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

Douglas N. Henry, Julia V. Busik, Frank C. Brosius, Charles W. Heilig

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)F97-F104
JournalAmerican Journal of Physiology - Renal Physiology
Volume277
Issue number1 46-1
DOIs
StatePublished - Jul 1999
Externally publishedYes

Keywords

  • Diabetic nephropathy
  • Facilitative glucose transport
  • Gene regulation
  • Genetics
  • Hyperglycemia

ASJC Scopus subject areas

  • Physiology
  • Urology

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