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, althou...

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Autores principales: Christian Frøsig, Thomas E Jensen, Jacob Jeppesen, Christian Pehmøller, Jonas T Treebak, Stine J Maarbjerg, Jonas M Kristensen, Lykke Sylow, Thomas J Alsted, Peter Schjerling, Bente Kiens, Jørgen F P Wojtaszewski, Erik A Richter
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/dc98e45ee71b43d38484f0835f31be3d
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spelling oai:doaj.org-article:dc98e45ee71b43d38484f0835f31be3d2021-11-18T07:46:49ZAMPK and insulin action--responses to ageing and high fat diet.1932-620310.1371/journal.pone.0062338https://doaj.org/article/dc98e45ee71b43d38484f0835f31be3d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23671593/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Christian FrøsigThomas E JensenJacob JeppesenChristian PehmøllerJonas T TreebakStine J MaarbjergJonas M KristensenLykke SylowThomas J AlstedPeter SchjerlingBente KiensJørgen F P WojtaszewskiErik A RichterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e62338 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Christian Frøsig
Thomas E Jensen
Jacob Jeppesen
Christian Pehmøller
Jonas T Treebak
Stine J Maarbjerg
Jonas M Kristensen
Lykke Sylow
Thomas J Alsted
Peter Schjerling
Bente Kiens
Jørgen F P Wojtaszewski
Erik A Richter
AMPK and insulin action--responses to ageing and high fat diet.
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.
format article
author Christian Frøsig
Thomas E Jensen
Jacob Jeppesen
Christian Pehmøller
Jonas T Treebak
Stine J Maarbjerg
Jonas M Kristensen
Lykke Sylow
Thomas J Alsted
Peter Schjerling
Bente Kiens
Jørgen F P Wojtaszewski
Erik A Richter
author_facet Christian Frøsig
Thomas E Jensen
Jacob Jeppesen
Christian Pehmøller
Jonas T Treebak
Stine J Maarbjerg
Jonas M Kristensen
Lykke Sylow
Thomas J Alsted
Peter Schjerling
Bente Kiens
Jørgen F P Wojtaszewski
Erik A Richter
author_sort Christian Frøsig
title 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_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_sort ampk and insulin action--responses to ageing and high fat diet.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/dc98e45ee71b43d38484f0835f31be3d
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