Sample records for stz-induced diabetic rats

  1. Hypoglycemic effect of Belamcanda chinensis leaf extract in normal and STZ-induced diabetic rats and its potential active faction

    Microsoft Academic Search

    Chongming Wu; Yan Li; Yan Chen; Xinyuan Lao; Linghui Sheng; Rongji Dai; Weiwei Meng; Yulin Deng

    2011-01-01

    Belamcanda chinensis (Iridaceae) belongs to the family of iridaceae and its rhizoma has been widely used for the treatment of throat ailment. Here we report a new pharmacological activity of B. chinensis leaf extract (BCL), that is, the hypoglycemic effect in normal and STZ-induced diabetic rats. Animals either healthy or STZ-induced diabetic show significantly lowered fasting blood glucose levels after

  2. Fenugreek Prevents the Development of STZ-Induced Diabetic Nephropathy in a Rat Model of Diabetes

    PubMed Central

    Jin, Yingli; Shi, Yan; Zou, Yinggang; Miao, Chunsheng; Sun, Bo; Li, Cai

    2014-01-01

    The present study aims to examine the protective effect of fenugreek and the underlying mechanism against the development of diabetic nephropathy (DN) in streptozotocin- (STZ-) induced diabetic rats. A rat model of diabetes was successfully established by direct injection of STZ and then the rats were administered an interventional treatment of fenugreek. Parameters of renal function, including blood glucose, albuminuria, hemoglobin A1c (HbA1c), dimethyl formamide (DMF), blood urine nitrogen (BUN), serum creatinine (Scr), and kidney index (KI), were detected in the three groups (Con, DN, and DF). Oxidative stress was determined by the activity of antioxidase. Extracellular matrix (ECM) accumulation and other morphological alterations were evaluated by means of immunohistochemistry and electron microscope. Quantitive (q)PCR was employed to detect the mRNA expression of transforming growth factor-?1 (TGF-?1) and connective tissue growth factor (CTGF) and protein expression was determined with western blot analysis. DN rats in the present study demonstrated a significant renal dysfunction, ECM accumulation, pathological alteration, and oxidative stress, while the symptoms were evidently reduced by fenugreek treatment. Furthermore, the upregulation of TGF-?1 and CTGF at a transcriptional and translational level in DN rats was distinctly inhibited by fenugreek. Consequently, fenugreek prevents DN development in a STZ-induced diabetic rat model. PMID:25057273

  3. Aliskiren improves insulin resistance and ameliorates diabetic renal vascular complications in STZ-induced diabetic rats.

    PubMed

    Gandhi, Sonia; Srinivasan, Bp; Akarte, Atul Sureshrao

    2013-03-01

    Aliskiren, a direct renin inhibitor (DRI), has therapeutic effects in patients with hypertension and associated complications, but its potential mechanism in diabetic nephropathy is lacking. The effects of aliskiren in Streptozotocin (STZ)-induced renal complication in diabetic rats were investigated. Aliskiren treatment for eight weeks at the dose of 10 mg/kg/day, via osmotic mini-pump, induced improvement in blood glucose levels, systolic blood pressure (BP) and serum creatinine. Improvement of insulin resistance by aliskiren was confirmed by increased glucose translocation in liver and muscle and hence insulin levels. The treated group also showed improvement in glomerulosclerosis and tubulointerstitial injury. Aliskiren treatment also improved albumin levels in plasma, suppressed profibrotic and proinflammatory cytokine synthesis viz TNF-? and TGF-? and angiogenesis by a decrease in VEGF. In addition, the level of total proteins and GFR via cystatin c and beta-2microglobulin along with adiponectin and erythropoietin were also improved. These results suggest that the beneficial organ protective effect of aliskiren is mediated by improvement in insulin resistance as well as a direct anti-fibrotic effect in the target organ in STZ-induced diabetic rats with a slight effect on blood pressure. Aliskiren may be a useful therapeutic agent in the treatment of type 2 diabetes and diabetic nephropathy. PMID:22791702

  4. Selective therapeutic effect of cornus officinalis fruits on the damage of different organs in STZ-induced diabetic rats.

    PubMed

    Han, Yunkyung; Jung, Hyo Won; Park, Yong-Ki

    2014-01-01

    The aim of the present study was to identify the selective therapeutic effects of Corni Fructus (Cornus officinalis Sieb. et Zucc.) on different organs in streptozotocin (STZ)-induced diabetic rats. Diabetes in rats was induced by intraperitonal injection with STZ at a dose of 30 mg/kg body weight (bw) for 3 days (once per a day). STZ-induced diabetic rats were orally administrated Corni Fructus (CF) extract at 300 mg/kg or metformin at 250 mg/kg daily for 4 weeks. Blood glucose and triglyceride (TG) in sera and urine total volume were measured. Histopathological changes of different organs, pancreas, liver, kidney, and lung tissues were observed by H&E staining. The expression of insulin and ?-smooth muscle actin (?-SMA) was investigated in pancreas, and kidney by immunohistochemistry, respectively. The results revealed that CF extract significantly decreased the serum levels of blood glucose, and TG, and also urine total volume in STZ-induced diabetic rats. The histological examinations revealed amelioration of diabetes-induced pancreas injury including pathological changes of the Langerhans's islet and glomerular with their loss after the administration of CF extraction. Moreover, the administration of CF extract increased the numbers of insulin releasing beta cells in pancreas and also inhibited the expression of ?-SMA in kidney of STZ-induced diabetic rats. On the other hand, CF extract showed no effect on the pathological damages of liver and lung in STZ-induced diabetic rats. These results demonstrated that CF extract may have a selective therapeutic potential through the control of hyperglycemia, and the protection of pancreas and kidney against diabetic damage. PMID:25169907

  5. Efficacy of natural diosgenin on cardiovascular risk, insulin secretion, and beta cells in streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Kalailingam, Pazhanichamy; Kannaian, Bhuvaneswari; Tamilmani, Eevera; Kaliaperumal, Rajendran

    2014-09-15

    Costus igneus, has been prescribed for the treatment of diabetic mellitus in India for several years. The aim of this study is to investigate the effects of plant derived diosgenin on cardiovascular risk, insulin secretion, and pancreatic composition through electron microscopical studies of normal and diabetic rats. Diosgenin at a dose of 5 or 10mg/kg per body weight (bw) was orally administered as a single dose per day to diabetic induced rats for a period of 30 days. The effect of diosgenin on blood glucose, HbA1c, PT, APTT, Oxy-LDL, serum lipid profile, electron microscopical studies of pancreas, antioxidant enzymes (in liver, kidney, pancreas) and hepatoprotective enzymes in plasma and liver were measured in normal and diabetic rats. The results showed that fasting blood glucose, PT, APTT, Oxy-LDL, TC, TG, LDL, ALT, AST, ALP, glucose-6-phosphatase, fructose-1,6-bisphosphatase and LPO levels were significantly (p<0.05) increased, whereas HDL, SOD, CAT, GSH and the glycolytic enzyme glucokinase levels were significantly (p<0.05) decreased in the diabetes induced rats and these levels were significantly (p<0.05) reversed back to normal in diabetes induced rats after 30 days of treatment with diosgenin. Electron microscopical studies of the pancreas revealed that the number of beta cells and insulin granules were increased in streptozotocin (STZ) induced diabetic rats after 30 days of treatment with diosgenin. In conclusion, the data obtained from the present study strongly indicate that diosgenin has potential effects on cardiovascular risk, insulin secretion and beta cell regeneration in STZ induced diabetic rats, these results could be useful for new drug development to fight diabetes and its related cardiovascular diseases. PMID:24889525

  6. Garlic Oil Alleviates MAPKs- and IL-6-mediated Diabetes-related Cardiac Hypertrophy in STZ-induced DM Rats

    PubMed Central

    Chang, Sheng-Huang; Liu, Chung-Jung; Kuo, Chia-Hua; Chen, Hong; Lin, Wen-Yuan; Teng, Kun-Yu; Chang, Sheng-Wei; Tsai, Chang-Hai; Tsai, Fuu-Jen; Huang, Chih-Yang; Tzang, Bor-Show; Kuo, Wei-Wen

    2011-01-01

    Garlic oil has been reported to protect the cardiovascular system; however, the effects and mechanisms behind the cardioprotection of garlic oil on diabetes-induced cardiaomyopathy are unclear. In this study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether garlic oil could protect the heart from diabetes-induced cardiomyopathy. Wistar STZ-induced diabetic rats received garlic oil (0, 10, 50 or 100?mg?kg_1 body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction and cardiac pathologic hypertrophy responses were observed in diabetic rat hearts. Cardiac function was examined using echocardiography. In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction. Garlic oil treatment significantly inhibited the up-regulation in MAPK (e.g., p38, JNK and ERK1/2) and IL-6/MEK5/ERK5 signaling pathways in the diabetic rat hearts, reducing the levels of cardiac pathologic hypertrophy markers such as ANP and BNP, and improving the cardiac contractile function. Collectively, data from these studies demonstrate that garlic oil shows the potential cardioprotective effects for protecting heart from diabetic cardiomyopathy. PMID:21792366

  7. The Effect of Stevia Rebaudiana on Serum Omentin and Visfatin Level in STZ-Induced Diabetic Rats.

    PubMed

    Akbarzadeh, Samad; Eskandari, Fatemeh; Tangestani, Hadis; Bagherinejad, Somaieh Tangerami; Bargahi, Afshar; Bazzi, Parviz; Daneshi, Adel; Sahrapoor, Azam; O'Connor, William J; Rahbar, Ali Reza

    2015-03-01

    ABSTRACT Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of ?-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats. PMID:24689449

  8. Increased peripherin in sympathetic axons innervating plantar metatarsal arteries in STZ-induced type I diabetic rats

    PubMed Central

    Johansen, Niloufer J.; Frugier, Tony; Hunne, Billie; Brock, James A.

    2014-01-01

    A common characteristic of axonopathy is the abnormal accumulation of cytoskeletal proteins. We recently reported that streptozotocin (STZ)-induced type 1 diabetes produced a change in the morphology of sympathetic nerve fibers supplying rat plantar metatarsal arteries (PMAs). Here we investigated whether these morphological changes are associated with axonal accumulation of the type III intermediate filament peripherin and the microtubule protein ?-tubulin III, as both are implicated in axonal remodeling. PMAs from hyperglycemic STZ-treated rats receiving a low dose of insulin (STZ-LI) were compared with those from normoglycemic STZ-treated rats receiving a high dose of insulin (STZ-HI) and vehicle-treated controls. Western blotting revealed an increase in protein expression level for peripherin in PMAs from STZ-LI rats but no change in that for ?-tubulin III. In addition, there was an increase in the number of peripherin immunoreactive nerve fibers in the perivascular nerve plexus of PMAs from STZ-LI rats. Co-labeling for peripherin and neuropeptide Y (a marker for sympathetic axons) revealed that peripherin immunoreactivity increased in sympathetic axons. None of these changes were detected in PMAs from STZ-HI rats, indicating that increased peripherin in sympathetic axons of STZ-LI rats is likely due to hyperglycemia and provides a marker of diabetes-induced nerve damage. PMID:24847201

  9. Effect of Hordeum vulgare L. (Barley) on blood glucose levels of normal and STZ-induced diabetic rats

    PubMed Central

    Minaiyan, M.; Ghannadi, A.; Movahedian, A.; Hakim-Elahi, I.

    2014-01-01

    Barley (Hordeum vulgare L.) is the world's fourth most important cereal crop after wheat, rice and maize. It is readily available with reasonable cost, and has the highest amount of dietary fiber among the cereals which may be beneficial for metabolic syndrome. In the present study, the effect of hydroalcoholic extract of barley seeds and a protein enriched fraction on blood glucose of normal and streptozotocin (STZ)-induced diabetic rats (STZ, 55 mg/kg, i.p) were investigated. Normal and diabetic male Wistar rats were treated daily with normal saline (1 ml), barley hydroalcoholic extract (BHE) (0.1, 0.25, 0.5 g/kg), protein enriched fraction (PEF) (0.1, 0.2, 0.4 g/kg) and glibenclamide (1 and 3 mg/kg), separately and the treatment was continued for 11 days. Blood samples were taken at 0, 1, 2, 3, 9 h in the first day and the days 5 (120 h) and 11 (264 h) for measuring the blood glucose levels (BGL). Our results indicated that none of the BHE and PEF, were effective to reduce BGL in normal or diabetic rats in acute phase of treatment (1st day). Nevertheless, BHE at doses of 0.25 and 0.5 g/kg, were only effective in detracting BGL of diabetic rats after 11 days of continued daily therapy. Moreover, BHE restored body weight of diabetic rats at the end of treatment. Glibenclamide had also hypoglycemic action in normal and diabetic rats after both acute and extended treatments. These findings suggest that barley seeds hydroalcoholic extract, has a role in diabetic control in long term consumption, and this effect might be at least due to its high fiber content. More detailed studies are warranted to demonstrate its mechanism of action and identify active components. PMID:25657786

  10. Protective effect of Monascus fermented rice against STZ-induced diabetic oxidative stress in kidney of rats.

    PubMed

    Rajasekaran, A; Kalaivani, M

    2015-03-01

    In the present study, anti-diabetic activity and nephroprotective effect of MMFR was evaluated by using STZ-induced diabetic rats. Administration of MMFR at 100 and 200 mg/kg bw showed significant (P?diabetic rats were restored to normal level on treatment with MMFR and showed significant (P?diabetic activity but also prevents nephropathy and hypercholesterolemia due to diabetes. PMID:25745211

  11. Histopathological findings of the pancreas, liver, and carbohydrate metabolizing enzymes in STZ-induced diabetic rats improved by administration of myrtenal.

    PubMed

    Rathinam, Ayyasamy; Pari, Leelavinothan; Chandramohan, Ramasamy; Sheikh, Bashir Ahmad

    2014-12-01

    This study aims to evaluate the efficacy of myrtenal, a natural monoterpene, for its antihyperglycemic effects and ? cell protective properties in streptozotocin (STZ)-induced diabetic rats. Oral administration of myrtenal at doses of 20, 40, and 80 mg/kg body weight to diabetic rats for 28 days resulted in a significant reduction (P < 0.05) in the levels of plasma glucose, glycosylated hemoglobin (HbA1c), and an increase in the levels of insulin and hemoglobin (Hb). Protection of body weight loss of diabetic rats by myrtenal was noted. The altered activities of the key metabolic enzymes involved in carbohydrate metabolism such as hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, and hepatic enzymes AST, ALT, and ALP levels of diabetic rats were significantly improved by the administration of myrtenal in STZ-induced diabetic rats. Moreover, myrtenal treatment improved hepatic and muscle glycogen content in diabetic rats. Histopathological studies further revealed that the reduced islet cells were restored to near-normal conditions on treatment with myrtenal in STZ-induced diabetic rats. An alteration in liver architecture was also prevented by myrtenal treatment. Our results suggest that myrtenal possess antihyperglycemic and ? cell protective effects. Hence, myrtenal could be considered as a potent phytochemical for development as a new antidiabetic agent. PMID:25292424

  12. Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats.

    PubMed

    Sato, K; Fujita, S; Iemitsu, M

    2014-09-01

    Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30 min for 150 min after injection of diosgenin or dioscorea (3mg/kg). On another day, muscle was resected 150 min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120 min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ?/?, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5?-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150 min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats. PMID:24607838

  13. Protective Effects of Luteolin on Diabetic Nephropathy in STZ-Induced Diabetic Rats

    PubMed Central

    Wang, Guo Guang; Lu, Xiao Hua; Li, Wei; Zhao, Xue; Zhang, Cui

    2011-01-01

    Diabetic nephropathy is a long-term complication of diabetic mellitus. Many experimental evidences suggest that persistent hyperglycaemia generates intracellular reactive oxygen species (ROS) and upregulates transforming growth factor-b1 and extracellular matrix expression in mesangial and tubular epithelial cells, which is involved of free radicals in the pathogenesis of diabetes and more importantly in the development of diabetic complications. Antioxidants effectively inhibit high-glucose- and H2O2-induced transforming growth factor-b1 and fibronectin upregulation, thus providing evidence that ROS play an important role in high glucose-induced renal injury. The flavonoid luteolin has been shown to possess direct antioxidant activity, therefore we hypothesize that it may be useful in treatment of many chronic disease associated with oxidative stress, such as diabetic nephropathy via its antioxidant properties. Our results suggested that protection against development of diabetic nephropathy by luteolin treatment involved changes in superoxide dismutase (SOD) activity, the malondialdehyde (MDA) content and expression of Heme Oxygenase-1 (HO-1) protein. PMID:21584231

  14. Aggravation by vanadium of magnesium deficiency in STZ-induced diabetic rats.

    PubMed

    Bermúdez-Peña, M C; López-Chaves, C; Llopis, J; Guerrero-Romero, F; Montes-Bayón, M; Sanz-Medel, A; Sánchez-González, C

    2013-01-01

    This study examined changes in the metabolism of magnesium (Mg), and related serum parameters, following treatment with vanadium (V) in streptozotocin-diabetic rats. Over a period of five weeks, four groups were examined: control, diabetic, diabetic-treated with 1 mg V/day or 3 mg V/day. The V was supplied in drinking water as bis(maltolato)oxovanadium(IV). The Mg levels were measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, heart and femur. Albumin, uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides, aspartate-aminotransferase and alkaline-phosphatase were determined in serum. In the diabetic group, Mg retained and Mg content in serum and femur decreased, while levels of uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides and alkaline-phosphatase and aspartate-aminotransferase activity increased compared with control rats. In the diabetic group treated with 1 mg?V/day, Mg retained, serum levels of Mg, urea and triglycerides, and alkaline-phosphatase activity remained unchanged, while levels of uric acid, total-cholesterol and LDL-cholesterol increased and the Mg content in femur and aspartate-aminotransferase activity decreased compared with the diabetic untreated group. In the diabetic rats treated with 3 mg?V/day, food intake and glycaemia were normal. In this group, Mg content in serum, kidney and femur, levels of urea and aspartate-aminotransferase and alkaline-phosphatase activity decreased, whereas LDL-cholesterol increased, uric acid and total-cholesterol levels remained unchanged in comparison with untreated diabetic rats. In conclusion, although treatment with 3 mg V/day normalised the glycaemia, the hypomagnesaemia and tissue depletion of Mg seen in the diabetic rats, caused by the treatment with V, could have partially contributed to the fact that V did not normalise other serum parameters altered by the diabetes. PMID:23823277

  15. Long term streptozotocin (STZ)-induced diabetes alters hepatic biotransformational capacity in rats

    SciTech Connect

    Watkins, J.B.; Sanders, R.; Beck, L.V.

    1986-03-01

    Adult male Sprague-Dawley rats injected with 45 mg STZ/kg rapidly developed the classical symptoms of diabetes which persisted throughout the 90 day test period. Serum ketone concentrations in control and STZ-treated rats were within normal limits. Diabetic animals exhibited depressed cytochrome P-450 content as well as decreased activities of benzphetamine N-demethylase, styrene oxide hydrolase, UDP-glucuronosyltransferase toward 1-naphthol and testosterone, and glutathione S-transferase toward ethacrynic acid, sulfobromophthalein (BSP) and 1-chloro-2,4-dinitrobenzene (CDNB). STZ-treated rats given 0.025 ml carbon tetrachloride (CCl/sub 4/)/kg had even greater decreases in enzyme activities toward benzphetamine, styrene oxide, CDNB, BSP, 1-naphthol and diethylstilbestrol. Similar changes were observed in normal rats given 0.4 ml CCl/sub 4//kg. In other STZ-treated rats, bromobenzene (0.5 ml/kg) did not depress enzyme activity toward these substrates. In normal rats, this same dose of bromobenzene produced decreased activities toward benzphetamine, styrene oxide, ethacrynic acid, and estrone, but increased activities toward 1-naphthol and diethylstilbestrol. Thus, diabetes potentiated the damaging effects of CCl/sub 4/, but not those of bromobenzene, on these hepatic biotransformation reactions.

  16. Effects of puerarin in STZ-induced diabetic rats by oxidative stress and the TGF-?1/Smad2 pathway.

    PubMed

    She, ShaoYi; Liu, WeiJuan; Li, Tong; Hong, YingKai

    2014-05-01

    The present study aimed to investigate the effects of pueraria on streptozotocine (STZ)-induced renal damage and its possible mechanisms. Wistar rats were randomly divided into five groups: the normal control group, diabetes untreated model group, two dosages (140 and 200 mg per kg bw per day) of puerarin treatment groups and a positive control group. Rats were studied 30 days after the STZ treatment, and the diabetes untreated model group presented significantly higher kidney index, blood glucose, triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), interferon-? (IFN-?), and IFN-?/IL-4 levels, lower body weight, fasting blood insulin (FPI), IL-4, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and nitric oxide (NO) levels and worse renal function (higher blood urea nitrogen (BUN), serum creatinine (SCr), urine protein (UP) levels and glomerular extracellular matrix (relative area)) compared with the normal control group (p < 0.05). Furthermore, RT-FQ-PCR and western blot analyses showed that TGF-?1, Smad2, CTGF and FN protein and mRNA expression was significantly increased in the diabetes untreated model group compared with the normal control group. In contrast, the puerarin treatment dose-dependently significantly decreased the kidney index, blood glucose, TG, TC, MDA, IFN-?, and IFN-?/IL-4 levels, increased the body weight, FPI, IL-4, SOD, CAT, GSH-Px and NO levels and improved the renal function (lower BUN, SCr, UP levels and glomerular extracellular matrix (relative area)) in puerarin treatment groups (p < 0.05). In addition, the mRNA and protein expression of TGF-?1, Smad2, CTGF and FN was downregulated. It can be concluded that puerarin exerted its anti-diabetic effect on the STZ-treated rats through the inhibition of the TGF-?1/Smad2 pathway. PMID:24595557

  17. Effects of antiplatelet drug dilazep dihydrochloride on anionic sites and extracellular matrix (ECM) components in glomerular basement membrane of STZ-induced diabetic rats.

    PubMed

    Yamamoto, M; Fukui, M; Kuramoto, T; Kabuki, K; Tomino, Y

    1995-01-01

    A study of anionic sites in the glomerular basement membrane (GBM) of streptozotocin (STZ)-induced diabetic rats with or without treatment by an antiplatelet drug, dilazep dihydrochloride, is described. Expression of glomerular extracellular matrix (ECM) components was examined by immunofluorescence. Renal specimens were immersed in polyethyleneimine (PEI) as a cationic probe and then examined by electron microscopy. Renal specimens were also incubated with rabbit antirat type IV collagen, laminin, and fibronectin antisera and then stained with fluorescein isothiocyanate (FITC)-labeled goat antirabbit IgG antiserum. Mean values of proteinuria in the dilazep-treated diabetic rats were significantly decreased compared with those in nontreated diabetic rats. There was no significant correlation between the levels of proteinuria and those of creatinine clearance (CCr). Number of anionic sites on the GBM in the dilazep-treated diabetic rats were greater than those in diabetic rats. There was no significant difference in the staining of such ECM components between both rat groups. The authors concluded that the dilazep dihydrochloride might prevent anionic charges on the GBM and decrease the urinary excretion of proteins in STZ-induced diabetic rats. PMID:8587006

  18. The effect of exercise on the peripheral nerve in streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Jin, Heung Yong; Lee, Kyung Ae; Park, Tae Sun

    2015-04-01

    The exact effectiveness of supportive care activities, such as exercise, in diabetes patients has yet to be elucidated in the diabetic peripheral neuropathy (DPN) field. Therefore, this study was designed to investigate the effect of regular exercise on the peripheral nerves of streptozotocin-induced diabetic rats. The animals were divided as follows into six groups according to exercise combination and glucose control: Normal group, normal group with exercise (EXE), diabetic group (DM), DM group with EXE, DM + glucose control with insulin (INS), and DM + INS + EXE. Animals in the exercise groups were made to walk on a treadmill machine everyday for 30 min at a setting of 8 m/min without inclination. After 8 weeks, sensory parameters were evaluated, and after 16 weeks, biochemicals and peripheral nerves were quantified by immunohistochemistry and compared among experimental groups. The resulting data showed that fasting blood glucose levels and HbA1c levels were not influenced significantly by exercise in normal and DM groups. However, the current perception threshold and the von Frey stimulation test revealed higher thresholds in the DM + INS + EXE group than in the DM + INS group (P < 0.05). Significantly lower thresholds were observed in untreated DM groups (DM or DM + EXE) compared to the normal and insulin-treated DM groups (P < 0.05). Intra-epidermal nerve fiber density was reduced in a lesser degree in the DM + INS + EXE group than in the DM + INS group (9.8 ± 0.4 vs. 9.1 ± 0.5, P < 0.05). Exercise alone was not associated with a significant protective effect on the peripheral nerve in the normal or DM groups; however, a beneficial effect from exercise was observed when hyperglycemia was controlled with insulin in the DM group. These findings suggest that exercise has a potential protective effect against DPN based on the preferential effort for glucose control, although exercise alone cannot prevent peripheral nerve damage from hyperglycemia. PMID:25253638

  19. Exercise Training and Grape Seed Extract Co-Administration Improves Lipid Profile, Weight Loss, Bradycardia, and Hypotension of STZ-Induced Diabetic Rats

    PubMed Central

    Badavi, Mohammad; Abedi, Hassan Ali; Dianat, Mahin; Sarkaki, Ali Reza

    2013-01-01

    Background: Exercise Training (ET) and Grape Seed Extract (GSE) as an antioxidant have many positive effects on controlling diabetes mellitus and its complications. Objectives: This study aimed to determine the effects of GSE alone or combined with ET on body weight, plasma lipid profile, blood pressure, and heart rate in STZ-induced diabetic rats. Methods: In this study, male Wistar rats were randomly assigned to five groups: sedentary control, sedentary diabetic, trained diabetic, GSE treated sedentary diabetic, and GSE treated trained diabetic. ET was conducted on the treadmill daily for 8 weeks. One way ANOVA followed by LSD test was used for statistical analysis. Results: Reduction of body weight, high density lipoproteins, heart rate, and systolic blood pressure and increment of total cholesterol, triglyceride, low density lipoprotein, and very low density lipoproteins were observed after STZ injection. Co-administration of GSE and ET had more positive effects on lipid profile compared to each method alone. In addition, GSE and ET modified heart rate partially, while their combination was more effective in improvement of heart rat in conscious rats. On the other hand, administration of ET or GSE alone did not affect systolic blood pressure and body weight, while their combination restored systolic blood pressure completely and improved body weight partially. Conclusions: The study findings indicated that ET combined with GSE had more beneficial effects compared to each one alone on the complications of STZ induced diabetes. This may constitute a convenient and inexpensive therapeutic approach to diabetic complications. PMID:24757634

  20. Improvement in nutrient handling in STZ induced diabetic rats treated with Ocimum gratissimum

    PubMed Central

    Okon, Uduak Akpan; Davies, Koofreh Godwin; Olubobokun, Titilope Helen

    2015-01-01

    Objective: Alteration in digestive and absorptive enzymatic activities has been reported in diabetes mellitus (DM), but not with Ocimum gratissimum (OG) treatment. This study was, therefore, designed to indirectly assess the effect of DM and treatment with OG on nutrient digestion and absorption, through estimation of their fecal excretion. Materials and Methods: Animals were randomly assigned into three groups of six per group for control, DM and diabetic mellitus treated (DMT). Diabetes was induced by single intraperitoneal injection of 65 mg/kg streptozotocin in the test groups. OG was administered to the DMT group at dose of 1500 mg/kg once daily for 28 days. Fecal glucose, protein and cholesterol were determined. Results: Fecal glucose was significantly (P < 0.001) lower in the DM group compared to the control and DMT groups, with the DMT groups significantly (P < 0.001) lower than the control. Fecal protein was significantly (P < 0.001) lower in the DM group than the control whereas it was significantly lower in the DMT groups than the DM. Fecal cholesterol was significantly (P < 0.001) higher in the DM than the DMT and control groups with DMT significantly (P < 0.01) higher than the control. Conclusion: This result indicates the propensity of OG to reverse impairment of nutrient digestion and absorption in DM. PMID:25664269

  1. Modulation of liver function, antioxidant responses, insulin resistance and glucose transport by Oroxylum indicum stem bark in STZ induced diabetic rats.

    PubMed

    Singh, Jyotsna; Kakkar, Poonam

    2013-12-01

    A decoction of stem bark of Oroxylum indicum Vent. (OI) is taken (2-3 times/day) by the tribal people of Sikkim, India to treat diabetes but scientific validation of its overall potential is lacking. Present study was aimed to assess in vitro antihyperglycemic activity of standardized OI extract using inhibition of ?-glucosidase, BSA glycation and enhancement of insulin sensitivity. Antidiabetic and antioxidant modulatory effects of OI extract along with the blood biomarkers of toxic response were studied in streptozotocin (STZ) induced diabetic rats. In vitro analysis showed strong antioxidant capacity of OI -and potential to inhibit BSA glycation and ?-glucosidase activity which was comparable to standard counterparts. Extract also improved insulin sensitivity in mature 3T3-L1 adipocytes. In vivo effects of OI extract (oral 250 mg/kg b.wt.) on STZ induced type II diabetic rats normalized the antioxidant status (p?0.01). Analysis of blood biomarkers of toxic response indicated its safety. Lowering of total cholesterol and HDL levels (p?0.05) and restoration of glycated Hb (p?0.01) were also found in OI treated diabetic rats. HOMA-IR, QUICKI analysis along with area under the curve analysis showed the capacity of OI extract to enhance the insulin sensitivity significantly (p?0.01) which was confirmed by increased GLUT-4 translocation in skeletal muscles. PMID:24140466

  2. Polyploidy Analysis and Attenuation of Oxidative Stress in Hepatic Tissue of STZ-Induced Diabetic Rats Treated with an Aqueous Extract of Vochysia rufa.

    PubMed

    Moraes, Izabela Barbosa; Manzan-Martins, Camilla; de Gouveia, Neire Moura; Calábria, Luciana Karen; Hiraki, Karen Renata Nakamura; Moraes, Alberto da Silva; Espindola, Foued Salmen

    2015-01-01

    Diabetes mellitus (DM) is characterized by hyperglycemia and alterations in the metabolism of lipids, carbohydrates, and proteins. Due to its hypoglycemic effect Vochysia rufa is frequently used in Uberlandia, Brazil, to treat DM. Despite its popularity, there is little information about its effect on hepatic tissue. Therefore, we evaluated the histoarchitecture, oxidative stress parameters, and polyploidy of liver tissue from streptozotocin- (STZ-) induced diabetic rats treated with aqueous extract of Vochysia rufa (AEV). Histology was determined by fixing the livers, processing, and staining with HE. Oxidative stress was determined by evaluating CAT, GPx, and SOD activity in liver homogenates and hepatic mitochondria fraction and by measuring GST, GSH levels and lipid peroxidation (MDA). Polyploidy was determined by subjecting isolated hepatocyte nuclei to flow cytometry. In the diabetic group, GST activity and GSH rates decreased whereas liver homogenate analysis showed that GPx, SOD activity and MDA increased. AEV treatment restored all parameters to normal levels. The oxidative stress analysis of hepatic mitochondria fraction showed similar results. Lower polyploid cell populations were found in the diabetic rat livers, even after glibenclamide treatment. Thus, AEV treatment efficiently reduced hepatic oxidative stress caused by STZ-induced diabetes and produced no morphological changes in the histological analysis. PMID:25763088

  3. Polyploidy Analysis and Attenuation of Oxidative Stress in Hepatic Tissue of STZ-Induced Diabetic Rats Treated with an Aqueous Extract of Vochysia rufa

    PubMed Central

    Moraes, Izabela Barbosa; Manzan-Martins, Camilla; de Gouveia, Neire Moura; Calábria, Luciana Karen; Hiraki, Karen Renata Nakamura; Moraes, Alberto da Silva; Espindola, Foued Salmen

    2015-01-01

    Diabetes mellitus (DM) is characterized by hyperglycemia and alterations in the metabolism of lipids, carbohydrates, and proteins. Due to its hypoglycemic effect Vochysia rufa is frequently used in Uberlandia, Brazil, to treat DM. Despite its popularity, there is little information about its effect on hepatic tissue. Therefore, we evaluated the histoarchitecture, oxidative stress parameters, and polyploidy of liver tissue from streptozotocin- (STZ-) induced diabetic rats treated with aqueous extract of Vochysia rufa (AEV). Histology was determined by fixing the livers, processing, and staining with HE. Oxidative stress was determined by evaluating CAT, GPx, and SOD activity in liver homogenates and hepatic mitochondria fraction and by measuring GST, GSH levels and lipid peroxidation (MDA). Polyploidy was determined by subjecting isolated hepatocyte nuclei to flow cytometry. In the diabetic group, GST activity and GSH rates decreased whereas liver homogenate analysis showed that GPx, SOD activity and MDA increased. AEV treatment restored all parameters to normal levels. The oxidative stress analysis of hepatic mitochondria fraction showed similar results. Lower polyploid cell populations were found in the diabetic rat livers, even after glibenclamide treatment. Thus, AEV treatment efficiently reduced hepatic oxidative stress caused by STZ-induced diabetes and produced no morphological changes in the histological analysis. PMID:25763088

  4. Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ)-Induced Diabetic Rats

    PubMed Central

    Liu, Jing; Zhou, Feng; Li, Guang-Yong; Wang, Lin; Li, Hui-Xi; Bai, Guang-Yi; Guan, Rui-Li; Xu, Yong-De; Gao, Ze-Zhu; Tian, Wen-Jie; Xin, Zhong-Cheng

    2013-01-01

    To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ? 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of ?-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment. PMID:23698784

  5. Antidiabetic and Hypolipidemic Activities of Curculigo latifolia Fruit:Root Extract in High Fat Fed Diet and Low Dose STZ Induced Diabetic Rats

    PubMed Central

    Ishak, Nur Akmal; Ismail, Maznah; Hamid, Muhajir; Ahmad, Zalinah; Abd Ghafar, Siti Aisyah

    2013-01-01

    Curculigo latifolia fruit is used as alternative sweetener while root is used as alternative treatment for diuretic and urinary problems. The antidiabetic and hypolipidemic activities of C. latifolia fruit:root aqueous extract in high fat diet (HFD) and 40?mg streptozotocin (STZ) induced diabetic rats through expression of genes involved in glucose and lipid metabolisms were investigated. Diabetic rats were treated with C. latifolia fruit:root extract for 4 weeks. Plasma glucose, insulin, adiponectin, lipid profiles, alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), urea, and creatinine levels were measured before and after treatments. Regulations of selected genes involved in glucose and lipid metabolisms were determined. Results showed the significant (P < 0.05) increase in body weight, high density lipoprotein (HDL), insulin, and adiponectin levels and decreased glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), urea, creatinine, ALT, and GGT levels in diabetic rats after 4 weeks treatment. Furthermore, C. latifolia fruit:root extract significantly increased the expression of IRS-1, IGF-1, GLUT4, PPAR?, PPAR?, AdipoR1, AdipoR2, leptin, LPL, and lipase genes in adipose and muscle tissues in diabetic rats. These results suggest that C. latifolia fruit:root extract exerts antidiabetic and hypolipidemic effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats. PMID:23762147

  6. Effects of vanadium (III, IV, V)-chlorodipicolinate on glycolysis and antioxidant status in the liver of STZ-induced diabetic rats.

    PubMed

    Xie, Mingxia; Chen, Deliang; Zhang, Fang; Willsky, Gail R; Crans, Debbie C; Ding, Wenjun

    2014-07-01

    Vanadium compounds exert various insulin-mimetic and anti-diabetic effects both in vitro and in vivo. Vanadium(III, IV, V)-chlorodipicolinate (Vdipic-Cl) compounds, including H[V(III)(dipic-Cl)2]·5H2O (V3dipic-Cl), V(IV)O(dipic-Cl)(H2O)2 (V4dipic-Cl) and K[V(V)O2(dipic-Cl)] (V5dipic-Cl), were synthesized with the indicated oxidation states. The present study was conducted to investigate if chemical valence and anti-oxidation effects of vanadium compounds are involved in the anti-diabetic effects observed in streptozotocin (STZ)-induced diabetic rats treated with these vanadium compounds. V3dipic-Cl, V4dipic-Cl, V5dipic-Cl, inorganic vanadium salts vanadyl sulfate (VOSO4) or sodium metavanadate (NaVO3) were orally administered in drinking water (50 ?gV/ml) to STZ-induced diabetic rats for 28 days. The results showed that Vdipic-Cl treatment significantly improved hyperglycemia and glucose intolerance, as well as increased hepatic glycogen synthesis in diabetic rats. The mRNA levels of key glycolytic enzymes in liver, phosphoenolpyruvate carboxykinase (PEPCK), glucokinase (GK), and L-pyruvate kinase (L-PK) altered in diabetic animals were significantly restored towards normal values by treatment with some of the vanadium compounds. Moreover, the diabetes elevated activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in serum were significantly decreased after treatment with Vdipic-Cl complexes. Furthermore, treatment of diabetic rats with V4dipic-Cl and V5dipic-Cl compounds significantly reduced malondialdehyde (MDA) production and increased glutathione peroxidase (GSH-Px) and catalase (CAT) activities. These data suggest that vanadium compounds with the indicated chemical valence promote glycogen synthesis and recover suppressed glycolysis in the liver of diabetic rats due to their capacity to reduce oxidative stress by stimulating antioxidant enzymes. PMID:24747360

  7. Protective Effect of Rutin and Naringin on Sperm Quality in Streptozotocin (STZ) Induced Type 1 Diabetic Rats

    PubMed Central

    Butchi Akondi, Raju; Kumar, Phani; Annapurna, Akula; Pujari, Manasa

    2011-01-01

    Oxidative stress is one of the important causes of the type 1 diabetes induced changes in the sperm quality. Bioflavonoids, Rutin 10 mg/Kg and Naringin 10 mg/Kg were evaluated for their protective effects on sperm parameters, oxidative stress, and histopathology of type 1 diabetic rats. Results demonstrated the reduction in sperm count, sperm motility and vitality in diabetic rats. Mass drug administration (MDA) levels were increased and superoxide dismutase (SOD) catalase levels were decreased. Histopathological changes were evident and in accordance with the above results. In the treatment groups, both Rutin and Naringin in combination with insulin treatment in diabetic rats produced protection from diabetes and improved all the sperm parameters, decreased the MDA levels and increased the SOD and catalase levels. Protection was evident in histological examination. Our data suggests that the possible protection of testicular tissue and reproduction from oxidative stress have been induced by type 1 diabetes mellitus. PMID:24250392

  8. Protective effect and mechanism of Ginkgo biloba extract-EGb 761 on STZ-induced diabetic cardiomyopathy in rats

    PubMed Central

    Saini, Arminder Singh; Taliyan, Rajeev; Sharma, Pyare Lal

    2014-01-01

    Diabetes mellitus (DM) is a complex metabolic disorder which leads to development of various long-term complications including cardiomyopathy. Oxidative stress due to hyperglycemia plays a key role in the development and progression of diabetic cardiomyopathy (DC). Oxidative stress causes the opening of mitochondrial permeability transition pore (mPTP) eventually leading to myocardium dysfunction. The Ginkgo biloba extract (EGb 761) has antioxidant and mitochondrial membrane potential stabilizing property. Therefore, this study was designed to evaluate the effect of EGb 761 and its possible mechanism of action in DC. Materials and Methods: DM was induced by single injection of Streptozotocin (STZ) (50 mg/kg, i.p.) and cardiac dysfunction was developed on 8th weeks after STZ injection. Cardiac dysfunction was assessed by measuring left ventricle weight/body weight (LVW/BW) ratio, left ventricle (LV) collagen content, LV protein content, serum lactate dehydrogenase (LDH) level. Results: EGb 761 treatment (started after 7th week of STZ injection and continued for 3 weeks) attenuated cardiac dysfunction in diabetic rats as evidenced by a decrease in LV collagen content, protein content, LVW/BW ratio, serum LDH level. Moreover, EGb 761 attenuated the oxido-nitrosative stress (thiobarbituric acid reactive substances, superoxide anion generation, myocardium nitrite) and concomitantly improved the antioxidant enzyme (reduced glutathione) level as compared to untreated diabetic rats. However, protective effect of EGb 761 was inhibited by atractyloside (mPTP opener) that was given for 3 weeks, 30 min before the EGb 761 treatment. These results indicate that EGb 761 corrects diabetic cardiac dysfunction probably by its direct radical scavenging activity and its ability to inhibit the opening of mPTP channel since the cardioprotective effect of EGb 761 was completely abolished by atractyloside. PMID:24914284

  9. A novel dihydroxy gymnemic triacetate isolated from Gymnema sylvestre possessing normoglycemic and hypolipidemic activity on STZ-induced diabetic rats

    Microsoft Academic Search

    Pitchai Daisy; James Eliza; Khanzan Abdul Majeed Mohamed Farook

    2009-01-01

    Aim of the studyGymnema sylvestre (Asclepiadaceae) is emerging as a potential treatment for the management of diabetes. The leaves are used in herbal medicine preparations. The present study was carried out to isolate and identify the putative antidiabetic compound based on bioassay-guided fractionation.

  10. Evaluation of Insulin and Ascorbic Acid Effects on Expression of Bcl2 Family Proteins and Caspase3 Activity in Hippocampus of STZ-Induced Diabetic Rats

    Microsoft Academic Search

    Iraj Jafari Anarkooli; Mojtaba Sankian; Fatemeh Vahedi; Shokoofeh Bonakdaran; Abdol-Reza Varasteh; Hossein Haghir

    2009-01-01

    Aims Effects of insulin and ascorbic acid on expression of Bcl-2 family proteins and caspase-3 activity in hippocampus of diabetic\\u000a rats were evaluated in this study. Methods Diabetes was induced in Wistar male rats by streptozotocin (STZ). Six weeks after verification of diabetes, the animals were\\u000a treated for 2 weeks with insulin or\\/and ascorbic acid in separate groups. Hippocampi of rats

  11. The Effect of Angipars on Diabetic Neuropathy in STZ-Induced Diabetic Male Rats: A Study on Behavioral, Electrophysiological, Sciatic Histological and Ultrastructural Indices

    PubMed Central

    Zangiabadi, Nasser; Mohtashami, Hossein; Hojatipour, Mahboobeh; Jafari, Mandana; Asadi-Shekaari, Majid; Shabani, Mohammad

    2014-01-01

    Diabetes mellitus is the most common metabolic disease with a high prevalence rate in human society that eventually leads to the peripheral nervous system complications in a great number of patients. In the present study, the effects of Angipars on nerve conduction velocity, histological alterations, and behavioral indices were investigated. Diabetes was induced in male rats by intraperitoneal injection of streptozotocin (STZ). Six weeks after STZ injection, animals were divided into five groups control, vehicle, and 3 experimental groups. The vehicle group received 1?mL distilled water daily for two weeks and three experimental groups received, respectively, intraperitoneal injection of 5, 10, and 20?mg/kg Angipars daily for two weeks. Intraperitoneal injection of Angipars, in some extent, could significantly improve behavioral indices of the experimental groups as compared to the vehicle group. Furthermore, mean nerve conduction velocity in the vehicle group showed significant difference with that in the control and the 2nd experimental groups; therefore, Angipars could increase nerve conduction velocity in neuropathic rats. Overall, Angipars exerted positive effects on the treatment and reduction of physiologic symptoms and improvement of sciatic morphological injuries in neuropathic rats. PMID:25614895

  12. Changes in Iron Metabolism and Oxidative Status in STZ-Induced Diabetic Rats Treated with Bis(maltolato) Oxovanadium (IV) as an Antidiabetic Agent

    PubMed Central

    Sánchez-González, Cristina; López-Chaves, Carlos; Trenzado, Cristina E.; Aranda, Pilar; López-Jurado, María; Gómez-Aracena, Jorge; Montes-Bayón, María; Sanz-Medel, Alfredo; Llopis, Juan

    2014-01-01

    The role of vanadium as a micronutrient and hypoglycaemic agent has yet to be fully clarified. The present study was undertaken to investigate changes in the metabolism of iron and in antioxidant defences of diabetic STZ rats following treatment with vanadium. Four groups were examined: control; diabetic; diabetic treated with 1?mgV/day; and Diabetic treated with 3?mgV/day. The vanadium was supplied in drinking water as bis(maltolato) oxovanadium (IV) (BMOV). The experiment had a duration of five weeks. Iron was measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, and femur. Superoxide dismutase, catalase, NAD(P)H: quinone-oxidoreductase-1 (NQO1) activity, and protein carbonyl group levels in the liver were determined. In the diabetic rats, higher levels of Fe absorbed, Fe content in kidney, muscle, and femur, and NQO1 activity were recorded, together with decreased catalase activity, in comparison with the control rats. In the rats treated with 3?mgV/day, there was a significant decrease in fasting glycaemia, Fe content in the liver, spleen, and heart, catalase activity, and levels of protein carbonyl groups in comparison with the diabetic group. In conclusion BMOV was a dose-dependent hypoglycaemic agent. Treatment with 3?mgV/day provoked increased Fe deposits in the tissues, which promoted a protein oxidative damage in the liver. PMID:24511298

  13. The effect of insulin treatment and of islet transplantation on the resistance artery function in the STZ-induced diabetic rat.

    PubMed

    Heygate, K M; Davies, J; Holmes, M; James, R F; Thurston, H

    1996-10-01

    1. This study was designed to investigate the influence of insulin treatment and islet transplantation on the smooth muscle contractility and endothelium-dependent and independent relaxation of resistance arteries in the chemically induced streptozotocin (STZ) diabetic rat after 6-8 weeks, and 12-14 weeks of diabetes, compared to non-diabetic age-matched controls. 2. The morphology, and contractile responses to high potassium physiological salt solution (KPSS), KPSS containing 10(-5) M noradrenaline (NAK), and concentration-response curves to noradrenaline (NA) of mesenteric resistance arteries were recorded, along with the endothelium-dependent relaxation responses to acetylcholine (ACh) and bradykinin (BK), and endothelium-independent relaxation to sodium nitroprusside (SNP). Concentration-response curves were then repeated in the presence of a nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NOARG). 3. Insulin-treated diabetic rats in the 12 week study demonstrated enhanced vascular contractility to KPSS, NAK and NA, compared to age-matched non-diabetic controls. 4. Incubation with L-NOARG resulted in both a significant increase in maximum contractile response, and sensitivity (pD2) to NA in the untreated diabetic group (6 weeks). A significant shift in sensitivity was also seen in the insulin-treated diabetic group. In the 12 week study, incubation with L-NOARG resulted in an increased maximum contractile response and sensitivity to NA in the insulin-treated diabetics. An increase in sensitivity was also observed in the untreated diabetic group. 5. Endothelium-dependent relaxation to ACh was significantly augmented in the untreated diabetics (6-weeks), compared to the control group. In the 12-week study, relaxation to both ACh and BK was not significantly different in any of the experimental groups when compared to the sham-operated non-diabetic controls. 6. Incubation with L-NOARG resulted in a significant attenuation of the maximum relaxation response to ACh and BK in all of the experimental groups, in the 6- and the 12-week study. 7. There was no significant difference in the maximum relaxation response or sensitivity to sodium nitroprusside between the diabetic groups and their age-matched controls in either the 6-week or the 12-week study. 8. The results of this study suggest an enhanced release of nitric oxide in the early stages of diabetes, which is more evident in the untreated diabetic rats than the insulin treated, and appears to normalize as the duration of diabetes progresses. This study also shows that the alteration in vascular reactivity of the resistance arteries can be restored to within normal limits by the transplantation of islets of Langerhans, and that islet transplantation is an effective strategy in the correction of the metabolic abnormalities associated with insulin-dependent diabetes. PMID:8894169

  14. Effects of L-3-n-butylphthalide on cognitive dysfunction and NR2B expression in hippocampus of streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Li, Jie; Zhang, Songyun; Zhang, Lihui; Wang, Ruiying; Wang, Mian

    2015-01-01

    Diabetes mellitus is associated with rapid cognitive decline. Currently, there is no effective treatment for cognitive dysfunction induced by diabetes. L-3-n-Butylphthalide (L-NBP) is a nerve protective drug extracted from seeds of celery, which has been proved to improve learning and memory in vascular dementia animal models by improving microcirculation, protecting mitochondria and increasing long-term potentiation (LTP). NR2B, one of the subunits of N-methyl-D-aspartate receptor, has been proved to be an important factor for the formation of LTP. The study aimed to investigate the role of NR2B in cognitive dysfunction in the rats with type 1 diabetes and define the protective effects of L-NBP on cognition. A rat model of type 1 diabetes was established by a single intraperitoneal injection of streptozotocin at 60 mg/kg. Animals were randomly allocated to four groups: normal control (NC); diabetic control (DC); diabetic + low L-NBP (DL, administered L-NBP 60 mg/kg per day for 12 weeks); and diabetic + high L-NBP (DH, administered L-NBP 120 mg/kg per day, for 12 weeks). After 12 weeks, cognitive and memory changes were investigated in the Morris water maze. The expression of NR2B was assessed by real-time polymerase chain reaction, Western blotting, and immunohistochemistry. Our results indicated that the escape latency was significantly increased and the number of crossing platform was significantly decreased in DC group compared to NC group. Also, the expression of NR2B was significantly declined in DC group. However, compared to DC group, the expression of NR2B of the L-NBP-treated groups was significantly increased and the escape latency was shortened with the DH group being the most obvious. Therefore, L-NBP can improve the cognitive function by up-regulating the expression of NR2B in STZ-diabetic rats, which may provide the direction for future diabetic encephalopathy therapy. PMID:25149651

  15. Insulin secreting and alpha-glucosidase inhibitory activity of hexane extract of Annona squamosa Linn. in streptozotocin (STZ) induced diabetic rats.

    PubMed

    Ranjana; Tripathi, Yamini B

    2014-06-01

    The hexane extract of A. squamosa (ASHE) in 100 and 400 mg/kg body weight dose raised the insulin level when compared with Glimepiride (1 mg/kg) and also inhibited alpha-glucosidase activity when compared with Acarbose (10 mg/kg) in streptozotocin induced diabetic rats. The ASHE significantly reduced peak blood glucose (Gp30) and area under curve (AUC) in diabetic rats in oral glucose (OGTT) and oral sucrose (OSTT) tolerance test, but there was more reduction of Gp30 value than AUC in OSTT. Thus, it can be suggested that the ASHE, has hypoglycemic role at 2 levels, i.e. it acts as secretagogue and also inhibits the intestinal enzymes, responsible for glucose metabolism. PMID:24956893

  16. A Novel Role for SIRT-1 in L-Arginine Protection against STZ Induced Myocardial Fibrosis in Rats

    PubMed Central

    Rizk, Sherine M.; El-Maraghy, Shohda A.; Nassar, Noha N.

    2014-01-01

    Background L-arginine (L-ARG) effectively protects against diabetic impediments. In addition, silent information regulator (SIRT-1) activators are emerging as a new clinical concept in treating diabetic complications. Accordingly, this study aimed at delineating a role for SIRT-1 in mediating L-ARG protection against streptozotocin (STZ) induced myocardial fibrosis. Methods Male Wistar rats were allocated into five groups; (i) normal control rats received 0.1 M sodium citrate buffer (pH 4.5); (ii) STZ at the dose of 60 mg/kg dissolved in 0.1 M sodium citrate buffer (pH 4.5); (iii) STZ + sirtinol (Stnl; specific inhibitor of SIRT-1; 2 mg/Kg, i.p.); (iv) STZ + L-ARG given in drinking water (2.25%) or (v) STZ + L-ARG + Stnl. Results L-ARG increased myocardial SIRT-1 expression as well as its protein content. The former finding was paralleled by L-ARG induced reduction in myocardial fibrotic area compared to STZ animals evidenced histopathologically. The reduction in the fibrotic area was accompanied by a decline in fibrotic markers as evident by a decrease in expression of collagen-1 along with reductions in myocardial TGF-?, fibronectin, CTGF and BNP expression together with a decrease in TGF-? and hydroxyproline contents. Moreover, L-ARG increased MMP-2 expression in addition to its protein content while decreasing expression of PAI-1. Finally, L-ARG protected against myocardial cellular death by reduction in NF?-B mRNA as well as TNF-? level in association with decline in Casp-3 and FAS expressions andCasp-3protein content in addition to reduction of FAS positive cells. However, co-administration of L-ARG and Stnl diminished the protective effect of L-ARG against STZ induced myocardial fibrosis. Conclusion Collectively, these findings associate a role for SIRT-1 in L-ARG defense against diabetic cardiac fibrosis via equilibrating the balance between profibrotic and antifibrotic mediators. PMID:25501750

  17. Rapid onset of cardiomyopathy in STZ-induced female diabetic mice involves the downregulation of pro-survival Pim-1

    PubMed Central

    2014-01-01

    Background Diabetic women are five times more likely to develop congestive heart failure compared with two fold for men. The underlying mechanism for this gender difference is not known. Here we investigate the molecular mechanisms responsible for this female disadvantage and attempt safeguarding cardiomyocytes viability and function through restoration of pro-survival Pim-1. Methods and Results Diabetes was induced by injection of streptozotocin in CD1 mice of both genders. Functional and dimensional parameters measurement using echocardiography revealed diastolic dysfunction in female diabetic mice within 8 weeks after STZ-induced diabetes. This was associated with significant downregulation of pro-survival Pim-1 and upregulation of pro-apoptotic Caspase-3, microRNA-1 and microRNA-208a. Male diabetic mice did not show any significant changes at this time point (P?diabetic). Further, the onset of ventricular remodelling was quicker in female diabetic mice showing marked left ventricular dilation, reduced ejection fraction and poor contractility (P?diabetic at 12 and 16 weeks of STZ-induced diabetes). Molecular analysis of samples from human diabetic hearts confirmed the results of pre-clinical studies, showing marked downregulation of Pim-1 in the female diabetic heart (P?diabetic). Finally, in vitro restoration of Pim-1 reversed the female disadvantage in diabetic cardiomyocytes. Conclusions We provide novel insights into the molecular mechanisms behind the rapid onset of cardiomyopathy in female diabetics. These results suggest the requirement for the development of gender-specific treatments for diabetic cardiomyopathy. PMID:24685144

  18. Anti-diabetic effects of polysaccharides from Talinum triangulare in streptozotocin (STZ)-induced type 2 diabetic male mice.

    PubMed

    Xu, Wei; Zhou, Qing; Yin, Jiao-jiao; Yao, Yong; Zhang, Jiu-liang

    2015-01-01

    The present study evaluated the anti-diabetic effects of the polysaccharides obtained from Talinum triangulare (TTP). Two TTP doses (150 mg/kg and 300 mg/kg · bw/d) were administered orally to normal and streptozotocin (STZ)-induced type 2 diabetic male Kunming mice, respectively. The TTP hypoglycemic and hypolipidemic effects were evaluated by testing the fast blood glucose (FBG) level, fasting serum insulin (FINS), and serum lipids (TC, TG, HDL, LDL) as well as the body, hepar and kidney weights. After four weeks administration, the low-dose group 150 mg/kg · bw/d) and high-dose group (300 mg/kg · bw/d) showed a marked FBG fall rate of 29.85% and 41.18% (FBG fall rate% = ((Diabetic control--TTP group)/Diabetic control) × 100%). The results of FBG and serum lipids indicate that TTP possess significant hypoglycemic effect, but no significant hypolipidemic effect. These results suggest the potential use of TTP as a functional food for the treatment of type 2 diabetic mellitus (T2DM). PMID:25236607

  19. Antidiabetic and hypolipidaemic properties of garlic (Allium sativum) in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Martha Thomson; Zainab M. Al-Amin; Khaled K. Al-Qattan; Lemia H. Shaban; Muslim Ali

    2007-01-01

    In this study the hypoglycaemic, hypocholesterolaemic and hypotriglyceridaemic effects of garlic were studied in streptozotocin (STZ)-induced diabetic rats. Compared to normal (non-diabetic) rats, STZ-induced diabetic rats had approximately 200% higher serum glucose, 50% higher serum cholesterol and 30% higher serum triglyceride levels as well as 86% higher urinary protein levels. Daily treatment of STZ-induced diabetic rats with an extract of

  20. Attenuation of diabetic disorders in experimentally induced diabetic rat by methanol extract of seed of Holarrhena antidysenterica

    Microsoft Academic Search

    Kazi Monjur Ali; Tushar Kanti Bera; Suvra Mandal; Bikash Ranjan Barik; Debidas Ghosh

    The study was undertaken to evaluate the therapeutic efficacy of methanol extract of seed of Holarrhena antidysenterica in streptozotocin (STZ) induced diabetic rats. Extract was administered orally at a dose of 400 mg \\/ kg body weight \\/ day for 21 days, to STZ-induced diabetic rats. The fasting blood glucose level was decreased significantly after the treatment of methanolic extract

  1. In Vivo Hypoglycaemic Effect and Inhibitory Mechanism of the Branch Bark Extract of the Mulberry on STZ-Induced Diabetic Mice

    PubMed Central

    Liu, Hua-Yu; Fang, Meng; Zhang, Yu-Qing

    2014-01-01

    Branch bark extract (BBE) derived from the mulberry cultivar Husang 32 (Morus multicaulis L.) with aqueous alcohol solution has been investigated as an inhibitor of ?-glycosidase in vitro. Mulberry BBE was orally administered to STZ-induced diabetic mice for three weeks, and it improved the weight gain and ameliorated the swelling of liver and kidney in diabetic mice. Obviously, mulberry BBE not only can reduce the abnormally elevated levels of serum insulin and ameliorate insulin resistance induced by STZ, but also it regulates dyslipidemia in diabetic mice. To understand this therapeutic effect and the regulatory mechanisms of BBE in diabetic mice, a qRT-PCR experiment was performed, indicating that the mulberry BBE can regulate the mRNA expression of glycometabolism genes in diabetic mice, including glucose-6-phosphatase (G6Pase), glucokinase (GCK), and phosphoenolpyruvate carboxykinase (PEPCK), thereby regulating sugar metabolism and reducing the blood glucose level in diabetic mice. The mulberry BBE can increase the mRNA expression of the genes Ins1, Ins2 and pancreatic duodenal homeobox-1 (PDX-1) and may decrease the insulin resistance in diabetic mice. Those results provide an important basis for making the best use of mulberry branch resources and producing biomedical drugs with added value. PMID:25177729

  2. A Novel Role of Globular Adiponectin in Treatment with HFD/STZ Induced T2DM Combined with NAFLD Rats

    PubMed Central

    You, Guo-Ping; Zhang, Xuan-Pu; Yang, Xiang-Jiu; Lu, Hua-Dong; Huang, Yan-Ling; Zhang, Wen-Qiang

    2014-01-01

    Aims. To evaluate the effects of globular adiponectin (gAd) on treatment of type 2 diabetic rats combined with NAFLD. Materials and Methods. Twenty-one male wistar rats were fed with normal diet (7 rats) or high fat diet (HFD) (14 rats) for 4 weeks, and then HFD-fed rats were injected with streptozotocin (STZ) to induce type 2 diabetes mellitus (T2DM). Half of T2DM rats were randomly injected with gAd intraperitoneally for 7 days. The expressions of adiponectin receptors (adipoR1/R2) in liver and skeletal muscle tissues were detected through western blotting or RT-qPCR, respectively. Results. Globular adiponectin alleviated the hepatic steatosis and increased insulin secretion. In liver, both the protein and mRNA expressions of adipoR2 in T2DM group decreased (P < 0.05, resp.) in contrast to NC group and increased (P < 0.05 and P < 0.001, resp.) after gAd treatment. But the protein and mRNA expressions of adipoR1 increased (P < 0.05, resp.) in T2DM group and no change was found in the gAd-treated group. In skeletal muscle, the protein and mRNA expressions of adipoR1 and adipoR2 were upregulated in T2DM group and were downregulated after gAd treatment. Conclusions. Globular adiponectin could ameliorate the hepatic steatosis and vary the expressions of adiponectin receptors in liver and skeletal muscle by stimulating insulin secretion. PMID:24683323

  3. Hypoglycemic effect of polysaccharides produced by submerged mycelial culture of Laetiporus sulphureus on streptozotocininduced diabetic rats

    Microsoft Academic Search

    Hee Sun Hwang; Jong Won Yun

    2010-01-01

    The hypoglycemic effect of the crude extracellular polysaccharides (EPS) produced from submerged mycelial culture of an edible\\u000a mushroom Laetiporus sulphureus var. miniatus in streptozotocin (STZ)-induced diabetic rat was investigated. Hypoglycemic effect of EPS was evaluated in STZ-induced diabetic\\u000a rats, and its possible mechanism was suggested by the results of western blot analysis and immunohistochemical staining. The\\u000a results revealed that orally

  4. Hypoglycemic effect of Lentinus strigosus (Schwein.) Fr. crude exopolysaccharide in streptozotocin-induced diabetic rats.

    PubMed

    Yamac, Mustafa; Kanbak, Gungor; Zeytinoglu, Melih; Bayramoglu, Gokhan; Senturk, Hakan; Uyanoglu, Mustafa

    2008-09-01

    ABSTRACT This study reports the hypoglycemic effects of the crude exopolysaccharide (EPS) produced from submerged mycelial culture of Lentinus strigosus (Schwein.) Fr. (Family Polyporaceae) in streptozotocin (STZ)-induced diabetic rats. In a dose-dependent study, diabetic rats were treated with EPS at doses of 50-150 mg/kg of body weight for 7 days. Serum glucose and plasma insulin levels were measured in normal, STZ-induced diabetic, and EPS-treated diabetic rats. Following oral administration of EPS dosages for 7 days, the serum glucose levels in the STZ-induced diabetic rats were reduced up to 21.1% at the dose of 150 mg/kg of body weight. The results revealed that orally administered L. strigosus EPS, at the dose of 150 mg/kg, exhibited a considerable hypoglycemic effect in STZ-induced diabetic rats. Plasma insulin levels of STZ-induced diabetic rats decreased as compared to control group rats (P < .05). Although insulin levels slightly increased in the EPS-treated groups the increase was not statistically significant. The hypoglycemic potential of the EPS was further supported by histological observations of pancreatic islets of Langerhans. PMID:18800900

  5. ANTIHYPERGLYCEMIC AND RENAL PROTECTIVE ACTIVITIES OF ANACARDIUM OCCIDENTALE (ANACARDIACEAE) LEAVES IN STREPTOZOTOCIN INDUCED DIABETIC RATS

    Microsoft Academic Search

    Leonard Tedong; Théophile Dimo; Paul Desire Djomeni Dzeufiet; Acha Emmanuel Asongalem; Dongmo Selestin Sokeng; Patrice Callard; Marie Curie

    2006-01-01

    Earlier studies from our laboratory have indicated hypoglycaemic action of Anacardium occidentale (AO) leaves in experimental type 1 diabetes. Streptozotocin- induced diabetes in rats had been shown to be associated with functional and\\/or morphological changes in the kidney. Therefore, in the present investigation, we carried out studies on streptozotocin (STZ)-induced type 1 diabetes in rats chronically treated with Anacardium occidentale

  6. Beneficial effects of dietary L-arginine supplementation to diabetic rats

    E-print Network

    Kohli, Ripla

    2004-09-30

    dysfunction. In experiment I, streptozotocin (STZ) induced-diabetic male Sprague Dawley (SD) rats (a model of type-I diabetes) were individually pair-fed a casein-based diet on the basis of feed intake (per kg body weight) of non-diabetic SD rats. Addition...

  7. Renoprotective effects of olmesartan medoxomil on diabetic nephropathy in streptozotocin-induced diabetes in rats.

    PubMed

    Si, Xiaofei; Li, Peng; Zhang, Yan; Zhang, Yan; Lv, Wei; Qi, Dong

    2014-01-01

    Olmesartan medoxomil (OM) is one of the newest members of the angiotensin receptor blocker (ARB) family. The renoprotective effects of the angiotensin II type 1 receptor antagonist OM was investigated in a streptozotocin (STZ)-induced diabetic rat model. In this study, we investigated whether OM was able to ameliorate diabetic nephropathy (DN). Thirty male Sprague Dawley rats were assigned to 3 groups: the non-diabetic (group A, n=10), the untreated STZ-induced DN control (group B, n=10) and the STZ-induced DN treated with OM (group C, n=10). Blood pressure (BP) and glucose, creatinine (Cr), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA) microalbumin and urinary protein concentrations were measured. In STZ diabetic rats, BP, glucose, Cr, BUN, MDA and urinary protein levels were significantly increased compared to the non-diabetic control group. OM significantly improved the biological indices in the DN rats. The renal pathological changes were also observed under a light microscope. Our results suggested that OM exerted renoprotective effects on rats with STZ-induced diabetes. PMID:24649063

  8. Renoprotective effects of olmesartan medoxomil on diabetic nephropathy in streptozotocin-induced diabetes in rats

    PubMed Central

    SI, XIAOFEI; LI, PENG; ZHANG, YAN; ZHANG, YAN; LV, WEI; QI, DONG

    2014-01-01

    Olmesartan medoxomil (OM) is one of the newest members of the angiotensin receptor blocker (ARB) family. The renoprotective effects of the angiotensin II type 1 receptor antagonist OM was investigated in a streptozotocin (STZ)-induced diabetic rat model. In this study, we investigated whether OM was able to ameliorate diabetic nephropathy (DN). Thirty male Sprague Dawley rats were assigned to 3 groups: the non-diabetic (group A, n=10), the untreated STZ-induced DN control (group B, n=10) and the STZ-induced DN treated with OM (group C, n=10). Blood pressure (BP) and glucose, creatinine (Cr), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA) microalbumin and urinary protein concentrations were measured. In STZ diabetic rats, BP, glucose, Cr, BUN, MDA and urinary protein levels were significantly increased compared to the non-diabetic control group. OM significantly improved the biological indices in the DN rats. The renal pathological changes were also observed under a light microscope. Our results suggested that OM exerted renoprotective effects on rats with STZ-induced diabetes. PMID:24649063

  9. Tocotrienol-Rich Fraction from Palm Oil Prevents Oxidative Damage in Diabetic Rats

    PubMed Central

    Matough, Fatmah A.; Budin, Siti B.; Hamid, Zariyantey A.; Abdul-Rahman, Mariati; Al-Wahaibi, Nasar; Mohammed, Jamaludine

    2014-01-01

    Objectives: This study was carried out to determine the effects of tocotrienol-rich fraction (TRF) (200 mg/Kg) on biomarkers of oxidative stress on erythrocyte membranes and leukocyte deoxyribonucleic acid (DNA) damage in streptozotocin (STZ)-induced diabetic rats. Methods: Male rats (n = 40) were divided randomly into four groups of 10: a normal group; a normal group with TRF; a diabetic group, and a diabetic group with TRF. Following four weeks of treatment, fasting blood glucose (FBG) levels, oxidative stress markers and the antioxidant status of the erythrocytes were measured. Results: FBG levels for the STZ-induced diabetic rats were significantly increased (P <0.001) when compared to the normal group and erythrocyte malondialdehyde levels were also significantly higher (P <0.0001) in this group. Decreased levels of reduced glutathione and increased levels of oxidised glutathione (P <0.001) were observed in STZ-induced diabetic rats when compared to the control group and diabetic group with TRF. The results of the superoxide dismutase and glutathione peroxidase activities were significantly lower in the STZ-induced diabetic rats than in the normal group (P <0.001). The levels of DNA damage, measured by the tail length and tail moment of the leukocyte, were significantly higher in STZ-induced diabetic (P <0.0001). TRF supplementation managed to normalise the level of DNA damage in diabetic rats treated with TRF. Conclusion: Daily supplementation with 200 mg/Kg of TRF for four weeks was found to reduce levels of oxidative stress markers by inhibiting lipid peroxidation and increasing the levels of antioxidant status in a prevention trial for STZ-induced diabetic rats. PMID:24516761

  10. Cavernous antioxidant effect of green tea, epigallocatechin-3-gallate with/without sildenafil citrate intake in aged diabetic rats.

