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The mechanisms of action of metformin

Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, ye...

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Detalles Bibliográficos
Autores principales: Rena, Graham, Hardie, D. Grahame, Pearson, Ewan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552828/
https://www.ncbi.nlm.nih.gov/pubmed/28776086
http://dx.doi.org/10.1007/s00125-017-4342-z
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author Rena, Graham
Hardie, D. Grahame
Pearson, Ewan R.
author_facet Rena, Graham
Hardie, D. Grahame
Pearson, Ewan R.
author_sort Rena, Graham
collection PubMed
description Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration. Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome. In the last 10 years, we have moved from a simple picture, that metformin improves glycaemia by acting on the liver via AMPK activation, to a much more complex picture reflecting its multiple modes of action. More work is required to truly understand how this drug works in its target population: individuals with type 2 diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-017-4342-z) contains a slideset of the figures for download, which is available to authorised users.
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spelling pubmed-55528282017-08-25 The mechanisms of action of metformin Rena, Graham Hardie, D. Grahame Pearson, Ewan R. Diabetologia Review Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration. Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome. In the last 10 years, we have moved from a simple picture, that metformin improves glycaemia by acting on the liver via AMPK activation, to a much more complex picture reflecting its multiple modes of action. More work is required to truly understand how this drug works in its target population: individuals with type 2 diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-017-4342-z) contains a slideset of the figures for download, which is available to authorised users. Springer Berlin Heidelberg 2017-08-03 2017 /pmc/articles/PMC5552828/ /pubmed/28776086 http://dx.doi.org/10.1007/s00125-017-4342-z Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Rena, Graham
Hardie, D. Grahame
Pearson, Ewan R.
The mechanisms of action of metformin
title The mechanisms of action of metformin
title_full The mechanisms of action of metformin
title_fullStr The mechanisms of action of metformin
title_full_unstemmed The mechanisms of action of metformin
title_short The mechanisms of action of metformin
title_sort mechanisms of action of metformin
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552828/
https://www.ncbi.nlm.nih.gov/pubmed/28776086
http://dx.doi.org/10.1007/s00125-017-4342-z
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