Document Detail


Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise.
MedLine Citation:
PMID:  15294034     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pyruvate dehydrogenase complex (PDC) has a key position in skeletal muscle metabolism as it represents the entry of carbohydrate-derived fuel into the mitochondria for oxidation. PDC is regulated by a phosphorylation-dephosphorylation cycle, in which the pyruvate dehydrogenase kinase (PDK) phosphorylates and inactivates the complex. PDK exists in four isoforms, of which the PDK4 isoform is predominantly expressed in skeletal and heart muscle. PDK4 transcription and PDK4 mRNA are markedly increased in human skeletal muscle during prolonged exercise and after both short-term high-intensity and prolonged low-intensity exercise. The exercise-induced transcriptional response of PDK4 is enhanced when muscle glycogen is lowered before the exercise, and intake of a low-carbohydrate high-fat diet during recovery from exercise results in increased transcription and mRNA content of PDK4 when compared with intake of a high-carbohydrate diet. The activity of pyruvate dehydrogenase (PDH) is increased during the first 2 h of low-intensity exercise, followed by a decrease towards resting levels, which is in line with the possibility that the increased PDK4 expressed influences the PDH activity already during prolonged exercise. PDK4 expression is also increased in response to fasting and a high-fat diet. Thus, increased PDK4 expression when carbohydrate availability is low seems to contribute to the sparing of carbohydrates by preventing carbohydrate oxidation. The impact of substrate availability on PDK4 expression during recovery from exercise also underlines the high metabolic priority given to replenishing muscle glycogen stores and re-establishing intracellular homeostasis after exercise.
Authors:
Henriette Pilegaard; P Darrell Neufer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  The Proceedings of the Nutrition Society     Volume:  63     ISSN:  0029-6651     ISO Abbreviation:  Proc Nutr Soc     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-08-05     Completed Date:  2005-04-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7505881     Medline TA:  Proc Nutr Soc     Country:  England    
Other Details:
Languages:  eng     Pagination:  221-6     Citation Subset:  IM    
Affiliation:
Copenhagen Muscle Research Centre, August Krogh Institute, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen Ø, Denmark. hpilegaard@aki.ku.dk
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MeSH Terms
Descriptor/Qualifier:
Carbohydrate Metabolism
Enzyme Activation
Exercise / physiology*
Gene Expression Regulation, Enzymologic
Humans
Mitochondria, Muscle / enzymology*
Muscle, Skeletal / enzymology*,  metabolism
Phosphorylation
Protein Kinases / genetics*
Grant Support
ID/Acronym/Agency:
AR-45372/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.-/Protein Kinases; EC 2.7.1.-/pyruvate dehydrogenase kinase 4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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