Glucose transport activity in L6 muscle cells is regulated by the coordinate control of subcellular glucose transporter distribution, biosynthesis, and mRNA transcription.
Glucose transport activity in L6 muscle cells is regulated by the coordinate control of subcellular glucose transporter distribution, biosynthesis, and mRNA transcription.
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DOI：
10.1016/s0021-9258(19)40047-1
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发表时间：
1990-01
期刊：
影响因子：
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通讯作者：
P. S. Walker;T. Ramlal;Vivian Sarabia;Ulla Maija Koivisto;P. Bilan;J. Pessin;A. Klip
中科院分区：
文献类型：
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作者：
P. S. Walker;T. Ramlal;Vivian Sarabia;Ulla Maija Koivisto;P. Bilan;J. Pessin;A. Klip
慢性（24小时）胰岛素治疗和/或葡萄糖剥夺分化的大鼠L 6骨骼肌细胞导致葡萄糖转运活性的增加和2-3倍的质膜相关细胞松弛素B结合位点和免疫反应性葡萄糖转运蛋白的数量增加。与胰岛素的急性效应相反，慢性给药并未减少细胞松弛素B结合位点或细胞内低密度微粒体中存在的免疫反应性葡萄糖转运蛋白的数量。放线菌酮对急性胰岛素刺激葡萄糖转运活性无影响，但对慢性胰岛素刺激葡萄糖转运活性和葡萄糖转运蛋白有降低作用。相反，急性和慢性葡萄糖剥夺对葡萄糖转运活性的刺激对环己酰亚胺不敏感。先前我们已经报道了慢性胰岛素治疗瞬时诱导大鼠脑/HepG 2葡萄糖转运子亚型（GLUT-1）mRNA，而葡萄糖剥夺诱导持续增加（步行者，P.S.，Ramlal，T.，多诺万，J.A.，Doering，T. P.，Sandra，A.，Klip，A.，和Pessin，J.E.（1989）J.Biol.Chem.264，6587-6595）。与这些数据一致，核连续分析表明，无论是慢性胰岛素治疗或葡萄糖剥夺诱导的GLUT-1葡萄糖转运蛋白mRNA转录的速率瞬时增加3倍。长期胰岛素治疗与葡萄糖剥夺的组合导致转录速率比单独治疗更持久的3-4倍增加。这些数据表明，葡萄糖转运蛋白功能的长期胰岛素和葡萄糖依赖性调节通过复杂的机制发生，包括增强GLUT-1 mRNA转录和葡萄糖转运蛋白合成，以及葡萄糖转运蛋白亚细胞分布的变化。
Chronic (24 h) insulin treatment and/or glucose deprivation of differentiated rat L6 skeletal muscle cells resulted in an increase in glucose transport activity and a 2-3-fold increase in the number of plasma membrane-associated cytochalasin B binding sites and immunoreactive glucose transporters. In contrast to the acute effect of insulin, chronic treatment did not decrease the number of cytochalasin B binding sites or immunoreactive glucose transporter proteins present in intracellular low density microsomes. Although acute insulin stimulation of glucose transport activity was not affected by cycloheximide, chronic insulin stimulation of glucose transport activity and glucose transporter protein were decreased. In contrast, the stimulation of glucose transport activity by both acute and chronic glucose deprivation were cycloheximide-insensitive. Previously we have reported that chronic insulin treatment transiently induces the rat brain/HepG2 glucose transporter subtype (GLUT-1) mRNA, whereas glucose deprivation induces a substained increase (Walker, P. S., Ramlal, T., Donovan, J. A., Doering, T. P., Sandra, A., Klip, A., and Pessin, J. E. (1989) J. Biol. Chem. 264, 6587-6595). Consistent with these data, nuclear run-on analysis demonstrated a transient 3-fold increase in the rate of GLUT-1 glucose transporter mRNA transcription induced by either chronic insulin treatment or glucose deprivation. The combination of chronic insulin treatment with glucose deprivation resulted in a more persistent 3-4-fold increase in transcription rate than either treatment alone. These data demonstrate that prolonged insulin- and glucose-dependent regulation of glucose transporter function occurs by a complex mechanism which includes enhanced GLUT-1 mRNA transcription and glucose transporter synthesis, as well as changes in the subcellular distribution of glucose transporter proteins.