Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA.
Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA.
Life Sci. 2014 May 2;102(2):105-10. doi: 10.1016/j.lfs.2014.03.017. Epub 2014 Mar 21.
Osthole, a coumarin derivative, has been used in Chinese medicine and studies have suggested a potential use in treatment of diabetes and cancers. Therefore, we investigated the effects of osthole and other coumarins on GLUT1 activity in two cell lines that exclusively express GLUT1.
We measured the magnitude and time frame of the effects of osthole and related coumarins on glucose uptake in two cells lines; L929 fibroblast cells which have low GLUT1 expression levels and low basal glucose uptake and HCLE cells which have high GLUT1 concentrations and high basal uptake. We also explored the effects of these coumarins in combination with other GLUT1 activators.
Osthole activates glucose uptake in L929 cells with a modest maximum 1.7-fold activation achieved by 50 μM with both activation and recovery occurring within minutes. However, osthole blocks full acute activation of glucose uptake by other, more robust activators. This behavior mimics the effects of other thiol reactive compounds and suggests that osthole is interacting with cysteine residues, possibly within GLUT1 itself. Coumarin, 7-hydroxycoumarin, and 7-methoxycoumarin, do not affect glucose uptake, which is consistent with the notion that the isoprenoid structure in osthole may be important to gain membrane access to GLUT1. In contrast to its effects in L929 cells, osthole inhibits basal glucose uptake in the more active HCLE cells.
The differential effects of osthole in L929 and HCLE cells indicated that regulation of GLUT1 varies, likely depending on its membrane concentration.
蛇床子素是香豆素的衍生物，在中国医学中被广泛应用，有研究表明其在治疗糖尿病和癌症方面有一定的应用潜力。因此，我们研究了蛇床子素和其他香豆素对两种专门表达 GLUT1 的细胞系中 GLUT1 活性的影响。
我们测量了蛇床子素和相关香豆素对两种细胞系（L929 成纤维细胞和 HCLE 细胞）中葡萄糖摄取的影响的幅度和时间框架；L929 成纤维细胞 GLUT1 表达水平较低，基础葡萄糖摄取量较低，而 HCLE 细胞 GLUT1 浓度较高，基础摄取量较高。我们还探索了这些香豆素与其他 GLUT1 激活剂联合使用的效果。
蛇床子素可激活 L929 细胞的葡萄糖摄取，最大激活幅度为 1.7 倍，50μM 即可达到，激活和恢复均在数分钟内完成。然而，蛇床子素会阻断其他更有效的激活剂对葡萄糖摄取的完全急性激活。这种行为类似于其他巯基反应性化合物的作用，表明蛇床子素与半胱氨酸残基相互作用，可能在 GLUT1 本身内。香豆素、7-羟基香豆素和 7-甲氧基香豆素不影响葡萄糖摄取，这与蛇床子素的异戊烯基结构对于获得 GLUT1 的膜通透性很重要的观点一致。与在 L929 细胞中的作用相反，蛇床子素抑制了更活跃的 HCLE 细胞中的基础葡萄糖摄取。
蛇床子素在 L929 和 HCLE 细胞中的不同作用表明，GLUT1 的调节可能因膜浓度而异。
