Department of Molecular Physiology and Biophysics and the Mouse Metabolic Phenotyping Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
J Exp Biol. 2011 Jan 15;214(Pt 2):254-62. doi: 10.1242/jeb.048041.
Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal muscle comprises the vast majority of insulin-sensitive tissue and is a site of dysregulation in the insulin-resistant state. The biochemical and histological composition of the muscle is well defined in a variety of species. However, the functional consequences of muscle biochemical and histological adaptations to physiological and pathophysiological conditions are not well understood. The physiological regulation of muscle glucose uptake is complex. Sites involved in the regulation of muscle glucose uptake are defined by a three-step process consisting of: (1) delivery of glucose to muscle, (2) transport of glucose into the muscle by GLUT4 and (3) phosphorylation of glucose within the muscle by a hexokinase (HK). Muscle blood flow, capillary recruitment and extracellular matrix characteristics determine glucose movement from the blood to the interstitium. Plasma membrane GLUT4 content determines glucose transport into the cell. Muscle HK activity, cellular HK compartmentalization and the concentration of the HK inhibitor glucose 6-phosphate determine the capacity to phosphorylate glucose. Phosphorylation of glucose is irreversible in muscle; therefore, with this reaction, glucose is trapped and the uptake process is complete. Emphasis has been placed on the role of the glucose transport step for glucose influx into muscle with the past assertion that membrane transport is rate limiting. More recent research definitively shows that the distributed control paradigm more accurately defines the regulation of muscle glucose uptake as each of the three steps that define this process are important sites of flux control.
骨骼肌对体育锻炼的葡萄糖摄取会显著增加。此外，骨骼肌构成了绝大多数胰岛素敏感组织，并且在胰岛素抵抗状态下失调。各种物种的肌肉的生化和组织学组成都有明确的定义。然而，肌肉生化和组织学适应生理和病理生理条件的功能后果尚不清楚。肌肉葡萄糖摄取的生理调节非常复杂。参与肌肉葡萄糖摄取调节的部位由三步过程定义，包括：（1）葡萄糖向肌肉的输送，（2）GLUT4 将葡萄糖运入肌肉，以及（3）肌肉内的己糖激酶 (HK) 将葡萄糖磷酸化。肌肉血流量、毛细血管募集和细胞外基质特征决定了葡萄糖从血液向间质的运动。质膜 GLUT4 含量决定了葡萄糖向细胞内的转运。肌肉 HK 活性、细胞内 HK 区室化和 HK 抑制剂葡萄糖 6-磷酸的浓度决定了磷酸化葡萄糖的能力。在肌肉中，葡萄糖的磷酸化是不可逆的；因此，通过这个反应，葡萄糖被捕获，摄取过程完成。人们一直强调葡萄糖转运步骤在葡萄糖进入肌肉中的作用，过去曾断言膜转运是限速步骤。最近的研究明确表明，分布式控制范式更准确地定义了肌肉葡萄糖摄取的调节，因为定义这一过程的三个步骤都是通量控制的重要部位。
