Antihyperglycemic activity of Piper betle leaf on streptozotocin-induced diabetic rats

Piper betle, an indigenous medicinal plant, has a folk (Siddha and Ayurvedha) reputation in the rural southern India. The present study was carried out to evaluate the effect of P. betle on glucose metabolism since it is consumed as betel-quid after meals. Plasma levels of glucose and glycosylated hemoglobin and activities of liver hexokinase and gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase in control and streptozotocin (STZ) diabetic rats were assayed. Oral administration of leaf suspension of P. betle (75 and 150 mg/kg of body weight) for 30 days resulted in significant reduction in blood glucose (from 205.00 +/- 10.80 mg/dL to 151.30 +/- 6.53 mg/dL) and glycosylated hemoglobin and decreased activities of liver glucose-6-phosphatase and fructose-1,6-bisphosphatase, while liver hexokinase increased (P < .05), in STZ diabetic rats when compared with untreated diabetic rats. P. betle at a dose of 75 mg/kg of body weight exhibited better sugar reduction than 150 mg/kg of body weight. In addition, protection against body weight loss of diabetic animals was also observed. The effects produced by P. betle were compared with the standard drug glibenclamide. Thus, the present study clearly shows that P. betle intake influences glucose metabolism beneficially.     

Antihyperglycemic property of Tragia cannabina in streptozotocin-induced diabetic rats

The present study was performed to investigate the efficacy of an ethanol extract of the roots of Tragia cannabina for antihyperglycemic and antioxidant effects in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were administered T. cannabina (250 mg/kg) orally for 21 days, and blood glucose level was measured weekly. At the end of 21 days, concentrations of serum lipids such as total cholesterol, triglycerides, and high-density lipoprotein (HDL) and protein markers such as total protein, albumin, globulin, and albumin:globulin ratio (A:G) were estimated. Also, levels of enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (ALP) were determined. Antioxidant activity of the extract was evaluated by estimating lipid peroxides (LPO), superoxide dismutase (SOD), and catalase in liver of normal control and STZ- and extract-treated rats. Histopathological changes of liver and kidney were also studied in STZ-induced diabetic animals and normal controls. All these effects produced by the extract were compared with glibenclamide, a standard antidiabetic drug. Oral administration of T. cannabina for 21 days resulted in a significant reduction in blood glucose level, lipid concentration, and SGOT, SGPT, ALP, and LPO levels accompanied by an increase in the levels of SOD and catalase in liver tissues of STZ-induced diabetic rats. Altered levels of protein markers also reverted back to normal. Histopathological changes of liver and kidney were returned to normal. The effects produced by the extract were comparable to that of glibenclamide. In conclusion, the T. cannabina showed significant antihyperglycemic and antioxidant effects in STZ-induced diabetic rats.     

Antihyperglycemic effect of Fomitopsis pinicola extracts in streptozotocin-induced diabetic rats

The antihyperglycemic effect of a water extract (WE) and an alkali extract (AE) of the Fomitopsis pinicola fruit body was studied in streptozotocin (STZ)-induced diabetic rats. The STZ-induced diabetes mellitus (DM) control group lost a significant amount of body weight, whereas the normal control group (NC) gained weight; however, the DM-AE group gained a significant amount of weight, with weight gain approaching normal. Feed intake by the DM-AE group was also similar to the NC group. The liver and kidney weights per body weight increased with the STZ treatment; however, the weights were lower in the F. pinicola-treated groups and nearly normalized in the DM-AE group. The weights of the heart, lungs, and spleen were not influenced by the STZ treatment. Blood glucose levels of F. pinicola-treated DM groups were significantly lower than that of the DM group. In particular, STZ-induced hyperglycemia was remarkably inhibited by the AE-supplemented diet. Serum insulin levels were decreased with STZ injection; however, the decreased levels were almost restored to the NC level with F. pinicola supplementation. The increased serum fructosamine levels associated with hyperglycemia were decreased with the F. pinicola treatment. Cells of the pericentral regions were found to have significant swelling, and some necrotic cells were observed in the pancreas of DM animals; however, pancreatic tissue damage by STZ in the F. pinicola-supplemented diet groups was ameliorated. In this study, the AE from F. pinicola showed the highest antidiabetic effect among the treatments. These results indicate that constituents of F. pinicola may regulate hyperglycemia via either increased insulin secretion during recovery or the prevention of STZ-induced pancreatic damage. This is the first report of antihyperglycemic effects of F. pinicola in STZ-induced DM rats.     

