Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells.
Item Type:Journal Article
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, e106710
pone.0106710.pdf (PDF) 1.446Mb
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.
Author: FINLAY, DAVID
Type of material:Journal Article
Series/Report no:PloS one
Availability:Full text available