Cargando…

Molecular mechanism of action of metformin: old or new insights?

Metformin is the first-line drug treatment for type 2 diabetes. Globally, over 100 million patients are prescribed this drug annually. Metformin was discovered before the era of target-based drug discovery and its molecular mechanism of action remains an area of vigorous diabetes research. An improv...

Descripción completa

Detalles Bibliográficos
Autores principales: Rena, Graham, Pearson, Ewan R., Sakamoto, Kei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737434/
https://www.ncbi.nlm.nih.gov/pubmed/23835523
http://dx.doi.org/10.1007/s00125-013-2991-0
_version_ 1782279853877231616
author Rena, Graham
Pearson, Ewan R.
Sakamoto, Kei
author_facet Rena, Graham
Pearson, Ewan R.
Sakamoto, Kei
author_sort Rena, Graham
collection PubMed
description Metformin is the first-line drug treatment for type 2 diabetes. Globally, over 100 million patients are prescribed this drug annually. Metformin was discovered before the era of target-based drug discovery and its molecular mechanism of action remains an area of vigorous diabetes research. An improvement in our understanding of metformin’s molecular targets is likely to enable target-based identification of second-generation drugs with similar properties, a development that has been impossible up to now. The notion that 5' AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting the AMPK-independent effects of the drug into the spotlight for the first time in more than a decade. Key AMPK-independent effects of the drug include the mitochondrial actions that have been known for many years and which are still thought to be the primary site of action of metformin. Coupled with recent evidence of AMPK-independent effects on the counter-regulatory hormone glucagon, new paradigms of AMPK-independent drug action are beginning to take shape. In this review we summarise the recent research developments on the molecular action of metformin.
format Online
Article
Text
id pubmed-3737434
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-37374342013-08-08 Molecular mechanism of action of metformin: old or new insights? Rena, Graham Pearson, Ewan R. Sakamoto, Kei Diabetologia Review Metformin is the first-line drug treatment for type 2 diabetes. Globally, over 100 million patients are prescribed this drug annually. Metformin was discovered before the era of target-based drug discovery and its molecular mechanism of action remains an area of vigorous diabetes research. An improvement in our understanding of metformin’s molecular targets is likely to enable target-based identification of second-generation drugs with similar properties, a development that has been impossible up to now. The notion that 5' AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting the AMPK-independent effects of the drug into the spotlight for the first time in more than a decade. Key AMPK-independent effects of the drug include the mitochondrial actions that have been known for many years and which are still thought to be the primary site of action of metformin. Coupled with recent evidence of AMPK-independent effects on the counter-regulatory hormone glucagon, new paradigms of AMPK-independent drug action are beginning to take shape. In this review we summarise the recent research developments on the molecular action of metformin. Springer Berlin Heidelberg 2013-07-09 2013 /pmc/articles/PMC3737434/ /pubmed/23835523 http://dx.doi.org/10.1007/s00125-013-2991-0 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Review
Rena, Graham
Pearson, Ewan R.
Sakamoto, Kei
Molecular mechanism of action of metformin: old or new insights?
title Molecular mechanism of action of metformin: old or new insights?
title_full Molecular mechanism of action of metformin: old or new insights?
title_fullStr Molecular mechanism of action of metformin: old or new insights?
title_full_unstemmed Molecular mechanism of action of metformin: old or new insights?
title_short Molecular mechanism of action of metformin: old or new insights?
title_sort molecular mechanism of action of metformin: old or new insights?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737434/
https://www.ncbi.nlm.nih.gov/pubmed/23835523
http://dx.doi.org/10.1007/s00125-013-2991-0
work_keys_str_mv AT renagraham molecularmechanismofactionofmetforminoldornewinsights
AT pearsonewanr molecularmechanismofactionofmetforminoldornewinsights
AT sakamotokei molecularmechanismofactionofmetforminoldornewinsights