REGULATION OF GLUCOSE TRANSPORTERS GLUT-4 AND GLUT-1 GENE-TRANSCRIPTION IN DENERVATED SKELETAL-MUSCLE

Because GLUT-4 expression is decreased whereas GLUT-1 expression is in creased in denervated skeletal muscle, we examined the effects of dene rvation on GLUT-4 and GLUT-1 gene transcription. The right hindlimb sk eletal muscle of male transgenic mice containing sequential truncation s (2,400, 1,639, 1,154, and 730 bp) of the human GLUT-4 promoter linke d to the chloramphenacol acyl transferase (CAT) gene was denervated, a nd the contralateral hindlimb was sham operated. RNase protection anal ysis revealed that after 72 h denervation decreased CAT mRNA and GLUT- 4 mRNA levels 64-85%, respectively (P < 0.05), in the gastrocnemius mu scles. In contrast, denervation of the right hindlimb of male rats inc reased GLUT-1 gene transcription and GLUT-1 mRNA levels by 94 and 213% , respectively (P < 0.05). In conclusion, GLUT-4 transcription is decr eased but GLUT-1 transcription is increased in denervated skeletal mus cle, suggesting that the effects of denervation on GLUT-4 and GLUT-1 e xpression are, in part, transcriptionally mediated. Furthermore, these data indicate that a DNA sequence regulated by denervation is located within 730 bp of the 5'-flanking promoter region of the human GLUT-4 gene.