| Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise. | |
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MedLine Citation:
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PMID: 15294034 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Henriette Pilegaard; P Darrell Neufer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
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Title: The Proceedings of the Nutrition Society Volume: 63 ISSN: 0029-6651 ISO Abbreviation: Proc Nutr Soc Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-08-05 Completed Date: 2005-04-08 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7505881 Medline TA: Proc Nutr Soc Country: England |
Other Details:
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Languages: eng Pagination: 221-6 Citation Subset: IM |
Affiliation:
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Copenhagen Muscle Research Centre, August Krogh Institute, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen Ø, Denmark. hpilegaard@aki.ku.dk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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AR-45372/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 2.7.-/Protein Kinases; EC 2.7.1.-/pyruvate dehydrogenase kinase 4 |
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