Hong Yet Hoi, Yang Christine, Betik Andrew C, Lee-Young Robert S, McConell Glenn K
College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia; Clinical Exercise Science Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia; Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; and
Cellular and Molecular Metabolism, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Am J Physiol Endocrinol Metab. 2016 May 15;310(10):E838-45. doi: 10.1152/ajpendo.00513.2015. Epub 2016 Mar 22.
Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase-μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSμ(+/+) and nNOSμ(-/-) mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17.7 ± 0.6 vs. 15.9 ± 0.9 min for nNOSμ(+/+) and nNOSμ(-/-), respectively, P > 0.05). Resting and exercise blood glucose levels were comparable between the genotypes. Very low levels of NOS activity were detected in skeletal muscle from nNOSμ(-/-) mice, and exercise increased NOS activity only in nNOSμ(+/+) mice (4.4 ± 0.3 to 5.2 ± 0.4 pmol·mg(-1)·min(-1), P < 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5- to 7-fold) and, surprisingly, more so in nNOSμ(-/-) than in nNOSμ(+/+) mice (P < 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOSμ(-/-) mice. In conclusion, nNOSμ is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOSμ(-/-) mice may be due to compensatory increases in AMPK activation.
一氧化氮影响肌肉内信号传导，进而影响运动期间骨骼肌对葡萄糖的摄取。在生理运动模型中，尚未研究在骨骼肌收缩过程中被激活的主要一氧化氮生成酶亚型——神经元型一氧化氮合酶-μ（nNOSμ）在调节葡萄糖摄取方面的作用。在本研究中，清醒且不受约束的慢性插管nNOSμ(+/+)和nNOSμ(-/-)小鼠要么静息，要么在跑步机上以17米/分钟的速度跑30分钟。在最大运动测试至疲劳时，两组小鼠表现出相似的运动能力（nNOSμ(+/+)和nNOSμ(-/-)分别为17.7±0.6分钟和15.9±0.9分钟，P>0.05）。不同基因型小鼠的静息和运动血糖水平相当。在nNOSμ(-/-)小鼠的骨骼肌中检测到极低水平的一氧化氮合酶（NOS）活性，而运动仅使nNOSμ(+/+)小鼠的NOS活性增加（从4.4±0.3皮摩尔·毫克(-1)·分钟(-1)增至5.2±0.4皮摩尔·毫克(-1)·分钟(-1)，P<0.05）。运动显著增加了腓肠肌对葡萄糖的摄取（5至7倍），令人惊讶的是，nNOSμ(-/-)小鼠的增加幅度比nNOSμ(+/+)小鼠更大（P<0.05）。这与nNOSμ(-/-)小鼠运动期间AMPK磷酸化的更大增加相一致。总之，nNOSμ对运动期间骨骼肌摄取葡萄糖并非必不可少，nNOSμ(-/-)小鼠运动期间较高的骨骼肌葡萄糖摄取可能归因于AMPK激活的代偿性增加。
