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1 Department of Biochemistry, East Carolina University School of Medicine, Greenville, North Carolina 27858; 2 Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73190; and 3 Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242
Because GLUT-4 expression is decreased whereas GLUT-1 expression is increased in denervated skeletal muscle, we examined the effects of denervation on GLUT-4 and GLUT-1 gene transcription. The right hindlimb skeletal muscle of male transgenic mice containing sequential truncations (2,400, 1,639, 1,154, and 730 bp) of the human GLUT-4 promoter linked to the chloramphenacol acyl transferase (CAT) gene was denervated, and the contralateral hindlimb was sham operated. RNase protection analysis revealed that after 72 h denervation decreased CAT mRNA and GLUT-4 mRNA levels 64-85%, respectively (P < 0.05), in the gastrocnemius muscles. In contrast, denervation of the right hindlimb of male rats increased GLUT-1 gene transcription and GLUT-1 mRNA levels by 94 and 213%, respectively (P < 0.05). In conclusion, GLUT-4 transcription is decreased but GLUT-1 transcription is increased in denervated skeletal muscle, suggesting that the effects of denervation on GLUT-4 and GLUT-1 expression 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.
gene expression; innervation; insulin resistance
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