Antioxidant effect of Phaseolus vulgaris in streptozotocin-induced diabetic rats

The antioxidant effect of an aqueous extract of Phaseolus vulgaris pods, an indigenous plant used in Ayurvedic medicine in India, was studied in rats with streptozotocin-induced diabetes. Oral administration of Phaseolus vulgaris pod extract (PPEt; 200 mg/kg body weight) for 45 days resulted in a significant reduction in thiobarbituric acid reactive substances and hydroperoxides. The extract also causes a significant increase in reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the liver and kidneys of rats with streptozotocin-induced diabetes. These results clearly show the antioxidant property of PPEt. The effect of PPEt at 200 mg/kg body weight was more effective than glibenclamide.     

Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice

Depression is highly prevalent in diabetics and is associated with poor glucose regulation and increased risk of diabetic complications. Identification and effective treatment of comorbid depression are increasingly being considered essential components of clinical care of diabetics. In the present study, the antidepressant activity of quercetin (50 and 100 mg/kg, i.p.), a bioflavonoid, was evaluated using the Porsolt forced swimming-induced behavioral despair test in control and 6-week-streptozotocin-induced diabetic mice. The effect of quercetin was compared with that of the classical antidepressants fluoxetine (5 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.). Streptozotocin-induced diabetic mice exhibited prolonged immobility duration during the test as compared with age-matched control mice. Quercetin dose-dependently reduced the immobility period in diabetic mice, and this effect was comparable to that of fluoxetine (5 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.). Fluoxetine and imipramine significantly lowered the immobility time in naive mice also, but quercetin failed to induce any antidepressant activity in naive mice. The results of our preliminary study indicate that quercetin has the potential to be employed as a therapy for depression associated with diabetes.     

Tissue zinc status of genetically diabetic and streptozotocin-induced diabetic mice

A structural and functional relationship exists between zinc and insulin. In the present study zinc concentrations of various tissues from genetically diabetic and streptozotocin-induced diabetic mice and their appropriate control mice were determined. The zinc concentrations were depressed in serum and femur of C57BL/Ks-db+/db+ mice (db/db) when compared with their nondiabetic heterozygote controls (db/m) and homozygous controls (m/m). No differences were noted in the hepatic or renal Zn concentration of the db/db, db/m, or m/m mice. Zinc supplementation in the drinking water for a 4-wk period had no effect on serum or tissue zinc concentration. Hyperzincuria was noted in the db/db mice. No differences were noted in the Zn concentration of serum or tissue in streptozotocin-induced diabetic mice compared to their controls. These data suggest that zinc deficiency may play a role in the pathogenesis of the insulin resistance present in type II (insulin independent) diabetics.     

Beta-carotene 15,15'-dioxygenase activity in streptozotocin-induced diabetic rats

We measured retinol levels and beta-carotene 15,15'-dioxygenase activity in rats with streptozotocin-induced diabetes mellitus to assess the relationship between the disease and the conversion of beta-carotene to retinol. The plasma retinol level was significantly lower in diabetic rats than in control rats, but the hepatic retinol level was significantly higher than the control. The hepatic dioxygenase activity, but not that of the intestinal mucosa, was significantly lower in diabetic rats than in control rats. The hepatic dioxygenase activity showed a significant negative correlation with the hepatic retinol levels. The results suggest the disturbed secretion of retinol from the liver and suppression of hepatic dioxygenase activity by the retinol increased in the liver in diabetic rats.     

