Exercise induces a transient increase in transcription of the GLUT-4 gene in skeletal muscle.
Endurance exercise training elicits an increase in mitochondrial density as well as GLUT-4 glucose transporter protein content in skeletal muscle. Corresponding increases in mRNA for respiratory enzymes and GLUT-4 indicate that pretranslational control mechanisms are involved in this adaptive process. To directly test whether transcription of the GLUT-4 gene is activated in response to exercise training, nuclei were isolated from red hindlimb skeletal muscle of rats after 1 wk of exercise training (8% grade, 32 m/min, 40 min, twice/day). Rats were killed either 30 min, 3 h, or 24 h after the last training session. GLUT-4 transcription, determined by nuclear run-on analysis, was unaltered after 30 min, increased by 1.8-fold after 3 h, but was no longer different from controls 24 h after exercise. A similar transient increase in GLUT-4 transcription was evident, but less pronounced (1.4-fold), in untrained rats after a single bout of exercise, suggesting that the postexercise induction in GLUT-4 gene transcription is enhanced by exercise training. GLUT-4 protein content was increased 1.7-fold after 1 wk of training in the absence of any corresponding change in GLUT-4 mRNA, providing evidence that the initial increase in GLUT-4 expression involves translational and/or posttranslational control mechanisms. These findings demonstrate that muscle GLUT-4 expression in response to exercise training is subject to both transcriptional and posttranscriptional regulation. We propose that the increase in GLUT-4 mRNA evident with extended periods of training may result from a shift to pretranslational control and is the cumulative effect of repeated postexercise transient increases in GLUT-4 gene transcription.
Neufer
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PD
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
Dohm
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GL
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D008297:Male; D008970:Molecular Weight; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D009124:Muscle Proteins; D009132:Muscles / Q000378:metabolism / Q000502:physiology*; D010805:Physical Conditioning, Animal; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014158:Transcription, Genetic
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D012313:RNA; D002950:Citrate (si)-Synthase