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1

Ameliorative potential of S-allyl cysteine on oxidative stress in STZ induced diabetic rats.  

PubMed

Increased oxidative stress and impaired antioxidant defense mechanism are important factors in the pathogenesis and progression of diabetes mellitus and other oxidant-related diseases. The present study was undertaken to evaluate the possible protective effects of S-allyl cysteine (SAC) against oxidative stress in streptozotocin (STZ) induced diabetic rats. SAC was administered orally for 45 days to control and STZ induced diabetic rats. The effects of SAC on glucose, plasma insulin, thiobarbituric acid reactive substances (TBARS), hydroperoxide, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG ratio were studied. The levels of glucose, TBARS, hydroperoxide, and GSSG were increased significantly whereas the levels of plasma insulin, reduced glutathione, GSH/GSSG ratio, superoxide dismutase, catalase and GPx were decreased in STZ induced diabetic rats. Administration of SAC to diabetic rats showed a decrease in plasma glucose, TBARS, hydroperoxide and GSSG. In addition, the levels of plasma insulin, superoxide dismutase, catalase, GPx and reduced glutathione (GSH) were increased in SAC treated diabetic rats. The above findings were supported by histological observations of the liver and kidney. The antioxidant effect of SAC was compared with glyclazide, a well-known antioxidant and antihyperglycemic drug. The present study indicates that the SAC possesses a significant favorable effect on antioxidant defense system in addition to its antidiabetic effect. PMID:20951120

Saravanan, Ganapathy; Ponmurugan, Ponnusamy

2010-10-14

2

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

PubMed

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

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

2012-07-12

3

Effects of STZ-induced diabetes and its treatment with vanadyl sulphate on cyclosporine A-induced nephrotoxicity in rats  

Microsoft Academic Search

The aim of this study was to analyze the effect of streptozotocin (STZ)-induced diabetic state and the insulin-like acting, vanadyl sulphate (VS) on cyclosporine A (CyA) related nephrotoxicity in rats. Male Wistar rats were divided into six groups, of 12 animals each: The control, diabetic rats and diabetic rats whose drinking VS in the drinking water in a concentration of

Sherif Y. Saad; Tawfeeg A. O. Najjar

2005-01-01

4

Effect of Rebaudioside A, a diterpenoid on glucose homeostasis in STZ-induced diabetic rats.  

PubMed

Rebaudioside A (Reb A), a major constituent of Stevia rebaudiana, was recently proposed as an insulinotropic agent. The aim of this investigation was to evaluate the antihyperglycemic effect of Reb A on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male Albino Wistar rats, weighing 180-200 g, by a single intraperitoneal injection at a dose of STZ (40 mg/kg body weight). Diabetic rats showed significant (P<0.05) increase in the levels of plasma glucose and glycosylated hemoglobin and significant (P<0.05) decrease in the levels of plasma insulin and hemoglobin. Activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly (P<0.05) increased while hexokinase and glucose-6-phosphate dehydrogenase were significantly (P<0.05) decreased in the liver along with glycogen. Oral treatment with Reb A to diabetic rats significantly (P<0.05) decreased blood glucose and reversed these hepatic carbohydrate metabolizing enzymes in a significant manner. Histopathology changes of pancreas confirmed the protective effects of Reb A in diabetic rats. Thus, the results show that Reb A possesses an antihyperglycemic activity and provide evidence for its traditional usage in the control of diabetes. PMID:22374587

Saravanan, Ramalingam; Vengatash babu, Kaliyappan; Ramachandran, Vinayagam

2012-02-29

5

Combined inhibition of aromatase activity and dihydrotestosterone supplementation attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats.  

PubMed

Our previous studies showed that streptozotocin (STZ)-induced diabetic male rats have increased estradiol and decreased testosterone levels that correlate with renal injury (Xu Q, Wells CC, Garman GH, Asico L, Escano CS, Maric C. Hypertension 51: 1218-1224, 2008). We further showed that either supplementing dihydrotestosterone (DHT) or inhibiting estradiol biosynthesis in these diabetic rats was only partially renoprotective (Manigrasso MB, Sawyer RT, Marbury DC, Flynn ER, Maric C. Am J Physiol Renal Physiol 301: F634-F640, 2011; Xu Q, Prabhu A, Xu S, Manigrassso MB, Maric C. Am J Physiol 297: F307-F315, 2009). The aim of this study was to test the hypothesis that the combined therapy of DHT supplementation and inhibition of estradiol synthesis would afford better renoprotection than either treatment alone. The study was performed in 12-wk-old male nondiabetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic rats that received the combined therapy of 0.75 mg/day of DHT along with 0.15 mg · kg(-1) · day(-1) of an aromatase inhibitor, anastrozole (Dta), for 12 wk. Treatment with the combined therapy resulted in attenuation of albuminuria by 84%, glomerulosclerosis by 55%, and tubulointerstitial fibrosis by 62%. In addition, the combined treatment decreased the density of renal cortical CD68-positive cells by 70% and decreased protein expression of transforming growth factor-? protein expression by 60%, collagen type IV by 65%, TNF-? by 55%, and IL-6 by 60%. We conclude that the combined treatment of DHT and blocking aromatase activity in diabetic male STZ-induced diabetic rats provides superior treatment than either treatment alone in the prevention of diabetic renal disease. PMID:22301628

Manigrasso, Michaele B; Sawyer, R Taylor; Hutchens, Zachary M; Flynn, Elizabeth R; Maric-Bilkan, Christine

2012-02-01

6

Combined inhibition of aromatase activity and dihydrotestosterone supplementation attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats  

PubMed Central

Our previous studies showed that streptozotocin (STZ)-induced diabetic male rats have increased estradiol and decreased testosterone levels that correlate with renal injury (Xu Q, Wells CC, Garman GH, Asico L, Escano CS, Maric C. Hypertension 51: 1218–1224, 2008). We further showed that either supplementing dihydrotestosterone (DHT) or inhibiting estradiol biosynthesis in these diabetic rats was only partially renoprotective (Manigrasso MB, Sawyer RT, Marbury DC, Flynn ER, Maric C. Am J Physiol Renal Physiol 301: F634–F640, 2011; Xu Q, Prabhu A, Xu S, Manigrassso MB, Maric C. Am J Physiol 297: F307–F315, 2009). The aim of this study was to test the hypothesis that the combined therapy of DHT supplementation and inhibition of estradiol synthesis would afford better renoprotection than either treatment alone. The study was performed in 12-wk-old male nondiabetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic rats that received the combined therapy of 0.75 mg/day of DHT along with 0.15 mg·kg?1·day?1 of an aromatase inhibitor, anastrozole (Dta), for 12 wk. Treatment with the combined therapy resulted in attenuation of albuminuria by 84%, glomerulosclerosis by 55%, and tubulointerstitial fibrosis by 62%. In addition, the combined treatment decreased the density of renal cortical CD68-positive cells by 70% and decreased protein expression of transforming growth factor-? protein expression by 60%, collagen type IV by 65%, TNF-? by 55%, and IL-6 by 60%. We conclude that the combined treatment of DHT and blocking aromatase activity in diabetic male STZ-induced diabetic rats provides superior treatment than either treatment alone in the prevention of diabetic renal disease.

Manigrasso, Michaele B.; Sawyer, R. Taylor; Hutchens, Zachary M.; Flynn, Elizabeth R.

2012-01-01

7

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

PubMed Central

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.

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

8

Hypoglycemic Effects of Exo-biopolymers Produced by Five Different Medicinal Mushrooms in STZ-induced Diabetic Rats.  

PubMed

Hypoglycemic effects of exo-biopolymers (EBP) produced by submerged mycelial cultures of Coriolus versicolor, Cordyceps sinensis, Paecilomyces japonica, Armillariella mellea, and Fomes fomentarius were investigated in streptozotocin (STZ)-induced diabetic rats. The rats from each experimental group were orally administered with EBPs (100 mg/kg BW) daily for 2 weeks. Though the hypoglycemic effect was achieved in all the cases, however, C. versicolor EBP proved as the most potent one. The administration of the C. versicolor EBP substantially reduced (29.9%) the plasma glucose level as compared to the saline administered group (control). It also reduced the plasma total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST) and, alanine aminotransferase (ALT) levels by 9.22, 23.83, 16.93, and 27.31%, respectively. The sugar and amino acid compositions of this EBP were also analyzed in detail. PMID:23997607

Yang, Byung-Keun; Kim, Guk-Nam; Jeong, Yong-Tae; Jeong, Hun; Mehta, Pradeep; Song, Chi-Hyun

2008-03-31

9

Hypoglycemic Effects of Exo-biopolymers Produced by Five Different Medicinal Mushrooms in STZ-induced Diabetic Rats  

PubMed Central

Hypoglycemic effects of exo-biopolymers (EBP) produced by submerged mycelial cultures of Coriolus versicolor, Cordyceps sinensis, Paecilomyces japonica, Armillariella mellea, and Fomes fomentarius were investigated in streptozotocin (STZ)-induced diabetic rats. The rats from each experimental group were orally administered with EBPs (100 mg/kg BW) daily for 2 weeks. Though the hypoglycemic effect was achieved in all the cases, however, C. versicolor EBP proved as the most potent one. The administration of the C. versicolor EBP substantially reduced (29.9%) the plasma glucose level as compared to the saline administered group (control). It also reduced the plasma total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST) and, alanine aminotransferase (ALT) levels by 9.22, 23.83, 16.93, and 27.31%, respectively. The sugar and amino acid compositions of this EBP were also analyzed in detail.