    PubMed

    Mostafa, T; Sabry, D; Abdelaal, A M; Mostafa, I; Taymour, M

    2013-08-01

    This study aimed to assess the cavernous antioxidant effect of green tea (GT), epigallocatechin-3-gallate (EGCG) with/without sildenafil citrate intake in aged diabetic rats. One hundred and four aged male white albino rat were divided into controls that received ordinary chow, streptozotocin (STZ)-induced aged diabetic rats, STZ-induced diabetic rats on infused green tea, induced diabetic rats on epigallocatechin-3-gallate and STZ-induced diabetic rats on sildenafil citrate added to EGCG. After 8 weeks, dissected cavernous tissues were assessed for gene expression of eNOS, cavernous malondialdehyde (MDA), glutathione peroxidase (GPx), cyclic guanosine monophosphate (cGMP), and serum testosterone (T). STZ-induced diabetic rats on GT demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats. Diabetic rats on EGCG demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats or diabetic rats on GT. Diabetic rats on EGCG added to sildenafil showed significant increase in cavernous eNOS, cGMP and significant decrease in cavernous MDA compared with other groups. Serum T demonstrated nonsignificant difference between the investigated groups. It is concluded that GT and EGCG have significant cavernous antioxidant effects that are increased if sildenafil is added. PMID:22928786

  11. Treatment with hydrogen sulfide alleviates streptozotocin-induced diabetic retinopathy in rats

    PubMed Central

    Si, Yan-Fang; Wang, Jun; Guan, Juan; Zhou, Li; Sheng, Yu; Zhao, Juan

    2013-01-01

    Background and Purpose Retinopathy, as a common complication of diabetes, is a leading cause of reduced visual acuity and acquired blindness in the adult population. The aim of present study was to investigate the therapeutic effect of hydrogen sulfide on streptozotocin (STZ)-induced diabetic retinopathy in rats. Experimental Approach Rats were injected with a single i.p. injection of STZ (60 mg·kg?1) to induce diabetic retinopathy. Two weeks later, the rats were treated with NaHS (i.p. injection of 0.1 mL·kg?1·d?1 of 0.28 mol·L?1 NaHS, a donor of H2S) for 14 weeks. Key Results Treatment with H2S had no significant effect on blood glucose in STZ-induced diabetic rats. Treatment with exogenous H2S enhanced H2S levels in both plasma and retinas of STZ-induced diabetic rats. Treatment with H2S in STZ-treated rats improved the retinal neuronal dysfunction marked by enhanced amplitudes of b-waves and oscillatory potentials and expression of synaptophysin and brain-derived neurotrophic factor, alleviated retinal vascular abnormalities marked by reduced retinal vascular permeability and acellular capillary formation, decreased vitreous VEGF content, down-regulated expressions of HIF-1? and VEGFR2, and enhanced occludin expression, and attenuated retinal thickening and suppressed expression of extracellular matrix molecules including laminin ?1 and collagen IV?3 expression in retinas of STZ-induced diabetic rats. Treatment with H2S in retinas of STZ-induced diabetic rats abated oxidative stress, alleviated mitochondrial dysfunction, suppressed NF-?B activation and attenuated inflammation. Conclusions and Implications Treatment with H2S alleviates STZ-induced diabetic retinopathy in rats possibly through abating oxidative stress and suppressing inflammation. PMID:23488985

  12. Long-term effects of Cinnamomum zeylanicum Blume oil on some physiological parameters in streptozotocin-diabetic and non-diabetic rats (Efectos a largo plazo del aceite esencial de Cinnamomum zeylanicum Blume en algunos parametros fisiológicos en ratas diabéticas inducidas por estreptozotocina)

    Microsoft Academic Search

    Talal A. ZARI; Ayed Sh

    2009-01-01

    The long-term effects of Cinnamomum zeylanicum Blume oil on some physiological parameters were investigated in streptozotocin (STZ)-induced diabetic and non-diabetic male Wistar rats. STZ-induced diabetic rats showed significant increases in the levels of blood glucose, triglycerides, cholesterol, low density lipoprotein LDL-cholesterol, urea, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) while high density lipoprotein HDL- cholesterol, total protein and uric acid

  13. A purified extract from prickly pear cactus ( Opuntia fuliginosa) controls experimentally induced diabetes in rats

    Microsoft Academic Search

    Augusto Trejo-González; Genaro Gabriel-Ortiz; Ana María Puebla-Pérez; María Dolores Huízar-Contreras; María del Rosario Munguía-Mazariegos; Silvia Mejía-Arreguín; Edmundo Calva

    1996-01-01

    The hypoglycemic activity of a purified extract from prickly pear cactus (Opuntia fuliginosa Griffiths) was evaluated on STZ-induced diabetic rats. Blood glucose and glycated hemoglobin levels were reduced to normal values by a combined treatment of insulin and Opuntia extract. When insulin was withdrawn from the combined treatment, the prickly pear extract alone maintained normoglycemic state in the diabetic rats.

  14. Protective effect of polysaccharides from Opuntia dillenii Haw. fruits on streptozotocin-induced diabetic rats.

    PubMed

    Gao, Jie; Han, Yu-Lu; Jin, Zheng-Yu; Xu, Xue-Ming; Zha, Xue-Qiang; Chen, Han-Qing; Yin, Yan-Yan

    2015-06-25

    In this study, a novel water-soluble polysaccharide fraction with molecular weight of 6479.1kDa was isolated from the fruits of Opuntia dillenii Haw., which consisted of rhamnose, xylose, mannose and glucose in the molar ratio of 14.99:1.14:1.00:6.47. The protective effect of O. dillenii Haw. fruits polysaccharide (ODFP) against oxidative damage in streptozotocin (STZ)-induced diabetic rats was investigated. The results showed that oral administration of ODFP significantly decreased food intake, water intake, urine production, organ weights and blood glucose level, and increased body weight in STZ-induced diabetic rats. ODFP also significantly increased the activities of SOD, GPx and CAT, and decreased malondialdehyde level in serum, liver, kidney, and pancreas in STZ-induced diabetic rats. Moreover, histopathological examination showed that ODFP could markedly improve the structure integrity of pancreatic islet tissue in STZ-induced diabetic rats. These results suggest that ODFP have hypoglycemic and antioxidant properties and can protect rats from STZ-induced oxidative damage. PMID:25839790

  15. Antihyperlipidemic effect of D-pinitol on streptozotocin-induced diabetic Wistar rats.

    PubMed

    Geethan, P K M Anu; Prince, P Stanely Mainzen

    2008-01-01

    D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant, Bougainvillea spectabilis, is claimed to exert insulin-like effects. This study was undertaken to evaluate the effect of D-pinitol on lipids and lipoproteins in streptozotocin (STZ)-induced diabetic Wistar rats. Rats were made type II diabetic by single intraperitoneal injection of STZ at a dose of 40 mg/kg body weight. STZ-induced diabetic rats showed significant (p < 0.05) increase in the levels of blood glucose and total cholesterol, triglycerides, free fatty acids, and phospholipids in serum, liver, kidney, heart, and brain. The levels of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol were significantly increased, and the level of high-density lipoprotein (HDL) cholesterol was significantly decreased in diabetic rats Oral administration of D-pinitol to STZ-induced diabetic rats showed significant (p < 0.05) decrease in the levels of blood glucose and total cholesterol, triglycerides, free fatty acids, and phospholipids in serum, liver, kidney, heart, and brain. The D-pinitol also lowered significantly (p < 0.05) LDL and VLDL cholesterol levels and increased significantly (p < 0.05) HDL cholesterol levels in the serum of diabetic rats. Thus, the present study clearly showed the antihyperlipidemic effect of D-pinitol in STZ-induced type II diabetic rats. PMID:18752266

  16. Gliclazide inhibits diabetic neuropathy irrespective of blood glucose levels in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Xiaoling Qiang; Jo Satoh; Mikio Sagara; Masamitsu Fukuzawa; Takayuki Masuda; Shuichi Miyaguchi; Kazuma Takahashi; Takayoshi Toyota

    1998-01-01

    N-acetylcysteine and pentoxifylline, free radical scavengers and inhibitors of tumor necrosis factor-ga (TNF-?) production, inhibit the development of peripheral neuropathy in streptozotocin (STZ)-induced diabetic rats. This study was designed to elucidate the effect of gliclazide, an oral hypoglycemic sulfonylurea, on diabetic neuropathy, because it has been indicated to be a free radical scavenger and TNF-? inhibitor. Rats were fed with

  17. Antidiabetic effect of Ficus religiosa extract in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Rucha Pandit; Ashish Phadke; Aarti Jagtap

    2010-01-01

    Aims of studyIn Indian traditional system of medicine, Ficus religiosa (Family Moraceae) is prescribed for the treatment of diabetes mellitus. In the present study, the antidiabetic effect of aqueous extract of Ficus religiosa bark (FRAE) was investigated in normal, glucose-loaded hyperglycemic and streptozotocin (STZ)-induced diabetic rats.

  18. Transplantation of Bone Marrow–Derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats

    PubMed Central

    Shibata, Taiga; Naruse, Keiko; Kamiya, Hideki; Kozakae, Mika; Kondo, Masaki; Yasuda, Yutaka; Nakamura, Nobuhisa; Ota, Kimiko; Tosaki, Takahiro; Matsuki, Takashi; Nakashima, Eitaro; Hamada, Yoji; Oiso, Yutaka; Nakamura, Jiro

    2008-01-01

    OBJECTIVE—Mesenchymal stem cells (MSCs) have been reported to secrete various cytokines that exhibit angiogenic and neurosupportive effects. This study was conducted to investigate the effects of MSC transplantation on diabetic polyneuropathy (DPN) in rats. RESEARCH DESIGN AND METHODS—MSCs were isolated from bone marrow of adult rats and transplanted into hind limb skeletal muscles of rats with an 8-week duration of streptozotocin (STZ)-induced diabetes or age-matched normal rats by unilateral intramuscular injection. Four weeks after transplantation, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) productions in transplanted sites, current perception threshold, nerve conduction velocity (NCV), sciatic nerve blood flow (SNBF), capillary number–to–muscle fiber ratio in soleus muscles, and sural nerve morphometry were evaluated. RESULTS—VEGF and bFGF mRNA expression were significantly increased in MSC-injected thigh muscles of STZ-induced diabetic rats. Furthermore, colocalization of MSCs with VEGF and bFGF in the transplanted sites was confirmed. STZ-induced diabetic rats showed hypoalgesia, delayed NCV, decreased SNBF, and decreased capillary number–to–muscle fiber ratio in soleus muscles, which were all ameliorated by MSC transplantation. Sural nerve morphometry showed decreased axonal circularity in STZ-induced diabetic rats, which was normalized by MSC transplantation. CONCLUSIONS—These results suggest that MSC transplantation could have therapeutic effects on DPN through paracrine actions of growth factors secreted by MSCs. PMID:18728233

  19. Hypoglycemic effect of the water extract of Smallantus sonchifolius (yacon) leaves in normal and diabetic rats

    Microsoft Academic Search

    Manuel J Aybar; Alicia N Sánchez Riera; Alfredo Grau; Sara S Sánchez

    2001-01-01

    The hypoglycemic effect of the water extract of the leaves of Smallantus sonchifolius (yacon) was examined in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Ten-percent yacon decoction produced a significant decrease in plasma glucose levels in normal rats when administered by intraperitoneal injection or gastric tube. In a glucose tolerance test, a single administration of 10% yacon decoction lowered

  20. Antihyperglycemic and Antihyperlipidemic Effects of Fruit Aqueous Extract of Berberis integerrima Bge. in Streptozotocin-induced Diabetic Rats.

    PubMed

    Ashraf, Hossein; Heidari, Reza; Nejati, Vahid

    2014-01-01

    Use of medicinal plants for attenuation of hyperglycemia and restoration of lipids disorder to normal level is clinically very important. The aim of present study was to evaluate the effects of Berberis integerrima Bge. fruit aqueous extract (BIFAE) on blood glucose and lipid profile in streptozotocin (STZ) - induced diabetic rats. The STZ-induced diabetic rats were treated by fruit aqueous extract of Berberis integerrima Bge. at doses (250 and 500 mg/Kg bw) and glibenclamide (0.6 mg/Kg bw) for 42 days by gavage. Blood glucose levels and body weights of rats were measured on weeks 0, 2, 4 and 6. Total lipid levels were determined in normal and STZ-induced diabetic rats after administration of the BIFAE and glibenclamide for 42 days. STZ-induced diabetic rats showed a significant (P<0.001) increases in the levels of blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C) while body weight and high density lipoprotein HDL-cholesterolan (HDL-C) were significantly(P<0.001) decreased compared to normal rats. Daily administration of BIFAE did not possess the hypoglycemic and hypolipidaemic activity in STZ- diabetic rats during 6-week treatment period. Results indicate the usage of BIFAE in traditional medicine for the treatment of diabetes may need more investigation. PMID:25587320

  1. Antihyperglycemic and Antihyperlipidemic Effects of Fruit Aqueous Extract of Berberis integerrima Bge. in Streptozotocin-induced Diabetic Rats

    PubMed Central

    Ashraf, Hossein; Heidari, Reza; Nejati, Vahid

    2014-01-01

    Use of medicinal plants for attenuation of hyperglycemia and restoration of lipids disorder to normal level is clinically very important. The aim of present study was to evaluate the effects of Berberis integerrima Bge. fruit aqueous extract (BIFAE) on blood glucose and lipid profile in streptozotocin (STZ) - induced diabetic rats. The STZ-induced diabetic rats were treated by fruit aqueous extract of Berberis integerrima Bge. at doses (250 and 500 mg/Kg bw) and glibenclamide (0.6 mg/Kg bw) for 42 days by gavage. Blood glucose levels and body weights of rats were measured on weeks 0, 2, 4 and 6. Total lipid levels were determined in normal and STZ-induced diabetic rats after administration of the BIFAE and glibenclamide for 42 days. STZ-induced diabetic rats showed a significant (P<0.001) increases in the levels of blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C) while body weight and high density lipoprotein HDL-cholesterolan (HDL-C) were significantly(P<0.001) decreased compared to normal rats. Daily administration of BIFAE did not possess the hypoglycemic and hypolipidaemic activity in STZ- diabetic rats during 6-week treatment period. Results indicate the usage of BIFAE in traditional medicine for the treatment of diabetes may need more investigation. PMID:25587320

  2. Hypoglycemic and hypolipidemic effect of Allopolyherbal formulations in streptozotocin induced diabetes mellitus in rats

    Microsoft Academic Search

    Ratendra Kumar; Vimal Arora; Veerma Ram; Anil Bhandari; Priti Vyas

    Aim of the studyIn the present study, we examined and compared the effect of Polyherbal (PH), Allopolyherbal-A (APH-A), Allopolyherbal-B (APH-B), and Allopolyherbal-C (APH-C) formulations on hyperglycemia, lipid profile, renal, and hepatic function in streptozotocin (STZ) induced diabetes mellitus in rats.

  3. Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats

    Microsoft Academic Search

    Jie Jia; Xi Zhang; Yong-Shan Hu; Yi Wu; Qing-Zhi Wang; Na-Na Li; Qing-Chuan Guo; Xin-Cun Dong

    2009-01-01

    Effect of Ganoderma lucidum polysaccharides treatment on blood glucose, serum insulin level, lipid peroxidation, nonenzymic and enzymic antioxidants in the plasma and liver of streptozotocin (STZ)-induced diabetic rats was studied. Adult male rats of Wistar strain, weighing 195 to 250g, were randomized into control and experimental groups. Experiment group rats were induced diabetes by administration of STZ (45mg\\/kgb.wt.) intraperitoneally. The

  4. Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats.

    PubMed

    Dominguez, James M; Yorek, Mark A; Grant, Maria B

    2015-02-01

    We previously showed that peripheral neuropathy of the bone marrow was associated with loss of circadian rhythmicity of stem/progenitor cell release into the circulation. Bone marrow neuropathy results in dramatic changes in hematopoiesis that lead to microvascular complications, inflammation, and reduced endothelial repair. This series of events represents early pathogenesis before development of diabetic retinopathy. In this study we characterized early alterations within the bone marrow of streptozotocin (STZ)-induced diabetic rats following treatments that prevent experimental peripheral neuropathy. We asked whether bone marrow neuropathy and the associated bone marrow pathology were reversed with treatments that prevent peripheral neuropathy. Three strategies were tested: inhibition of neutral endopeptidase, inhibition of aldose reductase plus lipoic acid supplementation, and insulin therapy with antioxidants. All strategies prevented loss of nerve conduction velocity resulting from STZ-induced diabetes and corrected the STZ-induced diabetes-associated increase of immunoreactivity of neuropeptide Y, tyrosine hydroxylase, and somatostatin. The treatments also reduced concentrations of interleukin-1?, granulocyte colony-stimulating factor, and matrix metalloproteinase 2 in STZ-induced diabetic bone marrow supernatant and decreased the expression of NADPH oxidase 2, nitric oxide synthase 2, and nuclear factor-?B1 mRNA in bone marrow progenitor cells. These therapies represent novel approaches to attenuate the diabetic phenotype within the bone marrow and may constitute an important therapeutic strategy for diabetic microvascular complications. PMID:25204979

  5. Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA)

    PubMed Central

    2012-01-01

    Background The prevalence, and associated healthcare burden, of diabetes mellitus is increasing worldwide. Mortality and morbidity are associated with diabetic complications in multiple organs and tissues, including the eye, kidney and cardiovascular system, and new therapeutics to treat these complications are required urgently. Triethylenetetramine (TETA) is one such experimental therapeutic that acts to chelate excess copper (II) in diabetic tissues and reduce oxidative stress and cellular damage. Methods Here we have performed two independent metabolomic studies of serum to assess the suitability of the streptozotocin (STZ)-induced rat model for studying diabetes and to define metabolite-related changes associated with TETA treatment. Ultraperformance liquid chromatography-mass spectrometry studies of serum from non-diabetic/untreated, non-diabetic/TETA-treated, STZ-induced diabetic/untreated and STZ-induced diabetic/TETA-treated rats were performed followed by univariate and multivariate analysis of data. Results Multiple metabolic changes related to STZ-induced diabetes, some of which have been reported previously in other animal and human studies, were observed, including changes in amino acid, fatty acid, glycerophospholipid and bile acid metabolism. Correlation analysis suggested that treatment with TETA led to a reversal of diabetes-associated changes in bile acid, fatty acid, steroid, sphingolipid and glycerophospholipid metabolism and proteolysis. Conclusions Metabolomic studies have shown that the STZ-induced rat model of diabetes is an appropriate model system to undertake research into diabetes and potential therapies as several metabolic changes observed in humans and other animal models were also observed in this study. Metabolomics has also identified several biological processes and metabolic pathways implicated in diabetic complications and reversed following treatment with the experimental therapeutic TETA. PMID:22546713

  6. Treatment with angiotensin-(1-9) alleviates the cardiomyopathy in streptozotocin-induced diabetic rats.

    PubMed

    Zheng, Hui; Pu, Su-Ying; Fan, Xiao-Fang; Li, Xue-Song; Zhang, Yu; Yuan, Jun; Zhang, Yue-Fan; Yang, Jia-Lin

    2015-05-01

    Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. We hypothesized that angiotensin-(1-9) [Ang-(1-9)] attenuates cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. Rats were injected with a single intraperitoneal injection of STZ (55mg/kg body weight) to induced diabetic cardiomyopathy. 4 weeks later, diabetic rats were treated with Ang-(1-9) (200ng/kg/min), angiotensin type 2 receptor (AT2R) blocker PD123319 (100ng/kg/min), or Mas antagonist A779 (100ng/kg/min) for 4 weeks. Although Ang-(1-9) treatment did not affect blood glucose and insulin levels, it significantly attenuated cardiac hypertrophy, reduced cardiac fibrosis and improved ventricular function in STZ-induced diabetic rats. Ang-(1-9) treatment suppressed cardiac NADPH oxidase activity and reduced formation of reactive oxygen species. Ang-(1-9) suppressed NF?B activation and reduced myeloperoxidase (MPO) activity and mRNA levels of TNF? and IL-1? in hearts of diabetic rats. In addition, Ang-(1-9) treatment suppressed activity of ACE and reduced angiotensin II (Ang II) formation in hearts of diabetic rats. The beneficial effect of Ang-(1-9) was blunted by coadministration of PD123319 but not by coadministration of A779. Finally, it was found that Ang-(1-9) treatment could alleviate STZ-induced cardiomyopathy in a dose-dependent manner. In conclusions, Ang-(1-9) attenuates cardiac dysfunction in STZ-induced diabetic rats. The Ang-(1-9)/AT2R axis should be investigated as a novel target for treatment of type 1 diabetic cardiomyopathy. PMID:25801006

  7. Antioxidant effect of Ajuga iva aqueous extract in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    D. Taleb-Senouci; H. Ghomari; D. Krouf; S. Bouderbala; J. Prost; M. A. Lacaille-Dubois; M. Bouchenak

    2009-01-01

    The purpose of this study was to investigate the possible antioxidant effect of an aqueous extract of Ajuga iva (Ai) in streptozotocin (STZ)-induced diabetic rats. Twelve diabetic rats were divided into two groups fed a casein diet supplemented or not with Ai (0.5%), for 4 weeks. In vitro, the Ai extract possessed a very high antioxidant effect (1mg\\/ml was similar

  8. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats

    Microsoft Academic Search

    Uma Bhandari; Raman kanojia; K. K. Pillai

    2005-01-01

    The lipid lowering and antioxidant potential of ethanolic extract of Zingiber officinale Roscoe (family, Zingiberaceae) was evaluated in streptozotocin (STZ)-induced diabetes in rats. Ethanolic extract of Zingiber officinale (200mg\\/kg) fed orally for 20 days produced, significant antihyperglycaemic effect (P<0.01) in diabetic rats. Further, the extract treatment also lowered serum total cholesterol, triglycerides and increased the HDL-cholesterol levels when compared with

  9. Study of the hypoglycaemic activity of Lepidium sativum L. aqueous extract in normal and diabetic rats

    Microsoft Academic Search

    M. Eddouks; M. Maghrani; N.-A. Zeggwagh; J. B. Michel

    2005-01-01

    The hypoglycaemic effect of an aqueous extract of Lepidium sativum L. (LS) seeds was investigated in normal and streptozotocin (STZ)-induced diabetic rats. After a acute (single dose) or chronic (15 daily repeated administration) oral treatments, the aqueous LS extract (20mg\\/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (p<0.001); the blood glucose levels were normalised 2

  10. Influence of Costus speciosus (Koen.) Sm. Rhizome Extracts on Biochemical Parameters in Streptozotocin Induced Diabetic Rats

    Microsoft Academic Search

    Pitchai Daisy; James Eliza; Savarimuthu Ignacimuthu

    2008-01-01

    Diabetes affects about 4% of the global popula- tion and management of diabetes without any side effects is still a challenge to the medical system. The present study investigated the possible protec- tive effects of Costus speciosus (Koen. )s m. (C. specio- sus )r hizome extracts on biochemical parameters in streptozotocin (STZ)-induced male diabetic Wistar rats. STZ treatment (50mg\\/kg, i.p.

  11. NO- and non-NO-, non-prostanoid-dependent vasodilatation in rat sciatic nerve during maturation and developing experimental diabetic neuropathy

    PubMed Central

    Thomsen, Kirsten; Rubin, Inger; Lauritzen, Martin

    2002-01-01

    This study examined NO- and non-NO-, non-prostanoid-dependent pathways of agonist-induced vasodilatation in streptozotocin (STZ)-induced diabetic rats and their age-matched controls at 1–2, 8–10 and 18–20 weeks after induction of diabetes. Using laser Doppler flowmetry, vasodilatory responses to acetylcholine (ACh; 0.1 mM) and morpholino-sydnonimine (SIN-1) were determined in the presence of Ringer solution, during inhibition of NO synthase (NOS) and cyclo-oxygenase (COX) with N?-nitro-L-arginine (L-NNA; 1 mM) + indomethacin (10?5 M), and during inhibition of K+ channels, NOS and COX with tetraethylammonium (TEA; 10 mM) + L-NNA + indomethacin. Basal NOS activity and nerve conduction velocity were also determined. In age-matched controls, SIN-1-induced vasodilatation in the presence of TEA + L-NNA + indomethacin, basal NOS activity and the initial vasodilatory response to ACh during NOS and COX inhibition all decreased with maturation. In STZ-induced diabetics, SIN-1-induced vasodilatation in the presence of TEA + L-NNA + indomethacin was impaired immediately after induction of diabetes, but not at 18–20 weeks. NOS activity in STZ-induced diabetics displayed a transient 2-fold increase at 8–10 weeks, decreasing to age-matched control levels at 18–20 weeks. At 18–20 weeks of STZ-induced diabetes, ACh-induced vasodilatation during NOS and COX inhibition was prolonged due to increased K+ channel activity and experimental diabetic sensory neuropathy (EDN) had developed. Thus, in sciatic nerve microcirculation of STZ-induced diabetic rats: (1) diabetic impairment of vasodilatation in response to exogenous NO was transient; (2) non-NO-, non-prostanoid-dependent vasodilatation and K+ channel activity were augmented in STZ-induced diabetes; and (3) alterations in NO bioactivity were not related to the development of EDN. PMID:12231652

  12. Expression of kinin receptor mRNA in the HPA axis of type 1 and type 2 diabetic rats.

    PubMed

    Qadri, Fatimunnisa; Stark, Eva; Häuser, Walter; Jöhren, Olaf; Dendorfer, Andreas; Dominiak, Peter

    2004-04-01

    mRNA levels of kinin B1 and B2 receptors were determined in HPA axis of type 1 (STZ-induced) and type 2 diabetic rats (ZDF and obese Zucker rats). B2 mRNA levels were elevated in hypothalamus of STZ-induced diabetic (STZ-D) and ZDF rats. Pituitary B2 mRNA levels were elevated in ZDF and obese rats. Adrenal B2 mRNA level was attenuated in STZ-D rats. Kinin B1 receptor may not play a role in HPA axis in diabetes since its expression was unchanged. Enhanced mRNA expression of B2 receptors in hypothalamus of STZ-D and ZDF rats parallels a rise in plasma glucose and reflect a functional relationship. Enhanced pituitary B2 mRNA in type 2 and reduced adrenal in type 1 diabetes account for a differential pattern in release of transmitters. PMID:15171237

  13. Alternation of hepatic antioxidant enzyme activities and lipid profile in streptozotocin-induced diabetic rats by supplementation of dandelion water extract

    Microsoft Academic Search

    Soo-Yeul Cho; Ji-Yeun Park; Eun-Mi Park; Myung-Sook Choi; Mi-Kyung Lee; Seon-Min Jeon; Moon Kyoo Jang; Myung-Joo Kim; Yong Bok Park

    2002-01-01

    Background: Dandelion water extract (DWE), an herbal medication, may have an effect on the activity and mRNA expression of hepatic antioxidant enzymes and lipid profile in streptozotocin (STZ)-induced diabetic rats. Methods: Male Sprague–Dawley rats were divided into nondiabetic (control), diabetic, and diabetic-DWE-supplemented groups. Diabetes was induced by injecting streptozotocin (55 mg\\/kg BW, i.p.) in a citrate buffer. The extract was

  14. Evaluation of antioxidants in the kidney of streptozotocin induced diabetic rats.

    PubMed

    Gomathi, D; Kalaiselvi, M; Ravikumar, G; Devaki, K; Uma, C

    2014-04-01

    Diabetes mellitus is one of the most common endocrine metabolic disorders. Dual endocrine deficits of impaired insulin action (insulin resistance) and inadequate insulin secretion create an environment of chronic hyperglycemia and general metabolic disarray. Oxidative stress plays an important role in diabetic pathogenesis. Oxidative stress induced by streptozotocin (STZ) has been shown to damage pancreatic beta cell and produce hyperglycemia in rats. The present study was made to evaluate the antioxidant activity of ethanolic extract of the Evolvulus alsinoides in STZ induced rats. The antioxidant activities were done by using standard protocols. For histopathological analysis, the pancreatic tissues of all experimental groups were fixed with 10 % formalin for 24 h then the samples were stained with hematoxylin-eosin for the microscopic observation. Our results showed the significant decrease in lipid peroxidation and increases in the antioxidant (both enzymatic and nonenzymatic) levels after treatment with standard as well as the E. alsinoides. There is no significant difference between control and plant alone group rats. The histopathology reports also revealed non-toxic effect and protective effect of E. alsinoides in the kidney of STZ induced diabetic rats. Our result indicated that the E. alsinoides extract effectively increased the antioxidant level thereby it prevents oxidative stress during diabetes mellitus and also it showed the protective effect on kidney of STZ induced rats. Hence it can be used to maintain the antioxidant level during diabetes mellitus. PMID:24757306

  15. Oxidative stress impairs skeletal muscle repair in diabetic rats.

    PubMed

    Aragno, Manuela; Mastrocola, Raffaella; Catalano, Maria Graziella; Brignardello, Enrico; Danni, Oliviero; Boccuzzi, Giuseppe

    2004-04-01

    Alongside increased proteolysis, the inability to repair damaged skeletal muscle is a characteristic feature of uncontrolled diabetes. This study evaluates the role of oxidative stress in muscle-specific gene regulatory regions and myosin chain synthesis in streptozotocin (STZ)-induced diabetic and ZDF rats. In the gastrocnemius muscle of diabetic rats, prooxidant compounds were seen to increase while antioxidant levels fell. Myogenic regulatory factors--Myo, myogenin, and Jun D--were also reduced, and muscle enhancer factor (MEF)-1 DNA binding activity was impaired. Moreover, synthesis of muscle creatine kinase and both heavy and light chains of myosin were impaired, suggesting that oxidative stress triggers the cascade of events that leads to impaired muscle repair. Dehydroepiandrosterone has been reported to possess antioxidant properties. When it was administered to diabetic rats, in addition to an improved oxidative imbalance there was a recovery of myogenic factors, MEF-1 DNA binding activity, synthesis of muscle creatine kinase, and myosin light and heavy chains. Vitamin E administration to STZ-induced diabetic rats reverses oxidative imbalance and improves muscle gene transcription, reinforcing the suggestion that oxidative stress may play a role in diabetes-related impaired muscle repair. PMID:15047625

  16. Testicular oxidative damage and role of combined antioxidant supplementation in experimental diabetic rats

    Microsoft Academic Search

    Magda Mohasseb; Samia Ebied; Mona A. H. Yehia; Neveen Hussein

    2011-01-01

    The present study was designated to assess oxidative damage and its effect on germ cell apoptosis in testes of streptozotocin\\u000a (STZ)-induced diabetic rats. The role of antioxidant supplementation with a mixture of vitamins E and C and alpha lipoic acid\\u000a for protection against such damage was also evaluated. Forty-five adult male rats were randomly divided into three groups:\\u000a group I, control,

  17. Brain antioxidant capacity in rat models of betacytotoxic-induced experimental sporadic Alzheimer’s disease and diabetes mellitus

    Microsoft Academic Search

    I. Tahirovic; E. Sofic; A. Sapcanin; I. Gavrankapetanovic; L. Bach-Rojecky; M. Salkovic-Petrisic; Z. Lackovic; S. Hoyer; P. Riederer

    It is believed that oxidative stress plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus\\u000a (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer’s\\u000a disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced diabetic rats and STZ-intracerebroventricularly\\u000a (STZ-icv) treated rats, in which antioxidant capacity against peroxyl (ORAC_roo

  18. Reduced Brain Antioxidant Capacity in Rat Models of Betacytotoxic-Induced Experimental Sporadic Alzheimer’s Disease and Diabetes Mellitus

    Microsoft Academic Search

    Ismet Tahirovic; Emin Sofic; Aida Sapcanin; Ismet Gavrankapetanovic; Lidija Bach-Rojecky; Melita Salkovic-Petrisic; Zdravko Lackovic; Siegfried Hoyer; Peter Riederer

    2007-01-01

    It is believed that oxidative stress (OS) plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus\\u000a (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer’s\\u000a disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced diabetic rats and STZ-intracerebroventricularly\\u000a (STZ-icv) treated rats, in which antioxidant capacity (AC) against

  19. Low Protein Diet Inhibits Uric Acid Synthesis and Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ma, Jing; Liu, Yan; Tan, Rongshao; Liu, Houqiang; Lao, Gancheng

    2014-01-01

    Aim. Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN). Meanwhile, low protein diet (LPD) retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ-) induced diabetic rats. Methods. STZ-induced and control rats were both fed with LPD (5%) and normal protein diet (18%), respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. Results. Diabetic rats developed into constantly high levels of serum UA (SUA), creatinine (SCr) and 24?h amounts of urinary albumin excretion (UAE), creatintine (UCr), urea nitrogen (UUN), and uric acid (UUA). LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-? in tubulointerstitium significantly decreased in LPD-fed diabetic rats. Conclusion. LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats. PMID:24772444

  20. Effects of Nefopam on Streptozotocin-Induced Diabetic Neuropathic Pain in Rats

    PubMed Central

    Nam, Jae Sik; Cheong, Yu Seon; Karm, Myong Hwan; Ahn, Ho Soo; Sim, Ji Hoon; Kim, Jin Sun; Leem, Jeong Gil

    2014-01-01

    Background Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats. Methods Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated. Results Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG. Conclusions These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG. PMID:25317281

  1. The effect of long-term streptozotocin-induced diabetes on contractile and relaxation responses of coronary arteries: selective attenuation of CGRP-induced relaxations

    PubMed Central

    Sheykhzade, Majid; Dalsgaard, Grethe T; Johansen, Tue; Nyborg, Niels C Berg

    2000-01-01

    This study investigates the effect of partially metabolic controlled long-term (34 weeks) streptozotocin (STZ)-induced diabetes on relaxation and contractile responses of isolated coronary arteries to seven different vasoactive agents. The average fasting and non-fasting blood glucose concentrations (mM) were significantly elevated in STZ-induced diabetic rats (P<0.0001; 10.4±0.4 and 16.6±1.1, n=15) compared to those (4.3±0.03 and 4.7±0.18, n=11) in age-matched controls. The level of glycated haemoglobin (HbA1) was also significantly (P<0.0001) increased in STZ-induced diabetic rats. In STZ-induced diabetic rats, the HbA1 levels were significantly correlated with the non-fasting blood glucose concentrations (r=0.76; P=0.003; n=13). In both groups, there was no significant correlation between the HbA1 levels and maximal responses or sensitivities to the vasoactive agents. The maximal relaxation induced by rat-?calcitonin gene-related peptide (rat-?CGRP) was significantly attenuated in the coronary arteries of STZ-induced diabetic rats (P<0.05; 40±7%, n=15) compared to that in age-matched controls (63±3%, n=11). However, there was no significant difference in the sensitivity to rat-?CGRP between the two groups. There was no significant difference in either maximal response or sensitivity to any of the six other vasoactive agents between STZ- induced diabetic rats (n=15) and age-matched controls (n=11). Our results show that partially metabolic controlled long-term (34 weeks) STZ-induced diabetes causes a selective depression of rat-?CGRP-induced relaxation in the intramural coronary arteries of Wistar rats. PMID:10725270

  2. Protective Effect of Polysaccharides from Inonotus obliquus on Streptozotocin-Induced Diabetic Symptoms and Their Potential Mechanisms in Rats

    PubMed Central

    Diao, Bao-zhong; Jin, Wei-rong; Yu, Xue-jing

    2014-01-01

    The present study aimed to evaluate the therapeutic effects of polysaccharides from Inonotus obliquus (PIO) on streptozotocin- (STZ-) induced diabetic symptoms and their potential mechanisms. The effect of PIO on body weight, blood glucose, damaged pancreatic ?-cells, oxidative stresses, proinflammatory cytokines, and glucose metabolizing enzymes in liver was studied. The results show that administration of PIO can restore abnormal oxidative indices near normal levels. The STZ-damaged pancreatic ?-cells of the rats were partly recovered gradually after the mice were administered with PIO 6 weeks later. Therefore, we may assume that PIO is effective in the protection of STZ-induced diabetic rats and PIO may be of use as antihyperglycemic agent. PMID:25093030

  3. Protective Effect of Polysaccharides from Inonotus obliquus on Streptozotocin-Induced Diabetic Symptoms and Their Potential Mechanisms in Rats.

    PubMed

    Diao, Bao-Zhong; Jin, Wei-Rong; Yu, Xue-Jing

    2014-01-01

    The present study aimed to evaluate the therapeutic effects of polysaccharides from Inonotus obliquus (PIO) on streptozotocin- (STZ-) induced diabetic symptoms and their potential mechanisms. The effect of PIO on body weight, blood glucose, damaged pancreatic ?-cells, oxidative stresses, proinflammatory cytokines, and glucose metabolizing enzymes in liver was studied. The results show that administration of PIO can restore abnormal oxidative indices near normal levels. The STZ-damaged pancreatic ?-cells of the rats were partly recovered gradually after the mice were administered with PIO 6 weeks later. Therefore, we may assume that PIO is effective in the protection of STZ-induced diabetic rats and PIO may be of use as antihyperglycemic agent. PMID:25093030

  4. Improved glycemic control, pancreas protective and hepatoprotective effect by traditional poly-herbal formulation “Qurs Tabasheer” in streptozotocin induced diabetic rats

    PubMed Central

    2013-01-01

    Background The present study was undertaken to evaluate the antihyperglycemic, antihyperlipidemic and hepatoprotective effect of a traditional unani formulation “Qurs Tabasheer” in streptozotocin (STZ) induced diabetic wistar rats. Up till now no study was undertaken to appraise the efficacy of “Qurs Tabasheer” in the diabetic rats. Qurs Tabasheer is a unani formulation restraining preparations from five various herbs namely Tukhme Khurfa (Portulaca oleracea seed), Gule Surkh (Rosa damascena flower), Gulnar (Punica granatum flower), Tabasheer (Bambusa arundinasia dried exudate on node), Tukhme Kahu (Lactuca sativa Linn seed). Methods Effect of Qurs Tabasheer was assessed in STZ (60 mg/kg, i.p single shot) induced diabetic wistar rats. STZ produced a marked increase in the serum glucose, Total Cholesterol, LDL cholesterol, VLDL Cholesterol, Triglycerides and trim down the HDL level. We have weighed up the effect of Qurs Tabasheer on hepatic activity through estimating levels of various liver enzymes viz. Hexokinase, Glucose-6-Phosphatase and Fructose-1-6-biphosphatase in STZ diabetic wistar rats. Results In STZ-induced diabetic wistar rats level of Hexokinase, and Glucose-6-Phosphatase was decreased to a significant level while the level of fructose-1-6-biphophatase was augmented. Therapy with Qurs Tabasheer for 28 days to STZ-induced diabetic rats significantly reduces the level of serum glucose, total cholesterol, triglycerides, glucose-6-phosphatase and fructose-1-6-biphosphatase, while magnitude of HDL cholesterol and hexokinase was amplified. Conclusion Antihyperglycemic, antihyperlipidemic activity of Qurs Tabasheer extract in STZ- induced wistar rats was found to be more effective than standard oral hypoglycemic drug Glimepiride. PMID:23305114

  5. Antioxidant enzyme alterations in experimental and clinical diabetes

    Microsoft Academic Search

    David V. Godin; Saleh A. Wohaieb; Maureen E. Garnett; A. D. Goumeniouk

    1988-01-01

    Previous studies from our laboratory have demonstrated the presence of complex alterations in the activities of antioxidant enzymes in various tissues of rats with streptozotocin (STZ)-induced diabetes. In the present investigation, it is shown that rats made diabetic with alloxan (ALX), an agent differing from STZ both chemically and in its mechanism of diabetogenesis, show virtually identical tissue antioxidant enzyme

  6. Antihyperglycemic, antihyperlipidemic and antioxidant effects of Dihar, a polyherbal ayurvedic formulation in streptozotocin induced diabetic rats.

    PubMed

    Patel, Snehal S; Shah, Rajendra S; Goyal, Ramesh K

    2009-07-01

    Present investigation was undertaken to evaluate antihyperglycemic, antihyperlipidemic and antioxidant activities of Dihar, a polyherbal formulation containing drugs from eight different herbs viz., Syzygium cumini, Momordica charantia, Emblica officinalis, Gymnema sylvestre, Enicostemma littorale, Azadirachta indica, Tinospora cordifolia and Curcuma longa in streptozotocin (STZ, 45 mg/kg iv single dose) induced type 1 diabetic rats. STZ produced a significant increase in serum glucose, cholesterol, triglyceride, very low density lipoprotein, low density lipoprotein, creatinine, and urea levels in diabetic rat. Treatment with Dihar (100 mg/kg) for 6 weeks produced decrease in STZ induced serum glucose and lipids levels and increased insulin levels as compared to control. Dihar produced significant decrease in serum creatinine and urea levels in diabetic rats. There was a significant decrease in reduced glutathione, superoxide dismutase, catalase levels and increase in thiobarbituiric acid reactive species levels in the liver of STZ-induced diabetic rats. Administration of Dihar to diabetic rats significantly reduced the levels of lipid paroxidation and increased the activities of antioxidant enzymes. The results suggest Dihar to be beneficial for the treatment of type 1 diabetes. PMID:19761040

  7. The protective effect of fucoidan in rats with streptozotocin-induced diabetic nephropathy.

    PubMed

    Wang, Jing; Liu, Huaide; Li, Ning; Zhang, Quanbin; Zhang, Hong

    2014-06-01

    Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the ?2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications. PMID:24886867

  8. The Protective Effect of Fucoidan in Rats with Streptozotocin-Induced Diabetic Nephropathy

    PubMed Central

    Wang, Jing; Liu, Huaide; Li, Ning; Zhang, Quanbin; Zhang, Hong

    2014-01-01

    Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the ?2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications. PMID:24886867

  9. Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin-induced diabetic rats

    PubMed Central

    Arokiyaraj, S; Balamurugan, R; Augustian, P

    2011-01-01

    Objective To evaluate the antihyperglycemic activity of ethyl acetate extract of Hypericum perforatum (H. perforatum) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity and oral glucose tolerance test were performed in normal rats. Male albino rats were rendered diabetic by STZ (40 mg/kg, intraperitoneally). H. perforatum ethyl acetate extract was orally administered to diabetic rats at 50, 100 and 200 mg/kg doses for 15 days to determine the antihyperglycemic activity. Biochemical parameters were determined at the end of the treatment. Results H. perforatum ethyl acetate extract showed dose dependant fall in fasting blood glucose (FBG). After 30 min of extract administration, FBG was reduced significantly when compared with normal rats. H. perforatum ethyl acetate extract produced significant reduction in plasma glucose level, serum total cholesterol, triglycerides, glucose-6-phosphatase levels. Tissue glycogen content, HDL-cholesterol, glucose-6-phosphate dehydrogenase were significantly increased compared with diabetic control. No death or lethal effect was observed in the toxic study. Conclusions The results demonstrate that H. perforatum ethyl acetate extract possesses potent antihyperglycemic activity in STZ induced diabetic rats. PMID:23569798

  10. Alterations in the neural circuits from peripheral afferents to the spinal cord: possible implications for diabetic polyneuropathy in streptozotocin-induced type 1 diabetic rats

    PubMed Central

    Kou, Zhen-Zhen; Li, Chun-Yu; Hu, Jia-Chen; Yin, Jun-Bin; Zhang, Dong-Liang; Liao, Yong-Hui; Wu, Zhen-Yu; Ding, Tan; Qu, Juan; Li, Hui; Li, Yun-Qing

    2014-01-01

    Diabetic polyneuropathy (DPN) presents as a wide variety of sensorimotor symptoms and affects approximately 50% of diabetic patients. Changes in the neural circuits may occur in the early stages in diabetes and are implicated in the development of DPN. Therefore, we aimed to detect changes in the expression of isolectin B4 (IB4, the marker for nonpeptidergic unmyelinated fibers and their cell bodies) and calcitonin gene-related peptide (CGRP, the marker for peptidergic fibers and their cell bodies) in the dorsal root ganglion (DRG) and spinal cord of streptozotocin (STZ)-induced type 1 diabetic rats showing alterations in sensory and motor function. We also used cholera toxin B subunit (CTB) to show the morphological changes of the myelinated fibers and motor neurons. STZ-induced diabetic rats exhibited hyperglycemia, decreased body weight gain, mechanical allodynia and impaired locomotor activity. In the DRG and spinal dorsal horn, IB4-labeled structures decreased, but both CGRP immunostaining and CTB labeling increased from day 14 to day 28 in diabetic rats. In spinal ventral horn, CTB labeling decreased in motor neurons in diabetic rats. Treatment with intrathecal injection of insulin at the early stages of DPN could alleviate mechanical allodynia and impaired locomotor activity in diabetic rats. The results suggest that the alterations of the neural circuits between spinal nerve and spinal cord via the DRG and ventral root might be involved in DPN. PMID:24523675

  11. Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Yay, A; Akku?, D; Yap?slar, H; Balc?oglu, E; Sonmez, M F; Ozdamar, S

    2014-11-01

    Nitric oxide (NO) plays a significant role in the development of diabetic nephropathy. We investigated the effects of an antioxidant, carnosine, on streptozotocin (STZ)-induced renal injury in diabetic rats. We used four groups of eight rats: group 1, control; group 2, carnosine treated; group 3, untreated diabetic; group 4, carnosine treated diabetic. Kidneys were removed and processed, and sections were stained with periodic acid-Schiff (PAS) and subjected to eNOS immunohistochemistry. Examination by light microscopy revealed degenerated glomeruli, thickened basement membrane and glycogen accumulation in the tubules of diabetic kidneys. Carnosine treatment prevented the renal morphological damage caused by diabetes. Moreover, administration of carnosine decreased somewhat the oxidative damage of diabetic nephropathy. Appropriate doses of carnosine might be a useful therapeutic option to reduce oxidative stress and associated renal injury in diabetes mellitus. PMID:24834928

  12. Cinnamon extract inhibits ?-glucosidase activity and dampens postprandial glucose excursion in diabetic rats

    PubMed Central

    2011-01-01

    Background ?-glucosidase inhibitors regulate postprandial hyperglycemia (PPHG) by impeding the rate of carbohydrate digestion in the small intestine and thereby hampering the diet associated acute glucose excursion. PPHG is a major risk factor for diabetic vascular complications leading to disabilities and mortality in diabetics. Cinnamomum zeylanicum, a spice, has been used in traditional medicine for treating diabetes. In this study we have evaluated the ?-glucosidase inhibitory potential of cinnamon extract to control postprandial blood glucose level in maltose, sucrose loaded STZ induced diabetic rats. Methods The methanol extract of cinnamon bark was prepared by Soxhlet extraction. Phytochemical analysis was performed to find the major class of compounds present in the extract. The inhibitory effect of cinnamon extract on yeast ?-glucosidase and rat-intestinal ?-glucosidase was determined in vitro and the kinetics of enzyme inhibition was studied. Dialysis experiment was performed to find the nature of the inhibition. Normal male Albino wistar rats and STZ induced diabetic rats were treated with cinnamon extract to find the effect of cinnamon on postprandial hyperglycemia after carbohydrate loading. Results Phytochemical analysis of the methanol extract displayed the presence of tannins, flavonoids, glycosides, terpenoids, coumarins and anthraquinones. In vitro studies had indicated dose-dependent inhibitory activity of cinnamon extract against yeast ?-glucosidase with the IC 50 value of 5.83 ?g/ml and mammalian ?-glucosidase with IC 50 value of 670 ?g/ml. Enzyme kinetics data fit to LB plot pointed out competitive mode of inhibition and the membrane dialysis experiment revealed reversible nature of inhibition. In vivo animal experiments are indicative of ameliorated postprandial hyperglycemia as the oral intake of the cinnamon extract (300 mg/kg body wt.) significantly dampened the postprandial hyperglycemia by 78.2% and 52.0% in maltose and sucrose loaded STZ induced diabetic rats respectively, compared to the control. On the other hand, in rats that received glucose and cinnamon extract, postprandial hyperglycemia was not effectively suppressed, which indicates that the observed postprandial glycemic amelioration is majorly due to ?-glucosidase inhibition. Conclusions The current study demonstrates one of the mechanisms in which cinnamon bark extract effectively inhibits ?-glucosidase leading to suppression of postprandial hyperglycemia in STZ induced diabetic rats loaded with maltose, sucrose. This bark extract shows competitive, reversible inhibition on ?-glucosidase enzyme. Cinnamon extract could be used as a potential nutraceutical agent for treating postprandial hyperglycemia. In future, specific inhibitor has to be isolated from the crude extract, characterized and therapeutically exploited. PMID:21711570

  13. Effects of preproglucagon-derived peptides and exendins on steroid-hormone secretion from dispersed adrenocortical cells of normal and streptozotocin-induced diabetic rats.

    PubMed

    Malendowicz, Ludwik K; Spinazzi, Raffaella; Nussdorfer, Gastone G; Trejter, Marcin

    2003-07-01

    Many lines of evidence have shown that preproglucagon-derived peptides affect steroid secretion from dispersed adrenocortical cells, and that streptozotocin (STZ)-induced experimental diabetes alters adrenocortical-cell function. Hence, we compared the effects of glucagon, glucagon-like peptide (GLP)-1 and GLP-2 on basal and ACTH-stimulated secretion of dispersed adrenocortical cells from normal and STZ-induced diabetic rats. We also examined the effects of exendins (EX) 3 and 4, because EX4 is known to be a potent and long-lasting agonist of GLP-1 receptors. STZ-induced diabetes moderately enhances basal and ACTH-stimulated secretion from dispersed zona glomerulosa (ZG) cells, without significantly affecting corticosterone production from dispersed zona fasciculata-reticularis (ZF/R) cells. In normoglycemic rats, glucagon increased basal aldosterone and corticosterone secretion from ZG and ZF/R cells, GLP-2 raised both basal and ACTH-stimulated aldosterone secretion and ACTH-stimulated corticosterone output, and EX4 increased basal corticosterone secretion. In contrast, glucagon, GLP-2 and EX4 did not elicit secretory responses from adrenocortical cells of diabetic rats. GLP-1 and EX3 did not alter secretion of dispersed adrenocortical cells of either normal or STZ-treated rats. Taken together, our findings indicate that preproglucagon-derived peptides enhance steroid secretion from adrenocortical cells of normal, but not STZ-induced diabetic rats. It is suggested that the prolonged exposure to low concentrations of insulin causes unresponsiveness of adrenocortical cells to glucagon, GLP-2 and EX4, which may contribute to the hyporeninemic hypoaldosteronism and alterations in glucocorticoid metabolism occurring in experimental diabetes. PMID:12792820

  14. Pharmacological Evaluation of “Sugar Remedy,” A Polyherbal Formulation, on Streptozotocin-Induced Diabetic Mellitus in Rats

    PubMed Central

    Singhal, Sandeep; Rathore, Arvind Singh; Lohar, Vikram; Dave, Rakesh; Dave, Jeetesh

    2014-01-01

    In the present study, Sugar Remedy, a polyherbal formulation (manufactured by Umalaxmi Organics Pvt Ltd, Jodhpur, Rajasthan, India) was evaluated for its antihyperglycemic, antihyperlipidemic, and antioxidant effects against normal and streptozotocin (STZ)-induced diabetic rats. Type II diabetes was induced in male Wistar rats by administration of a single intraperitoneal (IP) injection of STZ at a dose of 60 mg/kg. Effects of three different doses of Sugar Remedy suspension (185, 370, and 740 mg/kg/day, orally) and Metformin (500 mg/kg/day, orally) administered for 21 days were studied on parameters such as blood glucose, lipid profile, and antioxidant levels. Results were analyzed using one-way analysis of variance (ANOVA) followed by Dunnett's test. No significant changes were noticed in blood glucose, serum lipid levels, and kidney parameters in normal rats treated with Sugar Remedy suspension alone. The efficacy of Sugar Remedy as an antihyperglycemic, antihyperlipidemic, and antioxidant agent in STZ-induced diabetes was comparable to that of the standard, 500 mg/kg of Metformin. Present findings provide experimental evidence that Sugar Remedy has significant antihyperglycemic, antihyperlipidemic, and antioxidative effects in diabetic experimental rats. Hence, Sugar Remedy may be regarded as a promising natural and safe remedy for the prevention or delay of diabetic complications. PMID:25161924

  15. Effects of Aqueous Extract of Berberis integerrima Root on Some Physiological Parameters in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Ashraf, Hossein; Heidari, Reza; Nejati, Vahid; Ilkhanipoor, Minoo

    2013-01-01

    Diabetes mellitus is a common endocrine disorder. Anti-diabetic agents from natural and synthetic sources are available for the treatment of this disease. Berberis integerrima is a medicinal shrub used in conventional therapy for a number of diseases. The aim of the present study was to investigate the effects of aqueous extract of Berberis integerrima root (AEBI) on some physiological parameters in normal and streptozotocin-induced (STZ-induced) diabetic male Wistar rats. STZ-induced diabetic rats showed significant increases in the levels of blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C), creatinine (Cr), urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin while body weight, high density lipoprotein HDL-cholesterol (HDL-C) and total protein levels were significantly decreased compared to normal rats. Treatment of diabetic rats with different doses of aqueous extract of Berberis integerrima root (250 and 500 mg/Kg bw) resulted in a significant decrease in blood glucose, triglycerides, cholesterol, LDL-cholesterol, ALT, AST, ALP, total bilirubin, creatinine and urea while HDL-cholesterol and total protein levels were markedly increased after six weeks compared to untreated diabetic rats. The effects of the AEBI at dose of 500 mg/Kg in all parameters except blood glucose (similar) is more than to the standard drug, glibenclamide (0.6 mg/Kg, p.o.). The results of this study indicate that the tested aqueous extract of Berberis integerrima root possesses hypoglycemic, hypolipidemic and antioxidant effects in STZ-induced diabetic rats. PMID:24250618

  16. Effects of Aqueous Extract of Berberis integerrima Root on Some Physiological Parameters in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ashraf, Hossein; Heidari, Reza; Nejati, Vahid; Ilkhanipoor, Minoo

    2013-01-01

    Diabetes mellitus is a common endocrine disorder. Anti-diabetic agents from natural and synthetic sources are available for the treatment of this disease. Berberis integerrima is a medicinal shrub used in conventional therapy for a number of diseases. The aim of the present study was to investigate the effects of aqueous extract of Berberis integerrima root (AEBI) on some physiological parameters in normal and streptozotocin-induced (STZ-induced) diabetic male Wistar rats. STZ-induced diabetic rats showed significant increases in the levels of blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C), creatinine (Cr), urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin while body weight, high density lipoprotein HDL-cholesterol (HDL-C) and total protein levels were significantly decreased compared to normal rats. Treatment of diabetic rats with different doses of aqueous extract of Berberis integerrima root (250 and 500 mg/Kg bw) resulted in a significant decrease in blood glucose, triglycerides, cholesterol, LDL-cholesterol, ALT, AST, ALP, total bilirubin, creatinine and urea while HDL-cholesterol and total protein levels were markedly increased after six weeks compared to untreated diabetic rats. The effects of the AEBI at dose of 500 mg/Kg in all parameters except blood glucose (similar) is more than to the standard drug, glibenclamide (0.6 mg/Kg, p.o.). The results of this study indicate that the tested aqueous extract of Berberis integerrima root possesses hypoglycemic, hypolipidemic and antioxidant effects in STZ-induced diabetic rats. PMID:24250618

  17. Antihyperglycemic and antihyperlipidemic activities of aqueous extract of Hericium erinaceus in experimental diabetic rats

    PubMed Central

    2013-01-01

    Background Hericium erinaceus, as a commonly used medicine or food, has attracted much attention due to its health effects when used as a home remedy for some diseases. The aim of this work was to investigate the hypoglycemic and hypolipidemic effects of aqueous extract of Hericium erinaceus (AEHE) in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes was induced in Wistar rats by the administration of STZ (55 mg/kg BW.) intraperitoneally. AEHE (100 and 200 mg/kg BW.) was administered for a period of 28 days. The effects of AEHE on glucose, insulin, and lipid files in blood, and oxidative stress parameters in the liver were evaluated. The body weights of rats were recorded at day 0, 14 and 28th days. Results The administration of AEHE for 28 days in STZ diabetic rats resulted in a significant decrease in serum glucose level and a significant rise in serum insulin level. AEHE treatment attenuated lipid disorders. In addition, AEHE administration increased the activities of CAT, SOD, and GSH-Px, and GSH level, and reduced MDA level in the liver tissue significantly. Conclusion Our results suggest that AEHE possesses hypoglycemic, hypolipidemic, and antioxidant properties in STZ-induced diabetes rats. PMID:24090482

  18. Hypoglycemic Activity of Fumaria parviflora in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Fathiazad, Fatemeh; Hamedeyazdan, Sanaz; Khosropanah, Mohamad Karim; Khaki, Arash

    2013-01-01

    Purpose: Fumaria parviflora Lam (Fumariaceae) has been used in traditional medicine in the treatment of several diseases such as diabetes. The present work was designed to evaluate the hypoglycaemic effects of methanolic extract (ME) of F. parviflora in normal and streptozotocin-induced diabetic rats. Methods: The rats used were allocated in six (I, II, III, IV, V and VI) experimental groups (n=5). Group I rats served as ‘normal control’ animals received distilled water and group II rats served as ‘diabetic control’ animals. Diabetes mellitus was induced in groups II, V and VI rats by intraperitoneal single injection of streptozotocin (STZ, 55 mg kg-1). Group V and VI rats were addi-tionally treated with ME (150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively) 24 hour post STZ injection, for seven consecutive days. Groups III and IV rats received only ME 150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively for seven days. The levels of blood glucose were determined using a Glucometer. Results: Administra-tion of F. parviflora extract showed a potent glucose lowering effect only on streptozo-tocin (STZ) induced diabetic rats below 100 mg/dl (P<0.001). However, no significant differences in the blood glucose levels were recorded between diabetic rats received 125 or 250 mg/kg of plant extracts. Conclusion: The findings of the study indicated that F. parviflora has significant hypoglycemic effect on STZ-induced diabetic rats with no effects on blood glucose levels of normal rats. PMID:24312837

  19. Hemodynamic alterations in chronically conscious unrestrained diabetic rats

    SciTech Connect

    Carbonell, L.F.; Salmon, M.G.; Garcia-Estan, J.; Salazar, F.J.; Ubeda, M.; Quesada, T.

    1987-05-01

    Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. Plasma volume was measured by dilution of radioiodinated (/sup 125/I) human serum albumin. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dt/sub max/ and dP/dt/sub min/ of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic states, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.

  20. Antihyperglycemic activity of herb extracts on streptozotocin-induced diabetic rats.

    PubMed

    Jung, Chang Hwa; Zhou, Song; Ding, Guo Xun; Kim, Ji Hye; Hong, Myung Hee; Shin, Yong-Cheol; Kim, Gyung Jun; Ko, Seong-Gyu

    2006-10-01

    We investigated the effects of herb extracts, Rhus verniciflua, Agrimonia pilosa, Sophora japonica, and Paeonia suffruticosa, on the lowering of blood glucose levels and thiobarbituric acid reactive substances (TBARS) in streptozotocin (STZ)-induced diabetic rats. After 4 weeks, oral administration of Rhus verniciflua extract (50 mg/kg) exhibited a significant decrease in blood glucose levels in diabetic rats (P<0.05). Blood TBARS concentrations, the products of glucose oxidation in blood, were also lowered by Rhus verniciflua extract supplementation. In addition, Sophora japonica and Paeonia suffruticosa extracts significantly reduced TBARS levels versus diabetic controls. Serum concentrations of liver-function marker enzymes, GOT and GPT, were also restored by Rhus verniciflua (50 mg/kg) supplementation in diabetic rats. PMID:17031059

  1. Lignin-derived lignophenols attenuate oxidative and inflammatory damage to the kidney in streptozotocin-induced diabetic rats.

    PubMed

    Sato, Shin; Mukai, Yuuka; Yamate, Jyoji; Norikura, Toshio; Morinaga, Yae; Mikame, Keigo; Funaoka, Masamitsu; Fujita, Shuzo

    2009-12-01

    This study investigated the effects of lignin-derived lignophenols (LPs) on the oxidative stress and infiltration of macrophages in the kidney of streptozotocin (STZ)-induced diabetic rats. The diabetic rats were divided into four groups with 0%, 0.11%, 0.33% and 1.0% LP diets. The vehicle-injected controls were given a commercial diet. At 5 weeks, superoxide (O(2)(-)) production, macrophage kinetics, the degree of fibrosis in glomeruli and mRNA expression for monocyte chemoattractant protein-1 (MCP-1) were examined. The NADPH-stimulated O(2)(-) levels in the kidney of the diabetic rats treated with 1.0% LP were significantly lower than those in untreated diabetic rats. The number of macrophages, levels of MCP-1 mRNA expression and degree of glomerular fibrosis increased in untreated LP and these levels were significantly lower in 1.0%LP-treated rats. The results suggested that LPs suppress the excess oxidative stress, the infiltration and activation of macrophages and the glomerular expansion in STZ-induced diabetic kidneys. PMID:19905983

  2. Centella asiatica Attenuates Diabetes Induced Hippocampal Changes in Experimental Diabetic Rats

    PubMed Central

    Srinivasarao, Nelli; Swapna Rekha, Somesula; Muniandy, Sekaran

    2014-01-01

    Diabetes mellitus has been reported to affect functions of the hippocampus. We hypothesized that Centella asiatica, a herb traditionally being used to improve memory, prevents diabetes-related hippocampal dysfunction. Therefore, the aim of this study was to investigate the protective role of C. asiatica on the hippocampus in diabetes. Methods. Streptozotocin- (STZ-) induced adult male diabetic rats received 100 and 200?mg/kg/day body weight (b.w) C. asiatica leaf aqueous extract for four consecutive weeks. Following sacrifice, hippocampus was removed and hippocampal tissue homogenates were analyzed for Na+/K+-, Ca2+- and Mg2+-ATPases activity levels. Levels of the markers of inflammation (tumor necrosis factor, TNF-?; interleukin, IL-6; and interleukin, IL-1?) and oxidative stress (lipid peroxidation product: LPO, superoxide dismutase: SOD, catalase: CAT, and glutathione peroxidase: GPx) were determined. The hippocampal sections were visualized for histopathological changes. Results. Administration of C. asiatica leaf aqueous extract to diabetic rats maintained near normal ATPases activity levels and prevents the increase in the levels of inflammatory and oxidative stress markers in the hippocampus. Lesser signs of histopathological changes were observed in the hippocampus of C. asiatica leaf aqueous extract treated diabetic rats. Conclusions. C. asiatica leaf protects the hippocampus against diabetes-induced dysfunction which could help to preserve memory in this condition. PMID:25161691

  3. Antioxidant and toxicological evaluation of Cassia sopherain streptozotocin-induced diabetic Wistar rats

    PubMed Central

    Singh, Rambir; Bhardwaj, Priyanka; Sharma, Poonam

    2013-01-01

    Background: Multiple-organ failure is the main cause of death in diabetes mellitus (DM). Hyperglycemia-induced oxidative stress is responsible for major diabetic complications, including multiple-organ failure. Medicinal plants possessing antioxidant activity may reduce oxidative stress and improve the functions of various organs affected by hyperglycemia. Objectives: This study was designed to evaluate the antioxidant effect of Aqueous Extract of Cassia sophera (AECS) in streptozotocin (STZ)-induced diabetic Wistar rats. Materials and Methods: AECS (200 mg/kg body weight (bw)) and the standard antidiabetic drug glibenclamide (10 mg/kgbw) were administered orally by gavaging for 28 days. Results: Oral administration of AECS inhibited STZ-induced increase in lipid peroxidation (LPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, creatinine and urea in liver of diabetic rats. Significant increase in activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and a reduced level of glutathione (GSH), were observed in the liver, kidney, pancreas and testis on AECS treatment. Conclusion: The results demonstrate that AECS is not only useful in controlling blood glucose, but also has antioxidant potential to protect the liver, kidney, pancreas and testis against damage caused by hyperglycemia-induced oxidative stress. PMID:24174814

  4. Fermented soy permeate reduces cytokine level and oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Malardé, Ludivine; Groussard, Carole; Lefeuvre-Orfila, Luz; Vincent, Sophie; Efstathiou, Théo; Gratas-Delamarche, Arlette

    2015-01-01

    Oxidative stress and inflammation are involved in the development of type 1 diabetes and its complications. Because two compounds found in soy, that is, isoflavones and alpha-galactooligosaccharides, have been shown to exert antioxidant and anti-inflammatory effects, this study aimed to assess the effects of a dietary supplement containing these two active compounds, the fermented soy permeate (FSP). We hypothesized that FSP would be able to reduce in vivo oxidative stress and inflammation in streptozotocin (STZ)-induced type 1 diabetic rats. Thirty male Wistar rats were divided into the control placebo, diabetic placebo, and diabetic FSP-supplemented groups. They received daily, by oral gavage, water (placebo groups) or diluted FSP (0.1?g/day; FSP-supplemented group). After 3 weeks, glycemic regulation (glycemia and fructosamine level); the plasma level of carboxymethyllysine (CML), a marker of systemic oxidative stress in diabetes; and the plasma levels of inflammatory markers (CRP, IL-1?, IL-6, and uric acid) were evaluated. Markers of oxidative damage (isoprostanes and GSH/GSSG), antioxidant enzymatic activity (SOD and GPX), and Mn-SOD content were determined in skeletal muscle (gastrocnemius). Diabetic placebo rats exhibited higher CML levels, lower SOD and GPX activities, and decreased Mn-SOD contents. FSP supplementation in diabetic animals normalized the CML and antioxidant enzymatic activity levels and tended to increase Mn-SOD expression. The markers of inflammation whose levels were increased in the diabetic placebo group were markedly decreased by FSP (IL-1?: -75%, IL-6: -46%, and uric acid: -17%), except for CRP. Our results demonstrate that FSP exhibited antioxidant and anti-inflammatory properties in vivo in STZ-induced diabetic rats. PMID:25314273

  5. Occurrence of oxidative impairments, response of antioxidant defences and associated biochemical perturbations in male reproductive milieu in the Streptozotocin-diabetic rat.

    PubMed

    Shrilatha, B

    2007-12-01

    Oxidative stress is implicated to play a vital role in the pathogenesis of various diabetic complications. While reproductive dysfunction is a well recognized consequence of diabetes mellitus, the underlying mechanisms are poorly understood. The present study aims to obtain insights into the incidence, extent and progression of oxidative impairments in testis and epididymal sperm (ES) in streptozotocin (STZ)-induced diabetic rat during early and progressive phase. Adult rats (CFT-Wistar strain) rendered diabetic by an acute dose of STZ (60 mg/kg bw, i.p.) were examined for induction of hyperglycaemia at 72 h, followed by the assessment of oxidative impairments in testis and ES over a 6-week period. Oxidative damage was ascertained by measuring the malondialdehyde levels, reactive oxygen species (ROS) generation, alterations in antioxidant defences and extent of protein oxidation. STZ induced a significant (2.5-fold) increase in blood glucose levels. In diabetic rats, both testis and ES showed enhanced status of lipid peroxidation measured as increased TBARS and ROS from week 2 onwards. These impairments in testis were consistent, progressive and accompanied by marked alterations in antioxidant defences and elevated protein carbonyls. Varying degree of reduction in the specific activities of antioxidant enzymes was evident in testis and ES, while the activity of glutathione-S-transferase (GST) was significantly elevated. Reduced glutathione (GSH) and vitamin E levels were consistently reduced in testis. Lipid dysmetabolism measured in terms of increased cholesterol, triglycerides and phospholipids was evident only beyond week 2 in diabetic testis. Taken together, these results indicate that the testis and ES are indeed subjected to significant oxidative stress in the STZ-diabetic rat both during early as well as progressive phase. It is hypothesized that oxidative impairments in testis which develop over time may at least in part contribute towards the development of testicular dysfunction eventually leading to testicular degeneration which culminates in reduced fertility during the progressive phase of STZ-induced diabetes in adult rats. PMID:17573857

  6. MiR-29b protects dorsal root ganglia neurons from diabetic rat.

    PubMed

    Zhang, Xiaona; Gong, Xu; Han, Shuhai; Zhang, Yang

    2014-11-01

    Accumulated evidences implicated that microRNAs may be involved in diabetic neuropathy. Here, we investigated miR-29's roles in primary isolated dorsal root ganglion (DRG) neurons from STZ-induced diabetic rats. First, miR-29b was found down-regulated after STZ-injection. Inhibitions were increased with time course. Down-regulation of miR-29b was associated with higher apoptosis rate and more serious axonal swelling. Meanwhile, axonogeneration genes were inhibited, whereas neurodegenerative genes were stimulated. Restoration of miR-29b by mimic experiment could reverse the above neuropathy. Furthermore, western blot analysis disclosed that miR-29b could abolish Smad3 activation. In conclusion, the present study identifies that miR-29b could protect DRG from diabetic rats. This protective effects suggested potential therapeutic application of miR-29b in diabetic neuropathy. PMID:24819309

  7. Regulation of oxidative stress and somatostatin, cholecystokinin, apelin gene expressions by ghrelin in stomach of newborn diabetic rats.

    PubMed

    Coskun, Zeynep Mine; Sacan, Ozlem; Karatug, Ayse; Turk, Neslihan; Yanardag, Refiye; Bolkent, Sehnaz; Bolkent, Sema

    2013-09-01

    The aim of the study was to determine whether ghrelin treatment has a protective effect on gene expression and biochemical changes in the stomach of newborn streptozotocin (STZ) induced diabetic rats. In this study, four groups of Wistar rats were used: control, ghrelin control, diabetic and diabetic+ghrelin. The rats were sacrificed after four weeks of treatment for diabetes. The gene expressions of: somatostatin, cholecystokinin, apelin and the altered active caspase-3, active caspase-8, proliferating cell nuclear antigen, were investigated in the pyloric region of the stomach and antioxidant parameters were measured in all the stomach. Although ghrelin treatment to diabetic rats lowered the stomach lipid peroxidation levels, the stomach glutathione levels were increased. Exogenous ghrelin caused an increased activities of stomach catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase in diabetic rats. Numbers of somatostatin, cholecystokinin and proliferating cell nuclear antigen immunoreactive cells decreased in the diabetic+ghrelin group compared to the diabetic group. Apelin mRNA expressions were remarkably less in the diabetic+ghrelin rats than in diabetic rats. The results may indicate that ghrelin treatment has a protective effect to some extent on the diabetic rats. This protection is possibly accomplished through the antioxidant activity of ghrelin observed in type 2 diabetes. Consequently exogenous ghrelin may be a candidate for therapeutic treatment of diabetes. PMID:23566555

  8. Lespedeza davurica (Lax.) Schindl. Extract Protects against Cytokine-Induced ?-Cell Damage and Streptozotocin-Induced Diabetes.

