Calcineurin does not mediate exercise-induced increase in muscle GLUT4

被引:21
作者
Garcia-Roves, PM [1 ]
Jones, TE [1 ]
Otani, K [1 ]
Han, DH [1 ]
Holloszy, JO [1 ]
机构
[1] Washington Univ, Sch Med, Sect Appl Physiol, Dept Med, St Louis, MO 63110 USA
关键词
D O I
10.2337/diabetes.54.3.624
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 Ca2+. Myocyte enhancer factor 2A (MEF2A) is a transcription factor that is involved in the regulation of GLUT4 expression. It has been reported that the Ca2+-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 Ca2+ induce increased GLUT4 expression by activating calcineurin. However, we have obtained evidence that this response is mediated by a Ca2+-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 similar to80%, GLUT4 mRNA was increased similar to2.5fold, MEF2A protein was increased twofold, and hexokinase 11 protein was increased similar to2.5-fold 18 It after the last exercise bout. The cyciosporin 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.
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页码:624 / 628
页数:5
相关论文
共 27 条
[1]   Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity [J].
Baar, K ;
Song, Z ;
Semenkovich, CF ;
Jones, TE ;
Han, DH ;
Nolte, LA ;
Ojuka, EO ;
Chen, M ;
Holloszy, JO .
FASEB JOURNAL, 2003, 17 (12) :1666-1673
[2]   Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1 [J].
Baar, K ;
Wende, AR ;
Jones, TE ;
Marison, M ;
Nolte, LA ;
Chen, M ;
Kelly, DP ;
Holloszy, JO .
FASEB JOURNAL, 2002, 16 (14) :1879-1886
[3]   A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type [J].
Chin, ER ;
Olson, EN ;
Richardson, JA ;
Yano, Q ;
Humphries, C ;
Shelton, JM ;
Wu, H ;
Zhu, WG ;
Bassel-Duby, R ;
Williams, RS .
GENES & DEVELOPMENT, 1998, 12 (16) :2499-2509
[4]   Regulation of mitogen-activated protein kinases by a calcium/calmodulin-dependent protein kinase cascade [J].
Enslen, H ;
Tokumitsu, H ;
Stork, PJS ;
Davis, RJ ;
Soderling, TR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (20) :10803-10808
[5]   Prevention of glycogen supercompensation prolongs the increase in muscle GLUT4 after exercise [J].
Garcia-Roves, P ;
Han, DH ;
Song, Z ;
Jones, TE ;
Hucker, KA ;
Holloszy, JO .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2003, 285 (04) :E729-E736
[6]  
GULICK T, 2004, FASEB J, P8
[7]   Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation [J].
Han, J ;
Jiang, Y ;
Li, Z ;
Kravchenko, VV ;
Ulevitch, RJ .
NATURE, 1997, 386 (6622) :296-299
[8]  
Holloszy JO, 1996, REV PHYSIOL BIOCH P, V128, P99
[9]  
LIU ML, 1994, J BIOL CHEM, V269, P28514
[10]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265