Yang, Byung-Keun; Kim, Guk-Nam; Jeong, Yong-Tae; Jeong, Hun; Mehta, Pradeep

2008-01-01

10

Dose-dependent effect in the inhibition of oxidative stress and anticlastogenic potential of ginger in STZ induced diabetic rats.  

PubMed

Ginger is an important medicinal herb has numerous bioactive components and is used in the management, control and/or treatment of diseases including diabetes mellitus. The present study was undertaken to see the dose-response effect of ginger and evaluate the possible protective effects of dietary ginger on oxidative stress and genotoxicity induced by streptozotocin (STZ) diabetic rats. Inbred male Wistar/NIN rats of 8-9 weeks old were treated with 30 mg/kg of STZ. Rats were divided into different groups of control, diabetic non-treated, and diabetic treated with ginger powder at 0.5%, 1% and 5% respectively. After feeding for a month, blood and tissues were collected to see the effect of ginger on antioxidant status, DNA damage and bone marrow genotoxicity. In this study ginger exerted a protective effect against STZ-induced diabetes by modulating antioxidant enzymes and glutathione and down regulating lipid and protein oxidation and inhibition in genotoxicity in a dose-response manner. PMID:22980896

Kota, Nirmala; Panpatil, Virendra Vasant; Kaleb, Rajakumar; Varanasi, Bhaskar; Polasa, Kalpagam

2012-07-14

11

Beneficial effects of Momordica charantia seeds in the treatment of STZ-induced diabetes in experimental rats.  

PubMed

The aim of the present study was to evaluate the effect of the aqueous extract of seeds of two varieties, namely a country and hybrid variety of Momordica charantia (MCSEt1 and MCSEt2) on oxidative stress in plasma and pancreas of streptozotocin (STZ) induced diabetic rats. Oral administration of each of the seed extracts at a dosage of 150 mg/kg body weight for 30 d resulted in a significant reduction in plasma glucose, thiobarbituric acid-reactive substances, lipid-hydroperoxides, alpha-tocopherol and significant improvement in ascorbic acid, reduced glutathione and insulin. The treatment also resulted in a significant reduction in thiobarbituric acid reactive substances, lipid-hydroperoxides, superoxide dismutase, catalase, glutathione peroxidase and significant improvement in reduced glutathione in pancreas of drug treated diabetic rats when compared to the untreated diabetic rats. On the basis of results obtained, it may be concluded that the treatment of Momordica charantia seed varieties may effectively normalize the impaired oxidative stress in streptozotocin induced-diabetes than the glibenclamide treated groups. PMID:15930730

Sathishsekar, Dhanasekar; Subramanian, Sorimuthu

2005-06-01

12

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

SciTech Connect

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.

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

1986-03-01

13

[The changes of TSP-1 expression in the retina of STZ-induced rat diabetic mellitus model with pioglitazone].  

PubMed

To observe the changes of TSP-1 expression in the retina of STZ-induced rat diabetic mellitus model with pioglitazone and to elucidate the possible mechanism involved and the effects of thiazolidinediones compound pioglitazone on the early stages of diabetic retinopathy. 30 Male SD rats were randomly divided into 3 groups: control group, DM group and pioglitazone treated DM group (DP group). DM group and pioglitazone treated DM group were injected with STZ intraperitoneally. 8 weeks after the onset of diabetes, the expression of TSPI mRNA was quantified in retinal tissue by quantitative reverse transcription-polymerase chain reaction (RT-PCR) respectively. The locations of TSP-1 in three groups were also established by immunohistochemistry. 8 weeks after the onset of diabetes, every layer of the retina tissue had significant TSP-1 positive staining and when compared with the control group and DM group, the pioglitazone treated DM group had higher TSP-1 positive cell number per unit area; There were significant differences among the DM group, pioglitazone treated DM group and control group in TSP-1 mRNA level, DM group and pioglitazone treated DM group had significantly higher TSP-1 mRNA level than the control group. Our results showed that pioglitazone treatment can alleviate the pathological changes of DR and the expression level of TSP-1 was increased in pioglitazone treated DM rats compared with other DM rats. Our study suggests pioglitazone may have a role on early stage of DR by increased TSP-1 expression. PMID:17966456

Zhang, Hui Yan; Wang, Jian Yong; Zhang, Xiao Ming; Shen, Fang

2007-08-01

14

Synergic effects of bitter melon and ?-Glucan composition on STZ-induced rat diabetes and its complications.  

PubMed

?-Glucan purified from oats (OG) and bitter melon, Momordica charantia Linn (MC), water extracts have shown favorable effects on diabetes and its complications. We investigated to find out the optimal composition showing hypoglycemic and antidiabetic complication effects in variable compositions (OG:MC = 1:1, 1:2, 1:4, 1:6, 1:8, 1:10, 2:1, 4:1, 6:1, 8:1, 10:1). Extracts were administered orally once a day for 28 days following 7 days post streptozotocin (STZ) dosing. Five rats per group (total 15 groups; Intact, STZ, OG, MC, and the variable composition groups) were selected according to the blood glucose and body weight at 6 days after STZ dosing. After 28 days of extracts dosing, the changes on the body weight, liver and kidney weight, blood glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), low-density lipoprotein (LDL), and total-cholesterol levels were observed. As the result of STZ-induced diabetes, decreases of body weight, increases of the liver and kidney weights, blood glucose, BUN, creatinine, AST, ALT, LDL, and total-cholesterol levels in STZ control were detected compared with intact control. However, these changes of hyperglycemia, diabetic nephropathy, hepatopathy, and hyperlipemia were dramatically decreased in the OG and MC single-dosing group, and all composition groups. In addition, there were more favorable effects in all composition groups compared with the OG and MC single-dosing groups. Among variable compositions, the OG:MC 1:2 mixed group showed the most synergic effects in this study. PMID:22297232

Kim, Joo-Wan; Cho, Hyung-Rae; Moon, Seung-Bae; Kim, Ki-Young; Ku, Saekwang

2012-01-01

15

Effect of Curcuma longa freeze dried rhizome powder with milk in STZ induced diabetic rats  

Microsoft Academic Search

This study deals with the effects of freeze dried rhizome powder of Curcuma longa (C. longa) dissolved in milk on normal as\\u000a well as diabetic models. Diabetes of type II and type I was within 3 days of a single administration of doses of 45 and 65\\u000a mg kg?1 of streptozotocin respectively. Various parameters such as blood glucose levels, triglycerides,

P. K. Rai; D. Jaiswal; S. Mehta; D. K. Rai; B. Sharma; Geeta Watal

2010-01-01

16

Effect of Curcuma longa freeze dried rhizome powder with milk in STZ induced diabetic rats.  

PubMed

This study deals with the effects of freeze dried rhizome powder of Curcuma longa (C. longa) dissolved in milk on normal as well as diabetic models. Diabetes of type II and type I was within 3 days of a single administration of doses of 45 and 65 mg kg(-1) of streptozotocin respectively. Various parameters such as blood glucose levels, triglycerides, total cholesterol, high density lipoprotein, very low density lipoprotein, low density lipoprotein, serum glutamic oxaloacetic transaminase, serum glutamic pyruvate transaminase, alkaline phosphatase, creatinine, hemoglobin, urine protein and urine sugar in addition to body weight were taken in to consideration and were analyzed after administration of variable doses of rhizome powder. The dose of 200 mg kg(-1) was identified as the most effective dose as it increased HDL, Hb and bw (P<0.05) with significant decrease in the levels of blood glucose, lipid profile and hepatoprotective enzymes (P<0.001). PMID:23105906

Rai, P K; Jaiswal, D; Mehta, S; Rai, D K; Sharma, B; Watal, Geeta

2010-05-27

17

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

PubMed

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

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

2013-05-21

18

Effects of long-term high-fiber diet on macrovascular changes and lipid and glucose levels in STZ-induced diabetic SD rats.  

