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Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target?
Metformin has been used for treating diabetes mellitus since the late 1950s. In addition to its antihyperglycemic activity, it was shown to be a potential drug candidate for treating a range of other diseases that include various cancers, cardiovascular diseases, diabetic kidney disease, neurodegene...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521008/ https://www.ncbi.nlm.nih.gov/pubmed/34671273 http://dx.doi.org/10.3389/fphys.2021.730048 |
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author | Shoshan-Barmatz, Varda Anand, Uttpal Nahon-Crystal, Edna Di Carlo, Marta Shteinfer-Kuzmine, Anna |
author_facet | Shoshan-Barmatz, Varda Anand, Uttpal Nahon-Crystal, Edna Di Carlo, Marta Shteinfer-Kuzmine, Anna |
author_sort | Shoshan-Barmatz, Varda |
collection | PubMed |
description | Metformin has been used for treating diabetes mellitus since the late 1950s. In addition to its antihyperglycemic activity, it was shown to be a potential drug candidate for treating a range of other diseases that include various cancers, cardiovascular diseases, diabetic kidney disease, neurodegenerative diseases, renal diseases, obesity, inflammation, COVID-19 in diabetic patients, and aging. In this review, we focus on the important aspects of mitochondrial dysfunction in energy metabolism and cell death with their gatekeeper VDAC1 (voltage-dependent anion channel 1) as a possible metformin target, and summarize metformin’s effects in several diseases and gut microbiota. We question how the same drug can act on diseases with opposite characteristics, such as increasing apoptotic cell death in cancer, while inhibiting it in neurodegenerative diseases. Interestingly, metformin’s adverse effects in many diseases all show VDAC1 involvement, suggesting that it is a common factor in metformin-affecting diseases. The findings that metformin has an opposite effect on various diseases are consistent with the fact that VDAC1 controls cell life and death, supporting the idea that it is a target for metformin. |
format | Online Article Text |
id | pubmed-8521008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85210082021-10-19 Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? Shoshan-Barmatz, Varda Anand, Uttpal Nahon-Crystal, Edna Di Carlo, Marta Shteinfer-Kuzmine, Anna Front Physiol Physiology Metformin has been used for treating diabetes mellitus since the late 1950s. In addition to its antihyperglycemic activity, it was shown to be a potential drug candidate for treating a range of other diseases that include various cancers, cardiovascular diseases, diabetic kidney disease, neurodegenerative diseases, renal diseases, obesity, inflammation, COVID-19 in diabetic patients, and aging. In this review, we focus on the important aspects of mitochondrial dysfunction in energy metabolism and cell death with their gatekeeper VDAC1 (voltage-dependent anion channel 1) as a possible metformin target, and summarize metformin’s effects in several diseases and gut microbiota. We question how the same drug can act on diseases with opposite characteristics, such as increasing apoptotic cell death in cancer, while inhibiting it in neurodegenerative diseases. Interestingly, metformin’s adverse effects in many diseases all show VDAC1 involvement, suggesting that it is a common factor in metformin-affecting diseases. The findings that metformin has an opposite effect on various diseases are consistent with the fact that VDAC1 controls cell life and death, supporting the idea that it is a target for metformin. Frontiers Media S.A. 2021-10-04 /pmc/articles/PMC8521008/ /pubmed/34671273 http://dx.doi.org/10.3389/fphys.2021.730048 Text en Copyright © 2021 Shoshan-Barmatz, Anand, Nahon-Crystal, Di Carlo and Shteinfer-Kuzmine. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Shoshan-Barmatz, Varda Anand, Uttpal Nahon-Crystal, Edna Di Carlo, Marta Shteinfer-Kuzmine, Anna Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? |
title | Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? |
title_full | Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? |
title_fullStr | Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? |
title_full_unstemmed | Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? |
title_short | Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target? |
title_sort | adverse effects of metformin from diabetes to covid-19, cancer, neurodegenerative diseases, and aging: is vdac1 a common target? |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521008/ https://www.ncbi.nlm.nih.gov/pubmed/34671273 http://dx.doi.org/10.3389/fphys.2021.730048 |
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