Search

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.

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.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.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.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.

Background Many researches suggested that obesity increased the risk of breast cancer, but the mechanism was currently unknown. Adipocytokines might mediate the relationship. Our study was aimed to investigate the relationship between serum levels of resistin, adiponectin and leptin and the onset, invasion and metastasis of breast cancer. Methods Blood samples were collected from 80 newly diagnosed, histologically confirmed breast cancer patients and 50 age-matched healthy controls. Serum levels of resistin, adiponectin and leptin were determined by enzyme-linked immunosorbent assays (ELISA); fasting blood glucose (FBG), lipids, body mass index (BMI), and waist circumference (WC) were assayed simultaneously. Results Serum levels of adiponectin ((8.60 +/- 2.92) mg/L vs (10.37 +/- 2.81) mg/L, P = 0.001) and HDL-c were significantly decreased in breast cancer patients in comparison to controls. Serum levels of resistin ((26.35 +/- 5.36) microg/L vs (23.32 +/- 4.75) microg/L, P = 0.000), leptin ((1.35 +/- 0.42) microg/L vs (1.06 +/- 0.39) microg/L, P = 0.003), FBG and triglyceride (TG) in breast cancer patients were increased in contrast to controls, respectively. However, we did not find the significant difference of the serum levels of resistin, adiponectin and leptin between premenopausal breast cancer patients and healthy controls (P = 0.091, 0.109 and 0.084, respectively). The serum levels of resistin, adiponectin and leptin were significantly different between patients with lymph node metastasis (LNM) and those without LNM (P = 0.001, 0.000 and 0.006, respectively). The stepwise regression analysis indicated that the tumor size had the close correlation with leptin (R(2) = 0.414, P = 0.000) and FBG (R(2) = 0.602, P = 0.000). Logistic regression analysis showed that reduced serum levels of adiponectin (OR: 0.805; 95% CI: 0.704 - 0.921; P = 0.001), HDL (OR: 0.087; 95% CI: 0.011 - 0.691, P = 0.021), elevated leptin (OR: 2.235; 95% CI: 1.898 - 4.526; P = 0.004) and resistin (OR: 1.335; 95% CI: 1.114 - 2.354; P = 0.012) increased the risk for breast cancer; Reduced serum levels of adiponectin (OR: 0.742; 95% CI: 0.504 - 0.921; P = 0.003) and elevated leptin (OR: 2.134; 95% CI: 1.725 - 3.921; P = 0.001) were associated with lymph node metastasis of breast cancer. Conclusions The decreased serum adiponectin levels and increased serum resistin and leptin levels are risk factors of breast cancer. The low serum adiponectin levels and high serum leptin levels are independent risk factors for metastasis of cancer. The association between obesity and breast cancer risk might be explained by adipocytokines.