PubMed

The effects of long-term high-fiber diet on lipid and glucose levels and the histological changes in the coronary arteries and thoracic aorta in STZ-induced diabetic SD rats were investigated. During the first 4 weeks of the study period, all diabetic rats were given regular chow plus water after which, all were grouped according to the following diet regimen: group II, no added cholesterol and glucomannan; group III, no added cholesterol but with glucomannan supplement, group IV, with added cholesterol but no glucomannan supplement; and group V, with both cholesterol and glucomannan supplements. 15% weight of glucomannan and 1.5% weight of cholesterol in regular rat chow were used as supplements when indicated. Non-diabetic rats which received only regular chow served as the control group (group I). In the 18th week all rats were sacrificed and weight gain, glucose, total cholesterol, HDL-cholesterol, triglyceride and lipid peroxidase concentrations were determined. Selected portions of the heart and thoracic aorta were histologically examined. Weight gain was higher in rats supplemented with glucomannan than in those without glucomannan supplements, but the difference is not significant. A lowering tendency in glucose levels was likewise observed. Furthermore, total cholesterol and HDL-cholesterol levels were lower and higher, respectively in diabetic rats receiving glucomannan. Although the triglyceride levels were similar in all rats, lipid peroxidase levels were significantly lower in rats with high-fiber diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1659979

Yoshida, M; Sawa, J; Hozumi, T; Mimoto, H; Ishida, Y; Kazumi, T; Doi, K; Baba, S

1991-09-01

19

Effect of samh seeds supplementation (Mesembryanthemum forsskalei Hochst) on liver enzymes and lipid profiles of streptozotocin (STZ)-induced diabetic Wistar rats  

PubMed Central

Thirty streptozotocin (STZ)-induced diabetic of Wistar Albino rats were divided into five groups. The rat groups received different food (natural diet or high fat content diet) supplemented with 10% or 15% of samh seeds for 6 weeks. At the end of the study, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phophatase (ALP) and lactate dehydrogenase (LDH) enzymes have been measured in diabetic rats liver. In addition, liver lipid profile (total cholesterol (TC), triglyceride (TAG), lipid peroxide production malondialdehyde (MDA)) and reduced glutathione (GSH) in have been measured in diabetic rats liver, and the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were also determined. The samh seeds diet supplemented with cholesterol significantly increase (P < 0.05) the levels of liver peroxide production MDA, TC and TG in diabetic rats comparing to the samh diet not supplemented with the cholesterol. However, the samh seeds significantly decrease (P < 0.05) the level of GSH. These data suggest that the samh seeds diet not supplemented with the cholesterol regulated C and TG metabolism and decrease the lipid peroxidation in the diabetic rats.

Al-Faris, Nora A.; Al-sawadi, Ali D.; Alokail, Majed S.

2009-01-01

20

Effect of samh seeds supplementation (Mesembryanthemum forsskalei Hochst) on liver enzymes and lipid profiles of streptozotocin (STZ)-induced diabetic Wistar rats.  

PubMed

Thirty streptozotocin (STZ)-induced diabetic of Wistar Albino rats were divided into five groups. The rat groups received different food (natural diet or high fat content diet) supplemented with 10% or 15% of samh seeds for 6 weeks. At the end of the study, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phophatase (ALP) and lactate dehydrogenase (LDH) enzymes have been measured in diabetic rats liver. In addition, liver lipid profile (total cholesterol (TC), triglyceride (TAG), lipid peroxide production malondialdehyde (MDA)) and reduced glutathione (GSH) in have been measured in diabetic rats liver, and the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were also determined. The samh seeds diet supplemented with cholesterol significantly increase (P < 0.05) the levels of liver peroxide production MDA, TC and TG in diabetic rats comparing to the samh diet not supplemented with the cholesterol. However, the samh seeds significantly decrease (P < 0.05) the level of GSH. These data suggest that the samh seeds diet not supplemented with the cholesterol regulated C and TG metabolism and decrease the lipid peroxidation in the diabetic rats. PMID:23961054

Al-Faris, Nora A; Al-Sawadi, Ali D; Alokail, Majed S

2010-01-01

21

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

PubMed

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

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

2013-05-15

22

Effect of VIVO(dipic-Cl)(H2O)2 on Lipid Metabolism Disorders in the Liver of STZ-Induced Diabetic Rats  

PubMed Central

Vanadium complexes are potent antidiabetic agents for therapeutical treatment of diabetes. In the present study, we investigated the hypolipidemic effect of VIVO(dipic-Cl)(H2O)2 (V4dipic-Cl) in liver of streptozotocin- (STZ-)-induced diabetic rats. We found that diabetic animals exhibited hepatic inflammatory infiltration and impaired liver function along with triglyceride (TG) accumulation in the liver. V4dipic-Cl treatment not only ameliorated liver pathological state but also reduced hepatic TG level. Moreover, the upregulation of fatty acid translocase (FAT/CD36) mRNA (4.0-fold) and protein (8.2-fold) levels in the liver of diabetic rats were significantly reversed after V4dipic-Cl treatment. However, no significant effects of V4dipic-Cl on the mRNA expression of fatty acid metabolism-related fatty acid bounding protein 1 (FABP1) and fatty acid transporter 5 (FATP5) were observed. These results suggest that the modification of lipid metabolism-related FAT/CD36 in the liver of diabetic rats is likely involved in the hypolipidemic effects of V4dipic-Cl.

Xie, Mingxia; Chen, Deliang; Li, Jian; Ding, Wenjun

2013-01-01

23

Effect of V(IV)O(dipic-Cl)(H2O)2 on Lipid Metabolism Disorders in the Liver of STZ-Induced Diabetic Rats.  

PubMed

Vanadium complexes are potent antidiabetic agents for therapeutical treatment of diabetes. In the present study, we investigated the hypolipidemic effect of V(IV)O(dipic-Cl)(H2O)2 (V4dipic-Cl) in liver of streptozotocin- (STZ-)-induced diabetic rats. We found that diabetic animals exhibited hepatic inflammatory infiltration and impaired liver function along with triglyceride (TG) accumulation in the liver. V4dipic-Cl treatment not only ameliorated liver pathological state but also reduced hepatic TG level. Moreover, the upregulation of fatty acid translocase (FAT/CD36) mRNA (4.0-fold) and protein (8.2-fold) levels in the liver of diabetic rats were significantly reversed after V4dipic-Cl treatment. However, no significant effects of V4dipic-Cl on the mRNA expression of fatty acid metabolism-related fatty acid bounding protein 1 (FABP1) and fatty acid transporter 5 (FATP5) were observed. These results suggest that the modification of lipid metabolism-related FAT/CD36 in the liver of diabetic rats is likely involved in the hypolipidemic effects of V4dipic-Cl. PMID:23691525

Liu, Fang; Xie, Mingxia; Chen, Deliang; Li, Jian; Ding, Wenjun

2013-03-20

24

Telmisartan ameliorates germ cell toxicity in the STZ-induced diabetic rat: studies on possible molecular mechanisms.  

PubMed

Testicular damage is a common clinical problem in diabetic individuals that severely affects the quality of life. The present study investigates the possible protective mechanisms of telmisartan, an angiotensin II-receptor antagonist in the germ cell of diabetic rat. Male SD rats were used and randomized into six groups: control, telmisartan control, diabetic control and diabetic group treated with telmisartan at the doses of 3, 6 and 12mg/kg/day, per oral for 4 weeks. Diabetes was induced by injecting a single dose of streptozotocin (STZ), (55mg/kg) dissolved in ice-cold 10mM citrate buffer; pH 4.4 and administered i.p. immediately after preparation to the SD rats. At the end of the study, rats were sacrificed and the levels of nitrite, superoxide, malondialdehyde (MDA), glutathione (reduced and peroxidase) and superoxide dismutase (SOD) were measured. Germ cell toxicity was evaluated by using sperm count, sperm comet assay, histology of testes and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Further to confirm the oxidative and nitrosative damage, immunohistological quantification of 8-oxo-dG (8-oxo-7,8-dihydro-2'-deoxyguanosine) and 3-nitrotyrosine were evaluated respectively. Results showed that telmisartan significantly restored the levels of nitrite, superoxide, malondialdehyde, and glutathione and superoxide dismutase in diabetic testes. Further, telmisartan significantly increased the sperm counts, reduced apoptotic cell death, sperm DNA damage, oxidative and nitrosative damage in diabetic rat. Western blot analysis showed that telmisartan reduced the testicular inflammation and cell death by down-regulating the expression of NF-?B, IL-6, TNF-?, p-ERK1/2, iNOS, caspase-3 and increasing the PPAR-? expression. Results clearly indicate that telmisartan significantly reduced the both oxidative and nitrosative stress, inflammation and cell death in diabetic testes. The present results confirmed that telmisartan exhibited beneficial role in the germ cell of diabetic rat. PMID:23648321

Kushwaha, S; Jena, G B

2013-05-03

25

Sclerocarya birrea [(A. Rich.) Hochst.] [Anacardiaceae] stem-bark ethanolic extract (SBE) modulates blood glucose, glomerular filtration rate (GFR) and mean arterial blood pressure (MAP) of STZ-induced diabetic rats  

Microsoft Academic Search

Studies in our laboratories suggest that Sclerocarya birrea stem-bark ethanolic extract (SBE) has hypoglycemic properties. Accordingly, we investigated the effects of SBE on major complications of diabetes mellitus; blood glucose, renal function and mean arterial blood pressure (MAP) in non-diabetic and STZ-induced diabetic rats. Oral glucose tolerance test responses to various SBE doses (60, 120 and 240mgkg?1) were studied in

M. Gondwe; D. R. Kamadyaapa; M. Tufts; A. A. Chuturgoon; C. T. Musabayane

2008-01-01

26

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

Microsoft Academic Search

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.

Pitchai Daisy; James Eliza; Khanzan Abdul Majeed Mohamed Farook

2009-01-01

27

Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats.  

