Merck
  • Home
  • Search Results
  • Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells.

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

PloS one (2014-09-03)
Marouan Zarrouk, David K Finlay, Marc Foretz, Benoit Viollet, Doreen A Cantrell
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Metformin hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
1,1-Dimethylbiguanide hydrochloride, 97%
Sigma-Aldrich
5-Carboxy-fluorescein diacetate N-succinimidyl ester, for fluorescence, ≥95.0% (HPLC)
Sigma-Aldrich
5(6)-Carboxyfluorescein diacetate N-succinimidyl ester, BioReagent, suitable for fluorescence, ≥90% (HPLC)