糖尿病小鼠心脏组织miRNA分析及靶基因检测

目的 检测糖尿病模型小鼠心肌组织microRNA（miRNA）表达,并对差异miRNA调控的靶基因进行初步预测及检测。方法 C57BL/6小鼠随机分为对照组和糖尿病模型组2组,以150 mg/kg链脲佐菌素腹腔一次性注射建立糖尿病心肌模型,6周后检测小鼠体重、血糖,取心脏组织,利用实时定量PCR（qRT-PCR）法检测小鼠心肌组织中miRNAs的表达,利用TargetScan、miRarnada和PicTar等数据库预测靶基因,并选择与心肌肥大或心肌纤维化相关基因进行功能分析和检测。结果 组织学观察发现,糖尿病小鼠心肌细胞明显肥大,细胞间质呈纤维化,并且心脏/体重比增高;qRT-PCR结果显示,13个miRNA差异表达,其中miR-19a、miR-19b、miR-22、miR-503、miR-467e表达上调,miR-1、miR-29a、miR-30a、miR-96、miR-101a、miR-142-3p、miR-199-5p、miR-374表达下调;心肌肥大或心肌纤维化相关基因 Bnp、Myh7 和 Ccnd1表达上调,Hadc1、Col1a1和Vcam1表达下调。结论 miRNA可能通过调控糖尿病小鼠心肌组织中靶基因参与糖尿病心肌病发病过程。     

Determination of Ca2+-atpase activity in streptozotocin-induced diabetic rat liver

Microsomal Ca2+-ATPase activity was studied in control and streptozotocin (STZ)-induced diabetic rat livers. Male rats were rendered diabetic by injection of STZ (45 mg/kg body weight) via the tail vein. Diabetic rats at 1, 4, 8, 10 or 15 wk and control rats were sacrificed. Liver tissues were obtained for the isolation of Ca2+-ATPase. Ca2+-ATPase activity was determined spectrophotometrically and lipid peroxidation [measured as tiobarbituric acid reactive substances (TBARS)] in liver tissues was determined spectrofluorometrically. Total calcium was measured by atomic absorption spectrophotometry. Blood glucose levels of the diabetic animals were >500 mg/dl at 4, 8, 10 and 15 wk of diabetes. Ca2+-ATPase activity was significantly decreased at all weeks of diabetes compared to control group (p<0.001). Ca2+-ATPase activity of control rats was 0.193 +/- 0.015 U/I whereas activity was 0.130 +/- 0.015 U/I at 15 wk of diabetes. The difference in calcium levels of diabetic rat livers was not significantly different compared to control group. On the other hand TBARS were elevated by 67% at 15 wk of diabetes. The decrease in enzyme activity may have been caused by elevated TBARS levels observed in liver tissue sindicative of increased lipid peroxidation.     

Anti-diabetic activity of Eugenia jambolana seed kernels on streptozotocin-induced diabetic rats

The present study evaluated the hypoglycemic activity of different parts of Eugenia jambolana seeds such as whole seed, kernel, and seed coat on streptozotocin-induced diabetic rats. Administration of the ethanolic extract of kernel at a concentration of 100 mg/kg of body weight significantly decreased the levels of blood glucose, blood urea, and cholesterol, increased glucose tolerance and levels of total proteins and liver glycogen, and decreased the activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in experimental diabetic rats. Whole seed showed a moderate hypoglycemic effect, and seed coat did not show any hypoglycemic effect. The hypoglycemic efficacy was compared with that of glibenclamide, a standard hypoglycemic drug.     

Olive leaf down-regulates the oxidative stress and immune dysregulation in streptozotocin-induced diabetic mice

Type 1 diabetes is an endocrinologic disorder characterized by uncontrolled glucose regulation and oxidative stress. Olive leaves have been studied extensively for their antioxidant activity and capacity to improve immune function. We hypothesized that olive leaf powder supplementation will be effective in inhibiting the oxidative stress and immune dysregulation in streptozotocin (STZ)-induced diabetic mice. Mice were assigned to 1 of 5 groups: control (C), STZ-induced diabetes (D), and STZ-induced diabetes supplemented with very low dose (VLOL), low dose (LOL), or high dose of olive leaf powder (HOL). Blood glucose in the VLOL and LOL groups was lower than that in the D group (P < .05). Insulin levels were increased in all experimental groups in comparison with that in the D group, (P < .05). Superoxide dismutase, glutathione peroxidase, and catalase activities were shown to decrease in the D group, whereas these were increased in the VLOL and LOL groups. Nitric oxide levels decreased in the VLOL and LOL groups, as compared with the D group. The messenger RNA expression levels of inducible nitric oxide synthase were significantly decreased in the VLOL and HOL groups, and interferon-γ levels were significantly decreased in the liver of the VLOL, LOL, and HOL groups compared with the levels in the D group. Interleukin-17 levels were significantly decreased in the VLOL and HOL groups. Th1 and Th17 cytokine levels were increased in the D group but decreased in all the experimental groups. Th2 cytokine levels were increased in all olive leaf–supplemented groups compared with those in the D group. These results indicate a reduction in the levels of proinflammatory cytokines, suggesting that olive leaves have the potential to provide therapeutic inhibition of diabetic complications.     