PubMed

We previously demonstrated that intracerebroventricular streptozotocin (STZ-icv) injection induced cognitive dysfunction and led to decreased expression levels of phospho-cyclic AMP responsive element binding protein (pCREB), Akt, and insulin degrading enzyme (IDE) and increased amyloid beta (Ab) deposition in the hippocampus. In the present study, we aimed to investigate whether treatment with an insulin analogue could prevent STZ-induced cognitive decline by reducing or eliminating these changes in the hippocampus. To test this hypothesis, we administrated a long-acting insulin analogue, detemir, into the third ventricle (3V) of STZ-treated rats and assessed cognitive outcomes using the Morris water maze (MWM), immunohistochemistry, and Golgi-Cox staining. Insulin injection successfully rescued STZ-induced cognitive decline, as evidenced by a marked elevation in learning ability. Detemir treatment also resulted in changes in hippocampal levels of IDE, insulin receptor (IR), Akt, somatostatin (SST), and Ab. The STZ-induced decrease of granule cell layer neurons was also recovered by detemir administration. These results provide evidence that 'brain diabetes' and Alzheimer-type dementia involve similar mechanisms and show that insulin may be a promising therapeutic agent to attenuate cognitive decline. PMID:23238038

Shingo, Akiko Sheala; Kanabayashi, Tomomichi; Kito, Shozo; Murase, Toshio

2012-12-10

28

Antihyperglycemic and Antihyperlipidemic effect of combined plant extract of Cassia auriculata and Aegle marmelos in streptozotocin (STZ) induced diabetic albino rats  

Microsoft Academic Search

Cassia auriculata and Aegle marmelos are used extensively in the indigenous system of medicine as an anti-diabetic agent. The current investigation focuses on the serum insulin augmentation, anti-hyperglycemic and anti-hyperlipidemic property of a combined aqueous extracts of C.auriculata and A.marmelos on streptozotocin induced diabetic rats. The diabetes induced animals were fed with plant extracts at the increasing dosage of 250mg,

A. Sivaraj; K. Devi; S. palani; P. Vinoth; B. Senthil; E. David

29

Effect of dipyrone and thalidomide alone and in combination on STZ-induced diabetic neuropathic pain.  

PubMed

Diabetic neuropathy is recognized as one of the most common complications of chronic diabetes, but its pathophysiological mechanism is complex and yet to be completely explored. Monotherapy with conventional analgesics fails to provide adequate pain relief in peripheral diabetic neuropathy. There are a number of evidence suggesting that tumor necrosis factor (TNF-?) plays an important role in the pathogenesis of peripheral diabetic neuropathy. TNF-? up-regulation activates nuclear factor ?B, which further up-regulates cyclooxygenase (COX)-2 leading to altered prostaglandin profile. Inhibition of TNF-? and COX-2 provides beneficial effect on diabetic neuropathy by decreasing the oxidative stress level and by preventing neuronal hypersensitivity due to an increased prostaglandin level. The present study was designed to assess the effect of dipyrone and thalidomide on streptozotocin (STZ)-induced neuropathic pain behavior in rats. STZ 50 mg/kg, i.p. was administered to induce experimental diabetes in the rats. Three weeks following STZ, dipyrone (300 and 600 mg/kg, i.p.) and thalidomide (25 and 50 mg/kg, i.p.) alone and subeffective dose combination of dipyrone and thalidomide (300 and 25 mg/kg(-1), i.p.) administered daily for 2 weeks significantly attenuated thermal hyperalgesia, mechanical allodynia, and formalin-induced phase-2 flinching response. Moreover, the subeffective dose combination of dipyrone and thalidomide and preemptive treatment with thalidomide (50 mg/kg) reduces oxidative stress in diabetic rats. In conclusion, the combination of subeffective dose of dipyrone and thalidomide prevented the development and maintenance of experimental diabetic neuropathy. The combination of thalidomide (TNF-? inhibitor) and dipyrone (COX inhibitor) may be used as a potential therapeutic agent for the treatment of diabetic neuropathy. PMID:22249337

Chauhan, Neha; Taliyan, Rajeev; Sharma, Pyare Lal

2012-01-17

30

A novel insulin mimetic vanadium-flavonol complex: synthesis, characterization and in vivo evaluation in STZ-induced rats.  

PubMed

Since 1985, when Heyliger et al., first demonstrated a serendipitous discovery that oral administration of 0.8 mg/ml of sodium orthovanadate in drinking water to streptozotocin-induced diabetic rats resulted in normoglycemia, numerous extensive studies have been pursued on the anti-diabetic and insulinomimetic actions of vanadium. The acceptance of vanadium compounds as promising therapeutic antidiabetic agents has been slowed due to the concern for chronic toxicity associated with vanadium accumulation. In order to circumvent the toxic effects of vanadium, we have taken up a combinational approach wherein a novel vanadium-flavonol complex was synthesized, characterized and its toxic as well as insulin mimetic potential was evaluated in STZ-induced experimental diabetes in rats. The results indicate that the complex is non-toxic and possess anti-diabetic activity. PMID:23466606

Pillai, Subramanian Iyyam; Subramanian, Sorimuthu Pillai; Kandaswamy, Muthusamy

2013-02-16

31

Effect of the magnetized water supplementation on blood glucose, lymphocyte DNA damage, antioxidant status, and lipid profiles in STZ-induced rats  

PubMed Central

This study investigated the effects of magnetized water supplementation on blood glucose, DNA damage, antioxidant status, and lipid profiles in streptozotocin (STZ)-induced diabetic rats. There were three groups of 4-week-old male Sprague-Dawley rats used in the study: control group (normal control group without diabetes); diabetes group (STZ-induced diabetes control); and magnetized water group (magnetized water supplemented after the induction of diabetes using STZ). Before initiating the study, diabetes was confirmed by measuring fasting blood glucose (FBS > 200 dl), and the magnetized water group received magnetized water for 8 weeks instead of general water. After 8 weeks, rats were sacrificed to measure the fasting blood glucose, insulin concentration, glycated hemoglobin level, degree of DNA damage, antioxidant status, and lipid profiles. From the fourth week of magnetized water supplementation, blood glucose was decreased in the magnetized water group compared to the diabetes group, and such effect continued to the 8th week. The glycated hemoglobin content in the blood was increased in the diabetes group compared to the control group, but decreased significantly in the magnetized water group. However, decreased plasma insulin level due to induced diabetes was not increased by magnetized water supplementation. Increased blood and liver DNA damages in diabetes rats did significantly decrease after the administration of magnetized water. In addition, antioxidant enzyme activities and plasma lipid profiles were not different among the three groups. In conclusion, the supplementation of magnetized water not only decreased the blood glucose and glycated hemoglobin levels but also reduced blood and liver DNA damages in STZ-induced diabetic rats. From the above results, it is suggested that the long-term intake of the magnetized water over 8 weeks may be beneficial in both prevention and treatment of complications in diabetic patients.

Lee, Hye-Jin

2013-01-01

32

Genetic Deficiency of Anti-Aging Gene Klotho Exacerbates Early Nephropathy in STZ-Induced Diabetes in Male Mice.  

PubMed

Klotho is a recently discovered anti-aging gene and is primarily expressed in kidneys. In humans, the klotho level decreases with age whereas the prevalence of chronic kidney disease (CKD) increases with age. Diabetic nephropathy is the most common form of CKD, which leads to end-stage renal disease. A decrease in klotho has been found in kidneys of patients with diabetic nephropathy. The purpose of this study is to assess whether klotho gene deficiency affects early diabetic nephropathy in a mouse of model of type 1 diabetes induced by streptozotocin (STZ). Male KL(+/-) mutant and wild-type mice (6-8 weeks) were injected with multiple low doses of STZ. Renal functions and renal blood flow were assessed. Kidneys were collected for histological examination and molecular assays of TGF?1 and mammalian targets of rapamycin (mTOR) signaling. Klotho deficiency in KL(+/-) mutant mice exacerbated STZ-induced increases in urine albumin, blood urea nitrogen, expansion of mesangial matrix in renal glomeruli, and kidney hypertrophy, suggesting a protective role of klotho in kidney function and structure. Klotho deficiency did not affect renal blood flow. Notably, klotho deficiency significantly increased phosphorylation of Smad2, indicating enhanced TGF?1 signaling in kidneys. Klotho deficiency also increased phosphorylation of mTOR and S6 (a downstream effector of mTOR), indicating enhanced mTOR signaling in kidneys of early diabetic mice. Thus, klotho gene deficiency may make kidneys more susceptible to diabetic injury. Klotho gene deficiency exacerbated early diabetic nephropathy via enhancing both TGF?1 and mTOR signaling in kidneys. PMID:23928372

Lin, Yi; Kuro-O, Makoto; Sun, Zhongjie

2013-08-08

33

Interaction of insulin with prokinetic drugs in STZ-induced diabetic mice  

PubMed Central

AIM: To study the possible interactions of metoclopramide, domperidone and erythromycin in streptozotocin-induced diabetic mice treated with insulin by various parameters. METHODS: Effects of the individual as well as combined drugs were studied in diabetic mice via estimation of the blood glucose and serum insulin levels, small intestinal transit (SIT), gastric emptying (GE), xylose absorption and glucose tolerance tests. Groups were given insulin 2 IU/kg s.c., metoclopramide 20 mg/kg p.o., domperidone 20 mg/kg p.o. and erythromycin 6 mg/kg p.o. individually and in combination. There were also normal and diabetic control groups. The first set of experiments was carried out to investigate the subchronic effect on blood glucose and serum insulin levels in diabetic mice of one week of daily dose administration of the tested drugs individually as well as the combination of insulin with each prokinetic drug. The other five sets of experiments were carried out to investigate the acute effect of a single dose of each drug individually and in combination on blood glucose and serum insulin levels, SIT, GE, oral xylose absorption and glucose tolerance tests. RESULTS: The study included the prokinetic drugs metoclopramide (20 mg/kg), domperidone (20 mg/kg) and erythromycin (6 mg/kg), as well as insulin (2 IU/kg), which was individually effective in decreasing SIT, enhancing GE and increasing xylose absorption significantly in diabetic mice. Erythromycin tended to decrease blood glucose level and increase serum insulin level after 1 wk of daily administration in diabetic mice. Erythromycin potentiated the effect of insulin on blood glucose level and serum insulin level whereas other prokinetic agents failed to do so after repeated dose administration in diabetic mice. Metoclopramide or erythromycin in combination with insulin significantly decreased SIT, in diabetic mice, to lower levels than with insulin alone. Administration of prokinetic drugs along with insulin antagonized the action of insulin on xylose absorption. These combinations also increased the rate of glucose absorption from the gut. CONCLUSION: The present study suggests that prokinetic drugs could potentially improve glycemic control in diabetic gastroparesis by allowing a more predictable absorption of nutrients, matched to the action of exogenous insulin. The use of prokinetics, such as erythromycin, may be interesting in the clinic in decreasing the need for insulin in diabetic patients. The dose of insulin may be safely decreased with erythromycin in chronic treatments.

