Beta cell protective effects of sodium tungstate in streptozotocin-induced diabetic rats: glycemic control, blockage of oxidative stress and beta cell histochemistry

Background: Diabetes is a major public health problem. The development of new therapies that are able to improve glycemia management and even to cure diabetes is of great interest. In this study, protective effects of sodium tungstate against STZ-induced beta-cell damages were investigated. Methods: Sixty rats were divided into six groups: control, diabetic, sodium tungstate treated diabetic rats from one week before STZ injection (TDB), food-restricted diabetic (FRD), tungstate treated control, sodium tungstate treated diabetic rats from one week after STZ administration (TDA). We evaluated serum insulin, glucose and glucose tolerance; liver glycogen content, glucokinase (GK) activity; blood and pancreas antioxidant power, lipid peroxidation; and fuchsin-aldehyde histochemical staining of beta-cells. Results: Blood glucose levels of TDB group were lower than other diabetic groups (P<0.01). Blood insulin levels of all diabetic groups were lower than controls (P<0.01). Glucose intolerance improved in TDB animals. Blood and pancreas antioxidant power, liver glycogen contents and GK activities and granulated beta cells increased in TDB rats in comparison with other diabetic groups (P<0.01). Likewise, lipid peroxidation decreased significantly in TDB rats (P<0.01). Conclusions: Results suggested that sodium tungstate if administrated before STZ injection improves glycemic state by a direct effect on pancreatic beta-cells and preserves them by reducing the activity of these cells at the time of STZ injection, reducing STZ-induced oxidative stress, reducing insulin secretion, or all of the above mentioned.     

The effects of oral vitamin E on induction and consequence of experimental diabetes mellitus in rats

Streptozotocin destroys the beta-cells of pancreas by generation of reactive oxygen species and vitamin E has documented antioxidant properties. To evaluate the preventive effect of vitamin E on induction of diabetes by streptozotocin and effect of oral vitamin E consumption on carbohydrate and lipid metabolism, forty male Wistar rats divided randomly to control, E1, E2 and E3 groups. The diet of E1, E2 and E3 groups were supplemented with 1, 2 and 4 g kg(-1) of vitamin E, respectively. Four days later all rats were made diabetic by IP injection of 45 mg kg-' streptozotocin and blood glucose was measured 72 h later to determine the severity of blood glucose elevation. Glycosylated hemoglobin, triglyceride, total cholesterol and HDL-c were measured and LDL-c and VIDL-c calculated in plasma of 6 diabetic rats with glucose more than 200 mg dL(-1) in each groups 21 days after streptozotocin injection. Vitamin E had no effect on diabetes induction by streptozotocin, but elevation of glycosylated Hb and reduction of LDL-c in group E3 were significant. Vitamin E also increased HDL-c although it was not statistically significant. We suggest that oral vitamin E consumption may have some beneficial effect on the correction of lipid metabolism disorders of diabetes, although it may worsen carbohydrate metabolism in mild diabetes.     

Antioxidant Effect of Dietary Supplement Withania somnifera L. Reduce Blood Glucose Levels in Alloxan-Induced Diabetic Rats

The phenolic compounds and flavonoids were determined from the extracts of Withania somnifera root (WSREt) and leaf (WSLEt). The WSREt has 28.26 mg/g total phenolic compounds and 17.32 mg/g flavonoids, whereas WSLEt has 5.4 mg/g total phenolic compounds and 5.1 mg/g flavonoids. The WSREt, WSLEt and glibenclamide were orally administered daily to diabetic rats for 8 weeks. After the treatment, the levels of urine sugar, blood glucose, liver glycogen, and antioxidants like vitamin C and E in plasma and superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in liver, kidney and heart were determined. Diabetic rats showed a significant (p < 0.05) elevation in glucose and TBARS and a significant (p < 0.05) reduction in glycogen, vitamin C and E, SOD, CAT, GPx, GST, and GSH levels when compared to normal control rats. Administration of WSREt, WSLEt and glibenclamide to diabetic rats restored the levels to normal. In the light of aforesaid facts, it is suggested that the presence of phenolic compounds including flavonoids in W. somnifera root and leaf extracts and their antioxidant activity may play a vital role in reduction of blood glucose level in alloxan-induced diabetic rats.     