    PubMed

    Sharma, Bhesh Raj; Rhyu, Dong Young

    2015-01-01

    Lespedeza has been used for the management of diabetes in folklore medicine. The purpose of this study is to investigate the protective effects of the methanol extract of Lespedeza davurica (LD) on cytokine-induced ?-cell damage and streptozotocin- (STZ-) induced diabetes. RINm5F cells were treated with interleukin- (IL-) 1? and interferon- (IFN-) ? to induce pancreatic ?-cell damage. The exposure of LD extract significantly decreased cell death, nitric oxide (NO) production, nitric oxide synthase (iNOS) expression, and nucleus factor-kappa B (NF-?B) p65 activation. Antidiabetic effects of LD extract were observed by oral glucose tolerance test (OGTT) in normal rats and by checking the biochemical, physiological, and histopathological parameters in STZ-induced diabetic rats. In OGTT, glucose clearance levels improved by oral treatment of LD extract. The water intake, urine volume, blood glucose, and serum TG, TC, TBARS, and DPP-IV levels were significantly decreased, and liver glycogen content was significantly increased by treatment of LD extract (250?mg/kg BW) in STZ-induced diabetic rats. Also, insulin immunoreactivity of the pancreases was increased in LD extract administrated rats compared with diabetic control rats. These results indicate that LD extract may protect pancreatic ?-cell damage and regulate the blood glucose in STZ-induced diabetic rats. PMID:25793188

  9. Lespedeza davurica (Lax.) Schindl. Extract Protects against Cytokine-Induced ?-Cell Damage and Streptozotocin-Induced Diabetes

    PubMed Central

    2015-01-01

    Lespedeza has been used for the management of diabetes in folklore medicine. The purpose of this study is to investigate the protective effects of the methanol extract of Lespedeza davurica (LD) on cytokine-induced ?-cell damage and streptozotocin- (STZ-) induced diabetes. RINm5F cells were treated with interleukin- (IL-) 1? and interferon- (IFN-) ? to induce pancreatic ?-cell damage. The exposure of LD extract significantly decreased cell death, nitric oxide (NO) production, nitric oxide synthase (iNOS) expression, and nucleus factor-kappa B (NF-?B) p65 activation. Antidiabetic effects of LD extract were observed by oral glucose tolerance test (OGTT) in normal rats and by checking the biochemical, physiological, and histopathological parameters in STZ-induced diabetic rats. In OGTT, glucose clearance levels improved by oral treatment of LD extract. The water intake, urine volume, blood glucose, and serum TG, TC, TBARS, and DPP-IV levels were significantly decreased, and liver glycogen content was significantly increased by treatment of LD extract (250?mg/kg BW) in STZ-induced diabetic rats. Also, insulin immunoreactivity of the pancreases was increased in LD extract administrated rats compared with diabetic control rats. These results indicate that LD extract may protect pancreatic ?-cell damage and regulate the blood glucose in STZ-induced diabetic rats. PMID:25793188

  10. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats.

    PubMed

    Elbe, H; Vardi, N; Esrefoglu, M; Ates, B; Yologlu, S; Taskapan, C

    2015-01-01

    The role of oxygen radicals are known for the pathogenesis of kidney damage. The aim of the present study was to investigate the antioxidative effects of melatonin, quercetin, and resveratrol on streptozotocin (STZ)-induced diabetic nephropathy in rats. A total of 35 male Wistar rats were divided into 5 groups as follows: control, diabetes mellitus (DM), DM + melatonin, DM + quercetin, and DM + resveratrol. All the injections started on the same day of single-dose STZ injection and continued for 30 days. At the end of this period, kidneys were removed and processed for routine histological procedures. Biochemical parameters and morphological changes were examined. In DM group, blood glucose levels were significantly increased, whereas body weights were decreased compared with the control group. Significant increases in blood urea nitrogen and tissue malondialdehyde (MDA) levels and decreases in superoxide dismutase and catalase activities were detected in DM group. Administration of melatonin, quercetin, and resveratrol significantly reduced these values. Melatonin was more efficient in reducing MDA levels than other antioxidants (p < 0.05). STZ-induced histopathological alterations including epithelial desquamation, swelling, intracytoplasmic vacuolization, brush border loss and peritubular infiltration. Additionally, basement membrane thickening and sclerotic changes were observed in glomerulus. Transforming growth factor-?1 positive cells were also increased. Melatonin, quercetin, and resveratrol significantly reduced these histopathological changes. Our results indicate that melatonin, quercetin, and resveratrol might be helpful in reducing diabetes-induced renal damage. PMID:24812155

  11. Ameliorative Potentials of Ginger (Z. officinale Roscoe) on Relative Organ Weights in Streptozotocin induced Diabetic Rats

    PubMed Central

    Eleazu, C. O.; Iroaganachi, M.; Okafor, P. N.; Ijeh, I. I.; Eleazu, K. C.

    2013-01-01

    The ameliorating potentials of ginger incorporated feed (10%) on the relative organ weights of Streptozotocin (STZ) induced diabetic rats was investigated. The experiment lasted for three weeks. Results show that administration of 10% ginger feed to the diabetic rats of group 3, resulted in a 29.81% decrease in their resulting hyperglycemia with a corresponding amelioration of elevated urinary protein, sugars, specific gravity as well as renal growth. In addition, administration of the ginger incorporated feeds to the diabetic rats of group 3, resulted in 9.88% increase in body weight with a corresponding 60.24% increase in growth compared with the non-diabetic rats administered standard rat pellets that had 6.21% increase in weight with a corresponding 60.14% increase in growth unlike the diabetic control rats that recorded 28.62% decrease in body weight with a corresponding 239.9% decrease in growth rates. Analysis of the chemical composition of the flour of the ginger incorporated feed indicated that it contained moderate amounts of moisture, crude fibre, alkaloids, saponins, tannins, Fe and Zn but considerable amounts of proteins, lipids, carbohydrates, ash, flavonoids, calcium, magnesium, potassium, phosphorous and energy value. There was no significant difference (P>0.05) in the liver and relative liver weights of the diabetic control rats and the diabetic -ginger treated rats. In addition, there were no significant differences in the kidney weights of the non-diabetic, diabetic control and diabetic treated rats (P>0.05) while there were significant differences in the relative kidney weights of the non-diabetic rats and the diabetic rats treated with ginger feeds (P<0.05). Results show that the use of ginger in the dietary management of diabetes mellitus could be a breakthrough in the search for novel plants that could prevent the development of diabetic glomerular hypertrophy. PMID:23847458

  12. CNP-pGC-cGMP-PDE3-cAMP Signal Pathway Upregulated in Gastric Smooth Muscle of Diabetic Rats

    PubMed Central

    Cai, Ying-Lan; Zhang, Mo-Han; Huang, Xu; Jiang, Jing-Zhi; Piao, Li-Hua; Jin, Zheng; Xu, Wen-Xie

    2015-01-01

    Our previous studies have shown that CNP-NPR-B/pGC-cGMP is upregulated in the diabetic rats. The present study was designed to determine whether the upregulation of CNP-NPR-B/pGC-cGMP signal pathway affects cGMP-PDE3-cAMP signal pathway in diabetic gastric smooth muscle. The gastric smooth muscle motility was observed by using isometric measurement. PDEs expressions in diabetic gastric smooth muscle tissue were observed by using immunohistochemistry, Western blotting, and RT-PCR methods. The results demonstrated that the inhibitory effect of CNP on the spontaneous contraction of gastric antral circular smooth muscle was potentiated in STZ-induced diabetic rat. CNP-induced increase of cGMP and cAMP was much higher in diabetic gastric smooth muscle tissue than in controls. The expression of PDE3 is downregulated while the levels of gene expression of PDE1, PDE2, PDE4, and PDE5 were not altered in the diabetic gastric smooth muscle tissue. The results suggest that the sensitivity of gastric smooth muscle to CNP is potentiated via activation of CNP-pGC-cGMP-PDE3-cAMP signal pathway in STZ-induced diabetic rats, which may be associated with diabetes-induced gastric motility disorder.

  13. Nordihydroguairetic acid, a lignin, prevents oxidative stress and the development of diabetic nephropathy in rats.

    PubMed

    Anjaneyulu, Muragundla; Chopra, Kanwaljit

    2004-09-01

    Recent evidences indicate a pivotal role of reactive oxygen species in etiology of diabetic nephropathy, an important microvascular complication of diabetes mellitus. Moreover, oxidative stress leads to an increased production of lipoxygenase derivatives which also play a role in diabetic nephropathy. The present study was thus designed to examine the effect of an antioxidant and a lipoxygenase inhibitor, nordihydroguairetic acid (NDGA), on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) in rats. After the 4th week of STZ injection, NDGA (5 and 10 mg/kg) was given subcutaneously (s.c.) for another 4 weeks to both control and diabetic rats. At the end of the 8th week, diabetic rats exhibited renal dysfunction as evidenced by reduced creatinine and urea clearance along with enhanced albumin excretion rate as compared with control rats. Biochemical analysis of kidneys revealed a marked increase in oxidative stress demonstrated by increased lipid peroxidation and decreased activities of key antioxidant enzymes, glutathione (GSH), superoxide dismutase (SOD) and catalase in diabetic rats. Chronic treatment with NDGA in diabetic rats significantly prevented both renal dysfunction and oxidative stress as compared with vehicle-treated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening and moderate interstitial fibrosis and arteriolopathy, whereas NDGA administration in diabetic rats markedly prevented renal morphological alterations. These results emphasize the role of oxidative stress in the pathophysiology of diabetic nephropathy and point towards the potential of NDGA as a complementary therapy for the prevention/treatment of diabetic nephropathy. PMID:15292654

  14. Protective Effect of Ethyl Acetate Fraction of Stereospermum Suaveolens Against Hepatic Oxidative Stress in STZ Diabetic Rats

    PubMed Central

    Balasubramanian, Thirumalaiswamy; Senthilkumar, G. P; Karthikeyan, M.; Chatterjee, Tapan Kumar

    2013-01-01

    Stereospermum suaveolens is a folk remedy for the treatment of diabetes and liver disorders in southern parts of India. In the present study, the protective effect of the ethyl acetate fraction of ethanol extract from S. suaveolens against hepatic oxidative stress was evaluated in streptozotocin (STZ)-induced diabetic rats for 14 days. The ethyl acetate fraction was administered orally to the STZ diabetic rats at the doses of 200 and 400 mg/kg. Blood glucose level was measured according to glucose oxidase method. In order to determine hepatoprotective activity, changes in the levels of serum biomarker enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), and serum alkaline phosphatase (SALP) were assessed in the ethyl acetate fraction treated diabetic rats and were compared with the levels in diabetic control rats. In addition, the antioxidant activity of ethyl acetate fraction was evaluated using various hepatic parameters such as thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). It was found that administration of ethyl acetate fraction (200 and 400 mg/kg) produced a significant (P < 0.001) fall in fasting blood glucose level, TBARS, bilirubin, AST, ALT, and SALP, while elevating the GSH levels, and SOD and CAT activities in diabetic rats. Histopathologic studies also revealed the protective effect of ethyl acetate fraction on the liver tissues of diabetic rats. It was concluded from this study that the ethyl acetate fraction from ethanol extract of S. suaveolens modulates the activity of enzymatic and nonenzymatic antioxidants and enhances the defense against hepatic oxidative stress in STZ-induced diabetic rats. PMID:24716175

  15. Temporal dystrophic remodeling within the intrinsic cardiac nervous system of the streptozotocin-induced diabetic rat model

    PubMed Central

    2014-01-01

    Introduction The pathogenesis of heart failure (HF) in diabetic individuals, called “diabetic cardiomyopathy”, is only partially understood. Alterations in the cardiac autonomic nervous system due to oxidative stress have been implicated. The intrinsic cardiac nervous system (ICNS) is an important regulatory pathway of cardiac autonomic function, however, little is known about the alterations that occur in the ICNS in diabetes. We sought to characterize morphologic changes and the role of oxidative stress within the ICNS of diabetic hearts. Cultured ICNS neuronal cells from the hearts of 3- and 6-month old type 1 diabetic streptozotocin (STZ)-induced diabetic Sprague-Dawley rats and age-matched controls were examined. Confocal microscopy analysis for protein gene product 9.5 (PGP 9.5) and amino acid adducts of (E)-4-hydroxy-2-nonenal (4-HNE) using immunofluorescence was undertaken. Cell morphology was then analyzed in a blinded fashion for features of neuronal dystrophy and the presence of 4-HNE adducts. Results At 3-months, diabetic ICNS neuronal cells exhibited 30% more neurite swellings per area (p?=?0.01), and had a higher proportion with dystrophic appearance (88.1% vs. 50.5%; p?=?<0.0001), as compared to control neurons. At 6-months, diabetic ICNS neurons exhibited more features of dystrophy as compared to controls (74.3% vs. 62.2%; p?=?0.0448), with 50% more neurite branching (p?=?0.0015) and 50% less neurite outgrowth (p?=?<0.001). Analysis of 4-HNE adducts in ICNS neurons of 6-month diabetic rats demonstrated twice the amount of reactive oxygen species (ROS) as compared to controls (p?=?<0.001). Conclusion Neuronal dystrophy occurs in the ICNS neurons of STZ-induced diabetic rats, and accumulates temporally within the disease process. In addition, findings implicate an increase in ROS within the neuronal processes of ICNS neurons of diabetic rats suggesting an association between oxidative stress and the development of dystrophy in cardiac autonomic neurons. PMID:24894521

  16. Relationship between the level of hippocampal leptin receptor gene expression and learning performance in diabetic rats.

    PubMed

    Demirel, C; Balc?, S O; Korkmaz, H; Akarsu, E

    2014-11-01

    Diabetes mellitus may be associated with impaired cognitive function. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. Leptin that is a peptide hormone, acts in the hippocampus where it facilitates the induction of long-term potentiation and enhances NMDA receptor mediated transmission. The aim of the present study is to investigate possible relationship between the hippocampal leptin receptor gene expression and learning performance in streptozotocin (STZ) induced diabetic rats. In this study was conducted on a total of 40 Winstar albino female rats, including a control group consisting of 20 rats and experimental group comprising of 20 rats in which diabetes was induced by means of STZ administration. Leptin receptor gene expression was detected in hippocampal samples by using real time-PCR. According to the evaluation, the learning performance of rats with induced diabetes was found to be same throughout the first 3 days after STZ in comparison to the control group rats. End of the 45 days the learning performance of the control group was found to be better than the diabetic group (p<0.05). Hipocampal leptin receptor expression was found lower in diabetic group than the control group (p<0.05). The results provide evidence that leptin receptor gene may related to learning performance in diabetic rats. Further, detailed studies are needed to address the exact role of leptin and related molecules in learning performance. PMID:25380550

  17. Antiatherosclerotic Potential of Active Principle Isolated from Eugenia jambolana in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Tanwar, Reenu Singh; Sharma, Suman Bala; Singh, Usha Rani; Prabhu, Krishna Madhava

    2011-01-01

    The aim of the present study was to investigate the antiatherosclerotic effect of active principle (FIIc) isolated from aqueous fruit pulp extract of Eugenia jambolana. Crude aqueous extract of E. jambolana was subjected to purification using chromatographic techniques which yielded purified active compound (FIIc). Purity of FIIc was tested by HPLC. Phytochemical investigation of FIIc by NMR, IR, and UV spectra showed that the purified compound is ?-hydroxy succinamic acid. The streptozotocin- (STZ-) induced diabetic rats were fed atherosclerotic (Ath) diet containing 1.5?mL olive oil containing 8?mg (3, 20,000 IU) vitamin D2 and 40?mg cholesterol for 5 consecutive days. The STZ-induced diabetic rats receiving Ath diet were orally administered FIIc at doses of 10, 15, and 20?mg/kg, and results were compared with reference drug, that is, glibenclamide (600??g/mg) and healthy control. 30-day treatment with FIIc resulted in significant (P < .001) improvement in blood glucose, serum lipid profile, apolipoproteins (Apo A1 and apoB100), and endothelial dysfunction parameters. Histomorphological studies also confirmed biochemical findings. Our results showed that FIIc has protective effect on hyperglycemia-induced atherosclerosis. PMID:21584267

  18. Antioxidant Effects of Fermented Red Ginseng Extracts in Streptozotocin- Induced Diabetic Rats

    PubMed Central

    Kim, Hyun-Jeong; Lee, Sung-Gyu; Chae, In-Gyeong; Kim, Mi-Jin; Im, Nam-Kyung; Yu, Mi-Hee; Lee, Eun-Ju; Lee, In-Seon

    2011-01-01

    The antioxidant activities of fermented red ginseng (FRG) were investigated in vitro and in vivo. The contents of total polyphenol and total flavonoid in FRG extracts were 17.01±2.00 ?g/mg and 18.42±3.97 ?g/mg, respectively. These extracts were capable of directly scavenging ?, ?-diphenyl-picrylhydrazyl free radicals. The antioxidative effects of the FRG extracts in streptozotocin (STZ)-induced diabetic rats were also investigated. The activities of plasma alanine transaminase, aspartate transaminase, and ?-glutamyltransferase were significantly decreased by extract administration as compared to an STZ control group. Hepatic glutathione content depleted by STZ treatment was significantly increased by treatment of the FRG extracts, but the elevation of lipid peroxide content induced by STZ was significantly decreased by the extracts. Activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase decreased after STZ-treatment were recovered by the treatment of the FRG extracts. These results indicate that FRG extracts have antioxidative effets in STZ-induced diabetic rats. PMID:23717054

  19. Stress-strain analysis of contractility in the ileum in response to flow and ramp distension in streptozotocin-induced diabetic rats-Association with advanced glycation end product formation.

    PubMed

    Zhao, Jingbo; Chen, Pengmin; Gregersen, Hans

    2015-04-13

    This study compared the ileal contractility and analyzed the association between contractility with advanced glycation end product (AGE) formation in normal and streptozotocin (STZ)-induced diabetic rats. Nine STZ-induced diabetic rats (Diabetes group) and 9 normal rats (Normal group) were used. The motility experiments were carried out on ileums in organ baths containing physiological Krebs solution. Ileal pressure and diameter changes were obtained from basic, flow-induced and ramp distension-induced contractions. The frequency and amplitude of contractions were analyzed from pressure-diameter curves. Distension-induced contraction thresholds and maximum contraction amplitude of basic and flow-induced contractions were calculated in terms of stress and strain. AGE and its receptor (RAGE) in the layers were detected by immunohistochemistry staining. The maximum stress of flow-induced contractions was lowest in the Diabetes Group (P<0.05). During ramp distension, the pressure and stress thresholds and Young?s modulus to induce phasic contraction were lowest in the Diabetes Group (P<0.05 and P<0.01). AGE and RAGE expressions in the different ileum layers were highest in the Diabetes group. The contraction pressure and stress thresholds were significantly associated with AGE expression in the muscle layer and RAGE expression in mucosa epithelium and neurons. The diabetic intestine was hypersensitive to distension for contraction induction. However, the contraction force produced by smooth muscle was lowest in diabetic rats. Increased AGE/RAGE expression was associated with the contractility changes in diabetic rats. PMID:25682538

  20. Sesamin suppresses STZ induced INS-1 cell apoptosis through inhibition of NF-?B activation and regulation of Bcl-2 family protein expression.

    PubMed

    Zheng, Shuguo; Zhao, Mengqiu; Ren, Younan; Wu, Yuanjie; Yang, Jieren

    2015-03-01

    Diverse risk factors for diabetes can induce oxidative stress, leading to pancreatic beta cell damage and insulin secretion dysfunction. In the present study, we evaluated the effect of sesamin on streptozotocin (STZ) induced apoptosis in INS-1 cells and the possible mechanisms implicated. After preincubation with indicated concentrations of sesamin (0.1, 1.0 and 10.0?mol/l) for 24h, INS-1 cells were exposed to STZ (3mmol/l) for 12h. Sesamin effectively improved STZ induced cell damage as determined by MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] assay and insulin secretion capacity, and suppressed STZ induced cell apoptosis as evaluated by flow cytometry using annexin V and propidium iodide double staining. Western blot analysis demonstrated that sesamin markedly suppressed STZ induced nuclear factor kappa B (NF-?B) activation, with Bax protein down-regulated and Bcl-2 protein up-regulated significantly. Preincubation with sesamin resulted in an evident enhancement of total antioxidant capacity in INS-1 cells, accompanied by a significant reduction of intracellular reactive oxygen species and malondialdehyde, an end product of lipid peroxidation. Taken together, these findings suggested that sesamin was capable of suppressing STZ induced INS-1 cell apoptosis, which might be ascribed, at least partly, to the inhibition of NF-?B activation and subsequent regulation of Bcl-2 family protein expression. This study would provide a potential target for treatment of diabetes with sesamin as well as other antioxidants. PMID:25637086

  1. Protective effects of melatonin against the damages of neuroendocrine-immune induced by lipopolysaccharide in diabetic rats.

    PubMed

    Zhong, L-Y; Yang, Z-H; Li, X-R; Wang, H; Li, L

    2009-10-01

    The present study was to determine the protective effects of melatonin (MLT) against the damages of neuroendocrine-immune induced by lipopolysaccharide (LPS) in streptozotocin (STZ)-induced diabetic rats, and to analyze the parameters related to diabetes and oxidative stress. A total of 70 male Sprague-Dawley rats were assigned to this experiment. 10 of rats received STZ intraperitoneally (i.p.) alone as diabetic control; 40 of rats as the Diabetes+LPS received STZ plus LPS i.p. after induction of diabetes with STZ, then assigned to sub-groups as MLT (0.1) (mg), MLT (1) (mg), and Vehicle group, received two doses MLT and vehicle, i.p., respectively, q6 h for 12 h after LPS administration; and the remaining served as normal and LPS control. LPS significantly increased the serum levels of TNF-alpha and IL-6 in normal and diabetic rats; LPS also dramatically increased the plasma concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone. Both 0.1 and 1 mg/kg MLT doses significantly decreased the serum levels of TNF-alpha and IL-6. Significant inhibitory effects of MLT (1 mg/kg) were observed on the plasma concentrations of CRH, ACTH, and corticosterone of the HPA axis. The beneficial effects of MLT, such as the antioxidant activity and maintaining glucose homoeostasis, were also observed in this study, this resulted in a protective effect against the damages caused by LPS in STZ-induced diabetic rats. This finding probably provides a new approach for preventing the undesirable effects of the vicious cycle of hyperglycemia and stress factors such as severe infection in diabetic patients. PMID:19449282

  2. Neuroprotective effect of RYGB in Zucker fatty diabetic rats.

    PubMed

    Han, Xin-Sheng; Huang, Yong; Jing, Hong-Jian; Zhang, Ai-Wu; Jiang, Tao; Xu, Yu-Ming

    2014-01-01

    The aim of this study is to explore the therapeutic potential of RYGB, a common used bariatric surgery, on diabetic polyneuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats. In animal model experiments, rats were made diabetic by STZ administration, and after 12 weeks of diabetes, two groups were studied: RYGB and sham surgery control (PF). Change in oral glucose tolerance, insulin sensitivity, and the plasma concentrations of insulin, glucagon, glucagon-like peptide-1 (GLP-1) were measured. Peripheral nerve function was determined by the current perception threshold. Sciatic nerve blood flow (SNBF) and intraepidermal nerve fiber densities (IENFDs) also were evaluated. The results indicated that glucose tolerance and insulin sensitivity were significantly improved in the RYGB group. Fasting total GLP-1 were increased in the RYGB group. The increase seen in current perception threshold vales in RYGB group was reduced. The decreased IENFDs in sole skins of RYGB group were ameliorated by RYGB. In conclusion, the findings indicate that RYGB ameliorates the severity of DPN, which may be associated with increased GLP-1 and improved insulin sensitivity/action. PMID:25419361

  3. Antihyperlipidemic Effect of Peucedanum Pastinacifolium Extract in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Movahedian, Ahmad; Zolfaghari, Behzad; Sajjadi, S. Ebrahim; Moknatjou, Reza

    2010-01-01

    INTRODUCTION: Dyslipidemia is one of the most common complications of diabetes mellitus, significantly contributing to cardiovascular morbidity and mortality in diabetic patients. Peucedanum pastinacifolium Boiss. & Hausskn. is commonly used as an antihyperlipidemic vegetable in Iranian folk medicine. MATERIAL AND METHODS: In this study, we examined a hydroalcoholic extract of the aerial parts of Peucedanum pastinacifolium to determine its lipid-lowering activity in normal and streptozotocin (STZ)-induced diabetic rats. Experimental diabetes mellitus was induced by a single intraperitoneal administration of streptozotocin. Normal and streptozotocin-induced diabetic rats were separated into four groups. The groups were fed with 0, 125, 250 or 500 mg/kg body weight of Peucedanum Pastinacifolium hydroalcoholic Extract (PPE) in aqueous solution for 30 days. RESULTS: The results show that there were significant (P < 0.05) increases in total serum cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in streptozotocin-induced diabetic rats. Treatment of diabetic rats with PPE over a period of a month returned these levels close to control levels. CONCLUSION: These results suggest that PPE has hypolipidemic effects in streptozotocin-induced diabetic rats. PMID:20613940

  4. Effect of green tea on kidney tubules of diabetic rats.

    PubMed

    Renno, Waleed M; Abdeen, Suad; Alkhalaf, Mousa; Asfar, Sami

    2008-09-01

    It has been documented that green tea (GT) and its catechin components improve renal failure and inhibit the growth of mesangial cells. In the present study we examined the long-term effect of GT extract on streptozotocin (STZ)-induced diabetic nephropathy and on the glycogen accumulation in the kidney tubules. Male Sprague-Dawley rats were randomly assigned to normal control groups (2, 6, 8 and 12 weeks) and five diabetic groups (n 10) of comparable age. A GT diabetic group received 16 % concentration of GT for 12 weeks post-diabetes induction as their sole source of drinking water. GT treatment significantly (P < 0.01) reduced the serum glucose, glycosylated protein, serum creatinine and blood urea N levels by 29.6 (sem 3.7), 22.7 (sem 5.2), 38.9 (sem 10) and 41.7 (sem 1.9) %, respectively, compared with the diabetic group of comparable age. In addition, the GT-treated group showed a significant 44 (sem 10.8) % higher creatinine clearance (Ccr) compared with the untreated diabetic group. Likewise, GT reduced the urea N, creatinine, glucose and protein excretion rates by 30 (sem 7.6), 35.4 (sem 5.3), 34.0 (sem 5.3) and 46.0 (sem 13.0) % compared with the 12 weeks diabetic group. Administration of GT to 12 weeks diabetic rats significantly (P < 0.001) prevented (99.98 (sem 0.27) % less) the accumulation of glycogen in the kidney tubules. These results indicate that in STZ diabetes, kidney function appears to be improved with GT consumption which also prevents glycogen accumulation in the renal tubules, probably by lowering blood levels of glucose. Therefore, GT could be beneficial additional therapy in the management of diabetic nephropathy. PMID:18252021

  5. Heart-protective effect of n-3 PUFA demonstrated in a rat model of diabetic cardiomyopathy.

    PubMed

    Anna, Zhukovska; Angela, Shysh; Barbara, Bacova; Jana, Radosinska; Tamara, Benova; Csilla, Viczenczova; Victor, Dosenko; Oleksiy, Moybenko; Narcisa, Tribulova

    2014-04-01

    This study was designed to examine in vivo functional changes of the heart in the early stages of streptozotocin (STZ)-induced diabetic cardiomyopathy and to evaluate the effects of n-3 PUFA intake. Moreover, we investigated whether modulation of diabetes-related abnormalities of myocardial connexin-43 (Cx43), ?-myosin heavy chain (?-MHC), and ?1-adrenergic receptors (?1-AR) might be implicated in the cardioprotective mechanism of n-3 PUFA. Our results showed significantly reduced cardiac output and ejection fraction (using the microtip pressure-volume catheter technique) as well as stroke volume and stroke work, 4 weeks after STZ-induced diabetes, with improvement of these parameters due to n-3 PUFA consumption. Myocardial expression of Cx43 mRNA estimated by real-time polymerase chain reaction did not change in diabetic rats regardless of n-3 PUFA consumption (100 mg/100 g b.w./day). In contrast, the total and functional phosphorylated form of Cx43 protein increased significantly, and its cardiomyocyte-related distribution was disordered in the diabetic heart, but these changes normalized because of n-3 PUFA intake. Furthermore, acute diabetes was accompanied by decrease of myocardial ?1-AR mRNA expression and mild yet nonsignificant increase of ?-MHC mRNA. These alterations were not significantly affected by n-3 PUFA. In conclusion, the results point out that STZ-diabetic rats benefit from n-3 PUFA consumption particularly because of the attenuation of myocardial Cx43 abnormalities that most likely contributes to improvement of cardiac function. PMID:24378994

  6. Hypoglycemic and hypolipidemic effects of oxymatrine in high-fat diet and streptozotocin-induced diabetic rats.

    PubMed

    Guo, Changrun; Zhang, Chunfeng; Li, Lu; Wang, Zhenzhong; Xiao, Wei; Yang, Zhonglin

    2014-05-15

    Oxymatrine, a quinolizidine alkaloid, has been widely used for the treatment of hepatitis. In this study, we investigated the hypoglycemic and hypolipidemic effects and new pharmacological activities of oxymatrine, in a high-fat diet and streptozotocin (STZ)-induced diabetic rats. The results demonstrated that oxymatrine could significantly decrease fasting blood glucose, glycosylated hemoglobin (GHb), food and water intake, non-esterified fatty acid (NEFA), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol levels (LDL-c), and increase serum insulin, liver and muscle glycogen, high density lipoprotein cholesterol (HDL-c), glucagon-like peptide-1 (GLP-1) and muscle glucose transporter-4 (GLUT-4) content in diabetic rats. The results of the histological examinations of the pancreas and liver show that oxymatrine protected the islet architecture and prevented disordered structure of the liver. This study displays that oxymatrine can alleviate hyperglycemia and hyperlipemia in a high-fat diet and STZ-induced diabetic rats might by improving insulin secretion and sensitivity. PMID:24680614

  7. L-Glutamine Supplementation Prevents the Development of Experimental Diabetic Cardiomyopathy in Streptozotocin-Nicotinamide Induced Diabetic Rats

    PubMed Central

    Badole, Sachin L.; Jangam, Ganesh B.; Chaudhari, Swapnil M.; Ghule, Arvindkumar E.; Zanwar, Anand A.

    2014-01-01

    The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o.), II: diabetic control (distilled water, 10 ml/kg, p.o.), III: L-glutamine (500 mg/kg, p.o.) and IV: L-glutamine (1000 mg/kg, p.o.). All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity. PMID:24651718

  8. Ganoderma lucidum polysaccharides exert anti-hyperglycemic effect on streptozotocin-induced diabetic rats through affecting ?-cells.

    PubMed

    Zheng, Jusheng; Yang, Bin; Yu, Yinghua; Chen, Qi; Huang, Tao; Li, Duo

    2012-08-01

    Previous studies have demonstrated that Ganoderma lucidum polysaccharides (Gl-PS) exhibited potential antihyperglycemic effect in rats. The aim of the present study was to investigate the mechanism of the hypoglycemic effect of a low- molecular-weight Gl-PS in streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rats. Gl-PS was extracted and purified from Ganodema lucidum fruiting body. 50 male SD rats were included in the study; 10 were taken as healthy controls; 40 were induced to diabetes by a single injection of 65 mg/kg STZ, of which 30 were selected as successful diabetic rat models. The 30 diabetic rats were divided into three groups: Gl-PS (200 mg/kg Gl-PS), metformin (100 mg/kg metformin) and diabetic control (n = 10 per group). After eight weeks' oral administration, plasma concentrations of fasting glucose, triacylglyceride, total cholesterol and nitric oxide were significantly decreased in Gl-PS and metformin groups. Pancreatic superoxide dismutase, catalase and glutathione peroxidase were significantly increased in Gl-PS and metformin groups. Histopathological results showed that Gl-PS and metformin had protective effect on ?-cells. The mRNA expressions of Bcl-2 and PDX-1 in pancreas were up-regulated, but Bax, iNOS and Casp-3 down-regulated in Gl- PS and metformin groups compared to diabetic control group. The present results suggested that Gl-PS had a hypoglycemic effect in STZ-induced diabetic rats through preventing apoptosis of pancreatic ?-cells and enhancing ?-cells regeneration. PMID:22329512

  9. Glucose lowering efficacy of the aqueous stem bark extract of Trema orientalis (Linn) Blume in normal and streptozotocin diabetic rats.

    PubMed

    Dimo, T; Ngueguim, F T; Kamtchouing, P; Dongo, E; Tan, P V

    2006-03-01

    The glucose-lowering efficacy of the aqueous stem bark extract of Trema orientalis (Ulmaceae) was evaluated both in normal and streptozotocin-induced diabetic rats. In normoglycemic rats, the single oral administration of the aqueous extract of T. orientalis failed to reduce blood glucose levels while in STZ-diabetic rats, the plant extract (38-300 mg/kg) exhibited significant hypoglycaemic activity with a maximum effect of 29.67%, 5 hours after administration of the 75 mg/kg dose when compared with the diabetic untreated group. Glibenclamide was not able to lower blood glucose in STZ-diabetic rats, while it significantly lowered the blood sugar in normoglycemic rats. The hypoglycaemic property of T. orientalis was also assessed by an oral glucose tolerance test (OGTT) in STZ-diabetic rats. The aqueous extract of T. orientalis and the reference drug, glibenclamide, (10 mg/kg) produced significant blood glucose lowering effects in the diabetic rats when compared to the diabetic controls. One week after repeated administration of T. orientalis extract, blood glucose levels were significantly decreased (p < 0.05) and still remained low after 2 weeks (p < 0.01). The results indicated that T. orientalis stem bark extract significantly reduces blood glucose in STZ-induced diabetic rats by a mechanism different from that of sulfonylurea agents. The present investigation provides pharmacological evidence that the use of this plant extract in traditional medicine for cardiovascular disease can be of benefit particulary in diabetic patients. PMID:16599266

  10. Effect of pre-germinated brown rice intake on diabetic neuropathy in streptozotocin-induced diabetic rats

    PubMed Central

    Usuki, Seigo; Ito, Yukihiko; Morikawa, Keiko; Kise, Mitsuo; Ariga, Toshio; Rivner, Michael; Yu, Robert K

    2007-01-01

    Background To study the effects of a pre-germinated brown rice diet (PR) on diabetic neuropathy in streptozotocin (STZ)-induced diabetic rats. Methods The effects of a PR diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with those fed brown rice (BR) or white rice (WR) diets with respect to the following parameters: blood-glucose level, motor-nerve conduction velocity (NCV), sciatic-nerve Na+/K+-ATPase activity, and serum homocysteine-thiolactonase (HTase) activity. Results Compared with diabetic rats fed BR or WR diets, those fed a PR diet demonstrated significantly lower blood-glucose levels (p < 0.001), improved NCV (1.2- and 1.3-fold higher, respectively), and increased Na+/K+-ATPase activity (1.6- and 1.7-fold higher, respectively). The PR diet was also able to normalize decreased serum homocysteine levels normally seen in diabetic rats. The increased Na+/K+-ATPase activity observed in rats fed PR diets was associated with elevations in HTase activity (r = 0.913, p < 0.001). The in vitro effect of the total lipid extract from PR bran (TLp) on the Na+/K+-ATPase and HTase activity was also examined. Incubation of homocysteine thiolactone (HT) with low-density lipoprotein (LDL) in vitro resulted in generation of HT-modified LDL, which possessed high potency to inhibit Na+/K+-ATPase activity in the sciatic nerve membrane. The inhibitory effect of HT-modified LDL on Na+/K+-ATPase activity disappeared when TLp was added to the incubation mixture. Furthermore, TLp directly activated the HTase associated with high-density lipoprotein (HDL). Conclusion PR treatment shows efficacy for protecting diabetic deterioration and for improving physiological parameters of diabetic neuropathy in rats, as compared with a BR or WR diet. This effect may be induced by a mechanism whereby PR intake mitigates diabetic neuropathy by one or more factors in the total lipid fraction. The active lipid fraction is able to protect the Na+/K+-ATPase of the sciatic-nerve membrane from the toxicity of HT-modified LDL and to directly activate the HTase of HDL. PMID:18036220

  11. Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Wang, Jian-Qin; Yin, Jie; Song, Yan-Feng; Zhang, Lang; Ren, Ying-Xiang; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong

    2014-01-01

    Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). A? aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, A? aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies. PMID:25197672

  12. Early changes in pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide and related receptors expression in retina of streptozotocin-induced diabetic rats.

    PubMed

    Giunta, Salvatore; Castorina, Alessandro; Bucolo, Claudio; Magro, Gaetano; Drago, Filippo; D'Agata, Velia

    2012-09-01

    The retinal expression and distribution of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) and their receptors was investigated in early streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in rats by STZ injection (60 mg/kg i.p.). PACAP, VIP and their receptors in nondiabetic control and diabetic retinas were assayed by quantitative real-time PCR and Western blot 1 and 3 weeks after STZ injection. Effects of intravitreal treatment with PACAP38 on the expression of the two apoptotic-related genes Bcl-2 and p53 were also evaluated. PACAP and VIP, as well as VPAC1 and VPAC2 receptors, but not PAC1 mRNA levels, were transiently induced in retinas 1 week following STZ. These findings were confirmed by immunoblot analyses. Three weeks after the induction of diabetes, significant decreases in the expression of peptides and their receptors were observed, Bcl-2 expression decreased and p53 expression increased. Intravitreal injection of PACAP38 restored STZ-induced changes in retinal Bcl-2 and p53 expression to nondiabetic levels. The initial upregulation of PACAP, VIP and related receptors and the subsequent downregulation in retina of diabetic rats along with the protective effects of PACAP38 treatment, suggest a role for both peptides in the pathogenesis of diabetic retinopathy. PMID:22721946

  13. Evaluation of anti-diabetic potential of leaves and stem of Flacourtia jangomas in streptozotocin-induced diabetic rats

    PubMed Central

    Singh, Ajay Kumar; Singh, Jyoti

    2010-01-01

    Objectives: To study the efficacy of combination of Flacourtia jangomas leaf and stem (1:1) methanolic extract (MEFJ) in streptozotocin (STZ)-induced diabetic rats and to investigate the qualitative phytochemical present in the extract. The study also aims to evaluate acute and short-term general toxicity of the extract in rats. Material and Methods: MEFJ of leaves and stem was subjected to preliminary qualitative phytochemical investigations by using standard procedures. The extract (400 mg/kg p.o.) was screened for antidiabetic activity in STZ-induced diabetic rats (30 mg/kg, i.p.). Acute oral toxicity study for the test extract of the plant was carried out using OECD/OCED guideline 425. Results: Phytochemical analysis of MEFJ of leaves and stem revealed the presence of flavonoids, saponins, carbohydrates, steroids, tannins, and phenolic compounds. In acute toxicity study, no toxic symptoms were observed for MEFJ up to dose 2000 mg/kg. Oral administration of MEFJ for 21 days exhibited highly significant (P < 0.01) hypoglycemic activity and also correction of altered biochemical parameters, namely cholesterol and triglycerides significantly (P < 0.05). Urine analysis on 1st day showed the presence of glucose and traces of ketone in the entire group except normal control group. However, on 21st day glucose and ketone traces were absent in MEFJ- and glibenclamide-treated groups while they were present in diabetic control. The data were analyzed using analysis of variance followed by Dunnett’s test. Conclusion: The observations confirm that methanolic extract of the leaf and stem of the plant has antidiabetic activity and is also involved in correction of altered biological parameters. It also warrants further investigation to isolate and identify the hypoglycemic principles in this plant so as to elucidate their mode of action. PMID:21206623

  14. Effects of Dietary Onion (Allium cepa L.) in a High-Fat Diet Streptozotocin-Induced Diabetes Rodent Model

    Microsoft Academic Search

    M. Shahidul Islam; Haymie Choi; Du Toit Loots

    2008-01-01

    Background\\/Aims: The present study was conducted to investigate the effects of two dietary doses of freeze-dried onion powder on diabetes-related symptoms in a high-fat (HF) diet streptozotocin (STZ)-induced diabetes rat model. Methods: Five-week-old male Sprague-Dawley rats were fed a HF diet for 2 weeks and then randomly divided into 4 groups as follows: HF control (HFC), diabetic control (DBC), onion

  15. Effects of Syzygium aromaticum-Derived Triterpenes on Postprandial Blood Glucose in Streptozotocin-Induced Diabetic Rats Following Carbohydrate Challenge

    PubMed Central

    Khathi, Andile; Serumula, Metse R.; Myburg, Rene B.; Van Heerden, Fanie R.; Musabayane, Cephas T.

    2013-01-01

    Purpose Recent reports suggest that the hypoglycaemic effects of the triterpenes involve inhibition of glucose transport in the small intestine. Therefore, the effects of Syzygium spp-derived triterpenes oleanolic acid (OA) and maslinic acid (MA) were evaluated on carbohydrate hydrolyzing enzymes in STZ-induced diabetic rats and consequences on postprandial hyperglycaemia after carbohydrate loading. Methods We determined using Western blot analysis the expressions of ?-amylase and ?-glucosidase and glucose transporters SGLT1 and GLUT2 in the small intestine intestines isolated from diabetic rats treated with OA/MA for 5 weeks. In vitro assays were used to assess the inhibitory activities of OA and MA against ?-amylase, ?-glucosidase and sucrase. Results OA and MA ameliorated postprandial hyperglycemia in carbohydrate loaded diabetic rats as indicated by the significantly small glucose area under the curve (AUC) in treated diabetic animals compared with that in untreated diabetic rats. Western blotting showed that OA and MA treatment not only down-regulated the increase of SGLT1 and GLUT2 expressions in the small intestine of STZ-induced diabetic rats, but also inhibited small intestine ?-amylase, sucrase and ?-glucosidase activity. IC50 values of OA against ?-amylase (3.60 ± 0.18 mmol/L), ?-glucosidase (12.40 ± 0.11 mmol/L) and sucrase (11.50 ± 0.13 mmol/L) did not significantly differ from those of OA and acarbose. Conclusions The results of suggest that OA and MA may be used as potential supplements for treating postprandial hyperglycemia. Novelty of the Work The present observations indicate that besides improving glucose homeostasis in diabetes, OA and MA suppress postprandial hyperglycaemia mediated in part via inhibition of carbohydrate hydrolysis and reduction of glucose transporters in the gastrointestinal tract. Inhibition of ?-glucosidase and ?-amylase can significantly decrease the postprandial hyperglycaemia after a mixed carbohydrate diet and therefore can be an important strategy in the management of postprandial blood glucose levels in NIDDM patients. PMID:24278452

  16. Postnatal treadmill exercise alleviates short-term memory impairment by enhancing cell proliferation and suppressing apoptosis in the hippocampus of rat pups born to diabetic rats

    PubMed Central

    Kim, Young Hoon; Sung, Yun-Hee; Lee, Hee-Hyuk; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Kim, Bo-Kyun

    2014-01-01

    During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics. PMID:25210695

  17. Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin

    PubMed Central

    2013-01-01

    Background To study the pathogenesis of diabetic cardiomyopathy, reliable animal models of type 2 diabetes are required. Physiologically relevant rodent models are needed, which not only replicate the human pathology but also mimic the disease process. Here we characterised cardiac metabolic abnormalities, and investigated the optimal experimental approach for inducing disease, in a new model of type 2 diabetes. Methods and results Male Wistar rats were fed a high-fat diet for three weeks, with a single intraperitoneal injection of low dose streptozotocin (STZ) after fourteen days at 15, 20, 25 or 30 mg/kg body weight. Compared with chow-fed or high-fat diet fed control rats, a high-fat diet in combination with doses of 15–25 mg/kg STZ did not change insulin concentrations and rats maintained body weight. In contrast, 30 mg/kg STZ induced hypoinsulinaemia, hyperketonaemia and weight loss. There was a dose-dependent increase in blood glucose and plasma lipids with increasing concentrations of STZ. Cardiac and hepatic triglycerides were increased by all doses of STZ, in contrast, cardiac glycogen concentrations increased in a dose-dependent manner with increasing STZ concentrations. Cardiac glucose transporter 4 protein levels were decreased, whereas fatty acid metabolism-regulated proteins, including uncoupling protein 3 and pyruvate dehydrogenase (PDH) kinase 4, were increased with increasing doses of STZ. Cardiac PDH activity displayed a dose-dependent relationship between enzyme activity and STZ concentration. Cardiac insulin-stimulated glycolytic rates were decreased by 17% in 15 mg/kg STZ high-fat fed diabetic rats compared with control rats, with no effect on cardiac contractile function. Conclusions High-fat feeding in combination with a low dose of STZ induced cardiac metabolic changes that mirror the decrease in glucose metabolism and increase in fat metabolism in diabetic patients. While low doses of 15–25 mg/kg STZ induced a type 2 diabetic phenotype, higher doses more closely recapitulated type 1 diabetes, demonstrating that the severity of diabetes can be modified according to the requirements of the study. PMID:24063408

  18. Short-term effects of vanadate treatment in diabetic rats

    SciTech Connect

    Oster, M.H.; Llobet, J.M.; Domingo, J.L.; Keen, C.L. (Univ. of California, Davis (United States) Univ. of Barcelona (Spain))

    1991-03-11

    Based on findings that vanadium (V) can produce normoglycemia in diabetic rats, V has been proposed as a treatment for diabetics. However, since V is a strong prooxidant, its potential toxicity needs to be evaluated prior to human trials. STZ-induced diabetic (Diab) rats were given one of four water treatments: saline (S), or 0.12, 0.25, or 0.49 mM NaVO3 (V) in 80mM NaCl for one month. Six V rats, 2 from each group, died prior to one month. All V rats had lower plasma glucose and lower food and fluid intake compared to S rats. S rats had higher kidney Cu levels compared to V rats. RBC SOD activity decreased as the level of V increased. Liver TBAR production was evaluated with (+) and without (-) the addition of Fe. While homogenate -Fe TBARS were higher in the 0.12 V group compared to the S and 0.60 V groups, mitochondrial and microsomal -Fe TBARS were unaffected by V treatment. In the presence of Fe, homogenate and mitochondrial TBARS were higher in the 0.12 V group compared to other groups. Microsomal +Fe TBARS were similar among groups. To summarize, low levels of V may have a protective effect on membrane composition, possibly by altering PUFA content. However, higher levels of V may induce peroxidation causing conjugated diene formation which may alter membrane structure and function. Thus, V may have both prooxidant and antioxidant activity which depends on the V level, membrane integrity, and physiological state.

  19. Myocardial impulse propagation is impaired in right ventricular tissue of Zucker Diabetic Fatty (ZDF) rats

    PubMed Central

    2013-01-01

    Background Diabetes increases the risk of cardiovascular complications including arrhythmias, but the underlying mechanisms remain to be established. Decreased conduction velocity (CV), which is an independent risk factor for re-entry arrhythmias, is present in models with streptozotocin (STZ) induced type 1 diabetes. Whether CV is also disturbed in models of type 2 diabetes is currently unknown. Methods We used Zucker Diabetic Fatty (ZDF) rats, as a model of type 2 diabetes, and their lean controls Zucker Diabetic Lean (ZDL) rats to investigate CV and its response to the anti-arrhythmic peptide analogue AAP10. Gap junction remodeling was examined by immunofluorescence and western blotting. Cardiac histomorphometry was examined by Masson`s Trichrome staining and intracellular lipid accumulation was analyzed by Bodipy staining. Results CV was significantly slower in ZDF rats (56±1.9 cm/s) compared to non-diabetic controls (ZDL, 66±1.6 cm/s), but AAP10 did not affect CV in either group. The total amount of Connexin43 (C×43) was identical between ZDF and ZDL rats, but the amount of lateralized C×43 was significantly increased in ZDF rats (42±12 %) compared to ZDL rats (30±8%), p<0.04. Judged by electrophoretic mobility, C×43 phosphorylation was unchanged between ZDF and ZDL rats. Also, no differences in cardiomyocyte size or histomorphometry including fibrosis were observed between groups, but the volume of intracellular lipid droplets was 4.2 times higher in ZDF compared to ZDL rats (p<0.01). Conclusion CV is reduced in type 2 diabetic ZDF rats. The CV disturbance may be partly explained by increased lateralization of C×43, but other factors are likely also involved. Our data indicates that lipotoxicity potentially may play a role in development of conduction disturbances and arrhythmias in type 2 diabetes. PMID:23327647

  20. Achillea Millefolium L. Hydro- Alcoholic Extract Protects Pancreatic Cells by Down Regulating IL- 1? and iNOS Gene Expression in Diabetic Rats

    PubMed Central

    Zolghadri, Yalda; Fazeli, Mehdi; Kooshki, Marzieh; Shomali, Tahoora; Karimaghayee, Negar; Dehghani, Maryam

    2014-01-01

    Interleukin-1? (IL-1?) has a role in ?- cell destruction in autoimmune diabetes by stimulating the expression of inducible nitric oxide synthase (iNOS) that generates the free radical nitric oxide. We aimed to investigate the effect of Achillea millefolium L, as a traditional hypoglycemic agent, on IL-1? and iNOS gene expression of pancreatic tissue in the STZ- induced diabetic rats. Forty adult male Wistar rats were randomly divided into four groups: 1. diabetic control; 2. diabetic rats treated with Achillea millefolium L. extract; 3. normal rats received only extract and 4. negative control (n= 10 each). Diabetes was induced by single i.p. injection of 45 mg/ kg streptozotocin (STZ). Rats in groups 2 and 3 were treated with i.p. injection of Achillea millefolium L. extract (100 mg/ kg/ day) for 14 days. Body weight, serum glucose and insulin levels were assayed at baseline and on days 3, 7, 10 and 14 of the experiment. Finally, the quantity of pancreatic IL-1? and iNOS mRNA was determined by real- time PCR. The mRNA expression level of IL-1? and iNOS genes, was significantly (p<0.001) increased in diabetic rats of group 1. Treatment with Achillea millefolium L. caused a significant (p<0.01) reduction in both IL-1? and iNOS genes expression. Moreover, rats in group 2 had higher insulin level associated with lower glucose level and higher body weight compared to control diabetic group. It seems that beneficial effect of Achillea millefolium L. on STZ- induced diabetes is at least partly due to amelioration of IL-1? and iNOS gene over expression which can have a ?-cell protective effect. PMID:25635252

  1. Achillea Millefolium L. Hydro- Alcoholic Extract Protects Pancreatic Cells by Down Regulating IL- 1? and iNOS Gene Expression in Diabetic Rats.

    PubMed

    Zolghadri, Yalda; Fazeli, Mehdi; Kooshki, Marzieh; Shomali, Tahoora; Karimaghayee, Negar; Dehghani, Maryam

    2014-01-01

    Interleukin-1? (IL-1?) has a role in ?- cell destruction in autoimmune diabetes by stimulating the expression of inducible nitric oxide synthase (iNOS) that generates the free radical nitric oxide. We aimed to investigate the effect of Achillea millefolium L, as a traditional hypoglycemic agent, on IL-1? and iNOS gene expression of pancreatic tissue in the STZ- induced diabetic rats. Forty adult male Wistar rats were randomly divided into four groups: 1. diabetic control; 2. diabetic rats treated with Achillea millefolium L. extract; 3. normal rats received only extract and 4. negative control (n= 10 each). Diabetes was induced by single i.p. injection of 45 mg/ kg streptozotocin (STZ). Rats in groups 2 and 3 were treated with i.p. injection of Achillea millefolium L. extract (100 mg/ kg/ day) for 14 days. Body weight, serum glucose and insulin levels were assayed at baseline and on days 3, 7, 10 and 14 of the experiment. Finally, the quantity of pancreatic IL-1? and iNOS mRNA was determined by real- time PCR. The mRNA expression level of IL-1? and iNOS genes, was significantly (p<0.001) increased in diabetic rats of group 1. Treatment with Achillea millefolium L. caused a significant (p<0.01) reduction in both IL-1? and iNOS genes expression. Moreover, rats in group 2 had higher insulin level associated with lower glucose level and higher body weight compared to control diabetic group. It seems that beneficial effect of Achillea millefolium L. on STZ- induced diabetes is at least partly due to amelioration of IL-1? and iNOS gene over expression which can have a ?-cell protective effect. PMID:25635252

  2. Mangiferin from Salacia chinensis prevents oxidative stress and protects pancreatic ?-cells in streptozotocin-induced diabetic rats.

    PubMed

    Sellamuthu, Periyar Selvam; Arulselvan, Palanisamy; Muniappan, Balu Periamallipatti; Fakurazi, Sharida; Kandasamy, Murugesan

    2013-08-01

    Oxidative stress in diabetic tissues is a consequence of free radical accumulation with concurrently impaired natural antioxidants status and results in oxidative tissue damage. The present study investigated the protective effects of mangiferin against pancreatic ?-cell damage and on the antioxidant defense systems in streptozotocin (STZ)-induced diabetic rats. Diabetes was experimentally induced by a single intraperitoneal injection of STZ. Oxidative stress biomarkers such as tissue malondialdehyde, hydroperoxides, reduced glutathione (GSH) content, and nonenzymatic antioxidants were measured. Biochemical observations were further substantiated with histological examination and ultrastructural studies in the pancreas of diabetic, glibenclamide and mangiferin-treated diabetic rats (dosage of 40 mg/kg body weight daily for 30 days). Oral administration of mangiferin and glibenclamide to diabetic rats significantly decreased the level of blood glucose and increased levels of insulin. Additionally, mangiferin treatment significantly modulated the pancreatic nonenzymatic antioxidants status (vitamin C, vitamin E, ceruloplasmin, and reduced GSH content) and other oxidative stress biomarkers. The histoarchitecture of diabetic rats showed degenerated pancreas with lower ?-cell counts, but mangiferin treatment effectively regenerated insulin secreting islet cells. The electron microscopic study revealed damaged nuclear envelope and mitochondria and fewer secretory granules in pancreas of diabetic rats; however, mangiferin treatment nearly normalized pancreatic architecture. The present findings suggest that mangiferin treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and protecting against pancreatic ?-cell damage, which may be attributable to its antioxidative properties. PMID:23957355

  3. Time-Course Effect of Electrical Stimulation on Nerve Regeneration of Diabetic Rats

    PubMed Central

    Lin, Yu-Ching; Kao, Chia-Hong; Chen, Chung-Chia; Ke, Cherng-Jyh; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2015-01-01

    Background Electrical stimulation (ES) has been shown to promote nerve regeneration in rats with experimental diabetes induced using streptozotocin (STZ). However, the time-course effect of ES on nerve regeneration of diabetic animals has not been reported in previous studies. The present study attempted to examine the effect of different timing of ES after peripheral nerve transection in diabetic rats. Methodology/Findings Fifty Sprague-Dawley rats were used in the study. They were classified into five groups. STZ-induced diabetes was created in groups A to D. Normal animals in group E were used as the non-diabetic controls. The sciatic nerve was transected and repaired using a silicone rubber conduit across a 10-mm gap in all groups. Groups A to C received ES for 15 minutes every other day for 2 weeks. Stimulation was initiated on day 1 following the nerve repair for group A, day 8 for group B, and day 15 for group C. The diabetic control group D and the normal control group E received no ES. At 30 days after surgery in group A, histological evaluations showed a higher success percentage of regeneration across the 10-mm nerve gap, and the electrophysiological results showed significantly larger mean values of evoked muscle action potential area and amplitude of the reinnervated gastrocnemius muscle compared with group D. Conclusions/Significance It is concluded that an immediate onset of ES may improve the functional recovery of large nerve defect in diabetic animals. PMID:25689049

  4. Berberine Ameliorates Cold and Mechanical Allodynia in a Rat Model of Diabetic Neuropathy

    PubMed Central

    Kim, Si Oh

    2013-01-01

    Abstract This study evaluated the antiallodynic properties of berberine on cold and mechanical allodynia after streptozotocin (STZ)-induced diabetes using a rat model. Diabetic neuropathy was induced in rats by intraperitoneal injection of STZ. To measure cold and mechanical allodynia, a 4°C plate and von Frey filament were used, respectively. Cold and mechanical allodynia induced by diabetes were significantly decreased by single and repeated intraperitoneal treatment of amitriptyline at 10?mg/kg, and berberine at 10 and 20?mg/kg. The hepatic malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase activities were significantly increased in diabetic rats as compared with those in intact rats; however, in amitriptyline- and berberine-treated rats, they were significantly decreased as compared to the STZ control. The overall effects of berberine 20?mg/kg on cold and mechanical allodynia were quite similar to those of amitriptyline 10?mg/kg, and berberine exhibited similar antioxidant effects as the same dosage of amitriptyline. In conclusion, berberine (10 and 20?mg/kg) was observed to have antiallodynic effects against diabetes, which are presumed to be associated with antioxidative effects. It can be considered that the anti-inflammatory or antidepressant capacity of berberine could contribute to the antiallonynic effects shown in this study. PMID:23734996

  5. Hypoglycemic activity of Cassia javanica Linn. in normal and streptozotocin-induced diabetic rats

    PubMed Central

    Kumavat, Urmila C.; Shimpi, Shraddha N.; Jagdale, Sandesh P.

    2012-01-01

    In present work, one of the ornamentals and medicinally less known plant Cassia javanica has been explored for hypoglycemic potential. It aimed to check the hypoglycemic effect of C. javanica leaves on normal and streptozotocin (STZ)-induced diabetic rats by acute and sub-acute studies. Prior to the hypoglycemic study, acute oral toxicity testing of drug was performed. Later, the effects of single and multiple doses of test drug were studied using various parameters. Dried powdered leaf material was used as an oral drug. The preliminary phytochemistry of drug was done by standard qualitative tests. Diabetes was induced in rats by single intraperitoneal injection of STZ. Single and multiple doses of test drug (0.5 g/kg body weight/day) were given to normal and diabetic rats. The parameters studied were blood glucose, serum cholesterol, serum triglycerides, and serum proteins. The results of test drug were compared with standard hypoglycemic drug-glibenclamide (0.01 g/kg/day). Statistical analysis was done by ‘Student's ‘t’ test’ and one way ANOVA test. In preliminary phytochemistry, antidiabetic compounds were detected. Unlike acute, subacute treatment of test drug showed highly significant reduction (37.62%) in blood glucose level of diabetic rats in ten days. This effect was considerably good in comparison with standard drug (63.51%). The test drug and standard drug exhibited insignificant change in the abnormal levels of serum metabolites of diabetic rats. Preclinically, C. javanica was proved to be effective hypoglycemic agent. PMID:22470893

  6. Neuroprotective potential of sesamol and its loaded solid lipid nanoparticles in ICV-STZ-induced cognitive deficits: behavioral and biochemical evidence.

    PubMed

    Sachdeva, Anand Kamal; Misra, Shubham; Pal Kaur, Indu; Chopra, Kanwaljit

    2015-01-15

    Neuroinflammation is a prominent feature of Alzheimer disease (AD) and other chronic neurodegenerative disorders. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental paradigm of Alzheimer?s disease. Sesamol is a potent inhibitor of cytokine production as well as an antioxidant. The present study was designed to evaluate the effectiveness of sesamol in ICV-STZ-induced cognitive deficits in rats by incorporating it into solid lipid nanoparticles (SLNs). ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced nitrodative stress, altered acetylcholinesterase in rat brain along with significantly increased serum TNF-? levels. Chronic treatment with sesamol and sesamol loaded SLNs dose dependently restored cognitive deficits in ICV-STZ rats along with mitigation of nitrodative stress and cytokine release. Effectiveness of SLNs to deliver sesamol to the brain was shown by a significantly better alleviation of the oxidative stress parameters. Our findings demonstrate that loading of sesamol in SLNs is an effective strategy to mitigate ICV-STZ-induced neuronal dysfunction and memory deficits. PMID:25449035

  7. Role of naringenin in protection against diabetic hyperalgesia and tactile allodynia in male Wistar rats.

    PubMed

    Hasanein, Parisa; Fazeli, Farzaneh

    2014-12-01

    Hyperalgesia and allodynia are among the common manifestations of painful diabetic neuropathy. Naringenin (NA) has some biological activities, including anti-inflammatory, analgesic, and antidiabetic effects. We investigated the effects of NA administration at different doses, 20, 50, and 100 mg/kg, on streptozotocin (STZ)-induced hyperalgesia and allodynia in rats. The animals received saline or NA (20, 50, and 100 mg/kg, p.o.; once daily) for 8 weeks. Hyperalgesia was assessed by tail flick (TF) and formalin tests. Von Frey filaments were used for tactile allodynia evaluation. At the end, all rats were weighed and underwent plasma glucose and superoxide dismutase measurement. Diabetes caused significant hyperalgesia and allodynia during the above tests. NA 50 and 100 mg/kg reversed chemical and thermal hyperalgesia in diabetic rats. There were no significant differences in pain responses between NA (50 and 100 mg/kg)-treated diabetic rats and pregabalin-treated diabetic animals. Administration of NA 20 mg/kg did not alter pain-related behaviors in control and diabetic groups compared to the respective control ones. NA 50 and 100 mg/kg restored hyperglycemia as well as the decreased levels of (superoxide dismutase) SOD activity in diabetic rats. The body weight of treated diabetic rats increased significantly compared to untreated diabetics. Prolonged oral administration of NA (50 and 100 mg/kg) ameliorated some aspects of diabetic neuropathy by causing hypoglycemia and increasing the levels of antioxidant enzyme SOD. Therefore, NA makes a good candidate for treatment of diabetic neuropathy in clinical studies. PMID:25407136

  8. Hepatoprotective effects of melatonin against pronecrotic cellular events in streptozotocin-induced diabetic rats.

    PubMed

    Grigorov, Ilijana; Bogojevi?, Desanka; Jovanovi?, Sofija; Petrovi?, Anja; Ivanovi?-Mati?, Svetlana; Zolotarevski, Lidija; Poznanovi?, Goran; Martinovi?, Vesna

    2014-06-01

    Oxidative stress-mediated damage to liver tissue underlies the pathological alterations in liver morphology and function that are observed in diabetes. We examined the effects of the antioxidant action of melatonin against necrosis-inducing DNA damage in hepatocytes of streptozotocin (STZ)-induced diabetic rats. Daily administration of melatonin (0.2 mg/kg) was initiated 3 days before diabetes induction and maintained for 4 weeks. Melatonin-treated diabetic rats exhibited improved markers of liver injury (P?diabetes-related morphological deterioration of hepatocytes, DNA damage (P?diabetes-induced rise in lipid peroxidation and hydrogen peroxide increase in the liver. This was accompanied by improved necrotic markers of cellular damage: a significant reduction in cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1) into necrotic 55- and 62-kDa fragments, and inhibition of nucleus-to-cytoplasm translocation and accumulation in the serum of the high-mobility group box 1 (HMGB1) protein. We conclude that melatonin is hepatoprotective in diabetes. It reduces extensive DNA damage and resulting necrotic processes. Melatonin application could thus present a viable therapeutic option in the management of diabetes-induced liver injury. PMID:24604251

  9. The afterload-dependent peak efficiency of the isolated working rat heart is unaffected by streptozotocin-induced diabetes

    PubMed Central

    2014-01-01

    Background Diabetes is known to alter the energy metabolism of the heart. Thus, it may be expected to affect the efficiency of contraction (i.e., the ratio of mechanical work output to metabolic energy input). The literature on the subject is conflicting. The majority of studies have reported a reduction of myocardial efficiency of the diabetic heart, yet a number of studies have returned a null effect. We propose that these discrepant findings can be reconciled by examining the dependence of myocardial efficiency on afterload. Methods We performed experiments on streptozotocin?(STZ)-induced diabetic rats (7-8 weeks post-induction), subjecting their (isolated) hearts to a wide range of afterloads (40 mmHg to maximal, where aortic flow approached zero). We measured work output and oxygen consumption, and their suitably scaled ratio (i.e., myocardial efficiency). Results We found that myocardial efficiency is a complex function of afterload: its value peaks in the mid-range and decreases on either side. Diabetes reduced the maximal afterload to which the hearts could pump (105 mmHg versus 150 mmHg). Thus, at high afterloads (for example, 90 mmHg), the efficiency of the STZ heart was lower than that of the healthy heart (10.4% versus 14.5%) due to its decreased work output. Diabetes also reduced the afterload at which peak efficiency occurred (optimal afterload: 63 mmHg versus 83 mmHg). Despite these negative effects, the peak value of myocardial efficiency (14.7%) was unaffected by diabetes. Conclusions Diabetes reduces the ability of the heart to pump at high afterloads and, consequently, reduces the afterload at which peak efficiency occurs. However, the peak efficiency of the isolated working rat heart remains unaffected by STZ-induced diabetes. PMID:24387738

  10. Modulatory effects of l-arginine and soy enriched diet on bone homeostasis abnormalities in streptozotocin-induced diabetic rats.

    PubMed

    El-Maraghy, Shohda A; Mehana, Noha Ali

    2015-03-01

    Diabetes mellitus is a complex syndrome which is responsible for numerous complications affecting the whole body. Osteoporosis is regarded as one of the chronic complications of diabetes mellitus that results from reduced bone formation and increased resorption. In this context, we searched for dietary supplements that preserve diabetic bone loss. Parathyroid hormone (PTH) has been suggested as a possible mechanism affecting bone homeostasis in streptozotocin (STZ)-induced diabetic rats. The osteoprotective effects of l-arginine and soy enriched diet were also investigated. Male Wistar rats were allocated into four groups; normal control, untreated STZ-diabetic rats and STZ-diabetic rats treated with either l-arginine (10mg/kg/day) or fed soy enriched diet (200g/kg diet) for 12weeks. l-Arginine and soy enriched diet normalized serum PTH level and increased serum osteocalcin level; bone osteocalcin, osteoprotegerin and runt-related transcription factor2 mRNA levels compared to diabetic rats. A decrease in serum pyridinoline, C-terminal telopeptides of type I collagen, cathepsin k levels and bone cathepsin k mRNA level was observed in both treated groups. Both treatments increased serum insulin and insulin like growth factor-1 levels and decreased urinary calcium excretion. In conclusion, l-arginine and soy enriched diet are effective in prevention of osteoporosis associated with diabetes mellitus. PMID:25617479

  11. Puerarin attenuated early diabetic kidney injury through down-regulation of matrix metalloproteinase 9 in streptozotocin-induced diabetic rats.

    PubMed

    Zhong, Yifei; Zhang, Xianwen; Cai, Xianfan; Wang, Ke; Chen, Yiping; Deng, Yueyi

    2014-01-01

    Radix puerariae, a traditional Chinese herbal medication, has been used successfully to treat patients with early stage of diabetic nephropathy. However, the underlined mechanism of this renal protective effect has not been determined. In the current study, we investigated the effects and the mechanism of puerarin in Streptozotocin (STZ)-induced diabetic rats. We treated STZ-rats with either puerarin or losartan, an angiotensin II receptor blocker, as compared to those treated with vehicle. We found that both puerarin and losartan attenuated kidney hypertrophy, mesangial expansion, proteinuria, and podocyte foot process effacement in STZ rats. In addition, both puerarin and losartan increased expression of podocyte slit diaphragm proteins such as nephrin and podocin. Interestingly, we found that puerarin treatment induced a more pronounced suppression of oxidative stress production and S-nitrosylation of proteins in the diabetic kidneys as compared to losartan treatment. Furthermore, we found that matrix metalloproteinase-9 (MMP-9), which is known to be activated by oxidative stress and S-nitrosylation of proteins, was also suppressed more extensively by puerarin than losartan. In conclusion, these data provide for the first time the potential mechanism to support the use of puerarin in the treatment of early diabetic nephropathy. PMID:24454919

  12. Puerarin Attenuated Early Diabetic Kidney Injury through Down-Regulation of Matrix Metalloproteinase 9 in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Zhong, Yifei; Zhang, Xianwen; Cai, Xianfan; Wang, Ke; Chen, Yiping; Deng, Yueyi

    2014-01-01

    Radix puerariae, a traditional Chinese herbal medication, has been used successfully to treat patients with early stage of diabetic nephropathy. However, the underlined mechanism of this renal protective effect has not been determined. In the current study, we investigated the effects and the mechanism of puerarin in Streptozotocin (STZ)-induced diabetic rats. We treated STZ-rats with either puerarin or losartan, an angiotensin II receptor blocker, as compared to those treated with vehicle. We found that both puerarin and losartan attenuated kidney hypertrophy, mesangial expansion, proteinuria, and podocyte foot process effacement in STZ rats. In addition, both puerarin and losartan increased expression of podocyte slit diaphragm proteins such as nephrin and podocin. Interestingly, we found that puerarin treatment induced a more pronounced suppression of oxidative stress production and S-nitrosylation of proteins in the diabetic kidneys as compared to losartan treatment. Furthermore, we found that matrix metalloproteinase-9 (MMP-9), which is known to be activated by oxidative stress and S-nitrosylation of proteins, was also suppressed more extensively by puerarin than losartan. In conclusion, these data provide for the first time the potential mechanism to support the use of puerarin in the treatment of early diabetic nephropathy. PMID:24454919

  13. Trans-anethole, a terpenoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats.

    PubMed

    Sheikh, Bashir Ahmad; Pari, Leelavinothan; Rathinam, Ayyasamy; Chandramohan, Ramasamy

    2015-05-01

    Trans-anethole (TA), a terpenoid and a principle constituent of many essential oils from medicinal plants possess hypoglycemic and antioxidant activities. This study was undertaken to explore beneficial effects of TA on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced type 2 diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg BW). TA was administered to diabetic rats at a dose of 20, 40 and 80 mg/kg BW for 45 days. However, the dose at 80 mg/kg BW, resulted in a significant reduction in the levels of plasma glucose, glycosylated haemoglobin (HbA1c) and increase in the levels of insulin and haemoglobin (Hb). Upon administration of TA, the altered levels of liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase) and gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) in the liver and kidney of diabetic rats significantly reverted to near normal levels. In addition to this, TA also improved the hepatic and muscle glycogen content in diabetic rats. The histological studies showed the ameliorative effect of TA on the ?-cells of pancreas in diabetic rats. The results were compared with glibenclamide, a standard oral hypoglycemic drug. These encouraging findings suggest that TA may be used as a propitious bioactive compound in the development of therapeutic agents against type 2 diabetes mellitus. PMID:25708856

  14. Antidiabetic effect of Punica granatum flowers: Effect on hyperlipidemia, pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes

    Microsoft Academic Search

    Priyanka Bagri; Mohd. Ali; Vidhu Aeri; Malay Bhowmik; Shahnaz Sultana

    2009-01-01

    The present study investigated the effects of Punica granatum aqueous extract (PgAq) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, lipid profiles (atherogenic index), lipid peroxidation (LPO) and activities of both non-enzymatic and enzymatic antioxidants. Diabetes was induced by single intraperitoneal injection of STZ (60mg\\/kg) to albino Wistar rats. The increase in blood glucose level, total cholesterol

  15. Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-?B-mediated inflammatory genes expression.

