Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells.
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...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0106710 |
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| _version_ | 1849726635006230528 |
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| author | Marouan Zarrouk David K Finlay Marc Foretz Benoit Viollet Doreen A Cantrell |
| author_facet | Marouan Zarrouk David K Finlay Marc Foretz Benoit Viollet Doreen A Cantrell |
| author_sort | Marouan Zarrouk |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bb3fdc28cc38417b9055a44bcd4b5cbe |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-bb3fdc28cc38417b9055a44bcd4b5cbe2025-08-20T03:10:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10671010.1371/journal.pone.0106710Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells.Marouan ZarroukDavid K FinlayMarc ForetzBenoit ViolletDoreen A CantrellThe 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.https://doi.org/10.1371/journal.pone.0106710 |
| spellingShingle | Marouan Zarrouk David K Finlay Marc Foretz Benoit Viollet Doreen A Cantrell Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. PLoS ONE |
| title | Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. |
| title_full | Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. |
| title_fullStr | Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. |
| title_full_unstemmed | Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. |
| title_short | Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. |
| title_sort | adenosine mono phosphate activated protein kinase independent effects of metformin in t cells |
| url | https://doi.org/10.1371/journal.pone.0106710 |
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