ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Animals , Male , Rats , Blood Glucose , Brain , Metabolism , Diabetes Mellitus, Experimental , Metabolism , Glucose Transporter Type 1 , Genetics , Glucose Transporter Type 3 , Genetics , Glycated Hemoglobin , RNA, Messenger , Rats, Wistar , StreptozocinABSTRACT
Streptozotocin-induced diabetic model was prepared in Wistar rats and the blood glucose levels were controlled at 3 levels of＜10,10-14 mmol/L or＞16.7 mmol/L by insulin,and changes of glucose transporter(GLUT)1 and 3 protein expressions of brain were observed in control rats and diabetic rats with different blood glucose levels by immunohistochemistry.The results showed that chronic hyperglycemia could decrease the protein expressions of GLUT 1 and GLUT3.
