Fueger Patrick T, Heikkinen Sami, Bracy Deanna P, Malabanan Carlo M, Pencek R Richard, Laakso Markku, Wasserman David H
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E958-63. doi: 10.1152/ajpendo.00190.2003. Epub 2003 Jul 15.
Muscle glucose uptake (MGU) is distributively controlled by three serial steps: delivery of glucose to the muscle membrane, transport across the muscle membrane, and intracellular phosphorylation to glucose 6-phosphate by hexokinase (HK). During states of high glucose fluxes such as moderate exercise, the HK activity is of increased importance, since augmented muscle perfusion increases glucose delivery, and increased GLUT4 at the cell membrane increases glucose transport. Because HK II overexpression augments exercise-stimulated MGU, it was hypothesized that a reduction in HK II activity would impair exercise-stimulated MGU and that the magnitude of this impairment would be greatest in tissues with the largest glucose requirement. To this end, mice with a HK II partial knockout (HK+/-) were compared with their wild-type control (WT) littermates during either sedentary or moderate exercise periods. Rg, an index of glucose metabolism, was measured using 2-deoxy-[3H]glucose. No differences in glucose metabolism were detected between sedentary groups. The increase in Rg due to exercise was impaired in the highly oxidative heart and soleus muscles of HK+/- compared with WT mice (7 +/- 10 vs. 29 +/- 9 and 8 +/- 3 vs. 25 +/- 7 micromol. 100 g-1. min-1, respectively). However, the increase in Rg due to exercise was not altered in gastrocnemius and superficial vastus lateralis muscles in HK+/- and WT mice (8 +/- 2 vs. 12 +/- 3 and 5 +/- 2 vs. 8 +/- 2 micromol. 100 g-1. min-1, respectively). In conclusion, MGU is impaired by reductions in HK activity during exercise, a physiological condition characterized by high glucose flux. This impairment is critically dependent on the tissue's glucose metabolic rate and correlates with tissue oxidative capacity.
肌肉葡萄糖摄取（MGU）由三个连续步骤进行分布式控制：葡萄糖输送到肌肉膜、跨肌肉膜转运以及通过己糖激酶（HK）将细胞内磷酸化生成6-磷酸葡萄糖。在高葡萄糖通量状态下，如适度运动时，HK活性变得更加重要，因为增强的肌肉灌注增加了葡萄糖输送，而细胞膜上GLUT4的增加则增加了葡萄糖转运。由于HK II过表达会增强运动刺激的MGU，因此推测HK II活性降低会损害运动刺激的MGU，并且这种损害的程度在葡萄糖需求最大的组织中最为明显。为此，在久坐或适度运动期间，将HK II部分敲除（HK+/-）的小鼠与其野生型对照（WT）同窝小鼠进行比较。使用2-脱氧-[3H]葡萄糖测量葡萄糖代谢指标Rg。在久坐组之间未检测到葡萄糖代谢的差异。与WT小鼠相比，HK+/-的高氧化心脏和比目鱼肌中运动引起的Rg增加受到损害（分别为7±10与29±9以及8±3与25±7微摩尔·100克-1·分钟-1）。然而，HK+/-和WT小鼠的腓肠肌和股外侧肌中运动引起的Rg增加没有改变（分别为8±2与12±3以及5±2与8±2微摩尔·100克-1·分钟-1）。总之，在运动期间，HK活性降低会损害MGU，运动是一种以高葡萄糖通量为特征的生理状态。这种损害严重依赖于组织的葡萄糖代谢率，并与组织氧化能力相关。
