Pathological upregulation of inner blood-retinal barrier Glut1 glucose transporter expression in diabetes mellitus
Pathological upregulation of inner blood-retinal barrier Glut1 glucose transporter expression in diabetes mellitus
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DOI：
10.1016/0006-8993(95)01335-0
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发表时间：
1996-01-15
期刊：
影响因子：
2.9
通讯作者：
Pardridge, WM
中科院分区：
文献类型：
--
作者：
Kumagai, AK;Vinores, SA;Pardridge, WM
糖尿病性视网膜病变（DR）的视网膜微血管特征的病理变化是慢性暴露于升高的血糖的结果。由于葡萄糖进入微血管内皮细胞，包括内部血视网膜屏障（BRB）是由GLUT 1葡萄糖转运蛋白介导的，在长期存在的糖尿病的内部BRB上的GLUT 1表达的变化可能有一个直接影响视网膜病变的变化的后续发展。在本研究中，GLUT1的定量免疫金电子显微镜采用了3个人与长期糖尿病和最小或无临床视网膜病变和2个非糖尿病个体无眼部疾病的尸检视网膜标本的横截面。在非糖尿病视网膜毛细血管中，GLUT1免疫金不对称地分布在管腔和非管腔膜之间，管腔与非管腔比率为1：1.7。在糖尿病微血管中，观察到GLUT 1免疫反应性的双峰分布模式。在17的40糖尿病微血管检查，GLUT1的密度和分布是没有什么不同的非糖尿病血管，但是，在糖尿病微血管的亚群（23 40），一个显着增加GLUT1免疫反应的管腔和蛋白膜和细胞质中注意到。在管腔膜上，免疫反应性GLUT1的表达增加是非糖尿病微血管的18倍以上。这些研究结果表明，在内部BRB的GLUT1表达的局部上调发生在长期存在的糖尿病与最小或没有临床视网膜病变，并表明这种上调可能有助于放大慢性高血糖症对视网膜微血管的有害影响。
The pathological changes in the retinal microvasculature characteristic of diabetic retinopathy (DR) are the result of chronic exposure to elevated blood glucose. Since glucose entry into the microvascular endothelial cells comprising the inner blood-retinal barrier (BRB) is mediated by the GLUT1 glucose transporter, changes in GLUT1 expression on the inner BRB in long-standing diabetes mellitus may have a direct impact on the subsequent development of retinopathic changes. In the present study, quantitative immunogold electron microscopy for GLUT1 was employed on ultrathin cross-sections of postmortem retina specimens from 3 individuals with long-standing diabetes and minimal or no clinical retinopathy and from 2 non-diabetic individuals without ocular disorders. In the non-diabetic retinal capillaries, GLUT1 immunogold was distributed asymmetrically between the lumenal and ablumenal membranes with a lumenal-to-ablumenal ratio of 1 to 1.7. In the diabetic microvessels, a bimodal distribution pattern of GLUT1 immunoreactivity was observed. In 17 of 40 of the diabetic microvessels examined, the density and distribution of GLUT1 was no different from that of the non-diabetic vessels; however, in a subpopulation of the diabetic microvessels (23 of 40), a dramatic increase in GLUT1 immunoreactivity on the lumenal and albumenal membrane and in the cytoplasm was noted. On the lumenal membrane, the increased expression of immunoreactive GLUT1 was more than 18 times that of the non-diabetic microvessels. These findings demonstrate that localized upregulation of GLUT1 expression at the inner BRB occurs in long-standing diabetes mellitus with minimal or no clinical retinopathy and suggest that this upregulation may serve to amplify the deleterious effects of chronic hyperglycemia on the retinal microvasculature.