    PubMed

    Gui, Dingkun; Huang, Jianhua; Guo, Yongping; Chen, Jianguo; Chen, Yifang; Xiao, Wenzhen; Liu, Xusheng; Wang, Niansong

    2013-03-01

    Accumulating evidence suggests that inflammatory processes are involved in the development of diabetic nephropathy (DN). However, there are no effective interventions for inflammation in the diabetic kidneys. Here, we tested the hypothesis that Astragaloside IV(AS-IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bge, ameliorates DN in streptozotocin (STZ)-induced diabetic rats through anti-inflammatory mechanisms. Diabetes was induced with STZ (65 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats were divided into three groups (n=8/each group), namely, diabetic rats, diabetic rats treated with AS-IV at 5 and 10 mgkg(-1)d(-1), p.o., for 8 weeks. The normal rats were chosen as nondiabetic control group (n=8). The rats were sacrificed 10 weeks after induction of diabetes. AS-IV ameliorated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. Renal NF-?B activity, as wells as protein and mRNA expression were increased in diabetic kidneys, accompanied by an increase in mRNA expression and protein content of TNF-?, MCP-1 and ICAM-1 in kidney tissues. The ?1-chain type IV collagen mRNA was elevated in the kidneys of diabetic rats. All of these abnormalities were partially restored by AS-IV. AS-IV also decreased the serum levels of TNF-?, MCP-1 and ICAM-1 in diabetic rats. These findings suggest that AS-IV, a novel anti-inflammatory agent, attenuated DN in rats through inhibiting NF-?B mediated inflammatory genes expression. PMID:23434274

  16. Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes

    SciTech Connect

    Lohr, J.; Mazurchuk, R.J.; Acara, M.A.; Nickerson, P.A.; Fiel, R.J. (State Univ. of New York, Buffalo (USA))

    1991-01-01

    Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.

  17. C-peptide preserves the renal microvascular architecture in the streptozotocin-induced diabetic rat

    PubMed Central

    Flynn, Elizabeth R.; Lee, Jonathan; Hutchens, Zachary M.; Chade, Alejandro R.; Maric-Bilkan, Christine

    2013-01-01

    Aims C-peptide is renoprotective in type 1 diabetes, however, the mechanisms of its actions are not completely understood. We hypothesized that C-peptide attenuates diabetes-associated renal microvascular injury. Method After 4 or 8 weeks of streptozotocin (STZ)-induced diabetes, rats received either vehicle or C-peptide in the presence of low or high doses of insulin. Urine albumin excretion (UAE) was measured prior to initiation of treatment (baseline) and 2 or 4 weeks after treatment (sacrifice). Glomerular hypertrophy, glomerular filtration rate (GFR) and renal microvascular density, quantified ex vivo by 3D micro-CT reconstruction, were measured at sacrifice. Results In rats receiving low doses of insulin, treatment with C-peptide reduced HbA1c levels by 24%. In these rats, the 107% increase in UAE rate from baseline to sacrifice in vehicle-treated rats was largely prevented with C-peptide. C-peptide also reduced diabetes-associated glomerular hyperfiltration by 30%, glomerular hypertrophy by 22% and increased the density of microvessels between 0–500 ?m in diameter by an average of 31% compared with vehicle-treated groups. Similar renoprotective effects of C-peptide were observed in rats treated with higher doses of daily insulin, despite no differences in HbA1c levels. Conclusions The study suggests that C-peptide is renoprotective by preserving the integrity of the renal microvasculature irrespective of glucose regulation. PMID:23994433

  18. Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy

    PubMed Central

    LI, YANG-JUN; ZHANG, JIE; HAN, JING; DU, ZHAO-JIANG; WANG, PING; GUO, YONG

    2015-01-01

    This study used a streptozotocin (STZ)-induced rat model of diabetes to investigate whether Ras-related C3 botulinum toxin substrate 1 (Rac1) was involved in the pathogenesis of diabetic retinopathy. The effects of Rac1 inhibition on vascular endothelial (VE)-cadherin and ?-catenin expression in high glucose-induced rat retinal endothelial cells (RRECs) were additionally examined. Rac1 activation in the retinas from STZ-induced diabetic rats and in high glucose-induced RRECs was measured by reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. The expression levels of VE-cadherin and ?-catenin were also examined with or without Rac1 inhibition through small interfering (si)RNA transfection. STZ-induced diabetes was associated with an increase in the vascular permeability of the retina. Furthermore, Rac1 activation was increased in the retina of STZ-induced diabetic rats and in high glucose-induced RRECs compared with that in the controls. Immunohistochemistry showed that immunostaining of Rac1 was localized in the outer plexiform, inner nuclear, inner plexiform and ganglion cell layers and in the retinal microvasculature of rats. The expression of ?-catenin was increased in the retinas of the diabetic rats at four, eight and 12 weeks after the induction of diabetes compared with that in the controls. Additionally, Rac1 activation was required for the high glucose-induced VE-cadherin expression decrease and for ?-catenin expression in high glucose-induced RRECs. Rac1 inhibition by Rac1-siRNA transfection effectively prevented hyperpermeability, ?-catenin expression and the VE-cadherin expression decrease in high glucose-induced RRECs. In conclusion, diabetes affects the expression of Rac1 in the retina. Rac1 may be involved in the diabetes-induced damage and/or alterations to the blood-retinal barrier through changes in VE-cadherin and ?-catenin expression. PMID:25452781

  19. Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy.

    PubMed

    Li, Yang-Jun; Zhang, Jie; Han, Jing; DU, Zhao-Jiang; Wang, Ping; Guo, Yong

    2015-01-01

    This study used a streptozotocin (STZ)-induced rat model of diabetes to investigate whether Ras-related C3 botulinum toxin substrate 1 (Rac1) was involved in the pathogenesis of diabetic retinopathy. The effects of Rac1 inhibition on vascular endothelial (VE)-cadherin and ?-catenin expression in high glucose-induced rat retinal endothelial cells (RRECs) were additionally examined. Rac1 activation in the retinas from STZ-induced diabetic rats and in high glucose-induced RRECs was measured by reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. The expression levels of VE-cadherin and ?-catenin were also examined with or without Rac1 inhibition through small interfering (si)RNA transfection. STZ-induced diabetes was associated with an increase in the vascular permeability of the retina. Furthermore, Rac1 activation was increased in the retina of STZ-induced diabetic rats and in high glucose-induced RRECs compared with that in the controls. Immunohistochemistry showed that immunostaining of Rac1 was localized in the outer plexiform, inner nuclear, inner plexiform and ganglion cell layers and in the retinal microvasculature of rats. The expression of ?-catenin was increased in the retinas of the diabetic rats at four, eight and 12 weeks after the induction of diabetes compared with that in the controls. Additionally, Rac1 activation was required for the high glucose-induced VE-cadherin expression decrease and for ?-catenin expression in high glucose-induced RRECs. Rac1 inhibition by Rac1-siRNA transfection effectively prevented hyperpermeability, ?-catenin expression and the VE-cadherin expression decrease in high glucose-induced RRECs. In conclusion, diabetes affects the expression of Rac1 in the retina. Rac1 may be involved in the diabetes-induced damage and/or alterations to the blood-retinal barrier through changes in VE-cadherin and ?-catenin expression. PMID:25452781

  20. Protective effects of Salvia miltiorrhiza injection against learning and memory impairments in streptozotocin-induced diabetic rats

    PubMed Central

    CAI, HUABO; LIAN, LUYA; WANG, YU; YU, YUANYUAN; LIU, WEI

    2014-01-01

    The aim of this study was to explore the protective effects of Salvia miltiorrhiza injection against learning and memory impairment in streptozotocin (STZ)-induced diabetic rats and the possible mechanism involved. Sprague Dawley male rats (n=30) were randomized into three groups: Diabetes, diabetes treated with S. miltiorrhiza injection and normal control. Diabetes was induced by an intraperitoneal injection of STZ (65 mg/kg). The S. miltiorrhiza injection-treated rats received an intraperitoneal injection of S. miltiorrhiza (5 ml/kg/day) while the rats of the other two groups were administered an intraperitoneal injection of the same volume of 0.9% saline for four weeks. After four weeks of treatment, the escape latency and search strategies in the rats were assessed by the Morris water maze test. The protein levels of mitogen-activated protein kinase phosphatase-1 (MKP-1) were also assessed by immunohistochemistry. Four weeks after the induction of diabetes, the body weight of the diabetic rats was significantly lower and the blood glucose concentration was significantly higher than that of the control rats. S. miltiorrhiza injection was observed to improve the blood glucose and learning ability (P<0.05). Compared with the control group, the expression of MKP-1 was significantly decreased in the hippocampal area of the diabetes group; S. miltiorrhiza injection-treated rats showed an increased expression compared with the diabetic rats, but the expression remained lower than that of the normal control group (P<0.05). In conclusion, S. miltiorrhiza injection can improve the learning and memory decline of diabetic rats. The changes in expression of MKP-1 under hyperglycemia may play a role in the protective effects of S. miltiorrhiza against dementia in diabetic rats. PMID:25187809

  1. Bixin and norbixin have opposite effects on glycemia, lipidemia, and oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Roehrs, Miguel; Figueiredo, Cassieli Gehlen; Zanchi, Mariane Magalhães; Bochi, Guilherme Vargas; Moresco, Rafael Noal; Quatrin, Andréia; Somacal, Sabrina; Conte, Lisiane; Emanuelli, Tatiana

    2014-01-01

    The present study investigated the effects of oral administration of annatto carotenoids (bixin (BIX) and norbixin (NBIX)) on glucose levels, lipid profiles, and oxidative stress parameters in streptozotocin (STZ)-induced diabetic rats. Animals were treated for 30 days in the following groups: nondiabetic control, diabetic vehicle, diabetic 10?mg/kg BIX, diabetic 100?mg/kg BIX, diabetic 10?mg/kg NBIX, diabetic 100?mg/kg NBIX, diabetic metformin, and diabetic insulin. Blood glucose, LDL cholesterol, and triglyceride levels were reduced in the diabetic rats treated with BIX. BIX treatment prevented protein oxidation and nitric oxide production and restored superoxide dismutase activity. NBIX treatment did not change most parameters assessed, and at the highest dose, it increased LDL cholesterol and triglycerides levels and showed prooxidant action (increased protein oxidation and nitric oxide levels). These findings suggested that BIX could have an antihyperglycemic effect, improve lipid profiles, and protect against damage induced by oxidative stress in the diabetic state. Because NBIX is a water-soluble analog of BIX, we propose that lipophilicity is crucial for the protective effect of annatto carotenoids against streptozotocin-induced diabetes. PMID:24624139

  2. Bixin and Norbixin Have Opposite Effects on Glycemia, Lipidemia, and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Zanchi, Mariane Magalhães; Bochi, Guilherme Vargas; Somacal, Sabrina

    2014-01-01

    The present study investigated the effects of oral administration of annatto carotenoids (bixin (BIX) and norbixin (NBIX)) on glucose levels, lipid profiles, and oxidative stress parameters in streptozotocin (STZ)-induced diabetic rats. Animals were treated for 30 days in the following groups: nondiabetic control, diabetic vehicle, diabetic 10?mg/kg BIX, diabetic 100?mg/kg BIX, diabetic 10?mg/kg NBIX, diabetic 100?mg/kg NBIX, diabetic metformin, and diabetic insulin. Blood glucose, LDL cholesterol, and triglyceride levels were reduced in the diabetic rats treated with BIX. BIX treatment prevented protein oxidation and nitric oxide production and restored superoxide dismutase activity. NBIX treatment did not change most parameters assessed, and at the highest dose, it increased LDL cholesterol and triglycerides levels and showed prooxidant action (increased protein oxidation and nitric oxide levels). These findings suggested that BIX could have an antihyperglycemic effect, improve lipid profiles, and protect against damage induced by oxidative stress in the diabetic state. Because NBIX is a water-soluble analog of BIX, we propose that lipophilicity is crucial for the protective effect of annatto carotenoids against streptozotocin-induced diabetes. PMID:24624139

  3. Protective Nature of Mangiferin on Oxidative Stress and Antioxidant Status in Tissues of Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Sellamuthu, Periyar Selvam; Arulselvan, Palanisamy; Kamalraj, Subban; Fakurazi, Sharida; Kandasamy, Murugesan

    2013-01-01

    Oxidative stress plays an important role in the progression of diabetes complications. The aim of the present study was to investigate the beneficial effect of oral administration of mangiferin in streptozotocin (STZ)-induced diabetic rats by measuring the oxidative indicators in liver and kidney as well as the ameliorative properties. Administration of mangiferin to diabetic rats significantly decreased blood glucose and increased plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were significantly (P < 0.05) decreased while increases in the levels of lipidperoxidation (LPO) markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with mangiferin (40?mg/kg?b.wt/day) for a period of 30 days showed significant ameliorative effects on all the biochemical and oxidative parameters studied. Diabetic rats treated with mangiferin restored almost normal architecture of liver and kidney tissues, which was confirmed by histopathological examination. These results indicated that mangiferin has potential ameliorative effects in addition to its antidiabetic effect in experimentally induced diabetic rats. PMID:24167738

  4. Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats

    PubMed Central

    2014-01-01

    Background Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats. Methods Type 1 diabetes mellitus was induced in Sprague–Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (N?-nitro-l-arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats. Results Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (l-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals. Conclusions CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals. PMID:24923878

  5. Protective effect of chemically modified SOD on lipid peroxidation and antioxidant status in diabetic rats.

    PubMed

    Mansuro?lu, Banu; Derman, Serap; Yaba, Aylin; K?z?lbey, Kadriye

    2015-01-01

    Reactive oxygen species mediated oxidative stress play an important role on the injury of tissue damage and increased attention has been focused on the role of free radicals in diabetes mellitus (DM). In the present study firstly superoxide dismutase (SOD) enzyme was chemically modified with two different polymer and physicochemical properties of these conjugates clearly analyzed. Then, the stability of carboxymethylcellulose-SOD (CMC-SOD) and poly methyl vinyl ether-co-maleic anhydride-SOD (PMVE/MA-SOD) conjugates was investigated against temperature and externally added H2O2. Moreover, we investigated the effect of chemically modified SOD enzyme on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetic rats. PMVE/MA-SOD conjugate treatment significantly reduced MDA level compared with the control groups, native and CMC-SOD conjugate treated groups in brain, kidney and liver tissue. GSH and SOD enzyme activity in diabetic groups was significantly increased by treatment of CMC-SOD and PMVE/MA-SOD conjugates. The protective effects on degenerative changes in diabetic rats were also further confirmed by histopathological examination. This study provides the preventative activity of SOD-polymer conjugates against complication of oxidative stress in experimentally induced diabetic rats. These results suggest that chemically modified SOD is effective on the oxidative stress-associated disease and offer a therapeutic advantage in clinical use. PMID:25124383

  6. Streptozotocin Diabetes Attenuates the Effects of Nondepolarizing Neuromuscular Relaxants on Rat Muscles

    PubMed Central

    Huang, Lina; Chen, Dan

    2014-01-01

    The hypothesis of this study was that diabetes-induced desensitization of rat soleus (SOL) and extensor digitorum longus (EDL) to non-depolarizing muscle relaxants (NDMRs) depends on the stage of diabetes and on the kind of NDMRs. We tested the different magnitude of resistance to vecuronium, cisatracurium, and rocuronium at different stages of streptozotocin (STZ)-induced diabetes by the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations from rats after 4 and 16 weeks of STZ treatment. The concentration-twitch tension curves were significantly shifted from those of the control group to the right in the diabetic groups. Concentration giving 50% of maximal inhibition (IC50) was larger in the diabetic groups for all the NDMRs. For rocuronium and cisatracurium in both SOL and EDL, IC50 was significantly larger in diabetic 16 weeks group than those in the diabetic 4 weeks group. For SOL/EDL, the IC50 ratios were significantly largest in the diabetic 16 weeks group, second largest in the diabetic 4 weeks group, and smallest for the control group. Diabetes-induced desensitization to NDMRs depended on the stage of diabetes and on the different kind of muscles observed while was independent on different kind of NDMRs. The resistance to NDMRs was stronger in the later stage of diabetes (16 versus 4 weeks after STZ treatment). Additionally, when monitoring in SOL, diabetes attenuated the actions of neuromuscular blockade more intensely than that in EDL. Nonetheless, the hyposensitivity to NDMRs in diabetes was not relevant for the kind of NDMRs. PMID:25598659

  7. The antidiabetic effect of low doses of Moringa oleifera Lam. seeds on streptozotocin induced diabetes and diabetic nephropathy in male rats.

    PubMed

    Al-Malki, Abdulrahman L; El Rabey, Haddad A

    2015-01-01

    The antidiabetic activity of two low doses of Moringa seed powder (50 and 100?mg/kg body weight, in the diet) on streptozotocin (STZ) induced diabetes male rats was investigated. Forty rats were divided into four groups. The diabetic positive control (STZ treated) group showed increased lipid peroxide, increased IL-6, and decreased antioxidant enzyme in the serum and kidney tissue homogenate compared with that of the negative control group. Immunoglobulins (IgA, IgG), fasting blood sugar, and glycosylated hemoglobin (HbA1c) were also increased as a result of diabetes in G2 rats. Moreover albumin was decreased, and liver enzymes and ?-amylase were not affected. In addition, the renal functions and potassium and sodium levels in G2 were increased as a sign of diabetic nephropathy. Urine analysis showed also glucosuria and increased potassium, sodium, creatinine, uric acid, and albumin levels. Kidney and pancreas tissues showed also pathological alteration compared to the negative control group. Treating the diabetic rats with 50 or 100?mg Moringa seeds powder/kg body weight in G3 and G4, respectively, ameliorated the levels of all these parameters approaching the negative control values and restored the normal histology of both kidney and pancreas compared with that of the diabetic positive control group. PMID:25629046

  8. The Antidiabetic Effect of Low Doses of Moringa oleifera Lam. Seeds on Streptozotocin Induced Diabetes and Diabetic Nephropathy in Male Rats

    PubMed Central

    Al-Malki, Abdulrahman L.; El Rabey, Haddad A.

    2015-01-01

    The antidiabetic activity of two low doses of Moringa seed powder (50 and 100?mg/kg body weight, in the diet) on streptozotocin (STZ) induced diabetes male rats was investigated. Forty rats were divided into four groups. The diabetic positive control (STZ treated) group showed increased lipid peroxide, increased IL-6, and decreased antioxidant enzyme in the serum and kidney tissue homogenate compared with that of the negative control group. Immunoglobulins (IgA, IgG), fasting blood sugar, and glycosylated hemoglobin (HbA1c) were also increased as a result of diabetes in G2 rats. Moreover albumin was decreased, and liver enzymes and ?-amylase were not affected. In addition, the renal functions and potassium and sodium levels in G2 were increased as a sign of diabetic nephropathy. Urine analysis showed also glucosuria and increased potassium, sodium, creatinine, uric acid, and albumin levels. Kidney and pancreas tissues showed also pathological alteration compared to the negative control group. Treating the diabetic rats with 50 or 100?mg Moringa seeds powder/kg body weight in G3 and G4, respectively, ameliorated the levels of all these parameters approaching the negative control values and restored the normal histology of both kidney and pancreas compared with that of the diabetic positive control group. PMID:25629046

  9. Anti-diabetic effects of ethanol extract of Bryonia laciniosa seeds and its saponins rich fraction in neonatally streptozotocin-induced diabetic rats

    PubMed Central

    Patel, Sandip B.; Santani, Devdas; Patel, Veena; Shah, Mamta

    2015-01-01

    Context: Bryonia laciniosa Linn. (Cucurbitaceae) seed is used in traditional medicine for a number of ailments including metabolic disorders. Aim: This study evaluated the anti-diabetic action of the ethanol extract of B. laciniosa seeds and saponin fraction of it through its effect on hyperglycemia, dyslipidaemia and oxidative stress in neonatally streptozotocin (n-STZ)-induced diabetic rats (n-STZ diabetic rats). Materials and Methods: Ethanol extract (250 and 500 mg/kg; p.o.), saponin fraction (100 and 200 mg/kg; p.o.) and standard drug glibenclamide (3 mg/kg; p.o.) were administered to diabetic rats when the rats were 6 weeks old and continued for 10 consecutive weeks. Effects of ethanol extract and saponin fraction on various biochemical parameters were studied in diabetic rats. Results: The treatment with ethanol extract and saponin fraction for 10 weeks decrease in the levels of glucose, triglycerides, cholesterol, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, serum urea, serum creatinine and diminished activities of aspartate transaminase, and alanine transaminase. The anti-hyperglycemic nature of B. laciniosa is probably brought about by the extra- the pancreatic mechanism as evidenced from unchanged levels of plasma insulin. B. laciniosa modulated effect of diabetes on the liver malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity. Administration of ethanol extract and saponin fraction to diabetic rats showed a significant reversal of disturbed antioxidant status. Significant increase in SOD, CAT, and levels of GSH was observed in treated n-STZ diabetic rats. Conclusion: The present study reveals the efficacy of B. laciniosa seed extract and its saponin fraction in the amelioration of n-STZ diabetic rats. PMID:25598641

  10. Antihyperlipidemic Activity of the Ethyl-acetate Fraction of Stereospermum Suaveolens in Streptozotocin-induced Diabetic Rats

    PubMed Central

    Thirumalaisamy, Balasubramanian; Prabhakaran, Senthilkumar Gnanavadevel; Marimuthu, Karthikeyan; Chatterjee, Tapan Kumar

    2013-01-01

    Objectives: Dyslipidemia in diabetes mellitus is a significant risk factor for the development of cardiovascular complications. The aim of this study was to evaluate the effect of the ethyl-acetate fraction of an ethanolic extract from Streospermum suaveolens on lipid metabolism in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced by intraperitonial injection of STZ (50 mg/kg). Diabetic rats were treated with an ethyl-acetate fraction orally at doses of 200 and 400 mg/kg daily for 14 days. On the 15th day, serum lipid profiles, such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), were estimated in experimental rats. The atherogenic (AI) and the coronary risk (CRI) indices were also evaluated. Results: The ethyl-acetate fraction at doses of 200 and 400 mg/kg significantly (P< 0.001) and dose-dependently reduced serum cholesterol, triglycerides and LDL, but increased HDL towards near normal levels as compared to diabetic control rats. The fraction also significantly (P< 0.001) lowered the atherogenic index (AI) and coronary risk index (CAI) in a dose-dependent manner. Conclusion: The present study demonstrated that the ethyl-acetate fraction of Stereospermum suaveolens exhibits a potent antihyperlipidemic activity in hyperglycemic rats and suggests that the plant may have therapeutic value in treating the diabetic complication of hyperlipidemia.

  11. Rhinacanthus nasutus Improves the Levels of Liver Carbohydrate, Protein, Glycogen, and Liver Markers in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Visweswara Rao, Pasupuleti; Madhavi, K.; Dhananjaya Naidu, M.; Gan, Siew Hua

    2013-01-01

    The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200?mg/kg/day while glibenclamide was administered at 50?mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state. PMID:24204387

  12. Anti-diabetic effect of a preparation of vitamins, minerals and trace elements in diabetic rats: a gender difference

    PubMed Central

    2014-01-01

    Background Although multivitamin products are widely used as dietary supplements to maintain health or as special medical food in certain diseases, the effects of these products were not investigated in diabetes mellitus, a major cardiovascular risk factor. Therefore, here we investigated if a preparation of different minerals, vitamins, and trace elements (MVT) for human use affects the severity of experimental diabetes. Methods Two days old neonatal Wistar rats from both genders were injected with 100 mg/kg of streptozotocin or its vehicle to induce diabetes. At week 4, rats were fed with an MVT preparation or vehicle for 8 weeks. Well established diagnostic parameters of diabetes, i.e. fasting blood glucose and oral glucose tolerance test were performed at week 4, 8 and 12. Moreover, serum insulin and blood HbA1c were measured at week 12. Results An impaired glucose tolerance has been found in streptozotocin-treated rats in both genders at week 4. In males, fasting blood glucose and HbA1c were significantly increased and glucose tolerance and serum insulin was decreased at week 12 in the vehicle-treated diabetic group as compared to the vehicle-treated non-diabetic group. All of the diagnostic parameters of diabetes were significantly improved by MVT treatment in male rats. In females, streptozotocin treatment resulted in a less severe prediabetic-like phenotype as only glucose tolerance and HbA1c were altered by the end of the study in the vehicle-treated diabetic group as compared to the vehicle-treated non-diabetic group. MVT treatment failed to improve the diagnostic parameters of diabetes in female streptozotocin-treated rats. Conclusion This is the first demonstration that MVT significantly attenuates the progression of diabetes in male rats with chronic experimental diabetes. Moreover, we have confirmed that females are less sensitive to STZ-induced diabetes and MVT preparation did not show protection against prediabetic state. This may suggest a gender difference in the pathogenesis of diabetes. PMID:25160946

  13. Antidiabetic effect of some medicinal plants of Oriental Morocco in neonatal non-insulin-dependent diabetes mellitus rats.

    PubMed

    Bnouham, Mohamed; Merhfour, Fatima Zahra; Ziyyat, Abderrahim; Aziz, Mohamed; Legssyer, Abdelkhaleq; Mekhfi, Hassane

    2010-10-01

    The goal of the present study is to test the effect of water extract (WE) of four medicinal plants used as antidiabetics in Eastern Morocco (Arbutus unedo: Au, Ammoïdes pusilla: Ap, Thymelaea hirsuta: Th, and Urtica dioïca: Ud). These plants are used in cooking to bring out the flavor in a dish or to complement it. The first experiment was realized in order to determine the antidiabetic effect of the WE of these plants during 5 weeks' treatment. Seven groups of Wistar rats were used: Healthy controls, neonatal streptozotocin (n-stz) induced-diabetic rats (90 mg/kg; intraperitoneally [i.p.]), n-stz + tolbutamide (400 mg/l), and 4 groups n-stz + WE of plants (400 mg/l, drink water). The percentages of Plasma glucose lowering effect were, respectively for Au, Ap, Th, Ud and tolbutamide: 31.6 % p<0.01, 27.4 % p<0.05, 38.2 % p<0.01, 13 % and 33.9 % p<0.05 when compared with untreated diabetic controls. In a second experiment, oral glucose tolerance tests were carried out in n-stz induced-diabetic rats. The i.p. administration of the water extract (WE) of Ap and Ud (150 mg/kg) 30 minutes before the glucose overload (2 g/kg) showed a significant reduction glycemia, respectively of 36 % at 60 min (p<0.05) and 50 % at 180 min (p<0.05) after glucose overload compared with controls. In contrast, the effect of WE of Au and Th (150 mg/kg, i.p.) was not significant. The in vitro study of glucose utilization by isolated rat hemidiaphragm suggests that these extracts in combination with insulin potentiate its activity and enhance the utilization of glucose. In conclusion, it seems that these plants possess antidiabetic activity. PMID:20154101

  14. Pulsed electromagnetic fields inhibit bone loss in streptozotocin-induced diabetic rats.

    PubMed

    Zhou, Jun; Li, Xinhong; Liao, Ying; Feng, Weibing; Fu, Chengxiao; Guo, Xin

    2015-05-01

    Evidences have shown that pulsed electromagnetic fields (PEMFs) can partially prevent bone loss in streptozotocin (STZ)-induced diabetic rats. However, the precise mechanisms accounting for these favorable effects are unclear. This study aimed to investigate the effects of PEMFs on bone mass and receptor activator of nuclear factor ?B ligand (RANKL)/osteoprotegerin (OPG) and Wnt/?-catenin signaling pathway in STZ rats. Thirty 3-month-old Sprague Dawley rats were randomly divided into the following three groups (n = 10): control group (injection of saline vehicle), DM group (injection of STZ), and PEMFs group (injection of STZ + PEMFs exposure). One week following injection of STZ, rats in the PEMFs group were subject to PEMFs stimulus for 40 min/day, 5 days/week, and lasted for 12 weeks. After 12 week intervention, the results showed that PEMFs increased serum bone-specific alkaline phosphatase level and bone mineral density, and inhibited deterioration of bone microarchitecture and strength in STZ rats. Furthermore, PEMFs up-regulated the mRNA expressions of low-density lipoprotein receptor-related protein 5, ?-catenin and runt-related gene 2 (Runx2), and down-regulated dickkopf1 in STZ rats. However, mRNA expressions of RANKL and OPG were not affected by PEMFs. PEMFs can prevent the diabetes-induced bone loss and reverse the deterioration of bone microarchitecture and strength by restoring Runx2 expression through regulation of Wnt/?-catenin signaling, regardless of its no glucose lowering effect. PMID:25273319

  15. Efficacy of Biodegradable Curcumin Nanoparticles in Delaying Cataract in Diabetic Rat Model

    PubMed Central

    Patil, Madhoosudan A.; Raghu, Ganugula; Balakrishna, Nagalla; Kumar, M. N. V. Ravi; Reddy, Geereddy Bhanuprakash

    2013-01-01

    Curcumin, the active principle present in the yellow spice turmeric, has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Previously we have reported that dietary curcumin delays diabetes-induced cataract in rats. However, low peroral bioavailability is a major limiting factor for the success of clinical utilization of curcumin. In this study, we have administered curcumin encapsulated nanoparticles in streptozotocin (STZ) induced diabetic cataract model. Oral administration of 2 mg/day nanocurcumin was significantly more effective than curcumin in delaying diabetic cataracts in rats. The significant delay in progression of diabetic cataract by nanocurcumin is attributed to its ability to intervene the biochemical pathways of disease progression such as protein insolubilization, polyol pathway, protein glycation, crystallin distribution and oxidative stress. The enhanced performance of nanocurcumin can be attributed probably to its improved oral bioavailability. Together, the results of the present study demonstrate the potential of nanocurcumin in managing diabetic cataract. PMID:24155984

  16. Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats

    PubMed Central

    Yang, Chun; Zhu, Bin; Ding, Jie; Wang, Zhi-Gang

    2014-01-01

    Several lines of evidence demonstrate that isoflurane anesthesia would be a great risk factor for the patients undergoing surgeries to suffer from postoperative cognitive dysfunction (POCD). Additionally, diabetes is also an important pathogenic factor for the emergence of cognitive dysfunction. If patient is suffering from diabetes, the incidence of cognitive dysfunction greatly increased. We therefore aimed to investigate the effects of isoflurane anesthesia on cognitive dysfunction in a diabetic rat model induced by a single injection of streptozotocin (STZ). Wistar rats received 2 h of 2% isoflurane or oxygen exposure 1 month after a single intraperitoneal injection of 60 mg/kg of STZ or the vehicle. The results showed that isoflurane anesthesia significantly aggravates STZ-induced an increase of the latency to the platform and a decrease of the proportion of time spent in the target quadrant of rats in Morris water maze test. In addition to the expression of amyloid-? (A?), superoxide dismutase (SOD), malonyldialdehyde (MDA), tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?), isoflurane anesthesia significantly increased as compared with a single injection of STZ. However, isoflurane anesthesia had no effect on the blood glucose and leptin. In conclusion, our results suggested that isoflurane anesthesia aggravating cognitive impairment induced by STZ is probably related to the activation of oxidative stress and inflammatory response in rat hippocampus. PMID:24955160

  17. Effect of insulin deficiency on the rewarding properties of methamphetamine in streptozotocin-induced diabetic rats.

    PubMed

    Bayat, Amir-Hossein; Haghparast, Abbas

    2015-01-01

    The reward is a positive behavioural response to the pleasant stimuli that can be induced by drugs, such as psychostimulants. Furthermore, diabetes mellitus is a chronic disease that many people throughout the world suffer from. Methamphetamine (METH), as a psychostimulant, engages the dopaminergic system in the reward circuitry and the synapses of dopaminergic terminals can be modified by insulin. In this study, in order to assess the effect of insulin deficiency on reward, streptozotocin (STZ)-induced diabetic animals were used as an appropriate model. One hundred and thirty-two adult male rats were divided into nine groups (three non-diabetic and six diabetic groups) to determine the most effective dose of METH (0.25, 0.5, 1 and 2mg/kg ip), and insulin replacement (10U/kg; ip) during the acquisition period in a conditioned place preference (CPP) paradigm. The diabetes model was induced by a single injection of STZ (60mg/kg; ip). The conditioning score was considered to be the difference in time spent in drug- and saline-paired compartments. The results demonstrated that the most effective doses of METH were 1 and 2mg/kg in non-diabetic animals. Although the place preference was not shown in non-diabetic animals at the dose of 0.5mg/kg, this dose significantly induced place preference to METH in STZ-diabetic rats. Additionally, insulin replacement could reverse the METH-induced CPP in diabetic animals. Our findings suggest that the positive effect of insulin deficiency on METH rewarding properties is dependent on insulin level in part, and the replacement of the insulin in diabetic rats as a treatment can improve the rewarding properties of METH. PMID:25444864

  18. Role of tissue transglutaminase in the pathogenesis of diabetic cardiomyopathy and the intervention effect of rutin

    PubMed Central

    GAO, HAI-CHENG; ZHU, KUN; GAO, HAI-MEI; MIAO, CHUN-SHENG; ZHANG, LE-NING; LIU, WEI; XIN, HUA

    2015-01-01

    The aim of this study was to investigate the role of tissue transglutaminase (tTG) in the pathogenesis of diabetic cardiomyopathy (DCM) and the intervention effect of rutin. DCM was induced in rats by the injection of streptozotocin (STZ; 25 mg/kg). After a preliminary examination, the rats were randomly divided into four groups: Control (n=8), STZ-induced DCM (n=8), STZ + positive drug (captopril; n=6) and STZ + rutin (n=8) groups. The DCM model was evaluated using blood sugar values, serum enzyme levels, hematoxylin and eosin staining and Masson’s staining, ex vivo. The protein and mRNA expression of tTG was assessed with immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The rat model of DCM was successfully established by STZ administration, and the expression levels of tTG were significantly increased in the DCM model. Following the injection of captopril or rutin, the blood sugar values, collagen content and expression levels of tTG were gradually reduced and serum enzyme levels were increased, as compared with those in the STZ-induced DCM group. In conclusion, tTG plays an important role in STZ-induced DCM. In addition, rutin may inhibit the expression of tTG and regulate myocardial injury in STZ-induced DCM.

  19. Amylin and bone metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Horcajada-Molteni, M N; Chanteranne, B; Lebecque, P; Davicco, M J; Coxam, V; Young, A; Barlet, J P

    2001-05-01

    Amylin (AMY) is a 37 amino acid peptide cosecreted with insulin (INS) by pancreatic beta-cells and absent in type 1 diabetes, a condition frequently associated with osteopenia. AMY binds to calcitonin receptors, lowers plasma calcium concentration, inhibits osteoclast activity, and stimulates osteoblasts. In the present study, we examined the effects of AMY replacement on bone loss in a streptozotocin (STZ)-induced rodent model type 1 diabetes. Of 50 male Wistar rats studied, 40 were made diabetic with intraperitoneal STZ (50 mg/kg; plasma glucose concentrations > 11 mM within 5 days). Ten nondiabetic control (CONT) rats received citrate buffer without STZ. Diabetic rats were divided into four groups (n = 10/group) and injected subcutaneously with rat AMY (45 mg/kg), INS (12 U/kg), both (same doses), or saline (STZ; diabetic controls) once per day. After 40 days of treatment and five 24-h periods of urine collection for deoxypyridinoline (DPD), the animals were killed, blood was sampled, and femurs were removed. The left femur was tested for mechanical resistance (three-point bending). The right femur was tested for total, diaphyseal (cortical bone), and metaphyseal (trabecular bone) bone densities using dual-energy X-ray absorptiometry (DXA). Bone was ashed to determine total bone mineral (calcium) content. None of the treatments had any significant effect on femoral length and diameter. Untreated diabetic rats (STZ; 145+/-7N) had lower bone strength than did nondiabetic CONT (164+/-38; p < 0.05). Total bone mineral density (BMD; g/cm2) was significantly lower in STZ (0. 2523+/-0.0076) than in CONT (0.2826+/-0.0055), as were metaphyseal and diaphyseal densities. Diabetic rats treated with AMY, INS, or both had bone strengths and bone densities that were indistinguishable from those in nondiabetic CONT. Changes in bone mineral content paralleled those for total BMD (T-BMD). Plasma osteocalcin (OC) concentration, a marker for osteoblastic activity, was markedly lower in untreated diabetic rats (7. 6+/-0.9 ng/ml); p < 0.05) than in nondiabetic CONT (29.8+/-1.7; p < 0.05) or than in AMY (20.1+/-0.7; p < 0.05). Urinary DPD excretion, a marker for bone resorption, was similar in untreated and AMY-treated diabetic rats (35.0+/-3.1 vs. 35.1+/-4.4 nmol/mmol creatinine), intermediate in rats treated with INS (49.9+/-2.7), and normalized in diabetic rats treated with both agents (58.8+/-8.9 vs. 63.2+/-4.5 in CONT). Thus, in our STZ rat model of diabetic osteopenia, addition of AMY improved bone indices apparently by both inhibiting resorption and stimulating bone formation. PMID:11341342

  20. GC-MS analysis and screening of antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala oil in streptozotocin induced diabetes mellitus in rats

    PubMed Central

    2012-01-01

    Aim of the study This study was made to investigate the antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala, (Buch.-Ham.) Nees & Eberm (Tejpat) oil (CTO) in streptozotocin (STZ) induced diabetes in rats along with evaluation of chemical constituents. Materials and methods The GC-MS (Gas chromatography–mass spectrometry) analysis of the oil showed 31 constituents of which cinnamaldehyde was found the major component (44.898%). CTO and cinnamaldehyde was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic models. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. Results CTO (100?mg/kg and 200?mg/kg), cinnamaldehyde (20?mg/kg) and glibenclamide (0.6?mg/kg) in respective groups of diabetic animals administered for 28?days reduced the blood glucose level in streptozotocin induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in the blood glucose, glycosylated hemoglobin and total plasma cholesterol in test groups as compared to control group. The results of CTO and cinnamaldehyde were found comparable with standard drug glibenclamide. In vitro antioxidant studies on CTO using various models showed significant antioxidant activity. In vivo antioxidant studies on STZ induced diabetic rats revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH). Conclusion Thus the investigation results that CTO has significant antidiabetic, antioxidant and hypolipidemic activity. PMID:22882757

  1. Effect of Alpinia calcarata on glucose uptake in diabetic rats-an in vitro and in vivo model

    PubMed Central

    2014-01-01

    Background Diabetes mellitus is a heterogeneous metabolic disorders characterized by abnormally high levels of blood glucose The main objective of the present work is to study the effect of Alpinia calcarata on glucose uptake in streptozotocin (STZ) induced diabetic rats. Methods The diabetes was induced by single dose of STZ (45 mg/kg) in citrate buffer, while the normal control group was given the vehicle (citrate buffer) only. After induction of diabetes, the diabetic animals were treated with ethanolic extract of Alpinia calcarata (200 mg/kg) and glibenclamide (2 mg/kg) for 30 days. Blood glucose estimation was performed every week of the study. At the end of study period, animals were sacrificed for biochemical studies. Results Streptozotocin induced diabetic rats shows the altered levels of various biochemical profiles. Those levels were brought back to near normal upon treatment with ethanolic extract of Alpinia calcarata and standard drug glibanclamide. No significant changes were observed on treatment with plant extract alone group indicated that there are no toxic substances present in Alpinia calcarata. The antidiabetic activity of plant extract was also further confirmed by histopathological studies. The ethanolic extract of Alpinia calcarata shows significant inhibition of alpha glucosidase activity and also enhancing the glucose uptake in rat hemidiaphragm. Conclusions In conclusion, the ethanolic extract of Alpinia calcarata ameliorates the condition associated with diabetes. PMID:24502532

  2. Kinins are involved in the antiproteinuric effect of angiotensin-converting enzyme inhibition in experimental diabetic nephropathy

    Microsoft Academic Search

    Carsten Tschöpe; Ulrich Seidl; Alexander Reinecke; Udo Riester; Kristof Graf; Heinz-Peter Schultheiss; Ulrich Hilgenfeldt; Thomas Unger

    2003-01-01

    The present study examined non-insulin-treated streptozotocin (STZ)-induced diabetic rats to determine the role of kinins in diabetic nephropathy. Their involvement in the renoprotective effect of the angiotensin-converting enzyme inhibitor (ACEI) ramipril was investigated using the bradykinin (BK) B2-receptor antagonist, icatibant (HOE 140), or a combination of the two drugs.Although, none of the treatments prevented the decline of the glomerular filtration

  3. Bioactive fraction of Saraca indica prevents diabetes induced cataractogenesis: An aldose reductase inhibitory activity

    PubMed Central

    Somani, Gauresh; Sathaye, Sadhana

    2015-01-01

    Background: The present study was designed to investigate the effect of Saraca indica (SI) flowers extract and different bioactive fraction on in vitro aldose reductase (AR) inhibitory activity, high glucose-induced cataract in goat lens and in vivo streptozotocin (STZ; 45 mg/kg, i.p) induced cataract in rats. Methods: Extract of flowers of SI tested for inhibition against rat lens AR. Furthermore, bioactive fraction was investigated against high glucose-induced opacification of the lens in vitro lens culture and STZ induced diabetic cataract in rats. Identification of the bioactive component was attempted through high-performance thin-layer chromatography, high-performance liquid chromatography and liquid chromatography-mass spectrometry analysis. Results: Ethyl acetate fraction of S. indica (EASI) produced maximum inhibition that may be due to high phenolic content. Goat lenses in media containing glucose developed a distinctly opaque ring in 72 h and treatment with EASI fraction lowered lens opacity in 72 h. Prolonged treatment with EASI to STZ-induced diabetic rats inhibited the AR activity and delayed cataract progression in a dose dependent manner. Conclusion: Ethyl acetate fraction of S. indica fraction has potential to inhibit rat lens AR enzyme and prevent cataractogenesis not only in goat lens model (in vitro), but also in STZ induced diabetic rats (in vivo). This study is suggestive of the anticataract activity of EASI fraction that could be attributed to the phytoconstituents present in the same. PMID:25709218

  4. Evaluation of Antihyperglycemic Activity of Citrus limetta Fruit Peel in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    KunduSen, Sriparna; Haldar, Pallab K.; Gupta, Malaya; Mazumder, Upal K.; Saha, Prerona; Bala, Asis; Bhattacharya, Sanjib; Kar, Biswakanth

    2011-01-01

    The present paper aims to evaluate antihyperglycemic activity of methanol extract of Citrus limetta fruit peel (MECL) in streptozotocin-induced (STZ; 65?mg/kg b.w.) diabetic rats. Three days after STZ induction, diabetic rats received MECL orally at 200 and 400?mg kg?1 body weight daily for 15 days. Glibenclamide (0.5?mg kg?1 p. o.) was used as reference drug. Blood glucose levels were measured on 0th, 4th, 8th, and 15th days of study. Serum biochemical parameters namely, SGOT, SGPT and ALP were estimated. The TBARS and GSH levels of pancreas, kidney, and liver were determined. MECL significantly (P < 0.001) and dose dependently normalized blood glucose levels and serum biochemical parameters, decreased lipid peroxidation, and recovered GSH as compared to those of STZ control. The present paper infers that in STZ-induced diabetic Wistar rats, C. limetta fruit peel demonstrated a potential antihyperglycemic effect which may be attributed to its antioxidant property. PMID:22363893

  5. Antidiabetic and Hypolipidemic Effect of Salacia Oblonga in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Bhat, Bhagyajyothi M.; C.V., Raghuveer; D’Souza, Vivian; Manjrekar, Poornima A.

    2012-01-01

    Objectives The present study was conducted to evaluate the effect of a standardized hydroalcoholic root extract of Sala¬cia oblonga (SOE) on the Random Blood Glucose (RBG) levels, serum insulin, glycated haemoglobin (HbA1c) and the serum lipid profile in long standing, experimentally induced Diabetes Mellitus (DM) with glibenclamide (Glb) as the standard. Materials and Methods Streptozotocin (STZ) induced, dia-betic, Wistar rats of either sex were treated with two oral doses of SOE, 100 and 50mg/kg body wt /day, for a period of 16 weeks. The RBG was estimated at day-1 and at the end of the 16 weeks by using a glucometer. The fasting serum insulin was determined by an ELISA technique. The plasma HbA1c was evaluated by a Turbidimetric Inhibition Immunoassay (TINIA) and the lipid profile was estimated enzymatically. Results and Analysis A 45% decrease in the RBG was seen after the treatment with the higher dose of SOE, whereas a 44% decrease was observed with the lower dose as com¬pared to the diabetic control. Serum insulin was significantly increased (P<0.05) in all the treated groups as compared to the diabetic control. Plasma HbA1c was significantly decreased (P<0.05). The serum Triacyl Glycerol (TG) levels were signifi¬cantly decreased (P<0.05) in the treated rats as compared to the diabetic control. A significant increase in HDL-cholesterol (P<0.05) in the diabetic rats as a result of the 100mg/kg SOE treatment was a remarkable finding. Conclusion SOE improves the glycaemic parameters in diabetic rats after a prolonged treatment. The serum TG levels were normalized on treatment. A higher dose of the extract could not alter the parameters significantly, except for HDL-C. PMID:23373028

  6. Delivery of SAR 1118 to the Retina via Ophthalmic Drops and its Effectiveness in a Rat Streptozotocin (STZ) Model of Diabetic Retinopathy (DR)

    PubMed Central

    Rao, Vidhya R.; Prescott, Elizabeth; Shelke, Namdev B.; Trivedi, Ruchit; Thomas, Peter; Struble, Craig; Gadek, Tom; O'Neill, Charles A.; Kompella, Uday B.

    2010-01-01

    Purpose. To determine the pharmacokinetics of SAR 1118, a small-molecule antagonist of leukocyte function-associated antigen (LFA)-1, after administration of ophthalmic drops in normal rats, and to determine its pharmacologic activity by assessing the inhibition of retinal leukostasis and vascular leakiness in a streptozotocin (STZ)-induced diabetic retinopathy model. Methods. The ocular pharmacokinetics of SAR 1118 were studied in rats after a single topical dose of 14C-SAR 1118 (1 mg/eye; 40 ?Ci; 15.5 ?L). SAR 1118 concentration time profiles in plasma and ocular tissues were quantified by liquid scintillation counting (LSC). The pharmacologic activity of SAR 1118 eye drops administered thrice daily for 2 months at 1% (0.3 mg/eye/d) and 5% (1.5 mg/eye/d) was assessed in an STZ-induced diabetic rat model by determining retinal leukostasis and blood–retinal barrier breakdown. Diabetic rats treated with periocularly administered celecoxib microparticles served as the positive control, and vehicle-treated rats served as the negative control. Results. A single dose of 6.5% 14C-radiolabeled SAR 1118 ophthalmic drops delivered retinal drug levels greater than 1 ?M in less than 30 minutes and sustained levels greater than 100 nM for 8 hours. SAR 1118 eye drops significantly reduced leukostasis and blood–retinal barrier breakdown in a dose-dependent manner. Conclusions. SAR 1118 ophthalmic drops administered thrice daily deliver therapeutic levels of SAR 1118 in the retina and can alleviate the retinal complications associated with diabetes. PMID:20445119

  7. Antihyperglycemic and hypolipidemic effects of Melothria maderaspatana and Coccinia indica in Streptozotocin induced diabetes in rats

    PubMed Central

    Balaraman, Ashok Kumar; Singh, Jagadish; Dash, Sasmita; Maity, Tapan Kumar

    2010-01-01

    Antihyperglycemic and hypolipidemic effects of ethanol extract of aerial parts of Melothria maderaspatana and Coccinia indica were evaluated in STZ induced diabetes in Sprague–Dawley rats. The rats were concurrently treated with 100 or 200 mg/kg b.w. p.o. for 14 days. The changes in fasting blood glucose level and body weight were measured in 5 days interval. After 14 days experimental period, rats were sacrificed by cervical decapitation, blood and liver samples were collected. Biochemical estimation of plasma glucose, cholesterol, triglycerides, LDL, HDL, SGOT, SGPT and ALP were done from blood sample. The liver glycogen content was estimated using standard procedure from homogenized liver sample. Administration of EEMm or EECi to STZ-diabetic rats caused significant antihyperglycemic and hypolipidemic effects (p < 0.001). The extracts were also found to be significantly effective (p < 0.001; p < 0.05) on recovery of altered biochemical parameters and decreased body weight in treated animals. Glibenclamide (0.5 mg/kg b.w.) was used as standard in present study. PMID:23964177

  8. Effect of Unripe Plantain (Musa paradisiaca) and Ginger (Zingiber officinale) on Blood Glucose, Body Weight and Feed Intake of Streptozotocin-induced Diabetic Rats

    PubMed Central

    M, Iroaganachi; C.O, Eleazu; P.N, Okafor; N, Nwaohu

    2015-01-01

    Objective: To determine the effect of unripe plantain (Musa paradisiaca) and ginger (Zingiber officinale) on blood glucose (BG), feed intake (FI) and weight of streptozotocin (STZ) induced diabetic rats. Methods: Twenty four male albino rats were used and were divided into 4 groups of 6 rats each. Group 1 (non-diabetic) and Group 2 (diabetic) received standard rat feed; Group 3 received unripe plantain incorporated feed (810 /kg body weight) and Group 4 received unripe plantain+ginger incorporated feed (710:100 g/kg body weight). The weights and FI of the rats were measured daily throughout the experimentation. Results: Groups 3 and 4 rats had 159.52% and 71.83% decreases in BG but 24.91% and 35.32% decreases in weights compared with groups 1 and 2 rats that had 2.09% and 22.94% increases in BG with 13.42% increase and 45.36% decrease in weights respectively. The FI of the experimental rats did not differ significantly from each other (P>0.05) at the end of experimentation. The standard rat feed contained higher amounts of Ca but lower amounts of Mg and Fe compared with the unripe plantain and unripe plantain+ginger incorporated feeds. Conclusion: Combination of unripe plantain and ginger at the dose used in the management of diabetes was not very effective compared with unripe plantain alone. PMID:25674161

  9. Chronic central leptin infusion restores cardiac sympathetic-vagal balance and baroreflex sensitivity in diabetic rats

    PubMed Central

    do Carmo, Jussara M.; Hall, John E.; da Silva, Alexandre A.

    2008-01-01

    This study tested whether leptin restores sympathetic-vagal balance, heart rate (HR) variability, and cardiac baroreflex sensitivity (BRS) in streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were instrumented with arterial and venous catheters, and a cannula was placed in the lateral ventricle for intracerebroventricular (ICV) leptin infusion. Blood pressure (BP) and HR were monitored by telemetry. BRS and HR variability were estimated by linear regression between HR and BP responses to phenylephrine or sodium nitroprusside and autoregressive spectral analysis. Measurements were made during control period, 7 days after induction of diabetes, and 7 days after ICV leptin infusion. STZ diabetes was associated with hyperglycemia (422 ± 17 mg/dl) and bradycardia (?79 ± 4 beats/min). Leptin decreased glucose levels (165 ± 16 mg/dl) and raised HR to control values (303 ± 10 to 389 ± 10 beats/min). Intrinsic HR (IHR) and chronotropic responses to a full-blocking dose of propranolol and atropine were reduced during diabetes (260 ± 7 vs. 316 ± 6, ?19 ± 2 vs. ?43 ± 6, and 39 ± 3 vs. 68 ± 8 beats/min), and leptin treatment restored these variables to normal (300 ± 7, ?68 ± 10, and 71 ± 8 beats/min). Leptin normalized BRS (bradycardia, ?2.6 ± 0.3, ?1.7 ± 0.2, and ?3.0 ± 0.5; and tachycardia, ?3.2 ± 0.4, ?1.9 ± 0.3, and ?3.4 ± 0.3 beats·min?1·mmHg?1 for control, diabetes, and leptin) and HR variability (23 ± 4 to 11 ± 1.5 ms2). Chronic glucose infusion to maintain hyperglycemia during leptin infusion did not alter the effect of leptin on IHR but abolished the improved BRS. These results show rapid impairment of autonomic nervous system control of HR after the induction of diabetes and that central nervous system actions of leptin can abolish the hyperglycemia as well as the altered IHR and BRS in STZ-induced diabetes. PMID:18790839

  10. Effect of selenite treatment on ultrastructural changes in experimental diabetic rat bones

    Microsoft Academic Search

    Semir Ozdemir; Murat Ayaz; Belgin Can; Belma Turan

    2005-01-01

    It is known that streptozotocin (STZ)-induced diabetes causes functional and structural alterations in some types of tissue\\u000a and organ. A number of methods have been used to characterize the properties of diabetic tissues and their diagnosis. Selenium\\u000a compounds, playing an antioxidant role, can restore some altered metabolic parameters and diminished functions in experimental\\u000a diabetes. The first aim of the present

  11. Effects of lichen extracts on haematological parameters of rats with experimental insulin-dependent diabetes mellitus.

    PubMed

    Colak, Suat; Geyiko?lu, Fatime; Aslan, Ali; Deniz, Gül?ah Y?ld?z

    2014-11-01

    The prevalence of diabetes mellitus in the world is steadily increasing. Oxidative stress contributes to the development of diabetic complications, including diabetic haematological changes. Lichens are used as food supplements and are also used as possible natural antioxidant, antimicrobial and anticancer agents. We hypothesized that antioxidant activity of lichens may decrease hyperglycaemia-induced oxidative stress and prevent the development of diabetic complications, including abnormality in haematological condition. Therefore, the effects of Cetraria islandica water extract (CIWE) and Pseudevernia furfuracea water extract (PFWE) on the haematological parameters of rats with type 1 DM were investigated for the first time in the present study. Control Sprague-Dawley or streptozotocin (STZ)-induced diabetic rats were either untreated or treated with water lichen extracts (5-500 mg/kg body weight (bw)/day) for 2 weeks, starting at 72 h after STZ injection. On day 14, animals were anaesthetized and haematological and metabolic parameters were determined between control and experimental groups. In addition, the total oxidative stress (TOS), a specific indicator of oxidative stress, and the total antioxidant capacity (TAC) were measured by biochemical studies. In diabetic rats, CIWE of 250-500 mg/kg bw dose showed more prominent results when compared with doses of PFWE for TAC. The results obtained in the present study suggested that the antioxidant activities of lichens might be the possible reason behind the observed antihaematological status. However, the protective effect of lichen extracts were inadequate on diabetes-induced microcytic hypochromic anaemia. In addition, the extracts have no effect on metabolic complications. Our experimental data showed that high doses of CIWE and PFWE alone have no detrimental effect on blood cells and TOS status of plasma. Hence, they are safe and suitable for different administration routes. PMID:23114377

  12. Antihyperglycemic and hypolipidemic activity of methanolic extract of Amaranthus viridis leaves in experimental diabetes

    PubMed Central

    Krishnamurthy, Girija; Lakshman, Kuruba; Pruthvi, Nagaraj; Chandrika, Pulla Udaya

    2011-01-01

    To investigate the antihyperglycemic and hypolipidemic effects of methanolic extract of leaves of Amaranthus viridis (MEAV) in normal and Streptozotocin (STZ) induced diabetic rats. The anti-hyperglycemic and hypolipidemic activity of methanolic extract of leaves of Amaranthus viridis was evaluated by using normal and STZ induced diabetic rats at dose of 200 mg/kg and 400 mg/kg by mouth per day for 21 days. Blood glucose levels and body weight was monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed. The statistical data indicated a significant increase in the body weight, decrease in the blood glucose, total cholesterol and serum triglycerides after treatment with MEAV. High density lipoprotein (HDL) cholesterol level was significantly increased when treated with extract. Histologically, focal necrosis was observed in the diabetic rat pancreas; however, was less obvious in treated groups. The MEAV has beneficial effects in reducing the elevated blood glucose level and body weight changes, and improves the lipid profile of STZ induced rats. PMID:21845004

  13. Chronic streptozotocin diabetes in rats facilitates the acute stress response without altering pituitary or adrenal responsiveness to secretagogues.

    PubMed

    Scribner, K A; Walker, C D; Cascio, C S; Dallman, M F

    1991-07-01

    We have used streptozotocin (STZ)-induced diabetes in rats to determine whether this represents a sustained stimulus to the adrenocortical system and whether STZ-diabetic rats are able to mount an acute stress response. Furthermore, we compared pituitary responsiveness to CRF and/or arginine vasopressin, and adrenal responsiveness to ACTH in STZ- vs. vehicle-treated rats. We also compared the efficacy of dexamethasone inhibitory feedback in STZ-diabetic and control rats. Our results show that STZ-treated rats chronically hypersecrete corticosterone (B) as evidenced by their decreased thymus weights, their increased urinary B excretion, and their elevated mean plasma B levels during the light hours of the day. Despite the evidence for sustained hypersecretion of B, STZ-treated rats showed greater and more prolonged ACTH and B responses to the acute stress of histamine injection. However, when tested separately, neither pituitary nor adrenal responsiveness to their secretagogues were increased in STZ-diabetic compared to control rats. Dexamethasone inhibition of stress-induced B secretion was tested using two different paradigms: pentobarbital-anesthetized rats were given iv injections of acid saline, and awake rats were given ip injections of histamine. In both experiments the STZ-treated rats were relatively resistant to glucocorticoid inhibition of stress responses. This finding, taken together with the exaggerated ACTH and B responses to stress, strongly suggests that the facilitatory effects of chronic STZ-diabetes are a consequence of changes in sensitivity of central neural components of the adrenocortical system to stimulatory and/or inhibitory inputs, in conjunction with changes in glucocorticoid feedback sensitivity. PMID:1647314

  14. Transdermal Delivery of Insulin by Amidated Pectin Hydrogel Matrix Patch in Streptozotocin-Induced Diabetic Rats: Effects on Some Selected Metabolic Parameters

    PubMed Central

    Hadebe, Silindile I.; Ngubane, Phikelelani S.; Serumula, Metse R.; Musabayane, Cephas T.

    2014-01-01

    Purpose Studies in our laboratory are concerned with developing optional insulin delivery routes based on amidated pectin hydrogel matrix gel. We therefore investigated whether the application of pectin insulin (PI)-containing dermal patches of different insulin concentrations sustain controlled release of insulin into the bloodstream of streptozotocin (STZ)-induced diabetic rats with concomitant alleviation of diabetic symptoms in target tissues, most importantly, muscle and liver. Methods Oral glucose test (OGT) responses to PI dermal matrix patches (2.47, 3.99, 9.57, 16.80 µg/kg) prepared by dissolving pectin/insulin in deionised water and solidified with CaCl2 were monitored in diabetic rats given a glucose load after an 18-h fast. Short-term (5 weeks) metabolic effects were assessed in animals treated thrice daily with PI patches 8 hours apart. Animals treated with drug-free pectin and insulin (175 µg/kg, sc) acted as untreated and treated positive controls, respectively. Blood, muscle and liver samples were collected for measurements of selected biochemical parameters. Results After 5 weeks, untreated diabetic rats exhibited hyperglycaemia and depleted hepatic and muscle glycogen concentrations. Compared to untreated STZ-induced diabetic animals, OGT responses of diabetic rats transdermally applied PI patches exhibited lower blood glucose levels whilst short-term treatments restored hepatic and muscle glycogen concentrations. Plasma insulin concentrations of untreated diabetic rats were low compared with control non-diabetic rats. All PI treatments elevated plasma insulin concentrations of diabetic rats although the levels induced by high doses (9.57 and 16.80 µg/kg) were greater than those caused by low doses (2.47 and 3.99 µg/kg) but comparable to those in sc insulin treated animals. Conclusions The data suggest that the PI hydrogel matrix patch can deliver physiologically relevant amounts of pharmacologically active insulin. Novelty of the Work A new method to administer insulin into the bloodstream via a skin patch which could have potential future applications in diabetes management is reported. PMID:24987850

  15. Time-course changes in left ventricular myocardial deformation in STZ-induced rabbits on velocity vector imaging

    PubMed Central

    2014-01-01

    Objectives To clarify the time-course changes in left ventricular myocardial deformation using velocity vector imaging and to provide insights into our understanding of the cardiac pathophysiology in diabetes mellitus. Methods Thirty New Zealand white rabbits were randomly divided into either the control group (n?=?10) or the diabetes mellitus (DM) group (induced with STZ, n?=?20). For the myocardial deformation studies, echocardiography and syngo-vector velocity imaging (VVI) were performed at baseline and after 2, 4, 8, and 12 weeks in all of the rabbits. The left ventricular (LV) global longitudinal and circumferential strain and strain rate were measured. For histomorphological study of the heart structure, 2 of the STZ-induced rabbits were killed at 2, 4, 8, and 12 weeks. Routine hematoxylin and eosin staining was performed. Results At 2 weeks, the global longitudinal strain (GLS), systolic strain rate (GLSRs), and diastolic strain rate (GLSRd) were significantly lower in the DM group compared with the control group (-18.16% versus -24.00%, -1.86 s-1 versus -2.49 s-1, 1.93 s-1 versus 2.42 s-1, respectively, P?diabetes, the histoanatomical alterations intensified gradually beginning at 2 weeks. Conclusions The progressive impairments in LV myocardial deformation and structure occurred early in diabetic rabbits with normal LV ejection fraction (EF), FS, and E/A. VVI could be used to evaluate subtle cardiac dysfunction in the early phase of DM. PMID:24885095

  16. Antioxidant and hypoglycemic effect of Otostegia aucheri methanolic extract in streptozotocin-induced diabetic male long-Evans rats.

    PubMed

    Rashid, Rehana; Murtaza, Ghulam; Khan, Abida K; Mir, Sadullah

    2014-01-01

    Present study is based on the investigation of antioxidant and antihyperglycemic effect of methanolic extract from areal parts of Otostigea aucheri (OA). 2,2-Diphenyl-1 -picrylhydrazyl (DPPH) method was used to measure the antioxidant activity of extract of the species Otostigea aucheri. The observed scavenging activity for the free radicals was significant and it was compared with the standard BHT inhibition method. The IC50 value obtained of methanolic extract was 2.23 microg/mL. The methanolic extract of OA on the blood glucose level was further studied in normal (non-diabetic), streptozotocin (STZ)-induced type I and type II diabetic male Long-Evans rats at postprandial glucose load state. The results revealed that the oral administration of methanolic extract (1.25 g/kg) of OA showed no remarkable hypoglycemic effect in normal and type 1 (IDDM) diabetic rats. However, the methanolic extract significantly lowered (p < 0.005) serum glucose level in type II diabetic (NIDDM) models when simultaneous glucose was administered. This screening for antioxidant activity interprets the pernicious effects of diabetes that have been associated with mediation through the oxidation stress. The study also suggests to introduce natural source of the potential orally active antioxidant and active antihyperglycemic phytochemicals for the future. It may also improve the impaired antioxidant defense system. PMID:25272889

  17. Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract

    PubMed Central

    Patil, Madhoosudan A.; Suryanarayana, Palla; Putcha, Uday Kumar; Srinivas, Myadara

    2014-01-01

    Type 2 diabetes (T2D) generally follows prediabetes (PD) conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ) induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70%) of nSTZ injected pups developed IGT (nSTZ-PD) by two months but not cataract even after seven months, remaining (30%) nSTZ rats developed hyperglycemia (nSTZ-D) by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities. PMID:25505935

  18. Effect of Pleurotus tuber-regium polysaccharides supplementation on the progression of diabetes complications in obese-diabetic rats.

    PubMed

    Huang, Hui-Yu; Korivi, Mallikarjuna; Yang, Hui-Ting; Huang, Chi-Chang; Chaing, Ying-Ying; Tsai, Ying-Chieh

    2014-08-31

    In this study, the effect of mushroom extracellular polysaccharides on fatty acid composition and liver peroxisome proliferator-activated receptor-alpha (PPAR-?) expression in obese-diabetic rats was investigated, and distinguished the association among anti-obesity, hypoglycemic and hypolipidemic properties. Extracellular polysaccharides from three different strains of Pleurotus tuber-regium were extracted and labeled as HP (high-percentage), MP (medium-percentage) and LP (low-percentage). Obese- diabetes (OD) was induced by chronic high-fat diet plus streptozotocin (STZ) injections. Simultaneously to the diet, polysaccharides were orally administered to OD groups (20 mg/kg body weight/8-week), and categorized into OD+HP, OD+MP and OD+LP groups (n = 10/group), respectively. High-fat diet plus STZ-induced hyperglycemia was prominently attenuated by polysaccharides. Increased fatty acid component n-6/n-3 ratio in liver and plasma of obese-diabetic rats was attenuated, while, reduced MUFA/ PUFA and MUFA/SFA ratios were restored (P < 0.01) with polysaccharides treatment. Furthermore, elevated serum total cholesterol, triglycerides and low-density lipoprotein (LDL) concentrations were controlled, and parallel restoration of decreased high-density lipoprotein (HDL) levels were found with polysaccharides supplementation. This hypolipidemic property might be associated with up-regulated liver PPAR-? mRNA expression and protein levels (P < 0.01). These findings concluded that stable fatty acid components and activated PPAR-? by polysaccharides may contribute to its hypoglycemic and hypolipidemic properties. Therefore, P. tuber-regium could be considered as nutritional supplement to treat diabetic complications. PMID:25246061

  19. Therapeutic potential of some plant extracts used in Turkish traditional medicine on streptozocin-induced type 1 diabetes mellitus in rats.

    PubMed

    Ozkol, Halil; Tuluce, Yasin; Dilsiz, Nihat; Koyuncu, Ismail

    2013-01-01

    Diabetes mellitus (DM) is known to impair many physiological functions. Some reports claim that medicinal plants can reduce these alterations caused by DM. The aim of this study was to investigate the therapeutic potential of aqueous-methanol extracts of Urtica dioica, Thymus vulgaris (TV), Myrtus communis (MC), Scolymus hispanicus (SH) and Cinnamomun zeylanicum (CZ) on streptozotocin (STZ)-induced type 1 DM in rats. Diabetes was induced via a single i.p. injection of STZ (65 mg/kg body weight). After 1 week to allow for development of diabetes, each plant extract was administered to diabetic rats separately at a dose of 100 mg/kg body weight daily for 28 days. The results showed that only SH extract significantly (P < 0.05) amended fasting blood glucose level. The lipid profile was ameliorated especially by supplementations of TV, MC and CZ extracts. Almost all plant extract treatments markedly (P < 0.05) increased reduced glutathione content and decreased lipid peroxidation levels of erythrocyte, plasma, retina and lens tissues. They also significantly (P < 0.05) amended erythrocyte catalase activity, levels of marker serum enzymes (except amylase), urea and blood urea nitrogen when compared to diabetic rats treated with nothing. Furthermore, none of the plant extracts counteracted body weight loss of diabetic rats. Our data revealed that the aforementioned plant extracts have remarkable potential to counteract DM-caused alterations, probably through their antioxidant and free radical-defusing effects. PMID:23052826

  20. Protective role of 20-OH ecdysone on lipid profile and tissue fatty acid changes in streptozotocin induced diabetic rats.

    PubMed

    Naresh Kumar, Rajendran; Sundaram, Ramalingam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2013-01-01

    Hyperlipidemia is an associated complication of diabetes mellitus. The association of hyperglycemia with an alteration of lipid parameters presents a major risk for cardiovascular complications in diabetes. The present study was designed to examine the antihyperlipidemic effect of 20-OH ecdysone on lipid profile and tissue fatty acid changes in streptozotocin induced diabetic rats. The levels of blood glucose, cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density lipoprotein, high density lipoprotein, lipoprotein lipase, lecithin cholesterol acyl transferase, 3-hydroxy 3-methylglutaryl coenzyme A reductase and fatty acid composition were estimated in plasma, liver and kidneys of control and experimental groups of rats. Oral administration of 20-OH ecdysone at a dose of 5mg/kg bodyweight per day to STZ-induced diabetic rats for a period of 30 days resulted in a significant reduction in fasting blood glucose, cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density lipoprotein, 3-hydroxy 3-methylglutaryl coenzyme A reductase and elevation of high density lipoprotein, lipoprotein lipase and lecithin cholesterol acyl transferasein comparison with diabetic untreated rats. Moreover, administration of 20-OH ecdysone to diabetic rats also decreased the concentrations of fatty acids, viz., palmitic, stearic (16:1) and oleic acid (18:1), whereas linolenic (18:3) and arachidonic acid (20:4) were elevated. The antihyperlipidemic effect of 20-OH ecdysone was compared with glibenclamide a well-known antihyperglycemic drug. The result of the present study indicates that 20-OH ecdysone showed an antihyperlipidemic effect in addition to its antidiabetic effect in experimental diabetes. PMID:23110815

  1. Bradykinin B? antagonism inhibits oxidative stress and restores Na+K+ ATPase activity in diabetic rat peripheral nervous system.

