Sherlock Brock D, Boon Marko A A, Vlasiou Maria, Coster Adelle C F
School of Mathematics & Statistics, University of New South Wales, Sydney, 2052, NSW, Australia.
Department of Mathematics and Computer Science, Eindhoven University of Technology, P.O. Box 513, Eindhoven, 5600 MB, The Netherlands.
Bull Math Biol. 2025 Sep 2;87(10):141. doi: 10.1007/s11538-025-01490-6.
Mammalian cells regulate their glucose levels by redistributing glucose transporter proteins within the cell. Glucose Transporter 4 (GLUT4) is the main insulin-regulated glucose transporter in mammalian cells. Insulin signals the redistribution of GLUT4 from intracellular compartments to the cell surface. The mechanisms of the release of GLUT4 and subsequent transport to the plasma membrane remain an open question. Here, a biologically plausible model of GLUT4 translocation is presented. Using a stochastic queuing model, we find that changing only the number of fusion sites available for GLUT4-containing vesicles as a function of insulin is sufficient to explain experimental observations. Thus, the activity of the fusion sites could be the primary determinant of the dynamics of GLUT4.
哺乳动物细胞通过在细胞内重新分布葡萄糖转运蛋白来调节其葡萄糖水平。葡萄糖转运蛋白4(GLUT4)是哺乳动物细胞中主要的胰岛素调节型葡萄糖转运蛋白。胰岛素促使GLUT4从细胞内区室重新分布到细胞表面。GLUT4释放以及随后转运到质膜的机制仍然是一个悬而未决的问题。在此,我们提出了一个关于GLUT4转位的生物学上合理的模型。使用随机排队模型,我们发现仅将可用于含GLUT4囊泡的融合位点数量作为胰岛素的函数进行改变,就足以解释实验观察结果。因此,融合位点的活性可能是GLUT4动态变化的主要决定因素。