血糖对糖尿病大鼠脑内葡萄糖转运蛋白1和3表达的影响。

Influence of blood glucose on the expression of glucose trans-porter proteins 1 and 3 in the brain of diabetic rats.

作者信息

Hou Wei-kai, Xian Yu-xin, Zhang Li, Lai Hong, Hou Xin-guo, Xu Yu-xin, Yu Ting, Xu Fu-yu, Song Jun, Fu Chun-li, Zhang Wen-wen, Chen Li

机构信息

Department of Endocrinology, Qilu Hospital of Shandong University, Jinan 250012, China.

出版信息

Chin Med J (Engl). 2007 Oct 5;120(19):1704-9.

PMID:17935675

Abstract

BACKGROUND

The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier (BBB), which is mediated by the facilitative glucose transporter protein 1 (GLUT(1)), and then across the neural cell membranes, which is mediated by GLUT(3). This study aimed to evaluate the dynamic influence of hyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucose levels in a rat model of diabetes. This might help to determine the proper blood glucose threshold level in the treatment of diabetic apoplexy.

METHODS

Diabetes mellitus was induced with streptozotocin (STZ) in 30 rats. The rats were randomly divided into 3 groups: diabetic group without blood glucose control (group DM1), diabetic rats treated with low dose insulin (group DM2), and diabetic rats treated with high dose insulin (group DM3). The mRNA and protein levels of GLUT(1) and GLUT(3) were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively.

RESULTS

Compared with normal control rats, the GLUT(1) mRNA was reduced by 46.08%, 29.80%, 19.22% (P < 0.01) in DM1, DM2, and DM3 group, respectively; and the GLUT(3) mRNA was reduced by 75.00%, 46.75%, and 17.89% (P < 0.01) in DM1, DM2, and DM3 group, respectively. The abundance of GLUT(1) and GLUT(3) proteins had negative correlation with the blood glucose level (P < 0.01). The density of microvessels in the brain of diabetic rats did not change significantly compared with normal rats.

CONCLUSIONS

Chronic hyperglycemia downregulates GLUT(1) and GLUT(3) expression at both mRNA and protein levels in the rat brain, which is not due to the decrease of the density of microvessels. The downregulation of GLUT(1) and GLUT(3) expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to cell damage.

摘要

背景

葡萄糖从血液输送到大脑，需先穿过血脑屏障（BBB）的内皮细胞，此过程由易化葡萄糖转运蛋白1（GLUT(1)）介导，然后穿过神经细胞膜，由GLUT(3)介导。本研究旨在通过测量糖尿病大鼠模型在不同血糖水平下大脑中这些葡萄糖转运蛋白的表达，评估高血糖对其表达的动态影响。这可能有助于确定糖尿病性中风治疗中合适的血糖阈值水平。

方法

用链脲佐菌素（STZ）诱导30只大鼠患糖尿病。大鼠随机分为3组：未控制血糖的糖尿病组（DM1组）、低剂量胰岛素治疗的糖尿病大鼠组（DM2组）和高剂量胰岛素治疗的糖尿病大鼠组（DM3组）。分别采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学法检测GLUT(1)和GLUT(3)的mRNA和蛋白水平。

结果

与正常对照大鼠相比，DM1组、DM2组和DM3组的GLUT(1) mRNA分别降低了46.08%、29.80%、19.22%（P < 0.01）；DM1组、DM2组和DM3组的GLUT(3) mRNA分别降低了75.00%、46.75%和17.89%（P < 0.01）。GLUT(1)和GLUT(3)蛋白丰度与血糖水平呈负相关（P < 0.01）。与正常大鼠相比，糖尿病大鼠脑内微血管密度无明显变化。