Disruption of microtubules in rat skeletal muscle does not inhibit insulin- or contraction-stimulated glucose transport
Disruption of microtubules in rat skeletal muscle does not inhibit insulin- or contraction-stimulated glucose transport
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DOI：
10.1152/ajpendo.00238.2002
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发表时间：
2003-10-01
影响因子：
5.1
通讯作者：
Ploug, T
中科院分区：
文献类型：
--
作者：
Ai, H;Ralston, E;Ploug, T
胰岛素和肌肉收缩通过细胞内 GLUT4 葡萄糖转运蛋白易位至细胞表面来刺激骨骼肌中的葡萄糖转运。通过免疫荧光显微镜判断，部分 GLUT4 存储位点与所有肌纤维中发现的广泛微管细胞骨架相关。在这里，我们测试微管是否是胰岛素和收缩作用所需的介质。在具有不同纤维类型组成的三种不同培养的大鼠肌肉中，用秋水仙碱解聚微管小于或等于8小时不会抑制胰岛素或收缩刺激的2-脱氧葡萄糖转运或力产生。相反，秋水仙碱至少部分地阻止了胰岛素刺激转运的约30%的减少，这种减少是在比目鱼肌的孵育8小时期间特别发生的，但在指短屈肌或滑车上肌中却没有。相比之下，诺考达唑（另一种微管破坏药物）能够迅速且剂量依赖性地阻断胰岛素和收缩刺激的葡萄糖转运。秋水仙碱和诺考达唑之间也存在类似的差异，因为它们阻断肌肉巨型“幽灵”囊泡中葡萄糖转运的能力。这表明胰岛素和收缩刺激肌肉中葡萄糖转运的能力不需要完整的微管网络，并且诺考达唑抑制葡萄糖转运与其微管破坏作用无关。
Insulin and muscle contractions stimulate glucose transport in skeletal muscle through a translocation of intracellular GLUT4 glucose transporters to the cell surface. Judged by immunofluorescence microscopy, part of the GLUT4 storage sites is associated with the extensive microtubule cytoskeleton found in all muscle fibers. Here, we test whether microtubules are required mediators of the effect of insulin and contractions. In three different incubated rat muscles with distinct fiber type composition, depolymerization of microtubules with colchicine for less than or equal to 8 h did not inhibit insulin- or contraction-stimulated 2-deoxyglucose transport or force production. On the contrary, colchicine at least partially prevented the similar to30% decrease in insulin- stimulated transport that specifically developed during 8 h of incubation in soleus muscle but not in flexor digitorum brevis or epitrochlearis muscles. In contrast, nocodazole, another microtubule-disrupting drug, rapidly and dose dependently blocked insulin- and contraction-stimulated glucose transport. A similar discrepancy between colchicine and nocodazole was also found in their ability to block glucose transport in muscle giant "ghost" vesicles. This suggests that the ability of insulin and contractions to stimulate glucose transport in muscle does not require an intact microtubule network and that nocodazole inhibits glucose transport independently of its microtubule-disrupting effect.