    PubMed

    Catanzaro, Orlando; Capponi, Jorgelina Aria; Michieli, Jose; Labal, Emilio; Di Martino, Irene; Sirois, Pierre

    2013-06-01

    Diabetic peripheral neuropathy is one the most common complications of diabetes mellitus and frequently results in clinically significant morbidities such as pain, foot ulcers and amputations. The diabetic condition progresses from early functional changes to late, poorly reversible structural changes. The chronic hyperglycemia measured alongside diabetes development is associated with significant damage and failure of various organs. In the present study diabetes was induced in male Wistar rats by a single dose of streptozotocin (STZ) and the association between the BKB1-R and the oxidative stress and Na+-K+ ATPase activity in nervous tissues was analysed. The results showed that the resulting hyperglycemia induced a reduction of the neuronal electrical function integrity and increased oxidative stress in the sciatic nerve homogenates of 30 days diabetic rats. Malondialdehyde (MDA) used as a marker of oxidative stress was elevated whereas Biological Antioxidant Potential (BAP), glutathion (GSH) levels and superoxide dismutase (SOD) activity were decreased. Treatment of the rats 3 days before the end of the 4 week period with the BKB1 antagonist R-954 restored the neuronal activity and significantly attenuated the oxidative stress as shown by the level of the various markers returning close to levels found in control rats. Our results suggest that the BKB1-R subtype is overexpressed in sciatic nerve during the STZ-induced diabetes development as evidenced by inhibitory effects of the BKB1-R antagonist R-954. The beneficial role of BKB1-R antagonist R-954 for the treatment of diabetic neuropathy is also suggested. PMID:23528517

  2. The Effect of Chromium Picolinate Supplementation on the Pancreas and Macroangiopathy in Type II Diabetes Mellitus Rats

    PubMed Central

    Huang, Shan; Peng, Wenfang; Jiang, Xiaohong; Shao, Kan; Xia, Lili; Tang, Yubin; Qiu, Jiayin

    2014-01-01

    Purpose. The aim was to explore the effect of the chromium picolinate (CrPic) administration on the pancreas and macroangiopathy of type II diabetes mellitus rats. Methods. The type II diabetes mellitus (T2DM) rat model was induced by low-dose streptozotocin (STZ). The rats were randomly divided into 5 groups (ten rats in each group). After supplementing CrPic for 15 weeks, the histopathological examination was performed by hematoxylin-eosin (HE) staining. Serum insulin and NO level were determined by radioimmunoassay and colorimetry, respectively. Serum glycosylated hemoglobin (HbA1C), adiponectin (APN), advanced glycation end products (AGES), and apelin were measured by ELISA. Real-time reverse transcription polymerase chain reaction (RT-PCR) was applied for detecting the mRNA expression of APN and apelin. Results. After CrPic treatment, compared with the T2DM control group (group 2), pancreas sections stained with HE showed the completed pancreatic cells structure and no inflammatory infiltration in groups 4 and 5. In addition, the levels of serum NO and insulin were significantly increased and the serum levels of HbA1C, AGES, APN, and apelin were significantly decreased in groups 4 and 5 compared with group 2. The mRNA expression of APN and apelin in groups 4 and 5 was also recovered to the normal level. Conclusion. CrPic can recover the function of ?-cells and alleviate macroangiopathy in STZ-induced T2DM rats. PMID:25054160

  3. Oral administration of grape seed proanthocyanidin extracts downregulate RAGE dependant nuclear factor- kappa BP65 expression in the hippocampus of streptozotocin induced diabetic rats.

    PubMed

    Xu, L; Li, B; Cheng, M; Zhang, W; Pan, J; Zhang, C; Gao, H

    2008-04-01

    Chronic degenerative brain disease in diabetes, known as 'diabetic encephalopathy', is a recognized complication that can occur due to long-standing diabetes in patients. It is defined by chronic cognitive disturbance and it is thought to relate to regional tissue pathological changes in the brain. Furthermore, hyperglycemia induced activation of the AGE (S)/RAGE/NF-kappaB pathway may play an important role in the pathogenesis of the degenerative changes seen in the diabetic hippocampus. To help prevent the development of and to potentially treat this brain disease, effective interventions directed toward key molecular target(s) are required. Grape seed proanthocyanidin extracts (GSPE), which are the anti-oxidants derived from grape seeds, have been reported to possess a variety of potent properties. As a consequence, they may have therapeutic effects in the prevention and treatment of complications in patients with diabetes. In this study, we firstly examined whether GSPE could attenuate the structural degenerative changes in the diabetic hippocampus in a rodent model of diabetes. Secondly, we addressed if such effects of GSPE may be occurring through modulation of the receptor for advanced glycation end products (RAGE) and/or nuclear factor-kappa BP65 (NF-kappaBP65). Hippocampi from GSPE treated STZ induced diabetic rats were immunohistochemically stained for glial fibrillary acidic protein, RAGE and NF-kappaBP65 and for morphological observations. Western blot was used to detect the proteins of RAGE and NF-kappaBP65. Real time, reverse transcriptase coupled to polymerase chain reaction was used for quantitative determination of mRNA for RAGE and NF-kappaBP65. Analysis of data showed that long term chronic hyperglycemia caused the overexpression of AGE (S)/RAGE and NF-kappaBp65 in the CA region of hippocampus in STZ induced diabetic rats. GSPE decreased the expression of RAGE and NF-kappaBP65 at a daily oral dosage of 250 mg/kg. This study provides indication that GSPE can prevent structural changes of diabetes in the rat brain and it suggests that GSPE might be a useful remedy in the treatment of diabetic encephalopathy. In addition, it implicates the potential pathological role of RAGE and NF-kappaBP65 in diabetic encephalopathy. PMID:18273752

  4. Peripheral nerve metabolism and zinc levels in streptozotocin induced diabetic rats. Effect of diets high in fish and corn oil

    SciTech Connect

    Burke, J.P.; Fenton, M.R. (Pennsylvania College of Podiatric Medicine, Philadelphia (United States))

    1991-03-15

    This study was designed to assess the effects of diets high in fish and corn oil on peripheral nerve metabolism in streptozotocin (STZ) induced diabetic rats. A type I diabetic state was induced in female Sprague-Dawley rats by injection of STZ. Animals were divided into three dietary groups; normal rat chow, high corn oil diet and high fish oil diet. After 4 weeks animals were analyzed for nerve conduction velocity, bled and then sacrificed. Sciatic nerves were removed, processed and several biochemical parameters determined. Plasma zinc levels were elevated in the STZ normal chow group compared to non-diabetic controls. Both corn oil and fish oil diets tended to eliminate the rise in plasma zinc. Differences in subcellular distribution of zinc in sciatic nerves were also observed. Normal chow STZ animals displayed a 20% decrease in nerve conduction velocity compared to control. Dietary supplementation with either fish or corn oil seemed to ameliorate these effects. Biochemical analysis of Na{sup +}-K{sup +}-ATPase and protein kinase C revealed a decrease in activity in normal chow animals compared to control groups. Again, dietary intervention with either fish or corn oil seemed to return these activities back to normal. The results suggest a link between zinc metabolism and peripheral nerve metabolism which can be modified by dietary intervention.

  5. Mangiferin Attenuates Diabetic Nephropathy by Inhibiting Oxidative Stress Mediated Signaling Cascade, TNF? Related and Mitochondrial Dependent Apoptotic Pathways in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Pal, Pabitra Bikash; Sinha, Krishnendu; Sil, Parames C.

    2014-01-01

    Oxidative stress plays a crucial role in the progression of diabetic nephropathy in hyperglycemic conditions. It has already been reported that mangiferin, a natural C-glucosyl xanthone and polyhydroxy polyphenol compound protects kidneys from diabetic nephropathy. However, little is known about the mechanism of its beneficial action in this pathophysiology. The present study, therefore, examines the detailed mechanism of the beneficial action of mangiferin on STZ-induced diabetic nephropathy in Wister rats as the working model. A significant increase in plasma glucose level, kidney to body weight ratio, glomerular hypertrophy and hydropic changes as well as enhanced nephrotoxicity related markers (BUN, plasma creatinine, uric acid and urinary albumin) were observed in the experimental animals. Furthermore, increased oxidative stress related parameters, increased ROS production and decreased the intracellular antioxidant defenses were detected in the kidney. Studies on the oxidative stress mediated signaling cascades in diabetic nephropathy demonstrated that PKC isoforms (PKC?, PKC? and PKC?), MAPKs (p38, JNK and ERK1/2), transcription factor (NF-?B) and TGF-?1 pathways were involved in this pathophysiology. Besides, TNF? was released in this hyperglycemic condition, which in turn activated caspase 8, cleaved Bid to tBid and finally the mitochorndia-dependent apoptotic pathway. In addition, oxidative stress also disturbed the proapoptotic-antiapoptotic (Bax and Bcl-2) balance and activated mitochorndia-dependent apoptosis via caspase 9, caspase 3 and PARP cleavage. Mangiferin treatment, post to hyperglycemia, successfully inhibited all of these changes and protected the cells from apoptotic death. PMID:25233093

  6. Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic Sprague-Dawley rats.

    PubMed

    Sani, Nur Fathiah Abdul; Belani, Levin Kesu; Sin, Chong Pui; Rahman, Siti Nor Amilah Abdul; Das, Srijit; Chi, Thent Zar; Makpol, Suzana; Yusof, Yasmin Anum Mohd

    2014-01-01

    Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P < 0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P < 0.05) in STZ-induced diabetic rats compared to diabetic control rats. PMID:24822178

  7. Serum Biochemical, Histopathology and SEM Analyses of the Effects of the Indian Traditional Herb Wattakaka Volubilis Leaf Extract on Wistar Male Rats

    PubMed Central

    Gopal, Velmani; Mandal, Vivekananda; Tangjang, Sumpam; Mandal, Subhash C.

    2014-01-01

    Objectives: The present study investigated the protective effect of Wattakaka (W.) volubilis leaf extract against streptozotocin (STZ)-induced diabetes in rats. Methods: Male Wistar rats were divided into five groups (with six rats in each group) and were fed ad libitum. The rats were fasted for sixteen hours before diabetes was induced by injecting a single dose of 90 mg/kg body weight of STZ in 0.9-percent normal saline through an intraperitoneal route. The five groups were as follows: Group 1: normal control (saline-treated), Group 2: untreated diabetic rats, Groups 3 and 4: diabetic rats treated orally with petroleum ether cold maceration extract (PEME) of W. volubilis(50 and 100 mg/kg body weight), and Group 5: diabetic rats treated orally with metformin (250 mg/kg body weight). All rats received treatment for 21 days. For the STZ-induced diabetic rats, the blood-glucose, ?-amylase, total protein and alanine transaminase (ALT) levels were measured on days 7,14 and 21 of the treatment with PEME of W. volubilis and the treatment with metformin. Histopathological changes in the liver were examined with hematoxylin-eosin staining. Morphological changes in the liver were also examined with glutaraldehyde fixation. Results: The treatments with PEME of W. volubilis and with metformin in experimental rats by oral injections for 21 days produced reductions in the levels of serum biochemical markers. Histopathology and scanning electron microscopy results showed that the administrations of PEME of W. volubilis and of metformin suppressed the generation of abnormal liver cells in the STZ-treated rats. Conclusion: These results suggest that both PEME of W. volubilis and metformin have a protective effect against STZ-induced diabetes. PMID:25780685

  8. Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats.

    PubMed

    Hofni, Amal; El-Moselhy, Mohamed A; Taye, Ashraf; Khalifa, Mohamed M

    2014-12-01

    Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg). The diabetic rats were orally treated with spironolactone (50 mg/kg/day) and/or candesartan (1 mg/kg/day) for 8 weeks. Administration of STZ caused a marked elevation in the serum level of creatinine, urea and urinary albumin-creatinine ratio (ACR). This was associated with upregulated renal protein levels of nuclear factor-kappa B (NF-?B), transforming growth factor (TGF)-?, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) alongside increasing the renal superoxide anion (O2(-)) production, malondialdehyde (MDA) level and the systolic blood pressure. There was a marked decrease in nitric oxide (NO) bioavailability and antioxidant enzyme capacity. The combined therapy of spironolactone and candesartan significantly normalized the oxidative stress and fibrotic/inflammatory alterations. Additionally, the elevated blood pressure was attenuated by administration of candesartan alone or in combination. This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy. In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers. PMID:25446917

  9. Impact of gestational diabetes and lactational insulin replacement on structure and secretory function of offspring rat ventral prostate.

    PubMed

    Santos, Sérgio A A; Rinaldi, Jaqueline C; Martins, Amanda E; Camargo, Ana C L; Leonelli, Carina; Delella, Flávia K; Felisbino, Sérgio L; Justulin, Luis A

    2014-09-15

    Clinical and experimental studies have shown that exposure to adverse conditions during the critical stages of embryonic, fetal or neonatal development lead to a significantly increased risk of later disease. Diabetes during pregnancy has been linked to increased risk of obesity and diabetes in offspring. Here, we investigated whether mild gestational diabetes mellitus (GDM) followed or not by maternal insulin replacement affects the ventral prostate (VP) structure and function in male offspring at puberty and adulthood. Pregnant rats were divided into the following 3 groups: control (CT); streptozotocin (STZ)-induced diabetes (D); and D plus insulin replacement during lactation (GDI). The male offspring from different groups were euthanized at postnatal day (PND) 60 and 120. Biometrical parameters, hormonal levels and prostates were evaluated. Mild-GDM promoted reduction in the glandular parenchyma and increased collagen deposition. Insulin replacement during lactation restored the VP morphology. Most importantly, mild-GDM decreased the androgen-induced secretory function as determined by prostatein expression, and insulin replacement reversed this effect. Our results demonstrated that mild GDM impairs VP parenchyma maturation, which is associated with an increase in the fibromuscular stroma compartment. Functionally, the reduction in the VP parenchyma decreases the glandular secretory activity as demonstrated by low expression of prostatein, a potent immunosuppressor factor that protects sperm from immunologic damage into the feminine reproductive tract. This change could lead to impairment of reproductive function in male offspring from diabetic mothers. Maternal insulin replacement during the weaning period apparently restores the prostate function in male offspring. PMID:24983773

  10. Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of methanol/dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats

    PubMed Central

    2014-01-01

    Background Hypoglycemic and/or anti-hyperglycemic activities have been recorded with numerous plants, many of which are used as traditional herbal treatments of diabetes. Albizzia Lebbeck Benth. stem bark have been used in traditional medicine along with some preliminary reports on its hypoglycemic action. The aim of present investigation was to evaluate the antidiabetic and antioxidant activities of methanolic extract of stem bark of Albizzia Lebbeck Benth. in streptozotocin induced diabetic rats. Methods The powdered stem bark of Albizzia Lebbeck Benth.. was extracted with methanol (MeOH) using soxhlation method and subjected to phytochemical analysis. The methanol/dichloromethane extract of Albizzia Lebbeck Benth. (ALEx) was concentrated to dryness using Rotary Evaporator. Diabetes was experimentally induced in the rats by single intraperitoneal administration of Streptozotocin (60 mg/kg). They glycemic control was measured by the blood glucose, glycated heamoglobin and plasma insulin. The oxidative stress was evaluated in the liver and kidney by level of antioxidant markers and various biochemical parameters were assessed in diabetic control and extract treated rats. Results Streptozotocin induced diabetic rats depicted the increased blood glucose levels, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), diminished level of high density lipoprotein cholesterol (HDL-c) level and perturb level of antioxidant markers. Oral administration of MeAL at a concentration of 100, 200, 300 and 400 mg/kg b.w daily for 30 days results a momentous decrease in fasting blood glucose, glycated heamoglobin and enhancement of plasma insulin level as compared with STZ induced diabetic rats. Furthermore, it significantly (p?STZ induced diabetic rats. Histopathological studies suggest the diminution in the pancreatic, liver and cardiac muscle damage. Conclusion Our research exertion clearly indicates the considerable antihyperglycemic, antihyperlipidemic, antioxidant & pancreas/renal/hepatic/cardiac protective action of ALEx. PMID:25026962

  11. Streptozotocin-induced dynamic metabonomic changes in rat biofluids.

    PubMed

    Xu, Wenxin; Wu, Junfang; An, Yanpeng; Xiao, Chaoni; Hao, Fuhua; Liu, Hongbing; Wang, Yulan; Tang, Huiru

    2012-06-01

    Diabetes mellitus is a complex polygenic disease caused by gene-environment interactions with multiple complications, and metabonomic analysis is crucial for pathogenesis, early diagnosis, and timely interventions. Here, we comprehensively analyzed the dynamic metabolic changes in rat urine and plasma, which were induced by the well-known diabetogenic chemical streptozotocin (STZ), using (1)H NMR spectroscopy in conjunction with multivariate data analysis. The results showed that a single intraperitoneal injection of STZ with a moderate dosage (55 mg/kg) induced significant urinary metabonomic changes within 24 h. These changes showed time-dependence and heterogeneity among the treated animals with an animal recovered within 11 days. STZ-induced metabonomic alterations were related to suppression of glycolysis and TCA cycle, promotion of gluconeogenesis and oxidation of amino acids, alterations in metabolisms of basic amino acids associated with diabetic complications, and disruption of lipid metabolism and gut microbiota functions. With diffusion-edited NMR spectral data, we further observed the STZ-induced significant elevation of monounsaturated fatty acids and total unsaturated fatty acids together with reductions in PUFA-to-MUFA ratio in the blood plasma. These findings provided details of the time-dependent metabonomic changes in the progressive development of the STZ-induced diabetes mellitus and showed the possibility of detecting the biochemical changes in the early stage of type 1 diabetic genesis. PMID:22563680

  12. Extract of green tea leaves partially attenuates streptozotocin-induced changes in antioxidant status and gastrointestinal functioning in rats

    Microsoft Academic Search

    Jerzy Ju?kiewicz; Zenon Zdu?czyk; Adam Jurgo?ski; ?ucja Brzuzan; Irena Godycka-K?os; Ewa ?ary-Sikorska

    2008-01-01

    Rats with severe streptozotocin (STZ)-induced diabetes were subjected to dietary green tea extract supplementation at 2 doses (0.01% and 0.2%; GTL and GTH groups, respectively) to evaluate their effects on antioxidant, gastrointestinal, and renal parameters of experimental animals. The lower dietary supplementation reflects daily consumption of 3 cups of green tea for an average adult weighing 70 kg. Supplementation of

  13. Exercise Training Improves the Defective Centrally Mediated Erectile Responses in Rats with Type I Diabetes

    PubMed Central

    Zheng, Hong; Mayhan, William G.; Patel, Kaushik P.

    2011-01-01

    Introduction Erectile dysfunction is a serious and common complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for the penile erection. Aim The goal of the present study was to determine the impact of exercise training (ExT) on the centrally mediated erectile dysfunction in streptozotocin (STZ)-induced type I diabetic (T1D) rats. Methods Male Sprague-Dawley rats were injected with STZ to induce diabetes mellitus. Three weeks after STZ or vehicle injections, rats were assigned to either ExT (treadmill running for 3-4 weeks) or sedentary groups to produce four experimental groups: control+sedentary, T1D+sedentary, control+ExT and T1D+ExT. Main Outcome Measure After 3-4 weeks ExT, central N-methyl-D-aspartic acid (NMDA) or sodium nitroprusside (SNP)-induced penile erectile responses were measured. Neuronal nitric oxide synthase (nNOS) expression in the paraventricular neuleus (PVN) of the hypothalamus was measured by using histochemistry, real time PCR and Western blot approaches. Results In rats with T1D, ExT significantly improved the blunted erectile response and ICP changes to NMDA (50ng) microinjection within the PVN (T1D+ExT: 3.0±0.6 penile erection/rat; T1D+sedentary: 0.5±0.3 penile erection/rat within 20mins, P<0.05). ExT improved erectile dysfunction induced by central administration of exogenous nitric oxide (NO) donor, SNP in T1D rats. Other behavior responses including yawning and stretching, induced by central NMDA and SNP microinjection were also significantly increased in T1D rats after ExT. Furthermore, we found ExT restored the nNOS mRNA and protein expression in the PVN in T1D rats. Conclusions These results suggest that ExT may have beneficial effects on the erectile dysfunction in diabetes through improvement of NO bioavailability within the PVN. Thus, ExT may be used as therapeutic modality to up-regulate nNOS within the PVN and improve the central component of the erectile dysfunction in diabetes mellitus. PMID:21883945

  14. Limiting prolonged inflammation during proliferation and remodeling phases of wound healing in streptozotocin-induced diabetic rats supplemented with camel undenatured whey protein

    PubMed Central

    2013-01-01

    Background Impaired diabetic wound healing occurs as a consequence of excessive reactive oxygen species (ROS) and inflammatory cytokine production. We previously found that whey protein (WP) was able to normally regulate the ROS and inflammatory cytokines during the inflammatory phase (first day) in streptozotocin (STZ)-diabetic wound healing. This study was designed to assess the effect of WP on metabolic status, the inflammation and anti-inflammation response, oxidative stress and the antioxidant defense system during different phases of the wound healing process in diabetic rats. WP at a dosage of 100 mg/kg of body weight, dissolved in 1% CMC, was orally administered daily to wounded normal (non-diabetic) and STZ-induced diabetic rats for 8 days starting from the 1st day after wounding. Results The data revealed that WP enhanced wound closure and was associated with an increase in serum insulin levels in diabetic rats and an alleviation of hyperglycemic and hyperlipidemic states in diabetic animals. The increase in insulin levels as a result of WP administration is associated with a marked multiplication of ?-cells in the core of islets of Langerhans. WP induced a reduction in serum TNF-?, IL-1? and IL-6 levels and an increase in IL-10 levels, especially on the 4th day after wounding and treatment. WP also suppressed hepatic lipid peroxidation and stimulated the antioxidant defense system by increasing the level of glutathione and the activity of glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (SOD) in wounded diabetic rats. Conclusions WP was observed to enhance wound closure by improving the diabetic condition, limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats. PMID:23883360

  15. Promoted interaction of nuclear factor-?B with demethylated cystathionine-?-synthetase gene contributes to gastric hypersensitivity in diabetic rats.

    PubMed

    Zhang, Hong-Hong; Hu, Ji; Zhou, You-Lang; Hu, Shufen; Wang, Yong-Meng; Chen, Wei; Xiao, Ying; Huang, Li-Yen Mae; Jiang, Xinghong; Xu, Guang-Yin

    2013-05-22

    Patients with long-standing diabetes frequently demonstrate gastric hypersensitivity with an unknown mechanism. The present study was designed to investigate roles for nuclear factor-?B (NF-?B) and the endogenous H2S-producing enzyme cystathionine-?-synthetase (CBS) signaling pathways by examining cbs gene methylation status in adult rats with diabetes. Intraperitoneal injection of streptozotocin (STZ) produced gastric hypersensitivity in female rats in response to gastric balloon distention. Treatment with the CBS inhibitor aminooxyacetic acid significantly attenuated STZ-induced gastric hypersensitivity in a dose-dependent fashion. Aminooxyacetic acid treatment also reversed hyperexcitability of gastric-specific dorsal root ganglion (DRG) neurons labeled by the dye DiI in diabetic rats. Conversely, the H2S donor NaHS enhanced neuronal excitability of gastric DRG neurons. Expression of CBS and p65 were markedly enhanced in gastric DRGs in diabetic rats. Blockade of NF-?B signaling using pyrrolidine dithiocarbamate reversed the upregulation of CBS expression. Interestingly, STZ treatment led to a significant demethylation of CpG islands in the cbs gene promoter region, as determined by methylation-specific PCR and bisulfite sequencing. STZ treatment also remarkably downregulated the expression of DNA methyltransferase 3a and 3b. More importantly, STZ treatment significantly enhanced the ability of cbs to bind DNA at the p65 consensus site, as shown by chromatin immunoprecipitation assays. Our findings suggest that upregulation of cbs expression is attributed to cbs promoter DNA demethylation and p65 activation and that the enhanced interaction of the cbs gene and p65 contributes to gastric hypersensitivity in diabetes. This finding may guide the development and evaluation of new treatment modalities for patients with diabetic gastric hypersensitivity. PMID:23699514

  16. Modulatory effect of polyphenolic extracts of Ichnocarpus frutescens on oxidative stress in rats with experimentally induced diabetes

    PubMed Central

    Kumarappan, C. T.; Thilagam, E.; Vijayakumar, M.; Mandal, Subhash C.

    2012-01-01

    Background & objectives: The role of oxidative stress in the development of diabetes mellitus and its vascular complications are extensively studied. Hyperglycaemia causes oxidative damage by generation of reactive oxygen species and results in the development of complications. The present study was undertaken with the objective of exploring the anti-hyperglycaemic potential of polyphenolic enriched extract of Ichnocarpus frutescens in streptozotocin induced (n-STZ) neonatal diabetic rats (pups) for six weeks and to study oxidative stress and antioxidant status. Methods: Two days old pups were rendered diabetic by single injection of streptozotocin (90 mg/kg body wt, ip). At the end of the treatment period, the level of blood glucose, serum biochemical markers, serum lipid levels and liver malondialdehyde, tissue antioxidant levels were measured. Results: A marked rise was observed in the levels of fasting blood glucose (230.33 mg/dl), lipid profiles, lipid peroxidative products and a significant decrease in tissue antioxidants (superoxide dismuatase, catalase and reduced glutathione) and serum high density lipoprotein cholesterol levels in STZ treated rats. Oral administration of polyphenolic extract (150 and 300 mg/kg body wt, po) decreased fasting blood glucose levels (187.66 and 170.50 mg/dl, respectively) of STZ-treated diabetic rats significantly (P<0.01), when compared with control rats. In addition, the polyphenolic extract showed favourable effect (P<0.01) on the reduced tissues antioxidants level, liver glycogen level, high density lipoprotein level, with significant (P<0.01) reduction of elevated lipid peroxidation products. Histopathological study of the pancreas showed the protective role of polyphenolic extract. Interpretation & conclusions: Our study showed the antioxidant of effect polyphenolic extract of I. frutescens in STZ induced experimental diabetes. The results also suggested that this polyphenolic rich extract could be potentially useful for hyperglycaemia treatment to correct the diabetic state. PMID:23287129

  17. Therapeutic Effects of 15 Hz Pulsed Electromagnetic Field on Diabetic Peripheral Neuropathy in Streptozotocin-Treated Rats

    PubMed Central

    Jiang, Maogang; Li, Feijiang; Cai, Jing; Wu, Xiaoming; Tang, Chi; Xu, Qiaoling; Liu, Juan; Guo, Wei; Shen, Guanghao; Luo, Erping

    2013-01-01

    Although numerous clinical studies have reported that pulsed electromagnetic fields (PEMF) have a neuroprotective role in patients with diabetic peripheral neuropathy (DPN), the application of PEMF for clinic is still controversial. The present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague–Dawley rats were randomly divided into three weight-matched groups (eight in each group): the non-diabetic control group (Control), diabetes mellitus with 15 Hz PEMF exposure group (DM+PEMF) which were subjected to daily 8-h PEMF exposure for 7 weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. Meanwhile, ultrastructural examination and immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. During a 7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN. However, PEMF stimulation attenuated the development of the abnormalities observed in STZ-treated rats with DPN, which were demonstrated by increased hind paw withdrawal threshold to mechanical and thermal stimuli, slighter demyelination and axon enlargement and less VEGF immunostaining of sciatic nerve compared to those of the DM group. The current study demonstrates that treatment with PEMF might prevent the development of abnormalities observed in animal models for DPN. It is suggested that PEMF might have direct corrective effects on injured nerves and would be a potentially promising non-invasive therapeutic tool for the treatment of DPN. PMID:23637830

  18. Therapeutic effects of 15 Hz pulsed electromagnetic field on diabetic peripheral neuropathy in streptozotocin-treated rats.

    PubMed

    Lei, Tao; Jing, Da; Xie, Kangning; Jiang, Maogang; Li, Feijiang; Cai, Jing; Wu, Xiaoming; Tang, Chi; Xu, Qiaoling; Liu, Juan; Guo, Wei; Shen, Guanghao; Luo, Erping

    2013-01-01

    Although numerous clinical studies have reported that pulsed electromagnetic fields (PEMF) have a neuroprotective role in patients with diabetic peripheral neuropathy (DPN), the application of PEMF for clinic is still controversial. The present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague-Dawley rats were randomly divided into three weight-matched groups (eight in each group): the non-diabetic control group (Control), diabetes mellitus with 15 Hz PEMF exposure group (DM+PEMF) which were subjected to daily 8-h PEMF exposure for 7 weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. Meanwhile, ultrastructural examination and immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. During a 7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN. However, PEMF stimulation attenuated the development of the abnormalities observed in STZ-treated rats with DPN, which were demonstrated by increased hind paw withdrawal threshold to mechanical and thermal stimuli, slighter demyelination and axon enlargement and less VEGF immunostaining of sciatic nerve compared to those of the DM group. The current study demonstrates that treatment with PEMF might prevent the development of abnormalities observed in animal models for DPN. It is suggested that PEMF might have direct corrective effects on injured nerves and would be a potentially promising non-invasive therapeutic tool for the treatment of DPN. PMID:23637830

  19. Effects of perfusion pressure and insulin on (/sup 3/H) cytochalasin B (CB) binding to control and diabetic rat hearts

    SciTech Connect

    Pleta, M.; Chan, T.

    1987-05-01

    Using (/sup 3/H) CB, they attempted to quantitate the changes in the amount of glucose transporters in the plasma membrane (PM) and intracellular membranes (HSP) prepared from rat hearts perfused with insulin, under low and high pressure. Membranes isolated from non-perfused hearts showed a PM/HSP ratio of (0.593). Hearts perfused with low pressure showed a lower ratio of (0.474). Perfusion with insulin increased the ratio to (1.8), almost a 3-4 fold increase from low perfusion pressure. These data correlate with insulin effects in glucose transport and CB binding in the fat cells. High pressure perfusion increased the PM/HSP ratio by 1-2 fold. (/sup 3/H) 2-DG transport indicates a comparable increase in glucose uptake with high pressure, but with insulin only a 1.5 fold increase was observed. Initial data obtained from streptozotocin (STZ) injected diabetic rats indicate low CB binding in the PM fraction. Only insulin, but not high perfusion pressure increased PM/HSP ratio in the STZ-diabetic hearts. Their data imply that while both caused apparent translocation of glucose transporters, influences on cardiac glucose metabolism by work load are different. Furthermore, STZ induced diabetes affected only the high perfusion pressure-induced and not the insulin-stimulated change in CB binding.

  20. Comparison of the effects of fresh leaf and peel extracts of walnut (Juglans regia L.) on blood glucose and ?-cells of streptozotocin-induced diabetic rats

    PubMed Central

    Javidanpour, Somaye; Fatemi Tabtabaei, Seyed Reza; Siahpoosh, Amir; Morovati, Hasan; Shahriari, Ali

    2012-01-01

    There is some report about the hypoglycemic effect of Juglans rejia L. leaf in alloxan induced diabetic rats and hypoglycemic effect of its fruit peel administered intra peritoneally. Thirty male Wistar rats divided into five groups, to evaluate the hypoglycemic and pancreas ?-cells regenerative effects of oral methanolic extracts of leaf and fruit peel of walnut. Rats were made diabetic by intravenous (IV) injection of 50 mg kg-1 streptozotocin (STZ). Negative control group did not get STZ and any treatment. Positive control, leaf extract, peel extract and insulin groups were treated orally by extract solvent, 200 mg kg-1 leaf extract, 200 mg kg-1 peel extract and 5 IU kg-1 of subcutaneous neutral protamine Hagedorn (NPH) insulin, respectively. Four weeks later, blood was collected for biochemical analysis and pancreases were removed for ?-cells counts in histological sections. Diabetes leads to increase of fast blood sugar (FBS) and HbA1c, and decrease of ?-cell number and insulin. FBS decreased only in leaf extract group. HbA1c decreased in leaf extract and insulin groups. The ?-cells number increased in leaf and peel extract groups. Insulin increased moderately in all treatment groups. We showed the proliferative properties of leaves and peel of Juglans regia L. methanolic extract in STZ- induced diabetic rats, which was accompanied by hypoglycemic effect of leaf extract. PMID:25653767

  1. Microglia are selectively activated in endocrine and cardiovascular control centres in streptozotocin-induced diabetic rats.

    PubMed

    Rana, I; Badoer, E; Alahmadi, E; Leo, C H; Woodman, O L; Stebbing, M J

    2014-07-01

    Type 1 and 2 diabetes are associated with dysfunction in multiple hormone systems, as well as increased sympathetic nerve activity, which may contribute to the development of diabetic complications. In other pathologies, such as myocardial infarction, increased sympathetic drive is associated with neuroinflammation and microglial activation in the hypothalamic paraventricular nucleus (PVN), a brain region that regulates sympathetic drive and multiple endocrine responses. In the present study, we used immunohistochemistry to study microglial and neuronal activation in the PVN and related brain regions in streptozotocin (STZ)-induced diabetic rats. As expected, STZ treatment was associated with elevated blood glucose within 1 week. STZ injections also caused neuronal activation in the PVN and superoptic nucleus (SON) but not in the nucleus tractus solitarius (NTS), which was evident by 6 weeks. STZ-treated rats showed increased plasma osmolarity, which would be expected to activate PVN and SON neurones. There was no apparent increase in histochemical markers of microglial activation, including phospho-p38, phospho-extracellular signal regulated kinase, P2X4 receptor or interleukin 1-? even at 10 weeks after STZ-treatment. However, we did see a significant increase in the percentage of microglia with an activated morphology in the PVN, SON and NTS, although not in surrounding hypothalamic, brainstem or cortical regions. These morphological changes included a significant reduction in microglial process length and were evident by 8 weeks but not 6 weeks. The delayed onset of microglial changes compared to neuronal activation in the PVN and SON suggests the over-excitation of neurones as a mechanism of microglial activation. This delayed microglial activation may, in turn, contribute to the endocrine dysregulation and the elevated sympathetic nerve activity reported in STZ-treated rats. PMID:24762326

  2. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats.

    PubMed

    Rashid, Kahkashan; Sil, Parames C

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-?, IL1-? and IFN-?), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. PMID:25541178

  3. Aminoguanidine changes hippocampal expression of apoptosis-related genes, improves passive avoidance learning and memory in streptozotocin-induced diabetic rats.

    PubMed

    Firouzjaei, Maryam Arab; Jafari, Mohammad Reza; Eskandari, Mehdi; Anarkoli, Iraj Jafari; Alipour, Mohsen

    2014-04-01

    Cognitive dysfunction occurs in patients with diabetes mellitus. The objective of this study was to examine whether bilateral intrahippocampal CA1 (intra-CA1) injection of aminoguanidine (AG) can either affect the Bcl-2 family gene expression or reduce the diabetic imposing abnormalities of passive avoidance learning (PAL) and memory. Rats were divided into five groups: control (C), control treated with normal saline (CS), control treated with AG (S-AG), diabetics (D), and diabetics treated with AG (D-AG). Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg). AG (30 ?g/rat) or vehicle was administered intra-CA1 bilaterally at the onset of hyperglycemia. PAL was assessed 7 weeks later. Animals were killed, and hippocampus was dissected following the behavioral test. The expressions of Bax, Bcl-2, and Bcl-xl mRNAs were measured using semiquantitative RT-PCR technique. The result of passive avoidance task showed that AG significantly improved the cognitive performance in diabetic rats. Moreover, AG treatment decreased the levels of Bcl-2 and Bcl-xL expressions in diabetic group. The ratio of Bax/Bcl-2 and Bax/Bcl-xL decreased significantly in AG-treated diabetic animals. In conclusion, initial treatment with AG by intra-CA1 micro-injection improves the impaired passive avoidance task in STZ-induced diabetic rats which may be related to the decreased Bax/Bcl-2 and Bax/Bcl-xL ratios. PMID:24326522

  4. Effect of curcumin on diabetic peripheral neuropathic pain: possible involvement of opioid system.

    PubMed

    Banafshe, Hamid R; Hamidi, Gholam A; Noureddini, Mahdi; Mirhashemi, Seyyed Mehdi; Mokhtari, Rasool; Shoferpour, Mehdi

    2014-01-15

    Neuropathic pain is one of the most common complications of diabetes mellitus. As efficacy and tolerability of current therapy for neuropathic pain are not ideal, we need to develop the novel drug for better treatment. Curcumin as a natural flavonoid from Curcuma longa has considerable effects on nervous system such as, antidepressant, antinociceptive and neuroprotective effects. The present study was designed to investigate the effect of curcumin on diabetic peripheral neuropathic pain and possible involvement of opioid system. A single dose of 60mg/kg streptozotocin was injected intraperitoneally to induce diabetes in rats. STZ-induced diabetic rats were treated with curcumin (50mg/kg/day) acute and chronically. Thermal hyperalgesia and mechanical allodynia were measured on the days 0, 7, 14 and 21 after diabetes induction as behavioral scores of neuropathic pain. Chronic, but not acute, treatment with curcumin prevents the weight loss and attenuates mechanical allodynia in STZ-induced diabetic rats. Pretreatment with naloxone (1mg/kg) significantly reduced anti-allodynic effect of chronic curcumin in von Frey filament test. Our results suggest that curcumin can be considered as a new therapeutic potential for the treatment of diabetic neuropathic pain and the activation of opioid system may be involved in the antinociceptive effect of curcumin. PMID:24315931

  5. Ameliorating effect of mother tincture of Syzygium jambolanum on carbohydrate and lipid metabolic disorders in streptozotocin-induced diabetic rat: Homeopathic remedy

    PubMed Central

    Maiti, Soumyajit; Ali, Kazi M.; Jana, Kishalay; Chatterjee, Kausik; De, Debasis; Ghosh, Debidas

    2013-01-01

    Background: Syzygium jambolanum (S jambolanum) is widely used in homeopathy for treating patients with diabetes mellitus. In the present study, an attempt has been made to investigate the remedial effect of homeopathic drug S jambolanum on carbohydrate and lipid metabolic disorders on streptozotocin induced diabetic rat. Materials and Methods: Diabetes induction in Wistar strain rat was performed as per standard method using streptozotocin at the dose of 4 mg/100 gm body weight. Activities of carbohydrate metabolic enzymes in hepatic tissue, and glycogen content in hepatic and muscular tissues were assessed biochemically following the standard protocols. Serum lipid profile level and activities of GOT and GPT in serum were measured as per standard method using specific kits. Results: The homeopathic drug, mother tincture of S jambolanum significantly decreased fasting blood glucose levels and improved carbohydrate metabolic key enzyme activities in hepatic tissue i.e., hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase in diabetic rats. Alongside, serum lipid profile biomarkers i.e., triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc) and high density lipoprotein cholesterol (HDLc) levels were significantly ameliorated in homeopathic drug supplemented diabetic animals in compared with the untreated diabetic animal. Side by side, the S jambolanum has the capacity to attenuate diabetes induced hepatic injury in model animal, which has been assessed here by the recovery of GOT and GPT activities in serum of drug treated diabetic animal. Conclusion: The result of the present study indicated that the homeopathic drug S jambolanum (mother tincture) has a protective effect on diabetic induced carbohydrate and lipid metabolic disorders in STZ-induced diabetic animal. PMID:23633838

  6. Functional and Molecular Characterization of Hyposensitive Underactive Bladder Tissue and Urine in Streptozotocin-Induced Diabetic Rat

    PubMed Central

    Chuang, Yao-Chi; Lee, Wei-Chia; Yoshimura, Naoki; Huang, Chao-Cheng; Rajaganapathy, Bharathi; Chancellor, Michael B.

    2014-01-01

    Background The functional and molecular alterations of nerve growth factor (NGF) and Prostaglandin E2 (PGE2) and its receptors were studied in bladder and urine in streptozotocin (STZ)-induced diabetic rats. Methodology/Principal Findings Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p) in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI) and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP)1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12. Conclusions/Significance DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder. PMID:25050870

  7. Effect of Oral Administration of Magnesium on Cisplatin-Induced Nephrotoxicity in Normal and Streptozocin-Induced Diabetic Rats

    PubMed Central

    Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir; Ashrafi, Farzaneh

    2013-01-01

    Background Cisplatin (CP) therapy as the most common potent chemotherapeutic process is accompanied by nephrotoxicity. The diabetic state may protect rat kidney against this toxicity, and magnesium (Mg) on the other hand may reduce the glucose level in diabetic animals. Objectives Current study was planned to investigate the effect of oral administration of magnesium supplementation on CP-induced nephrotoxicity in normal and Streptozocin (STZ)-induced diabetic rats. Materials and Methods Male Wistar rats were divided into seven groups and underwent two experiment protocols. As protocol 1, group 1 was considered as the sham group. Group 2 (CP group) received CP (2 mg/kg/d) for five consecutive days. Group 3 (CP + Mg group) received magnesium sulphate (MgSO4, 10 g/L added to the drinking water) for 10 days and then treated with CP from sixth day. As protocol 2, animals received a single dose of STZ (65 mg/kg i.p.). Three days after diabetes induction, animals were divided into four groups; Groups 4 (D group), 5 (D + CP group), and 7 (D + Mg + CP group) followed the same manner as groups 1 to 3, respectively; and group 6 (D + Mg group) was treated with MgSO4 alone for 10 days. Finally, blood samples were obtained, and all animals were killed for kidney tissue investigation. Results CP administration in normoglycemic rats significantly elevated the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) (P < 0.05). However, coadministration of CP and Mg statistically increased the serum levels of BUN and Cr in both normoglycemic and diabetic animals when compared to the rats treated with CP alone (P < 0.05), while the serum level of Mg was significantly increased in nondiabetic groups (P < 0.05). No significant changes were observed in serum and kidney levels of nitrite; as well as the testis weight between all normoglycemic groups, whereas Mg decreased kidney levels of nitrite in diabetic groups when accompanied by CP (P < 0.05). The kidney and serum levels of malondialdehyde (MDA) enhanced significantly in nondiabetic rats treated with Mg and CP (P < 0.05). Kidney tissue damage score (KTDS), kidney weight, and body weight loss were significantly different among normoglycemic groups (P < 0.05), and Mg promoted the KTDS in diabetic animals treated with CP. Conclusions Oral Mg supplementation did not protect the CP induced nephrotoxicity in diabetic rats. PMID:24350087

  8. Diabetic Complications in Obese Type 2 Diabetic Rat Models

    PubMed Central

    Katsuda, Yoshiaki; Ohta, Takeshi; Miyajima, Katsuhiro; Kemmochi, Yusuke; Sasase, Tomohiko; Tong, Bin; Shinohara, Masami; Yamada, Takahisa

    2014-01-01

    We overviewed the pathophysiological features of diabetes and its complications in obese type 2 diabetic rat models: Otsuka Long-Evans Tokushima fatty (OLETF) rat, Wistar fatty rat, Zucker diabetic fatty (ZDF) rat and Spontaneously diabetic Torii (SDT) fatty rat. Pancreatic changes with progression of diabetes were classified into early changes, such as islet hypertrophy and degranulation of ? cells, and degenerative changes, such as islet atrophy and fibrosis of islet with infiltration of inflammatory cells. Renal lesions in tubuli and glomeruli were observed, and nodular lesions in glomeruli were notable changes in OLETF and SDT fatty rats. Among retinal changes, folding and thickening were interesting findings in SDT fatty rats. A decrease of motor nerve conduction velocity with progression of diabetes was presented in obese diabetic rats. Other diabetic complications, osteoporosis and sexual dysfunction, were also observed. Observation of bone metabolic abnormalities, including decrease of osteogenesis and bone mineral density, and sexual dysfunction, including hypotestosteronemia and erectile dysfunction, in obese type 2 diabetic rats have been reported. PMID:24770637

  9. Diabetic complications in obese type 2 diabetic rat models.

    PubMed

    Katsuda, Yoshiaki; Ohta, Takeshi; Miyajima, Katsuhiro; Kemmochi, Yusuke; Sasase, Tomohiko; Tong, Bin; Shinohara, Masami; Yamada, Takahisa

    2014-01-01

    We overviewed the pathophysiological features of diabetes and its complications in obese type 2 diabetic rat models: Otsuka Long-Evans Tokushima fatty (OLETF) rat, Wistar fatty rat, Zucker diabetic fatty (ZDF) rat and Spontaneously diabetic Torii (SDT) fatty rat. Pancreatic changes with progression of diabetes were classified into early changes, such as islet hypertrophy and degranulation of ? cells, and degenerative changes, such as islet atrophy and fibrosis of islet with infiltration of inflammatory cells. Renal lesions in tubuli and glomeruli were observed, and nodular lesions in glomeruli were notable changes in OLETF and SDT fatty rats. Among retinal changes, folding and thickening were interesting findings in SDT fatty rats. A decrease of motor nerve conduction velocity with progression of diabetes was presented in obese diabetic rats. Other diabetic complications, osteoporosis and sexual dysfunction, were also observed. Observation of bone metabolic abnormalities, including decrease of osteogenesis and bone mineral density, and sexual dysfunction, including hypotestosteronemia and erectile dysfunction, in obese type 2 diabetic rats have been reported. PMID:24770637

  10. Neuromodulatory Effects of Hesperidin in Mitigating Oxidative Stress in Streptozotocin Induced Diabetes

    PubMed Central

    Varshney, Laxmi; Khan, Mohammad Haaris Ajmal; Salman, Mohd.; Naseem, Mehar; Wajid, Saima

    2014-01-01

    Oxidative stress has been implicated in pathogenesis of streptozotocin- (STZ-) induced diabetes mellitus and its complication in central nervous system (CNS). Recent studies have provided insights on antioxidants and their emergence as potential therapeutic and nutraceutical. The present study examined the hypothesis that hesperidin (HP) ameliorates oxidative stress and may be a limiting factor in the extent of CNS complication following diabetes. To test this hypothesis rats were divided into four groups: control, diabetic, diabetic-HP treated, and vehicle for HP treatment group. Diabetes mellitus was induced by a single injection of STZ (65?mg/kg body weight). Three days after STZ injection, HP was given (50?mg/kg b.wt. orally) once daily for four weeks. The results of the present investigation suggest that the significant elevated levels of oxidative stress markers were observed in STZ-treated animals, whereas significant depletion in the activity of nonenzymatic antioxidants and enzymatic antioxidants was witnessed in diabetic rat brain. Neurotoxicity biomarker activity was also altered significantly. HP treatment significantly attenuated the altered levels of oxidative stress and neurotoxicity biomarkers. Our results demonstrate that HP exhibits potent antioxidant and neuroprotective effects on the brain tissue against the diabetic oxidative damage in STZ-induced rodent model. PMID:25050332

  11. In vivo Antidiabetic and Antioxidant Potential of Stephania hernandifolia in Streptozotocin-Induced-Diabetic Rats

    PubMed Central

    Sharma, U; Sahu, RK; Roy, A; Golwala, DK

    2010-01-01

    Stephania hernandifolia (Menispermaceae) is a medicinal plant, used by herbalists for treating various diseases, one of which is diabetes mellitus, in Darjeeling. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study, therefore, is to investigate the antidiabetic and antioxidant potential of the powdered corm of Stephania hernandifolia. This was tested in normal and Streptozotocin (STZ)-induced diabetic rats, using oral administration of ethanol and an aqueous extract (400 mg/kg body weight) of Stephania hernandifolia corm. After the oral administration of water and ethanol extracts at doses of 400 mg/kg body weight, blood glucose levels were monitored at specific intervals and it was found that they were significant lowered. Glibenclamide was used as a standard drug at a dose of 0.25 mg/kg. The experimental data revealed that both extracts has significant antihyperglycemic and antioxidant activity in Streptozotocin-induced rats compared to the standard drug. The antioxidant activity in vitro was measured by means of the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and Superoxide-free radical scavenging assay. Ascorbic acid, a natural antioxidant, was used as a control. The extracts of ethanol and aqueous were strongly scavenged DPPH radicals, with IC50 being 265.33 and 217.90 µg/ml, respectively. Although the extracts of ethanol and aqueous were moderately scavenged, the superoxide radical were with IC50 values of 526.87 and 440.89 µg/ml. The study revealed that the ethanolic extract exhibited more significant antidiabetic and antioxidant activity then the aqueous extract. PMID:21042481

  12. Regulation of cardiac oxidative stress and lipid peroxidation in streptozotocin-induced diabetic rats treated with aqueous extract of Pimpinella tirupatiensis tuberous root.

    PubMed

    Saddala, Rajeswara Reddy; Thopireddy, Lavanya; Ganapathi, Narasimhulu; Kesireddy, Sathyavelu Reddy

    2013-01-01

    Plants with antidiabetic activities provide important source for the development of new drugs in the management of diabetes mellitus. The main aim of this study was to evaluate the protective effect of aqueous extract (AE) of Pimpinella tirupatiensis (Pt) tuberous root on cardiac oxidative stress and lipid peroxidation (LPO) in non-diabetic and streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar rats by a single administration of STZ (40 mg/kg intraperitoneal (i.p). AE (750 mg/kg/b.w./day) and glibenclamide (GLB) (20 mg/kg/b.w./day) were administrated orally by intra oral gastric tube for 30 days. After 4 weeks of hyperglycaemia the enzymatic and non-enzymatic factors were measured in cardiac tissue of diabetic and control groups. Xanthine oxidase activity (XOD), Uric acid (UA) and malondialdehyde (MDA) content were significantly (p<0.01) elevated by 48, 48 and 50% respectively and the contents of glutathione (GSH), ascorbic acid (AA) were significantly (p<0.01) diminished by 45 and 42% respectively in diabetic rats when compared to normal. Treatment with AE and GLB normalized the content of UA, GSH, AA, MDA and the activity of XOD. No significant changes were observed in control rats treated with AE. This data suggests that hyperglycemia induces oxidative stress in the heart, but the oxidative stress defense mechanisms in the heart tissue are fairly efficacious against oxidative injury by the treatment with AE and GLB. The present study reveals that AE may provide a useful therapeutic option in the reversal of oxidative stress induced cardiac dysfunction in diabetes mellitus. PMID:21640568

  13. Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats.

    PubMed

    Hamouda, N N; Sydorenko, V; Qureshi, M A; Alkaabi, J M; Oz, M; Howarth, F C

    2015-02-01

    In the management of type 2 diabetes mellitus, Dapagliflozin (DAPA) is a newly introduced selective sodium-glucose co-transporter 2 inhibitor which promotes renal glucose excretion. Little is known about the effects of DAPA on the electromechanical function of the heart. This study investigated the effects of DAPA on ventricular myocyte shortening and intracellular Ca(2+) transport in streptozotocin (STZ)-induced diabetic rats. Shortening, Ca(2+) transients, myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+), and intracellular Ca(2+) current were measured in isolated rats ventricular myocytes by video edge detection, fluorescence photometry, and whole-cell patch-clamp techniques. Diabetes was characterized in STZ-treated rats by a fourfold increase in blood glucose (440 ± 25 mg/dl, n = 21) compared to Controls (98 ± 2 mg/dl, n = 19). DAPA reduced the amplitude of shortening in Control (76.68 ± 2.28 %, n = 37) and STZ (76.58 ± 1.89 %, n = 42) ventricular myocytes, and reduced the amplitude of the Ca(2+) transients in Control and STZ ventricular myocytes with greater effects in STZ (71.45 ± 5.35 %, n = 16) myocytes compared to Controls (92.01 ± 2.72 %, n = 17). Myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+) were not significantly altered by DAPA in either STZ or Control myocytes. L-type Ca(2+) current was reduced in STZ myocytes compared to Controls and was further reduced by DAPA. In conclusion, alterations in the mechanism(s) of Ca(2+) transport may partly underlie the negative inotropic effects of DAPA in ventricular myocytes from STZ-treated and Control rats. PMID:25351341

  14. Anti-hyperglycaemic activity of swietenia macrophylla king (meliaceae) seed extracts in normoglycaemic rats undergoing glucose tolerance tests

    PubMed Central

    2013-01-01

    Background Swietenia macrophylla King (Meliaceae) is used to treat diabetes mellitus in Malaysia. This study aims to evaluate the anti-hyperglycaemic potential of petroleum ether (PE), chloroform (CE) and methanol (ME) extracts of S. macrophylla seeds, in normoglycaemic and streptozotocin (STZ)-induced diabetic rats. Methods Following treatment of normoglycaemic rats with S. macrophylla seed extracts, hypoglycaemic and intraperitoneal glucose tolerance tests (IPGTT) were performed, and blood glucose concentrations were measured. Similarly, glucose concentrations were measured after 1 and 14 days of extract treatment of STZ-induced diabetic rats. Glucose absorption by isolated everted intestine and glucose uptake by isolated abdominal muscle were tested after treatment with seed extracts. Gas chromatography mass spectrometry (GC-MS) analysis was performed on PE of S. macrophylla seeds to identify the compounds responsible for its activity. Results None of the extracts had a significant effect on the blood glucose levels of 60 randomly selected normoglycaemic (normal) and diabetic rats undergoing hypoglycaemic tests. PE, however, significantly reduced blood glucose levels in 30 randomly selected normoglycaemic rats undergoing IPGTT tests 30–120 minutes after glucose administration. Repeated doses of 1000 mg/kg and 500 mg/kg PE to STZ-induced diabetic rats for 14 days did not reduce blood glucose levels significantly. PE did not significantly reduced the intestinal absorption of glucose, but significantly increased glucose uptake by abdominal muscle in the absence or presence of insulin. GC-MS analysis indicated that diterpenes, triterpenoids, fatty acid methyl esters, aldehydes and phytosterols may be responsible for the glucose lowering effects of PE. Conclusion PE extracts of S. macrophylla seeds showed anti-hyperglycaemic activity on IPGTTs . GC-MS analysis on the PE revealed that several compounds, including fucosterol and ?-sitosterol, may be responsible for these anti-hyperglycaemic properties. PMID:23684219

  15. Modulation of Adipocytokines Production and Serum NEFA Level by Metformin, Glimepiride, and Sitagliptin in HFD/STZ Diabetic Rats

    PubMed Central

    Saad, Mohamed I.; Kamel, Maher A.; Hanafi, Mervat Y.

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a group of metabolic disorders characterized by hyperglycemia owing to insulin resistance and/or insulin deficiency. Current theories of T2DM pathophysiology include a decline in ?-cells function, a defect in insulin signaling pathways, and a dysregulation of secretory function of adipocytes. This study aimed to investigate the effect of different antidiabetic drugs on serum levels of certain adipocytokines and nonesterified fatty acids (NEFA) in high-fat diet (HFD)/streptozotocin- (STZ-) induced diabetic rats. All treatments significantly decreased serum NEFA level. Metformin and sitagliptin increased serum adiponectin level, whereas they decreased serum leptin level. Glimepiride showed significant decline in serum levels of both adiponectin and leptin. All treatments remarkably ameliorated insulin resistance, suggested by an improvement of glycemic control, a significant reduction in homeostasis model assessment of insulin resistance (HOMA-IR), and a correction in lipid profile. Modulation of adipocytokines production (i.e., increased serum adiponectin and decreased serum leptin) may also underlie the improvement of insulin resistance and could be a possible mechanism for the beneficial cardiovascular effects of metformin and sitagliptin.

  16. Redox regulation of antioxidant enzymes: post-translational modulation of catalase and glutathione peroxidase activity by resveratrol in diabetic rat liver.

    PubMed

    Sadi, Gökhan; Bozan, Davut; Yildiz, Huseyin Bekir

    2014-08-01

    Resveratrol is a strong antioxidant that exhibits blood glucose-lowering effects, which might contribute to its usefulness in preventing complications associated with diabetes. The present study aimed to investigate resveratrol effects on catalase (CAT) and glutathione peroxidase (GPx) gene and protein expression, their phosphorylation states and activities in rat liver of STZ-induced diabetes. Diabetes increased the levels of total protein phosphorylation and p-CAT, while mRNA expression, protein levels, and activity were reduced. Although diabetes induced transcriptional repression over GPx, it did not affect the protein levels and activity. When resveratrol was administered to diabetic rats, an increase in activity was associated with an increase in p-GPx levels. Decrease in Sirtuin1 (SIRT1) and nuclear factor erythroid 2-related factor (Nrf2) and increase in nuclear factor kappa B (NF?B) gene expression in diabetes were associated with a decrease in CAT and GPx mRNA expression. A possible compensatory mechanism for reduced gene expression of antioxidant enzymes is proved to be nuclear translocation of redox-sensitive Nrf2 and NF?B in diabetes which is confirmed by the increase in nuclear and decrease in cytoplasmic protein levels of Nrf2 and NF?B. Taken together, these findings revealed that an increase in the oxidized state in diabetes intricately modified the cellular phosphorylation status and regulation of antioxidant enzymes. Gene regulation of antioxidant enzymes was accompanied by nuclear translocation of Nrf2 and NF?B. Resveratrol administration also activated a coordinated cytoprotective response against diabetes-induced changes in liver tissues. PMID:24740756

  17. Beneficial effect of 17{beta}-estradiol on hyperglycemia and islet {beta}-cell functions in a streptozotocin-induced diabetic rat model

    SciTech Connect

    Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting, E-mail: BTZhu@kumc.ed

    2010-11-15

    The modulating effect of estrogen on glucose homeostasis remains a controversial issue at present. In this study, we sought to determine the beneficial effect of 17{beta}-estradiol (E{sub 2}) on hyperglycemia and islet {beta}-cell functions in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected i.p. with STZ to induce a relatively mild diabetic condition. The rats were then treated with E{sub 2} orally at 500 {mu}g/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet {beta}-cell proliferation. E{sub 2} administration for 10 days significantly lowered plasma glucose levels, increased plasma insulin levels, and improved glucose tolerance by attenuating insulin response to oral glucose loading. These beneficial effects of E{sub 2} were accompanied by increases in islet number and volume, rate of islet cell proliferation, and the amount of insulin secreted. The growth-stimulatory effect of E{sub 2} on islet cells was linked to the functions of the estrogen receptor {alpha}. Notably, these protective effects of E{sub 2} on diabetic conditions were basically not observed when the STZ-treated rats had a more severe degree of islet damage and hyperglycemia. Taken together, we conclude that E{sub 2} can promote the regeneration of damaged pancreatic islets by stimulating {beta}-cell proliferation in diabetic rats, and this effect is accompanied by improvements in glucose tolerance and a decrease in plasma glucose levels. These findings suggest that oral administration of E{sub 2} may be beneficial in diabetic patients with an accelerated loss of islet {beta}-cells.

  18. Effect of coenzyme Q10 on catalase activity and other antioxidant parameters in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Ketan Modi; D. D. Santani; R. K. Goyal; P. A. Bhatt

    2006-01-01

    Although coenzyme Q10 (CoQ10) is a component of the oxidative phosphorylation process in mitochondria that converts the energy\\u000a in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis, its effect in type I diabetes is not\\u000a clear. We have studied the effect of 4 wk of treatment with CoQ10 (10 mg\\/kg, ip, daily) in streptozotocin (STZ)-induced (40

  19. Upregulation of podocyte-secreted angiopoietin-like-4 in diabetic nephropathy.

    PubMed

    Ma, Jing; Chen, Xiao; Li, Jian-Si; Peng, Lei; Wei, Shi-Yao; Zhao, Shi-Lei; Li, Tong; Zhu, Dan; He, Yi-Xin; Wei, Qiu-Ju; Li, Bing

    2014-11-26

    Podocyte injury plays a key role in the development of diabetic nephropathy (DN). Understanding the changes in podocyte structure and function in diabetes mellitus may lead to novel diagnostic tools and treatment strategies for DN. Albuminuria, histological alterations, and podocyte injury were detected at different time points in streptozotocin (STZ)-induced diabetic rats. Increased urinary albumin-to-creatinine ratios (ACR) and podocyte injury were significantly observed 4 weeks post-STZ injection. We determined the glomerular expression and distribution of angiopoietin-like 4 (Angptl4) by immunofluorescence and real-time PCR. Glomerular Angptl4 expression was mostly colocalized with synaptopodin, a podocyte marker, with substantial additional overlap with the glomerular basement membrane (GBM). This finding indicated that Angptl4 might be primarily secreted by podocytes and moved toward the GBM. Moreover, we observed by Western blot analysis and ELISA that the urinary Angptl4 level was gradually upregulated in both STZ-induced rats and diabetic patients with microalbuminuria and macroalbuminuria. We further found that the increased glomerular Angptl4 expression was closely related to the urinary ACR level and podocyte injury. In addition, the urinary Angptl4 expression was closely associated with albuminuria in the rats and patients with DN. This study is the first to show that podocyte-secreted Angptl4 is upregulated in DN and can be detected in urine. Angptl4 might function as a podocyte injury marker and could be a potential and novel diagnostic and therapeutic biomarker for DN. PMID:25424436

  20. Preventive Effect of Garlic (Allium sativum L.) on Serum Biochemical Factors and Histopathology of Pancreas and Liver in Streptozotocin- Induced Diabetic Rats

    PubMed Central

    Masjedi, Fatemeh; Gol, Ali; Dabiri, Shahriar

    2013-01-01

    Antidiabetic action of garlic is established in animal studies. Since all of the pervious studies have focused on the therapeutic role of garlic, this study investigated the preventive effect of garlic juice on biochemical factors and histological features in Streptozotocin (STZ)- induced diabetic rats. Forty male rats were divided into five groups (n = 8): 1-Normal group (N), 2-Normal+Garlic group (N+G) received garlic juice (1 mL/100g BW) for 6 weeks, 3-Diabetic group (D) was injected with STZ (60 mg/kg, IP), 4-Diabetic+Garlic-before group (D+Gb) received garlic juice for 3 weeks before STZ injection and continued for another 3 weeks, 5-Diabetic+Garlic-after group (D+Ga), three days after STZ injection, they received garlic juice for 3 weeks. Serum biochemical factors were measured by the enzymatic methods and H&E stained sections of pancreas and liver were prepared for light microscopy. In diabetic rats, elevated levels of glucose, cholesterol and triglycerides, the increment of the activities of ALT and AST, increased food and water consumption were observed. The abnormal increases were significantly (p < 0.05) decreased in D+Gb groups compared to D group. In D group, scattered degeneration of the hepatocytes with lymphocytic infiltration in the portal areas, decrease of pancreatic islets numbers and diameter, atrophy of pancreatic islets were observed. These abnormal histological signs were dramatically ameliorated in D+Gb group compared to D group. In D+Ga group compared to D+Gb group slighter effects of garlic juice on histopathological and biochemical changes were seen. These results indicate that garlic juice may help in the prevention of the complications of diabetes. PMID:24250639

  1. Increased expression of heparanase in overt diabetic nephropathy.

    PubMed

    van den Hoven, M J; Rops, A L; Bakker, M A; Aten, J; Rutjes, N; Roestenberg, P; Goldschmeding, R; Zcharia, E; Vlodavsky, I; van der Vlag, J; Berden, J H

    2006-12-01

    In overt diabetic nephropathy (DNP), an increase in the permeability of the glomerular basement membrane (GBM) has been associated with a loss of negatively charged heparan sulfates (HS) in the GBM. Heparanase (HPSE), an endo-beta(1-4)-D-glucuronidase, can cleave HS and could be a potential candidate for the degradation of glomerular HS, leading to the development of proteinuria. We analyzed whether changes in HS expression are associated with HPSE expression in overt DNP. Immunofluorescence staining was performed to analyze HS, HPSE, and agrin core protein expression in kidney biopsies from patients with overt DNP and from rats and mice with streptozotocin (STZ)-induced diabetes. We also investigated the effect of transgenic HPSE overexpression in mice on glomerular HS and agrin expression. We demonstrate that the loss of GBM HS (-50%) and tubular HS (-60%) is associated with a four-fold increased HPSE expression in overt DNP. In addition, glomerular HPSE expression is upregulated in rats (messenger RNA (mRNA) 2.5-fold, protein three-fold) and mice (mRNA seven-fold, protein 1.5-fold) with STZ-induced diabetes. Furthermore, transgenic HPSE overexpression results in disappearance of HS, whereas expression of the core protein agrin remains unaltered. Our observations suggest that HPSE is involved in the pathogenesis of proteinuria in overt DNP by degradation of HS. PMID:17051139

  2. Effects of 4-phenylbutyric acid on the process and development of diabetic nephropathy induced in rats by streptozotocin: Regulation of endoplasmic reticulum stress-oxidative activation

    SciTech Connect

    Luo Zhifeng [Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Feng Bing, E-mail: fxb12@yahoo.com.c [Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Mu Jiao; Qi Wei; Zeng Wei; Guo Yanhong; Pang Qi; Ye Zilin; Liu Li; Yuan Fahuan [Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China)

    2010-07-15

    Oxidative stress may contribute to the pathogenesis of diabetic nephropathy (DN), although the precise regulatory mechanism is still unclear. Recent reports have shown that chemical molecular chaperone 4-phenylbutyric acid (4-PBA) can suppress oxidative stress by attenuating endoplasmic reticulum (ER) stress. We therefore hypothesized that 4-PBA could provide renoprotection through the suppression of oxidative stress in DN rats. Male Sprague-Dawley (SD) rats were randomly divided into three groups: a normal control (NC) group, a streptozotocin (STZ)-induced DN model group, and a DN plus 4-PBA (1 g/kg) treatment group. At the end of 4, 8, and 12 weeks, hydroxyproline content, NADPH oxidase activity and the expression of phosphorylation of inositol-requiring enzyme-1{alpha} (p-IRE1{alpha}), p47phox, nitrotyrosine (NT) and NF-E2-related factor 2 (Nrf2) in the kidneys of all rats were determined; malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in serum and urine were also detected; renal nuclear factor {kappa}B (NF-{kappa}B) activity in all of the rats was examined at the end of 12 weeks. Compared with the NC group, the DN rats showed a significant increase in hydroxyproline content, NADPH oxidase activity, NF-{kappa}B activity, the expression of p-IRE1{alpha}, p47phox, NT and Nrf2 in renal tissue; markedly, MDA levels were higher and SOD activity was lower in serum and urine of DN rats than in NC rats for the indicated time. These alterations were inhibited by the administration of 4-PBA. These findings first demonstrated that treatment with 4-PBA significantly inhibits the process and development of diabetic nephropathy in rats through the regulation of ER stress-oxidative activation.

  3. Nutraceutical potential of Aerva lanata (L.) Juss. ex Schult ameliorates secondary complications in streptozotocin-induced diabetic rats.

    PubMed

    Riya, M P; Antu, K A; Pal, S; Srivastava, A K; Sharma, S; Raghu, K G

    2014-09-01

    Nutraceuticals provide health benefits beyond their basic nutrition by modulating a number of biochemical pathways. They are derived from natural products and have gained recognition worldwide as an adjuvant or therapy in the treatment of metabolic disorders such as diabetes. Although the regulation of blood glucose with drugs and insulin greatly reduces the incidence of secondary complications, the need for long-term treatment raises issues of tolerance and affordability. Therefore, the aim of the present study is to explore the nutraceutical potential of Aerva lanata, a herb widely used for its culinary and therapeutic potential in streptozotocin (STZ)-induced diabetic rats. Treatment with 70% ethanolic extract (ALE) at 500 mg per kg b.w per day for 21 days significantly improved the fasting blood glucose (120.33 ± 1.99 mg dL(-1)), insulin level (9.81 ± 0.38 mU L(-1)), HbA1c (7.3 ± 0.36%) and glycogen content in the liver (35.33 ± 1.38 mg g(-1) protein) and muscle (7.67 ± 0.11 mg g(-1) protein) compared to diabetic controls. The extract also showed a significant decrease in blood glucose by 47.29% towards the end of 2 h in oral glucose tolerance test on Day 21. Its therapeutic potential could be partly attributable to the presence of flavonoids, tannins and terpenes (alpha amyrin, betulin and beta sitosterol) along with micronutrients such as potassium, magnesium, calcium and zinc. Hence, we suggest the suitability of Aerva lanata as a nutraceutical for diabetic patients. PMID:24993661

  4. Isolation and structural characterization of 2R, 3R taxifolin 3-O-rhamnoside from ethyl acetate extract of Hydnocarpus alpina and its hypoglycemic effect by attenuating hepatic key enzymes of glucose metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Balamurugan, Rangachari; Vendan, Subramanian Ezhil; Aravinthan, Adithan; Kim, Jong-Hoon

    2015-04-01

    Hydnocarpus alpina Wt. (Flacourtiaceae) (H. alpina) is a large tree traditionally used to treat leprosy; it also posses antidiabetic property. The present study was undertaken to isolate, characterize and to evaluate the antidiabetic effect of 2R, 3R taxifolin 3-O-rhamnoside. (rhamnoside) and its impact on carbohydrate metabolic key enzymes in control and streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ) (40 mg/kg). Oral administration of rhamnoside for 21 days significantly reduced food intake, calorie intake, blood glucose and glycosylated hemoglobin levels, and improved plasma insulin levels. Administration of rhamnoside showed significant increase in the body weight, body composition (Lean body weight (LBW) and retro body fat), glycolytic hexokinase, glucose-6-phophate dehydrogenase and pyruvate kinase levels where as significant decrease was observed in the levels of glucose-6-phosphatase fructose-1, 6-bisphosphatase and lactate dehydrogenase in diabetic treated rats. Further, administration of rhamnoside significantly improved the glycogen content, glycogen synthase and glycogen phosphorylase, suggesting the antihyperglycemic potential of rhamnoside in diabetic rats. The results obtained were compared with glibenclamide a standard hypoglycaemic drug. Immunohistopathological study of pancreas revealed increased number of ?-cells and insulin granules in diabetes-induced rats after treatment with rhamnoside for 21 days. Furthermore, Co-administration of rhamnoside (50 mg/kg) with nifedipine (13.6 mg/kg), a Ca(2+)ion channel blocker, or nicorandil (6.8 mg/kg), an ATP-sensitive K(+) ion channel opener, reveals the insulin secretion property of rhamnoside via a K(+)-ATP channels dependent pathway in diabetic rats. In conclusion, rhamnoside normalized blood glucose, glycosylated hemoglobin, key hepatic enzymes and glycogen content by increasing insulin secretion via K(+)-ATP channels dependent signaling pathway. The results suggest that the rhamnoside from H. alpina could be used as a therapeutic agent to treat diabetes mellitus. PMID:25698613

  5. Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats.