Shalaby, Mohamed A Fouad; Latif, Hekma A Abd El; Sayed, Mostafa E El

2013-01-01

34

Role of bittergourd fruit juice in stz-induced diabetic state in vivo and in vitro  

Microsoft Academic Search

The aqueous juice of bittergourd fruit (BF) (Momordica charantia L.) of the family Cucurbitaceae has been shown to possess hypoglycemic activity. However, the mechanism of its action is not known. Hence in vitro and in vivo experiments were carried out to study the role of BF juice on the diabetic status. The activity of BF juice was tested on STZ

Sandhya L Sitasawad; Yogita Shewade; Ramesh Bhonde

2000-01-01

35

Antidiabetic Activity of Some Herbal Plants in Streptozotocin Induced Diabetic Albino Rats  

Microsoft Academic Search

Aqueous extract of leaves of 3 herbs (Murraya koenigii, MK; Psidium guajava, PG and Catharanthus roseus, CR) were used to test their antidiabetic activity in Streptozotocin (STZ) induced diabetic albino rats. MK, PG and CR are given to the STZ induced diabetic rats at the concentration of 500 mg\\/kg body weight in different groups of 6 diabetic rats each orally

S. K. Prasad; Alka Kulshreshtha; Taj N. Qureshi

2009-01-01

36

Neuroprotective effect of cyclooxygenase inhibitors in ICV-STZ induced sporadic Alzheimer's disease in rats.  

PubMed

Sporadic Alzheimer's disease is an age-related neurological and psychiatric disorder characterized by impaired energy metabolism. Oxidative stress and neuroinflammation have been implicated in pathophysiology of sporadic type of dementia. The central streptozotocin administration induces behavioral and biochemical alterations resembling those in sporadic type of Alzheimer's patients. The present study was designed to investigate the effects of chronic pretreatment with cyclooxygenase-1 or cyclooxygenase-2 or cyclooxygenase-3 selective inhibitors on cognitive dysfunction and oxidative stress markers in intracerebroventricular streptozotocin-treated rats. Chronic treatment with valeryl salicylate (5 and 10 mg/kg, i.p.) and etoricoxib (5 and 10 mg/kg, i.p.) on a daily basis for a period of 21 days, beginning 1 h prior to first intracerebroventricular streptozotocin injection, significantly improved streptozotocin-induced cognitive impairment. However, phenacetin (20 and 40 mg/kg, i.p.) failed to restore the cognitive performances of streptozotocin-treated rats. Besides, improving cognitive dysfunction, chronic administration of highly selective cyclooxygenase-1 and/or cyclooxygenase-2 inhibitors (valeryl salicylate and etoricoxib, respectively), but not cyclooxygenase-3 inhibitor (phenacetin), significantly reduced elevated malondialdehyde, nitrite levels, and restored reduced glutathione and superoxide dismutase levels. Furthermore, cyclooxygenase-1 and/or cyclooxygenase-2 inhibitors significantly increased the survival of pyramidal neurons. In summary, we demonstrate for the first time that both cyclooxygenase-1 and cyclooxygenase-2 isoforms, but not cyclooxygenase-3, are involved in the progression of neuronal damage in intracerebroventricular streptozotocin-treated rats. PMID:21701788

Dhull, Dinesh Kumar; Jindal, Ankur; Dhull, Rakesh K; Aggarwal, Saurabh; Bhateja, Deepak; Padi, Satyanarayana S V

2011-06-24

37

2, 3, 5, 4?-Tetrahydroxystilbene-2-O-Beta-D-Glucoside Improves Gastrointestinal Motility Disorders in STZ-Induced Diabetic Mice  

PubMed Central

Oxidative stress has recently been considered as a pivotal player in the pathogenesis of diabetic gastrointestinal dysfunction. We therefore investigated the role of 2, 3, 5, 4?-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) that has a strong anti-oxidant property, in diabetic gastrointestinal dysmotility as well as the underlying protective mechanisms. THSG restored the delayed gastric emptying and the increased intestinal transit in streptozotocin (STZ)-induced diabetic mice. Loss of neuronal nitric oxide synthase (nNOS) expression and impaired nonadrenergic, noncholinergic (NANC) relaxations in diabetic mice were relieved by long-term preventive treatment with THSG. Meanwhile, THSG (10?7?10?4 mol/L) enhanced concentration-dependently NANC relaxations of isolated colons in diabetic mice. Diabetic mice displayed a significant increase in Malondialdehyde (MDA) level and decrease in the activity of glutathione peroxidase (GSH-Px), which were ameliorated by THSG. Inhibition of caspase-3 and activation of ERK phosphorylation related MAPK pathway were involved in prevention of enhanced apoptosis in diabetes afforded by THSG. Moreover, THSG prevented the significant decrease in PPAR-? and SIRT1 expression in diabetic ileum. Our study indicates that THSG improves diabetic gastrointestinal disorders through activation of MAPK pathway and upregulation of PPAR-? and SIRT1.

Chang, Mu-Jun; Xiao, Jun-Hua; Wang, Yong; Yan, Yong-Li; Yang, Jun; Wang, Jia-Ling

2012-01-01

38

Anti-diabetic effect of Coptis Chinensis polysaccharide in high-fat diet with STZ-induced diabetic mice.  

PubMed

For the past few years, numerous polysaccharides and polysaccharide-protein complexes have been isolated from plant or animal and used as a promising source of therapeutic agents for diabetes mellitus (DM). In this study, a water-soluble polysaccharide, named as CCPW-1, was extracted and fractioned from the roots of Coptis Chinensis by DEAE Sepharose Fast Flow anion-exchange and Sephadex G-100 column chromatography. The determination of the monosaccharide composition in CCPW-1 with gas chromatography (GC) showed that CCPW-1 was composed of glucose (54.8%), arabinose (22.3%), xylose (11.5%), galactose (7.6%) and galacturonic acid (3.8%). Diabetic mice induced by high-fat diet (HFD) with streptozotocin (STZ) were administered CCPW-1 (100, 50, 25 mg/kg b.w.). Effects of CCPW-1 on bodyweight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), fasting serum insulin (FINS), total glycerin (TG), total cholesterol (TC), super oxygen dehydrogenises (SOD), catalase (CAT) and methane dicarboxylic aldehyde (MDA) were investigated. CCPW-1 could improve the bodyweight, reduce the content of FBG and enhance FINS level. Meanwhile, CCPW-1 significantly suppressed the rise in blood glucose after 30 min in OGTT. TG and TC levels of diabetic mice also decreased after CCPW-1 treatment. Furthermore, CCPW-1 showed an obvious antioxidant effect through increasing SOD, CAT activities and decreasing MDA content in pancreas. These results indicate that CCPW-1 could be developed to a potent drug used for the treatment of DM in the future. PMID:23295205

Jiang, Shuang; Du, Peige; An, Liping; Yuan, Guangxin; Sun, Zhiwei

2013-01-04

39

Supplementation of fenugreek leaves lower lipid profile in streptozotocin-induced diabetic rats.  

