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人肾小球上皮细胞长期暴露于高糖浓度会导致高亲和力葡萄糖转运蛋白表达的调节。

Chronic exposure of human glomerular epithelial cells to high glucose concentration results in modulation of high-affinity glucose transporters expression.

作者信息

Moutzouris Dimitrios-Anestis D, Kitsiou Paraskevi V, Talamagas Argiris A, Drossopoulou Garyfallia I, Kassimatis Theodore I, Katsilambros Nikolaos K

机构信息

First Department of Propaedeutic Medicine, University of Athens Medical School, Laiko University Hospital, Athens, Greece.

出版信息

Ren Fail. 2007;29(3):353-8. doi: 10.1080/08860220601184126.

Abstract

INTRODUCTION

GLUTs are specific membrane proteins that transport glucose down a concentration gradient. There have been few studies on their expression in the kidney. The aim of this study was to identify the expression of GLUTs 1, 3, and 4 in HGEC and their regulation under diabetic milieu.

MATERIAL AND METHODS

An immortalized cell line of HGEC was used. Cells were cultured in medium containing 5 or 25 mM D-glucose. Western blotting and flow cytometry were used to examine the presence of GLUTs (1, 3, 4) and alterations in expression.

RESULTS

Western blotting analysis revealed that GLUT-1 levels were increased by 53% in HGEC cultured under experimental diabetes compared to cells grown in 5mM glucose. GLUT-3 levels were also increased by 15% under diabetic conditions. GLUT-4 levels were decreased by 20% in diabetes. Fluorescence Activated Cell Sorting (FACS) analysis demonstrated that cell surface expression of GLUT-1 was increased by 28% in cells grown in 25mM glucose. High glucose concentration did not affect cell surface expression of GLUT-3 and GLUT-4.

DISCUSSION

These findings suggest that depressed GLUT4 expression in glomerulus and overexpression of GLUT-1 and in a lesser extent of GLUT-3 may alter the glucose uptake in these cells. It has been suggested that the overexpression of GLUT-1 in glomerulus, being the major isoform, may lead to the initial pathologic hallmarks of diabetic nephropathy.

摘要

引言

葡萄糖转运蛋白(GLUTs)是一类特定的膜蛋白,可顺着浓度梯度转运葡萄糖。关于它们在肾脏中的表达研究较少。本研究旨在确定人肾小球内皮细胞(HGEC)中GLUT1、GLUT3和GLUT4的表达情况以及它们在糖尿病环境下的调控机制。

材料与方法

使用HGEC的永生化细胞系。细胞在含有5或25 mM D-葡萄糖的培养基中培养。采用蛋白质免疫印迹法和流式细胞术检测GLUTs(1、3、4)的存在情况及表达变化。

结果

蛋白质免疫印迹分析显示,与在5 mM葡萄糖中生长的细胞相比,实验性糖尿病条件下培养的HGEC中GLUT-1水平增加了53%。糖尿病条件下GLUT-3水平也增加了15%。糖尿病状态下GLUT-4水平降低了20%。荧光激活细胞分选(FACS)分析表明,在25 mM葡萄糖中生长的细胞中GLUT-1的细胞表面表达增加了28%。高糖浓度不影响GLUT-3和GLUT-4的细胞表面表达。

讨论

这些发现表明,肾小球中GLUT4表达降低以及GLUT-1的过表达和程度较轻的GLUT-3过表达可能会改变这些细胞对葡萄糖的摄取。有人提出,作为主要异构体的肾小球中GLUT-1过表达可能导致糖尿病肾病的初始病理特征。

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