloS one9
9
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T-cellsDOI:
http://dx.doi10.1371/journal.pone.0106710Metadata
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