Glucose transporters control gene expression of aldose reductase, PKCα, and GLUT1 in mesangial cells in vitro

Author:

Henry Douglas N.12,Busik Julia V.1,Brosius Frank C.3,Heilig Charles W.4

Affiliation:

1. Department of Physiology,

2. Department of Pediatrics and Human Development, Division of Pediatric Endocrinology, College of Human Medicine, Michigan State University, East Lansing 48824-1101;

3. Department of Medicine, Division of Nephrology, University of Michigan Medical School and Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan 48109; and

4. Department of Medicine, Division of Nephrology, University of Rochester School of Medicine, Rochester, New York 14642

Abstract

The process linking increased glucose utilization and activation of metabolic pathways leading to end-organ damage from diabetes is not known. We have previously described rat mesangial cells that were transduced to constitutively express the facilitative glucose transporter 1 (GLUT1, MCGT1 cells) or bacterial β-galactosidase (MCLacZ, control cells). Glucose transport was rate limiting for extracellular matrix production in the MCGT1 cells. In the present work, we investigated the effect of GLUT1 overexpression in mesangial cells on aldose reductase (AR), protein kinase Cα (PKCα), and native GLUT1 transcript levels, to determine whether changes in GLUT1 alone could regulate their expression in the absence of high extracellular glucose concentrations. MCGT1 cells grown in normal (8 mM) or elevated (20 mM) glucose had elevated abundance of AR, PKCα, and the native GLUT1 transcripts compared with control cells. AR protein levels, AR activity, sorbitol production, and PKCα protein content were also greater in the MCGT1 cells than in control cells grown in the same media. This is the first report of the concomitant activation of AR, PKCα, and GLUT1 genes by enhanced GLUT1 expression. We conclude that increased GLUT1 expression leads to a positive feedback of greater GLUT1 expression, increased AR expression and activity with polyol accumulation, and increased total and active PKCα protein levels, which leads to detrimental stimulation of matrix protein synthesis by diabetic mesangial cells.

Publisher

American Physiological Society

Subject

Physiology

Reference58 articles.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3