Chronic Exposure of Human Glomerular Epithelial Cells to High Glucose Concentration Results in Modulation of High-Affinity Glucose Transporters Expression

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.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Separation
  • Diabetes Mellitus, Experimental / metabolism
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Glucose / metabolism
  • Glucose / pharmacology*
  • Glucose Transport Proteins, Facilitative / biosynthesis*
  • Glucose Transport Proteins, Facilitative / drug effects*
  • Glucose Transporter Type 1 / biosynthesis
  • Glucose Transporter Type 1 / drug effects
  • Glucose Transporter Type 3 / biosynthesis
  • Glucose Transporter Type 3 / drug effects
  • Glucose Transporter Type 4 / biosynthesis
  • Glucose Transporter Type 4 / drug effects
  • Humans
  • Podocytes / drug effects*
  • Podocytes / metabolism*
  • Rabbits
  • Sweetening Agents / pharmacology*
  • Time Factors

Substances

  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Glucose Transporter Type 4
  • Sweetening Agents
  • Glucose