Castelló A, Cadefau J, Cussó R, Testar X, Hesketh J E, Palacín M, Zorzano A
Departament de Bioquímica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.
J Biol Chem. 1993 Jul 15;268(20):14998-5003.
Mammalian skeletal muscle expresses GLUT-4 and GLUT-1 glucose transporters. Here, we have investigated whether GLUT-1 and GLUT-4 expression is regulated in muscle by contractile activity. GLUT-1 mRNA levels were high in skeletal muscle at days 16 and 17 of fetal life and decreased markedly by days 19 and 21. In contrast, GLUT-4 mRNA levels were clearly detectable at day 21 of fetal life, and they increased progressively during postnatal life. The timing data for GLUT-4 induction and GLUT-1 repression suggest that these processes are related to skeletal muscle innervation. GLUT-4 mRNA decreased markedly in adult rat and rabbit tibialis anterior muscle after severage of peroneal nerve. In contrast, GLUT-1 mRNA levels showed a 9-fold increase in rat muscle 3 days after denervation. Direct stimulation of rabbit tibialis anterior muscle with extracellular electrodes protected GLUT-4 mRNA levels against the effect of denervation. This indicates that the repression of GLUT-4 mRNA associated with denervation is due, at least in part, to electrical activity. Increased contractile activity induced for 24 h by indirect electrical stimulation at low frequency caused a marked and specific increase in GLUT-1 mRNA levels in rabbit tibialis anterior muscle. Our results indicate that (a) innervation-dependent basal contractile activity regulates in an inverse manner the expression of GLUT-1 and GLUT-4 in skeletal muscle, and (b) enhanced contractile activity stimulates GLUT-1 expression in the absence of modifications to GLUT-4 expression. This suggests the existence of different factors which depend on contractile activity and which control GLUT-1 and GLUT-4 glucose transporter expression in skeletal muscle.
哺乳动物骨骼肌表达葡萄糖转运蛋白GLUT - 4和GLUT - 1。在此，我们研究了收缩活动是否会调节肌肉中GLUT - 1和GLUT - 4的表达。在胎儿期第16和17天，骨骼肌中GLUT - 1 mRNA水平较高，而到第19和21天则显著下降。相反，在胎儿期第21天可明显检测到GLUT - 4 mRNA水平，且在出生后其水平逐渐升高。GLUT - 4诱导和GLUT - 1抑制的时间数据表明，这些过程与骨骼肌神经支配有关。切断腓总神经后，成年大鼠和兔的胫前肌中GLUT - 4 mRNA显著下降。相比之下，去神经支配3天后，大鼠肌肉中GLUT - 1 mRNA水平增加了9倍。用细胞外电极直接刺激兔胫前肌可保护GLUT - 4 mRNA水平免受去神经支配的影响。这表明与去神经支配相关的GLUT - 4 mRNA抑制至少部分是由于电活动。低频间接电刺激诱导24小时的收缩活动增加，导致兔胫前肌中GLUT - 1 mRNA水平显著且特异性升高。我们的结果表明：(a) 依赖神经支配的基础收缩活动以相反方式调节骨骼肌中GLUT - 1和GLUT - 4的表达；(b) 在不改变GLUT - 4表达的情况下，增强的收缩活动刺激GLUT - 1表达。这表明存在不同的依赖收缩活动的因素，它们控制骨骼肌中GLUT - 1和GLUT - 4葡萄糖转运蛋白的表达。