Effect of Diet Supplemented with Quinoa Seeds on Oxidative Status in Plasma and Selected Tissues of High Fructose-Fed Rats

Oxidative stress plays an important role as a mediator of damage produced by fructose metabolism. This work was designed to investigate the effect of diet supplemented with quinoa seeds on oxidative stress in plasma, heart, kidney, liver, spleen, lung, testis and pancreas of fructose administered rats. Fructose administration (310 g/kg fodder for 5 weeks) caused oxidative stress that was manifested by the increase in plasma malondialdehyde (MDA) (p<0.05), and by the non-significant changes in the enzymatic antioxidant potential in plasma and most of tissues. Co-administration of quinoa seeds (310 g/kg fodder) maintained normal activities of some enzymes. It also influenced the oxidative stress as was evidenced by decreasing MDA in plasma, and decreasing the activities of antioxidant enzymes (erythrocyte superoxide dismutase - eSOD, catalase -CAT, plasma glutathione peroxidase - pGPX). These findings demonstrate that quinoa seeds can act as a moderate protective agent against potential of fructose-induced changes in rats by reducing lipid peroxidation and by enhancing the antioxidant capacity of blood (plasma) and heart, kidney, testis, lung and pancreas.     

Cooked Common Beans (Phaseolus vulgaris) Protect Against β-cell Damage in Streptozotocin-Induced Diabetic Rats

Diabetes is a disease characterized by a hyperglycemic stage that leads to a chronic inflammatory state. We evaluated the in vivo effect of a diet supplemented with 25 % cooked black bean cultivar Negro 8025 (N8025) flour in streptozotocin-induced diabetic rats. The effect was assessed before (preventive-treatment) and after (treatment) the onset of diabetes. There is a significant decrease of total phenolic, tannins and anthocyanins content after cooking, and the concentration of most of the single phenols analyzed are only slightly decreased. The treatment group showed a significant reduction of glucose (22.8 %), triglycerides (21.9 %), total cholesterol (29.9 %) and LDL (56.1 %) that correlates with a protection of pancreatic ß-cells. The diet with N8025 flour before the induction of diabetes did not exert a protective effect (glucose levels are similar to the diabetic control) but they have low levels of total cholesterol (47.5 %) and LDL (56.1 %). The preventive-treatment group did not inhibit the increase of TNF-α and IL-1β, whereas the treatment group did, compared to the diabetic control. Therefore, N8025 bean supplementation can be recommended to control diabetes.     

Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats

In the traditional system ofmedicine, Ayurveda, several spices and herbsare thought to possess medicinal properties. Amongthe spices, turmeric rhizomes (Curcumalonga. Linn.) are used as flavoring and coloringagents in the Indian diet everyday. In this research,we studied the effect of turmeric and itsactive principle, curcumin, on diabetes mellitus in arat model. Alloxan was used to induce diabetes.Administration of turmeric or curcumin to diabeticrats reduced the blood sugar, Hb and glycosylatedhemoglobin levels significantly. Turmeric andcurcumin supplementation also reduced the oxidativestress encountered by the diabetic rats. This wasdemonstrated by the lower levels of TBARS (thiobarbituric acid reactive substances), which mayhave been due to the decreased influx of glucose intothe polyol pathway leading to an increased NADPH/NADPratio and elevated activity of the potent antioxdiantenzyme GPx. Moreover, the activity of SDH (soorbitol dehydrogenase), whichcatalyzes the conversion of sorbitol to fructose, waslowered significantly on treatment with turmeric orcurcumin. These results also appeared to reveal thatcurcumin was more effective in attenuating diabetesmellitus related changes than turmeric.     

