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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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) |
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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 |
work_keys_str_mv |
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