Brain tryptophan uptake and sodium-potassium ATPase activity in long-term streptozotocin diabetic rats

Serum, liver and brain tryptophan concentrations and brain Na⁺K⁺-ATPase activity were studied in streptozotocin diabetic rats after an acute tryptophan load. Results show that tryptophan administration in the experimental diabetic group produces a generalized fall in tryptophan uptake in all the brain regions studied, though it does not increase serum and hepatic tryptophan concentrations. These parameters are normalized in insulin-treated diabetic rats. With regard to Na⁺K⁺-ATPase, diabetic animals showed a diminished and unchanged activity; whereas, the other two experimental groups showed a gradual decrease and a negative correlation with brain tryptophan uptake.     

Insulin secretagogue effect of Ichnocarpus frutescence leaf extract in experimental diabetes: a dose-dependent study

Ichnocarpus frutescence (L.) R.Br. is an evergreen plant and many preparations have been used in traditional Indian medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. In the present study we prepared various extracts of I. frutescence (IF) leaves which were tested against streptozotocin-induced diabetic rats. IF leaf methanolic extract (IFLMExt) showed significant plasma glucose lowering effect. Therefore, we prepared IFLMExt, which was tested against different types of glycemia (normal, glucose-fed hyperglycemic and streptozotocin-induced diabetic rats) for their potential to induce insulin secretion and cellular insulin responses. Fasting plasma glucose (FPG) levels were determined at different doses and times following treatment with IFLMExt or with vehicle in normal, glucose fed-hyperglycemic and diabetic rats. Oral administration of IFLMExt led to a significant blood glucose-lowering effect in glucose-fed hyperglycemic and diabetic rats. The hypoglycemic effect was observed at doses of 100 and 200 mg/(kg bw) after 6 and 2 h administration, respectively, in glucose-fed hyperglycemic rats. The maximum effect of IFLMExt was detected at 2 h with 200 mg/(kg bw) in diabetic animals and this profile was maintained for the next 6 h (37.23%) but increased after that at 24 h. Oral administration of IFLMExt daily for 45 days to diabetic rats significantly reduced the FPG (54.5%) to near normal. After 7 days of streptozotocin administration plasma insulin decreased in diabetic controls compared to normal controls. Treatment with IFLMExt significantly prevented the decrease in plasma insulin levels from day 0 to 45 in comparison to diabetic controls. Oral administration of n-hexane fraction led to a significant glucose-lowering effect in diabetic rats (54.50%). Histopathological examination showed that IFLMExt extract protected the pancreatic tissue from streptozotocin-induced damage enormously. Oral administration of IFLMExt extract and n-hexane fraction to normal and streptozotocin-induced diabetic rats decreased plasma glucose levels without hypoglycemic effect. The results suggest that methanolic extract and n-hexane fraction of IF may provide new therapeutic avenues against diabetes.     

链尿佐菌素加高糖高脂饮食复制大鼠2型糖尿病模型

目的链尿佐菌素加高糖高脂饮食诱导大鼠2型糖尿病模型的建立。方法SD雄性大鼠高糖高脂饲料喂养3周后,采血检测空腹血糖及血清胰岛素,按25mg/g体重剂量一次性腹腔内注射链尿佐菌素,3d后,行糖耐量实验,对糖耐量异常大鼠继续喂以高糖高脂饲料,在第2、第4周再两次采血检测糖尿病鼠空腹血糖及血清胰岛素。结果与对照组比较,高糖高脂喂养大鼠血清胰岛素明显上升（P〈0.01）,但血糖无变化（P〉0.05）,糖尿病鼠血糖及血清胰岛素均显著的高于对照组（P〈0.01）。结论高糖高脂喂养能致大鼠明显的高胰岛素血症,辅以小剂量一次性注射链尿佐菌素而造成的糖耐量异常,可成功复制出2型糖尿病大鼠模型。     

Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats

We have recently shown free radical generation is associated with cognitive impairment in intracerebroventricular (ICV) streptozotocin (STZ) model of sporadic dementia of Alzheimer's type in rats. Trans resveratrol is a polyphenolic compound and is known to have antioxidant activity. In the present study, the effect of trans resveratrol was investigated on ICV STZ induced cognitive impairment and oxidative stress in rats. Adult male Wistar rats were injected with ICV STZ bilaterally, on day 1 and day 3. The learning and memory behavior was assessed using passive avoidance paradigms, elevated plus maze and the closed field activity test while the parameters of oxidative stress assessed were malondialdehyde [MDA] and glutathione. The rats were treated with trans resveratrol chronically at doses of 10 and 20 mg/kg,i.p. for 21 days starting from day 1 of STZ injection. Trans resveratrol treatment significantly prevented ICV STZ induced cognitive impairment. There was a rise in brain glutathione and an insignificant increase in brain MDA in trans resveratrol treated ICV STZ rats as compared to significantly elevated brain MDA levels in the vehicle treated ICV STZ animals. The study demonstrates the effectiveness of trans resveratrol in preventing the cognitive deficits as well as the oxidative stress caused by ICV STZ in rats and it's potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.     

Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice

Reactive oxygen species (ROS) may play key roles in vascular inflammation and atherogenesis in patients with diabetes. In this study, xanthine oxidase (XO) system was examined as a potential source of superoxide in mice with streptozotocin (STZ)-induced experimental diabetes. Plasma XO activity increased 3-fold in diabetic mice (50±33 μU/ml) 2 weeks after the onset of diabetes, as compared with non-diabetic control mice (15±6 μU/ml). In vivo superoxide generation in diabetic mice was evaluated by an in vivo electron spin resonance (ESR)/spin probe method. Superoxide generation was significantly enhanced in diabetic mice, and the enhancement was restored by the administration of superoxide dismutase (SOD) and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), which was reported to scavenge superoxide. Pretreatment of diabetic mice with XO inhibitors, allopurinol and its active metabolite oxipurinol, normalized the increased superoxide generation. In addition, there was a correlation (r=0.78) between the level of plasma XO activity and the relative degree of superoxide generation in diabetic and non-diabetic mice. Hence, the results of this study strongly suggest that superoxide should be generated through the increased XO seen in the diabetic model mice, which may be involved in the pathogenesis of diabetic vascular complications.     

Effects of beta-carotene on oxidative stress in normal and diabetic rats

Increasing interest in the role of oxidative stress and beta-carotene in disease and prevention led us to examine the results of beta-carotene's administration in diabetic rats, a model for high-oxidative stress. In this experiment, amounts of lipid peroxidation, glutathione, and glutathione disulfide, and activity levels of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and gamma-glutamyl transpeptidase were measured in the liver, kidney, and heart of Sprague-Dawley rats with streptozotocin-induced diabetes, and after treatment with 10 mg/kg/day of beta-carotene for 14 days. Beta-carotene treatment resulted in the reversal of the diabetes-induced increase in hepatic and cardiac catalase activity, the decreased levels of glutathione disulfide in the heart, and the increased cardiac and renal levels of lipid peroxidation. Treatment with beta-carotene exacerbated the increased glutathione peroxidase activity in the heart and the decreased catalase activity in the kidneys. In contrast to reduced hepatic glutathione levels in untreated diabetic rats, beta-carotene treatment increased glutathione levels in diabetic rats. Increased hepatic gamma-glutamyl transpeptidase activity in diabetic rats was not reduced by treatment. Thus, beta-carotene therapy for 14 days prevented/reversed some, but not all, diabetes-induced changes in oxidative stress parameters.     

Diabetic changes in the redox status of the microsomal protein folding machinery

Changes in assisted protein folding are largely unexplored in diabetes. In the present studies, we have identified a reductive shift in the redox status of rat liver microsomes after 4 weeks of streptozotocin-induced diabetes. This change was reflected by a significant increase in the total- and protein-sulfhydryl content, as well as in the free sulfhydryl groups of the major protein disulfide isomerases (PDIs), the 58 kDa PDI and the 57 kDa ERp57 but not other chaperones. A parallel decrease of the protein-disulfide oxidoreductase activity was detected in the microsomal fraction of diabetic livers. The oxidant of PDI, Ero1-Lalpha showed a more oxidized status in diabetic rats. Our results reveal major changes in the redox status of the endoplasmic reticulum and its redox chaperones in diabetic rats, which may contribute to the defective protein secretion of the diabetic liver.     

Effect of Eugenia Jambolana seed kernel on antioxidant defense system in streptozotocin-induced diabetes in rats

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. The aim of this study was to investigate the effect of ethanolic extract of Eugenia jambolana seed kernel on antioxidant defense systems of plasma and pancreas in streptozotocin-induced diabetes in rats. The levels of glucose, vitamin-C, vitamin-E, ceruloplasmin, reduced glutathione and lipidperoxides were estimated in plasma of control and experimental groups of rats. The levels of lipidperoxides, reduced glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were assayed in pancreatic tissue of control and experimental groups of rats. A significant increase in the levels of plasma glucose, vitamin-E, ceruloplasmin, lipid peroxides and a concomitant decrease in the levels of vitamin-C, reduced glutathione were observed in diabetic rats. The activities of pancreatic antioxidant enzymes were altered in diabetic rats. These alterations were reverted back to near normal level after the treatment with Eugenia jambolana seed kernel and glibenclamide. Histopathological studies also revealed that the protective effect of Eugenia jambolana seed kernel on pancreatic beta-cells. The present study shows that Eugenia jambolana seed kernel decreased oxidative stress in diabetic rats, which inturn may be due to its hypoglycemic property.     

链脲佐菌素诱导糖尿病恒河猴胰岛细胞数量的变化

目的观察链脲佐菌素（STZ）诱导恒河猴糖尿病动物模型胰岛细胞数量变化和激素表达情况。方法健康恒河猴5只,小剂量（30 mg/kg）多次静脉注射STZ,濒死状态时将动物安乐死。取胰腺制成石蜡切片,用免疫组化染色法显示胰岛A、B、D和PP细胞,并对结果进行图像分析和统计学处理。结果与对照组比较,模型组B细胞数量减少,胰岛素表达降低（P〈0.01）。A细胞增生,胰高血糖素表达增加（P〈0.01）。PP细胞增生,胰多肽表达增加（P〈0.05）。D细胞数量与对照组比较无显著性差异。结论恒河猴糖尿病动物模型胰岛各种细胞的数量和激素表达情况与人类糖尿病类似。     

STZ诱导恒河猴糖尿病动物模型的建立

目的复制稳定的链脲佐菌素诱导糖尿病恒河猴动物模型。方法健康恒河猴5只,小剂量（30mg/kg）多次静脉注射链脲佐菌素,分别在注射后2、3个月进行葡萄糖耐量实验并连续观察血糖、胰岛素、C肽的变化。连续观察12个月。结果随着时间推移,动物出现典型的糖尿病症状。3只动物的血糖静脉注射1次后持续10周稳定,另外2只分别进行了第2、3次注射。动物血糖在12个月内平稳上升、胰岛素、C肽分泌持续下降。2个月时葡萄糖耐量减低明显（P〈0.01）。结论小剂量多次注射STZ后恒河猴可出现持续、稳定的糖尿病表现,可作为相关研究的动物模型。