August Krogh Bldg., Dept. of Biology, Universitetsparken 13, 2100 Copenhagen, Denmark.
J Appl Physiol (1985). 2011 Sep;111(3):751-7. doi: 10.1152/japplphysiol.00063.2011. Epub 2011 Jun 16.
To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), six healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an oral glucose tolerance test (OGTT) and a one-legged knee extensor exercise bout [45 min at 60% maximal load (W(max))] with muscle biopsies obtained from vastus lateralis before, immediately after exercise, and at 3 h of recovery. Blood samples were taken from the femoral vein and artery before and after 40 min of exercise. Glucose intake elicited a larger (P ≤ 0.05) insulin response after bed rest than before, indicating glucose intolerance. There were no differences in lactate release/uptake across the exercising muscle before and after bed rest, but glucose uptake after 40 min of exercise was larger (P ≤ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05< P ≤ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1α protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased (P ≤ 0.05) the activity of PDH in the active form (PDHa) and induced (P ≤ 0.05) dephosphorylation of PDH-E1α on Ser²⁹³, Ser²⁹⁵ and Ser³⁰⁰, with no difference before and after bed rest. In conclusion, although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed. This suggests that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant (e.g., insulin resistant) individuals.
为了验证体力活动不足会损害丙酮酸脱氢酶(PDH)的运动诱导调节这一假说,六名健康、经常进行体力活动的男性受试者完成了为期 7 天的卧床休息。在卧床休息之前和之后,受试者完成了口服葡萄糖耐量试验(OGTT)和单腿伸膝运动(45 分钟,60%最大负荷(W(max))),并从股外侧肌中采集肌肉活检样本,分别在运动前、运动后和恢复 3 小时进行。在运动前 40 分钟和运动后,从股静脉和股动脉采集血液样本。卧床休息后,葡萄糖摄入引起的胰岛素反应更大(P ≤ 0.05),表明存在葡萄糖耐量受损。卧床休息前后,运动肌肉的乳酸释放/摄取没有差异,但卧床休息前 40 分钟的葡萄糖摄取量更大(P ≤ 0.05)。股外侧肌的肌糖原含量在卧床休息后趋于升高(0.05<P ≤ 0.10),但卧床休息前后对运动的肌糖原分解相似。PDH-E1α 蛋白含量对卧床休息或运动干预没有反应。运动增加了(P ≤ 0.05)PDH 的活性形式(PDHa)的活性,并诱导了(P ≤ 0.05)PDH-E1α 在 Ser²⁹³、Ser²⁹⁵ 和 Ser³⁰⁰ 上的去磷酸化,卧床休息前后没有差异。总之,尽管 7 天的卧床休息导致了全身葡萄糖耐量受损,但骨骼肌中运动诱导的 PDH 调节没有改变。这表明,在葡萄糖不耐受(例如胰岛素抵抗)个体中,骨骼肌中运动诱导的 PDH 调节得以维持。