葡萄糖转运载体1的表达及活性调控

The Regulation of Expression and Activity of Glucose Transporter 1

葡萄糖转运蛋白家族(glucose transporters,GLUTs)属于主要协助转运蛋白超家族(major facilitator superfamily,MFS),由溶质运载蛋白家族(solute carrier family 2,SLC2)基因编码,主要协助葡萄糖进行跨细胞膜转运。GLUT1是发现最早的GLUTs家族成员,主要存在于血脑屏障及红细胞膜上,对于维持血糖浓度稳定和大脑供能发挥重要作用。GLUT1的跨膜转运能力一方面与膜上SLC2 A1基因表达量有关,另一方面与GLUT1的转运动力学调控有关。SLC2 A1基因表达调控主要涉及转录、转录后、翻译和翻译后水平调控。转运动力学调控主要包括一系列GLUT1抑制剂,例如膜内糖结合位点抑制剂、膜外糖结合位点抑制剂、腺苷结合效应类抑制剂以及高选择性抑制剂BAY-876。SLC2 A1基因缺失和突变会导致胚胎致死和GLUT1缺乏症;而SLC2 A1表达异常增高则与多种糖尿病合并症(例如糖尿病视网膜病变、糖尿病肾病)、神经认知性障碍及肿瘤等发生相关。本文围绕GLUT1结构功能、表达和活性调控及其与疾病的关系进行综述,以期为GLUT1相关的临床研究和药物研发提供参考。

Glucose transporters(GLUTs)encoded by the solute carrier family 2(SLC2)gene belong to the major facilitator superfamily(MFS)and are responsible for the transmembrane transport of glucose in the body.As the earliest discovered member of the GLUTs,glucose transporter 1(GLUT1)is mainly found in the blood-brain barrier and erythrocyte membrane,and plays an important role in maintaining stable blood glucose concentration and energy supply to the brain.The transmembrane transport capacity of GLUT1 is not only related to the gene expression of SLC2 A1 on the cellular membrane,but also to the transport kinetic regulation of GLUT1.Generally,SLC2 A1 expression is regulated at the transcriptional,post-transcriptional,translational and post-translational levels,and the transport kinetics regulation includes a series of GLUT1 inhibitors,such as intramembrane glycan-binding site inhibitor,extramembrane glycan-binding site inhibitor,adenosine-binding effect inhibitors and the highly selective inhibitor BAY-876.SLC2 A1 gene deletions and mutations can cause embryonic mortality and GLUT1 deficiency syndrome.In contrast,abnormally high SLC2 A1 expression is associated with various diabetic complications(e.g.diabetic retinopathy and diabetic nephropathy),neurocognitive impairment and tumorigenesis.In this paper,the structure,function,expression and activity regulation of GLUT1 and its relationship with diseases were reviewed to provide a reference for the GLUT1-related clinical research and drug develop-ment.