Cohen Guy, Livovsky Dan M, Kapitulnik Jaime, Sasson Shlomo
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, POBox 12272, Jerusalem 91120, Israel.
Rev Diabet Stud. 2006 Fall;3(3):127-33. doi: 10.1900/RDS.2006.3.127. Epub 2006 Nov 10.
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.
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.
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.
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.
血管中的内皮细胞单层与血浆紧密接触，使得疏水性未结合胆红素（BR）能够自由扩散进入这些细胞。BR 可在多种类型细胞中以剂量依赖方式发挥抗氧化和促氧化作用。高血糖水平会下调血管内皮细胞（VEC）中葡萄糖转运蛋白 1（GLUT -1）的表达以及葡萄糖摄取速率。另一方面，促氧化剂会上调 VEC 中的这一系统。我们旨在研究 BR 对 VEC 中葡萄糖转运系统的潜在影响。
将原代培养的牛主动脉内皮细胞暴露于 BR 中，测定己糖转运速率、GLUT -1 表达及质膜定位。
BR 在 VEC 中诱导氧化应激，并显著提高这些细胞中的葡萄糖转运速率、GLUT -1 表达及质膜定位。BR 还逆转了高血糖诱导的 VEC 中葡萄糖转运系统的下调。
BR 的促氧化特性是其对血管内皮中葡萄糖转运调节作用的原因。血管腔室中病理性浓度的 BR（黄疸）可能会影响糖尿病中细胞对葡萄糖的处理。
