Napoli R, Cittadini A, Chow J C, Hirshman M F, Smith R J, Douglas P S, Horton E S
Joslin Diabetes Center, Boston, MA, USA.
Biochem J. 1996 May 1;315 ( Pt 3)(Pt 3):959-63. doi: 10.1042/bj3150959.
Whether skeletal muscle glucose transport system is impaired in the basal, post-prandial state during chronic growth hormone treatment is unknown. The current study was designed to determine whether 4 weeks of human growth hormone (hGH) treatment (3.5 mg/kg per day) would impair glucose transport and/or the number of glucose transporters in plasma membrane vesicles isolated from hindlimb skeletal muscle of Sprague-Dawley rats under basal, post-prandial conditions. hGH treatment was shown to have no effect on glucose influx (Vmax or K(m)) determined under equilibrium exchange conditions in isolated plasma membrane vesicles. Plasma membrane glucose transporter number (Ro) measured by cytochalasin B binding was also unchanged by hGH treatment. Consequently, glucose transporter turnover number (Vmax/Ro), a measure of average glucose transporter intrinsic activity, was similar in hGH-treated and control rats. hGH did not change GLUT4 protein content in whole muscle or in the plasma membrane, and muscle content of GLUT4 mRNA also was unchanged. In contrast, GLUT1 protein content in the plasma membrane fraction was significantly reduced by hGH treatment. This was associated with a modest, although not significant, decrease in muscle content of GLUT1 mRNA. In conclusion, high-dose hGH treatment for 4 weeks did not alter post-prandial skeletal muscle glucose transport activity. Neither the muscle level nor the intracellular localization of GLUT4 was changed by the hormone treatment. On the contrary, the basal post-prandial level of GLUT1 in the plasma membrane was reduced by hGH. The mRNA data suggest that this reduction might result from a decrease in the synthesis of GLUT1.
慢性生长激素治疗期间,基础状态和餐后状态下骨骼肌葡萄糖转运系统是否受损尚不清楚。本研究旨在确定4周的人生长激素(hGH)治疗(每天3.5mg/kg)是否会损害基础状态和餐后状态下从Sprague-Dawley大鼠后肢骨骼肌分离的质膜囊泡中的葡萄糖转运和/或葡萄糖转运蛋白数量。结果显示,hGH治疗对分离的质膜囊泡在平衡交换条件下测定的葡萄糖内流(Vmax或K(m))没有影响。用细胞松弛素B结合法测定的质膜葡萄糖转运蛋白数量(Ro)也未因hGH治疗而改变。因此,葡萄糖转运蛋白周转数(Vmax/Ro),即平均葡萄糖转运蛋白内在活性的指标,在hGH治疗组和对照组大鼠中相似。hGH没有改变全肌肉或质膜中GLUT4蛋白含量,GLUT4 mRNA的肌肉含量也未改变。相反,hGH治疗使质膜部分的GLUT1蛋白含量显著降低。这与GLUT1 mRNA的肌肉含量适度但不显著的降低有关。总之,4周的高剂量hGH治疗并未改变餐后骨骼肌葡萄糖转运活性。激素治疗既未改变GLUT4的肌肉水平,也未改变其细胞内定位。相反,hGH降低了质膜中GLUT1的基础餐后水平。mRNA数据表明,这种降低可能是由于GLUT1合成减少所致。