DIFFERENTIAL REGULATION OF GLUCOSE-TRANSPORT AND TRANSPORTERS BY GLUCOSE IN VASCULAR ENDOTHELIAL AND SMOOTH-MUSCLE CELLS
DIFFERENTIAL REGULATION OF GLUCOSE-TRANSPORT AND TRANSPORTERS BY GLUCOSE IN VASCULAR ENDOTHELIAL AND SMOOTH-MUSCLE CELLS
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DOI：
10.2337/diabetes.42.1.80
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发表时间：
1993-01-01
期刊：
影响因子：
7.7
通讯作者：
KING, GL
中科院分区：
文献类型：
--
作者：
KAISER, N;SASSON, S;KING, GL
高血压与糖尿病微血管和大血管并发症的发病机制有关。然而，对葡萄糖转运蛋白及其在血管系统中的调节知之甚少。在这项研究中，葡萄糖的葡萄糖转运蛋白的调节，在培养的BAECs和BSMCs，并在人动脉平滑肌细胞。BAECs和BSMCs均通过易化扩散转运系统转运葡萄糖。血管平滑肌细胞的葡萄糖转运活性受葡萄糖的可逆性负调控。BSMCs和HSMCs暴露于高糖降低了2DG和3-O-MG摄取的V（max），而K（m）保持不变。BAECs的己糖转运系统表现出较低的2DG和3-O-MG摄取与BSMCs相比，并表现出很少或没有适应环境葡萄糖的变化。北方印迹分析表明，BAECs和BSMCs的GLUT 1 mRNA水平不受培养基中葡萄糖浓度的影响。北方印迹分析未检测到GLUT 2 -5 mRNA。GLUT 1蛋白，定量Western印迹分析，是更丰富的BSMC比BAECs和减少了约50%，当培养基葡萄糖从1.2到22 mM升高24小时。GLUT 1蛋白水平的改变与运输活动中观察到的变化相关。这些观察结果表明，平滑肌和内皮细胞之间的葡萄糖转运蛋白的差异调节响应葡萄糖。自动调节的位点可能涉及平滑肌细胞中蛋白质的翻译控制和/或稳定性。血管平滑肌细胞响应慢性高血糖而下调葡萄糖转运的能力可作为对抗细胞内葡萄糖增加的可能不利影响的保护机制。
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 V(max) for 2DG and 3-O-MG uptake, whereas K(m) 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. The ability of vascular smooth muscle cells to down-regulate glucose transport in response to chronic hyperglycemia may serve as a protective mechanism against possible adverse effects of increased intracellular glucose.