Dynamic expression of glucose transporters 1 and 3 in the brain of diabetic rats with cerebral ischemia reperfusion.

Background: Blood glucose control improves the outcome of diabetic patients with stroke, but the target range of blood glucose control remains controversial. The functional recruitment of ischemia penumbra is extremely important to the recovery after stroke. The present study aimed to explore the expression of brain-type glucose transporters (GLUT1 and GLUT3) in cerebral ischemic penumbra at different blood glucose levels and different ischemic-reperfusion time in diabetic hypoxia-ischemia rats. The results might provide an experimental basis for clinical treatment of diabetic patients with stroke.

Methods: The Wistar rats included in this study were randomly assigned to 4 groups (50 rats each): normal control group (NC), uncontrolled diabetic group (DM1), poorly-controlled diabetic group (DM2), and well-controlled diabetic group (DM3). Diabetic rats were induced by single intraperitoneal injection of streptozotocin, and the focal ischemic rat model of middle artery occlusion (MCAO) was made by insertion of fishing thread in 6 weeks after the establishment of the diabetic model. Each group was divided into 5 subgroups (10 rats each): four focal ischemic subgroups at different ischemic-reperfusion time (at 3,12, 24 and 72 hours after reperfusion, respectively) and one sham-operated subgroup. The mRNA and protein expression of GLUT1 and GLUT3 was assessed by RT-PCR and Western blotting, respectively.

Results: There was significant difference in the mRNA expression of GLUT1 and GLUT3 between the four focal ischemic subgroups and the sham-operated subgroup at different reperfusion time in each group. The mRNA expression of GLUT1 and GLUT3 in the 4 ischemic groups began to increase at 3 hours, peaked at 24 hours after reperfusion and maintained at a higher level even at 72 hours compared with that of the sham-operated subgroup. The mRNA expression of GLUT1 increased more significantly than that of GLUT3. The mRNA expression of GLUT1 and GLUT3 was significantly different between the diabetic groups and normal control group. The mRNA expression of GLUT1 and GLUT3 was increased more significantly in the diabetic groups than that in the normal control group. There was a significant difference in the mRNA expression in the groups with different blood glucose levels. The mRNA expression tended to decrease with increased blood glucose levels. The expression trend of GLUT1 and GLUT3 protein was similar to that of GLUT1 and GLUT3 mRNA.

Conclusions: GLUT1 and GLUT3 expression was notably up-regulated in the penumbra region after cerebral ischemia in this study. But the up-regulated amplitude of GLUT1 and GLUT3 in the diabetic rats with cerebral ischemic injury became smaller than that of the normal controls. In the treatment of diabetic patients with cerebral embolism, blood glucose control should not be too strict, otherwise the up-regulation of GLUT1 and GLUT3 induced by cerebral ischemic injury might not be able to meet the needs of energy metabolism in cells.