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J. Biol. Chem., Vol. 268, Issue 19, 13824-13829, 07, 1993
PD Neufer, JO Carey and GL Dohm
GLUT4 glucose transporter protein and mRNA levels in rat skeletal muscle
are decreased with streptozotocin (STZ)-induced diabetes and increased by
fasting, indicating that GLUT4 expression may be regulated at the
pretranslational level. The purpose of the present study was to determine
whether GLUT4 is subject to transcriptional regulation in skeletal muscle
under the altered metabolic conditions of diabetes and fasting. Nuclei were
isolated from red and white portions of the quadriceps and
gastrocnemius/plantaris muscles of control, 7-day STZ- diabetic, and 3-day
fasted rats. STZ-induced diabetes resulted in a 35% reduction in GLUT4
transcription in red skeletal muscle and thus accounted for a major portion
of the corresponding 50% reduction in GLUT4 mRNA observed in red skeletal
muscle. STZ-induced diabetes had no significant effect on GLUT4
transcription or mRNA in white skeletal muscle. Fasting, however,
significantly increased both GLUT4 transcription (2.2-fold) and mRNA
(2.9-fold) in white skeletal muscle with no change detected for either
parameter in red skeletal muscle. The nearly 2-fold higher steady-state
GLUT4 mRNA in red versus white skeletal muscle of control rats was not
associated with any difference in basal transcription. These findings
demonstrate that expression of the GLUT4 glucose transporter protein in
skeletal muscle is subject to regulation in vivo at the level of
transcription of the GLUT4 gene. In addition, GLUT4 transcription is
regulated in a fiber type-specific manner in response to the metabolic
challenges elicited by STZ-induced diabetes and fasting.
Transcriptional regulation of the gene for glucose transporter GLUT4 in skeletal muscle. Effects of diabetes and fasting
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
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