Preimplantation development in the streptozotocin-induced diabetic mouse

Streptozotocin (STZ) was used to develop a diabetic mouse model in which to study the development of the preimplantation embryo. STZ doses of 0, 160, 190, 210 and 240 mg kg-1 were given; 190 mg kg-1 was found to be the most suitable as the standard diabetogenic dose, providing about 60% mice with plasma glucose greater than 20 mM. The STZ-diabetic mice responded to superovulation with 10 i.u. of gonadotrophin in the same manner as control mice, producing similar embryo numbers at 48 h, 72 h and 96 h post-hCG. Furthermore, the proportion of 2-cell embryos collected from STZ-diabetic mice which developed to blastocysts in vitro was similar to that of 2-cell embryos from control mice. The STZ-diabetic mouse model after superovulation thus produced normal early preimplantation embryos whose development can be examined in detail in a diabetic environment.     

Oral administration of insulin-like growth factor-I from colostral whey reduces blood glucose in streptozotocin-induced diabetic mice

The aim of the present study was to investigate the effects of oral administration of the insulin-like growth factor-I-rich fraction (IGF-I-RF) from bovine colostral whey on the regulation of blood glucose levels in streptozotocin (STZ)-induced diabetic mice. We obtained a peptide fraction containing IGF-I (10 ng/mg protein) from Holstein colostrum within 24 h after parturition by using ultrafiltration. The blood glucose levels of STZ-induced diabetic mice fed with IGF-I-RF (50 μg/kg per d) were significantly reduced by 11 and 33 % at weeks 2 and 4, respectively (P < 0·05). The body weights of STZ-induced diabetic mice increased following the oral administration of the IGF-I-RF. The kidney weights of STZ-induced diabetic mice decreased significantly (P < 0·05) following the administration of the IGF-I-RF, and the liver weights of STZ-induced diabetic mice decreased significantly (P < 0·05) following the administration of 50 μg/kg per d of the IGF-I-RF. The present results indicate that the IGF-I-RF obtained from Holstein colostrum could be a useful component for an alternative therapeutic modality for the treatment of diabetes in insulin-resistant patients.     

Antidiabetic activity of isoquercetin in diabetic KK -Ay mice

Background

Protective effects of omega-3 fatty acids against cellular damages of high glucose were studied on retinal pigmented epithelial (RPE) cells.

Methods

Retinal epithelial cells were incubated with omega-3 marine oils rich in EPA and DHA and then with high glucose (25 mM) for 48 hours. Cellular responses were compared to normal glucose (5 mM): intracellular redox status, reactive oxygen species (ROS), mitochondrial succinate deshydrogenase activity, inflammatory cytokines release and caveolin-1 expression were evaluated using microplate cytometry, ELISA and flow cytometry techniques. Fatty acids incorporation in retinal cell membranes was analysed using chromatography.

Results

Preincubation of the cells with fish oil decreased ROS overproduction, mitochondrial alterations and TNFα release. These protective effects could be attributed to an increase in caveolin-1 expression induced by marine oil.

Conclusion

Marine formulations rich in omega-3 fatty acids represent a promising therapeutic approach for diabetic retinopathy.     

Antihyperglycemic activity of new 1,2,4-oxadiazolidine-3,5-diones

A series of 1,2,4-oxadiazolidine-3,5-diones was synthesized and evaluated as oral antihyperglycemic agents in the obese insulin resistant db/db and ob/ob mouse - the two models for Type 2 diabetes mellitus. The majority of the prepared methoxy- and ethoxy-linked oxazole 1,2,4-oxadiazolidine-3,5-diones normalized plasma glucose levels at the 100 mg kg(-1) oral dose in the db/db diabetic mouse model, and several amongst them reduced the glucose levels at the 20 mg kg(-1) oral dose. The most potent compounds in the db/db mouse model were also active in the ob/ob mouse model normalizing the plasma glucose levels at the 20 mg kg(-1) oral dose. The trifluoromethoxy analog 32 was the most active compound of the series, reducing significantly the plasma glucose levels at the 5 mg kg(-1) oral dose. Oxadiazole-tailed 1,2,4-oxadiazolidine-3,5-diones were also active in both the db/db and ob/ob diabetic mouse models normalizing plasma glucose levels at the 100 mg kg(-1) oral dose.     

