Effects of Cyclohexanonic Long-Chain Fatty Alcohol, tCFA15 on Amino Acids in Diabetic Rat Brain: A Preliminary Study

The aim of this study was to evaluate the effects of streptozotocin-induced type 1diabetes and a subchronic treatment with cyclohexanonic long-chain fatty alcohol, 3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen 1-one (tCFA15) on contents of amino acids including aspartate, glutamate, glutamine, GABA, glycine, taurine, alanine, serine, threonine, and arginine in the prefrontal cortex, hippocampus and striatum. Levels of glutamate, threonine, taurine, alanine, arginine, and the ratio of glutamate/glutamine were altered region-differently in the brain of diabetic rats. However, tCFA15 region-specifically antagonized the changes in taurine and arginine levels and the ratio of glutamate/glutamine. The alteration in glutamate/glutamine ratio may indicate that experimental models of type 1 diabetes have abnormalities of neuron-gria interaction in brain.     

A novel alternatively spliced transcript of cytosolic alanine aminotransferase gene associated with enhanced gluconeogenesis in liver of Sparus aurata

Increased alanine aminotransferase (ALT) activity is associated with insulin resistance and the development of type 2 diabetes. The aim of this study was to characterize the modulation of cytosolic ALT expression in liver of gilthead sea bream (Sparus aurata) under conditions associated with increased gluconeogenesis and in streptozotocin (STZ)-treated fish. RT- and RACE-PCR assays allowed us to isolate a novel ALT isozyme (cALT2) generated from alternative splicing of cALT gene in S. aurata. HEK293 cells transfected with constructs expressing cALT2 as a C-terminal fusion with the enhanced green fluorescent protein allowed us to demonstrate that cALT2 is cytosolic. To unravel the molecular functions of cALT1 and cALT2 in liver of S. aurata, we examined tissue distribution, kinetic characterization of piscine cALT isozymes expressed in Saccharomyces cerevisiae, and regulation of hepatic cALT1 and cALT2 expression in various metabolic conditions. Kinetic analysis indicates that cALT2 is more efficient in catalysing the conversion of l-alanine to pyruvate than cALT1. Starvation increased cALT2 expression and decreased cALT1 mRNA in liver. Opposite effects were found in regularly fed fish at postprandial time 4–8 h, and 6 h after treatment with glucose or insulin. From these results we conclude that increased cALT2 expression occurred in liver under gluconeogenic conditions, while cALT1 was predominant during postprandial utilization of dietary nutrients. Since up-regulation of hepatic cALT2 expression occurred in STZ-induced diabetic S. aurata, increased hepatic cALT2 expression may be a promising marker in the prognosis of diabetes.     

恒河猴糖尿病动物模型血清及组织中细胞因子的变化

目的探讨恒河猴糖尿模型病细胞因子的水平和变化规律。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(STZ),血糖稳定后3、9、12和19个月检测血清中白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的含量。安乐濒死状态的动物,取胰腺、肝脏、肾脏制成石蜡切片,用免疫组化染色法显示组织中IL-6、IL-10、TNF-α的表达,并对结果进行图像分析和统计学处理。结果造模后9个月动物血清中IL-10浓度显著降低(P<0.01)。IL-6、TNF-α水平在采样的各个时间点均显著高于造模前(P<0.01)。胰腺组织中IL-6中等强度着色,对照组弱阳性表达(P<0.05)。对照组IL-10强阳性表达,模型组弱阳性(P<0.01)。模型组TNF-α中等强度表达,对照组弱阳性(P<0.05)。模型组肝脏组织TNF-α中等阳性表达,对照组弱阳性(P<0.05)。结论小剂量多次注射STZ后恒河猴细胞因子的含量及变化与临床类似,可作为相关研究的动物模型。     

2型糖尿病大鼠的尿液代谢组学改变

目的 通过检测2型糖尿病大鼠尿液代谢谱的变化.探讨代谢组学在糖尿病研究中的应用.方法 SD大鼠高糖高脂饲料喂养6周后,腹腔注射链脲菌素(Streptozotocin,STZ)37 mg/kg建立2型糖尿病模型,动态检测空腹血糖(FBG)变化,检测甘油三酯(TC)、总胆固醇(TC)、游离脂肪酸(FFA)及胰岛素(INS)...     

