Jung Suryun, Koh Jinho, Kim Sanghyun, Kim Kijin
Keimyung University Sports Science Research Institute.
Department of Sports Science, Chonbuk National University.
J Nutr Sci Vitaminol (Tokyo). 2017;63(6):365-371. doi: 10.3177/jnsv.63.365.
While lithium is known to stimulate glucose transport into skeletal muscle, the mechanisms of the increased glucose transport by lithium in skeletal muscle are not well defined yet. We excised epitrochlearis muscles from male Wistar rats and measured the transport rates of a glucose analog into lithium-, insulin-, and muscular contraction-stimulated skeletal muscle tissue and we also analyzed the levels of cell surface glucose transport 4 using a photolabeling and multicolor immunofluorescence method. In addition, we generated a cell line that stably expresses myc-tagged GLUT4 to measure the rates of GLUT4 internalization and externalization. Lithium significantly increased 2-DG glucose transport rate in skeletal muscles; however, it was significantly lower than the stimulation induced by the maximum concentration of insulin or tetanic contraction. But co-treatment of lithium with insulin or tetanic contraction increased glucose transport rate by ∼200% more than lithium alone. When skeletal muscle tissues were treated with lithium, insulin, and muscular contraction, the levels of cell surface GLUT4 protein contents were increased similarly by ∼6-fold compared with the basal levels. When insulin or lithium stimuli were maintained, the rate of GLUT4myc internalization was significantly lower, and lithium was found to suppress the internalization of GLUT4myc more strongly. The lithium-induced increase in glucose uptake of skeletal muscles appears to increase in cell surface GLUT4 levels caused by decreased internalization of GLUT4. It is concluded that co-treatment of lithium with insulin and muscular contraction had a synergistic effect on glucose transport rate in skeletal muscle.
虽然已知锂能刺激葡萄糖转运至骨骼肌，但锂增加骨骼肌葡萄糖转运的机制尚未明确。我们从雄性Wistar大鼠身上切除肱三头肌，测量葡萄糖类似物向锂、胰岛素和肌肉收缩刺激的骨骼肌组织中的转运速率，并且我们还使用光标记和多色免疫荧光方法分析了细胞表面葡萄糖转运蛋白4的水平。此外，我们构建了一个稳定表达myc标签的葡萄糖转运蛋白4（GLUT4）的细胞系，以测量GLUT4内化和外化的速率。锂显著增加了骨骼肌中2-脱氧葡萄糖（2-DG）的葡萄糖转运速率；然而，它明显低于最大浓度胰岛素或强直收缩所诱导的刺激。但是锂与胰岛素或强直收缩联合处理比单独使用锂使葡萄糖转运速率提高了约200%。当骨骼肌组织用锂、胰岛素和肌肉收缩处理时，细胞表面GLUT4蛋白含量水平与基础水平相比同样增加了约6倍。当维持胰岛素或锂刺激时，GLUT4myc的内化速率显著降低，并且发现锂更强烈地抑制GLUT4myc的内化。锂诱导的骨骼肌葡萄糖摄取增加似乎是由于GLUT4内化减少导致细胞表面GLUT4水平升高。结论是锂与胰岛素和肌肉收缩联合处理对骨骼肌葡萄糖转运速率具有协同作用。
