Bilirubin increases the expression of glucose transporter-1 and the rate of glucose uptake in vascular endothelial cells.
OBJECTIVE
The close contact between the endothelial cell monolayer in blood vessels and blood plasma allows free diffusion of the hydrophobic unconjugated bilirubin (BR) into these cells. BR can exert both anti- and pro-oxidative effects in various types of cells in a dose-dependent manner. High glucose levels downregulate the expression of the glucose transporter-1 (GLUT-1) and the rate of glucose uptake in vascular endothelial cell (VEC). Pro-oxidants, on the other hand, up-regulate this system in VEC. We aimed to investigate potential effects of BR on the glucose transport system in VEC.


METHODS
Primary cultures of bovine aortic endothelial cells were exposed to BR, and the rate of hexose transport, GLUT-1 expression and plasma membrane localization were determined.


RESULTS
BR induced oxidative stress in VEC, and significantly augmented the rate of glucose transport and GLUT-1 expression and plasma membrane localization in these cells. BR also reversed the high glucose-induced downregulation of the glucose transport system in VEC.


CONCLUSIONS
The pro-oxidative properties of BR are responsible for its effects on the regulation of glucose transport in vascular endothelium. Pathological concentrations of BR in the vascular compartment (jaundice) may influence the cellular handling of glucose in diabetes.
Cohen
Guy
G
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, POBox 12272, Jerusalem 91120, Israel.
Livovsky
Dan M
DM
Kapitulnik
Jaime
J
Sasson
Shlomo
S