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葡萄糖对血管内皮细胞和平滑肌细胞中葡萄糖转运及转运体的差异性调节

Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells.

作者信息

Kaiser N, Sasson S, Feener E P, Boukobza-Vardi N, Higashi S, Moller D E, Davidheiser S, Przybylski R J, King G L

机构信息

Department of Endocrinology and Metabolism, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

出版信息

Diabetes. 1993 Jan;42(1):80-9. doi: 10.2337/diab.42.1.80.

DOI:10.2337/diab.42.1.80
PMID:7678404
Abstract

Hyperglycemia has been implicated in the pathogenesis of both micro- and macrovascular complications in diabetes. Little is known, however, about glucose transporters and their regulation in the vascular system. In this study, the regulation of glucose transporters by glucose was examined in cultured BAECs and BSMCs, and in human arterial smooth muscle cells. Both BAECs and BSMCs transported glucose via the facilitated diffusion transport system. Glucose-transport activity in vascular smooth muscle cells was inversely and reversibly regulated by glucose. Exposure of BSMCs and HSMCs to high glucose decreased Vmax for 2DG and 3-O-MG uptake, whereas Km remained unchanged. The hexose-transport system of BAECs exhibited lower 2DG and 3-O-MG uptake compared with BSMCs and showed little or no adaptation to changes in ambient glucose. Northern blot analysis demonstrated that GLUT1 mRNA levels in BAECs and BSMCs were unaffected by the concentration of glucose in the medium. GLUT2-5 mRNA could not be detected by Northern blot analysis. GLUT1 protein, quantified by Western blot analysis, was more abundant in BSMCs than in BAECs and was decreased by approximately 50% when medium glucose was elevated from 1.2 to 22 mM for 24 h. The alterations in the level of GLUT1 protein correlated with the changes observed in transport activity. These observations suggest differential regulation of glucose transporter in response to glucose between smooth muscle and endothelial cells. The sites of autoregulation may involve translational control and/or the stability of the protein in the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

高血糖已被认为与糖尿病微血管和大血管并发症的发病机制有关。然而,关于血管系统中的葡萄糖转运蛋白及其调节机制,人们所知甚少。在本研究中,我们检测了葡萄糖对培养的牛主动脉内皮细胞(BAECs)、牛主动脉平滑肌细胞(BSMCs)以及人动脉平滑肌细胞中葡萄糖转运蛋白的调节作用。BAECs和BSMCs均通过易化扩散转运系统转运葡萄糖。血管平滑肌细胞中的葡萄糖转运活性受到葡萄糖的反向和可逆调节。将BSMCs和人动脉平滑肌细胞(HSMCs)暴露于高糖环境中会降低2-脱氧葡萄糖(2DG)和3-O-甲基葡萄糖(3-O-MG)摄取的最大转运速率(Vmax),而米氏常数(Km)保持不变。与BSMCs相比,BAECs的己糖转运系统对2DG和3-O-MG的摄取较低,并且对周围葡萄糖变化几乎没有适应性。Northern印迹分析表明,BAECs和BSMCs中葡萄糖转运蛋白1(GLUT1)的信使核糖核酸(mRNA)水平不受培养基中葡萄糖浓度的影响。通过Northern印迹分析未检测到葡萄糖转运蛋白2 - 5(GLUT2 - 5)的mRNA。通过蛋白质免疫印迹分析定量的GLUT1蛋白在BSMCs中比在BAECs中更丰富,当培养基葡萄糖浓度从1.2 mM升高到22 mM持续24小时时,其含量下降约50%。GLUT1蛋白水平的变化与转运活性的变化相关。这些观察结果表明,平滑肌细胞和内皮细胞对葡萄糖的反应存在葡萄糖转运蛋白的差异调节。自我调节的位点可能涉及翻译控制和/或平滑肌细胞中蛋白质的稳定性。(摘要截短至250字)

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