Alpert E, Gruzman A, Riahi Y, Blejter R, Aharoni P, Weisinger G, Eckel J, Kaiser N, Sasson S
Department of Pharmacology, Hebrew University School of Medicine, P.O. Box 12272, Jerusalem, 91120, Israel.
Diabetologia. 2005 Apr;48(4):752-5. doi: 10.1007/s00125-005-1681-y. Epub 2005 Mar 1.
AIMS/HYPOTHESIS: We aimed to characterise the development of autoregulation of glucose transport in vascular endothelial cells and its relationship to 12-lipoxygenase (12-LO) expression.
Bovine aortic endothelial cells were exposed to 5.5 and 23.0 mmol/l glucose for up to 48 h. The rates of glucose transport, GLUT-1 and 12-LO expression and of 12-hydroxyeicosatetraenoic acid (12-HETE) production were determined.
We showed high glucose-dependent downregulation of glucose transport and transporter in vascular endothelial cells within 36-48 h. A similar time-dependent increase in the expression of 12-LO and the generation of its product 12-HETE was also observed. This downregulatory process was prevented when lipoxygenase activity was inhibited.
CONCLUSIONS/INTERPRETATION: Vascular endothelial cells, which were previously thought to be "glucose-blind", do in fact downregulate GLUT-1 expression and the rate of glucose transport in response to extended exposure to high glucose concentrations. This slow development of glucose-induced downregulation in vascular endothelial cells is related to the slower basal rate of glucose transport in these cells and the slow induction of 12-LO. These data are interesting in view of current hypotheses that attribute vascular endothelial cell dysfunction in diabetes to the lack of a glucose-induced autoregulatory response.
目的/假设：我们旨在描述血管内皮细胞中葡萄糖转运自动调节的发展及其与12-脂氧合酶（12-LO）表达的关系。
将牛主动脉内皮细胞暴露于5.5和23.0 mmol/l葡萄糖中长达48小时。测定葡萄糖转运速率、GLUT-1和12-LO表达以及12-羟基二十碳四烯酸（12-HETE）的产生。
我们发现，在36-48小时内，血管内皮细胞中葡萄糖转运和转运蛋白存在高度的葡萄糖依赖性下调。还观察到12-LO表达及其产物12-HETE的生成有类似的时间依赖性增加。当脂氧合酶活性受到抑制时，这种下调过程被阻止。
结论/解读：血管内皮细胞以前被认为是“对葡萄糖不敏感的”，但实际上在长时间暴露于高葡萄糖浓度后，确实会下调GLUT-1表达和葡萄糖转运速率。血管内皮细胞中葡萄糖诱导的下调发展缓慢，这与这些细胞中葡萄糖转运的基础速率较慢以及12-LO的缓慢诱导有关。鉴于目前将糖尿病血管内皮细胞功能障碍归因于缺乏葡萄糖诱导的自动调节反应的假设，这些数据很有意思。
