Differential Glucose Uptake in Retina- and Brain-Derived Endothelial Cells

Abstract

Microangiopathy is a systemic complication of diabetes that is especially severe in the retinal microcirculation. The objective of this study was to compare glucose uptake and glucose transporter expression between retinal endothelial cells and the closely related endothelial cells derived from the cerebral microcirculation. Endothelial cells isolated from bovine brain, bovine retinal, and rat heart microvessels were cultured in the presence of control (5 mM) and high levels of (30 mM) d-glucose for 1–5 days. Glucose uptake by cultured endothelial cells was determined by measuring the uptake of [3H]deoxy-d-glucose and glucose transporter protein expression was assessed by Western blot. Our results showed that glucose uptake was significantly (P < 0.001) higher in brain- and heart-derived endothelial cells than in retinal endothelial cells at both physiologic and high concentrations of glucose. High levels of glucose caused a significant (P < 0.05) decrease in glucose uptake in brain-derived and heart endothelial cells but had no effect on retinal endothelial cells. Similarly, in response to high glucose levels there was a significant (P < 0.01) down regulation of GLUT-1 in brain-derived endothelial cells but not in retinal endothelial cells. These results suggest that despite a low basal level of glucose uptake the inability of retinal endothelial cells to down regulate glucose uptake in the presence of high glucose levels could make them especially sensitive to the deleterious effects of hyperglycemia in diabetes.