PubMed

The present study was undertaken to evaluate the lipid-lowering effect of fenugreek leaves in diabetes mellitus. Albino Wistar rats were randomly divided into six groups: normal untreated rats; streptozotocin (STZ)-induced diabetic rats; STZ-induced rats + fenugreek leaves (0.5 g/kg of body weight); STZ-induced rats + fenugreek leaves (1 g/kg of body weight); STZ-induced rats + glibenclamide (600 microg/kg of body weight); and STZ-induced rats + insulin (6 units/kg of body weight). Rats were made diabetic by STZ (40 mg/kg) injected intraperitoneally. Fenugreek leaves were supplemented in the diet daily to diabetic rats for 45 days, and food intake was recorded daily. Blood glucose, total cholesterol, triglycerides, and free fatty acids were determined in serum, liver, heart, and kidney. Our results show that blood glucose and serum and tissue lipids were elevated in STZ-induced diabetic rats. Supplementation of fenugreek leaves lowered the lipid profile in STZ-induced diabetic rats. PMID:15298761

Annida, B; Stanely Mainzen Prince, P

2004-01-01

40

Biochemical evaluation of antihyperglycemic and antioxidative effects of Morinda citrifolia fruit extract studied in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The hypoglycemic and antioxidative effects of Morinda citrifolia fruit extract were evaluated in streptozotocin (STZ)-induced diabetic rats. The ethanolic extract of Morinda citrifolia fruit at a concentration of 300 mg\\/kg body weight\\/rat\\/day was orally administered to STZ-induced diabetic rats for a period\\u000a of 30 days. The elevated levels of blood glucose, glycosylated hemoglobin, blood urea, and serum creatinine in the diabetic\\u000a rats

S. Subramanian

2009-01-01

41

Acid Secretory Changes in Streptozotocin-Diabetic Rats  

Microsoft Academic Search

We examined gastric acid secretion in response to various stimuli in streptozotocin (STZ) induced diabetic rats and characterized the alteration of acid secretory responses in diabetic conditions. Animals were injected STZ (70 mg\\/kg, intraperitoneally) and used after five weeks of diabetes with blood glucose >350 mg\\/dl. Under urethane anesthesia, the experiment was performed in a chambered stomach or a whole

Kimihito Tashima; Masato Nishijima; Akinobu Fujita; Masafumi Kubomi; Koji Takeuchi

2000-01-01

42

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

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

Talal A. ZARI; Ayed Sh

2009-01-01

43

Short-term effects of vanadate treatment in diabetic rats  

Microsoft Academic Search

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)

M. H. Oster; J. M. Llobet; J. L. Domingo; C. L. Keen

1991-01-01

44

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

Microsoft Academic Search

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.

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

45

The Effects of Vanadium (V) Absorbed by Coprinus comatus on Bone in Streptozotocin-induced Diabetic Rats  

Microsoft Academic Search

The purpose of this study was to evaluate the effects of vanadium absorbed by Coprinus comatus (VACC) treatment on bone in streptozotocin (STZ)-induced diabetic rats. Forty-five Wistar female rats used were divided into\\u000a three groups: (1) normal rats (control), (2) diabetic rats, and (3) diabetic rats treated with VACC. Normal and diabetic rats\\u000a were given physiological saline, and VACC-treated rats

Yi Pei; Qin Fu

46

Changes in the Function and Ultrastructure of Vessels in the Rat Model of Multiple Low Dose Streptozotocin-Induced Diabetes  

Microsoft Academic Search

In this study we investigated functional changes in the femoral artery and ultrastructural alterations in mesenteric vessels and capillaries in the rat model of multiple low dose streptozotocin (STZ)-induced diabetes. Participation of oxida- tive stress in this model of diabetes was established by studying the effect of the pyridoindole antioxidant stobadine (STB) on diabetes-induced impairment. Experimental diabetes was induced by

R. Sotnikova; S. Skalsk; L. Okruhlicova; J. Navarova; Z. Kyselova; J. Zurova; M. Stefek; R. Hozova; V. Nosalova

2006-01-01

47

Hypoglycemic activity of Buchholzia coriacea (Capparaceae) seeds in streptozotocin-induced diabetic rats and mice  

Microsoft Academic Search

The present study evaluates the possible hypoglycemic activity and ameliorative effects of oral administration of ethanol extracts (EEBC) and butanol fraction (BFBC) of Buchholzia coriacea seeds, a plant in use traditionally for treating diabetes, hypertension, rheumatism, cold, cough and catarrh, in streptozotocin (STZ)-induced diabetic mice and rats. Fasting blood glucose (FBG) levels were evaluated before and after extracts administration. EEBC

Rahmat A. Adisa; Mohammed I. Choudhary; Olufunso O. Olorunsogo

2011-01-01

48

Neuroprotective role of curcumin in the cerebellum of streptozotocin-induced diabetic rats  

Microsoft Academic Search

AimsChronic hyperglycaemia in diabetes involves a direct neuronal damage caused by intracellular glucose which leads to altered neurotransmitter functions and reduced motor activity. The present study investigated the effect of curcumin in the functional regulation of muscarinic and ?7 nicotinic acetylcholine receptors, insulin receptors, acetylcholine esterase and Glut3 in the cerebellum of streptozotocin (STZ)-induced diabetic rats.

Kumar T. Peeyush; G. Gireesh; Mathew Jobin; C. S. Paulose

2009-01-01

49

Antidiabetic effects of sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The evaluation of the anti-diabetic effects of an organic vanadium(V) complex in streptozotocin (STZ)-induced diabetic rats was investigated. The STZ-induced diabetic rats were orally administrated with sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate (V5dipic-NH2), a vanadium(V) coordination compound. The compound was administered through drinking water at a concentration of 0.1mg\\/mL for 20 days, and then the concentration was increased to 0.3mg\\/mL for the following

Ming Li; Jason J. Smee; Wenjun Ding; Debbie C. Crans

2009-01-01

50

Effect of Melatonin on Testicular Damage in Streptozotocin-Induced Diabetes Rats  

Microsoft Academic Search

Background: It is well known that diabetes mellitus is associated with impairment of testicular function. In the present study, we aimed to demonstrate the effect of melatonin on testicular damage in male rats with streptozotocin (STZ)-induced diabetes. Methods: Male Wistar rats were divided into 4 groups: (1) control group, (2) melatonin-treated nondiabetic group, (3) diabetic group and (4) melatonin-treated diabetic

E. Guneli; K. Tugyan; H. Ozturk; M. Gumustekin; S. Cilaker; N. Uysal

2008-01-01

51

Effects of modified rice bran on serum lipids and taste preference in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The present study was designed to determine whether or not the administration of modified rice bran could improve streptozotocin (STZ)-induced diabetes. Taste preferences were also compared in diabetic and control rats. Male Sprague-Dawley rats were divided into control and diabetic groups. A single STZ injection, 65 mg per kg body mass i.p., induced diabetes. Rats were given free access to

Ikuo Ohara; Ritsuko Tabuchi; Kumiko Onai; M Home Econ

2000-01-01

52

Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes  

Microsoft Academic Search

The impact of streptozotocin (STZ)-induced, insulino- penic diabetes on the GH axis of rats and mice differs from study to study, where this variation may be related to the induction scheme, severity of the diabetes and\\/or the genetic background of the animal model used. In order to begin differentiate between these possibilities, we compared the effects of two different STZ

E Kim; S Sohn; M Lee; J Jung; R D Kineman

2006-01-01

53

The augmentation of pituitary adenylate cyclase-activating polypeptide (PACAP) in streptozotocin-induced diabetic rats  

Microsoft Academic Search

Pituitary adenylate cyclase activating polypeptide (PACAP), which was isolated from ovine hypothalamic extract, has been shown to have a physiological role in the regulation of insulin or islet functions. In streptozotocin (STZ)-induced diabetic rats, we examined the content of PACAP immunoreactivity and gene expression of three specific receptors. Four weeks after administration of STZ (50 mg\\/kg), plasma glucose levels increased

Hiroki Tamakawa; Atsuro Miyata; Kumi Satoh; Yoshihiro Miyake; Hisayuki Matsuo; Akira Arimura; Kenji Kangawa

1998-01-01

54

Effect of Lycopene Administration on Plasma Glucose, Oxidative Stress and Body Weight in Streptozotocin Diabetic Rats  

Microsoft Academic Search

Duzguner, V., Kucukgul, A., Erdogan, S., Celik, S. and Sahin, K. 2008. Effect of lycopene administration on plasma glucose, oxidative stress and body weight in streptozotocin diabetic rats. J. Appl. Anim. Res., 33: 17–20.To evaluate the role of lycopene, a carotenoid antioxidant, on streptozotocin (STZ)-induced diabetic rats, 12 female rats received a single intraperitonial injection of STZ at a dose

Vesile Duzguner; Altug Kucukgul; Suat Erdogan; Sefa Celik; Kazim Sahin

2008-01-01

55

Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats  

Microsoft Academic Search

Aim:To examine whether implantation of islet preparation-derived proliferating islet cells (PIC) could ameliorate diabetes in rats.Methods:PIC were expanded from rat islet preparation by supplementation of basic fibroblast growth factor (bFGF) and implanted into rats with streptozotocin (STZ)-induced diabetes through the portal vein. Body weight and blood glucose levels were measured. Serum insulin levels were measured by radioimmunoassay. The presence of

Ge Li; Li-song Huang; Ming-hong Jiang; Hui-ling Wu; Jing Chen; Yin Huang; Yan Shen; SaiYin He-Xi-Ge; Wei-wei Fan; Zhi-qiang Lu; Da-ru Lu

2010-01-01

56

A quantitative study of sodium tungstate protective effect on pancreatic beta cells in streptozotocin-induced diabetic rats.  