Protective Effect of Potato Peel Powder in Ameliorating Oxidative Stress in Streptozotocin Diabetic Rats

The potential of dietary potato peel (PP) powder in ameliorating oxidative stress (OS) and hyperglycemia was investigated in streptozotocin (STZ)-induced diabetic rats. In a 4-week feeding trial, incorporation of potato peel powder (5 and 10%) in the diet of diabetic rats was found to significantly reduce the plasma glucose level and also reduce drastically the polyuria of STZ diabetic rats. The total food intake was significantly reduced in the diabetic rats fed 10% PP powder compared to the control diabetic rats. However, the body weight gain over 28 days was nearly four times greater in PP powder supplemented diabetic rats (both at 5 and 10%) compared to the control diabetic rats. PP powder in the diet also decreased the elevated activities of serum transaminases (ALT and AST) and nearly normalized the hepatic MDA and GSH levels as well as the activities of specific antioxidant enzymes in liver of diabetic rats. The result of these studies clearly establishes the modulatory propensity of PP against diabetes induced alterations. Considering that potato peels are discarded as waste and not effectively utilized, these results suggest the possibility that PP waste could be effectively used as an ingredient in health and functional food to ameliorate certain disease states such as diabetes.     

Influence of Coffee Brew in Metabolic Syndrome and Type 2 Diabetes

This study aimed to evaluate the effect of coffee drinking on clinical markers of diabetes and metabolic syndrome in Zucker rats. Diabetic Zucker rats with metabolic syndrome and control Zucker rats were used for in vivo tests. The animals received daily doses of coffee drink by gavage for 30 days. After the treatment, the levels of glucose, triglycerides, total cholesterol and fractions, creatinine, uric acid, activity of aspartate aminotransferase and alanine aminotransferase were evaluated. Urea and creatinine levels were also analyzed in urine. By collaborating in the modulation of the metabolic syndrome and diabetes mellitus type 2, coffee drink helped in reducing serum glucose, total cholesterol and triglycerides. The results demonstrate that treatment with roasted coffee drink, because of its hypoglycemic and hypolipidemic effect, is efficient in the protection of animals with metabolic syndrome and diabetes mellitus type 2.     

The potential toxicity of diazinon on physiological factors in male rat

Diazinon is an Organophosphate Insecticide (OPI) is commonly used in agriculture to protect of crops and to control pests in home gardens and farms. Many alterations observed by diazinon have been described, such as; alterations in blood factors (RBC, Hb and Hct), plasma testosterone and glucose levels. We selected 12 albino Wistar rats weighting between 220-280 g were divided into two experimental groups, as follow, control group and diazinon treated group. The effects of diazinon, on rat interstitial cell testosterone production, blood factors and plasma glucose levels were evaluated. Male rats were treated orally with a single dose of 1/4 LD50 of diazinon. Animals received treatment for 28 days. Present results indicated that in diazinon treated group, plasma glucose and testosterone levels increased compared to control. Also in diazinon group, reduce of blood factors were observed than control. In conclusion, diazinon disturbs the synthesis of testosterone and glucose release from liver into blood and it led to anemia.     

Glucose Uptake and Oxidative Stress in Caco-2 Cells: Health Benefits from Posidonia oceanica (L.) Delile

Posidonia oceanica (L.) Delile is an endemic Mediterranean marine plant of extreme ecological importance. Previous in vitro and in vivo studies have demonstrated the potential antidiabetic properties of P. oceanica leaf extract. Intestinal glucose transporters play a key role in glucose homeostasis and represent novel targets for the management of diabetes. In this study, the ability of a hydroalcoholic P. oceanica leaf extract (POE) to modulate intestinal glucose transporters was investigated using Caco-2 cells as a model of an intestinal barrier. The incubation of cells with POE significantly decreased glucose uptake by decreasing the GLUT2 glucose transporter levels. Moreover, POE had a positive effect on the barrier integrity by increasing the Zonulin-1 levels. A protective effect exerted by POE against oxidative stress induced by chronic exposure to high glucose concentrations or tert-butyl hydroperoxide was also demonstrated. This study highlights for the first time the effect of POE on glucose transport, intestinal barrier integrity, and its protective antioxidant effect in Caco-2 cells. These findings suggest that the P. oceanica phytocomplex may have a positive impact by preventing the intestinal cell dysfunction involved in the development of inflammation-related disease associated with oxidative stress.     

