Marshall B A, Ren J M, Johnson D W, Gibbs E M, Lillquist J S, Soeller W C, Holloszy J O, Mueckler M
Department of Cell Biology, Washington University Medical School, St. Louis, Missouri 63110.
J Biol Chem. 1993 Sep 5;268(25):18442-5.
Transgenic mice were constructed that overexpress the human Glut1 glucose transporter in skeletal muscle. Transcription of the human Glut1 cDNA was driven by the rat myosin light chain 2 promoter. Soleus and quadriceps muscles from transgenic mice expressed increased levels of Glut1 protein relative to muscles obtained from nontransgenic littermates, but there was no difference in the level of Glut4 protein between the two groups. Skeletal muscles isolated from the transgenic animals exhibited 3-4-fold increases in basal glucose uptake relative to muscles obtained from nontransgenic littermates. Muscles isolated from nontransgenic littermates exhibited 2-3-fold increases in glucose transport after incubation in the presence of insulin, but no insulin-stimulated increase in transport was observed in the muscles of transgenic mice. Plasma glucose levels were reduced by 18 and 30%, respectively, in fed and fasted transgenic mice relative to their nontransgenic siblings, but insulin and glucagon levels were not significantly different between the two groups. Glucose disposal following an oral glucose load was markedly enhanced in the transgenic animals, and plasma lactate and beta-OH-butyrate levels were elevated in both fed and fasted transgenic mice. These data strongly support the hypothesis that glucose transport plays a key role in whole body glucose homeostasis. They also demonstrate that the level of a glucose transporter in skeletal muscle can significantly influence the blood glucose set point and alter the levels of other fuel metabolites in the blood.
构建了在骨骼肌中过表达人葡萄糖转运蛋白1（Glut1）的转基因小鼠。人Glut1 cDNA的转录由大鼠肌球蛋白轻链2启动子驱动。与从非转基因同窝小鼠获得的肌肉相比，转基因小鼠的比目鱼肌和股四头肌中Glut1蛋白水平升高，但两组之间Glut4蛋白水平没有差异。与从非转基因同窝小鼠获得的肌肉相比，从转基因动物分离的骨骼肌基础葡萄糖摄取增加了3 - 4倍。在胰岛素存在下孵育后，从非转基因同窝小鼠分离的肌肉葡萄糖转运增加了2 - 3倍，但在转基因小鼠的肌肉中未观察到胰岛素刺激的转运增加。与它们的非转基因同窝小鼠相比，喂食和禁食的转基因小鼠的血浆葡萄糖水平分别降低了18%和30%，但两组之间胰岛素和胰高血糖素水平没有显著差异。转基因动物口服葡萄糖负荷后的葡萄糖处置明显增强，喂食和禁食的转基因小鼠的血浆乳酸和β-羟基丁酸水平均升高。这些数据有力地支持了葡萄糖转运在全身葡萄糖稳态中起关键作用的假说。它们还表明骨骼肌中葡萄糖转运蛋白的水平可显著影响血糖设定点并改变血液中其他燃料代谢物的水平。
