Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of theblood-brain barrier (BBB),which is mediated by the facilitative glucose transporter protein 1 (GLUT_1),and then across theneural cell membranes,which is mediated by GLUT_3.This study aimed to evaluate the dynamic influence ofhyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucoselevels in a rat model of diabetes.This might help to determine the proper blood glucose threshold level in the treatment ofdiabetic apoplexy.Methods Diabetes mellitus was induced with streptozotocin(STZ)in 30 rats.The rats were randomly divided into 3groups: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 wereassayed 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) inDM1,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 withthe blood glucose level (P<0.01).The density of microvessels in the brain of diabetic rats did not change significantlycompared with normal rats.Conclusions Chronic hyperglycemia downregulates GLUT_1 and GLUT_3 expression at both mRNA and protein levels inthe rat brain,which is not due to the decrease of the density of microvessels.The downregulation of GLUT_1 and GLUT_3expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to celldamage.Chin Med J 2007;120(19):1704-1709 Background The delivery of glucose from the blood to the brain to 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 ofhyglyglycemia 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 wereassayed by reverse transcriptase-polymerase chain reactio (RT-PCR) and immunohistochemistry, respectively. Compared with normal control rats, the GLUT_1 mRNA was reduced by 46.08%, 29.80%, 19.22% (P <0.01) The mRNA was reduced by 75.00%, 46.75%, and 17.89% respectively (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) density of microvessels in the brain of diabetic rats did not change significantlycompared with normal rats. Conclusions Chronic hyperglycemia downregulates GLUT_1 and GLUT_3 expression at both mRNA and protein levels inthe rat brain, which is not due to the decrease of the density of microvessels.The downregulation of GLUT_1 and GLUT_3expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to celldamage. Chin Med J 2007; 120 (19): 1704-1709