    PubMed

    Semaming, Yoswaris; Kumfu, Sirinart; Pannangpetch, Patchareewan; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2014-10-01

    Oxidative stress has been shown to play an important role in the pathogenesis of diabetes-induced cardiac dysfunction. Protocatechuic acid (PCA) is a phenolic compound, a main metabolite of anthocyanin, which has been reported to display various pharmacological properties. We proposed the hypothesis that PCA exerts cardioprotection in type 1 diabetic (T1DM) rats. T1DM was induced in male Sprague-Dawley rats by a single i.p. injection of 50?mg/kg streptozotocin (STZ) and groups of these animals received the following treatments for 12 weeks: i) oral administration of vehicle, ii) oral administration of PCA at a dose of 50 ?mg/kg per day, iii) oral administration of PCA at a dose of 100?mg/kg per day, iv) s.c. injection of insulin at a dose of 4?U/kg per day, and v) a combination of PCA, 100?mg/kg per day and insulin, 4?U/kg per day. Metabolic parameters, results from echocardiography, and heart rate variability were monitored every 4 weeks, and the HbA1c, cardiac malondialdehyde (MDA), cardiac mitochondrial function, and cardiac BAX/BCL2 expression were evaluated at the end of treatment. PCA, insulin, and combined drug treatments significantly improved metabolic parameters and cardiac function as shown by increased percentage fractional shortening and percentage left ventricular ejection fraction and decreased low-frequency:high-frequency ratio in T1DM rats. Moreover, all treatments significantly decreased plasma HbA1c and cardiac MDA levels, improved cardiac mitochondrial function, and increased BCL2 expression. Our results demonstrated for the first time, to our knowledge, the efficacy of PCA in improving cardiac function and cardiac autonomic balance, preventing cardiac mitochondrial dysfunction, and increasing anti-apoptotic protein in STZ-induced T1DM rats. Thus, PCA possesses a potential cardioprotective effect and could restore cardiac function when combined with insulin treatment. These findings indicated that supplementation with PCA might be helpful for the prevention and alleviation of cardiovascular complications in T1DM. PMID:25074852

  6. Hematological Changes in Opium Addicted Diabetic Rats

    PubMed Central

    Asadikaram, Gholamreza; Sirati-Sabet, Majid; Asiabanha, Majid; Shahrokhi, Nader; Jafarzadeh, Abdollah; Khaksari, Mohammad

    2013-01-01

    Background Chronic opioid treatment in animal models has shown to alter hematological parameters. Objectives The aim of this study was to evaluate the biological effects of opium on the number of peripheral blood cells and red blood cells (RBCs) indices in diabetic rats. Materials and Methods Peripheral blood samples were collected from diabetic, opium-addicted, diabetic opium-addicted and normal male and female rats and hematological parameters were measured. Results The mean number of white blood cells (WBCs) was significantly higher in diabetic opium-addict females compared to diabetic non-addict female group. In both male and female, the mean number of neutrophils was significantly higher and the mean number of lymphocytes was lower in diabetic opium-addicted rats than those observed in diabetic non-addicted group. In diabetic opium-addicted male group the mean counts of RBC significantly increased as compared with diabetic male group. However, in diabetic addicted female, the mean number of RBCs was significantly lower than diabetic non-addicted female group. In both males and females, the mean number of platelets was significantly lower in diabetic addict rats compared to diabetic non-addict group. Conclusions Generally, the results indicated that opium addiction has different effects on male and female rats according to the number of WBC, RBC and RBC indices. It could also be concluded that in the opium-addicts the risk of infection is enhanced due to the weakness of immune system as a result of the imbalance effect of opium on the immune cells. PMID:24971253

  7. The Attenuation of Moutan Cortex on Oxidative Stress for Renal Injury in AGEs-Induced Mesangial Cell Dysfunction and Streptozotocin-Induced Diabetic Nephropathy Rats

    PubMed Central

    Zhang, Minghua; Feng, Liang; Gu, Junfei; Ma, Liang; Qin, Dong; Wu, Chan; Jia, Xiaobin

    2014-01-01

    Oxidative stress (OS) has been regarded as one of the major pathogeneses of diabetic nephropathy (DN) through damaging kidney which is associated with renal cells dysfunction. The aim of this study was to investigate whether Moutan Cortex (MC) could protect kidney function against oxidative stress in vitro or in vivo. The compounds in MC extract were analyzed by HPLC-ESI-MS. High-glucose-fat diet and STZ (30?mg?kg?1) were used to induce DN rats model, while 200??g?mL?1 AGEs were for HBZY-1 mesangial cell damage. The treatment with MC could significantly increase the activity of SOD, glutathione peroxidase (GSH-PX), and catalase (CAT). However, lipid peroxidation malondialdehyde (MDA) was reduced markedly in vitro or in vivo. Furthermore, MC decreased markedly the levels of blood glucose, serum creatinine, and urine protein in DN rats. Immunohistochemical assay showed that MC downregulated significantly transforming growth factor beta 2 (TGF-?2) protein expression in renal tissue. Our data provided evidence to support this fact that MC attenuated OS in AGEs-induced mesangial cell dysfunction and also in high-glucose-fat diet and STZ-induced DN rats. PMID:24876912

  8. Total parenteral nutrition in diabetic rats

    SciTech Connect

    Norcross, E.D.; Stein, T.P.

    1986-03-01

    Parenteral Nutrition with hypertonic glucose is frequently given to diabetic patients. Large amounts of insulin can be required. The purpose of this investigation was to develop a totally parenterally nourished diabetic rat model. 200 g Female Sprague Dawley rats were made diabetic by i.v. injection of streptozotocin (50 mg/kg). Rats were then allowed to recover for at least 1 week before undergoing surgical insertion of a central venous catheter for parenteral feeding. TPN was begun 3 days after surgery. Prior to this they were allowed unlimited access to food and water. Control (non-streptozotocin treated) rats were run at the same time. Protein turnover was investigated by using /sup 15/N glycine. Preliminary results: diabetic rats given mostly fat as a calorie source survived well in the absence of exogenous insulin whereas those that were given glucose only as their non-protein calorie source showed poor survival even with exogenous insulin. N balance and protein turnover in the lipid treated diabetic rats were comparable to the non-diabetic control rats.

  9. Streptozotocin is responsible for the induction and progression of renal tumorigenesis in diabetic Wistar-Furth rats treated with insulin or transplanted with agarose encapsulated porcine islets.

    PubMed

    Vinerean, Horatiu V; Gazda, Lawrence S; Hall, Richard D; Smith, Barry H

    2011-01-01

    Streptozotocin (STZ), a nitrosourea with DNA alkylating properties, has been widely used to induce hyperglycemia by specifically destroying the insulin-producing ?-cells of the islets of Langerhans in experimental models of Type I diabetes. STZ's known carcinogenic properties, however, raise concerns about its suitability for long-term studies. We conducted a formal study of STZ's carcinogenic effects in long-term surviving diabetic Wistar-Furth rats. To determine if insulin therapy or islet transplantation exacerbated tumorigenesis, rats were randomly assigned to one of four experimental groups: normal animals with no treatment (Group 1, n=12); normal animals that underwent peritoneal implantation of porcine islets encapsulated in a double layer of agarose to form islet macrobeads (normal + islets; group 2, n=12); STZ treatment followed by daily exogenous insulin (STZ + insulin; group 3, n=18) and STZ treatment followed by the intraperitoneal implantation of porcine islet macrobeads (STZ + islets; group 4, n=14). At 215 days post-STZ induction, no renal proliferative lesions were observed in animals that did not receive STZ (group 1 and group 2) whereas adenoma incidences of 57% for group 3 and 34% for group 4 were observed. By terminal necropsy at day 351, the incidence and severity of renal proliferative lesions increased with tubular carcinoma observed in 67% of group 3 and 60% of group 4 animals. We conclude that the STZ-induced diabetic rat model is not suitable for long-term studies because of progressive renal tumorigenesis. Our experiments also demonstrate the safety and effectiveness of porcine islet macrobeads for the treatment of diabetes. PMID:21633194

  10. Chlorophytum borivilianum Root Extract Maintains near Normal Blood Glucose, Insulin and Lipid Profile Levels and Prevents Oxidative Stress in the Pancreas of Streptozotocin-Induced Adult Male Diabetic Rats

    PubMed Central

    Giribabu, Nelli; Kumar, Kilari Eswar; Rekha, Somesula Swapna; Muniandy, Sekaran; Salleh, Naguib

    2014-01-01

    The effect of C. borivilianum root on blood glucose, glycated hemoglobin (HbAIc), insulin and lipid profile levels in diabetes mellitus are not fully understood. This study therefore investigated the effect of C. borivilianum root on the above parameters and oxidative stress of the pancreas in diabetes. Methods: C. borivilianum root aqueous extract (250 and 500 mg/kg/day) was administered to streptozotocin (STZ)-induced male diabetic rats for 28 days. Body weight, blood glucose, HbA1c, insulin, lipid profile levels and glucose homeostasis indices were determined. Histopathological changes and oxidative stress parameters i.e. lipid peroxidation (LPO) and antioxidant enzymes activity levels of the pancreas were investigated. Results: C. borivilianum root extract treatment to diabetic rats maintained near normal body weight, blood glucose, HbA1c, lipid profile and insulin levels with higher HOMA-? cell functioning index, number of Islets/pancreas, number of ?-cells/Islets however with lower HOMA-insulin resistance (IR) index as compared to non-treated diabetic rats. Negative correlations between serum insulin and blood glucose, HbA1c, triglyceride (TG) and total cholesterol (TC) levels were observed. C. borivilianum root extract administration prevented the increase in lipid peroxidation and the decrease in activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) with mild histopathological changes in the pancreas of diabetic rats. Conclusions: C. borivilianum root maintains near normal levels of these metabolites and prevented oxidative stress-induced damage to the pancreas in diabetes. PMID:25249786

  11. Arginine metabolism in enterocytes of diabetic rats

    E-print Network

    Morrow, Natalie Anne

    2002-01-01

    Diabetic rats and patients exhibit decreased plasma arginine concentrations. Arginine is important in numerous cellular pathways, including the synthesis of nitric oxide and the release of insulin from pancreatic ? cells. At present, little...

  12. Paeoniflorin Prevents Diabetic Nephropathy in Rats

    PubMed Central

    Fu, Jianfang; Li, Yuan; Wang, Li; Gao, Bin; Zhang, Nanyan; Ji, Qiuhe

    2009-01-01

    The aim of this study was to test the hypothesis that paeoniflorin prevents the progression of diabetic nephropathy by modulating the inflammatory process. Sprague–Dawley rats were divided into 5 groups: nondiabetic control rats; untreated diabetic model (DM) rats; and DM rats treated with 5, 10, or 20 mg/kg paeoniflorin in drinking water once daily. Rats received a single intravenous injection of streptozotocin to induce diabetes; 9 wk after injection, rats began the 8-wk daily paeoniflorin treatment regimen. Compared with that of nonDM controls, the urinary albumin:creatinine ratio was increased significantly in untreated DM rats; this ratio was decreased in DM rats treated with 5, 10, or 20 mg/kg paeoniflorin compared with that of untreated DM rats. In addition, paeoniflorin treatment effectively suppressed glomerular hypertrophy; blood glucose; the expression of transforming growth factor ?, type IV collagen, and intercellular adhesion molecule 1; and renal infiltration of macrophages compared with levels in untreated DM rats. Furthermore, renal nuclear factor ?B activity was increased in untreated but not paeoniflorin-treated DM rats. In conclusion, our data suggest that the preventive effects of paeoniflorin may be mediated by its antiinflammatory actions. PMID:20034431

  13. N-Acetylcysteine and Allopurinol Confer Synergy in Attenuating Myocardial Ischemia Injury via Restoring HIF-1?/HO-1 Signaling in Diabetic Rats

    PubMed Central

    Mao, Xiaowen; Wang, Tingting; Liu, Yanan; Irwin, Michael G.; Ou, Jing-song; Liao, Xiao-long; Gao, Xia; Xu, Yuan; Ng, Kwok F. J.; Vanhoutte, Paul M.; Xia, Zhengyuan

    2013-01-01

    Objectives To determine whether or not the antioxidants N-acetylcysteine (NAC) and allopurinol (ALP) confer synergistic cardioprotection against myocardial ischemia/reperfusion (MI/R) injury by stabilizing hypoxia inducible factor 1? (HIF-1?)/heme oxygenase 1 (HO-1) signaling in diabetic myocardium. Methods Control or diabetic [streptozotocin (STZ)-induced] Sprague Dawley rats received vehicle or NAC, ALP or their combination for four weeks starting one week after STZ injection. The animals were then subjected to thirty minutes of coronary artery occlusion followed by two hours reperfusion in the absence or presence of the selective HO-1 inhibitor, tin protoporphyrin-IX (SnPP-IX) or the HIF-1? inhibitor 2-Methoxyestradiol (2ME2). Cardiomyocytes exposed to high glucose were subjected to hypoxia/re-oxygenation in the presence or absence of HIF-1? and HO-1 achieved by gene knock-down with related siRNAs. Results Myocardial and plasma levels of 15-F2t-isoprostane, an index of oxidative stress, were significantly increased in diabetic rats while cardiac HO-1 protein and activity were reduced; this was accompanied with reduced cardiac protein levels of HIF-1?, and increased post-ischemic myocardial infarct size and cellular injury. NAC and ALP given alone and in particular their combination normalized cardiac levels of HO-1 and HIF-1? protein expression and prevented the increase in 15-F2t-isoprostane, resulting in significantly attenuated post-ischemic myocardial infarction. NAC and ALP also attenuated high glucose-induced post-hypoxic cardiomyocyte death in vitro. However, all the above protective effects of NAC and ALP were cancelled either by inhibition of HO-1 or HIF-1? with SnPP-IX and 2ME2 in vivo or by HO-1 or HIF-1? gene knock-down in vitro. Conclusion NAC and ALP confer synergistic cardioprotection in diabetes via restoration of cardiac HIF-1? and HO-1 signaling. PMID:23874823

  14. Controlled release of thymosin Beta 4 using a collagen-chitosan sponge scaffold augments cutaneous wound healing and increases angiogenesis in diabetic rats with hindlimb ischemia.

    PubMed

    Ti, Dongdong; Hao, Haojie; Xia, Lei; Tong, Chuan; Liu, Jiejie; Dong, Liang; Xu, Shenjun; Zhao, Yali; Liu, Huiling; Fu, Xiaobing; Han, Weidong

    2015-02-01

    It is important to establish an efficient vascularization for the long-term acceptance of bioengineered skin equivalents treating the cutaneous wounds of diabetic rats with hindlimb ischemia. This study investigates the possible use of a collagen-chitosan sponge scaffold encapsulated with thymosin beta 4 (CCSS-eT?4), an angiogenic factor, to accelerate cutaneous wound healing in streptozotocin (STZ)-induced diabetic rats with hindlimb ischemia. CCSSs-eT?4 was fabricated using a freeze-drying method. The scaffolds were analyzed by scanning electron microscopy, swelling and degradation assays, mechanical properties, and scaffolds of 50:50 collagen-chitosan were selected and applied. The controlled release of T?4 from the scaffolds elicited localized and prolonged effects over 12 days, as shown by an enzyme-linked immunosorbent assay (ELISA). In vivo, CCSSs-eT?4 improved diabetic cutaneous wound healing, with faster wound reepithelialization, better dermal reorganization, and higher wound vascularization. Furthermore, CCSSs-eT?4 downregulated inflammatory genes and upregulated angiogenic genes in the wound tissue. Significant increases in CD31-positive endothelial cells and new vessel density were also observed. In vitro, T?4 increased the migratory and proliferative activity of high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). Meanwhile, we found that T?4 could promote HG-treated HUVECs migration and improve angiogenesis by activation of the VEGF/AKT pathway. Overall, these findings demonstrated the promising potential of CCSSs-eT?4 to promote more effective wound healing and suggest its possible application for diabetic cutaneous wound treatment. PMID:25204972

  15. Effect of fibrin-binding synthetic oligopeptide on the healing of full-thickness skin wounds in streptozotocin-induced diabetic rats.

    PubMed

    Chung, Jae-Eun; Kim, Yun-Jeong; Park, Yoon-Jeong; Koo, Ki-Tae; Seol, Yang-Jo; Lee, Yong-Moo; Rhyu, In-Chul; Ku, Young

    2013-01-01

    The aim of this study was to investigate whether topical application of fibrin-binding oligopeptides derived from FN promotes wound healing in streptozotocin (STZ)-induced diabetic rats. Oligopeptides including fibrin-binding sequences (FF3: CFDKYTGNTYRV, FF5 : CTSRNRCNDQ) of FN repeats were synthesized. Each peptide was loaded in 15 x 15 mm fibrous alginate dressings, and the release kinetics of the peptides was evaluated using trinitrobenzene sulfonic acid for 336 hours. Two full-thickness cutaneous wounds were prepared on the dorsal skin of each 75 diabetes induced rats. Each wound was divided into FF3-loaded alginate dressing group, FF5-loaded alginate dressing group, alginate dressing group and negative control group. Animals were sacrificed at day 0,3,7 and 14. The wound closure rate, inflammation degree, expression of TGF-?1 and hydroxyproline contents were evaluated. Both FF3 and FF5 peptides were released rapidly within the first 24 hours. FF3-loaded dressing treated wounds closed significantly faster than other wounds at day 3. And at day 14, FF3- & FF5- loaded dressing treated wounds demonstrated less inflammatory cells infiltration than alginate dressing treated and negative group wounds. TGF-?1 positive cells were more abundant in FF3-, FF5-treated alginate dressing treated wound at day 3 and 14. At last, the hyrdroxyproline contents in the FF3, FF5 group were higher at day 7 and day 14. Topical application of fibrin-binding domain synthetic oligopeptides from FN resulted in acceleration of full-thickness cutaneous wound healing in diabetic rats. PMID:23151183

  16. Spatio-Temporal Expression and Functional Involvement of Transient Receptor Potential Vanilloid 1 in Diabetic Mechanical Allodynia in Rats

    PubMed Central

    Wu, Huang-Hui; Qi, Jian; Shi, Juan; Li, Yun-Qing

    2014-01-01

    Diabetic neuropathic pain (DNP) is one of the most common clinical manifestations of diabetes mellitus (DM), which is characterized by prominent mechanical allodynia (DMA). However, the molecular mechanism underlying it has not fully been elucidated. In this study, we examined the spatio-temporal expression of a major nociceptive channel protein transient receptor potential vanilloid 1 (TRPV1) and analyzed its functional involvement by intrathecal (i.t.) application of TRPV1 antagonists in streptozocin (STZ)-induced DMA rat models. Western blot and immunofluorescent staining results showed that TRPV1 protein level was significantly increased in the soma of the dorsal root ganglion (DRG) neurons on 14 days after STZ treatment (DMA 14 d), whereas those in spinal cord and skin (mainly from the central and peripheral processes of DRG neurons) had already been enhanced on DMA 7 d to peak on DMA 14 d. qRT-PCR experiments confirmed that TRPV1 mRNA level was significantly up-regulated in the DRG on DMA 7 d, indicating a preceding translation of TRPV1 protein in the soma but preferential distribution of this protein to the processes under the DMA conditions. Cell counting assay based on double immunostaining suggested that increased TRPV1-immunoreactive neurons were likely to be small-sized and CGRP-ergic. Finally, single or multiple intrathecal applications of non-specific or specific TRPV1 antagonists, ruthenium red and capsazepine, at varying doses, effectively alleviated DMA, although the effect of the former was more prominent and long-lasting. These results collectively indicate that TRPV1 expression dynamically changes during the development of DMA and this protein may play important roles in mechanical nociception in DRG neurons, presumably through facilitating the release of CGRP. PMID:25020137

  17. Spatio-temporal expression and functional involvement of transient receptor potential vanilloid 1 in diabetic mechanical allodynia in rats.

    PubMed

    Cui, Yuan-Yuan; Xu, Hao; Wu, Huang-Hui; Qi, Jian; Shi, Juan; Li, Yun-Qing

    2014-01-01

    Diabetic neuropathic pain (DNP) is one of the most common clinical manifestations of diabetes mellitus (DM), which is characterized by prominent mechanical allodynia (DMA). However, the molecular mechanism underlying it has not fully been elucidated. In this study, we examined the spatio-temporal expression of a major nociceptive channel protein transient receptor potential vanilloid 1 (TRPV1) and analyzed its functional involvement by intrathecal (i.t.) application of TRPV1 antagonists in streptozocin (STZ)-induced DMA rat models. Western blot and immunofluorescent staining results showed that TRPV1 protein level was significantly increased in the soma of the dorsal root ganglion (DRG) neurons on 14 days after STZ treatment (DMA 14 d), whereas those in spinal cord and skin (mainly from the central and peripheral processes of DRG neurons) had already been enhanced on DMA 7 d to peak on DMA 14 d. qRT-PCR experiments confirmed that TRPV1 mRNA level was significantly up-regulated in the DRG on DMA 7 d, indicating a preceding translation of TRPV1 protein in the soma but preferential distribution of this protein to the processes under the DMA conditions. Cell counting assay based on double immunostaining suggested that increased TRPV1-immunoreactive neurons were likely to be small-sized and CGRP-ergic. Finally, single or multiple intrathecal applications of non-specific or specific TRPV1 antagonists, ruthenium red and capsazepine, at varying doses, effectively alleviated DMA, although the effect of the former was more prominent and long-lasting. These results collectively indicate that TRPV1 expression dynamically changes during the development of DMA and this protein may play important roles in mechanical nociception in DRG neurons, presumably through facilitating the release of CGRP. PMID:25020137

  18. Dendrobium chrysotoxum Lindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

    PubMed Central

    Yu, Zengyang; Gong, Chenyuan; Lu, Bin; Yang, Li; Sheng, Yuchen; Ji, Lili; Wang, Zhengtao

    2015-01-01

    Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. This study aimed to observe the alleviation of the ethanol extract of Dendrobium chrysotoxum Lindl. (DC), a traditional Chinese herbal medicine, on DR and its engaged mechanism. After DC (30 or 300?mg/kg) was orally administrated, the breakdown of blood retinal barrier (BRB) in streptozotocin- (STZ-) induced diabetic rats was attenuated by DC. Decreased retinal mRNA expression of tight junction proteins (including occludin and claudin-1) in diabetic rats was also reversed by DC. Western blot analysis and retinal immunofluorescence staining results further confirmed that DC reversed the decreased expression of occludin and claudin-1 proteins in diabetic rats. DC reduced the increased retinal mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor ? (TNF?), interleukin- (IL-) 6, and IL-1? in diabetic rats. In addition, DC alleviated the increased 1 and phosphorylated p65, I?B, and I?B kinase (IKK) in diabetic rats. DC also reduced the increased serum levels of TNF?, interferon-? (IFN-?), IL-6, IL-1?, IL-8, IL-12, IL-2, IL-3, and IL-10 in diabetic rats. Therefore, DC can alleviate DR by inhibiting retinal inflammation and preventing the decrease of tight junction proteins, such as occludin and claudin-1. PMID:25685822

  19. The Rho-kinase inhibitor fasudil restores normal motor nerve conduction velocity in diabetic rats by assuring the proper localization of adhesion-related molecules in myelinating Schwann cells.

    PubMed

    Kanazawa, Yasushi; Takahashi-Fujigasaki, Junko; Ishizawa, Sho; Takabayashi, Naoko; Ishibashi, Kumiko; Matoba, Keiichiro; Kawanami, Daiji; Yokota, Tamotsu; Tajima, Naoko; Utsunomiya, Kazunori

    2013-09-01

    The Rho/Rho-kinase signaling pathway has been shown to be involved in the complications of diabetes. In this study, we found that fasudil, a specific Rho-kinase inhibitor, had a beneficial effect on the motor nerve conduction velocity (MNCV), which is delayed in rats with streptozotocin (STZ)-induced diabetes. Cadherin-dependent adherens junctions (AJs) in myelinating Schwann cells, necessary for proper myelin formation and rapid propagation of action potentials, are regulated by Rho/Rho-kinase signaling. These AJ structures are maintained by E-cadherin and catenin complexes such as ?-catenin and p120 catenin. To elucidate the mechanism underlying the effect of fasudil on MNCV, we examined alterations in AJ structure in the peripheral nerves of the experimental rats. Our results showed that the activities of Rho and Rho-kinase increased simultaneously in the sciatic nerves of the diabetic rats. Fasudil restored the MNCV by suppressing the up-regulation of the Rho-kinase. In the diabetic state, enhanced Rho and Rho-kinase activity reduced p120 catenin expression and altered the distribution of p120 catenin and E-cadherin, which are normally localized in the paranodal compartment of the nodes of Ranvier and Schmidt-Lanterman incisures where autotypic AJs stabilize myelin structure. Fasudil restored normal p120 catenin expression and the distribution of p120 catenin and E-cadherin in the myelin sheath. In conclusion, reduced expression and altered distribution of the adhesion molecules in the myelin sheath might contribute to the slowing of the MNCV in the diabetic rats. Fasudil, through its effect on the distribution of the adhesion-related molecules, might prevent slowing of the MNCV. PMID:23337773

  20. Ozone partially prevents diabetic neuropathy in rats.

    PubMed

    Erken, H A; Genç, O; Erken, G; Ayada, C; Gündo?du, G; Do?an, H

    2015-02-01

    Neuropathy is one of the most common complications of diabetes mellitus. Although the beneficial effects of good blood glucose control on diabetic neuropathy are known, this control cannot completely prevent the occurrence and progression of diabetic neuropathy. The aim of this study was to investigate whether ozone prevents diabetic neuropathy. 36 adult female Sprague-Dawley rats were randomly divided into 6 groups (n=6): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). Diabetes was induced by a single injection of streptozotocin (60?mg/kg, intraperitoneal [i.p.]), after which insulin was administered (3 IU, i.p.) to the DI and DOI groups for 28 days, and 1.1?mg/kg (50?µg/ml) ozone was given to the O, DO, and DOI groups for 15 days. 4 weeks after the induction of diabetes, the nerve conduction velocity (NCV), amplitude of the compound action potential (CAP), total oxidant status (TOS), and total antioxidant status (TAS) were measured, and the oxidative stress index (OSI) was calculated. The NCV, amplitude of CAP, and TAS of the DI and DOI groups were higher than those of the D group; the amplitudes of CAP and TAS of the DO group were higher than those of the D group; and the TOS and OSI of the DO, DI, and DOI groups were lower than those of the D group. These findings indicate that ozone partially prevents diabetic neuropathy in rats. It appears that the preventive effects of ozone are mediated through oxidant/antioxidant mechanisms. PMID:25502578

  1. Promotion of immune and glycaemic functions in streptozotocin-induced diabetic rats treated with un-denatured camel milk whey proteins

    PubMed Central

    2014-01-01

    T cell mediated autoimmune diabetes is characterized by immune cell infiltration of pancreatic islets and destruction of insulin-producing ?-cells. This study was designed to assess the effect of whey proteins (WP) on the responsiveness of lymphocytes in rats after four months of Streptozotocin (STZ)-induced Type 1 diabetes (T1D). A diabetic group was supplemented with WP daily for five weeks at a dose of 100 mg/kg. Ribonucleic acid (RNA) was extracted from stimulated lymphocytes in order to analyse gene expressions using real time PCR and RT-PCR. PCR results were confirmed with ELISA. The proliferation capacity of lymphocytes and their homing to the spleen were studied. Antigen-activated lymphocytes showed that diabetes impaired the mRNA expression of the protein kinase B (Akt1), Cdc42, and the co-stimulatory molecule, CD28, which are important for cell survival, actin polymerization and T cell activation, respectively. Accordingly, proliferation of lymphocytes was found to be suppressed in diabetic rats, both in vivo and in vitro. WP was found to restore Akt1, Cdc42 and CD28 mRNA expression during diabetes to normal levels. WP, therefore, served to activate the proliferation of B lymphocytes in diabetic rats both in vivo and in vitro. Although WP was found to up-regulate mRNA expression of both interleukin (IL)-2 and interferon gamma (IFN-?), it suppressed the proliferation activity of almost all T cell subsets. This was confirmed by WP normalizing the structure and function of ß cells. Meanwhile, WP was found to down regulate the mRNA expression of Tumor necrosis factor-alpha (TNF-?) and its programmed cell death-receptor (Fas). Taken together, the results of this study provide evidence for the potential impact of WP in the treatment of immune impairment in T1D, suggesting that it serves to reverse autoimmunity by suppressing autoreactive T cells and down regulating TNF-? and Fas, resulting in improved pancreatic ß cell structure and function. PMID:25009576

  2. Saffron (Crocus sativus L.) powder as an ingredient of rye bread: an anti-diabetic evaluation.

    PubMed

    Bajerska, Joanna; Mildner-Szkudlarz, Sylwia; Podgórski, Tomasz; Oszmatek-Pruszy?ska, Ewa

    2013-09-01

    In this study, a most consumer-acceptable rye bread (RB) containing saffron (S) powder (RB+S) was designed to verify its anti-diabetic properties, and to compare these effects with those of RB and S separately, matched to a similar dose of bioactive components, used in the high-fat (HF) diet in streptozotocin (STZ)-induced Wistar rats. After baking, beneficial antioxidant and sensory properties for RB enriched with 0.12% S were achieved. Twenty-four severely diabetic rats (fasting blood glucose (FBG) ?350 mg/dL) were randomized to incorporate either 0.08% of pure S, or RB enriched with 0.12% S (the diet provided 0.08% of S), or RB alone into their diet for 5 weeks. As controls, nontreated, HF-feeding STZ-induced rats (positive control-HF/STZ) and rats receiving normal laboratory diet (negative control-C) were used. A significant FBG-lowering effect was observed (47%, 53%, and 54% reduction vs. HF/STZ; P<.05) after S, RB, and RB+S treatment. Improvements in the rats' glycemia were achieved by ?-cell regeneration and increases in insulin secretion. Only in the S and RB+S group of rats, a significant (P<.05) increase in relative pancreas (vs. HF/STZ) was noted. A significant (P<.05) reduction in the concentration of thiobarbituric acid-reactive substances (TBARS) was achieved, whereas the ferric-reducing ability of plasma (FRAP) was not changed after S, RB and RB+S treatment (vs. HF/STZ). Triglyceride (TG) concentrations after S, RB, and RB+S treatment were significantly decreased (P<.05) versus HF/STZ. Both S and RB can be used in diabetic therapy, but no additional metabolic effect was achieved after consumption of RB+S. PMID:23909906

  3. Protective effects of polysaccharides from Lilium lancifolium on streptozotocin-induced diabetic mice.

    PubMed

    Zhang, Ting; Gao, Jie; Jin, Zheng-Yu; Xu, Xue-Ming; Chen, Han-Qing

    2014-04-01

    In this study, the protective effect of Lilium lancifolium polysaccharides (LLP) on streptozotocin (STZ)-induced diabetic mice and possible mechanism were investigated. The diabetic mice were administered with LLP for 28 days. The results showed that oral administration of LLP could significantly decrease blood glucose level and increase body weight loss in STZ-induced diabetic mice. LLP also significantly increased the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and decreased the level of malondialdehyde (MDA) in serum, liver, and kidney in STZ-induced diabetic mice. Moreover, histopathological examination showed that LLP could markedly improve the structure integrity of pancreatic islet tissue in STZ-induced diabetic mice. However, LLP had no significant effect on organ weight of liver and pancreas of diabetic mice, but significantly decreased kidney weight compared with diabetic control mice. This study suggested that LLP had hypoglycemic and antioxidant properties and could provide protective effect on STZ-induced diabetic mice. PMID:24508917

  4. Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats.

    PubMed

    Kandhare, Amit D; Ghosh, Pinaki; Bodhankar, Subhash L

    2014-08-01

    Chronic, unhealed diabetic foot ulcer (DFU) is one of the most severe complications of diabetes mellitus (DM). Naringin, a flavanone glycoside antioxidant, was reported to have antidiabetic and anti-apoptotic properties. In the present study DM was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.). In surgically introduced wounds on the dorsal surface of the hind paw of rats, the healing potential of naringin was investigated. Rats were treated with naringin (20, 40 and 80 mg/kg, p.o.), insulin (10 IU/kg, s.c.) and tetrachlorodecaoxide (TCDO) (1 drop, twice a day, topically) for 16 days. The wound area was measured every second day, and on day 17 various biochemical parameters were determined in serum, wound tissue, and histopathological examination of the wound was performed. Naringin (40 and 80 mg/kg) significantly (P<0.05) improved wound area, serum glucose level, glycated Hb and serum insulin. Naringin treatment at 40 and 80 mg/kg resulted in significant (P<0.05) up-regulation of mRNA expression of growth factor (IFG-1, TGF-? and VEGF-c), Ang-1 and collagen-1 whereas mRNA expression of inflammatory mediators (TNF-?, IL-1? and IL-6) was down-regulated. Furthermore, naringin significantly (P<0.05) attenuated STZ-induced apoptosis and stimulated angiogenesis in the wound tissue. Further results suggest that angiogenesis was improved via naringin-mediated inhibition of hyperglycemia, oxidative stress, down-regulation of inflammatory mediator expression and up-regulation of growth factor expression, leading to improved wound healing of DFU. PMID:24880026

  5. Nutrient excess and altered mitochondrial proteome and function contribute to neurodegeneration in diabetes

    Microsoft Academic Search

    Subir K. Roy Chowdhury; Rick T. Dobrowsky; Paul Fernyhough

    2011-01-01

    Diabetic neuropathy is a major complication of diabetes that results in the progressive deterioration of the sensory nervous system. Mitochondrial dysfunction has been proposed to play an important role in the pathogenesis of the neurodegeneration observed in diabetic neuropathy. Our recent work has shown that mitochondrial dysfunction occurs in dorsal root ganglia (DRG) sensory neurons in streptozotocin (STZ) induced diabetic

  6. Glomerular renin angiotensin system in streptozotocin diabetic and Zucker diabetic fatty rats.

    PubMed

    Leehey, David J; Singh, Ashok K; Bast, Joseph P; Sethupathi, Periannan; Singh, Rekha

    2008-04-01

    Substantial evidence suggests that the intrarenal renin-angiotensin system (RAS) plays a role in the pathogenesis of diabetic nephropathy. Although the glomerular RAS is activated in the streptozotocin (STZ)-diabetic rat, the status of the glomerular RAS in the Zucker diabetic fatty (ZDF) rat, which is a commonly used genetic model of diabetes, is not known. Angiotensinogen (AGT), angiotensin II (Ang II), angiotensin converting enzyme (ACE), and angiotensin converting enzyme 2 (ACE2) were measured in glomeruli isolated from 4-week-old STZ-diabetic rats and 32-week-old ZDF rats. Glomerular injury was evaluated by histopathologic methods. Both STZ-diabetic and ZDF rats exhibited marked hyperglycemia and renal hypertrophy, but only ZDF rats demonstrated proteinuria and glomerulosclerosis. Glomerular AGT and Ang II levels were increased significantly in STZ-diabetic compared with nondiabetic control rats, accompanied by a reduction in ACE2 activity. In contrast, glomerular AGT, Ang II, and ACE2 were similar in ZDF rats and lean controls. ACE levels were not affected by diabetes in either diabetic model. In conclusion, the glomerular RAS is activated in the STZ diabetic rat but not in the ZDF rat despite a similar degree of hyperglycemia. The mechanism of nephropathy in the ZDF rat may involve factors other than hyperglycemia and RAS activation, such as hypertension and hyperlipidemia. PMID:18355768

  7. Protective effect of aqueous extract of seed of Psoralea corylifolia (Somraji) and seed of Trigonella foenum-graecum L. (Methi) in streptozotocin-induced diabetic rat: A comparative evaluation

    PubMed Central

    Bera, Tushar Kanti; Ali, Kazi Monjur; Jana, Kishalay; Ghosh, Abhinandan; Ghosh, Debidas

    2013-01-01

    Background: Psoralea corylifolia (Somraji) and Trigonella foenum-graecum L. (Methi), important medicinal plants widely used in India as folk medicine. Local people of West Bengal traditionally used the seeds of these plants to cure diabetes. Objective: Present study was designed to investigate the antidiabetic efficacy of aqueous extract of seeds of these plants in separate or in composite manner in streptozotocin (STZ)-induced diabetic rat. Materials and Methods: Diabetes was induced by intramuscular injection of STZ at the dose of 40 mg/ml of citrate buffer/kg body weight. Fasting blood glucose (FBG), glyclated hemoglobin (HbA1C) and activities of hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase of liver in experimental animals were assessed. Hyperlipidemic state developed in the experimental diabetic rat was assessed by measuring the levels of total cholesterol, triglyceride, and lipoproteins in serum. Results: There was significant increased in the levels of FBG, HbA1C and lipid profiles along with diminution (P < 0.001) in the activities of hepatic hexokinase, glucose-6-phosphate dehydrogenase and elevation in glucose-6-phosphatase in diabetic control animals in respect to the untreated control. Significant recovery (P < 0.05) in the activities of above mentioned enzymes along with the correction in the levels of FBG, HbA1C and serum lipid profiles were noted towards the control level after the treatment of composite extract (i.e. 100 mg of Somraji: 100 mg of Methi, total 200 mg/kg body weight) than the individual extract (i.e. 200 mg of Somraji or 200 mg of Methi, per kg body weight) treatment. Conclusion: Results suggest that composite extract of above plant parts has more potent antidiabetic efficacy than the individual extract. PMID:24174822

  8. Nerve electrophysiological changes in rats with early induced diabetes.

    PubMed

    Tarhzaoui, K; Behar, A; Lestrade, R A; Hort-Legrand, C; Cohen-Boulakia, F E; Valensi, P E

    2008-06-01

    In rats with diabetes induced at weaning, pathological examinations have shown that the reduction of myelin thickness occurs earlier than axon size reduction. The aim of this study was to provide a detailed description of neurophysiological changes during nerve growth and maturation in rats with streptozotocin-induced diabetes in prepubertal stage. Five-day male Wistar rats received an injection of streptozotocin. Motor and sensory conduction velocities increased until 6.5 months in diabetic and control rats and at this age it became lower in diabetic rats. In diabetic rats, the amplitudes of the compound motor action potentials (CMAP) were lower by the 3 months and did not increase later. The amplitudes and areas of sensory action potentials (SNAP) increased until 9 months in both groups. SNAP duration decreased with ageing. Sensory peak 1 and peak 2 latencies became longer from 6.5 to 9 months in diabetic rats, with a longer latency difference between the 2 sensory peaks by 4 months. At 3 and 4 months of age, peak 1 and peak 2 latencies correlated with SNAP amplitude and duration in control rats but not in diabetic rats. In conclusion, in rats with early induced diabetes, the earliest electrophysiological impairments consist of lower CMAP amplitudes, and longer difference between latencies of sensory peaks 1 and 2. These sequential neurophysiological changes should be considered when testing new therapeutic approaches in diabetic neuropathy. PMID:18642759

  9. Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: a multimodal analysis.

    PubMed

    Leonelli, E; Bianchi, R; Cavaletti, G; Caruso, D; Crippa, D; Garcia-Segura, L M; Lauria, G; Magnaghi, V; Roglio, I; Melcangi, R C

    2007-02-23

    One important complication of diabetes is damage to the peripheral nervous system. However, in spite of the number of studies on human and experimental diabetic neuropathy, the current therapeutic arsenal is meagre. Consequently, the search for substances to protect the nervous system from the degenerative effects of diabetes has high priority in biomedical research. Neuroactive steroids might be interesting since they have been recently identified as promising neuroprotective agents in several models of neurodegeneration. We have assessed whether chronic treatment with progesterone (P), dihydroprogesterone (DHP) or tetrahydroprogesterone (THP) had neuroprotective effects against streptozotocin (STZ)-induced diabetic neuropathy at the neurophysiological, functional, biochemical and neuropathological levels. Using gas chromatography coupled to mass-spectrometry, we found that three months of diabetes markedly lowered P plasma levels in male rats, and chronic treatment with P restored them, with protective effects on peripheral nerves. In the model of STZ-induced of diabetic neuropathy, chronic treatment for 1 month with P, or with its derivatives, DHP and THP, counteracted the impairment of nerve conduction velocity (NCV) and thermal threshold, restored skin innervation density, and improved Na(+),K(+)-ATPase activity and mRNA levels of myelin proteins, such as glycoprotein zero and peripheral myelin protein 22, suggesting that these neuroactive steroids, might be useful protective agents in diabetic neuropathy. Interestingly, different receptors seem to be involved in these effects. Thus, while the expression of myelin proteins and Na(+),K(+)-ATPase activity are only stimulated by P and DHP (i.e. two neuroactive steroids interacting with P receptor, PR), NCV, thermal nociceptive threshold and intra-epidermal nerve fiber (IENF) density are also affected by THP, which interacts with GABA-A receptor. Because, a therapeutic approach with specific synthetic receptor ligands could avoid the typical side effects of steroids, future experiments will be devoted to evaluating the role of PR and GABA-A receptor in these protective effects. PMID:17187935

  10. Diabetes-Induced Changes in the Alternative Splicing of the Slo Gene in Corporal Tissue

    PubMed Central

    Davies, Kelvin P.; Zhao, Weixin; Tar, Moses; Figueroa, Johanna C.; Desai, Pratik; Verselis, Vytas K.; Kronengold, Jack; Wang, Hong-Zhan; Melman, Arnold; Christ, George J.

    2007-01-01

    Objectives Erectile dysfunction is a common diabetic complication. Preclinical studies have documented that the Slo gene (encoding the BK or Maxi-K channel ?-subunit) plays a critical role in erectile function. Therefore, we determined whether diabetes induces changes in the splicing of the Slo gene relevant to erectile function. Methods Reverse transcriptase-polymerase chain reaction was used to compare Slo splice variant expression in corporal tissue excised from control and streptozotocin (STZ)-induced diabetic Fischer F-344 rats. Splice variants were sequenced, characterized by patch clamping, and fused to green fluorescent protein to determine cellular localization. The impact of altered Slo expression on erectile function was further evaluated in vivo. Results A novel Slo splice variant (SVcyt, with a cytoplasmic location) was predominantly expressed in corporal tissue from control rats. STZ-diabetes caused upregulation of a channel-forming transcript SV0. Preliminary results suggest that SV0 was also more prevalent in the corporal tissue of human diabetic compared with nondiabetic patients. The change in isoform expression in STZ-treated rats was partially reversed by insulin treatment. Intracorporal injection of a plasmid expressing the SV0 transcript, but not SVcyt, restored erectile function in STZ-diabetic rats. Conclusions Alternative splicing of the Slo transcript may represent an important compensatory mechanism to increase the ease with which relaxation of corporal tissue may be triggered as a result of a diabetes-related decline in erectile capacity. PMID:17150299

  11. Pentoxifylline Diminishes the Oxidative Damage to Renal Tissue Induced by Streptozotocin in the Rat

    PubMed Central

    Martínez-Morales, F.

    2004-01-01

    Oxidative damage has been suggested to be a contributing factor in the development to diabetic nephropathy (DN). Recently, there has been evidence that pentoxifylline (PTX) has free radical-scavenging properties; thus, its antiinflammatory and renoprotective effects may be related to a reduction in reactive oxygen species production. It is likely that the pharmacological effects of PTX include an antioxidant mechanism as shown in in vitro assays. The aim of this study was to evaluate whether the reported renoprotective effects of PTX could be the result of its antioxidant actions in streptozotocin (STZ)-induced DN in rats. The administration of PTX over a period of 8 weeks, in addition to displaying renoprotective effects, caused a significant reduction in lipoperoxide levels (LPOS) in the diabetic kidney (P < 0.05), compared to untreated rats. These levels were comparable to those in the healthy kidney of experimental animals (P > 0.05). All untreated STZ rats exhibited an increase in LPOS as opposed to healthy controls (H) (P < 0.001). The total antioxidant activity (TAA) in plasma was increased significantly already after 2 days of STZ (P < 0.05). When we examined the progression of TAA in STZ rats, there was a significant decrease over 8 weeks (P < 0.05). PTX treatment caused an increase in TAA when compared to untreated STZ rats (P < 0.05). Renal hypertrophy was less evident in PTX-treated STZ than in untreated STZ rats, evaluated by kidney weight/body weight ratio. These results indicate that PTX decreases the oxidative damage induced by these experimental procedures and may increase antioxidant defense mechanisms in STZ-induced diabetes in rats. PMID:15763938

  12. Melatonin improves spatial navigation memory in male diabetic rats

    PubMed Central

    Babaei-Balderlou, Farrin; Zare, Samad

    2012-01-01

    The aim of the present study was to evaluate the effect of melatonin as an antioxidant on spatial navigation memory in male diabetic rats. Thirty-two male white Wistar rats weighing 200 ± 20 g were divided into four groups, randomly: control, melatonin, diabetic and melatonin-treated diabetic. Experimental diabetes was induced by intraperitoneal injection of 50 mg kg-1 streptozotocin. Melatonin was injected (10 mg kg-1 day-1, ip) for 2 weeks after 21 days of diabetes induction. At the end of administration period, the spatial navigation memory of rats was evaluated by cross-arm maze. In this study lipid peroxidation levels, glutathione-peroxidase and catalase activities were measured in hippocampus. Diabetes caused to significant decrease in alternation percent in the cross-arm maze, as a spatial memory index, compared to the control group (p < 0.05), whereas administration of melatonin prevented the spatial memory deficit in diabetic rats. Also melatonin injection significantly increased the spatial memory in intact animals compared to the control group (p < 0.05). Assessment of hippocampus homogenates indicated an increase in lipid peroxidation levels and a decrease in GSH-Px and CAT activities in the diabetic group compared to the control animals, while melatonin administration ameliorated these indices in diabetic rats. In conclusion, diabetes induction leads to debilitation of spatial navigation memory in rats, and the melatonin treatment improves the memory presumably through the reduction of oxidative stress in hippocampus of diabetic rats. PMID:25610567

  13. Genetic Difference in Susceptibility to the Blood-Retina Barrier Breakdown in Diabetes and Oxygen-Induced Retinopathy

    PubMed Central

    Zhang, Sarah X.; Ma, Jian-xing; Sima, Jing; Chen, Ying; Hu, Mark S.; Ottlecz, Anna; Lambrou, George N.

    2005-01-01

    The breakdown of the blood-retina barrier (BRB) is a common feature of diabetic retinopathy. The purpose of the present study is to determine whether there are genetic differences in susceptibility to the breakdown of the BRB in diabetic retinopathy using two rat models. In streptozotocin (STZ)-induced diabetes, Brown Norway (BN) rats developed sustained vascular hyperpermeability in the retina during the entire experimental period (16 weeks of diabetes), while diabetic Sprague Dawley (SD) rats only showed retinal hyperpermeability from 3 to 10 days after the onset of diabetes. The strain difference in permeability was not correlated with the blood glucose levels in these two strains. In oxygen-induced retinopathy (OIR), BN rats developed retinal vascular hyperpermeability from postnatal day 12 (P12) to P22 with a peak at P16, which was 8.7-fold higher than that in the age-matched normal controls. In OIR-SD rats, however, hyperpermeability was observed from P14 to P18, with a peak only 2.2-fold higher than that in the controls. The strain difference in vascular hyperpermeability was correlated with the different overexpression of vascular endothelial growth factor (VEGF) in the retina of these two models. This finding suggests that genetic backgrounds contribute to the susceptibility to diabetic retinopathy. PMID:15632023

  14. Influences of crude extract of tea leaves, Camellia sinensis, on streptozotocin diabetic male albino mice

    Microsoft Academic Search

    Atef M. Al-Attar; Talal A. Zari

    2010-01-01

    Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for diabetes mellitus. The aim of the present study was to investigate the hypoglycemic activity of the crude tea leaves extract on streptozotocin (STZ)-induced diabetic mice. The average body weight of animals with diabetes and their percentage changes of body weight gain after 15 and 30days

  15. Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm.

    PubMed

    Noda, Kousuke; Nakao, Shintaro; Zandi, Souska; Sun, Dawei; Hayes, K C; Hafezi-Moghadam, Ali

    2014-05-01

    The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and type 2 diabetes (T2D) is not well studied, partly because an appropriate model has not been developed. Recently, we introduced a novel model of spontaneous T2D and MetS that replicates the relevant features of the human disease. In the current study, we investigated the retinal vascular changes in these animals. Experimental DR in streptozotocin (STZ)-injected rodents is described as an inflammatory disease, in which intercellular adhesion molecule 1 (ICAM-1) plays a key role. In comparison, advanced diabetes (HbA1c>10%) in the Nile grass rat (NGR) was associated with lower ICAM-1 protein expression when compared with that in normal or moderately diabetic animals. Vascular cell adhesion molecule 1 (VCAM-1) expression, however, was unaffected by the disease state. As opposed to the STZ-induced model of DR, in diabetic NGRs, most leukocytes accumulated in the retinal arteries. Consistent with the ICAM-1 reduction, leukocyte accumulation was significantly reduced in advanced disease. Similarly, leukocyte adhesions were significantly lower, with elevated plasma triglycerides (>200 mg/dl), and cholesterol (>240 mg/dl). However, these adhesions were significantly higher in animals with higher plasma insulin (>5 ?IU/ml) and leptin (>20 ng/ml), suggesting a role for these hormones in diabetic retinal leukostasis. Diabetic NGRs showed substantial retinal endothelial injury, primarily in the microvessels, including vascular tortuosity, obliterated acellular capillaries, and pericyte ghosts. The NGR provides a convenient and realistic model for investigation of retinal changes in MetS/T2D with convincing advantages over the commonly used STZ-induced T1D. PMID:24571922

  16. Antihyperglycaemic effect of 'Ilogen-Excel', an ayurvedic herbal formulation in streptozotocin-induced diabetes mellitus.

    PubMed

    Umamaheswari, Selvaraj; Mainzen Prince, Ponnaian Stanely

    2007-01-01

    'Ilogen-Excel', an Ayurvedic herbal formulation is composed of eight medicinal plants (Curcuma longa, Strychnos potatorum, Salacia oblonga, Tinospora cordifolia, Vetivelia zizanioides, Coscinium fenestratum, Andrographis paniculata and Mimosa pudica). The present study evaluates the antihyperglycemic effect of 'Ilogen-Excel' in streptozotocin induced diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg/kg body weight). Oral administration of 'Ilogen-Excel' (50 mg/kg and 100 mg/kg) for 60 days resulted in significantly lowered levels of blood glucose and significantly increased levels of plasma insulin, hepatic glycogen and total hemoglobin. 'Ilogen-Excel' administration also decreased the levels of glycosylated hemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and vitamin E in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of 'Ilogen-Excel'. Administration of insulin normalized all the biochemical parameters studied in diabetic rats. The effect at a dose of 100 mg/kg was more pronounced than 50 mg/kg and brought back all the parameters to near normal levels. Thus, our study shows the antihyperglycemic effects of 'Ilogen-Excel' in STZ-induced diabetic rats. Our study also shows that combined therapy is better than individual therapy. PMID:17665851

  17. Role of hydrogen sulfide in the pain processing of non-diabetic and diabetic rats.

    PubMed

    Velasco-Xolalpa, M E; Barragán-Iglesias, P; Roa-Coria, J E; Godínez-Chaparro, B; Flores-Murrieta, F J; Torres-López, J E; Araiza-Saldaña, C I; Navarrete, A; Rocha-González, H I

    2013-10-10

    Hydrogen sulfide (H2S) is a gasotransmitter endogenously generated from the metabolism of L-cysteine by action of two main enzymes called cystathionine ?-synthase (CBS) and cystathionine ?-lyase (CSE). This gas has been involved in the pain processing and insulin resistance produced during diabetes development. However, there is no evidence about its participation in the peripheral neuropathy induced by this metabolic disorder. Experimental diabetes was induced by streptozotocin (50mg/kg, i.p.) in female Wistar rats. Streptozotocin injection increased formalin-evoked flinching in diabetic rats as compared to non-diabetic rats after 2 weeks. Peripheral administration of NaHS (an exogenous donor of H2S) and L-cysteine (an endogenous donor of H2S) dose-dependently increased flinching behavior in diabetic and non-diabetic rats. Contrariwise, hydroxylamine (HA, a CBS inhibitor) and DL-propargylglycine (PPG, a CSE inhibitor) decreased formalin-induced nociceptive behavior in both experimental groups. In addition, an ineffective dose of HA and PPG partially prevented the L-cysteine-induced hyperalgesia in diabetic and non-diabetic rats. Interestingly, HA and PPG were three order of magnitude more potent in diabetic rats respect to non-diabetic rats, whereas NaHS was ten times more potent in the streptozotocin-diabetic group. Nine to 11 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, subcutaneous administration of PPG or HA reduced tactile allodynia in diabetic rats. Paradoxically, H2S levels were decreased in nerve sciatic, dorsal root ganglion and spinal cord, but not paw nor blood plasma, during diabetes-associated peripheral neuropathy development. Collectively, results suggest that H2S synthesized by CBS and CSE participate in formalin-induced nociception in diabetic and non-diabetic rats, as well as; in tactile allodynia in streptozotocin-injected rats. In addition, data seems to indicate that diabetic rats are more sensible to H2S-induced hyperalgesia than normoglycemic rats. PMID:23830907

  18. Effect of Trasina, an Ayurvedic herbal formulation, on pancreatic islet superoxide dismutase activity in hyperglycaemic rats.

    PubMed

    Bhattacharya, S K; Satyan, K S; Chakrabarti, A

    1997-03-01

    Diabetes mellitus was induced in male CF strain rats by streptozotocin (STZ) and hyperglycaemia and superoxide dismutase (SOD) activity of pancreatic islet cells was assessed on days 7, 14, 21 and 28. STZ induced significant hyperglycaemia and a concomitant decrease in islet cell SOD activity. Transina (TR), an Ayurvedic herbal formulation comprising of Withania somnifera, Tinospora cordifolia, Eclipta alba, Ocimum sanctum, Picrorrhiza kurroa and shilajit, had little per se effect on blood sugar concentrations and islet SOD activity in euglycaemic rats, in the doses of 100 and 200 mg/kg, p.o. administered once daily for 28 days. However, these doses of TR induced a dose- related decrease in STZ hyperglycaemia and attenuation of STZ induced decrease in islet SOD activity. The results indicate that the earlier reported anti-hyperglycaemic effect of TR may be due to pancreatic islet free radical scavenging activity, the hyperglycaemic activity of STZ being the consequence of decrease in islet SOD activity leading to the accumulation of degenerative oxidative free radicals in islet beta-cells. PMID:9332177

  19. Sodium selenate corrects glucose tolerance and heart function in STZ diabetic rats

    Microsoft Academic Search

    Mary L. Battell; Heather L. M. Delgatty; John H. McNeill

    1998-01-01

    Sodium selenate, administered intraperitoneally (i.p.), resulted in an improvement in glucose tolerance in treated diabetic rats. Fed rat plasma glucose levels were reduced by selenate treatment in streptozotocin diabetic rats. The lowest values of blood glucose were reached within 3 weeks of beginning the treatment. Food and fluid consumption was reduced in treated compared to untreated diabetic rats. Diabetic treated

  20. Characterization of Diabetic Neuropathy in the Zucker Diabetic Sprague-Dawley Rat: A New Animal Model for Type 2 Diabetes

    PubMed Central

    Davidson, Eric P.; Coppey, Lawrence J.; Holmes, Amey; Lupachyk, Sergey; Dake, Brian L.; Oltman, Christine L.; Peterson, Richard G.; Yorek, Mark A.

    2014-01-01

    Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy. PMID:25371906

  1. Characterization of diabetic neuropathy in the Zucker diabetic Sprague-Dawley rat: a new animal model for type 2 diabetes.

    PubMed

    Davidson, Eric P; Coppey, Lawrence J; Holmes, Amey; Lupachyk, Sergey; Dake, Brian L; Oltman, Christine L; Peterson, Richard G; Yorek, Mark A

    2014-01-01

    Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy. PMID:25371906

  2. Decrease of hyperglycemia by syringaldehyde in diabetic rats.

    PubMed

    Kuo, S C; Chung, H H; Huang, C H; Cheng, J T

    2014-01-01

    Syringaldehyde is one of the active principles from the stems of Hibiscus taiwanensis (Malvaceae) that has been mentioned to lower hyperglycemia. However, the potential mechanisms for this action of syringaldehyde remain obscure. In the present study, we used streptozotocin to induce diabetic rats (STZ-diabetic rats) as type 1-like diabetic rats and fed fructose-rich chow to rats as type 2-like diabetic rats. Then, we performed the postprandial glucose test and applied the hyperinsulinemic euglycemic clamp to investigate the actions of syringaldehyde. Also, the changes of gene expressions of enzyme relating to glucose homeostasis in muscle and liver were characterized. Syringaldehyde significantly decreased the postprandial plasma glucose in rats, while the plasma insulin was not modified by syringaldehyde. The glucose infusion rate (GIR) in fructose chow-fed rats using hyperinsulinemic euglycemic clamp was markedly improved by syringaldehyde. Additionally, repeated administration of syringaldehyde for 3 days in STZ-diabetic rats resulted in a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. Our results suggest that syringaldehyde may increase glucose utilization to lower hyperglycemia in diabetic rats. PMID:23918689

  3. Pharmacokinetics of oltipraz in diabetic rats with liver cirrhosis

    PubMed Central

    Ahn, CY; Bae, SK; Bae, SH; Kim, T; Jung, YS; Kim, YC; Lee, MG; Shin, WG

    2009-01-01

    Background and purpose: The incidence of diabetes mellitus is increased in patients with liver cirrhosis. Oltipraz is currently in trials to treat patients with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus on pharmacokinetics of oltipraz and on expression of hepatic, CYP1A, 2B1/2, 2C11, 2D and 3A in rats with experimental liver cirrhosis. Experimental approach: Oltipraz was given intravenously (10 mg·kg?1) or orally (30 mg·kg?1) to rats with liver cirrhosis induced by N-dimethylnitrosamine (LC rats) or with diabetes, induced by streptozotocin (DM rats) or to rats with both liver cirrhosis and diabetes (LCD rats) and to control rats, and pharmacokinetic variables measured. Protein expression of hepatic CYP1A, 2B1/2, 2C11, 2D and 3A was measured using Western blot analysis. Key results: After i.v. or p.o. administration of oltipraz to LC and DM rats, the AUC was significantly greater and smaller, respectively, than that in control rats. In LCD rats, the AUC was that of LC and DM rats (partially restored towards control rats). Compared with control rats, the protein expression of hepatic CYP1A increased, that of CYP2C11 and 3A decreased, but that of CYP2B1/2 and 2D was not altered in LCD rats. Conclusions and implications: In rats with diabetes and liver cirrhosis, the AUC of oltipraz was partially restored towards that of control rats. PMID:19226288

  4. Evaluation of level of DNA damage in blood leukocytes of non-diabetic and diabetic rat exposed to cigarette smoke

    Microsoft Academic Search

    Paula Helena Ortiz Lima; Yuri Karen Sinzato; Maricelma da Silva Soares de Souza; Mariana Gobbo Braz; Marilza Vieira Cunha Rudge; Débora Cristina Damasceno

    2007-01-01

    The objective of the present study was to use the comet assay to evaluate the steady-state level of DNA damage in peripheral blood leukocytes from diabetic and non-diabetic female Wistar rats exposed to air or to cigarette smoke. A total of 20 rats were distributed into four experimental groups (n=5rats\\/group): non-diabetic (control) and diabetic exposed to filtered air; non-diabetic and

  5. Foreign Body Response to Subcutaneous Implants in Diabetic Rats

    PubMed Central

    Socarrás, Teresa Oviedo; Vasconcelos, Anilton C.; Campos, Paula P.; Pereira, Nubia B.; Souza, Jessica P. C.; Andrade, Silvia P.

    2014-01-01

    Implantation of synthetic matrices and biomedical devices in diabetic individuals has become a common procedure to repair and/or replace biological tissues. However, an adverse foreign body reaction that invariably occurs adjacent to implant devices impairing their function is poorly characterized in the diabetic environment. We investigated the influence of this condition on the abnormal tissue healing response in implants placed subcutaneously in normoglycemic and streptozotocin-induced diabetes in rats. In polyether-polyurethane sponge discs removed 10 days after implantation, the components of the fibrovascular tissue (angiogenesis, inflammation, fibrogenesis, and apoptosis) were assessed. Intra-implant levels of hemoglobin and vascular endothelial growth factor were not different after diabetes when compared with normoglycemic counterparts. However, there were a lower number of vessels in the fibrovascular tissue from diabetic rats when compared with vessel numbers in implants from non-diabetic animals. Overall, the inflammatory parameters (neutrophil accumulation - myeloperoxidase activity, tumor necrosis factor alpha, and monocyte chemotactic protein-1 levels and mast cell counting) increased in subcutaneous implants after diabetes induction. However, macrophage activation (N-acetyl-?-D-glucosaminidase activity) was lower in implants from diabetic rats when compared with those from normoglycemic animals. All fibrogenic markers (transforming growth factor beta 1 levels, collagen deposition, fibrous capsule thickness, and foreign body giant cells) decreased after diabetes, whereas apoptosis (TUNEL) increased. Our results showing that hyperglycemia down regulates the main features of the foreign body reaction induced by subcutaneous implants in rats may be relevant in understanding biomaterial integration and performance in diabetes. PMID:25372281

  6. Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats.

    PubMed

    Barzegar-Fallah, Anita; Alimoradi, Houman; Asadi, Firouzeh; Dehpour, Ahmad Reza; Asgari, Mojgan; Shafiei, Massoumeh

    2015-04-01

    It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti-inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin-induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor-? were also determined. Streptozotocin-treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor-?, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor-?, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti-oxidative and anti-inflammatory mechanisms that appear to be independent of the 5-HT3 receptor. PMID:25676798

  7. Oxidative stress-dependent impairment of cardiac-specific transcription factors in experimental diabetes.

    PubMed

    Aragno, Manuela; Mastrocola, Raffaella; Medana, Claudio; Catalano, Maria Graziella; Vercellinatto, Ilenia; Danni, Oliviero; Boccuzzi, Giuseppe

    2006-12-01

    Oxidative stress plays a key role in the pathogenesis of diabetic cardiomyopathy, which is characterized by myocyte loss and fibrosis, finally resulting in heart failure. The study looked at the downstream signaling whereby oxidative stress leads to reduced myocardial contractility in the left ventricle of diabetic rats and the effects of dehydroepiandrosterone (DHEA), which production is suppressed in the failing heart and prevents the oxidative damage induced by hyperglycemia in several experimental models. DHEA was given orally at a dose of 4 mg/rat per day for 21 d to rats with streptozotocin (STZ)-induced diabetes and genetic diabetic-fatty (ZDF) rats. Oxidative balance, advanced glycated end products (AGEs) and AGE receptors, cardiac myogenic factors, and myosin heavy-chain gene expression were determined in the left ventricle of treated and untreated STZ-diabetic rats and ZDF rats. Oxidative stress induced by chronic hyperglycemia increased AGE and AGE receptors and led to activation of the pleoitropic transcription factor nuclear factor-kappaB. Nuclear factor-kappaB activation triggered a cascade of signaling, which finally led to the switch in the cardiac myosin heavy-chain (MHC) gene expression from the alpha-MHC isoform to the beta-MHC isoform. DHEA treatment, by preventing the activation of the oxidative pathways induced by hyperglycemia, counteracted the enhanced AGE receptor activation in the heart of STZ-diabetic rats and ZDF rats and normalized downstream signaling, thus avoiding impairment of the cardiac myogenic factors, heart autonomic nervous system and neural crest derivatives (HAND) and myogenic enhancer factor-2, and the switch in MHC gene expression, which are the early events in diabetic cardiomyopathy. PMID:16935841

  8. Renal Processing of Albumin in Diabetes and Hypertension in Rats

    Microsoft Academic Search

    Leileata M. Russo; Tanya M. Osicka; Gail C. Brammar; Riccardo Candido; George Jerums; Wayne D. Comper

    2003-01-01

    Background\\/Aims: Recent studies show that albuminuria may be the result of changes in post-glomerular cellular uptake and processing of albumin. This study aims to determine whether this processing is disrupted in diabetes and\\/or hypertension. Methods: Diabetes (d) was induced using streptozotocin in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) and studied after 8, 16 and 24 weeks

  9. Renal ACE and ACE2 Expression in Early Diabetic Rats

    Microsoft Academic Search

    Ju-Young Moon; Kyung-Hwan Jeong; Sang-Ho Lee; Tae-Won Lee; Chun-Gyoo Ihm; Sung Jig Lim

    2008-01-01

    Background\\/Aim: The role of angiotensin-converting enzyme (ACE)-related carboxypeptidase-2 (ACE2) in the regulation of the renin-angiotensin system is not well characterized. This study investigated the changes in the expression of ACE and ACE2 in the kidney in early diabetic rats. Methods: Streptozotocin-induced diabetic rats were examined. The concentrations of angiotensin II in plasma, urine, and renal cortex were measured by radioimmunoassay.

  10. Changes in the daily rhythm of lipid metabolism in the diabetic retina.

    PubMed

    Wang, Qi; Tikhonenko, Maria; Bozack, Svetlana N; Lydic, Todd A; Yan, Lily; Panchy, Nicholas L; McSorley, Kelly M; Faber, Matthew S; Yan, Yuanqing; Boulton, Michael E; Grant, Maria B; Busik, Julia V

    2014-01-01

    Disruption of circadian regulation was recently shown to cause diabetes and metabolic disease. We have previously demonstrated that retinal lipid metabolism contributed to the development of diabetic retinopathy. The goal of this study was to determine the effect of diabetes on circadian regulation of clock genes and lipid metabolism genes in the retina and retinal endothelial cells (REC). Diabetes had a pronounced inhibitory effect on the negative clock arm with lower amplitude of the period (per) 1 in the retina; lower amplitude and a phase shift of per2 in the liver; and a loss of cryptochrome (cry) 2 rhythmic pattern in suprachiasmatic nucleus (SCN). The positive clock arm was increased by diabetes with higher amplitude of circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (bmal1) and phase shift in bmal1 rhythmic oscillations in the retina; and higher bmal1 amplitude in the SCN. Peroxisome proliferator-activated receptor (PPAR) ? exhibited rhythmic oscillation in retina and liver; PPAR? had lower amplitude in diabetic liver; sterol regulatory element-binding protein (srebp) 1c had higher amplitude in the retina but lower in the liver in STZ- induced diabetic animals. Both of Elongase (Elovl) 2 and Elovl4 had a rhythmic oscillation pattern in the control retina. Diabetic retinas lost Elovl4 rhythmic oscillation and had lower amplitude of Elovl2 oscillations. In line with the in vivo data, circadian expression levels of CLOCK, bmal1 and srebp1c had higher amplitude in rat REC (rREC) isolated from diabetic rats compared with control rats, while PPAR? and Elovl2 had lower amplitude in diabetic rREC. In conclusion, diabetes causes dysregulation of circadian expression of clock genes and the genes controlling lipid metabolism in the retina with potential implications for the development of diabetic retinopathy. PMID:24736612

  11. Changes in the Daily Rhythm of Lipid Metabolism in the Diabetic Retina

    PubMed Central

    Wang, Qi; Tikhonenko, Maria; Bozack, Svetlana N.; Lydic, Todd A.; Yan, Lily; Panchy, Nicholas L.; Mcsorley, Kelly M.; Faber, Matthew S.; Yan, Yuanqing; Boulton, Michael E.; Grant, Maria B.; Busik, Julia V.

