Halseth A E, Bracy D P, Wasserman D H
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
J Appl Physiol (1985). 1998 Dec;85(6):2305-13. doi: 10.1152/jappl.1998.85.6.2305.
The hypothesis of this investigation was that insulin and muscle contraction, by increasing the rate of skeletal muscle glucose transport, would bias control so that glucose delivery to the sarcolemma (and t tubule) and phosphorylation of glucose intracellularly would exert more influence over glucose uptake. Because of the substantial increases in blood flow (and hence glucose delivery) that accompany exercise, we predicted that glucose phosphorylation would become more rate determining during exercise. The transsarcolemmal glucose gradient (TSGG; the glucose concentration difference across the membrane) is inversely related to the degree to which glucose transport determines the rate of glucose uptake. The TSGG was determined by using isotopic methods in conscious rats during euglycemic hyperinsulinemia [Ins; 20 mU/(kg. min); n = 7], during treadmill exercise (Ex, n = 6), and in sedentary, saline-infused rats (Bas, n = 13). Rats received primed, constant intravenous infusions of trace 3-O-[3H]methyl-D-glucose and [U-14C]mannitol. Then 2-deoxy-[3H]glucose was infused for the calculation of a glucose metabolic index (Rg). At the end of experiments, rats were anesthetized, and soleus muscles were excised. Total soleus glucose concentration and the steady-state ratio of intracellular to extracellular 3-O-[3H]methyl-D-glucose (which distributes on the basis of the TSGG) were used to calculate ranges of possible glucose concentrations ([G]) at the inner and outer sarcolemmal surfaces ([G]im and [G]om, respectively). Soleus Rg was increased in Ins and further increased in Ex. In Ins, total soleus glucose, [G]om, and the TSGG were decreased compared with Bas, while [G]im remained near 0. In Ex, total soleus glucose and [G]im were increased compared with Bas, and there was not a decrease in [G]om as was observed in Ins. In addition, accumulation of intracellular free 2-deoxy-[3H]glucose occurred in soleus in both Ex and Ins. Taken together, these data indicate that, in Ex, glucose phosphorylation becomes an important limitation to soleus glucose uptake. In Ins, both glucose delivery and glucose phosphorylation influence the rate of soleus glucose uptake more than under basal conditions.
本研究的假设是，胰岛素和肌肉收缩通过提高骨骼肌葡萄糖转运速率，会使调控偏向于让葡萄糖向肌膜（和横小管）的递送以及细胞内葡萄糖的磷酸化对葡萄糖摄取产生更大影响。由于运动伴随有显著的血流量增加（进而葡萄糖递送增加），我们预测在运动过程中葡萄糖磷酸化将对葡萄糖摄取速率起更大的决定作用。跨肌膜葡萄糖梯度（TSGG；跨膜的葡萄糖浓度差）与葡萄糖转运决定葡萄糖摄取速率的程度呈负相关。在正常血糖高胰岛素血症[胰岛素；20 mU/（kg·分钟）；n = 7]期间、跑步机运动期间（Ex，n = 6）以及久坐的、输注生理盐水的大鼠（基础状态，Bas，n = 13）中，采用同位素方法测定TSGG。大鼠接受微量3 - O - [3H]甲基 - D - 葡萄糖和[U - 14C]甘露醇的初始、持续静脉输注。然后输注2 - 脱氧 - [3H]葡萄糖以计算葡萄糖代谢指数（Rg）。在实验结束时，将大鼠麻醉，切除比目鱼肌。利用比目鱼肌总葡萄糖浓度以及细胞内与细胞外3 - O - [3H]甲基 - D - 葡萄糖的稳态比率（其根据TSGG分布）来计算肌膜内、外表面可能的葡萄糖浓度范围（分别为[G]im和[G]om）。比目鱼肌Rg在高胰岛素血症时升高，在运动时进一步升高。在高胰岛素血症时，与基础状态相比，比目鱼肌总葡萄糖、[G]om和TSGG降低，而[G]im保持在接近0的水平。在运动时，与基础状态相比，比目鱼肌总葡萄糖和[G]im升高，并且未出现如在高胰岛素血症时观察到的[G]om降低。此外，在运动和高胰岛素血症时，比目鱼肌细胞内游离2 - 脱氧 - [3H]葡萄糖均有蓄积。综合来看，这些数据表明，在运动时，葡萄糖磷酸化成为比目鱼肌葡萄糖摄取的一个重要限制因素。在高胰岛素血症时，与基础条件下相比，葡萄糖递送和葡萄糖磷酸化对比目鱼肌葡萄糖摄取速率的影响都更大。
