EXERCISE INDUCES A TRANSIENT INCREASE IN TRANSCRIPTION OF THE GLUT-4 GENE IN SKELETAL-MUSCLE

Endurance exercise training elicits an increase in mitochondrial densi ty as well as GLUT-4 glucose transporter protein content in skeletal m uscle. Corresponding increases in mRNA for respiratory enzymes and GLU T-4 indicate that pretranslational control mechanisms are involved in this adaptive process. To directly test whether transcription of the G LUT-4 gene is activated in response to exercise training, nuclei were isolated from red hindlimb skeletal muscle of rats after 1 wk of exerc ise 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 t ranscription, determined by nuclear run-on analysis, was unaltered aft er 30 min, increased by 1.8-fold after 3 h, but was no longer differen t from controls 24 h after exercise. A similar transient increase in G LUT-4 transcription was evident, but less pronounced (1.4-fold), in un trained rats after a single bout of exercise, suggesting that the post exercise induction in GLUT-4 gene transcription is enhanced by exercis e training. GLUT-4 protein content was increased 1.7-fold after 1 wk o f training in the absence of any corresponding change in GLUT-4 mRNA, providing evidence that the initial increase in GLUT-4 expression invo lves translational and/or posttranslational control mechanisms. These findings demonstrate that muscle GLUT-4 expression in response to exer cise training is subject to both transcriptional and posttranscription al regulation. We propose that the increase in GLUT-4 mRNA evident wit h extended periods of training may result from a shift to pretranslati onal control and is the cumulative effect of repeated postexercise tra nsient increases in GLUT-4 gene transcription.