Insulin-like Growth Factor-1 (IGF-1) is involved in the normal development and survival of retinal cells. Low-density lipoprotein Receptor-related Protein-1 (LRP1) plays a key role on the regulation of several membrane proteins, such as the IGF-1 receptor (IGF-1R). In brain astrocytes, LRP1 interact with IGF-1R and the glucose transporter type 1 (GLUT1), regulating the glucose uptake in these cells. Although GLUT1 is expressed in retinal Müller Glial Cells (MGCs), its regulation is not clear yet. Here, we investigated whether IGF-1 modulates GLUT1 traffic to plasma membrane (PM) and glucose uptake, as well as the involvement of LRP1 in this process in the human Müller glial-derived cell line (MIO-M1). We found that IGF-1 produced GLUT1 translocation to the PM, in a time-dependent manner involving the intracellular signaling activation of MAPK/ERK and PI₃K/Akt pathways, and generated a significant glucose uptake. Moreover, we found a molecular association between LRP1 and GLUT1, which was significantly reduced by IGF-1. Finally, cells treated with specific siRNA for LRP1 showed an impaired GLUT1 expression on PM and decreased glucose uptake induced by IGF-1. We conclude that IGF-1 regulates glucose homeostasis in MGCs involving the expression of LRP1.

胰岛素样生长因子-1 (IGF-1) 参与视网膜细胞的正常发育和存活。低密度脂蛋白受体相关蛋白 1 (LRP1) 在多种膜蛋白的调节中起关键作用，例如 IGF-1 受体 (IGF-1R)。在脑星形胶质细胞中，LRP1 与 IGF-1R 和 1 型葡萄糖转运蛋白 (GLUT1) 相互作用，调节这些细胞中的葡萄糖摄取。尽管 GLUT1 在视网膜穆勒神经胶质细胞 (MGC) 中表达，但其调控尚不清楚。在这里，我们研究了 IGF-1 是否调节 GLUT1 向质膜 (PM) 和葡萄糖摄取的运输，以及 LRP1 在此过程中参与人 Müller 神经胶质衍生细胞系 (MIO-M1)。我们发现 IGF-1 产生 GLUT1 易位到 PM，₃ K/Akt 通路，并产生显着的葡萄糖摄取。此外，我们发现 LRP1 和 GLUT1 之间存在分子关联，IGF-1 显着降低了这种关联。最后，用针对 LRP1 的特定 siRNA 处理的细胞在 PM 上显示出 GLUT1 表达受损和由 IGF-1 诱导的葡萄糖摄取减少。我们得出结论，IGF-1 调节 MGC 中的葡萄糖稳态，涉及 LRP1 的表达。