GLUT-4 AND GLUT-1 GLUCOSE-TRANSPORTER EXPRESSION IS DIFFERENTIALLY REGULATED BY CONTRACTILE ACTIVITY IN SKELETAL-MUSCLE

Mammalian skeletal muscle expresses GLUT-4 and GLUT-1 glucose transpor ters. Here, we have investigated whether GLUT- 1 and GLUT-4 expression is regulated in muscle by contractile activity. GLUT-1 mRNA levels we re high in skeletal muscle at days 16 and 17 of fetal life and decreas ed markedly by days 19 and 21. In contrast, GLUT-4 mRNA levels were cl early detectable at day 21 of fetal life, and they increased progressi vely during postnatal life. The timing data for GLUT-4 induction and G LUT- 1 repression suggest that these processes are related to skeletal muscle innervation. GLUT-4 mRNA decreased markedly in adult rat and r abbit tibialis anterior muscle after severage of peroneal nerve. In co ntrast, GLUT-1 mRNA levels showed a 9-fold increase in rat muscle 3 da ys after denervation. Direct stimulation of rabbit tibialis anterior m uscle with extracellular electrodes protected GLUT-4 mRNA levels again st the effect of denervation. This indicates that the repression of GL UT-4 mRNA associated with denervation is due, at least in part, to ele ctrical activity. Increased contractile activity induced for 24 h by i ndirect electrical stimulation at low frequency caused a marked and sp ecific increase in GLUT-1 mRNA levels in rabbit tibialis anterior musc le. Our results indicate that (a) innervation-dependent basal contract ile activity regulates in an inverse manner the expression of GLUT-1 a nd GLUT-4 in skeletal muscle, and (b) enhanced contractile activity st imulates GLUT-1 expression in the absence of modifications to GLUT-4 e xpression. This suggests the existence of different factors which depe nd on contractile activity and which control GLUT-1 and GLUT-4 glucose transporter expression in skeletal muscle.