Evidence from transgenic mice that glucose transport is rate-limiting for glycogen deposition and glycolysis in skeletal muscle.
Evidence from transgenic mice that glucose transport is rate-limiting for glycogen deposition and glycolysis in skeletal muscle.
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发表时间：
1993-08
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通讯作者：
J. Ren;B. Marshall;E. Gulve;Jiaping Gao;David W. Johnson;J. Holloszy;M. Mueckler
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作者：
J. Ren;B. Marshall;E. Gulve;Jiaping Gao;David W. Johnson;J. Holloszy;M. Mueckler
构建了一系列转基因小鼠，其中人Glut 1葡萄糖转运蛋白在骨骼肌中过表达。Glut 1蛋白的过表达在滑车上肌、趾长伸肌（EDL）和四头肌中是明显的，并导致在离体肌肉中测量的基础葡萄糖转运活性升高6.6-7.4倍。转基因小鼠骨骼肌中葡萄糖转运蛋白活性升高与EDL和四头肌中糖原浓度增加10倍相关，这不是由于肌肉糖原合酶活性增加或糖原磷酸化酶活性降低所致。增加的葡萄糖转运活性也导致肌肉乳酸浓度增加2倍，而肌肉葡萄糖6-磷酸没有增加。尽管肌肉己糖激酶活性略有增加（10%），但转基因小鼠的总肌肉游离葡萄糖增加了4倍，表明当葡萄糖转运速率非常高时，己糖激酶成为葡萄糖摄取的限速因子。这些结果表明，肌肉糖原含量可以显着提高，通过增加肌肉Glut 1蛋白水平和葡萄糖转运是一个限速步骤，在正常的，休息小鼠肌肉葡萄糖处置。
A line of transgenic mice was constructed in which the human Glut1 glucose transporter is overexpressed in skeletal muscle. Overexpression of Glut1 protein was evident in epitrochlearis, extensor digitorum longus (EDL), and quadriceps muscles, and resulted in 6.6-7.4-fold elevations in basal glucose transport activity as measured in isolated muscles in vitro. The elevated glucose transporter activity in the skeletal muscles of transgenic mice was associated with a 10-fold increase in glycogen concentration in EDL and quadriceps muscles that was not due to an increase in muscle glycogen synthase activity or a decrease in glycogen phosphorylase activity. The increased glucose transport activity also resulted in a 2-fold increase in muscle lactate concentration, with no increase in muscle glucose 6-phosphate. Despite a slight (10%) increase in muscle hexokinase activity, there was a 4-fold increase in total muscle free glucose in transgenic mice, indicating that hexokinase becomes rate-limiting for glucose uptake when the rate of glucose transport is very high. These results demonstrate that the muscle glycogen content can be dramatically elevated by increasing the muscle Glut1 protein level and that glucose transport is a rate-limiting step for muscle glucose disposal in normal, resting mice.