PubMed

Diabetes is a major public health problem. Development of new therapies that are able to improve glycemia management, cure diabetes, and can even protect from it, are of great interest. This study investigated the protective effect of sodium tungstate against STZ-induced beta-cell damages by means of stereological methods. Sixty rats were divided into six groups: control (C), tungstate-treated control (TC), STZ-induced diabetic (D), STZ-induced diabetic rats were treated by sodium tungstate from 1 week before STZ injection (TDB), food-restricted diabetic (FRD), and diabetic rats treated with sodium tungstate 1 week after STZ administration (TDA). Stereological estimation of pancreas volume, islets volume density, volume-weighted mean islets volume and mass of beta cells, islets, and pancreas and total number of islets were done. Islets volume density, volume-weighted mean islets volume, and mass of beta cells, islets, and pancreas of TDB group was significantly higher than D, FRD and TDA groups (P<0.001) and was comparable to controls (C and TC groups). Total number of islets, pancreas wet weight and volume did not show any significant changes between these groups (P>0.05). Results suggested that sodium tungstate preserves pancreatic beta cells from STZ-induced damages and diabetes induction in rats. PMID:18400503

Heidari, Zahra; Mahmoudzadeh-Sagheb, Hamidreza; Moudi, Bita

2008-03-02

57

Increased cathepsin K and tartrate-resistant acid phosphatase expression in bone of streptozotocin-induced diabetic rats  

Microsoft Academic Search

The effect of insulin-dependent diabetes mellitus (IDDM) on bone metabolism was evaluated using the streptozotocin (STZ)-induced diabetic rat 1 week after the induction of diabetes. The urinary excretion of cross-linked N-telopeptides of type I collagen (NTx) and deoxypyridinoline (Dpd) in diabetic rats increased to 3.6-fold and 1.2-fold the control level, respectively. The amount of hydroxyproline and calcium in the distal femur

Mamiko Hie; Masumi Shimono; Kayoko Fujii; Ikuyo Tsukamoto

2007-01-01

58

Decrease of Heatstroke-Induced Multiorgan Dysfunction by Whole Body Cooling in Streptozotocin-Induced Diabetic Rats  

Microsoft Academic Search

The present study was conducted to assess the effects of whole body cooling on multiorgan dysfunction that occurred during heatstroke in streptozotocin (STZ)-induced diabetic rats. The rats were randomly divided into four groups: (1) the normal control, (2) diabetic control, (3) diabetic heatstroke, and (4) diabetic heatstroke-whole body cooling (WBC). They were exposed to ambient temperature of 43°C for exactly

Chuan-Chih Hsu; Chiang-Shan Niu; Mao-Tsun Lin

59

Effects of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract on plasma glucose and hepatic glycogen in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The present study investigates the hypoglycaemic effect of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract in non-diabetic and streptozotocin (STZ)-induced diabetic rats. Oral glucose tolerance tests (OGGT) were conducted in non-diabetic and STZ-diabetic rats using orally administered glucose (1.4g100g?1 body weight) followed by either the leaf extract (6mg100?1g body weight) or subcutaneous (sc) injection of metformin (50mg100g?1). Weekly plasma glucose and

C. T. Musabayane; N. Mahlalela; F. O. Shode; J. A. O. Ojewole

2005-01-01

60

Induction of gastric lesions and hypoglycemic response by food deprivation in streptozotocin-diabetic rats  

Microsoft Academic Search

Overnight fasting causes hemorrhagic lesions in the stomach of streptozotocin (STZ)-induced diabetic rats, but the pathogenetic mechanism remains unknown. The present study was performed to investigate the pathogenesis of such lesions developed in STZ-diabetic rats after starvation, mainly in relation to blood glucose changes. A single injection of STZ (70 mg\\/kg, intraperitoneally) induced hyperglycemic conditions one week after the administration,

Koji Takeuchi; Koji Ueshima; Tomohisa Ohuchi; Susumu Okabe

1994-01-01

61

Modifications in the metabolic pathways of benzene in streptozotocin-induced diabetic rat  

Microsoft Academic Search

Benzene is a ubiquitous environmental pollutant primarily metabolized by a cytochrome P-450 (CYP-450) isoenzyme, CYP-450\\u000a IIE1. A consistent induction of CYP450 IIE1 has been observed in both rat and human affected by diabetes mellitus. The aim\\u000a of this study was to evaluate whether streptozotocin (STZ)-induced diabetes determines modifications in the metabolic pathways\\u000a of benzene in rat. Benzene (100?mg\\/kg?per day, dissolved

Chiara Costa; Calcedonio Pupo; Giuseppina Viscomi; Stefania Catania; Monica Salemi; Claudia Imperatore

1999-01-01

62

Quercitrin a bioflavonoid improves the antioxidant status in streptozotocin: induced diabetic rat tissues  

Microsoft Academic Search

Quercitrin, a bio flavonoid, was investigated for its antioxidant potential in streptozotocin (STZ)-induced diabetic rats.\\u000a Rats were induced diabetic by a single intraperitoneal injection of streptozotocin (50 mg\\/kg). The levels of fasting plasma\\u000a glucose and insulin were estimated. Lipid peroxidative products and antioxidants were estimated in pancreas, liver, and kidney.\\u000a Histopathological studies were carried out in these tissues. A significant (P < 0.05)

Ranganathan Babujanarthanam; Purushothaman Kavitha; Moses Rajasekara Pandian

63

Short-term bioaccumulation of vanadium when ingested with a tea decoction in streptozotocin-induced diabetic rats  

Microsoft Academic Search

Sodium orthovanadate suspended in a lichee black tea decoction effectively regulates blood glucose levels in rats with insulin-dependent, streptozotocin (STZ)-induced diabetes. The primary advantage of vanadate delivery with the tea decoction over conventional systems that use water suspensions of vanadate is a significant reduction in the toxic side effects of vanadate. It is unknown if the tea alters the bioavailability

Andrea L. Edel; Melanie Kopilas; Tod A. Clark; Floribeth Aguilar; Pallub K. Ganguly; Clayton E. Heyliger; Grant N. Pierce

2006-01-01

64

Protective effect of secoisolariciresinol diglucoside against streptozotocin-induced diabetes and its mechanism  

Microsoft Academic Search

Objectives: Reactive oxygen species (ROS) have been implicated in the development of streptozotocin (STZ)-induced diabetes mellitus. Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is an antioxidant. An investigation was made of the effects of SDG on the development of STZ-induced diabetes in rat, to determine if SDG can prevent\\/reduce the development of diabetes and if this prevention\\/reduction is associated with reduction

Kailash Prasad; Subrahmanyam V. Mantha; Alister D. Muir; Neil Westcott

2000-01-01

65

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

PubMed

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 the plasma glucose levels in normal rats. In contrast, a single oral or intraperitoneal administration of yacon decoction produced no effect on the plasma glucose levels of STZ-induced diabetic rats. However, the administration of 2% yacon tea ad libitum instead of water for 30 days produced a significant hypoglycemic effect on STZ-induced diabetic rats. After 30 days of tea administration, diabetic rats showed improved body (plasma glucose, plasma insulin levels, body weight) and renal parameters (kidney weight, kidney to body weight ratio, creatinine clearance, urinary albumin excretion) in comparison with the diabetic controls. Our results suggest that yacon water extract produces an increase in plasma insulin concentration. PMID:11167030

Aybar, M J; Sánchez Riera, A N; Grau, A; Sánchez, S S

2001-02-01

66

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

Microsoft Academic Search

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

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

67

The vasorelaxant effect of hydrogen sulfide is enhanced in streptozotocin-induced diabetic rats  

Microsoft Academic Search

Hydrogen sulfide (H2S) is an endogenous gas which has potent relaxant effect in vascular and nonvascular smooth muscles. In the present study,\\u000a we have investigated how streptozotocin (STZ)-induced diabetes affected the relaxant effect of H2S in rat isolated thoracic aorta and mesenteric and pulmonary arteries. Diabetes was induced by IV injection of STZ (35 mg\\/kg).\\u000a Insulin treatment was applied by using

Merve Denizalti; Turgut Emrah Bozkurt; U?ur Akpulat; Inci Sahin-Erdemli; Nurettin Abac?o?lu

2011-01-01

68

Effects of diabetes, vanadium, and insulin on glycogen synthase activation in Wistar rats  

Microsoft Academic Search

In vivo effects of insulin and vanadium treatment on glycogen synthase (GS), glycogen synthase kinase-3 (GSK-3) and protein phosphatase-1 (PP1) activity were determined in Wistar rats with streptozotocin (STZ)-induced diabetes. The skeletal muscle was freeze-clamped before or following an insulin injection (5 U\\/kg i.v.). Diabetes, vanadium, and insulin in vivo treatment did not affect muscle GSK-3ß activity as compared to

Sabina Semiz; Chris Orvig; John H. McNeill

2002-01-01

69

Effect of Long-Term Type 1 Diabetes on Renal Sodium and Water Transporters in Rats  

Microsoft Academic Search

The effects of long-term diabetes in the presence of established nephropathy on tubular function remains poorly understood. We evaluated the levels of the main sodium and water transport proteins expressed in the kidney after long-term (8 weeks) of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) in untreated (D) and insulin (4 U\\/s.c.\\/day)-treated (D+I) rats. D animals presented upregulation (?4.5-fold) of

Daniela B. Vidotti; Carine P. Arnoni; Edgar Maquigussa; Mirian A. Boim

2008-01-01

70

Differential effects of diazepam on anxiety in streptozotocin induced diabetic and non-diabetic rats  

