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哺乳动物葡萄糖转运蛋白的分子生物学

Molecular biology of mammalian glucose transporters.

作者信息

Bell G I, Kayano T, Buse J B, Burant C F, Takeda J, Lin D, Fukumoto H, Seino S

机构信息

Howard Hughes Medical Institute, University of Chicago, IL 60637.

出版信息

Diabetes Care. 1990 Mar;13(3):198-208. doi: 10.2337/diacare.13.3.198.

DOI:10.2337/diacare.13.3.198
PMID:2407475
Abstract

The oxidation of glucose represents a major source of metabolic energy for mammalian cells. However, because the plasma membrane is impermeable to polar molecules such as glucose, the cellular uptake of this important nutrient is accomplished by membrane-associated carrier proteins that bind and transfer it across the lipid bilayer. Two classes of glucose carriers have been described in mammalian cells: the Na(+)-glucose cotransporter and the facilitative glucose transporter. The Na(+)-glucose cotransporter transports glucose against its concentration gradient by coupling its uptake with the uptake of Na+ that is being transported down its concentration gradient. Facilitative glucose carriers accelerate the transport of glucose down its concentration gradient by facilitative diffusion, a form of passive transport. cDNAs have been isolated from human tissues encoding a Na(+)-glucose-cotransporter protein and five functional facilitative glucose-transporter isoforms. The Na(+)-glucose cotransporter is expressed by absorptive epithelial cells of the small intestine and is involved in the dietary uptake of glucose. The same or a related protein may be responsible for the reabsorption of glucose by the kidney. Facilitative glucose carriers are expressed by most if not all cells. The facilitative glucose-transporter isoforms have distinct tissue distributions and biochemical properties and contribute to the precise disposal of glucose under varying physiological conditions. The GLUT1 (erythrocyte) and GLUT3 (brain) facilitative glucose-transporter isoforms may be responsible for basal or constitutive glucose uptake. The GLUT2 (liver) isoform mediates the bidirectional transport of glucose by the hepatocyte and is responsible, at least in part, for the movement of glucose out of absorptive epithelial cells into the circulation in the small intestine and kidney. This isoform may also comprise part of the glucose-sensing mechanism of the insulin-producing beta-cell. The subcellular localization of the GLUT4 (muscle/fat) isoform changes in response to insulin, and this isoform is responsible for most of the insulin-stimulated uptake of glucose that occurs in muscle and adipose tissue. The GLUT5 (small intestine) facilitative glucose-transporter isoform is expressed at highest levels in the small intestine and may be involved in the transcellular transport of glucose by absorptive epithelial cells. The exon-intron organizations of the human GLUT1, GLUT2, and GLUT4 genes have been determined. In addition, the chromosomal locations of the genes encoding the Na(+)-dependent and facilitative glucose carriers have been determined. Restriction-fragment-length polymorphisms have also been identified at several of these loci.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

葡萄糖氧化是哺乳动物细胞代谢能量的主要来源。然而,由于质膜对葡萄糖等极性分子不可渗透,这种重要营养物质的细胞摄取是通过与膜相关的载体蛋白来完成的,这些载体蛋白结合并将其转运穿过脂质双层。在哺乳动物细胞中已描述了两类葡萄糖载体:钠 - 葡萄糖共转运体和易化葡萄糖转运体。钠 - 葡萄糖共转运体通过将葡萄糖摄取与顺着浓度梯度转运的钠离子摄取相偶联,逆着葡萄糖浓度梯度转运葡萄糖。易化葡萄糖载体通过易化扩散加速葡萄糖顺着其浓度梯度的转运,易化扩散是一种被动转运形式。已从人类组织中分离出编码钠 - 葡萄糖共转运蛋白和五种功能性易化葡萄糖转运体同工型的cDNA。钠 - 葡萄糖共转运体由小肠的吸收上皮细胞表达,参与膳食中葡萄糖的摄取。相同或相关蛋白可能负责肾脏对葡萄糖的重吸收。易化葡萄糖载体在大多数(如果不是全部)细胞中表达。易化葡萄糖转运体同工型具有不同的组织分布和生化特性,并有助于在不同生理条件下精确处置葡萄糖。GLUT1(红细胞)和GLUT3(脑)易化葡萄糖转运体同工型可能负责基础或组成性葡萄糖摄取。GLUT2(肝脏)同工型介导肝细胞对葡萄糖的双向转运,并且至少部分负责葡萄糖从小肠和肾脏的吸收上皮细胞进入循环的转运。这种同工型也可能构成产生胰岛素的β细胞葡萄糖感应机制的一部分。GLUT4(肌肉/脂肪)同工型的亚细胞定位会因胰岛素而改变,并且这种同工型负责肌肉和脂肪组织中大部分胰岛素刺激的葡萄糖摄取。GLUT5(小肠)易化葡萄糖转运体同工型在小肠中表达水平最高,可能参与吸收上皮细胞对葡萄糖的跨细胞转运。已确定了人类GLUT1、GLUT2和GLUT4基因的外显子 - 内含子组织。此外,已确定了编码钠依赖性和易化葡萄糖载体的基因的染色体位置。在其中几个位点也鉴定出了限制性片段长度多态性。(摘要截断于400字)

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J Biol Chem. 1990 Aug 5;265(22):13276-82.
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