Document Detail


Calcineurin does not mediate exercise-induced increase in muscle GLUT4.
MedLine Citation:
PMID:  15734836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exercise induces a rapid increase in expression of the GLUT4 isoform of the glucose transporter in skeletal muscle. One of the signals responsible for this adaptation appears to be an increase in cytosolic Ca(2+). Myocyte enhancer factor 2A (MEF2A) is a transcription factor that is involved in the regulation of GLUT4 expression. It has been reported that the Ca(2+)-regulated phosphatase calcineurin mediates the activation of MEF2 by exercise. It has also been shown that the expression of activated calcineurin in mouse skeletal muscle results in an increase in GLUT4. These findings suggest that increases in cytosolic Ca(2+) induce increased GLUT4 expression by activating calcineurin. However, we have obtained evidence that this response is mediated by a Ca(2+)-calmodulin-dependent protein kinase. The purpose of this study was to test the hypothesis that calcineurin is involved in mediating exercise-induced increases in GLUT4. Rats were exercised on 5 successive days using a swimming protocol. One group of swimmers was given 20 mg/kg body weight of cyclosporin, a calcineurin inhibitor, 2 h before exercise. A second group was given vehicle. GLUT4 protein was increased approximately 80%, GLUT4 mRNA was increased approximately 2.5-fold, MEF2A protein was increased twofold, and hexokinase II protein was increased approximately 2.5-fold 18 h after the last exercise bout. The cyclosporin treatment completely inhibited calcineurin activity but did not affect the adaptive increases in GLUT4, MEF2A, or hexokinase expression. We conclude that calcineurin activation does not mediate the adaptive increase in GLUT4 expression induced in skeletal muscle by exercise.
Authors:
Pablo M Garcia-Roves; Terry E Jones; Kenichi Otani; Dong-Ho Han; John O Holloszy
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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.    
Journal Detail:
Title:  Diabetes     Volume:  54     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-28     Completed Date:  2005-04-22     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  624-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological
Animals
Calcineurin / antagonists & inhibitors,  physiology*
Cyclosporine / pharmacology
DNA-Binding Proteins / biosynthesis
Gene Expression Regulation / drug effects,  physiology*
Glucose Transporter Type 4
Hexokinase / biosynthesis
Male
Monosaccharide Transport Proteins / biosynthesis*
Muscle Proteins / biosynthesis*
Muscle, Skeletal / drug effects,  metabolism*,  physiology
Myogenic Regulatory Factors
Physical Exertion / physiology*
Rats
Rats, Wistar
Transcription Factors / biosynthesis
Grant Support
ID/Acronym/Agency:
AG-00425/AG/NIA NIH HHS; DK-18986/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Glucose Transporter Type 4; 0/Monosaccharide Transport Proteins; 0/Muscle Proteins; 0/Myogenic Regulatory Factors; 0/Slc2a4 protein, rat; 0/Transcription Factors; 0/myocyte-specific enhancer-binding factor 2; 59865-13-3/Cyclosporine; EC 2.7.1.1/Hexokinase; EC 3.1.3.16/Calcineurin

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