MUSCLE GLUCOSE-METABOLISM FOLLOWING EXERCISE IN THE RAT - INCREASED SENSITIVITY TO INSULIN
MUSCLE GLUCOSE-METABOLISM FOLLOWING EXERCISE IN THE RAT - INCREASED SENSITIVITY TO INSULIN
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DOI：
10.1172/jci110517
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发表时间：
1982-01-01
影响因子：
15.9
通讯作者：
RUDERMAN, NB
中科院分区：
文献类型：
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作者：
RICHTER, EA;GARETTO, LP;RUDERMAN, NB
肌肉糖原储备在运动过程中耗尽，并在恢复期间迅速补充。为了研究这种现象的机制，未经训练的雄性大鼠在电机驱动的跑步机上跑了45分钟，然后在其孤立的后躯灌注期间评估其肌肉利用葡萄糖的能力。在没有添加胰岛素的情况下，运动和灌注的对照大鼠的后躯葡萄糖利用率相同;然而，当将胰岛素（30- 40，000 μ U/ml）添加到灌注液中时，运动后葡萄糖利用率更高。先前的运动降低了半最大刺激葡萄糖利用的胰岛素浓度（运动，150 μ U/ml;对照，480 μ U/ml），并适度增加了其最大效应。运动后胰岛素敏感性的增加持续4小时，但24小时后不存在。先前运动增强葡萄糖利用的限速步骤似乎是葡萄糖跨细胞膜的转运，因为在对照组和运动组大鼠中，游离葡萄糖都没有在肌肉细胞中积累。运动后，胰岛素刺激乳酸盐释放到灌注液中的能力没有改变;然而，它刺激[14 C]葡萄糖掺入某些肌肉中糖原的能力增强了。因此，在75 μ U/ml的浓度下，胰岛素在红色腓肠肌的快速收缩红色纤维中刺激的糖原合成比在未运动大鼠的相同肌肉中多8倍。相比之下，胰岛素仅极轻微地增加腓肠肌快缩白色纤维的糖原合成，其未耗尽糖原。这些肌肉的2-脱氧葡萄糖的摄取遵循类似的模式，表明葡萄糖转运也差异增强。先前的运动不能增强胰岛素将糖原合成酶从葡萄糖-6-磷酸依赖型（D）转化为葡萄糖-6-磷酸非依赖型（1）的能力。运动后，胰岛素阻止了肌肉葡萄糖-6-磷酸的显著下降，这可能降低了原位合成酶的活性。运动增强胰岛素将糖原合成酶D转化为对葡萄糖-6-磷酸更敏感的酶的中间形式的能力的可能性仍有待探索。运动后，骨骼肌中的葡萄糖转运和糖原合成明显增强，至少部分是由于胰岛素敏感性的增加。这种胰岛素敏感性的增加显然主要发生在运动期间去糖原化的肌纤维中。
Muscle glycogen stores are depleted during exercise and are rapidly repleted during the recovery period. To investigate the mechanism for this phenomenon, untrained male rats were run for 45 min on a motor-driven treadmill and the ability of their muscles to utilize glucose was then assessed during perfusion of their isolated hindquarters. Glucose utilization by the hindquarter was the same in exercised and control rats perfused in the absence of added insulin; however, when insulin (30-40,000 .mu.U/ml) was added to the perfusate, glucose utilization was greater after exercise. Prior exercise lowered both, the concentration of insulin that half-maximally stimulated glucose utilization (exercise, 150 .mu.U/ml; control, 480 .mu.U/ml) and modestly increased its maximum effect. The increase in insulin sensitivity persisted for 4 h following exercise, but was not present after 24 h. The rate-limiting step in glucose utilization enhanced by prior exercise appeared to be glucose transport across the cell membrane, as in neither control nor exercised rats did free glucose accumulate in the muscle cell. Following exercise, the ability of insulin to stimulate the release of lactate into the perfusate was unaltered; however its ability to stimulate the incorporation of [14C]glucose into glycogen in certain muscles was enhanced. Thus at a concentration of 75 .mu.U/ml insulin stimulated glycogen synthesis 8-fold more in the fast-twitch red fibers of the red gastrocnemius than it did in the same muscle of nonexercised rats. In contrast, insulin only minimally increased glycogen synthesis in the fast-twitch white fibers of the gastrocnemius, which were not glycogen-depleted. The uptake of 2-deoxyglucose by these muscles followed a similar pattern suggesting that glucose transport was also differentially enhanced. Prior exercise did not enhance the ability of insulin to convert glycogen synthase from its glucose-6-phosphate-dependent (D) to its glucose-6-phosphate-independent (1) form. Following exercise, insulin prevented a marked decrease in muscle glucose-6-phosphate, which could have diminished synthase activity in situ. The possibility that exercise enhanced the ability of insulin to convert glycogen synthase D to an intermediate form of the enzyme, more sensitive to glucose-6-phosphate, remains to be explored. Following exercise, glucose transport and glycogen synthesis in skeletal muscle apparently are enhanced due to at least in part to an increase in insulin sensitivity. This increase in insulin sensitivity evidently occurs predominantly in muscle fibers deglycogenated during exercise.