- Authors:
-
-
Frøsig, Christian
;
Close
0000-0001-9302-9328
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet -
Jensen, Thomas Elbenhardt
;
Close0000-0001-6139-8268
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet - Jeppesen, Jacob ;
- Pehmøller, Christian ;
-
Treebak, Jonas Thue
;
Close0000-0003-1488-7012
Section for Integrative Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet - Maarbjerg, Stine Just ;
-
Kristensen, Jonas Møller
;
Close0000-0002-8296-975X
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet - Sylow, Lykke ;
- Alsted, Thomas Junker ;
- Schjerling, Peter ;
-
Kiens, Bente
;
Close0000-0001-5705-5625
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet -
Wojtaszewski, Jørgen
;
Close0000-0001-9785-6830
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet -
Richter, Erik
Close0000-0002-6850-3056
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
-
Frøsig, Christian
;
- 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
