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AMPK and insulin action

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Authors:
  • Frøsig, Christian ;
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    Orcid logo0000-0001-9302-9328
    Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
  • Jensen, Thomas Elbenhardt ;
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    Orcid logo0000-0001-6139-8268
    Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
  • Jeppesen, Jacob ;
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    Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
  • Pehmøller, Christian ;
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    LUKKET: 2012 Undervisningsudvalg, Department of Exercise and Sport Sciences, Faculty of Science, Københavns Universitet
  • Treebak, Jonas Thue ;
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    Orcid logo0000-0003-1488-7012
    Section for Integrative Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
  • Maarbjerg, Stine Just ;
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    Department of Exercise and Sport Sciences, Faculty of Science, Københavns Universitet
  • Kristensen, Jonas Møller ;
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    Orcid logo0000-0002-8296-975X
    Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
  • Sylow, Lykke ;
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    unknown
  • Alsted, Thomas Junker ;
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    Department of Exercise and Sport Sciences, Faculty of Science, Københavns Universitet
  • Schjerling, Peter ;
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    Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
  • Kiens, Bente ;
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    Orcid logo0000-0001-5705-5625
    Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
  • Wojtaszewski, Jørgen ;
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    Orcid logo0000-0001-8185-3408
    Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
  • Richter, Erik
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    Orcid logo0000-0002-6850-3056
    Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
Subtitle:
Responses to ageing and high fat diet
DOI:
10.1371/journal.pone.0062338
Abstract:
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 a2AMPK 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 a2AMPK 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 a2AMPK in muscle. It is concluded that a2AMPK 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 a2AMPK activity does not increase susceptibility for insulin resistance in skeletal muscle.
Type:
Journal article
Language:
English
Published in:
P L O S One, 2013, Vol 8, Issue 5
Keywords:
Journal Article; Research Support, Non-U.S. Gov't; AMP-Activated Protein Kinases; Aging; Animals; Area Under Curve; Blood Glucose; Body Composition; Diet, High-Fat; GTPase-Activating Proteins; Glucose Tolerance Test; Glucose Transporter Type 4; Hexokinase; Homeostasis; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Muscle Proteins; Muscle, Skeletal; Phosphorylation; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2013
Scientific Level:
Scientific
ID:
241564784

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