Metalloproteinase 2 activity and modulation in uterus from neonatal streptozotocin-induced diabetic rats during embryo implantation

Matrix metalloproteinases (MMPs) are responsible for the remodelling of the uterine extracellular matrix during embryo implantation. Nitric oxide (NO) production is increased at the time when implantation begins. Abnormal tissue levels of MMPs are present in diabetes; elevated NO levels in tissues and an increased oxidative stress are also found. The present work evaluates the uterine MMP2 activity and levels during embryo implantation, as well as the influence of nitridergic compounds and reactive oxygen species (ROS) on the MMP2 enzymatic activity in a model of neonatal streptozotocin-induced diabetic rat. Metalloproteinase 2 activity and levels are increased in diabetic tissues compared with controls (P < 0.05 and P < 0.002 respectively). The uterine enzymatic activity in diabetic animals decreases in the presence of the NOS inhibitor NG-nitro-L-arginine methyl ester (P < 0.01) and is enhanced (P < 0.005) when a generating ROS system (xanthine/xanthine oxidase) is added to the incubating medium. It was also found that uterine superoxide dismutase activity is higher in diabetic rats than in control rats on the day of implantation (P < 0.001), suggesting a compensatory antioxidant ability. In conclusion, the results show that the uterine MMP2 activity, which is higher in diabetic animals than in control animals, is modulated positively by NO and ROS during embryo implantation in a model of streptozotocin-induced diabetic rats.     

Vanadyl sulfate treatment improves oxidative stress and increases serum paraoxonase activity in streptozotocin-induced diabetic rats

Vanadyl sulfate (VS) may reduce oxidative stress related to its hypoglycemic and hypolipidemic effects in diabetes mellitus; besides, as a catalytic element, it may induce lipid peroxidation. Studies investigating effects of VS on the oxidative-antioxidative systems in diabetes yielded conflicting results, and this study was designed to investigate the effects of VS on the oxidative-antioxidative systems in streptozotocin-induced (65 mg/kg) diabetic rats. Vanadyl sulfate was administered in drinking water 0.75 mg/mL during 5 weeks after the induction of diabetes. Thirty-two male Wistar rats were randomly divided into four groups: control (C), control + vanadyl sulfate (C + VS), diabetes (D), and diabetes + vanadyl sulfate (D + VS). Vanadyl sulfate reduced the enhanced glucose, lipid, and tissue malondialdehyde levels and increased the reduced serum paraoxonase and arylesterase activity in the D + VS group. Plasma malondialdehyde level was significantly increased in the C + VS group, compared with the control group. Erythrocyte glutathione peroxidase activity was significantly higher in the C + VS and D + VS groups, compared with the C and the D groups, respectively.

The results of the present study suggest that (i) VS has antioxidative potential in streptozotocin-treated rats, and it might be used as a supportive therapeutic agent in uncontrolled diabetes; (ii) VS treatment might play a role in the improvement of serum paraoxonase activity and, thus, inhibit the progression of atherosclerosis; (iii) the prooxidant potential of the VS should be taken into account.     

运动对糖尿病大鼠肥胖蛋白的作用

为了观察适量运动对糖尿病大鼠肥胖蛋白、胰岛素及血糖的影响 ,以探讨适量运动改善糖尿病大鼠糖代谢紊乱的可能机制。将 40只SD大鼠分为 4组 :糖尿病非运动组、糖尿病运动组、正常非运动组和正常运动组。运动组进行 12周的中等强度的跑步训练。结果显示 :(1)糖尿病大鼠血糖浓度增高 ,血胰岛素及血C肽浓度降低 ;血浆肥胖蛋白水平下降 ,脑组织和脂肪组织中肥胖蛋白水平下降 ;(2 )糖尿病运动组大鼠经 12周跑步训练后 ,血糖浓度下降 ,血胰岛素和C肽浓度升高 ;血浆及脑组织和脂肪组织肥胖蛋白水平相应上升。提示适量运动通过对肥胖蛋白和胰岛素的作用改善糖尿病的能量代谢失衡状态 ,这可能是运动改善糖尿病糖代谢紊乱的机制之一。