Changes in Glycoprotein Components in Streptozotocin - Nicotinamide Induced Type 2 Diabetes: Influence of Tetrahydrocurcumin from <Emphasis Type="Italic">Curcuma longa</Emphasis>

Curcuma longa (Zingiberaceae) has been used traditionally as antidiabetic, and has been proven scientifically to possess high antioxidant activity and anticancer properties. The active components of Curcuma longa such as curcumin and tetrahydrocurcumin (THC), a major colourless metabolite of curcumin also possesses antidiabetic, antiinflammatory and antioxidant activity. The ethnopharmacological value of this plant, the effect of THC on glycoproteins was carried out in normal and streptozotocin-nicotiniamide induced type 2 hyperglycaemic rats for 45 days. Glucose, plasma insulin and glycoprotein components in plasma and tissues (hexose, hexosamine, fucose and sialic acid) were determined. Oral administration of THC to diabetic rats showed a decrease in the level of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased where as the levels of tissue hexose, hexosamine and fucose were near normal in diabetic rats treated with THC. The present study indicates that the THC possesses a significant beneficial effect on glycoprotein moiety in addition to its antidiabetic effect. The effect of THC is more prominent than curcumin.     

茶黄素-3,3'-O-双没食子酸酯对糖尿病大鼠血管内皮损伤及炎症反应的保护作用

探讨茶黄素-3,3'-O-双没食子酸酯（TFDG）对糖尿病大鼠血管内皮损伤及炎症反应的保护作用及相关机制。以高脂饲料喂养加链脲佐菌素注射制造糖尿病大鼠,将其分为模型组（CON）、5 mg·kg^-1和10 mg·kg^-1 TFDG干预组（TFDG5和TFDG10）,另取正常大鼠为对照组（NC）,分组处理8周,监测体重和空腹血糖变化,观察大鼠腹主动脉病理形态学变化,ELISA检测血浆IL-6、IL-1β和TNF-α水平,Western blot检测蛋白表达水平。结果表明,与CON组相比,TFDG干预对体重和血糖无显著影响,病理切片观察显示TFDG干预组大鼠腹主动脉组织损伤较CON组有所改善,同时TFDG干预组大鼠血浆炎症因子水平显著降低,血浆NO水平显著升高,腹主动脉组织MDA水平降低。进一步研究显示,TFDG下调了糖尿病大鼠腹主动脉组织NLRP3、caspase-1和IL-1β的表达,抑制NLRP3炎症通路激活。TFDG能够有效保护糖尿病大鼠血管内皮损伤并抑制炎症反应,其机制可能是通过下调NLRP3炎症通路实现的。     

Effect of flax seeds and date palm leaves extracts on serum concentrations of glucose and lipids in alloxan diabetic rats

The aim of the present investigation was to examine the effect of Flax Seeds (FS) and Date Palm Leaves (DPL) extracts on the concentration of serum glucose and lipids in alloxan diabetic rats. Rats were divided into six groups, normal control rats (without treatment with either FS or DPL), normal control rats treated with either FS or DPL extract for four weeks, diabetic control rats and diabetic rats treated with either FS or DPL extract for four weeks. The concentration of glucose in diabetic rats treated with FS (D+FS) for four weeks was significantly decreased from 17.20 +/- 2.33 to 8.14 +/- 0.54 mmol L(-1) (p < 0.001). Serum total cholesterol concentration (TC) of diabetic rats treated with either FS or DPL extract showed significant decrease by 40 and 31% respectively in the fourth week. Also, serum low density lipoprotein cholesterol (LDL-C) concentration was significantly decreased after two weeks of treatment (p < 0.001 and p < 0.01, respectively). However, no significant changes were obtained in serum high density lipoprotein cholesterol (HDL-C) concentration. Results of the present study showed that FS extract has a hypoglycaemic effect against alloxan diabetic rats. Present findings also showed that treatment of alloxan diabetic rats with either FS or DPL extract significantly decreased serum concentration of TC and LDL-C. Present findings suggest that both of FS and DPL extracts could have a protective effect against diabetes complications as well as against hyperlipidemia through improvement of lipid profile.     

