The mechanism of decreased insulin sensitivity in glycogen supercompensated muscles

肌肉对葡萄糖摄取的胰岛素敏感性在急性糖原耗竭运动后降低。运动后肌肉对胰岛素的敏感性增加会导致运动过程中肌肉快速合成糖原，如果这些肌肉有足够的碳水化合物可用的话。尽管在运动后的几个小时里，肌肉会旺盛地吸收血糖以重新合成糖原，但在糖原过度补偿的肌肉中，胰岛素刺激的葡萄糖摄取量会减少。在糖原耗竭运动4、8、16h后补充碳水化合物，大鼠肌肉对葡萄糖摄取的胰岛素反应性降低的时程伴随着胰岛素刺激的蛋白激酶B/Akt活性降低。这一结果有力地表明，糖原过度补偿肌肉中葡萄糖摄取的胰岛素反应性降低是Th…的结果。更多的PKB/Akt信号的缺失。在我们的研究中，糖原过度代偿肌肉中PKB/Akt信号的受损也不是由于磷酸肌醇磷酸酶、SHIP2、SKIP或PTEN蛋白丰度的增加。先前的一些研究表明，ACC的激活可能导致脂质中间产物如二酰甘油和神经酰胺的积聚，这与胰岛素抵抗有关。我们之前的研究也提供了证据，证明蛋白质的合成介导了糖原过度补偿肌肉中的胰岛素抵抗。在我们的研究中，糖原超补偿肌肉中乙酰辅酶A羧化酶(ACC)的丰度增加，提示ACC蛋白的表达增加可能与糖原超补偿肌肉的胰岛素抵抗有关。此外，在我们的研究中，糖摄取的胰岛素反应性降低和G0/G1开关蛋白mRNA的表达增加是运动后碳水化合物再摄取的同时发生的。G0/G1开关蛋白表达增加可能与糖原过度代偿肌肉的胰岛素抵抗有关。较少

Muscle insulin sensitivity to glucose uptake is decreased after acute bout of glycogen-depleting exercise. Increased muscle insulin sensitivity after exercise leads to rapid glycogen synthesis in the muscles recruited during exercise, if enough carbohydrate is available for these muscles. Although muscles vigorously take up blood glucose to re-synthesize glycogen for several hours after exercise, insulin-stimulated glucose uptake is decreased in glycogen supercompensated muscles. We tried to examine the mechanism of insulin resistance in glycogen supercompensated muscles.When rats were refed carbohydrate after glycogen-depleting exercise for 4,8, and 16 h, the time course of the decrease in insulin responsiveness of glucose uptake in rat muscles occurred concomitantly with a decrease in insulin- stimulated activation of protein kinase B/Akt. This result strongly suggests that the decreased insulin responsiveness of glucose uptake in glycogen supercompensated muscles is the result of th … More e impairement of PKB/Akt signaling. In our study, impairement of PKB/Akt signaling in glycogen supercompensated muscles was also not due to a increase in the abundance of phosphoinositide phosphatase, SHIP2,SKIP, or PTEN protein.Some previous studies suggested the posibiity that activation of ACC causes the accumulation of lipid intermediates, e.g. diacylglycerol and ceramide, which is involved in the insulin resistance. Our previous study also provided evidence that synthesis of a protein mediates insulin resistance in glycogen supercompensated muscles. In our present study, the abundance of Acetyl CoA Carboxylase (ACC) was increased in glycogen supercompensated muscles, suggesting that increased ACC protein expression might be responsible for insulin resistance in glycogen supercompensated muscles.Furthermore, in our present study, the decrease in insulin responsiveness of glucose uptake and increase in G0/G1 switch protein mRNA expression occurred concurrently during carbohydrate refeeding after exercise. Increased G0/G1 switch protein expression could be involved in the insulin resistance in glycogen supercompensated muscles. Less