    2014-01-01

    Disruption of circadian regulation was recently shown to cause diabetes and metabolic disease. We have previously demonstrated that retinal lipid metabolism contributed to the development of diabetic retinopathy. The goal of this study was to determine the effect of diabetes on circadian regulation of clock genes and lipid metabolism genes in the retina and retinal endothelial cells (REC). Diabetes had a pronounced inhibitory effect on the negative clock arm with lower amplitude of the period (per) 1 in the retina; lower amplitude and a phase shift of per2 in the liver; and a loss of cryptochrome (cry) 2 rhythmic pattern in suprachiasmatic nucleus (SCN). The positive clock arm was increased by diabetes with higher amplitude of circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (bmal1) and phase shift in bmal1 rhythmic oscillations in the retina; and higher bmal1 amplitude in the SCN. Peroxisome proliferator-activated receptor (PPAR) ? exhibited rhythmic oscillation in retina and liver; PPAR? had lower amplitude in diabetic liver; sterol regulatory element-binding protein (srebp) 1c had higher amplitude in the retina but lower in the liver in STZ- induced diabetic animals. Both of Elongase (Elovl) 2 and Elovl4 had a rhythmic oscillation pattern in the control retina. Diabetic retinas lost Elovl4 rhythmic oscillation and had lower amplitude of Elovl2 oscillations. In line with the in vivo data, circadian expression levels of CLOCK, bmal1 and srebp1c had higher amplitude in rat REC (rREC) isolated from diabetic rats compared with control rats, while PPAR? and Elovl2 had lower amplitude in diabetic rREC. In conclusion, diabetes causes dysregulation of circadian expression of clock genes and the genes controlling lipid metabolism in the retina with potential implications for the development of diabetic retinopathy. PMID:24736612

  12. Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine

    Microsoft Academic Search

    H. P. Hammes; A. Bartmann; L. Engel; P. Wülfroth

    1997-01-01

    Summary   In order to study the contribution of oxidant stress to the pathogenesis of experimental diabetic retinopathy, male streptozotocin\\u000a diabetic Lewis rats were treated with the antioxidant and lipid-lowering compound nicanartine (80 mg\\/kg; n = 8, blood glucose level 16.7 ± 3.9 mmol\\/l; HbA1 11.8 ± 1.6 %) by oral supplementation for 6 months and compared with untreated diabetic (n

  13. Hypoglycemic Activity of Phoradendron tomentosum in Streptozotocin-diabetic Rats

    Microsoft Academic Search

    Jacinto Careaga-Olivares; Gloria Aguilar-Cuestas; María Julia Verde-Star; Ricardo M. Cerda-Flores; Gerardo Lozano-Garza; Miguel Ángel Echávarri-Guzmán; Carmina Calzado-Flores

    2006-01-01

    Mistletoe, Phoradendron tomentosum (D.C.) Engelm (Loranthaceae), is used in Mexico as a folk medicine in the treatment of diabetes mellitus (DM). The objective of this study was to test the hypoglycemic effect of an aqueous extract of this plant on normoglycemic and streptozotocin (STZ)-diabetic male rats. Blood glucose concentrations were measured at the beginning and at the end of the

  14. Effect of FK 506 on Spontaneous Diabetes in BB Rats

    PubMed Central

    MURASE, NORIKO; LIEBERMAN, IRVING; NALESNIK, MICHAEL A.; MINTZ, DANIEL H.; TODO, SATORU; DRASH, ALLAN L.; STARZL, THOMAS E.

    2010-01-01

    From days 30–120 after birth, 59 BB rats were treated with water (n = 20) or FK 506 in intragastric doses of 1 mg · kg?1 · day?1 (n = 19) or 2 mg · kg?1 · day?1 (n = 20). Diabetes developed in 75, 15, and 0% of the 3 groups, respectively. Animals protected from diabetes by FK 506 had normal intraperitoneal glucose tolerance tests, virtual absence histopathologically of autoimmune insulitis, and normal pancreatic insulin content. Forty-five to 75 days after stopping FK 506, ~75% of the rats that were diabetes free at 120 days remained so. PMID:1700959

  15. Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats

    Microsoft Academic Search

    Lina Åkesson; Johan Trygg; Jessica M. Fuller; Rasmus Madsen; Jon Gabrielsson; Stephen Bruce; Hans Stenlund; Terry Tupling; Ranae Pefley; Torbjörn Lundstedt; Åke Lernmark; Thomas Moritz

    The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period\\u000a of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing\\u000a the serum metabolite profile detected with combined gas chromatography\\/mass spectrometry (GC\\/MS) and liquid chromatography\\/mass\\u000a spectrometry (LC\\/MS). We found that the

  16. Polychromatic LED Therapy in Burn Healing of Non-diabetic and Diabetic Rats

    Microsoft Academic Search

    Farouk A. H. Al-Watban; Bernard L. Andres

    2003-01-01

    Objective: We determined the effect of polychromatic light-emitting diodes (LED) in burn healing of non- diabetic and streptozotocin-induced diabetic rats. Background Data: LEDs were used as the light source for phototherapy. Materials and Methods: The polychromatic LED is a cluster of 25 diodes emitting photons at wavelengths of 510- 543, 594- 599, 626- 639, 640- 670, and 842- 879 nm

  17. Ghrelin reverses experimental diabetic neuropathy in mice

    SciTech Connect

    Kyoraku, Itaru; Shiomi, Kazutaka [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)] [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan)] [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Nakazato, Masamitsu, E-mail: nakazato@med.miyazaki-u.ac.jp [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)] [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)

    2009-11-20

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  18. Increased intraretinal PO2 in short-term diabetic rats.

    PubMed

    Lau, Jennifer C M; Linsenmeier, Robert A

    2014-12-01

    In diabetic retinopathy, neovascularization is hypothesized to develop due to hypoxia in the retina. However, evidence for retinal hypoxia is limited, and the progressive changes in oxygenation are unknown. The objective of this study was to determine if retinal hypoxia occurs early in the development of diabetes. Intraretinal oxygen (PO2) profiles were recorded with oxygen-sensitive microelectrodes in control and diabetic Long-Evans rats at 4 and 12 weeks after induction of diabetes. Diabetes did not affect oxygen consumption in the photoreceptors in either dark or light adaptation. Oxygenation of the inner retina was not affected after 4 weeks of diabetes, although vascular endothelial growth factor levels increased. At 12 weeks, average inner retinal PO2, normalized to choriocapillaris PO2, was higher in diabetic rats than in age-matched controls, which was opposite to what was expected. Thus retinal hypoxia is not a condition of early diabetes in rat retina. Increased inner retinal PO2 may occur because oxygen consumption decreases in the inner retina. PMID:25028524

  19. Astragaloside IV ameliorates diabetic nephropathy involving protection of podocytes in streptozotocin induced diabetic rats.

    PubMed

    Chen, Jianguo; Chen, Yifang; Luo, Yunling; Gui, Dingkun; Huang, Jianhua; He, Dongyuan

    2014-08-01

    Podocyte loss and dysfunction play key role during the development of diabetic nephropathy (DN). The aim of this study was to observe the protective effects of astragaloside IV on podocyte in diabetic rats and explore its mechanisms preliminary. Healthy male Sprague-Dawley (SD) rats were randomized into normal control group, diabetic nephropathy group and diabetic nephropathy with AS-IV treatment group. DN was induced by intraperitoneal injection of streptozotocin (STZ). AS-IV treatment started 2 weeks before STZ injection and lasted 14 weeks. 24h Urinary proteins were measured 4, 8 and 12 weeks after STZ injection. Body weight, blood glucose, blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured 12 weeks after STZ injection. Renal pathology, podocyte morphological changes, podocyte density, protein and mRNA expression of integrin ?3, integrin ?1 and integrin-linked kinase (ILK) were detected by histopathology, electron microscopy, immunohistochemistry, western blot and real-time PCR, respectively. Hyperglycemia, proteinuria, mesangial expansion and podocyte loss, increased protein expression of ILK and decreased protein expression of integrin ?3 and integrin ?1 were detected in diabetic rats. AS-IV treatment ameliorated podocyte loss, renal histopathology and podocyte foot process effacement, decreased proteinuria, partially restored protein expression of integrin ?3, integrin ?1 and ILK. These findings suggested that AS-IV may protect podocyte and ameliorate diabetic nephropathy by inhibiting the expression of ILK and restoring the expression of integrin ?3?1 in diabetic rats. PMID:24809932

  20. The effect of streptozotocin-induced diabetes on the EDHF-type relaxation and cardiac function in rats.

    PubMed

    Absi, Mais; Oso, Hani; Khattab, Marwan

    2013-07-01

    The endothelium-derived hyperpolarizing factor (EDHF) response is a critical for the functioning of small blood vessels. We investigated the effect of streptozotocin-induced diabetes on the EDHF response and its possible role in the regulation of cardiac function. The vasorelaxant response to ACh- or NS309- (direct opener endothelial small- (SKCa)- and intermediate-conductance (IKCa) calcium-activated potassium channels; main components of EDHF response) were measured in pressurized mesenteric arteries (diameter 300-350 ?m). The response to 1 ?M ACh was reduced in diabetes (84.8 ± 2.8% control vs 22.5 ± 5.8% diabetics; n ? 8; P < 0.001). NS309 (1 ?M) relaxations were also decreased in diabetic arteries (78.5 ± 8.7% control vs 32.1 ± 5.8% diabetics; n ? 5; P < 0.001). SKCa and IKCa-mediated EDHF relaxations in response ACh or NS309 were also significantly reduced by diabetes. Ruthenium red, RuR, a blocker of TRP channels, strongly depress the response to ACh and NS309 in control and diabetic arteries. RuR decreased SKCa and IKCa-mediated EDHF vasodilatation in response to NS309 but not to ACh. An elevation in systolic blood pressure was observed in diabetic animals. ECG recording of control hearts showed shortening of PR interval. RuR reduced PR interval and R wave amplitude in diabetic hearts. In conclusion, the reduced EDHF-type relaxations in STZ-induced diabetes is due impairment of KCa channels function. TRP channels possibly contribute to EDHF vasodilatation via direct opening of endothelial KCa. It is possible that EDHF and TRP channels contribute to the regulation of cardiac function and therefore can be considered as therapeutic targets to improve cardiovascular complications of diabetes. PMID:25685443

  1. The effect of streptozotocin-induced diabetes on the EDHF-type relaxation and cardiac function in rats

    PubMed Central

    Absi, Mais; Oso, Hani; Khattab, Marwan

    2012-01-01

    The endothelium-derived hyperpolarizing factor (EDHF) response is a critical for the functioning of small blood vessels. We investigated the effect of streptozotocin-induced diabetes on the EDHF response and its possible role in the regulation of cardiac function. The vasorelaxant response to ACh- or NS309- (direct opener endothelial small- (SKCa)- and intermediate-conductance (IKCa) calcium-activated potassium channels; main components of EDHF response) were measured in pressurized mesenteric arteries (diameter 300–350 ?m). The response to 1 ?M ACh was reduced in diabetes (84.8 ± 2.8% control vs 22.5 ± 5.8% diabetics; n ? 8; P < 0.001). NS309 (1 ?M) relaxations were also decreased in diabetic arteries (78.5 ± 8.7% control vs 32.1 ± 5.8% diabetics; n ? 5; P < 0.001). SKCa and IKCa-mediated EDHF relaxations in response ACh or NS309 were also significantly reduced by diabetes. Ruthenium red, RuR, a blocker of TRP channels, strongly depress the response to ACh and NS309 in control and diabetic arteries. RuR decreased SKCa and IKCa-mediated EDHF vasodilatation in response to NS309 but not to ACh. An elevation in systolic blood pressure was observed in diabetic animals. ECG recording of control hearts showed shortening of PR interval. RuR reduced PR interval and R wave amplitude in diabetic hearts. In conclusion, the reduced EDHF-type relaxations in STZ-induced diabetes is due impairment of KCa channels function. TRP channels possibly contribute to EDHF vasodilatation via direct opening of endothelial KCa. It is possible that EDHF and TRP channels contribute to the regulation of cardiac function and therefore can be considered as therapeutic targets to improve cardiovascular complications of diabetes. PMID:25685443

  2. Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity

    SciTech Connect

    Sawant, Sharmilee P. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Sugar Hall 306, Monroe, LA 71209-0470 (United States); Dnyanmote, Ankur V. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Sugar Hall 306, Monroe, LA 71209-0470 (United States); Warbritton, Alan [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Latendresse, John R. [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Mehendale, Harihara M. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Sugar Hall 306, Monroe, LA 71209-0470 (United States)]. E-mail: mehendale@ulm.edu

    2006-03-15

    Previously, we reported high hepatotoxic sensitivity of type 2 diabetic (DB) rats to three dissimilar hepatotoxicants. Additional work revealed that a normally nonlethal dose of CCl{sub 4} was lethal in DB rats due to inhibited compensatory tissue repair. The present study was conducted to investigate the importance of compensatory tissue repair in determining the final outcome of hepatotoxicity in diabetes, using another structurally and mechanistically dissimilar hepatotoxicant, thioacetamide (TA), to initiate liver injury. A normally nonlethal dose of TA (300 mg/kg, ip), caused 100% mortality in DB rats. Time course studies (0 to 96 h) showed that in the non-DB rats, liver injury initiated by TA as assessed by plasma alanine or aspartate aminotransferase and hepatic necrosis progressed up to 48 h and regressed to normal at 96 h resulting in 100% survival. In the DB rats, liver injury rapidly progressed resulting in progressively deteriorating liver due to rapidly expanding injury, hepatic failure, and 100% mortality between 24 and 48 h post-TA treatment. Covalent binding of {sup 14}C-TA-derived radiolabel to liver tissue did not differ from that observed in the non-DB rats, indicating similar bioactivation-based initiation of hepatotoxicity. S-phase DNA synthesis measured by [{sup 3}H]-thymidine incorporation, and advancement of cells through the cell division cycle measured by PCNA immunohistochemistry, were substantially inhibited in the DB rats compared to the non-DB rats challenged with TA. Thus, inhibited cell division and compromised tissue repair in the DB rats resulted in progressive expansion of liver injury culminating in mortality. In conclusion, it appears that similar to type 1 diabetes, type 2 diabetes also increases sensitivity to dissimilar hepatotoxicants due to inhibited compensatory tissue repair, suggesting that sensitivity to hepatotoxicity in diabetes occurs in the absence as well as presence of insulin.

  3. Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats

    Microsoft Academic Search

    Hong Yan; Yong Guo; Jie Zhang; Zhenghua Ding; Wenjing Ha; J. J. Harding

    2008-01-01

    Purpose: To investigate the effect of carnosine (CA), aminoguanidine (AG), and aspirin (ASA) drops, all inhibitors of glycation, on the development of diabetic cataract in rat. Methods: Rats were made diabetic with streptozotocin, and based on the level of plasma glucose, they were assigned as non-diabetic rats (<14 mmol\\/l plasma glucose) and diabetic rats (>14 mmol\\/l plasma glucose). Animals in

  4. Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

    PubMed Central

    Wang, Xin-ting; Li, Jia; Liu, Li; Hu, Nan; Jin, Shi; Liu, Can; Mei, Dan; Liu, Xiao-dong

    2012-01-01

    Aim: Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions. The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications. Methods: Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats. On d 35 after the injection, liver, heart, intestine, kidney, pancreas, cerebral cortex and hippocampus were isolated from the rats. The content of total and free cholesterol in the tissues was determined using HPLC. The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses, respectively. Results: In diabetic rats, the level of free cholesterol was significantly decreased in the peripheral tissues, but significantly elevated in hippocampus, as compared with those in the control rats. Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues, but significant change was only found in kidney and liver. In diabetic rats, the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex, but the change had no statistical significance. Conclusion: Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus. The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein. PMID:22705727

  5. Red Cabbage (Brassica oleracea) Ameliorates Diabetic Nephropathy in Rats

    PubMed Central

    Kataya, Hazem A. H.

    2008-01-01

    The protective action against oxidative stress of red cabbage (Brassica oleracea) extract was investigated. Diabetes was induced in male Wistar rats using streptozotocin (60 mg/kg body weight). Throughout the experimental period (60 days), diabetic rats exhibited many symptoms including loss of body weight, hyperglycemia, polyuria, polydipsia, renal enlargement and renal dysfunction. Significant increase in malondialdehyde, a lipid peroxidation marker, was observed in diabetic kidney. This was accompanied by a significant increase in reduced glutathione and superoxide dismutase activity and a decrease in catalase activity and in the total antioxidant capacity of the kidneys. Daily oral ingestion (1 g/kg body weight) of B. oleracea extract for 60 days reversed the adverse effect of diabetes in rats. B. oleracea extract lowered blood glucose levels and restored renal function and body weight loss. In addition, B. oleracea extract attenuated the adverse effect of diabetes on malondialdehyde, glutathione and superoxide dismutase activity as well as catalase activity and total antioxidant capacity of diabetic kidneys. In conclusion, the antioxidant and antihyperglycemic properties of B. oleracea extract may offer a potential therapeutic source for the treatment of diabetes. PMID:18830445

  6. Homocysteine metabolism in ZDF (type 2) diabetic rats.

    PubMed

    Wijekoon, Enoka P; Hall, Beatrice; Ratnam, Shobhitha; Brosnan, Margaret E; Zeisel, Steven H; Brosnan, John T

    2005-11-01

    Mild hyperhomocysteinemia is a risk factor for many diseases, including cardiovascular disease. We determined the effects of insulin resistance and of type 2 diabetes on homocysteine (Hcy) metabolism using Zucker diabetic fatty rats (ZDF/Gmi fa/fa and ZDF/Gmi fa/?). Plasma total Hcy was reduced in ZDF fa/fa rats by 24% in the pre-diabetic insulin-resistant stage, while in the frank diabetic stage there was a 59% reduction. Hepatic activities of several enzymes that play a role in the removal of Hcy:cystathionine beta-synthase (CBS), cystathionine gamma-lyase, and betaine:Hcy methyltransferase (BHMT) were increased as was methionine adenosyltransferase. CBS and BHMT mRNA levels and the hepatic level of S-adenosylmethionine were also increased in the ZDF fa/fa rats. Studies with primary hepatocytes showed that Hcy export and the transsulfuration flux in cells from ZDF fa/fa rats were particularly sensitive to betaine. Interestingly, liver betaine concentration was found to be significantly lower in the ZDf fa/fa rats at both 5 and 11 weeks. These results emphasize the importance of betaine metabolism in determining plasma Hcy levels in type 2 diabetes. PMID:16249451

  7. Antiallodynic Effects of Electroacupuncture Combined with MK-801 Treatment through the Regulation of p35/p25 in Experimental Diabetic Neuropathy.

    PubMed

    Hwang, Hye Suk; Yang, Eun Jin; Lee, Sang Min; Lee, Soon Cheol; Choi, Sun-Mi

    2011-09-01

    The anti-allodynic effect of NMDA receptor antagonist and acupuncture treatments were explored through spinal p35 regulation of diabetic neuropathic rat. We evaluated the change over time of p35/p25 protein levels in the spinal cord compared with behavioral responses to thermal and mechanical stimulation in streptozotocin (STZ)-induced diabetic rats. Additionally, we studied p35 expression when electroacupuncture (EA) and a sub-effective dose of NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) were used to treat hyperalgesia in the diabetic neuropathic pain (DNP). Thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were significantly decreased in the early stage of diabetes in rats. p35 expression after STZ injection gradually decreased from 1 week to 4 weeks compared to normal controls. p25 expression in 4-week diabetic rats was significantly higher than that of 2-week diabetic rats, and thermal PWL in 4-week diabetic rats showed delayed responses to painful thermal stimulation compared with those at 2 weeks. EA applied to the SP-9 point (2 Hz frequency) significantly prevented the thermal and mechanical hyperalgesia in the DNP rat. Additionally, EA combined with MK-801 prolonged anti-hyperalgesia, increased p35 expression, and decreased the cleavage of p35 to p25 during diabetic neuropathic pain. In this study we show EA combined with a sub-effective dose of MK-801 treatment in DNP induced by STZ that is related to p35/p25 expression in spinal cord. PMID:22110373

  8. Prevention of Arterial Stiffening by Using Low-Dose Atorvastatin in Diabetes Is Associated with Decreased Malondialdehyde

    PubMed Central

    Wang, Chih-Hsien; Chang, Ru-Wen; Ko, Ya-Hui; Tsai, Pi-Ru; Wang, Shoei-Shen; Chen, Yih-Sharng; Ko, Wen-Je; Chang, Chun-Yi; Young, Tai-Horng; Chang, Kuo-Chu

    2014-01-01

    Introduction Without affecting the lipid profile, a low-dose treatment with atorvastatin contributes to the reduction of oxidative stress, inflammation, and adverse cardiovascular events in diabetes. In this study, we investigated whether low-dose atorvastatin exerts any beneficial effect on vascular dynamics in streptozotocin (STZ)-induced diabetes in male Wistar rats. Methods Diabetes was induced using a single tail-vein injection of STZ at 55 mg kg?1. The diabetic rats were treated daily with atorvastatin (10 mg kg?1 by oral gavage) for 6 weeks. They were also compared with untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. A thiobarbituric acid reactive substances measurement was used to estimate the malondialdehyde content. Results The high plasma level of total cholesterol in the diabetic rats did not change in response to this low-dose treatment with atorvastatin. Atorvastatin resulted in a significant increase of 15.4% in wave transit time and a decrease of 33.5% in wave reflection factor, suggesting that atorvastatin may attenuate the diabetes-induced deterioration in systolic loads imposed on the heart. This was in parallel with its lowering of malondialdehyde content in plasma and aortic walls in diabetes. Atorvastatin therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the diminished ratio of left ventricular weight to body weight. Conclusion These findings indicate that low-dose atorvastatin might protect diabetic vasculature against diabetes-associated deterioration in aorta stiffness and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived malondialdehyde. PMID:24595201

  9. Skeletal Muscle Sorbitol Levels in Diabetic Rats with and without Insulin Therapy and Endurance Exercise Training

    PubMed Central

    Sánchez, O. A.; Walseth, T. F.; Snow, L. M.; Serfass, R. C.; Thompson, L. V.

    2009-01-01

    Sorbitol accumulation is postulated to play a role in skeletal muscle dysfunction associated with diabetes. The purpose of this study was to determine the effects of insulin and of endurance exercise on skeletal muscle sorbitol levels in streptozotocin-induced diabetic rats. Rats were assigned to one experimental group (control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary no-insulin). Diabetic rats received daily subcutaneous insulin. The exercise-trained rats ran on a treadmill (1 hour, 5X/wk, for 12 weeks). Skeletal muscle sorbitol levels were the highest in the diabetic sedentary no-insulin group. Diabetic sedentary rats receiving insulin had similar sorbitol levels to control sedentary rats. Endurance exercise did not significantly affect sorbitol levels. These results indicate that insulin treatment lowers sorbitol in skeletal muscle; therefore sorbitol accumulation is probably not related to muscle dysfunction in insulin-treated diabetic individuals. Endurance exercise did not influence intramuscular sorbitol values as strongly as insulin. PMID:20016800

  10. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

    PubMed Central

    Nagayach, Aarti; Patro, Nisha; Patro, Ishan

    2014-01-01

    Behavioral impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45 mg/kg body weight; intraperitoneally). Motor function alterations were studied using Rotarod test (motor coordination) and grip strength (muscle activity) at 2nd, 4th, 6th, 8th, 10th, and 12th week post-diabetic confirmation. Scenario of glial (astroglia and microglia) activation, cell death and glutamate transportation was gaged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labeling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioral alterations following STZ-induced diabetes. PMID:25400546

  11. MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy

    PubMed Central

    Li, X; Du, N; Zhang, Q; Li, J; Chen, X; Liu, X; Hu, Y; Qin, W; Shen, N; Xu, C; Fang, Z; Wei, Y; Wang, R; Du, Z; Zhang, Y; Lu, Y

    2014-01-01

    Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which can result in cardiac hypertrophy and subsequent heart failure, associated with pyroptosis, the pro-inflammatory programmed cell death. MicroRNAs (miRNAs), small endogenous non-coding RNAs, have been shown to be involved in diabetic cardiomyopathy. However, whether miRNAs regulate pyroptosis in diabetic cardiomyopathy remains unknown. Our study revealed that mir-30d expression was substantially increased in streptozotocin (STZ)-induced diabetic rats and in high-glucose-treated cardiomyocytes as well. Upregulation of mir-30d promoted cardiomyocyte pyroptosis in diabetic cardiomyopathy; conversely, knockdown of mir-30d attenuated it. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic property of mir-30d, we found that forced expression of mir-30d upregulated caspase-1 and pro-inflammatory cytokines IL-1? and IL-18. Moreover, mir-30d directly repressed foxo3a expression and its downstream protein, apoptosis repressor with caspase recruitment domain (ARC). Furthermore, silencing ARC by siRNA mimicked the action of mir-30d: upregulating caspase-1 and inducing pyroptosis. These findings promoted us to propose a new signaling pathway leading to cardiomyocyte pyroptosis under hyperglycemic conditions: mir-30d??foxo3a?? ARC??caspase-1??IL-1?, IL-18??pyroptosis?. Therefore, mir-30d may be a promising therapeutic target for the management of diabetic cardiomyopathy. PMID:25341033

  12. Protein turnover in adipose tissue from fasted or diabetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.; Ost, Alan H.; Coffman, Julia

    1986-01-01

    Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

  13. Pharmacodynamics and pharmacokinetics of the insulin-mimetic agent vanadyl acetylacetonate in non-diabetic and diabetic rats

    Microsoft Academic Search

    Shuang-Qing Zhang; Xu-Ying Zhong; Wan-Liang Lu; Li Zheng; Xuan Zhang; Feng Sun; Gui-Ying Fu; Qiang Zhang

    2005-01-01

    The objectives of this study were to evaluate the pharmacodynamics and pharmacokinetics of vanadyl acetylacetonate (VAC) in rats. Pharmacodynamic study was carried out using non-diabetic and diabetic rats by subcutaneous (s.c.) and intragastric (i.g.) administrations at single dose or multiple doses. Pharmacokinetic study was performed using non-diabetic rats. Results showed that VAC resulted in a significant decrease of plasma glucose

  14. Biochemical studies on the effect of medicinal plants gymnema and andrographis species on diabetes induced wistar rats

    Microsoft Academic Search

    A. Roja Rani; K. Venkatesh; P. Chakrapani

    2009-01-01

    Diabetic mellitus was induced in adult wistar rats using the chemical compound streptozotocin which induces a type of diabetes which is similar to diabetes mellitus with non-ketosis hyperglycemia in some animal species. The changes in MDA (lipid peroxidation) and glucose (by GOD method) levels in blood of both normal and diabetic rat were analyzed. Diabetes induced rats were treated with

  15. Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes.

    PubMed

    Bagri, Priyanka; Ali, Mohd; Aeri, Vidhu; Bhowmik, Malay; Sultana, Shahnaz

    2009-01-01

    The present study investigated the effects of Punica granatum aqueous extract (PgAq) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, lipid profiles (atherogenic index), lipid peroxidation (LPO) and activities of both non-enzymatic and enzymatic antioxidants. Diabetes was induced by single intraperitoneal injection of STZ (60 mg/kg) to albino Wistar rats. The increase in blood glucose level, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL), LPO level with decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione (GSH) content and antioxidant enzymes namely, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were the salient features observed in diabetic rats. On the other hand, oral administration of PgAq at doses of 250 mg/kg and 500 mg/kg for 21 days resulted in a significant reduction in fasting blood glucose, TC, TG, LDL-C, VLDL-C and tissue LPO levels coupled with elevation of HDL-C, GSH content and antioxidant enzymes in comparison with diabetic control group. The results suggest that PG could be used, as a dietary supplement, in the treatment of chronic diseases characterized by atherogenous lipoprotein profile, aggravated antioxidant status and impaired glucose metabolism and also in their prevention. PMID:18950673

  16. Microarray analysis of thioacetamide-treated type 1 diabetic rats

    SciTech Connect

    Devi, Sachin S. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Ave, Sugar Hall 306, Monroe, LA 71209-0470 (United States); Mehendale, Harihara M. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Ave, Sugar Hall 306, Monroe, LA 71209-0470 (United States)]. E-mail: mehendale@ulm.edu

    2006-04-01

    It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats.

  17. Characterisation of Pain Responses in the High Fat Diet/Streptozotocin Model of Diabetes and the Analgesic Effects of Antidiabetic Treatments

    PubMed Central

    Byrne, Frederika Maria; Cheetham, Sharon; Vickers, Steven; Chapman, Victoria

    2015-01-01

    Chronic pain is a common complication of diabetes. The aim of the present study was to characterise pain behaviour in a high fat diet/streptozotocin (HFD/STZ) model of diabetes in the rat, investigate spinal mechanisms, and determine the effects of antidiabetic interventions. Three-week consumption of a high fat diet followed by single injection of STZ (45?mgkg?1) produced sustained changes in plasma insulin and glucose until day 120. Hindpaw mechanical withdrawal thresholds were significantly lowered in the model, but mechanically evoked responses of spinal neurones were unaltered, compared to HFD/vehicle rats. HFD/STZ rats had significantly lower numbers of spinal Iba-1 positive cells (morphologically identified as activated microglia) and spinal GFAP immunofluorescence (a marker of astrogliosis) in the spinal cord at day 50, compared to time-matched controls. The PPAR? ligand pioglitazone (10?mgkg?1) did not alter HFD/STZ induced metabolic changes or hindpaw withdrawal thresholds of HFD/STZ rats. Daily linagliptin (3?mgkg?1) and metformin (200?mgkg?1) from day 4 after model induction did not alter plasma glucose or insulin in HFD/STZ rats but significantly prevented changes in the mechanical withdrawal thresholds. The demonstration that currently prescribed antidiabetic drugs prevent aberrant pain behaviour supports the use of this model to investigate pain mechanisms associated with diabetes.

  18. Intervention of D-glucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat

    SciTech Connect

    Vikram, A.; Tripathi, D.N.; Ramarao, P. [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062 (India); Jena, G.B. [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062 (India)], E-mail: gbjena@gmail.com

    2008-01-01

    Streptozotocin (STZ) is a naturally occurring compound isolated from Streptomyces achromogens. It is used extensively for inducing diabetes in experimental animals. Diabetes mellitus is known to have proven adverse effects on male sexual organs and their reproductive functions. The atrophy of prostate gland and other organs of the genitourinary tract were observed in experimental diabetic animals. STZ exhibits a structural resemblance to D-glucose due to the presence of sugar moiety in its structure. Pancreatic {beta}-cells mainly contain GLUT1 and GLUT2 glucose transporters. Possibly due to structural resemblance, STZ and D-glucose, share a common recognition site for entry into the {beta}-cells. The objective of the present study is to evaluate the effect of D-glucose on STZ-induced toxicity in accessory sex organs of male rats. Animals were kept on overnight fasting. One group received vehicle and served as negative control, while all other groups were given STZ (45 mg/kg). Animals that received only STZ served as positive control. The effect of D-glucose was studied on STZ treated animals with different dosage of D-glucose (250, 500, 1000 and 2000 mg/kg). Restoration of body weight, plasma glucose and plasma insulin was evident only at 1000 and 2000 mg/kg of D-glucose. The protective effect of D-glucose is evident only when it is administered simultaneously with STZ. In the present investigation, we report that simultaneous administration of D-glucose along with STZ ameliorates STZ-induced toxicity. This is evident from the restoration of accessory sex organ's weight, cellular morphology as well as insulin level.

  19. Carvedilol Ameliorates Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Morsy, Mohamed A.; Ibrahim, Salwa A.; Amin, Entesar F.; Kamel, Maha Y.; Abdelwahab, Soha A.; Hassan, Magdy K.

    2014-01-01

    Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65?mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10?mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor-?, and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury. PMID:24991534

  20. Involvement of 1,2-diacylglycerol in improvement of heart function by etomoxir in diabetic rats.

    PubMed

    Hayashi, K; Okumura, K; Matsui, H; Murase, K; Kamiya, H; Saburi, Y; Numaguchi, Y; Toki, Y; Hayakawa, T

    2001-02-16

    Abnormal lipid metabolism has been proposed to be involved in the pathogenesis of diabetic cardiomyopathy. In this study, we measured myocardial lipid levels, including 1,2-diacylglycerol (1,2-DAG) and ceramide (CM), and myocardial function in diabetic rats. We also evaluated the effects of etomoxir (ETM), a carnitine palmitoyl transferase I inhibitor, on diabetic rat hearts from the viewpoints of alterations in lipid second messengers and myocardial function. Rats were injected with streptozotocin (60 mg/kg) to induce diabetes and were treated 5 weeks later with ETM (18 mg/kg) for 8 days. In diabetic rats, heart rate, systolic blood pressure, and fractional shortening were significantly reduced compared with those in controls. Treatment of diabetic rats with ETM ameliorated myocardial dysfunction other than heart rate. Myocardial 1,2-DAG levels in diabetic rats were significantly elevated compared with those in controls, while myocardial CM levels were not. ETM treatment caused an additional increase in myocardial 1,2-DAG levels in diabetic rats, but the CM levels did not change. There was a marked difference in fatty acid pattern of 1,2-DAG between diabetic and ETM-treated diabetic rat hearts. The fatty acids 18:1 and 18:2 were significantly increased and the fatty acids 16:0, 18:0, 20:4, and 22:6 were significantly reduced in ETM-treated diabetic rat hearts. These data suggest 1,2-DAG is involved in ameliorating myocardial dysfunction in diabetic rats and that its source is different between diabetic and ETM-treated diabetic rats. CM is unlikely to be involved in the pathogenesis of diabetic cardiomyopathy or the improvement of cardiac contractility in diabetic rats by ETM. PMID:11253168

  1. Histochemical and morphometrical analysis of skeletal muscle in spontaneous diabetic WBN\\/Kob rat

    Microsoft Academic Search

    Kiyokazu Ozaki; Tetsuro Matsuura; Isao Narama

    2001-01-01

    Spontaneous diabetic WBN\\/Kob rats develop diabetic peripheral neuropathy characterized by primary segmental demyelination and secondary axonal degeneration. The objective of this study was to evaluate the histochemical and morphometric characteristics of the lesions of skeletal muscles innervated by the affected nerves in diabetic rats. The following groups of rats were investigated: 24-month-old males that had been diabetic for less than

  2. Antioxidant potential of bilirubin-accelerated wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumar, Dhirendra; Kumawat, Sanjay; Gopalakrishnan, Anu; Lingaraju, Madhu C; Gupta, Priyanka; Tandan, Surendra Kumar; Kumar, Dinesh

    2014-10-01

    Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats. PMID:24969350

  3. A potent sorbitol dehydrogenase inhibitor exacerbates sympathetic autonomic neuropathy in rats with streptozotocin-induced diabetes.

    PubMed

    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Parvin, Curtis A; Yarasheski, Kevin E; Smith, Samuel R; Williamson, Joseph R; Peterson, Richard G; Oates, Peter J

    2005-04-01

    We have developed an animal model of diabetic sympathetic autonomic neuropathy which is characterized by neuroaxonal dystrophy (NAD), an ultrastructurally distinctive axonopathy, in chronic streptozotocin (STZ)-diabetic rats. Diabetes-induced alterations in the sorbitol pathway occur in sympathetic ganglia and therapeutic agents which inhibit aldose reductase or sorbitol dehydrogenase improve or exacerbate, respectively, diabetes-induced NAD. The sorbitol dehydrogenase inhibitor SDI-711 (CP-470711, Pfizer) is approximately 50-fold more potent than the structurally related compound SDI-158 (CP 166,572) used in our earlier studies. Treatment with SDI-711 (5 mg/kg/day) for 3 months increased ganglionic sorbitol (26-40 fold) and decreased fructose content (20-75%) in control and diabetic rats compared to untreated animals. SDI-711 treatment of diabetic rats produced a 2.5- and 4-5-fold increase in NAD in the SMG and ileal mesenteric nerves, respectively, in comparison to untreated diabetics. Although SDI-711 treatment of non-diabetic control rat ganglia increased ganglionic sorbitol 40-fold (a value 8-fold higher than untreated diabetics), the frequency of NAD remained at control levels. Levels of ganglionic sorbitol pathway intermediates in STZ-treated rats (a model of type 1 diabetes) and Zucker Diabetic Fatty rats (ZDF, a genetic model of type 2 diabetes) were comparable, although STZ-diabetic rats develop NAD and ZDF-diabetic rats do not. SDI failed to increase diabetes-related ganglionic NGF above levels seen in untreated diabetics. Initiation of Sorbinil treatment for the last 4 months of a 9 month course of diabetes, substantially reversed the frequency of established NAD in the diabetic rat SMG without affecting the metabolic severity of diabetes. These findings indicate that sorbitol pathway-linked metabolic alterations play an important role in the development of NAD, but sorbitol pathway activity, not absolute levels of sorbitol or fructose per se, may be most critical to its pathogenesis. PMID:15755558

  4. Response of immature diabetic rat bone-ligament junctions to insulin and exercise

    Microsoft Academic Search

    K-C Li; RF Zernicke; RJ Barnard; A F-Y Li

    1995-01-01

    The mechanical and morphological characteristics of femur-medial collateral ligament-tibia units and the histomorphometry of medial collateral ligament-tibial insertion were examined in female Sprague-Dawley rats with diabetes mellitus (type I, insulin-dependent diabetes). Diabetes was induced with the streptozotocin, a drug with toxic effects on insulin-producing islet cells in the pancreas. The groups studied included rats with untreated streptozotocin-induced diabetes mellitus (Diabetes),

  5. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus.

    PubMed

    Liu, J-Y; Yao, J; Li, X-M; Song, Y-C; Wang, X-Q; Li, Y-J; Yan, B; Jiang, Q

    2014-01-01

    Long noncoding RNAs (lncRNAs) have important roles in diverse biological processes. Our previous study has revealed that lncRNA-MALAT1 deregulation is implicated in the pathogenesis of diabetes-related microvascular disease, diabetic retinopathy (DR). However, the role of MALAT1 in retinal vasculature remodeling still remains elusive. Here we show that MALAT1 expression is significantly upregulated in the retinas of STZ-induced diabetic rats and db/db mice. MALAT1 knockdown could obviously ameliorate DR in vivo, as shown by pericyte loss, capillary degeneration, microvascular leakage, and retinal inflammation. Moreover, MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. The crosstalk between MALAT1 and p38 MAPK signaling pathway is involved in the regulation of endothelial cell function. MALAT1 upregulation represents a critical pathogenic mechanism for diabetes-induced microvascular dysfunction. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for diabetes-related microvascular complications. PMID:25356875

  6. Combating Combination of Hypertension and Diabetes in Different Rat Models

    PubMed Central

    Rosenthal, Talma; Younis, Firas; Alter, Ariela

    2010-01-01

    Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD), and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH) rats. The use of various drugs, such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs), various angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment.

  7. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

    PubMed Central

    A. Bakheet, Saleh; M. Attia, Sabry

    2011-01-01

    We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients. PMID:21941606

  8. Permeability of blood nerve barriers in the diabetic rat1

    Microsoft Academic Search

    K. N. Seneviratne

    1972-01-01

    An albumin-Evans blue conjugate has been used as a fluorescent tracer to demonstrate the increased permeability of endoneurial capillaries and perineurial sheath of the sciatic nerve of the alloxan-diabetic rat. The significance of the extravasation of protein into the endoneurial space is discussed in relation to the altered dynamics of the endoneurial microcirculation. It is suggested that tissue hypoxia produced

  9. Comparison of metabolic and neuropathy profiles of rats with streptozotocin-induced overt and moderate insulinopenia

    PubMed Central

    Romanovsky, Dmitry; Wang, Jing; Al-Chaer, Elie D.; Stimers, Joseph R.; Dobretsov, Maxim

    2010-01-01

    To assess the relative roles of insulinopenia, hyperglycemia and dyslipidemia in pathogenesis of diabetic neuropathy, we compared plasma insulin, glucose and lipid metabolism and peripheral nerve function in rats with streptozotocin (STZ) – induced overt and moderate insulinopenia (hyperglycemic, STZ-HG; random glucose > 11 mM and normoglycemic, STZ-NG rats). While being slightly insulinopenic, STZ-NG rats are metabolically not different from control, naïve animals, by having normal glucose tolerance and normal levels of plasma glucose, glycated HbA1c, cholesterol and triglycerides. Two weeks following injection of STZ, STZ-HG but not STZ-NG rats had suppressed motor nerve conduction velocity, F-wave prevalence, withdrawal responses to heat and von Frey filament stimuli. In apparent correlation with plasma insulin level, both STZ-HG and –NG rats manifested exaggerated responses in paw pressure and colorectal distension tests. These data suggest that insulinopenia may play a leading role in the diabetic impairment of deep muscle and visceral afferent pathways while hyperglycemia/dyslipidemia may represent a key requirement for the onset and progression of electrophysiological nerve impairment and loss of superficial heat and tactile perception. STZ-NG rats offer a convenient model for the investigation of the short-term effects of insulinopenia on peripheral nerve function. PMID:20600635

  10. Effects of apomorphine, physostigmine and vasoactive intestinal peptide on penile erection and yawning in diabetic rats.

    PubMed

    Yamaguchi, Y; Kobayashi, H

    1994-03-11

    The present report describes for the first time the effects of systemic administration of apomorphine and of physostigmine, as well as the effects of central and systemic administration of vasoactive intestinal peptide (VIP), on penile erection and yawning in rats with streptozotocin-induced diabetes. Systemic administration of apomorphine induced both penile erection and yawning in non-diabetic rats but not in diabetic rats, while that of physostigmine induced only yawning in non-diabetic rats, and neither yawning nor penile erection in diabetic rats. Intracerebroventricular administration of VIP induced both penile erection and yawning in non-diabetic rats, but neither was induced in diabetic rats. Application of VIP as an ointment to the surface of the glans penis induced penile erection but not yawning in both non-diabetic and diabetic rats. Thus, penile erection and yawning are less easily induced in diabetic rats than in non-diabetic rats. Grooming occurred whenever penile erection was induced, but was not associated with yawning. PMID:8206121

  11. Anti-diabetic properties of rice-based herbal porridges in diabetic Wistar rats.

    PubMed

    Senadheera, Senadheera Pathirannehelage Anuruddhika Subhashinie; Ekanayake, Sagarika; Wanigatunge, Chandanie

    2014-10-01

    The present study aims to investigate anti-hyperglycaemic, anti-hyperlipidaemic and toxic effects of long-term consumption of selected green leafy porridges in a streptozotocin-induced diabetic Wistar rat model. Porridges made with Asparagus racemosus Willd. (AR), Hemidesmus indicus (L) R. Br. W. T. Aiton (HI), Scoparia dulcis L. (SD) and coconut milk porridge (CM) were incorporated into diets of diabetic Wistar rats. Diabetic control (DM) and normal control groups (NC) were provided with standard rat diet. Fasting blood glucose (FBG), HbA1c , C reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), liver enzymes and creatinine were measured. Feed and water intake among diabetic groups were significantly high when compared with those of NC (p?rats in SD (mean?=?39?±?19?g) and NC (mean?=?114?±?7?g) groups gained weight, whereas most rats in other diabetic groups lost weight. Among the diabetic groups, SD group had the lowest mean FBG, FBG increment percentage (45%) and HbA1c (5.8?±?2.1). FBG increment percentage and HbA1c of SD group were not significantly different to those of NC (38%; 4.7?±?0.7) (p?>?0.05). Among the diabetic groups, lowest TC (119?±?20.6?mg/dL) and highest HDL-C (33?±?6.3?mg/dL) were also detected in SD group. Alanine transaminase and creatinine were not significantly different (p?>?0.05) among diabetic groups but significant when compared with those of NC. When compared with those of NC, aspartate transaminase levels were significantly (p?diabetes-induced Wistar rats. PMID:24840113

  12. Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats.

    PubMed

    Jatobá, Carlos André Nunes; de Rezende, Adriana Augusto; de Paiva Rodrigues, Sarah Jane; de Almeida Câmara, Maria Margareth; das Graças Almeida, Maria; Freire-Neto, Francisco; da Rocha, Luiz Reginaldo Menezes; da Medeiros, Aldo Cunha; Brandão-Neto, José; de Carvalho Formiga, Maria Célia; de Azevedo, Italo Medeiros; de Oliveira Ramos, Ana Maria

    2008-04-01

    Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism. PMID:17636394

  13. Carnosine treatment in combination with ACE inhibition in diabetic rats.

    PubMed

    Peters, V; Riedl, E; Braunagel, M; Höger, S; Hauske, S; Pfister, F; Zschocke, J; Lanthaler, B; Benck, U; Hammes, H-P; Krämer, B K; Schmitt, C P; Yard, B A; Köppel, H

    2014-11-01

    In humans, we reported an association of a certain allele of carnosinase gene with reduced carnosinase activity and absence of nephropathy in diabetic patients. CN1 degrades histidine dipeptides such as carnosine and anserine. Further, we and others showed that treatment with carnosine improves renal function and wound healing in diabetic mice and rats. We now investigated the effects of carnosine treatment alone and in combination with ACE inhibition, a clinically established nephroprotective drug in diabetic nephropathy. Male Sprague-Dawley rats were injected i.v. with streptozotocin (STZ) to induce diabetes. After 4 weeks, rats were unilaterally nephrectomized and randomized for 24 weeks of treatment with carnosine, lisinopril or both. Renal CN1 protein concentrations were increased under diabetic conditions which correlated with decreased anserine levels. Carnosine treatment normalized CN1 abundance and reduced glucosuria, blood concentrations of glycosylated hemoglobin (HbA1c), carboxyl-methyl lysine (CML), N-acetylglucosamine (GlcNac; all p<0.05 vs. non-treated STZ rats), reduced cataract formation (p<0.05) and urinary albumin excretion (p<0.05), preserved podocyte number (p<0.05) and normalized the increased renal tissue CN1 protein concentration. Treatment with lisinopril had no effect on HbA1C, glucosuria, cataract formation and CN1 concentration, but reduced albumin excretion rate more effectively than carnosine treatment (p<0.05). Treatment with both carnosine and lisinopril combined the effects of single treatment, albeit without additive effect on podocyte number or albuminuria. Increased CN1 amount resulted in decreased anserine levels in the kidney. Both carnosine and lisinopril exert distinct beneficial effects in a standard model of diabetic nephropathy. Both drugs administered together combine the respective effects of single treatment, albeit without exerting additive nephroprotection. PMID:25234296

  14. In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue

    PubMed Central

    Matsen, Miles E.; Thaler, Joshua P.; Wisse, Brent E.; Guyenet, Stephan J.; Meek, Thomas H.; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D.; Kaiyala, Karl J.; Schwartz, Michael W.

    2013-01-01

    Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)?-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a ?3-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting. PMID:23384771

  15. Comparison of the development of tolerance to nitroglycerin in aortic preparations isolated from non-diabetic and diabetic rats

    Microsoft Academic Search

    Toshihiro Matsuzaki; Matao Sakanashi

    1992-01-01

    Summary To clarify whether or not tolerance to nitroglycerin is developed more easily in a diabetic than in a non-diabetic state, the effects of nitroglycerin on aortic preparations isolated from diabetic and nondiabetic rats were examined and compared with those of nicorandil, which has been known to develop less tolerance than does nitroglycerin. Contractile responses to norepinephrine, relaxant responses to

  16. Effect of Polyherbal Mixtures on the Treatment of Diabetes

    PubMed Central

    Panda, Aparajeya; Jena, Somanatha; Sahu, Pramod Kumar; Nayak, Sanghamitra; Padhi, Payodhar

    2013-01-01

    The study focuses on polyherbal antidiabetic formulations of different plants used in the treatment of diabetes mixed in different concentrations. In the present study eleven medicinal plants with proven antidiabetic and related beneficial effects were selected for the preparation of five mixtures. The efficacy of prepared mixtures has been tested on streptozotocin- (STZ-) induced diabetic rats and compared with a commercially available drug glibenclamide. The mixtures at the dose levels of 400?mg/kg b.w. produced a significant decrease in blood glucose level by 69.6%, 70.97%, 64.45%, 71.82%, and 64.44% after 21?days of treatment. The elevated level of SGPT, SGOT, and ALP in the diabetic controlled group reflected the significant alteration of liver function by STZ induction and was found to be equipotent to glibenclamide in restoration of the elevated enzyme levels to normal. The elevated lipid levels (triglyceride and total cholesterol) were restored to near normal by these mixtures for all the estimated parameters. The results of the mixtures on treated group were found to restore the glycemic level to the near normal level thereby indicating antihyperglycemic activity of the formulated mixtures. PMID:23691349

  17. Effect of Biophytum sensitivum on streptozotocin and nicotinamide-induced diabetic rats

    PubMed Central

    Ananda, Prabu K; Kumarappan, CT; Sunil, Christudas; Kalaichelvan, VK

    2012-01-01

    Objective To investigate the effect of aqueous solution of Biophytum sensitivum leaf extract (BSEt) on normal and streptozotocin (STZ)-nicotinamide-induced diabetic rats. Methods Diabetes was induced in adult male Wistar rats by the administration of STZ-nicotinamide (40, 110 mg/kg b.w., respectively) intraperitoneally. BSEt (200 mg/kg) was administered to diabetic rats for 28 days. The effect of extract on blood glucose, plasma insulin, total haemoglobin, glycosylated haemoglobin, liver glycogen and carbohydrate metabolism regulating enzymes of liver was studied in diabetic rats. Results BSEt significantly reduced the blood glucose and glycosylated haemoglobin levels and significantly increased the total haemoglobin, plasma insulin and liver glycogen levels in diabetic rats. It also increased the hexokinase activity and decreased glucose-6-phosphatase, fructose-1, 6-bisphosphatase activities in diabetic rats. Conclusions The results of our study suggest that BSEt possesses a promising effect on STZ-nicotinamide-induced diabetes. PMID:23569830

  18. The influence of dietary Cu and diabetes on tissue sup 67 Cu retention kinetics in rats

    SciTech Connect

    Uriu-Hare, J.Y.; Rucker, R.B.; Keen, C.L. (Univ. of California, Davis (United States))

    1991-03-11

    Compared to controls, diabetes results in higher plasma, liver and kidney Cu concentrations. Since alterations in Cu metabolism may be associated with diabetic pathology, the authors investigated how Cu metabolism is affected by diabetes and dietary Cu intake. Nondiabetic and STZ diabetic rats were fed Cu suppl. or Cu def. diets for 5 wks. Rats were intubated with 28 {mu}Ci {sup 67}Cu and killed after 8, 16, 24, 32, 64, or 128 h. There were marked effects of both diet and diabetes on {sup 67}Cu metabolism. Independent of diabetes, deficient rats had a higher % of retained {sup 67}Cu, in liver, plasma, RBC, muscle, spleen, brain, lung, uterus, and intestine than adequate Cu rats. Independent of dietary Cu, diabetic rats had a lower % of retained {sup 67}Cu in liver, plasma, RBC, muscle, spleen, lung, bone, pancreas, skin, uterus and heart than controls. Differential effects were noted for kidney; adequate Cu diabetic rats had a higher % of retained {sup 67}Cu than all other groups. Marked effects of both diet and diabetes were evident when tissue Cu turnover was examined. Compared to Cu suppl. rats, Cu def. rats had a slower turnover of {sup 67}Cu, in liver, plasma, intestine, pancreas, eye, brain, muscle, spleen, lung and heart. Diabetic rats had a slower turnover of {sup 67}Cu than nondiabetic rats in liver, plasma, intestine, pancreas, eye, kidney, RBC and uterus. The data imply that a focus on Cu metabolism with regard to cellular Cu trafficking and pathology may be warranted.

  19. Diabetes provides an unfavorable environment for muscle mass and function after muscle injury in mice.

    PubMed

    Vignaud, A; Ramond, F; Hourdé, C; Keller, A; Butler-Browne, G; Ferry, A

    2007-01-01

    It is of common knowledge that diabetes decreases skeletal muscle contractility and induces atrophy. However, how hyperglycemia and insulin deficiency modify muscle mass and neuromuscular recovery after muscle injury is not well known. We have analyzed two models of diabetes: streptozotocin (STZ)-treated Swiss mice and Akita mice that spontaneously develop diabetes. A fast muscle, the tibialis anterior, was injured following injection of a myotoxic agent (cardiotoxin). Neuromuscular function was evaluated by examining in situ isometric contractile properties of regenerating muscles in response to nerve stimulation 14, 28 and 56 days after myotoxic injury. We found that STZ-induced diabetes reduces muscle weight and absolute maximal tetanic force in both regenerating and uninjured muscles (p = 0.0001). Moreover, it increases specific maximal tetanic force and tetanic fusion in regenerating and uninjured muscles (p = 0.04). In the Akita mice, diabetes decreases muscle weight and absolute maximal tetanic force, and increases tetanic fusion in both regenerating and uninjured muscles (p < or = 0.003). Interestingly, STZ-induced diabetes exerts more marked effects than diabetes of genetic origin, in particular on muscle weight. This reduction in muscle mass was not due to an increased expression of the atrogenes MuRF1 and atrogin-1 during STZ-induced diabetes. The present study in mice demonstrates that both models of diabetes impair regenerating muscles as well as uninjured muscles. Regenerating fast muscles are weaker, lighter and slower in diabetic compared with nondiabetic mice. PMID:17890896

  20. Islet Remodeling in Female Mice with Spontaneous Autoimmune and Streptozotocin-Induced Diabetes

    PubMed Central

    Plesner, Annette; ten Holder, Joris T.; Verchere, C. Bruce

    2014-01-01

    Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core. We determined how islet remodeling in autoimmune diabetes compares to streptozotocin (STZ)-induced diabetes. Islet cell mass, proliferation, and immune cell infiltration in pancreas sections from diabetic NOD mice and mice with STZ-induced diabetes was assessed using quantitative image analysis. Serial sections were stained for various beta-cell markers and Ngn3, typically restricted to embryonic tissue, was only upregulated in diabetic NOD mouse islets. Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state. Total pancreatic alpha-cell mass did not change as autoimmune diabetes developed in NOD mice despite the proportion of islet area comprised of alpha- and delta-cells increased. By contrast, alpha- and delta-cell mass was increased in mice with STZ-induced diabetes. Serum levels of glucagon reflected these changes in alpha-cell mass: glucagon levels remained constant in NOD mice over time but increased significantly in STZ-induced diabetes. Increased serum GLP-1 levels were found in both models of diabetes, likely due to alpha-cell expression of prohormone convertase 1/3. Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation. Hence, the inflammatory milieu in NOD mouse islets may restrict alpha-cell expansion highlighting important differences between these two diabetes models and raising the possibility that increased alpha-cell mass might contribute to the hyperglycemia observed in the STZ model. PMID:25101835

  1. Dietary polyunsaturated fatty acids slow the progression of diabetic nephropathy in streptozotocin-induced diabetic rats.

    PubMed

    Yokoyama, Meiko; Tanigawa, Kanae; Murata, Tomoko; Kobayashi, Yukiko; Tada, Eriko; Suzuki, Isao; Nakabou, Yukihiro; Kuwahata, Masashi; Kido, Yasuhiro

    2010-03-01

    Diabetic nephropathy is associated with lipid deposits in the kidney. We hypothesized that a diet containing polyunsaturated fatty acids (PUFAs) could ameliorate pathogenesis of diabetic kidney diseases associated with lipid depositions in the kidneys. We examined if the pathogenesis and progression of diabetic nephropathy are affected by the type of dietary fat using streptozotocin (45 mg/kg body weight, intravenous)-induced diabetic rats (5-week-old male Sprague-Dawley rats). Streptozotocin-induced diabetic rats were fed a lard diet containing saturated fatty acids or a rapeseed oil diet containing PUFAs (DML and DMR, respectively) for 11 days. Similarly, streptozotocin-nontreated rats were fed a lard diet or a rapeseed oil diet (NL and NR, respectively) for 11 days. Hyperglycemia was induced in DML and DMR, compared with NL and NR groups. The levels of plasma ketone, total cholesterol, and triglyceride (TG) were significantly increased in the DML group. Moreover, albuminuria and renal TG content were enhanced in the DML group. The renal TG content correlated positively with urinary albumin excretion (P < .001). Oil-Red O staining of kidney sections indicated a marked accumulation of neutral lipids in both glomerular and tubular cells in the DML group. In addition, a renal sterol regulatory element-binding protein-1 mature protein increment was induced in the DML group. Conversely, sterol regulatory element-binding protein-1 expression in the kidney was maintained at normal levels in the DMR group. These results suggest that dietary PUFAs may slow the progression of diabetic nephropathy associated with lipid depositions in the kidney. PMID:20417883

  2. Autoimmunity in type 1 diabetes mellitus: a rat model

    SciTech Connect

    Liu, Z.

    1987-01-01

    In this study, we have sought to isolate in vitro, from acutely diabetic BB rats, cytotoxic T lymphocytes, which exhibit specific cytotoxicity toward islet cells. Thoracic duct lymphocytes (TDL) from acutely diabetic BB rats cultured with irradiated MHC matched (RT1.u) islet cells and dendritic cells in vitro were shown to be specifically cytotoxic to MHC matched and mismatched allogeneic (RT1.1) and xenogeneic (hamster) islet target cells in a /sup 3/H-leucine release assay. Two cell lines (V1A8 and V1D11) derived from the TDL culture showed similar patterns of non-MHC restricted islet cell killing which could be blocked by islet cells and cultured rat insulinoma cells (RIN5mF) but not by non-islet cells of various tissue origins. Both V1A8 and V1D11 were not cytotoxic to Natural Killer (NK) sensitive target cells, G1TC and YAC-1. Conventional surface markers for rat helper and suppressor/cytotoxic T cells were not detectable on either cell lines. The V1D11 cell line was positive for W 3/13 (rat T/NK marker) on OX-19 (rat T/macrophage marker), whereas the V1A8 cell line was only positive for W 3/13.

  3. Peripheral participation of cholecystokinin in the morphine-induced peripheral antinociceptive effect in non-diabetic and diabetic rats

    Microsoft Academic Search

    Jorge E. Torres-López; Isela E. Juárez-Rojop; Vinicio Granados-Soto; Juan C. Diaz-Zagoya; Francisco J. Flores-Murrieta; Jorge Cruz-Vera

    2007-01-01

    The effects of cholecystokinin (CCK-8) and the CCK receptor antagonist proglumide, on antinociception induced by local peripheral (subcutaneous) injected morphine in non-diabetic (ND) and streptozotocin-induced diabetic (D) rats, were examined by means of the formalin test. Morphine induced dose-dependent antinociception both in ND and D rats. However, in D rats, antinociceptive morphine potency was about twofold less than in ND

  4. Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy

    Microsoft Academic Search

    Ulf Janssen; Stephen G. Riley; Athina Vassiliadou; Jürgen Floege; Aled O. Phillips

    2003-01-01

    Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy.BackgroundType II diabetes in the Goto Kakizaki (GK) rats (derived from Wistar rats) is not associated with the development of obesity, hyperlipidemia, hypertension, or pronounced renal functional changes. The aim of this study was to investigate the effect of superimposed hypertension on renal function and morphology under conditions

  5. Increased severity of acute Trypanosoma brucei brucei infection in rats with alloxan-induced diabetes

    E-print Network

    Paris-Sud XI, Université de

    -induced diabetes Ikechukwu Onyebuchi Igbokwea Sani Isaa Umma Kalsum Aliyub Hajja Gana Hamzab Tobias Egbe made diabetic by treatment with alloxan monohydrate (10 % solution, 100 mg/kg body weight). Ten diabetic and ten non-diabetic rats were intraperitoneally infected with the same infective doses

  6. Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats

    Microsoft Academic Search

    Bryan J Tucker; Christen M Anderson; R Scott Thies; Rose C Collins; Roland C Blantz

    1992-01-01

    Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats. Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein,

  7. Collagen and reticular fibers in left ventricular muscle in diabetic rats: Physical exercise prevents its changes?

    Microsoft Academic Search

    A. Castellar; R. N. Remedio; R. A. Barbosa; R. J. Gomes; F. H. Caetano

    2011-01-01

    Diabetic cardiomyopathy contributes to the high incidence of mortality in both types of diabetes. We aimed to investigate the histochemical aspects of collagen and reticular fibers in the cardiac muscle and evaluate the influence of physical exercise on these aspects. Wistar rats were divided in 4 groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD).

  8. Antihyperglycemic and antihyperlipidemic effects of guar gum on streptozotocin-induced diabetes in male rats

    PubMed Central

    Saeed, Samarghandian; Mosa-Al-Reza, Hadjzadeh; Fatemeh, Amin Nya; Saeideh, Davoodi

    2012-01-01

    Background: Herbal medicine is widely used in the treatment of diseases like diabetes mellitus. We investigated the effects of guar gum in diabetic rats for the reduction of the risk of diabetes and cardiovascular disease. Dietary pattern emphasizing foods high in complex carbohydrates and fiber are associated with low blood glucose and cholesterol levels. Materials and Methods: Diet containing 0%, 5%, 10% and 20% (w/w) guar gum was fed to diabetic rats for 28 days. Blood serum glucose, triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol levels, atherogenic index levels, body weights and food intake were monitored at 0, 7.14 and 28 days after induction of diabetes. Results: In spite of the fact that diabetes elevated blood lipids in all rats after 14 days, the guar gum diet significantly decreased the serum concentration of cholesterol, triacylglicerols and LDL-C and atherogenic index. The most significant result in this study was the reduction of blood glucose in diabetic rats treated with the guar gum diet after 28 days versus non- and glibenclamide-treated rats. The gum promoted a general improvement in the condition of the diabetic rats in body weight and food intake in comparison with nontreated rats. Conclusion: The results of this research suggest that guar gum was significantly effective in comparison with glibenclamide in the treatment of hyperlipidemia and hyperglycemia in diabetes rats. Therefore, it may be suggested as a reliable fiber in diabetic regimes in diabetic patients. PMID:22438666

  9. Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

    SciTech Connect

    Winocour, P.D.; Colwell, J.A.

    1985-05-01

    Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis.

  10. Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist

    NASA Astrophysics Data System (ADS)

    Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev

    1982-02-01

    The glucagon analog [l-N?-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

  11. Effect of Nigella sativa fixed and essential oils on antioxidant status, hepatic enzymes, and immunity in streptozotocin induced diabetes mellitus

    PubMed Central

    2014-01-01

    Background Nigella sativa fixed (NSFO) and essential (NSEO) oils have been used to treat diabetes mellitus and its complications. Present study was undertaken to explore and validate these folkloric uses. Methods Sprague dawley rats having streptozotocin (STZ) induced diabetes mellitus were used to assess the role of NSFO and NSEO in the management of diabetes complications. Parameters investigated were antioxidant potential, oxidative stress, and the immunity by in vivo experiments. Results The results indicated that STZ decreased the glutathione contents (25.72%), while NSFO and NSEO increased the trait significantly (P?diabetes complications. Conclusions Overall, results of present study supported the traditional use of N. sativa and its derived products as a treatment for hyperglycemia and allied abnormalities. Moreover, N. sativa fixed and essential oils significantly ameliorate free radicals and improve antioxidant capacity thus reducing the risk of diabetic complications. PMID:24939518

  12. Growth pattern switch of renal cells and expression of cell cycle related proteins at the early stage of diabetic nephropathy

    SciTech Connect

    Zhang Yanling [Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang 050051 (China); Shi Yonghong [Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017 (China); Liu Yaling [Department of Dermatology, Third Hospital, Hebei Medical University, Shijiazhuang 050051 (China); Dong Hui [Department of Neurology, Second Hospital, Hebei Medical University, Shijiazhuang 050003 (China); Liu, Maodong; Li Ying [Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang 050051 (China); Duan Huijun [Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017 (China)], E-mail: duanhj999@163.com

    2007-11-09

    Renal hypertrophy, partly due to cell proliferation and hypertrophy, has been found correlated to renal function deterioration in diabetes mellitus. We screened the up-regulated cell cycle related genes to investigate cell growth and the expression of cell cycle regulating proteins at the early stage of diabetic nephropathy using STZ-induced diabetic rats. Cyclin E, CDK{sub 2} and P{sup 27} were found significantly up-regulated in diabetic kidney. Increased cell proliferation in the kidney was seen at day 3, peaked at day 5, and returned to normal level at day 30. Cyclin E and CDK{sub 2} expression also peeked at day 5 and P{sup 27} activity peaked at day 14. These findings indicate that a hyperplastic growth period of renal cells is followed by a hypertrophic growth period at the early stage of diabetes. The growth pattern switch may be regulated by cell cycle regulating proteins, Cyclin E, CDK{sub 2}, and P{sup 27}.

  13. Elevation of circulating LOX-1 ligand levels in Zucker obese and diabetic rats.

    PubMed

    Wakabayashi, Ichiro; Shimomura, Tomoko; Nakanishi, Mamoru; Uchida, Kagehiro

    2015-01-01

    LOX-1 ligands containing apolipoprotein B (LAB) reflect ligand activity of LOX-1, which is a key molecule for initiation of atherosclerosis. The Zucker rat is a well-known model used for research on obesity and diabetes. Blood levels of LAB were compared among Zucker fatty (ZF), Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. Log-transformed LAB was significantly higher in ZF and ZDF rats than in control ZL rats, while no significant difference was found in log-transformed LAB of ZF and ZDF rats. This study for the first time demonstrated that circulating LOX-1 ligands were elevated in obesity and diabetes model rats. PMID:25434992

  14. Angelica sinensis polysaccharide regulates glucose and lipid metabolism disorder in prediabetic and streptozotocin-induced diabetic mice through the elevation of glycogen levels and reduction of inflammatory factors.

    PubMed

    Wang, Kaiping; Cao, Peng; Shui, Weizhi; Yang, Qiuxiang; Tang, Zhuohong; Zhang, Yu

    2015-03-11

    The present study was designed to evaluate the potential hypoglycemic and hypolipidemic effects of Angelica sinensis polysaccharide (ASP), purified from the fresh roots of Angelica sinensis (AS), in prediabetic and streptozotocin (STZ)-induced diabetic BALB/c mice. It was observed that fasting blood glucose (FBG) levels in both models were reduced after a 4-week oral administration of ASP or metformin, and abnormal fasting serum insulin (FINS) concentrations were ameliorated as well. Moreover, the homeostasis model assessment-insulin resistance (HOMA-IR) index was decreased strikingly and body weight (BW) was reduced significantly in prediabetic mice after treatment with ASP. In addition, ASP also contributed to improving the dyslipidemia conditions. Elevated serum total cholesterol (TC) or triglyceride (TG) concentrations were reduced after treatment with ASP in prediabetic mice or STZ-induced diabetic mice. Meanwhile, hepatic glycogen (HG) and muscle glycogen (MG) concentrations were increased while insulin resistance (IR)-related inflammatory factors IL-6 and TNF-? in serum were reduced in STZ-induced diabetic mice. Histopathological examination indicated that the impaired pancreatic/hepatic tissues or adipose tissues were effectively restored in STZ-induced diabetic mice or prediabetic mice after the ASP treatment. Taken together, these results revealed that ASP efficiently exerted hypoglycemic and hypolipidemic benefits, and its potential effect was associated with the amelioration of IR. ASP can be applied in the prevention and treatment of diabetes. PMID:25630053

  15. Anti-diabetic effect mediated by Ramulus mori polysaccharides.

    PubMed

    Xu, Lingyuan; Yang, Fenglian; Wang, Junli; Huang, Hao; Huang, Yanqiang

    2015-03-01

    Diabetes mellitus is a complicated metabolic disease, whose pathogenesis is related to apoptosis within pancreatic tissue. In this study, the potential therapeutic benefits of Ramulus mori polysaccharides (RMP) on streptozotocin (STZ)-induced diabetic mice were evaluated. Our experiments indicated that RMP lowered hyperglycemia and increased insulin levels in diabetic mice. Histopathological examination revealed that RMP contributed to the reduction of STZ-lesioned pancreatic cells. In addition, the serum level of HbA1c was decreased. RMP treatment also showed increased Bcl-2 expression and reduced Bax protein level in pancreatic tissue. Furthermore, intrapancreatic expressions of p-JNK, p-p38 and cleaved-caspase-3 were down-regulated by RMP treatment. Collectively, the findings demonstrate that RMP exerts the pronounced hypoglycemic effect via regulation of the intrapancreatic JNK/p38 pathway to protect against STZ-induced apoptosis in pancreatic tissue, eventually ameliorating metabolic function in the pancreas. PMID:25498609

  16. The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats

    PubMed Central

    Feng, Qianjin; Niu, Xin; Liu, Xinshe; Xu, Kaixia; Yang, Xiangzhu; Wang, Huifeng

    2014-01-01

    In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the control group (group II, n = 11), and (3) rats of normal pregnancy group (group III, n = 11). Compared with gestational diabetes mellitus rats as the control group, Zuogui Wan can change the indexes of fasting blood glucose, body weight, total cholesterol, insulin, and metabolism cage index significantly in Zuogui Wan gestational diabetes mellitus group. We can conclude that Zuogui Wan has the therapeutic effect on gestational diabetes mellitus. PMID:25136475

  17. Blunted diuretic and natriuretic responses to central administration of clonidine in streptozocin-induced diabetic rats.

