AJP - Endo AJP: Advances in Physiology Education
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 293: E1242-E1249, 2007. First published August 21, 2007; doi:10.1152/ajpendo.00382.2007
0193-1849/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
293/5/E1242    most recent
00382.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (4)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Klein, D. K.
Right arrow Articles by Wojtaszewski, J. F. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Klein, D. K.
Right arrow Articles by Wojtaszewski, J. F. P.

Lack of AMPK{alpha}2 enhances pyruvate dehydrogenase activity during exercise

Ditte K. Klein,1 Henriette Pilegaard,2 Jonas T. Treebak,1 Thomas E. Jensen,1 Benoit Viollet,4,5 Peter Schjerling,3 and Jørgen F. P. Wojtaszewski1

1Section of Human Physiology, Department of Exercise and Sport Sciences, and 2Department of Molecular Biology, Copenhagen Muscle Research Centre, University of Copenhagen; 3Department of Molecular Muscle Biology, Rigshospitalet, Copenhagen, and Department of Biomedical Science, University of Copenhagen, Copenhagen, Denmark; 4Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR8104); and 5Institut National de la Santé et de la Recherche Médicale, U567, Paris, France

Submitted 18 June 2007 ; accepted in final form 19 August 2007

5'-AMP-activated protein kinase (AMPK) was recently suggested to regulate pyruvate dehydrogenase (PDH) activity and thus pyruvate entry into the mitochondrion. We aimed to provide evidence for a direct link between AMPK and PDH in resting and metabolically challenged (exercised) skeletal muscle. Compared with rest, treadmill running increased AMPK{alpha}1 activity in {alpha}2KO mice (90%, P < 0.01) and increased AMPK{alpha}2 activity in wild-type (WT) mice (110%, P < 0.05), leading to increased AMPK{alpha} Thr172 (WT: 40%, {alpha}2KO: 100%, P < 0.01) and ACCbeta Ser227 phosphorylation (WT: 70%, {alpha}2KO: 210%, P < 0.01). Compared with rest, exercise significantly induced PDH-E1{alpha} site 1 (WT: 20%, {alpha}2KO: 62%, P < 0.01) and site 2 (only {alpha}2KO: 83%, P < 0.01) dephosphorylation and PDHa [~200% in both genotypes (P < 0.01)]. Compared with WT, PDH dephosphorylation and activation was markedly enhanced in the {alpha}2KO mice both at rest and during exercise. The increased PDHa activity during exercise was associated with elevated glycolytic flux, and muscles from the {alpha}2KO mice displayed marked lactate accumulation and deranged energy homeostasis. Whereas mitochondrial DNA content was normal, the expression of several mitochondrial proteins was significantly decreased in muscle of {alpha}2KO mice. In isolated resting EDL muscles, activation of AMPK signaling by AICAR did not change PDH-E1{alpha} phosphorylation in either genotype. PDH is activated in mouse skeletal muscle in response to exercise and is independent of AMPK{alpha}2 expression. During exercise, {alpha}2KO muscles display deranged energy homeostasis despite enhanced glycolytic flux and PDHa activity. This may be linked to decreased mitochondrial oxidative capacity.

adenosine 5'-monophosphate-activated protein kinase; 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside; treadmill running; glucose metabolism


Address for reprint requests and other correspondence: J. F. P. Wojtaszewski, Copenhagen Muscle Research Centre, Section of Human Physiology, Dept. of Exercise and Sport Sciences, Univ. of Copenhagen, 13, Universitetsparken, 2100 Copenhagen (e-mail: JWojtaszewski{at}ifi.ku.dk)




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
J. T. Treebak, J. B. Birk, B. F. Hansen, G. S. Olsen, and J. F. P. Wojtaszewski
A-769662 activates AMPK {beta}1-containing complexes but induces glucose uptake through a PI3-kinase-dependent pathway in mouse skeletal muscle
Am J Physiol Cell Physiol, October 1, 2009; 297(4): C1041 - C1052.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. S. Lee-Young, S. R. Griffee, S. E. Lynes, D. P. Bracy, J. E. Ayala, O. P. McGuinness, and D. H. Wasserman
Skeletal Muscle AMP-activated Protein Kinase Is Essential for the Metabolic Response to Exercise in Vivo
J. Biol. Chem., September 4, 2009; 284(36): 23925 - 23934.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. D. L. Folmes, C. S. Wagg, M. Shen, A. S. Clanachan, R. Tian, and G. D. Lopaschuk
Suppression of 5'-AMP-activated protein kinase activity does not impair recovery of contractile function during reperfusion of ischemic hearts
Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H313 - H321.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
R. W. Schwenk, J. J.F.P. Luiken, A. Bonen, and J. F.C. Glatz
Regulation of sarcolemmal glucose and fatty acid transporters in cardiac disease
Cardiovasc Res, July 15, 2008; 79(2): 249 - 258.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.