Antidiabetic and Antioxidant Effects of Polyphenols in Brown Alga <Emphasis Type="Italic">Ecklonia stolonifera</Emphasis> in Genetically Diabetic KK-A<Superscript>y</Superscript> Mice

The dietary intake and control of blood glucose levels are very important in hyperglycemic patients and α-glucosidase inhibitors are a cost-effective means to preventing the progression of diabetes. In search of a natural inhibitor from food materials, α-glucosidase inhibitory activity and the anti-hyperglycemic effects of a brown alga, Ecklonia stolonifera, were investigated using non-insulin dependent diabetic mice. Methanolic extract of E. stolonifera (MEE), which contains a high content of polyphenols, showed strong inhibition of α-glucosidase in vitro. Male KK-A^y mice, a genetically non-insulin dependent diabetic model, showed hyperglycemia with aging, but the ingestion of MEE suppressed the increase in plasma glucose and lipid peroxidation levels in unfasted KK-A^y mice dose dependently. In KK-A^y mice, which were fed the MEE diet for 4 weeks, MEE moderated the elevation of plasma glucose levels after the oral administration of maltose. The polyphenols in MEE were estimated to be phlorotannins by HPLC-PDA and LC/MS analyses. These results demonstrate that E. stolonifera, seaweed typically used as a health food, has strong antidiabetic and antioxidant effects in vivo, thus, it may have beneficial properties in the prevention of diabetes and could be useful in the development of an antidiabetic pharmaceutical and functional food.     

Dynamics of phytate-zinc balance of fungi fermented cassava products (gari and flour)

Parsley is one of the medicinal herbs used by diabetics in Turkey. It has been reported to reduce blood glucose levels. In this study the effects of feeding parsley on diabetes-induced free radical mediated injury in rat aorta and heart tissues were investigated. Swiss albino rats were divided into six groups: Control, diabetic, parsley, diabetic + parsley, glibornurid, and diabetic + glibornurid. Rats were subjected to i.p. streptozotocin (STZ, 65 mg/kg) to induce diabetes. On the fourteenth day of the study, either parsley (2 g/kg) or glibornurid (5 mg/kg) were given for 28 days to the diabetic rats. Aorta and heart tissue lipid peroxidation and glutathione levels as well as blood glucose levels were determined. The results of the present study indicate that lipid peroxidation was increased and glutathione levels were decreased in both aorta and heart tissue of the diabetic rats. However, treatment of the diabetic rats with either parsley or glibornurid reversed the effects of diabetes on blood glucose, and tissue lipid peroxidation and glutathione levels.     

A Shark Liver Gene-Derived Active Peptide Expressed in the Silkworm,Bombyx mori: Preliminary Studies for Oral Administration of the Recombinant Protein

Active peptide from shark liver (APSL) is a cytokine from Chiloscyllium plagiosum that can stimulate liver regeneration and protects the pancreas. To study the effect of orally administered recombinant APSL (rAPSL) on an animal model of type 2 diabetes mellitus, the APSL gene was cloned, and APSL was expressed in Bombyx mori N cells (BmN cells), silkworm larvae and silkworm pupae using the silkworm baculovirus expression vector system (BEVS). It was demonstrated that rAPSL was able to significantly reduce the blood glucose level in mice with type 2 diabetes induced by streptozotocin. The analysis of paraffin sections of mouse pancreatic tissues revealed that rAPSL could effectively protect mouse islets from streptozotocin-induced lesions. Compared with the powder prepared from normal silkworm pupae, the powder prepared from pupae expressing rAPSL exhibited greater protective effects, and these results suggest that rAPSL has potential uses as an oral drug for the treatment of diabetes mellitus in the future.     

Chronic Aerobic Exercise Decreases Lectin-Like Low Density Lipoprotein (LOX-1) Receptor Expression in Heart of Diabetic Rat

Background:

Overexpression of lectin-like low density lipoprotein (LOX-1) receptor plays an important role in hyperglycemia-induced vascular complications such as atherosclerosis. Based on the beneficial effects of exercise on preventing cardiovascular complications of diabetes, we aimed to examine the protective effects of aerobic exercise on expression of LOX-1 receptor and production of free radicals in the heart of diabetic rats.