Anti-diabetic effect of a novel N-Trisaccharide isolated from Cucumis prophetarum on streptozotocin–nicotinamide induced type 2 diabetic rats

Ethnopharmacological relevanceCucumis prophetarum (L.) is used in traditional Indian medicine for the treatment of inflammation related problems.Aim of the studyThe present investigation was designed to study the effect of N-Trisaccharide (a new compound isolated from the fruit of C. prophetarum (L.)) on hyperglycemia in streptozotocin (STZ)–nicotinamide (NA) induced type 2 diabetic rats.Materials and methodsDifferent doses of N-Trisaccharide (25 and 50 mg/kg b.w.) were administered once daily for 28 days to STZ–NA induced diabetic rats. Plasma insulin and glycogen levels were measured. The activities of hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase were measured. Further, histological studies on pancreas were also carried out.ResultsThe active compound at doses of 25 and 50 mg/kg b.w. given orally for 14 days showed 47.7% and 69.3% antihyperglycemic activity, respectively. Treatment at the same doses for 28 days provided complete protection against STZ–NA challenge (65 and 230 mg/kg b.w., respectively), intraperitoneally. N-Trisaccharide significantly (p ≤ 0.05) increased the plasma insulin and liver glycogen levels in diabetic rats. The altered enzyme activities of carbohydrate metabolism in the liver and kidney of the diabetic rats were significantly (p ≤ 0.05) improved. Additionally, N-Trisaccharide increased glycogen synthase and decreased glycogen phosphorylase activity in diabetic rats. Histological studies confirmed an increase in insulin level is due to stimulation of injured pancreatic β-cells.ConclusionThe results of the study suggested that N-Trisaccharide possesses propitious effect on STZ–NA induced type 2 diabetes, indicating its usefulness in diabetes management.     

The effect of treadmill exercise on inflammatory responses in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type

[Purpose]

The aim of this study was to investigate the effect of treadmill exercise on inflammatory response in streptozotocin (STZ)-induced animal model of Alzheimer’s disease (AD).

[Methods]

To induce the animal model of AD, Sprague-Dawley rats were injected into intracerebroventricular (ICV) injection with 1.5 mg/kg of STZ. Rats were divided into three groups as Sham-con group (n = 7), STZ-con group (n = 7) and STZ-exe group (n = 7). Exercise group ran on the treadmill for 30 min/day, 5 days/week during 6 weeks.

[Results]

The results of this study were as follows: First, STZ-exe group was improved on cognitive function when compared to STZ-con group in water maze test. Second, STZ-exe group help reduce the expression level of amyloid-beta (Aβ). In addition, Toll-like receptors-4 (TLR4), Nuclear factor-kB (NF-kB), Tumor necrosis factor-α (TNF-α) and Interleukin-1α (IL-1α) level of STZ-exe group was significantly decreased when compared to STZ-con group.

[Conclusion]

These results show that treadmill exercise had positive effect on cognitive function and reduced inflammatory response in STZ-induced animal model of AD.     

