Fish glucose transporter (GLUT)-4 differs from rat GLUT4 in its traffic characteristics but can translocate to the cell surface in response to insulin in skeletal muscle cells
Fish glucose transporter (GLUT)-4 differs from rat GLUT4 in its traffic characteristics but can translocate to the cell surface in response to insulin in skeletal muscle cells
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DOI：
10.1210/en.2007-0265
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发表时间：
2007-11-01
期刊：
影响因子：
4.8
通讯作者：
Planas, Josep V.
中科院分区：
文献类型：
--
作者：
Diaz, Monica;Antonescu, Costin N.;Planas, Josep V.
在哺乳动物中，葡萄糖转运蛋白（GLUT）-4在葡萄糖稳态中起重要作用，介导胰岛素作用以增加胰岛素应答组织中的葡萄糖摄取。在基础状态下，GLUT 4位于细胞内区室中，并且在胰岛素刺激时被募集到质膜，允许葡萄糖进入细胞。与哺乳动物相比，鱼类在饮食或外源性葡萄糖施用后恢复血浆葡萄糖的效率较低。最近，我们的小组克隆了骨骼肌中的GLUT 4同源物从褐鳟鱼（btGLUT 4），不同的蛋白质基序被认为是重要的内吞作用和哺乳动物GLUT 4的分选。为了研究btGLUT 4的运输，我们产生了稳定的L 6肌肉细胞系过表达myc标记的btGLUT 4（btGLUT 4 myc）。胰岛素刺激btGLUT 4 myc的招聘到细胞表面，虽然在较小程度上比大鼠GLUT 4 myc，并增强葡萄糖摄取。有趣的是，btGLUT 4 myc在基础条件下比大鼠GLUT 4 myc在细胞表面显示出更高的稳态水平，这是由于btGLUT 4 myc的再循环速率更高，而不是与大鼠GLUT 4 myc相比更慢的内吞速率。此外，与大鼠GLUT 4 myc不同，btGLUT 4 myc在L 6成肌细胞的整个细胞质中弥漫分布。在原代褐鳟鱼骨骼肌细胞中，胰岛素也促进了内源性btGLUT 4向质膜的易位，并增强了葡萄糖的转运。此外，btGLUT 4表现出弥漫性的细胞内定位在未经刺激的鳟鱼肌细胞。我们的数据表明，btGLUT 4受到不同的细胞内交通从大鼠GLUT 4，并可能解释相对葡萄糖不耐受观察鱼类。
In mammals, glucose transporter (GLUT)- 4 plays an important role in glucose homeostasis mediating insulin action to increase glucose uptake in insulin-responsive tissues. In the basal state, GLUT4 is located in intracellular compartments and upon insulin stimulation is recruited to the plasma membrane, allowing glucose entry into the cell. Compared with mammals, fish are less efficient restoring plasma glucose after dietary or exogenous glucose administration. Recently our group cloned a GLUT4-homolog in skeletal muscle from brown trout (btGLUT4) that differs in protein motifs believed to be important for endocytosis and sorting of mammalian GLUT4. To study the traffic of btGLUT4, we generated a stable L6 muscle cell line overexpressing myc-tagged btGLUT4 (btGLUT4myc). Insulin stimulated btGLUT4myc recruitment to the cell surface, although to a lesser extent than rat-GLUT4myc, and enhanced glucose uptake. Interestingly, btGLUT4myc showed a higher steady-state level at the cell surface under basal conditions than rat-GLUT4myc due to a higher rate of recycling of btGLUT4myc and not to a slower endocytic rate, compared with rat-GLUT4myc. Furthermore, unlike rat-GLUT4myc, btGLUT4myc had a diffuse distribution throughout the cytoplasm of L6 myoblasts. In primary brown trout skeletal muscle cells, insulin also promoted the translocation of endogenous btGLUT4 to the plasma membrane and enhanced glucose transport. Moreover, btGLUT4 exhibited a diffuse intracellular localization in unstimulated trout myocytes. Our data suggest that btGLUT4 is subjected to a different intracellular traffic from rat-GLUT4 and may explain the relative glucose intolerance observed in fish.