Diabetes downregulates GLUT1 expression in the retina and its microvessels but not in the cerebral cortex or its microvessels
Diabetes downregulates GLUT1 expression in the retina and its microvessels but not in the cerebral cortex or its microvessels
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DOI：
10.2337/diabetes.49.6.1016
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发表时间：
2000-06-01
期刊：
影响因子：
7.7
通讯作者：
Kern, TS
中科院分区：
文献类型：
--
作者：
Badr, GA;Tang, J;Kern, TS
在糖尿病中，视网膜中的毛细血管比胚胎学上类似的大脑皮层中的毛细血管更容易发生微血管病变。由于现有证据表明高血糖症与糖尿病视网膜病变的发病机制有关，因此葡萄糖转运至视网膜和大脑的差异可能导致观察到的对糖尿病诱导的微血管疾病易感性的组织差异。因此，我们通过Western印迹分析比较了GLUT 1和GLUT 3在视网膜、大脑及其各自微血管中的表达水平。在非糖尿病动物中，视网膜及其微血管中的GLUT 1蛋白含量是大脑皮质灰质及其微血管中的数倍。链脲佐菌素诱导的糖尿病2周或2个月的持续时间减少GLUT1在视网膜和其微血管的表达相似的50%，但它不会导致GLUT1在大脑或其微血管的表达减少。糖尿病动物视网膜中毛细血管的密度与正常相比没有变化，因此观察到的糖尿病动物视网膜和视网膜毛细血管中GLUT 1表达的降低不能归因于血管减少。尽管糖尿病大鼠视网膜GLUT1表达减少，但神经视网膜仍比大脑有更多的GLUT1。视网膜色素上皮细胞（RPE）具有更多的GLUT 1比神经视网膜或其微血管，并在RPE中的转运蛋白的表达不受糖尿病的影响，GLUT 3水平在大脑灰质比在视网膜中，他们不受糖尿病在任何组织。糖尿病对GLUT1表达的影响在视网膜和大脑皮层之间不同，这表明葡萄糖转运在这些胚胎学相似的组织中受到不同的调节。由于糖尿病导致视网膜微血管中GLUT1表达下调，但不导致RPE中GLUT1表达下调，因此在糖尿病中进入视网膜的葡萄糖的分数在整个RPE中可能比在整个视网膜血管系统中更大。
Capillaries in the retina are more susceptible to develop microvascular lesions in diabetes than capillaries in the embryologically similar cerebral cortex. Because available evidence implicates hyperglycemia in the pathogenesis of diabetic retinopathy, differences in glucose transport into the retina and brain might contribute to this observed tissue difference in susceptibility to diabetes-induced microvascular disease. Thus, we compared levels of GLUT1 and GLUT3 expression in the retina, cerebrum, and their respective microvessels by Western blot analysis, In nondiabetic animals, the con tent of GLUT1 protein in retina and its microvessels was multifold greater than that of cerebral cortex gray matter and its microvessels. Streptozotocin-induced diabetes of a 2-week or 2-month duration reduced GLUT1 expression in the retina and its microvasculature by similar to 50%, but it resulted in no reduction in GLUT1 expression in cerebrum or its microvessels. The density of capillaries in retinas of diabetic animals did not change from normal, and so the observed decrease in GLUT1 expression in the retina and retinal capillaries of diabetic animals cannot be attributed to fewer vessels. Despite the diabetes-induced reduction of GLUT1 expression in retina, neural retina of diabetic rats still possessed more GLUT1 than the cerebrum. Retinal pigment epithelium (RPE) possessed more GLUT1 than neural retina or its microvessels, and expression of the transporter in the RPE was not affected by diabetes, GLUT3 levels were greater in cerebral gray matter than in retina, and they were unaffected by diabetes in either tissue. The effect of diabetes on GLUT1 expression differs between retina and cerebral cortex, suggesting that glucose transport is regulated differently in these embryologically similar tissues. Because diabetes results in downregulation of GLUT1 expression in retinal microvessels, but not in RPE, the fraction of the glucose entering the retina in diabetes is likely to be greater across the RPE than across the retinal vasculature.