金黄地鼠胰岛素抵抗和糖尿病动物模型的建立

目的建立胰岛素抵抗和糖尿病动物模型。方法给金黄地鼠喂以高脂果糖饲料,部分给小剂量链脲菌素(30mg/kg)腹腔注射,以正常金黄地鼠作为对照,测定动物体重、空腹血糖、血脂、胰岛素水平,计算胰岛素敏感指数,并对肝脏、胰腺及主动脉弓组织进行形态学比较。结果金黄地鼠经高脂果糖喂养6周制成胰岛素抵抗、肥胖和脂质代谢紊乱的动物模型。再经小剂量一次性腹腔注射链脲菌素后,约80%的胰岛素抵抗和肥胖的金黄地鼠出现显性糖尿病。结论高脂果糖饲料结合小剂量链脲菌素腹腔注射可以制成胰岛素抵抗的2型糖尿病金黄地鼠模型。     

Phytotherapeutic efficacy of the medicinal plant Terminalia catappa L.

Diabetes is a chronic, lifelong condition due to inadequate production of insulin or the cells does not properly respond it. Recently, the significance and effectiveness of herbal drugs associated with diabetes has emerged. The aim of the present study was to determine the anti-diabetic effects of Terminalia catappa L. leaves on streptozotocin (STZ)-treated rats. Two different concentrations of ethanolic leaf extract (300 and 500 mg/kg) of T. catappa were used to treat diabetic rats, and biochemical parameters were analyzed in blood samples. The results of herbal treatments were compared with the standard drug, glibenclamide. The ethanol extract (500 mg/kg) had significant anti-diabetic activity by altering blood glucose, glycosylated hemoglobin, liver glycogen, glucose 6-phosphatase, fructose 1,6-bisphosphatase, glucokinase, aspartate transaminase, alanine transaminase, alkaline phosphatase, urea, uric acid and creatinine levels while increasing insulin levels. Thus, the present study suggests that the supplementation of the diabetic patients with T. catappa leaves can lead to recovery from diabetic effects.     

Biotin amelioration of nephrotoxicity in streptozotocin-induced diabetic mice

The current study was carried out to investigate the protective role of biotin in kidney injury and oxidative stress in diabetic mice type 1. Male Swiss albino mice were randomly divided into 3 groups. Control group received saline. Diabetes type 1 was induced in second and third groups by intraperitoneal injection of streptozotocin as a single dose (150 mg/kg). Second group remained as the untreated diabetic group and the third group received 15 mg/kg daily oral dose of biotin for 12 successive days. Biochemical results showed significant elevation in blood glucose and urea levels in both diabetic groups. Also, there is an increase in glomerular areas and decrease in glomerular cellularity in both diabetic groups. Histopathological results showed severe alterations in the untreated diabetic group represented by distorted glomeruli, inflammatory cells, and giant macrophages. In addition, there was an intense immune-reaction response toward acrolein indicator of oxidative damage. Upon biotin administration of diabetic mice, the above mentioned histopathological changes were reduced and also acroline reaction of oxidative damage was diminished. Our findings prove that biotin has a protective role against streptozotocin-induced oxidative damage in kidneys of laboratory mice.     

Electroacupuncture alleviates diabetic neuropathic pain in rats by suppressing P2X3 receptor expression in dorsal root ganglia

Diabetic neuropathic pain (DNP) is a troublesome diabetes complication all over the world. P2X3 receptor (P2X3R), a purinergic receptor from dorsal root ganglion (DRG), has important roles in neuropathic pain pathology and nociceptive sensations. Here, we investigated the involvement of DRG P2X3R and the effect of 2 Hz electroacupuncture (EA) on DNP. We monitored the rats’ body weight, fasting blood glucose level, paw withdrawal thresholds, and paw withdrawal latency, and evaluated P2X3R expression in DRG. We found that P2X3R expression is upregulated on DNP, while 2 Hz EA is analgesic against DNP and suppresses P2X3R expression in DRG. To evaluate P2X3R involvement in pain modulation, we then treated the animals with A317491, a P2X3R specific antagonist, or α β-me ATP, a P2X3R agonist. We found that A317491 alleviates hyperalgesia, while α β-me ATP blocks EA’s analgesic effects. Our findings indicated that 2 Hz EA alleviates DNP, possibly by suppressing P2X3R upregulation in DRG.