    PubMed

    Zhang, P L; Patel, K P

    1991-03-01

    The purpose of this study was to determine whether diuretic and natriuretic effects are altered in response to intracerebroventricular (ICV) infusion of clonidine in diabetic rats. Diabetes was induced in male Sprague-Dawley rats by 65 mg/kg i.p. injection of streptozocin, and control rats were injected with vehicle 2 wk before the experiment. Blood glucose levels were significantly elevated in the diabetic group (26.3 +/- 1.3 mM) compared with the control group (8.4 +/- 1.6 mM). Before and during ICV infusion of clonidine (2 micrograms.kg-1.min-1 for 45 min), urine flow and sodium excretion were measured from intact and denervated kidneys in anesthetized diabetic and control rats. The ICV infusion of clonidine significantly increased urine flow in both innervated and denervated kidneys from control rats but not from diabetic rats. There was a significant increase in sodium excretion during ICV infusion of clonidine from innervated kidneys of control rats, and denervation abolished this effect. In diabetic rats, clonidine failed to promote natriuresis from intact kidneys, and similar to control rats, did not promote natriuresis in denervated kidneys. This study demonstrates that 1) the diuretic response to the ICV infusion of clonidine is blunted in diabetic rats, and 2) a natriuretic response to the ICV infusion of clonidine is blunted in innervated kidneys of diabetic rats. PMID:1999276

  18. Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes

    PubMed Central

    WANG, YONG-BIN; GE, ZHI-MING; KANG, WEI-QIANG; LIAN, ZHE-XUN; YAO, JIAN; ZHOU, CHANG-YONG

    2015-01-01

    Diabetic cardiomyopathy (DCM), an independent coronary heart disease that develops in diabetic individuals, is characterized by changes in the myocardial structure and function. The aim of the present study was to investigate the protective effect of rutin on DCM in a streptozotocin-induced diabetic rat model. Rutin was orally administrated at a dose of 8 mg/kg body weight. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. The expression levels of cellular proteins associated with apoptosis were measured by western blot analysis, while the levels of inflammatory factors were assessed by immunohistochemical analyses. Rats with DCM exhibited an abnormal metabolic profile, aberrant myocardial enzymes, elevation of oxidative stress markers, increased levels of inflammatory factors and enhanced apoptotic cell death. Notably, rutin was shown to protect and improve myocardial dysfunction, oxidative stress, apoptosis and inflammation in the hearts of the diabetic rats. In conclusion, these results indicated that rutin may have great therapeutic potential in the treatment of DCM, and possibly other cardiovascular disorders, by preventing oxidative stress, inflammation and cell death. However, further detailed studies are required to reveal the exact mechanisms underlying the protective effect of rutin. PMID:25574214

  19. Dysregulated pyruvate dehydrogenase complex in Zucker diabetic fatty rats.

    PubMed

    Schummer, Christoph M; Werner, Ulrich; Tennagels, Norbert; Schmoll, Dieter; Haschke, Guido; Juretschke, Hans-Paul; Patel, Mulchand S; Gerl, Martin; Kramer, Werner; Herling, Andreas W

    2008-01-01

    The mitochondrial pyruvate dehydrogenase complex (PDC) is inactivated in many tissues during starvation and diabetes. We investigated carbohydrate oxidation (CHO) and the regulation of the PDC in lean and obese Zucker diabetic fatty (ZDF) rats during fed and starved conditions as well as during an oral glucose load without and with pharmacologically reduced levels of free fatty acids (FFA) to estimate the relative contribution of FFA on glucose tolerance, CHO, and PDC activity. The increase in total PDC activity (20-45%) was paralleled by increased protein levels ( approximately 2-fold) of PDC subunits in liver and muscle of obese ZDF rats. Pyruvate dehydrogenase kinase-4 (PDK4) protein levels were higher in obese rats, and consequently PDC activity was reduced. Although PDK4 protein levels were rapidly downregulated (57-62%) in both lean and obese animals within 2 h after glucose challenge, CHO over 3 h as well as the peak of PDC activity (1 h after glucose load) in liver and muscle were significantly lower in obese rats compared with lean rats. Similar differences were obtained with pharmacologically suppressed FFA by nicotinic acid, but with significantly improved glucose tolerance in obese rats, as well as increased CHO and delta increases in PDC activity (0-60 min) both in muscle and liver. These results demonstrated the suppressive role of FFA acids on the measured parameters. Furthermore, the results clearly demonstrate a rapid reactivation of PDC in liver and muscle of lean and obese rats after a glucose load and show that PDC activity is significantly lower in obese ZDF rats. PMID:17957038

  20. Improvement of Lipid Profile by Amaranth (Amaranthus esculantus) Supplementation in Streptozotocin-Induced Diabetic Rats

    Microsoft Academic Search

    Hye Kyung Kim; Mi-Jeong Kim; Dong-Hoon Shin

    2006-01-01

    Background\\/Aims: Lipid disorders may exacerbate some complications of diabetes. Amaranth has been reported to exhibit a cholesterol-lowering effect in hyperlipidemic animals. The present study was designed to investigate the effect of amaranth on serum glucose and the lipid profile in diabetic rats. Methods: Male Sprague-Dawley rats were assigned to normal control, diabetic control, diabetic amaranth-grain (AG)-supplemented (500 g\\/kg diet) and

  1. Folic acid attenuates cognitive dysfunction in streptozotocin-induced diabetic rats.

    PubMed

    Yang, Rui; Chen, Rong-Ping; Chen, Hong; Zhang, Hua; Cai, De-Hong

    2014-01-01

    Diabetic cognitive dysfunction is common in patients with diabetes but its pathogenesis is not clear. The aim of the present study is to investigate the role of 5', 10' methylene tetrahydrofolate reductase (MTHFR) in the development of diabetic cognitive impairment and test whether folic acid (FA) supplementation prevents cognitive dysfunction in diabetic rats. In the current study, three months after streptozotocin-induced diabetes onset, rats showed cognitive dysfunction including the prolonged escape latency, the decreased time spent in the target quadrant and the declined number of crossing the platform in Morris water maze test. Diabetic rats also presented elevated plasma homocysteine level and downregulation of MTHFR in hippocampus revealed by Western blotting. The diabetic cognitive dysfunction was attenuated by 30-day dietary FA treatment with a significantly decreased homocysteine level. In conclusion, these results suggest that MTHFR plays a crucial role in diabetic cognitive dysfunction and folate fortification might become a potent therapeutic strategy against diabetic cognitive impairment. PMID:25550933

  2. Folic acid attenuates cognitive dysfunction in streptozotocin-induced diabetic rats

    PubMed Central

    Yang, Rui; Chen, Rong-Ping; Chen, Hong; Zhang, Hua; Cai, De-Hong

    2014-01-01

    Diabetic cognitive dysfunction is common in patients with diabetes but its pathogenesis is not clear. The aim of the present study is to investigate the role of 5’, 10’ methylene tetrahydrofolate reductase (MTHFR) in the development of diabetic cognitive impairment and test whether folic acid (FA) supplementation prevents cognitive dysfunction in diabetic rats. In the current study, three months after streptozotocin-induced diabetes onset, rats showed cognitive dysfunction including the prolonged escape latency, the decreased time spent in the target quadrant and the declined number of crossing the platform in Morris water maze test. Diabetic rats also presented elevated plasma homocysteine level and downregulation of MTHFR in hippocampus revealed by Western blotting. The diabetic cognitive dysfunction was attenuated by 30-day dietary FA treatment with a significantly decreased homocysteine level. In conclusion, these results suggest that MTHFR plays a crucial role in diabetic cognitive dysfunction and folate fortification might become a potent therapeutic strategy against diabetic cognitive impairment. PMID:25550933

  3. Reversal of Diabetes Through Gene Therapy of Diabetic Rats by Hepatic Insulin Expression via Lentiviral Transduction

    PubMed Central

    Elsner, Matthias; Terbish, Taivankhuu; Jörns, Anne; Naujok, Ortwin; Wedekind, Dirk; Hedrich, Hans-Jürgen; Lenzen, Sigurd

    2012-01-01

    Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5–7 days after the virus injection of 7 × 109 INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50–100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic ?-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach. PMID:22354377

  4. Asymmetric dimethylarginine reduced erythrocyte deformability in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Zhi-Chun Yang; Ke Xia; Li Wang; Su-Jie Jia; Dai Li; Zhe Zhang; Shen Deng; Xiao-Hong Zhang; Han-Wu Deng; Yuan-Jian Li

    2007-01-01

    To investigate the effect of asymmetric dimethylarginine on erythrocyte deformability in streptozotocin-induced diabetic rats, a single intraperitoneal injection of streptozotocin (STZ, 65 mg\\/kg) in male Sprague–Dawley rats was carried out to induce diabetes and normal erythrocytes were incubated with asymmetric dimethylarginine or aortic rings from diabetic rats in the presence of l-arginine or vitamin E. We found that erythrocyte deformability was

  5. Antioxidant therapy and streptozotocin-induced diabetes in pregnant rats

    Microsoft Academic Search

    M. Kinalski; A. ?ledziewski; B. Telejko; W. Zarzycki; I. Kinalska

    1999-01-01

    The aim of our study was to analyse the effect of chronic hyperglycaemia on lipid peroxidation and scavenging enzyme activity\\u000a in pregnant animals and their offspring supplemented and not supplemented with vitamin E – a natural antioxidant. Thirty pregnant\\u000a female Wistar rats were used in our experiments. Diabetes was induced on day 7 of pregnancy using a single does of

  6. The effect of endotoxin on heart rate dynamics in diabetic rats.

    PubMed

    Meamar, Morvarid; Dehpour, Tara; Mazloom, Roham; Sharifi, Fatemeh; Raoufy, Mohammad R; Dehpour, Ahmad R; Mani, Ali R

    2015-05-01

    The effect of endotoxin on heart rate variability (HRV) was assessed in diabetic and controls rats using a telemetric system. Endotoxin induced a reduction in sample entropy of cardiac rhythm in control animals. However, this effect was significantly blunted in streptozotocin-induced diabetic rats. Since uncoupling of cardiac pacemaker from cholinergic control is linked to reduced HRV in endotoxemia, chronotropic responsiveness to cholinergic stimulation was assessed in isolated atria. Endotoxemia was associated with impaired responsiveness to carbacholine in control rats. However, endotoxemia did not impair cholinergic responsiveness in diabetic atria. These findings corroborates with development of endotoxin tolerance in diabetic rats. PMID:25578644

  7. Modulation of Glucose Metabolism by Balanced Deep-Sea Water Ameliorates Hyperglycemia and Pancreatic Function in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Ha, Byung Geun; Park, Jung-Eun; Shin, Eun Ji; Shon, Yun Hee

    2014-01-01

    The aim of this study was to determine the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in streptozotocin (STZ)-induced diabetic mice. BDSW was prepared by mixing DSW mineral extracts and desalinated water to yield a final hardness of 1000–4000 ppm. Male ICR mice were assigned to 6 groups; mice in each group were given tap water (normal and STZ diabetic groups) or STZ with BDSW of varying hardness (0, 1000, 2000, and 4000 ppm) for 4 weeks. The STZ with BDSW group exhibited lowered fasting plasma glucose levels than the STZ-induced diabetic group. Oral glucose tolerance tests showed that BDSW improves impaired glucose tolerance in STZ-induced diabetic mice. Histopathological evaluation of the pancreas showed that BDSW restores the morphology of the pancreatic islets of Langerhans and increases the secretion of insulin in STZ-induced diabetic mice. Quantitative real-time PCR assay revealed that the expression of hepatic genes involved in gluconeogenesis, glucose oxidation, and glycogenolysis was suppressed, while the expression of the genes involved in glucose uptake, ?-oxidation, and glucose oxidation in muscle were increased in the STZ with BDSW group. BDSW stimulated PI3-K, AMPK, and mTOR pathway-mediated glucose uptake in C2C12 myotubes. BDSW increased AMPK phosphorylation in C2C12 myotubes and improved impaired AMPK phosphorylation in the muscles of STZ-induced diabetic mice. Taken together, these results suggest that BDSW is a potential anti-diabetic agent, owing to its ability to suppress hyperglycemia and improve glucose intolerance by modulating glucose metabolism, recovering pancreatic islets of Langerhans and increasing glucose uptake. PMID:25013896

  8. Lowering plasma 1-deoxysphingolipids improves neuropathy in diabetic rats.

    PubMed

    Othman, Alaa; Bianchi, Roberto; Alecu, Irina; Wei, Yu; Porretta-Serapiglia, Carla; Lombardi, Raffaella; Chiorazzi, Alessia; Meregalli, Cristina; Oggioni, Norberto; Cavaletti, Guido; Lauria, Giuseppe; von Eckardstein, Arnold; Hornemann, Thorsten

    2015-03-01

    1-Deoxysphingolipids (1-deoxySLs) are atypical neurotoxic sphingolipids that are formed by the serine-palmitoyltransferase (SPT). Pathologically elevated 1-deoxySL concentrations cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), an axonal neuropathy associated with several missense mutations in SPT. Oral L-serine supplementation suppressed the formation of 1-deoxySLs in patients with HSAN1 and preserved nerve function in an HSAN1 mouse model. Because 1-deoxySLs also are elevated in patients with type 2 diabetes mellitus, L-serine supplementation could also be a therapeutic option for diabetic neuropathy (DN). This was tested in diabetic STZ rats in a preventive and therapeutic treatment scheme. Diabetic rats showed significantly increased plasma 1-deoxySL concentrations, and L-serine supplementation lowered 1-deoxySL concentrations in both treatment schemes (P < 0.0001). L-serine had no significant effect on hyperglycemia, body weight, or food intake. Mechanical sensitivity was significantly improved in the preventive (P < 0.01) and therapeutic schemes (P < 0.001). Nerve conduction velocity (NCV) significantly improved in only the preventive group (P < 0.05). Overall NCV showed a highly significant (P = 5.2E-12) inverse correlation with plasma 1-deoxySL concentrations. In summary, our data support the hypothesis that 1-deoxySLs are involved in the pathology of DN and that an oral L-serine supplementation could be a novel therapeutic option for treating DN. PMID:25277395

  9. Chromium and manganese interactions in streptozocin-diabetic rats

    SciTech Connect

    Davis, M.L.; Jarrett, C.R.; Adeleye, B.O.; Stoecker, B.J. (Oklahoma State Univ., Stillwater (United States))

    1991-03-15

    Weanling male rats were fed casein-based diets low in chromium and manganese ({minus}Cr-MN) or supplemented with 1 ppm chromium as chromium chloride (+Cr) and/or 55 ppm manganese as manganous carbonate in a factorial design. After 7 weeks on the experimental diets, half of the rats in each group were injected on 2 consecutive days with 55 mg/kg streptozocin (STZ) in citrate buffer pH 4. Four weeks after injection, serum glucose in the diabetic group supplement with both Cr and Mn was not different from non-diabetic animals; however, diabetic animals in {minus}Cr groups or in the +Cr-Mn group had significantly elevated serum glucose. Serum insulin was reduced by STZ. A significant interaction between Mn and diabetes affected serum cortisol concentrations. More new tissue was formed on a polyvinyl sponge inserted under the skin in +Mn animals. In this study, the STZ animals were more sensitive than the control animals to dietary Cr and Mn concentrations.

  10. Tissue noradrenaline and the polyol pathway in experimentally diabetic rats.

    PubMed Central

    Lucas, P. D.; Qirbi, A.

    1989-01-01

    1. The effects of a six week period of streptozotocin-induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats. 2. Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals. 3. Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with alpha-methyl-p-tyrosine. Turnover was found to be increased in all three tissues. 4. The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo-inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo-inositol treatment also partially prevented the rise in adrenal adrenaline. 5. It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo-inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na+, K+-ATPase depression. PMID:2503223

  11. Raloxifene Prevents Skeletal Fragility in Adult Female Zucker Diabetic Sprague-Dawley Rats

    PubMed Central

    Hill Gallant, Kathleen M.; Gallant, Maxime A.; Brown, Drew M.; Sato, Amy Y.; Williams, Justin N.; Burr, David B.

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n?=?24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies. PMID:25243714

  12. A Phytooxysterol, 28-Homobrassinolide Modulates Rat Testicular Steroidogenesis in Normal and Diabetic Rats

    PubMed Central

    Premalatha, R.; Jubendradass, Rajamanickam; Rani, S. Judith Amala; Srikumar, K.; Mathur, Premendu Prakash

    2013-01-01

    Steroidogenesis in testicular cells depends upon the availability of cholesterol within testicular mitochondria besides the activities of 3?-hydroxysteroid dehydrogenase (3?-HSD, 17?-hydroxysteroid dehydrogenase [17b-HSD]), and the tissue levels of steroidogenic acute regulatory protein (StAR), androgen-binding protein (ABP), and testosterone (T). Cellular cholesterol biosynthesis is regulated by endogenous oxycholesterols acting through nuclear hormone receptors. Plant oxysterols, such as 28-homobrassinolide (28-HB), available to human through diet, was shown to exhibit antihyperglycemic effect in diabetic male rat. Its role in rat testicular steroidogenesis and lipid peroxidation (LPO) was therefore assessed using normal and streptozotocin-induced diabetic male rats. Administration of 28-HB (333 µg/kg body weight) by oral gavage for 15 consecutive days to experimental rats diminished LPO, increased antioxidant enzyme, 3?-HSD and 17?-HSD activities, and elevated StAR and ABP expression and T level in rat testis. We report that 28-HB induced steroidogenesis in normal and diabetic rat testis. PMID:23012313

  13. Altered glucose kinetics in diabetic rats during Gram-negative infection

    SciTech Connect

    Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J. (Louisiana State Univ. Medical Center, New Orleans (USA))

    1987-08-01

    The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge.

  14. Injury to the Endothelial Surface Layer Induces Glomerular Hyperfiltration Rats with Early-Stage Diabetes

    PubMed Central

    Zhang, Chunyang; Meng, Yao; Liu, Qi; Xuan, Miao; Zhang, Lanyu; Deng, Bo; Zhang, Keqin; Liu, Zhimin; Lei, Tao

    2014-01-01

    Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidence in vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes. PMID:24812636

  15. Antidiabetic Effect of Sida cordata in Alloxan Induced Diabetic Rats

    PubMed Central

    Shah, Naseer Ali; Khan, Muhammad Rashid

    2014-01-01

    Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120?mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties. PMID:25114914

  16. Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats

    SciTech Connect

    Myers, T.O.; Messina, E.J.; Rodrigues, A.M.; Gerritsen, M.E.

    1985-10-01

    Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous (1- UC)arachidonic acid by thoracic aortic rings and minced cremaster muscle. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis.

  17. Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

    PubMed Central

    Malatiali, Slava; Francis, Issam; Barac-Nieto, Mario

    2008-01-01

    The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor) was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin) and protein excretion rate (PER) were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P < .001), Cinulin increased 80% (P < .01). Kidney wet and dry weights increased 10%–12% (P < .05), and glomerular tuft area increased 9.3% (P < .001). Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control. PMID:18769499

  18. Effects of Sesame Oil on the Reproductive Parameters of Diabetes Mellitus-Induced Male Rats

    PubMed Central

    Abbasi, Zahra; Tabatabaei, Seyed Reza Fatemi; Mazaheri, Yazdan; Morovvati, Hasan

    2013-01-01

    Purpose The purpose of the present study was to investigate the effect of sesame oil on the reproductive parameters of diabetic male Wistar rats. Materials and Methods The adult male rats in a split plot design were divided into normal (n=10), normal 5% (n=5; 5% sesame oil enriched diet), diabetic (Streptozocin induced diabetes; n=9), diabetic 5% (n=9; 5% sesame oil enriched diet), and diabetic 10% (n=9; 10% sesame oil enriched diet) groups. Diet supplementation continued for 56 days. Results Sesame oil supplementation did not reduce the plasma glucose concentration of rats in the diabetic groups (p>0.05). The total spermatogonia, spermatocytes, Leydig cells/tubule, and the germ cell to Sertoli cell ratio were lower in the diabetic rats than the normal ones (p<0.05), and with the exception of spermatogonia counts, these values improved by the addition of sesame oil to the diet (p<0.05). The sperm progressive motility and viability were lower in the diabetic rats (p<0.05) and sesame oil supplementation did not improve them. Incorporation of sesame oil into the diet improved the plasma testosterone concentration of the diabetic rats in a dose-dependent manner (p<0.05). Conclusions In summary, sesame oil supplementation improved the reproductive parameters of diabetic rats at the levels of the testicular microstructure and function, but was not effective in protecting the epididymal sperm. PMID:24044109

  19. Aminoguanidine Reverses the Loss of Functional Hyperemia in a Rat Model of Diabetic Retinopathy

    PubMed Central

    Mishra, Anusha; Newman, Eric A.

    2011-01-01

    Flickering light dilates retinal arterioles and increases retinal blood flow, a response termed functional hyperemia. This response is diminished in diabetic patients even before the appearance of overt clinical retinopathy. The loss of functional hyperemia could deprive retinal neurons of oxygen and nutrients, possibly exacerbating the development of diabetic retinopathy. We have tested whether inhibiting inducible nitric oxide synthase (iNOS) reverses the loss of functional hyperemia in diabetic rat retinas in vivo. Changes in retinal arteriole diameter were measured following diffuse flickering light stimulation in control rats, streptozotocin-induced type 1 diabetic rats and diabetic rats treated with aminoguanidine (AG; an iNOS inhibitor), either acutely via IV injection or chronically in drinking water. Flickering light-evoked large arteriole dilations (10.8?±?1.1%) in control rats. This response was diminished by 61% in diabetic animals (4.2?±?0.3%). Both acute and chronic treatment with AG restored flicker-induced arteriole dilations in diabetic rats (8.8?±?0.9 and 9.5?±?1.3%, respectively). The amplitude of the corneal electroretinogram b-wave was similar in control and diabetic animals. These findings demonstrate that inhibiting iNOS with AG is effective in preventing the loss of, and restoring, normal functional hyperemia in the diabetic rat retina. Previous work has demonstrated the efficacy of iNOS inhibitors in slowing the progression of diabetic retinopathy. This effect could be due, in part, to a restoration of functional hyperemia. PMID:22291637

  20. Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats

    Microsoft Academic Search

    P. Suresh Babu; K. Srinivasan

    1998-01-01

    Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT, alkaline and acid phosphatases. The integrity of

  1. The effects of galanin on neuropathic pain in streptozotocin-induced diabetic rats.

    PubMed

    Xu, Xiaofeng; Liu, Zhen; Liu, Huaxiang; Yang, Xiangdong; Li, Zhenzhong

    2012-04-01

    Diabetic neuropathy is a common complication associated with diabetes and is frequently painful. However, mechanisms responsible for diabetic neuropathic pain are still unclear. Experimental evidence has shown that the galanin and its receptor are involved in pain sensitization. The objective of the present study was to investigate the role of galanin and its receptor antagonist or agonist on neuropathic pain in streptozotocin-induced diabetic rats. The expression of galanin, galanin receptors 1 and 2 in dorsal root ganglion (DRG) and spinal dorsal horn (SDH) in diabetic rats were detected by Western blot assay. The effects of galanin, galanin receptor antagonist M35, galanin receptor 1 agonist M617, and galanin receptor 2 agonist AR-M1896 on neuropathic pain were evaluated by mechanical stimuli. The results showed that (1) the diabetic rats showed a significant mechanical hyperalgesia between 4 and 12weeks; (2) galanin receptor 1 expression decreased in SDH in diabetic rats; (3) galanin receptor 2 expression decreased in DRG and SDH in diabetic rats; (4) intrathecal administration of exogenous galanin attenuated diabetic neuropathic pain, this effect could be blocked by pre-treatment with galanin receptor antagonist M35; and (5) intrathecal administration of galanin receptor 1 agonist M617, but not galanin receptor 2 agonist AR-M1896, attenuated diabetic neuropathic pain. These results imply that galanin acts through receptor 1, but not galanin receptor 2, to exert analgesic effect in diabetic neuropathic pain and is one of the potential therapeutic targets on diabetic neuropathic pain sensitization. PMID:22306246

  2. Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats

    PubMed Central

    Guo, Yong; Zhang, Jie; Ding, Zhenghua; Ha, Wenjing; Harding, J.J.

    2008-01-01

    Purpose To investigate the effect of carnosine (CA), aminoguanidine (AG), and aspirin (ASA) drops, all inhibitors of glycation, on the development of diabetic cataract in rat. Methods Rats were made diabetic with streptozotocin, and based on the level of plasma glucose, they were assigned as non-diabetic rats (<14 mmol/l plasma glucose) and diabetic rats (>14 mmol/l plasma glucose). Animals in the treated groups received CA, AG, and ASA as drops to the left eyes starting from the day of streptozotocin injection. Progression of lens opacification was recorded using the slit lamp at regular time intervals. All the rats were killed after the week 13, and the levels of advanced glycation end products (AGE), glutathione reductase (GR), catalase (CAT), and glutathione (GSH) were determined. Results Lens opacification progressed in a biphasic manner in the diabetic rats, an initial slow increase during the first eight weeks of diabetes followed by a steep increase in the next five weeks. Carnosine treatment delayed the progression of cataracts in diabetic rats, and the delay was statistically significant on the fourth week of diabetes (p<0.05, when compared with untreated moderately diabetic rats). A decrease in the antioxidant enzymes of CAT and the level of GSH was found in the lens of the untreated diabetic rats at 13 weeks after injection. Some protection was provided in the treated eyes. The level of glycation in the untreated diabetic rats was significantly higher than that in the normal rats (p<0.001). After treatment with CA, AG, and ASA, those diabetic rats had a lower level of glycated lens protein compared to the untreated diabetic rats (p<0.001). Conclusions These results thus suggest that the effect of CA, AG, and ASA is indeed inhibition of the formation of AGEs. However, the effect of CA, AG, and ASA is overwhelmed by the excessive accumulation of AGEs in the severely diabetic rats. CA compared with AG and ASA treatment can delay the progression of lens opacification in the diabetic rats only during the earlier stages. It also protects against the inactivation of enzymes. PMID:19081783

  3. The BBZDR/Wor rat model for investigating the complications of type 2 diabetes mellitus.

    PubMed

    Tirabassi, Rebecca S; Flanagan, Joan F; Wu, Tiangen; Kislauskis, Edward H; Birckbichler, Paul J; Guberski, Dennis L

    2004-01-01

    Congenic and inbred strains of rats offer researchers invaluable insight into the etiopathogenesis of diabetes and associated complications. The inbred Bio-Breeding Zucker diabetic rat (BBZDR)/Wor rat strain is a relatively new and emerging model of type 2 diabetes. This strain was created by classical breeding methods used to introgress the defective leptin receptor gene (Lepr(fa)) from insulin-resistant Zucker fatty rats into the inbred BBDR/Wor strain background. The diabetic male BBZDR/Wor rat is homozygous for the fatty mutation and shares the genetic background of the original BB strain. Although lean littermates are phenotypically normal, obese juvenile BBZDR/Wor rats are hyperlipidemic and hyperleptinemic, become insulin resistant, and ultimately develop hyperglycemia. Furthermore, the BBZDR/Wor rat is immune competent and does not develop autoimmunity. Similar to patients with clinical diabetes, the BBZDR/Wor rat develops complications associated with hyperglycemia. The BBZDR/Wor rat is a model system that fully encompasses the ability to study the complications that affect human type 2 diabetic patients. In this review, recent work that has evaluated type 2 diabetic complications in BBZDR/Wor rats is discussed, including the authors' preliminary unpublished studies on cardiovascular disease. PMID:15229376

  4. Streptozotocin-nicotinamide-induced rat model of type 2 diabetes (review).

    PubMed

    Ghasemi, Asghar; Khalifi, S; Jedi, S

    2014-12-01

    Diabetes is one of the five leading causes of death in the world, with type 2 diabetes occurring more frequently than type 1. Management of diabetes without side effects is still a challenge and therefore new strategies need to be examined. Because of difficulties in human research, animal models of diabetes are useful research tools for this purpose and rodent models of type 2 diabetes are the first choice. The aim of this study is an overview on one of the most frequently used models of type 2 diabetes in rat, induced by streptozotocin and nicotinamide, considering its advantages and disadvantages for diabetes research in humans. PMID:25532953

  5. A Diet Producing a Low Diabetes Incidence Modifies Immune Abnormalities in Diabetes-Prone BB Rats123

    Microsoft Academic Search

    CATHERINE J. FIELD

    The effect of feeding a diet that produces a high or low incidence of diabetes on immune abnor malities proposed to contribute to the pathogenesis of autoimmune-mediated diabetes was investigated. Di abetes-prone (BBdp) and nondiabetes-prone (BBn) BB rats (21 d) were fed for 21 da non pur ¡fled (high inci dence) or purified (low diabetes incidence) diet. Com pared with

  6. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats

    Microsoft Academic Search

    Zhikun Yang; Kanghua Li; Xi Yan; Fangtian Dong; Chunhua Zhao

    2010-01-01

    Background  Diabetic retinopathy is a common complication of diabetes, which is caused by injury to retinal microvasculature and neurons.\\u000a Mesenchymal stem cells (MSCs), which proved to have multi-linkage differentiation capacity, including endothelial cells and\\u000a neurons, might be a promising cell therapy resource. The current pilot study was performed using the streptozotocin (STZ)\\u000a rat model of diabetic retinopathy injected intravenously with human

  7. Impaired amyloid ?-degrading enzymes in brain of streptozotocin-induced diabetic rats.

    PubMed

    Liu, Y; Liu, L; Lu, S; Wang, D; Liu, X; Xie, L; Wang, G

    2011-01-01

    Enzymes that degrade the amyloid ?-peptide (A?) are important regulators of cerebral A? levels. High level of A? was found in the brain of diabetic patients and diabetic animals. Aim of the study was to investigate whether activities of A?-degrading enzymes neprilysin (NEP), endothelin-converting enzyme 1 (ECE-1) and insulin-degrading enzyme (IDE) were impaired in the brain of diabetic rats. Diabetes was induced in rats by ip administration of 65 mg/kg streptozotocin. The temporal cortex and hippocampus were obtained for activity and mRNA level assays of the three enzymes on the 35th day after induction. ECE-1 activity was significantly decreased both in the hippocampus and cortex of diabetic rats, while for IDE significantly lower activity occurred only in the cortex. NEP activity was slightly decreased in both brain regions. The hippocampus of diabetic rats showed significant decrease in mRNA levels of NEP and ECE-1 and moderate increase in IDE mRNA level. The cortex of diabetic rats showed slight decrease in mRNA levels of the three enzymes. The results indicated that the three A?-degrading enzymes were damaged to different extents in the brain of diabetic rats, and impairment of ECE-1 and IDE partly contributed to the elevated A?(1-40) levels in brain of diabetic rats. PMID:20414044

  8. Exacerbation of intestinal brush border enzyme activities and oxidative stress in streptozotocin-induced diabetic rats by monocrotophos.

    PubMed

    Vismaya; Rajini, P S

    2014-03-25

    The present study was undertaken to investigate the potential of monocrotophos (MCP), one of the widely used broad spectrum systemic organophosphorus insecticides (OPI) in India, to alter small intestinal structure and function. Further, its potential to exacerbate diabetes induced alterations in intestinal structure and function was also studied in experimentally induced diabetic rats. Rats were rendered diabetic with an acute dose of streptozotocin (60 mg/kg b.w.). MCP was orally administered at a sublethal dose (1/20 LD50 i.e. 0.9 mg/kg b.w./d) for 15 days to both normal and diabetic rats. MCP significantly increased unit weight of intestine in diabetic rats. MCP alone increased (up to 57%) the activities of intestinal brush border disaccharidases in normal rats and further augmented the enzyme activities in diabetic rats. Similar results were found with intestinal alkaline phosphatase activity. In addition, Na(+)/K(+)-ATPase activity was found to be aggravated in diabetic rats by MCP treatment. Oxidative stress markers showed similar degree of change in both MCP and diabetic rats while MCP aggravated oxidative stress condition in diabetic rats. Scanning electron microscopy and histological analysis of the small intestine revealed increased length of villi, congestion, goblet cell hyperplasia and infiltration of inflammatory cells in MCP and diabetic rats while MCP also induced necrotic lesions in diabetic rats. Collectively, our findings provide evidence that multiple doses of MCP has the propensity to augment diabetes associated intestinal dysfunctions in rats. PMID:24440807

  9. Regulation of Retinal Inflammation by Rhythmic Expression of MiR-146a in Diabetic Retina

    PubMed Central

    Wang, Qi; Bozack, Svetlana N.; Yan, Yuanqing; Boulton, Michael E.; Grant, Maria B.; Busik, Julia V.

    2014-01-01

    Purpose. Chronic inflammation and dysregulation of circadian rhythmicity are involved in the pathogenesis of diabetic retinopathy. MicroRNAs (miRNAs) can regulate inflammation and circadian clock machinery. We tested the hypothesis that altered daily rhythm of miR-146a expression in diabetes contributes to retinal inflammation. Methods. Nondiabetic and STZ-induced diabetic rats kept in 12/12 light/dark cycle were killed every 2 hours over a 72-hour period. Human retinal endothelial cells (HRECs) were synchronized with dexamethasone. Expression of miR-146a, IL-1 receptor-associated kinase 1 (IRAK1), IL-1?, VEGF and ICAM-1, as well as clock genes was examined by real-time PCR and Western blot. To modulate expression levels of miR-146a, mimics and inhibitors were used. Results. Diabetes inhibited amplitude of negative arm (per1) and enhanced amplitude of the positive arm (bmal1) of clock machinery in retina. In addition to clock genes, miR-146a and its target gene IRAK1 also exhibited daily oscillations in antiphase; however, these patterns were lost in diabetic retina. This loss of rhythmic pattern was associated with an increase in ICAM-1, IL-?, and VEGF expression. Human retinal endothelial cells had robust miR-146a expression that followed circadian oscillation pattern; however, HRECs isolated from diabetic donors had reduced miR-146a amplitude but increased amplitude of IRAK1 and ICAM-1. In HRECs, miR-146a mimic or inhibitor caused 1.6- and 1.7-fold decrease or 1.5- and 1.6-fold increase, respectively, in mRNA and protein expression levels of ICAM-1 after 48 hours. Conclusions. Diabetes-induced dysregulation of daily rhythms of miR-146a and inflammatory pathways under miR-146a control have potential implications for the development of diabetic retinopathy. PMID:24867582

  10. Effect of human umbilical cord blood CD34+ progenitor cells transplantation in diabetic mice

    Microsoft Academic Search

    Mona AbdElabry Hasein; Fadia Mostafa Attia; Mohamed Mohy Eldin Awad; Howedya Ahmed Abdelaal; Magady Elbarabary

    Shortage of donor organs spurs research into alternative means of generating ? cells. Stem cells might represent a potential\\u000a source of tissues for cell therapy protocols, and diabetes is a candidate disease that may benefit from cell replacement protocols.\\u000a We examined the effect of transplanted human umbilical cord blood CD34+ cells on some detailed parameters in streptozotocin-\\u000a (STZ) induced diabetic

  11. Antihyperglycemic and antihyperlipidemic effects of Clitoria ternatea Linn. in alloxan-induced diabetic rats

    Microsoft Academic Search

    P. Daisy; Kanakappan Santosh; M. Rajathi

    This study aims to investigate the therapeutic effects of Clitoria ternatea Linn. leaves and flowers extract on alloxan-induced diabetic rats. The effect of aqueous extract of C. ternatea leaves and flowers on serum glucose, glycosylated hemoglobin, insulin, total cholesterol, triglycerides, HDL-cholesterol, protein, urea, creatinine were examined in control and extract treated diabetic rats. Glycogen was examined both in the liver

  12. Caraway and caper: potential anti-hyperglycaemic plants in diabetic rats

    Microsoft Academic Search

    M Eddouks; A Lemhadri; J.-B Michel

    2004-01-01

    The hypoglycaemic effect of aqueous extracts of Carum carvi (CC) and Capparis spinosa L. (CS) fruit were investigated in normal and streptozotocin (STZ) diabetic rats. After a single dose or 14 daily doses, oral administration of the aqueous CC and CS extracts (20mg\\/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (P < 0.001); the blood

  13. LEW.1WR1 rats develop autoimmune diabetes spontaneously and in response to environmental perturbation.

    PubMed

    Mordes, John P; Guberski, Dennis L; Leif, Jean H; Woda, Bruce A; Flanagan, Joan F; Greiner, Dale L; Kislauskis, Edward H; Tirabassi, Rebecca S

    2005-09-01

    We describe a new rat model of autoimmune diabetes that arose in a major histocompatibility complex congenic LEW rat. Spontaneous diabetes in LEW.1WR1 rats (RT1(u/u/a)) occurs with a cumulative frequency of approximately 2% at a median age of 59 days. The disease is characterized by hyperglycemia, glycosuria, ketonuria, and polyuria. Both sexes are affected, and islets of acutely diabetic rats are devoid of beta-cells, whereas alpha- and delta-cell populations are spared. The peripheral lymphoid phenotype is normal, including the fraction of ART2(+) regulatory T-cells. We tested the hypothesis that the expression of diabetes would be increased by immunological perturbation of innate or adaptive immunity. Treatment of young rats with depleting anti-ART2.1 monoclonal antibody increased the frequency of diabetes to 50%. Treatment with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid increased the frequency of diabetes to 100%. All diabetic rats exhibited end-stage islets. The LEW.1WR1 rat is also susceptible to collagen-induced arthritis but is free of spontaneous thyroiditis. The LEW.1WR1 rat provides a new model for studying autoimmune diabetes and arthritis in an animal with a genetic predisposition to both disorders that can be amplified by environmental perturbation. PMID:16123363

  14. LEW.1WR1 RATS DEVELOP AUTOIMMUNE DIABETES SPONTANEOUSLY AND IN RESPONSE TO ENVIRONMENTAL PERTURBATION

    PubMed Central

    Mordes, John P.; Leif, Jean H.; Woda, Bruce A.; Flanagan, Joan F.; Greiner, Dale L.; Kislauskis, Edward H.; Tirabassi, Rebecca S.

    2005-01-01

    We describe a new rat model of autoimmune diabetes that arose in a major histocompatibility complex (MHC) congenic LEW rat. Spontaneous diabetes in LEW.1WR1 rats (RT1u/u/a) occurs with a cumulative frequency of ?2% at a median age of 59 days. The disease is characterized by hyperglycemia, glycosuria, ketonuria and polyuria. Both sexes are affected, and islets of acutely diabetic rats are devoid of beta cells whereas alpha and delta cell populations are spared. The peripheral lymphoid phenotype is normal, including the fraction of ART2+ regulatory T cells (Tregs). We tested the hypothesis that the expression of diabetes would be increased by immunological perturbation of innate or adaptive immunity. Treatment of young rats with depleting anti-ART2.1 mAb increased the frequency of diabetes to 50%. Treatment with the toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid increased the frequency of diabetes to 100%. All diabetic rats exhibited end-stage islets. The LEW.1WR1 rat is also susceptible to collagen-induced arthritis but is free of spontaneous thyroiditis. The LEW.1WR1 rat provides a new model for studying autoimmune diabetes and arthritis in an animal with a genetic predisposition to both disorders that can be amplified by environmental perturbation. PMID:16123363

  15. Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats.

    PubMed

    Castoldi, Giovanna; di Gioia, Cira R T; Bombardi, Camila; Maestroni, Silvia; Carletti, Raffaella; Steckelings, U Muscha; Dahlöf, Bjorn; Unger, Thomas; Zerbini, Gianpaolo; Stella, Andrea

    2014-11-15

    The aim of this study was to evaluate the effect of compound 21 (C21), a selective AT2 receptor agonist, on diabetic nephropathy and the potential additive effect of C21, when associated with losartan treatment, on the development of albuminuria and renal fibrosis in Zucker diabetic fatty (ZDF) rats. The experiments lasted 15 wk (from 5 to 20 wk of age) and were performed in 40 ZDF rats and 12 control lean rats. ZDF rats were divided into 4 groups: 1) 9 rats were treated with losartan; 2) 10 rats were treated with C21; 3) 9 rats were treated with losartan plus C21; and 4) 12 rats were maintained without any treatment. ZDF rats showed an increase in blood glucose level, albuminuria, renal fibrosis, macrophage infiltration, and TNF-? expression and a reduction of glomerular nephrin expression compared with control lean rats. C21 treatment reduced renal glomerular, tubulointerstitial, and perivascular fibrosis, and macrophage infiltration and TNF-? expression in ZDF rats. C21 treatment caused a decrease in albuminuria in ZDF rats up to 11 wk of age. Losartan decreased macrophage infiltration, TNF-? expression, and renal glomerular and perivascular fibrosis, restored glomerular nephrin expression, but did not affect tubulointerstitial fibrosis. Losartan treatment caused a decrease in albuminuria in ZDF rats up to 15 wk of age. At the end of the protocol, only the combination of C21 plus losartan significantly reduced albuminuria in ZDF rats. These data demonstrate that C21 has beneficial effects on diabetic nephropathy, suggesting the combination of C21 and losartan as a novel pharmacological tool to slow the progression of nephropathy in type II diabetes. PMID:25186297

  16. The Protective Effect of Cordymin, a Peptide Purified from the Medicinal Mushroom Cordyceps sinensis, on Diabetic Osteopenia in Alloxan-Induced Diabetic Rats.

    PubMed

    Qi, Wei; Zhang, Yang; Yan, Ya-Bo; Lei, Wei; Wu, Zi-Xiang; Liu, Ning; Liu, Shuai; Shi, Lei; Fan, Yong

    2013-01-01

    The aim of this study was to investigate the protective effect of cordymin on diabetic osteopenia in alloxan-induced diabetic rats and the possible mechanisms involved. The diabetic rats received daily intraperitoneal injection with cordymin (20, 50, and 100?mg/kg/day) for 5 weeks. Cordymin could restore the circulating blood glucose, glycosylated hemoglobin (HbA1c), serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), and insulin levels in a dose-dependent manner. Also, the treatment of diabetic rats with cordymin could partially reverse the ? cells death and decrease the total antioxidant status (TAOS) in the diabetic rats. The results may directly and indirectly account for the possible mechanism of the beneficial effect of cordymin on diabetic osteopenia, which was confirmed with the increased bone mineral content (BMC) and bone mineral density (BMD) in diabetic rats (P < 0.05). All those findings indicate that cordymin may play a protective role in diabetic osteoporosis. PMID:24174985

  17. Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats.

    PubMed

    Navarro-Alarcon, Miguel; Ruiz-Ojeda, Francisco J; Blanca-Herrera, Rosa M; Kaki, Abdullah; Adem, Abdu; Agil, Ahmad

    2014-03-01

    The use of melatonin, a neurohormone present in plants, represents an exciting approach for the maintenance of optimum health conditions. Melatonin administration ameliorates glucose homeostasis in Zucker diabetic fatty (ZDF) rats. The objective of this study was to investigate the effects of melatonin in diabetes in relation to the levels and regulation of plasma chromium (Cr), vanadium (V), and magnesium (Mg) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. At the age of 6 weeks, ZDF (n = 30) and ZL (n = 30) groups were each subdivided into three groups: control (C) (n = 10), vehicle-treated (V') (n = 10) and melatonin-treated (M) (10 mg kg(-1) per day; n = 10) groups for a 6 week period. After treatment, plasma mineral concentrations were measured by flame (Mg) and electrothermal (Cr and V) atomic absorption spectrometry. No significant differences were found between the C and V' groups (p > 0.05). Plasma Mg levels were significantly lower in C-ZDF vs. C-ZL rats, demonstrating the presence of hypomagnesemia in this diabetes mellitus model. Plasma V and Cr levels were significantly higher in M-ZDF vs. C-ZDF rats. Plasma Mg levels in ZDF rats were not affected by melatonin treatment (p > 0.05). Melatonin administration ameliorates the diabetic status of ZDF rats by enhancing plasma Cr and V concentrations. This appears to be the first report of a beneficial effect of melatonin treatment on plasma Cr and V regulation in ZDF rats. PMID:24441643

  18. Effect of Vanadate on Elevated Blood Glucose and Depressed Cardiac Performance of Diabetic Rats

    NASA Astrophysics Data System (ADS)

    Heyliger, Clayton E.; Tahiliani, Arun G.; McNeill, John H.

    1985-03-01

    The trace element vanadium has an unclear biological function. Vanadate, an oxidized form of vanadium, appears to have an insulin-like action. The effect of vanadate on blood glucose and cardiac performance was assessed in female Wistar rats 6 weeks after they were made diabetic with streptozotocin. When vanadate was administered for a 4-week period to the diabetic rats, their blood glucose was not significantly different from that of nondiabetic controls despite a low serum insulin. In contrast, blood glucose was increased about threefold in the diabetic rats that were not treated with vanadate; these rats also had low insulin levels. Cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the vanadate-treated diabetic animals was not significantly different from that of nondiabetic controls. Thus vanadate controlled the high blood glucose and prevented the decline in cardiac performance due to diabetes.

  19. Protein synthesis in wound after tooth extraction in pancreatectomized diabetic rats.

    PubMed

    Grandini, S A; Brentegani, L G; Novaes, A B; Migliorini, R H

    1990-01-01

    The incorporation of alanine C14 in protein synthesis was analyzed in recently formed alveolar tissue after tooth extraction in partially-pancreatectomized diabetic rats. The incorporation of alanine C14 was higher in diabetic animals than in treated diabetic and control groups. The results can be explained by a delay in bone tissue repair. PMID:2135874

  20. Treatment of Zucker diabetic fatty rats with AVE7688 improves vascular and neural dysfunction

    PubMed Central

    Oltman, C. L.; Davidson, E. P.; Coppey, L. J.; Kleinschmidt, T. L.; Yorek, M. A.

    2009-01-01

    Aim Vasopeptidase inhibitors are drugs that inhibit angiotensin-converting enzyme and neutral endopeptidase (NEP). The latter is a protease that degrades vasoactive peptides and is increased in diabetes. We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with AVE7688, a vasopeptidase inhibitor, improves neurovascular and neural function. In this study, we determined the effect of treating Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes, with AVE7688 on vascular and neural function. Methods ZDF rats at 12 weeks of age were treated for 12 weeks with AVE7688 (500 mg/kg diet). Afterwards, vascular reactivity of epineurial arterioles of the sciatic nerve and nerve conduction velocity and blood flow was determined. Results Vascular and neural function was significantly impaired in ZDF rats compared with age-matched lean (control) rats. Treating ZDF rats with AVE7688 improved vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Motor and sensory nerve conduction velocity, endoneurial blood flow and thermal nociception end-points were also improved by treatment compared with untreated ZDF rats. Superoxide and expression of NEP were increased in epineurial arterioles from ZDF rats and attenuated by treatment with AVE7688. Conclusions AVE7688 is an effective treatment for microvascular and neural disease in ZDF rats. Thus, vasopeptidase inhibitors may be an effective treatment for diabetic microvascular and neural complication in type 2 diabetes. PMID:18564175

  1. Resistance to hypoxic conduction block in sciatic nerves of rats with streptozotocin-induced diabetes mellitus.

    PubMed

    Calcutt, N A; Ettlinger, C B; Carrington, A L; Diemel, L; Tomlinson, D R

    1991-05-01

    This study describes the electrophysiological responses of endoneurial preparations derived from rat sciatic nerve to acute hypoxia in vitro. Preparations from control rats exhibited a marked decline in compound action potential (CAP) amplitude coupled with an increase in latency, during 40 minutes exposure to 8% O2. In contrast, preparations from 4 week streptozotocin-diabetic rats showed a greatly reduced decline in CAP amplitude, with an increase in latency. Twice-daily insulin treatment of diabetic rats resulted in a pattern of CAP amplitude decline that initially resembled that of untreated diabetics but by 40 min was similar to controls, with latency again increasing during hypoxia. Nerves were also maintained in 25 mmol/l glucose, rather than the 5 mmol/l glucose of the above studies. Under such conditions the performance of nerves from diabetic rats was unaltered. Nerves from control rats exhibited an initial resistance to hypoxia but by 40 min CAP had declined to values of control rats maintained in 5 mmol/l glucose. An increase in latency during hypoxia was also noted in preparations from control or diabetic rats maintained in 25 mmol/l glucose. The maintenance of CAP amplitude during hypoxia by diabetic preparations is initially related to increased substrate availability, with an additional component that is not related to external glucose levels in vitro, and is absent after insulin treatment of diabetic rats. PMID:1865225

  2. Levels of DNA damage in blood leukocyte samples from non-diabetic and diabetic female rats and their fetuses exposed to air or cigarette smoke

    Microsoft Academic Search

    Paula Helena Ortiz Lima; Débora Cristina Damasceno; Yuri Karen Sinzato; Maricelma da Silva Soares de Souza; Daisy Maria Fávero Salvadori; Iracema de Mattos Paranhos Calderon; Marilza Vieira Cunha Rudge

    2008-01-01

    The objective of the present study was to evaluate DNA damage level in blood leukocytes from diabetic and non-diabetic female Wistar rats exposed to air or to cigarette smoke, and to correlate the findings with levels of DNA damage detected in blood leukocyte samples from their fetuses. A total of 20 rats were distributed into four experimental groups: non-diabetic (control;

  3. Angiotensin-(1-7) attenuates diabetic nephropathy in Zucker diabetic fatty rats.

    PubMed

    Giani, Jorge F; Burghi, Valeria; Veiras, Luciana C; Tomat, Analía; Muñoz, Marina C; Cao, Gabriel; Turyn, Daniel; Toblli, Jorge E; Dominici, Fernando P

    2012-06-15

    Angiotensin (ANG)-(1-7) is known to attenuate diabetic nephropathy; however, its role in the modulation of renal inflammation and oxidative stress in type 2 diabetes is poorly understood. Thus in the present study we evaluated the renal effects of a chronic ANG-(1-7) treatment in Zucker diabetic fatty rats (ZDF), an animal model of type 2 diabetes and nephropathy. Sixteen-week-old male ZDF and their respective controls [lean Zucker rats (LZR)] were used for this study. The protocol involved three groups: 1) LZR + saline, 2) ZDF + saline, and 3) ZDF + ANG-(1-7). For 2 wk, animals were implanted with subcutaneous osmotic pumps that delivered either saline or ANG-(1-7) (100 ng·kg(-1)·min(-1)) (n = 4). Renal fibrosis and tissue parameters of oxidative stress were determined. Also, renal levels of interleukin-6 (IL-6), tumor necrosis factor-? (TNF-?), ED-1, hypoxia-inducible factor-1? (HIF-1?), and neutrophil gelatinase-associated lipocalin (NGAL) were determined by immunohistochemistry and immunoblotting. ANG-(1-7) induced a reduction in triglyceridemia, proteinuria, and systolic blood pressure (SBP) together with a restoration of creatinine clearance in ZDF. Additionally, ANG-(1-7) reduced renal fibrosis, decreased thiobarbituric acid-reactive substances, and restored the activity of both renal superoxide dismutase and catalase in ZDF. This attenuation of renal oxidative stress proceeded with decreased renal immunostaining of IL-6, TNF-?, ED-1, HIF-1?, and NGAL to values similar to those displayed by LZR. Angiotensin-converting enzyme type 2 (ACE2) and ANG II levels remained unchanged after treatment with ANG-(1-7). Chronic ANG-(1-7) treatment exerts a renoprotective effect in ZDF associated with a reduction of SBP, oxidative stress, and inflammatory markers. Thus ANG-(1-7) emerges as a novel target for treatment of diabetic nephropathy. PMID:22492942

  4. Involvement of 1,2-diacylglycerol in improvement of heart function by etomoxir in diabetic rats

    Microsoft Academic Search

    Kazunori Hayashi; Kenji Okumura; Hideo Matsui; Kichiro Murase; Hiroki Kamiya; Yoshihiro Saburi; Yasushi Numaguchi; Yukio Toki; Tetsuo Hayakawa

    2001-01-01

    Abnormal lipid metabolism has been proposed to be involved in the pathogenesis of diabetic cardiomyopathy. In this study, we measured myocardial lipid levels, including 1,2-diacylglycerol (1,2-DAG) and ceramide (CM), and myocardial function in diabetic rats. We also evaluated the effects of etomoxir (ETM), a carnitine palmitoyl transferase I inhibitor, on diabetic rat hearts from the viewpoints of alterations in lipid

  5. Acute Kidney Injury in the Diabetic Rat: Studies in the Isolated Perfused and Intact Kidney

    Microsoft Academic Search

    Christian Rosenberger; Mogher Khamaisi; Marina Goldfarb; Ahuva Shina; Vitali Shilo; Fanni Zilbertrest; Seymour Rosen; Samuel N. Heyman

    2008-01-01

    Background\\/Aim: Diabetes leads to chronic renal hypoxia and cellular hypoxia response (mediated by hypoxia-inducible factors) and predisposes to acute kidney injury. We studied the impact of acute and chronic hypoxic stress on the development of acute kidney injury in the diabetic rat kidney. Methods: Control (CTR) and streptozotocin (STZ)-diabetic rats were studied following acute medullary hypoxic stress, induced by combinations

  6. Effect of diabetes mellitus induced by streptozotocin on renal Superoxide dismutases in the rat

    Microsoft Academic Search

    Kazushige Dobashi; Kohtaro Asayama; Hidemasa Hayashibe; Norihiko Uchida; Makio Kobayashi; Akira Kawaoi; Kiyohiko Kato

    1991-01-01

    Summary  Two forms of Superoxide dismutase, CuZnSOD and MnSOD, have been investigated in the kidneys of streptozotocin-induced diabetic\\u000a rats using both radioimmunoassay and immunoenzyme staining. The rats were killed 2, 8 and 12 weeks after the induction of\\u000a diabetes mellitus and the kidneys excised. Two weeks after the induction of diabetes, the kidneys were hypertrophied because\\u000a of the proliferation of renal

  7. Intermittent fasting modulation of the diabetic syndrome in sand rats. II. In vivo investigations.

    PubMed

    Belkacemi, Louiza; Selselet-Attou, Ghalem; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J

    2010-11-01

    This study deals with the effects of daily intermittent fasting for 15 h upon the development of diabetes in sand rats exposed to a hypercaloric diet. The same pattern of daily intermittent fasting was imposed on sand rats maintained on a purely vegetal diet (control animals). Over the last 30 days of the present experiments, non-fasting animals gained weight, whilst intermittently fasting sand rats lost weight. In this respect, there was no significant difference between control animals and either diabetic or non-diabetic sand rats exposed to the hypercaloric diet. The postprandial glycemia remained fairly stable in the control animals. During a 3-week transition period from a purely vegetal to a hypercaloric diet, the post-prandial glycemia increased by 5.95 ± 1.26 mM (n=6) in diabetic sand rats, as distinct from an increase of only 0.45 ± 0.56 mM (n=6) in the non-diabetic animals. During the intermittent fasting period, the postprandial glycemia decreased significantly in the diabetic animals, but not so in the non-diabetic sand rats. Before the switch in food intake, the peak glycemia at the 30th min of an intraperitoneal glucose tolerance test was already higher in the diabetic than non-diabetic rats. In both the non-diabetic and diabetic sand rats, intermittent fasting prevented the progressive deterioration of glucose tolerance otherwise observed in non-fasting animals. These findings reveal that, at least in sand rats, intermittent daily fasting prevents the progressive deterioration of glucose tolerance otherwise taking place when these animals are exposed to a hypercaloric diet. PMID:20878099

  8. Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin.

    PubMed

    Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Sahin, Nurhan; Kucuk, Osman; Ozercan, Ibrahim H; Juturu, Vijaya; Komorowski, James R

    2013-07-28

    The objective of the present study was to evaluate anti-diabetic effects of chromium picolinate (CrPic) and biotin supplementations in type 2 diabetic rats. The type 2 diabetic rat model was induced by high-fat diet (HFD) and low-dose streptozotocin. The rats were divided into five groups as follows: (1) non-diabetic rats fed a regular diet; (2) diabetic rats fed a HFD; (3) diabetic rats fed a HFD and supplemented with CrPic (80 ?g/kg body weight (BW) per d); (4) diabetic rats fed a HFD and supplemented with biotin (300 ?g/kg BW per d); (5) diabetic rats fed a HFD and supplemented with both CrPic and biotin. Circulating glucose, cortisol, total cholesterol, TAG, NEFA and malondialdehyde concentrations decreased (P< 0·05), but serum insulin concentrations increased (P< 0·05) in diabetic rats treated with biotin and CrPic, particularly with a combination of the supplements. Feeding a HFD to diabetic rats decreased PPAR-? expression in adipose tissue and phosphorylated insulin receptor substrate 1 (p-IRS-1) expression of liver, kidney and muscle tissues, while the supplements increased (P< 0·001) PPAR-? and p-IRS-1 expressions in relevant tissues. Expression of NF-?B in the liver and kidney was greater in diabetic rats fed a HFD, as compared with rats fed a regular diet (P< 0·01). The supplements decreased the expression of NF-?B in diabetic rats (P< 0·05). Results of the present study revealed that supplementing CrPic and biotin alone or in a combination exerts anti-diabetic activities, probably through modulation of PPAR-?, IRS-1 and NF-?B proteins. PMID:23211098

  9. Aberrant Pregnancy Adaptations in the Peripheral Immune Response in Type 1 Diabetes: A Rat Model

    PubMed Central

    Groen, Bart; Links, Thera P.; Lefrandt, Joop D.; van den Berg, Paul P.; de Vos, Paul; Faas, Marijke M.

    2013-01-01

    Introduction Despite tight glycemic control, pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy. Other etiological factors may be responsible for the development of adverse pregnancy outcome. Acceptance of the semi-allogeneic fetus is accompanied by adaptations in the maternal immune-response. Maladaptations of the immune-response has been shown to contribute to pregnancy complications. We hypothesized that type 1 diabetes, as an autoimmune disease, may be associated with maladaptations of the immune-response to pregnancy, possibly resulting in pregnancy complications. Methods We studied pregnancy outcome and pregnancy-induced immunological adaptations in a normoglycemic rat-model of type 1 diabetes, i.e. biobreeding diabetes-prone rats (BBDP; 5 non-pregnant rats, 7 pregnant day 10 rats and 6 pregnant day 18 rats) , versus non-diabetic control rats (i.e. congenic non-diabetic biobreeding diabetes-resistant (BBDR; 6 non-pregnant rats, 6 pregnant day 10 rats and 6 pregnant day 18 rats) and Wistar-rats (6 non-pregnant, 6 pregnant day 10 rats and 5 pregnant day 18 rats)). Results We observed reduced litter size, lower fetal weight of viable fetuses and increased numbers of resorptions versus control rats. These complications are accompanied by various differences in the immune-response between BBDP and control rats in both pregnant and non-pregnant animals. The immune-response in non-pregnant BBDP-rats was characterized by decreased percentages of lymphocytes, increased percentages of effector T-cells, regulatory T-cells and natural killer cells, an increased Th1/Th2-ratio and activated monocytes versus Wistar and BBDR-rats. Furthermore, pregnancy-induced adaptations in BBDP-rats coincided with an increased Th1/Th2-ratio, a decreased mean fluorescence intensity CD161a/NKR-P1b ratio and no further activation of monocytes versus non-diabetic control rats. Conclusion This study suggests that even in the face of strict normoglycemia, pregnancy complications still occur in type 1 diabetic pregnancies. This adverse pregnancy outcome may be related to the aberrant immunological adaptations to pregnancy in diabetic rats. PMID:23805184

  10. Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats

    PubMed Central

    Radhika, P.; Annapurna, A.; Rao, S. Nageswara

    2012-01-01

    Background & objectives: A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Methods: Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. Results: A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. Interpretation & conclusions: The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats. PMID:22771592

  11. Use of unripe plantain (Musa paradisiaca) in the management of diabetes and hepatic dysfunction in streptozotocin induced diabetes in rats

    PubMed Central

    Okafor, Polycarp

    2015-01-01

    Aim This study aims to investigate the effect of unripe plantain (Musa paradisiaca) on markers of hepatic dysfunction in streptozotocin induced diabetic rats. Methods Blood glucose; relative liver weight (RLW); relative kidney weight (RKW); relative heart weight (RHW); relative pancreatic weight (RPW); serum and hepatic serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP); serum amylase, lipase, total, and conjugated bilirubin; and chemical analysis of the test feed were determined using standard techniques. Results The diabetic rats had significant alteration (P < 0.05) of blood glucose; RLW; RKW; RPW; serum and hepatic AST, ALT, and ALP; serum total and conjugated bilirubin; and serum lipase activities compared with nondiabetic while these parameters were significantly improved (P < 0.05) in the rats fed unripe plantain. There were no significant differences (P > 0.05) in the RHW of the rats in the three groups, as well as significant decreases (P < 0.05) in the amylase levels of the diabetic rats compared with the nondiabetic, but there was nonsignificant increase (P > 0.05) in the amylase levels of the rats fed unripe plantain compared with the nondiabetic rats. The test and standard rat feeds contained considerable amount of proteins, carbohydrates, fats, phenols, and crude fiber. Conclusion Amelioration of acute pancreatitis by unripe plantain could play a key role in its management of diabetes and related complications.

  12. Irbesartan ameliorates diabetic cardiomyopathy by regulating protein kinase D and ER stress activation in a type 2 diabetes rat model.

    PubMed

    Liu, Xiangjuan; Xu, Qun; Wang, Xiaomeng; Zhao, Zhuo; Zhang, Liping; Zhong, Ling; Li, Li; Kang, Weiqiang; Zhang, Yun; Ge, Zhiming

    2015-03-01

    Recent studies demonstrate an important role of protein kinase D (PKD) in the cardiovascular system. However, the potential role of PKD in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. Irbesartan has beneficial effects against diabetes-induced heart damage, while the mechanisms were still poorly understood. Our present study was designed to investigate the effects of irbesartan in DCM and whether the cardioprotective effects of irbesartan were mediated by PKD and endoplasmic reticulum (ER) stress. We induced the type 2 diabetic rat model by high fat diet and low dose streptozotocin injection. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. 8-weeks administration of irbesartan (15, 30 and 45mg/kg/day) was used to evaluate the effect irbesartan in DCM. Diabetic rats revealed severe metabolic abnormalities, left ventricular dysfunction, myocardial fibrosis and apoptosis. PKD and ER stress were excessive activated in the myocardium of diabetic rats. Furthermore, cardiac fibrosis, apoptosis, diastolic dysfunction and ER stress were all significantly related to PKD activation in diabetic rats. Irbesartan treatment attenuated the activation of PKD and ER stress, which paralleled its cardioprotective effects. Our study suggests that irbesartan could ameliorate cardiac remodeling and dysfunction in type 2 diabetes, and these beneficial effects were associated with its ability to suppress the activation of PKD and ER stress. PMID:25617729

  13. Intense exercise training induces adaptation in expression and responsiveness of cardiac ?-adrenoceptors in diabetic rats

    PubMed Central

    2010-01-01

    Background Informations about the effects of intense exercise training on diabetes-induced myocardial dysfunctions are lacking. We have examined the effects of intense exercise training on the cardiac function of diabetic rats, especially focusing on the Langendorff ?-adrenergic responsiveness and on the ?-adrenoceptors protein expression. Methods Control or Streptozotocin induced-diabetic male Wistar rats were randomly assigned to sedentary or trained groups. The training program consisted of 8 weeks running on a treadmill (10° incline, up to 25 m/min, 60 min/day) and was considered to be intense for diabetic rats. Results This intense exercise training amplified the in vivo diabetes-induced bradycardia. It had no effect on Langendorff basal cardiac contraction and relaxation performances in control and diabetic rats. In diabetic rats, it accentuated the Langendorff reduced responsiveness to ?-adrenergic stimulation. It did not blunt the diabetes-induced decrease of ?1-adrenoceptors protein expression, displayed a significant decrease in the ?2-adrenoceptors protein expression and normalized the ?3-adrenoceptors protein expression. Conclusions Intense exercise training accentuated the decrease in the myocardial responsiveness to ?-adrenergic stimulation induced by diabetes. This defect stems principally from the ?2-adrenoceptors protein expression reduction. Thus, these results demonstrate that intense exercise training induces specific effects on the ?-adrenergic system in diabetes. PMID:21054861

  14. Antihyperglycaemic and anti-oxidant properties of Anoectochilus formosanus in diabetic rats.

    PubMed

    Shih, Chun-Ching; Wu, Yueh-Wern; Lin, Wen-Chuan

    2002-08-01

    1. In the present study, we investigated aqueous extracts of Anoectochilus formosanus (AFE) for antihyperglycaemic and anti-oxidant effects in diabetic rats induced by streptozotocin (STZ). 2. Diabetic rats were randomly divided into groups and treated orally by gavage with vehicle (distilled water) or AFE (1 and 2 g/kg), once a day for 21 days. 3. At the end of the 21 day period, AFE (2 g/kg) significantly reduced fasting blood glucose, serum fructosamine, triglycerides and total cholesterol compared with vehicle-treated diabetic rats. In vehicle-treated diabetic rats, levels of renal lipid peroxidation were increased, whereas glutathione concentrations were not affected. Renal lipid peroxidation levels were significantly lower and renal reduced glutathione (GSH) concentrations were significantly higher in AFE-treated diabetic rats compared with vehicle-treated diabetic rats. The diabetic kidney in the vehicle-treated group showed a decrease in catalase, but the activity of glutathione peroxidase (GSH-Px) was increased. 4. The activity of catalase, but not GSH-Px, was significantly reversed by AFE treatment. These results indicate that AFE (1 and 2 g/kg) not only possesses an antihyperglycemic effect, but that it may also reduce oxidative stress in diabetic rats. PMID:12100000

  15. An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer

    PubMed Central

    Daburkar, Mohan; Lohar, Vikram; Rathore, Arvind Singh; Bhutada, Pravin; Tangadpaliwar, Shrikant

    2014-01-01

    Aim: To examine the preventive effect of Aloe vera gel ethanolic extract using diabetic foot ulcer (DFUs) protocol in Wistar rats. Materials and Methods: Male Wistar rats were divided into untreated control (Group I), untreated DFUs (Group II), DFUs treated with A. vera gel ethanolic extract (Group III), DFUs treated with topical A. vera gel (Group IV), DFUs treated with A. vera gel ethanolic extract and topical A. vera gel (Group V). The rats in the treatment groups were daily administered the A. vera gel and ethanolic extract for 9 days. Fasting blood glucose levels and percentage of wound ulcer contraction were measured on day 3, 6, and 9. Statistical Analysis used: The results are expressed as a mean ± Standard Error Mean (SEM). Data were analyzed using one-way analysis of variance (ANOVA) after Newman–Keuls test. P < 0.05 were considered statistically significant in all cases. Results: Oral administration of A. vera gel ethanolic extract at a dose of 300 mg/kg body weight per day to diabetic rats for a period of 9 days resulted in a significant reduction in fasting blood glucose and a significant improvement in plasma insulin. Topical application of A. vera gel at a dose 30 mg/kg body weight per day to streptozotocin (STZ)-induced diabetic rats for a period of 9 days resulted in no change in blood glucose and plasma insulin. Oral administration as well as topical application of A. vera gel ethanolic extract and gel significantly reduced the blood glucose, improved the plasma insulin, and significantly increased DNA and glycosaminoglycans (GAGs) to improve the wound ulcer healing as well as the breaking strength on day 9. Conclusions: Present findings provide a scientific rationale for the use of A. vera gel ethanolic extract, and showed that the gel attenuated the diabetic foot wound in rats. PMID:25035641

  16. Long-term type 1 diabetes enhances in-stent restenosis after aortic stenting in diabetes-prone BB rats.

    PubMed

    Onuta, Geanina; Groenewegen, Hendrik C; Klatter, Flip A; Walther Boer, Mark; Goris, Maaike; van Goor, Harry; Roks, Anton J M; Rozing, Jan; de Smet, Bart J G L; Hillebrands, Jan-Luuk

    2011-01-01

    Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long-term autoimmune diabetes on development of in-stent restenosis. We here describe the development of in-stent restenosis in long-term (~7 months) spontaneously diabetic and age-matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP) rats (n = 6-7 in each group). Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA(1c) levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long-term diabetic rats compared with nondiabetic controls. In conclusion, long-term autoimmune diabetes in BBDP rats enhances in-stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes-enhanced in-stent restenosis as well as to test new therapeutic modalities. PMID:21331346

  17. Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.

    PubMed

    Sathya, S; Kokilavani, R; Gurusamy, K

    2008-10-01

    The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level. PMID:22557305

  18. Wound healing activity of Malva sylvestris and Punica granatum in alloxan-induced diabetic rats.

    PubMed

    Pirbalouti, Abdollah Ghasemi; Azizi, Shahrzad; Koohpayeh, Abed; Hamedi, Behzad

    2010-01-01

    The flowers of Malva sylvestris Linn. (Malvaceae) and Punica granatum Linn. (Punicaceae) are important medicinal plants in Iranian traditional medicine (Unani) whose have been used as remedy against edema, bum, wound and for their carminative, antimicrobial and anti-inflammatory activities. The diethyl ether extract of M. sylvestris and P. granatum flowers were used to evaluate the wound healing activity at 200 mg/kg/day dose in alloxan-induced diabetic rats. Wounds were induced in Wister rats divided into six groups as following; Group I, normal rats were treated with simple ointment base. Group II, diabetic rats were treated with simple ointment base (control). Groups III and IV, diabetic rats were treated with simple ointment base containing of extracts (diabetic animals), Groups V, diabetic rats were treated with simple ointment base containing of mixed extracts (1:1), Group VI, diabetic rats received the standard drug (nitrofurazone). The efficacy of treatment was evaluated based on wound area relative and histopathological characteristics. The extract-treated diabetic animals showed significant reduction in the wound area when compared with control. Also, histological studies of the tissue obtained on days 9th and 18th from the extract-treated by extract of M. sylvestris showed increased well organized bands of collagen, more fibroblasts and few inflammatory cells. These findings demonstrate that extract of M. sylvestis effectively stimulates wound contraction as compared to control group and other groups. M. sylvestris accelerated wound healing in rats and thus supports its traditional use. PMID:20873419

  19. Preventive effects of Prangos ferulacea (L.) Lindle on liver damage of diabetic rats induced by alloxan

    PubMed Central

    Farokhi, Farah; Kaffash Farkhad, Najme; Togmechi, Amir; Soltani band, Khosro

    2012-01-01

    Objectives: Diabetes mellitus is associated with biochemical, physiological and pathological alterations in the liver. The aim of this study was to investigate the effects of hydroalcoholic extract of Prangos ferulacea (L.) Lindle (P.f) on changes in rats´ liver structure and serum activities of alanin and aspartate aminotransferases after alloxan injection. Materials and Methods: In this study, forty female Wistar rats with body weight of 200±20 g were randomly divided into 5 groups with 8 rats per group. Diabetes was induced in rats by alloxan monohydrate at dose of 120 mg/kg body weight (BW) injected intraperitoneally. Root and leaves with stems hydroalcoholic extract of P.f at dose of 100