Methods:

Four groups of rats were used: (n = 5 per group): sedentary normal, trained normal, sedentary diabetes and trained diabetes. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg). The exercise protocol was consisted of swimming 30 min/day, 5 days/week for eight weeks. Plasma glucose was evaluated at initiation, weeks 4 and 8 of experiment. At the end of experiment, rats were sacrificed and the heart was removed for determination of nitrate, malondialdehyde, and LOX-1 gene expression.

Results:

In normal non-diabetic rats, the blood glucose level was <150 mg/dl; however, the induction of diabetes resulted in levels more than >400 mg/dl. Gene expression of LOX-1 was increased in the heart of diabetic rats. Exercise reduced the gene expression of this protein in diabetic states without reducing the blood glucose. Finally, swimming exercise decreased the malondialdehyde and nitrate levels in heart tissue both in control and diabetic rats.

Conclusion:

Swimming exercise reduces heart expression of the LOX-1 receptor in accompany with reduction of free radicals production. Since these parameters are important in generation of diabetic complications, swimming exercise is a good candidate for reducing these complications. Key Words: Hyperglycemia, Diabetic complications, LOX-1 receptor, Exercise, Free radicals     

Use of Red Blood Cell Membranes to Evaluate the Antioxidant Potential of Plant Extracts

Antioxidant phytochemicals in fruits and vegetables of a vegetarian diet may account for the reduced risk of aging and stress oxidative associated diseases. In this study, a simple, rapid and accurate new bioassay for the determination of the antioxidant activity of purified or crude plant extracts and thier interactions is described, based on the fluorimetric determination of thiobarbituric acid reactive substances (TBARS) released by UV-B radiated red blood cell (RBC) ghosts. Pure resveratrol, white and red wine and pomegranate juice (PJ) were used as antioxidant source to test the biological method. TBARS production is a function of radiation time, the number of RBC ghosts in the radiated sample and the loaded antioxidant. The antioxidant activity of resveratrol was detected at a submicromolar concentration range [0.02 μg/mL–0.1 μmol/L]. The activity of red wine was almost 10 times higher than that of white wine, and PJ juice had the highest activity. Submaximal protective effects of PJ and red wine were additive.     

Antidiabetic Activity of Differently Regioselective Chitosan Sulfates in Alloxan-Induced Diabetic Rats

The present study investigated and compared the hypoglycemic activity of differently regioselective chitosan sulfates in alloxan-induced diabetic rats. Compared with the normal control rats, significantly higher blood glucose levels were observed in the alloxan-induced diabetic rats. The differently regioselective chitosan sulfates exhibited hypoglycemic activities at different doses and intervals, especially 3-O-sulfochitosan (3-S). The major results are as follows. First, 3,6-di-O-sulfochitosan and 3-O-sulfochitosan exhibited more significant hypoglycemic activities than 2-N-3, 6-di-O-sulfochitosan and 6-O-sulfochitosan. Moreover, 3-S-treated rats showed a more significant reduction of blood glucose levels than those treated by 3,6-di-O-sulfochitosan. These results indicated that –OSO₃⁻ at the C3-position of chitosan is a key active site. Second, 3-S significantly reduced the blood glucose levels and regulated the glucose tolerance effect in the experimental rats. Third, treatment with 3-S significantly increased the plasma insulin levels in the experimental diabetic rats. A noticeable hypoglycemic activity of 3-S in the alloxan-induced diabetic rats was shown. Clinical trials are required in the future to confirm the utility of 3-S.     

茶多酚改善胰岛素抵抗的初步研究

研究了茶多酚（Tea Polyphenols,TP）降低肝脏中甘油三酯（Triglyceride, TG）含量从而对2型糖尿病性脂肪肝模型大鼠胰岛素抵抗的改善作用。健康SD大鼠分为6组：健康组、模型组、TP组、二甲双胍组、FL组和FL+TP组。所有大鼠在实验结束时测量体重、血清甘油三酯、肝脏中甘油三酯、空腹血糖、血清胰岛素等指标。TP组和二甲双胍组较模型组空腹血糖、血清胰岛素含量和胰岛素敏感指数下降;FL+TP组、TP组较FL组、模型组肝脏中甘油三酯含量下降。茶多酚可显著降低肝脏中的甘油三酯含量,调节脂代谢紊乱并改善胰岛素抵抗。