Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre s/n, Ciudad Universitaria, 5000, Córdoba, Argentina.
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
Sci Rep. 2021 Feb 26;11(1):4742. doi: 10.1038/s41598-021-84090-3.
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 PIK/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）在调节几种膜蛋白（如 IGF-1 受体（IGF-1R））方面发挥着关键作用。在脑星形胶质细胞中，LRP1 与 IGF-1R 和葡萄糖转运蛋白 1（GLUT1）相互作用，调节这些细胞中的葡萄糖摄取。虽然 GLUT1 在视网膜 Müller 胶质细胞（MGCs）中表达，但它的调节尚不清楚。在这里，我们研究了 IGF-1 是否调节 GLUT1 向质膜（PM）的运输和葡萄糖摄取，以及 LRP1 是否参与了这个过程在人 Müller 胶质细胞衍生细胞系（MIO-M1）中。我们发现 IGF-1 以时间依赖性方式产生 GLUT1 向 PM 的易位，涉及 MAPK/ERK 和 PIK/Akt 途径的细胞内信号激活，并产生显著的葡萄糖摄取。此外，我们发现 LRP1 和 GLUT1 之间存在分子关联，IGF-1 显著降低了这种关联。最后，用 LRP1 的特异性 siRNA 处理的细胞显示 PM 上 GLUT1 的表达受损，并且 IGF-1 诱导的葡萄糖摄取减少。我们的结论是，IGF-1 通过 LRP1 的表达调节 MGCs 中的葡萄糖稳态。
