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AMPK and Insulin Action - Responses to Ageing and High Fat Diet

The 5′-AMP-activated protein kinase (AMPK) is considered “a metabolic master-switch” in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact ro...

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Autores principales: Frøsig, Christian, Jensen, Thomas E., Jeppesen, Jacob, Pehmøller, Christian, Treebak, Jonas T., Maarbjerg, Stine J., Kristensen, Jonas M., Sylow, Lykke, Alsted, Thomas J., Schjerling, Peter, Kiens, Bente, Wojtaszewski, Jørgen F. P., Richter, Erik A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645997/
https://www.ncbi.nlm.nih.gov/pubmed/23671593
http://dx.doi.org/10.1371/journal.pone.0062338
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author Frøsig, Christian
Jensen, Thomas E.
Jeppesen, Jacob
Pehmøller, Christian
Treebak, Jonas T.
Maarbjerg, Stine J.
Kristensen, Jonas M.
Sylow, Lykke
Alsted, Thomas J.
Schjerling, Peter
Kiens, Bente
Wojtaszewski, Jørgen F. P.
Richter, Erik A.
author_facet Frøsig, Christian
Jensen, Thomas E.
Jeppesen, Jacob
Pehmøller, Christian
Treebak, Jonas T.
Maarbjerg, Stine J.
Kristensen, Jonas M.
Sylow, Lykke
Alsted, Thomas J.
Schjerling, Peter
Kiens, Bente
Wojtaszewski, Jørgen F. P.
Richter, Erik A.
author_sort Frøsig, Christian
collection PubMed
description The 5′-AMP-activated protein kinase (AMPK) is considered “a metabolic master-switch” in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact role of AMPK is not well understood. Here we hypothesized that mice lacking α2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (∼4 month) or old (∼18 month) wild type and muscle specific α2AMPK kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis and insulin stimulated glucose uptake in both the soleus and extensor digitorum longus muscle, coinciding with reduced insulin signaling at the level of Akt (pSer473 and pThr308), TBC1D1 (pThr590) and TBC1D4 (pThr642). In contrast to our hypothesis, the impact of ageing and high fat diet on insulin action was not worsened in mice lacking functional α2AMPK in muscle. It is concluded that α2AMPK deficiency in mouse skeletal muscle does not cause muscle insulin resistance in young and old mice and does not exacerbate obesity-induced insulin resistance in old mice suggesting that decreased α2AMPK activity does not increase susceptibility for insulin resistance in skeletal muscle.
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spelling pubmed-36459972013-05-13 AMPK and Insulin Action - Responses to Ageing and High Fat Diet Frøsig, Christian Jensen, Thomas E. Jeppesen, Jacob Pehmøller, Christian Treebak, Jonas T. Maarbjerg, Stine J. Kristensen, Jonas M. Sylow, Lykke Alsted, Thomas J. Schjerling, Peter Kiens, Bente Wojtaszewski, Jørgen F. P. Richter, Erik A. PLoS One Research Article The 5′-AMP-activated protein kinase (AMPK) is considered “a metabolic master-switch” in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact role of AMPK is not well understood. Here we hypothesized that mice lacking α2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (∼4 month) or old (∼18 month) wild type and muscle specific α2AMPK kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis and insulin stimulated glucose uptake in both the soleus and extensor digitorum longus muscle, coinciding with reduced insulin signaling at the level of Akt (pSer473 and pThr308), TBC1D1 (pThr590) and TBC1D4 (pThr642). In contrast to our hypothesis, the impact of ageing and high fat diet on insulin action was not worsened in mice lacking functional α2AMPK in muscle. It is concluded that α2AMPK deficiency in mouse skeletal muscle does not cause muscle insulin resistance in young and old mice and does not exacerbate obesity-induced insulin resistance in old mice suggesting that decreased α2AMPK activity does not increase susceptibility for insulin resistance in skeletal muscle. Public Library of Science 2013-05-06 /pmc/articles/PMC3645997/ /pubmed/23671593 http://dx.doi.org/10.1371/journal.pone.0062338 Text en © 2013 Frøsig et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Frøsig, Christian
Jensen, Thomas E.
Jeppesen, Jacob
Pehmøller, Christian
Treebak, Jonas T.
Maarbjerg, Stine J.
Kristensen, Jonas M.
Sylow, Lykke
Alsted, Thomas J.
Schjerling, Peter
Kiens, Bente
Wojtaszewski, Jørgen F. P.
Richter, Erik A.
AMPK and Insulin Action - Responses to Ageing and High Fat Diet
title AMPK and Insulin Action - Responses to Ageing and High Fat Diet
title_full AMPK and Insulin Action - Responses to Ageing and High Fat Diet
title_fullStr AMPK and Insulin Action - Responses to Ageing and High Fat Diet
title_full_unstemmed AMPK and Insulin Action - Responses to Ageing and High Fat Diet
title_short AMPK and Insulin Action - Responses to Ageing and High Fat Diet
title_sort ampk and insulin action - responses to ageing and high fat diet
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645997/
https://www.ncbi.nlm.nih.gov/pubmed/23671593
http://dx.doi.org/10.1371/journal.pone.0062338
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