Insulin stimulates glucose transport by triggering regulated delivery of intracellular vesicles containing the GLUT4 glucose transporter to the plasma membrane. This process is defective in diseases such as type 2 diabetes (T2DM). While studies in rodent cells have been invaluable in understanding GLUT4 traffic, evolutionary plasticity must be considered when extrapolating these findings to humans. Recent work has identified species-specific distinctions in GLUT4 traffic, notably the participation of a novel clathrin isoform, CHC22, in humans but not rodents. Here, we discuss GLUT4 sorting in different species and how studies of CHC22 have identified new routes for GLUT4 trafficking. We further consider how different sorting-protein complexes relate to these routes and discuss other implications of these pathways in cell biology and disease.

胰岛素通过触发含有GLUT4葡萄糖转运蛋白的细胞内囊泡向质膜的调节递送来刺激葡萄糖转运。此过程在2型糖尿病（T2DM）等疾病中存在缺陷。虽然在啮齿动物细胞中进行的研究对于了解GLUT4的运输是非常宝贵的，但将这些发现推论给人类时，必须考虑进化可塑性。最近的工作已经确定了GLUT4交易中特定物种的区别，特别是新型网格蛋白亚型CHC22在人类中的参与，但在啮齿动物中却没有。在这里，我们讨论了不同物种中的GLUT4分选，以及CHC22的研究如何确定GLUT4贩运的新途径。我们进一步考虑不同的分类蛋白复合物如何与这些途径相关，并讨论这些途径在细胞生物学和疾病中的其他含义。