Microsoft Academic Search

The anxiolytic activity of diazepam (DZP) (0.25–1?mg\\/kg) was investigated in streptozotocin (STZ)-induced diabetic adult\\u000a Charles Foster albino rats of either sex. Diabetes was induced by injecting STZ IP (50?mg\\/kg; in citrate buffer, pH 4.5).\\u000a Experiments were performed 72 h later. The rats were subjected to various anxiety paradigms, including the open-field exploratory\\u000a behaviour, elevated plus maze and elevated zero maze

M. Ramanathan; Arun K. Jaiswal; S. K. Bhattacharya

1998-01-01

71

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

Microsoft Academic Search

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,

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

2011-01-01

72

T-1095, a renal Na +-glucose transporter inhibitor, improves hyperglycemia in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The effect of T-1095, an inhibitor of renal glucose reabsorption, on hyperglycemia and the expression of Na+-glucose cotransporters (SGLTs) and facilitative glucose transporter 2 (GLUT2) in streptozotocin (STZ)-induced diabetic rats was examined. There was an elevation of blood glucose, hemoglobin A1c (HbA1c), kidney weight, and urinary excretion of both glucose and albumin in STZ rats. Administration of 0.03% and 0.1%

Tetsuya Adachi; Koichiro Yasuda; Yoshimasa Okamoto; Nobuyuki Shihara; Akira Oku; Kiichiro Ueta; Kazuyuki Kitamura; Akira Saito; Toshio Iwakura; Yuichiro Yamada; Hideki Yano; Yutaka Seino; Kinsuke Tsuda

2000-01-01

73

Effect of lignin-derived lignophenols on vascular oxidative stress and inflammation in streptozotocin-induced diabetic rats  

Microsoft Academic Search

Lignophenols (LP) are the derivatives of native lignin, which is an abundant organic polymer in the plant kingdom. This study\\u000a investigated whether LP can attenuate vascular oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic\\u000a rats. The diabetic rats induced by a single intravenous injection of STZ were randomly divided into two groups fed either\\u000a 0 or 1.0% LP-containing diet. After

Yuuka Mukai; Toshio Norikura; Shuzo Fujita; Keigo Mikame; Masamitsu Funaoka; Shin Sato

2011-01-01

74

In vivo effects of vanadium on GLUT4 translocation in cardiac tissue of STZ-diabetic rats  

Microsoft Academic Search

The effect of vanadium treatment on insulin-stimulated glucose transporter type 4 (GLUT4) translocation was studied in cardiac tissue of streptozotocin (STZ)-induced diabetic rats by determining the subcellular distribution of GLUT4. Four groups of rats were examined: control and diabetic, with or without bis(maltolato)oxovanadium(IV) (BMOV, an organic form of vanadium) treatment for 8 weeks. The effect of vanadium on insulin-induced GLUT4

Shu Hong Li; John H. McNeill

2001-01-01

75

Hypoglycemic effect of crude exopolysaccharides produced by a medicinal mushroom Phellinus baumii in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The antidiabetic effect of the crude exopolysaccharides (EPS) produced from submerged mycelial culture of Phellinus baumii in streptozotocin (STZ)-induced diabetic rats was investigated. The produced EPS consisted of two different heteropolysaccharides and two proteoglycans. The food intake of the diabetic control rats (STZ) was increased by 28.1%, whereas body weight gain was reduced by 44.1% as compared to the nondiabetic

Hye-Jin Hwang; Sang-Woo Kim; Jong-Min Lim; Ji-Hoon Joo; Hyun-Oh Kim; Hyun-Mi Kim

2005-01-01

76

Localization of glycogen in the placenta and fetal and maternal livers of cadmium-exposed diabetic pregnant rats  

Microsoft Academic Search

This study was designed to investigate the effects of Cd exposure on the glycogen localization in the placenta and in fetal\\u000a and maternal livers in streptozotocin (STZ)-induced-diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200–220\\u000a g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups\\u000a (control,

Mecit Yoruk; Mehmet Kanter; Ismail Meral; Zahid Agaoglu

2003-01-01

77

Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus  

Microsoft Academic Search

Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression

C-T Lee; Y-H H Lien; L-W Lai; J-B Chen; C-R Lin; H-C Chen

2006-01-01

78

Embelin accelerates cutaneous wound healing in diabetic rats.  

PubMed

This study reports the effect of embelin (1) on cutaneous wound in streptozotocin (STZ)-induced diabetic rats. The effect was studied using excision, incision, and dead space models. In diabetic rats, topical application of embelin 5% (w/w) ointment showed a significant increase in wound contraction and better epithelialization, thereby facilitating the healing. Embelin was also active by the oral route (25 and 50 mg/kg) in the incision and dead space wound models. In incision wound model, wound granulation tissues were removed on 8th post-wounding day, and the hydroxyproline, hexosamine, total protein, and DNA contents were determined. In STZ diabetic rats, topical and oral applications of embelin showed an increase in hydroxyproline, hexosamine, total protein, and DNA contents. It also showed a significant increase in wound breaking strength. Embelin significantly increased granuloma tissue weight and breaking strength in dead space model. These results indicated that embelin accelerated wound healing in diabetic rat. PMID:23327735

Deshmukh, Pradeep T; Gupta, Vipin B

2013-01-17

79

Enantioselective determination of 3-hydroxybutyrate in the tissues of normal and streptozotocin-induced diabetic rats of different ages  

Microsoft Academic Search

l-3-Hydroxybutyrate (3HB) and d-3HB are enantiomers that exist in various rat tissues, and the ratio of the 2 compounds is of importance since it may affect glucose utilization in cardiomyocytes. In this study, we determined the concentrations of l-3HB and d-3HB in the tissues of normal and streptozotocin (STZ)-induced diabetic rats of different ages by column-switching high-performance liquid chromatography using

Wei-Yu Hsu; Chen-Yi Kuo; Takeshi Fukushima; Kazuhiro Imai; Chien-Ming Chen; Pen-Yuan Lin; Jen-Ai Lee

2011-01-01

80

Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats  

PubMed Central

We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks). These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively) production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III) and cytochrome c oxidase (Complex IV) were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I) and succinate:ubiquinone oxidoreductase (Complex II) were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications.

Raza, Haider; Prabu, Subbuswamy K.; John, Annie; Avadhani, Narayan G.

2011-01-01

81

The role of adrenomedullin and receptors in glomerular hyperfiltration in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The role of adrenomedullin and receptors in glomerular hyperfiltration in streptozotocin-induced diabetic rats.BackgroundSince adrenomedullin (AM) elicits vasodilatation by binding to specific AM receptors consisted of calcitonin-receptor-like receptor (CRLR)\\/receptor-activity-modifying protein 2 (RAMP2) or CRLR\\/receptor-activity-modifying protein 3 (RAMP3) on endothelial cells and stimulating nitric oxide production, AM possibly involves in glomerular capillary dilatation in early phase of diabetic nephropathy.MethodsStreptozotocin (STZ)-induced diabetic Sprague-Dawley

KEITA HIRAGUSHI; JUN WADA; JUN EGUCHI; TAKASHI MATSUOKA; AKIHIRO YASUHARA; IZUMI HASHIMOTO; TETSUJI YAMASHITA; KAZUYUKI HIDA; YOSHIO NAKAMURA; KENICHI SHIKATA; NAOTO MINAMINO; KENJI KANGAWA; HIROFUMI MAKINO

2004-01-01

82

Assessment of antidiabetogenic potential of fermented soybean extracts in streptozotocin-induced diabetic rat.  

PubMed

Most of the available drugs for the treatment of diabetes mellitus (DM) produce detrimental side effects, which has prompted an ongoing search for plant with the antidiabetic potential. The present study investigated the effect of soybean extracts fermented with Bacillus subtilis MORI, fermented soybean extracts (BTD-1) was investigated in streptozotocin (STZ)-induced diabetic rats. The possible effects of BTD-1 against hyperglycemia and free radical-mediated oxidative stress was investigated by assaying the plasma glucose level and the activity of enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA). A significant increase in the levels of both plasma glucose and reactive oxygen species (ROS) was observed in the diabetic rats when compared to normal control group. After administration of BTD-1 (500 and 1000 mg/kg/day), the elevated plasma glucose level was significantly reduced while the plasma insulin level and the activities of SOD, GSH-Px, CAT and MDA were significantly increased. The results suggest that administration of BTD-1 can inhibit hyperglycemia and free radical-mediated oxidative stress. The administration of BTD-1 also inhibited the contractile response by norepinephrine (10(-10)-10(-5) M) in the presence of endothelium, and caused significant relaxation by carbachol (10(-8)-10(-5) M) in rat aorta. These findings indicate that BTD-1 improves vascular functions on STZ-induced diabetic rats. Therefore, subchronic administration of BTD-1 could prevent the functional changes in vascular reactivity in STZ-induced diabetic rats. The collective findings support that administration of BTD-1 may prevent some diabetes-related changes in vascular reactivity directly and/or indirectly due to its hypoglycaemic effect and inhibition of production of ROS. PMID:22943971

Lim, Kyu Hee; Han, Ji-Hui; Lee, Jae Yeon; Park, Young Shik; Cho, Yong Seok; Kang, Kyung-Don; Yuk, Won Jeong; Hwang, Kyo Yeol; Seong, Su-Il; Kim, Bumseok; Kwon, JungKee; Kang, Chang-Won; Kim, Jong-Hoon

2012-08-24

83

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

PubMed

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

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

2009-07-01

84

Initial Ultrastructural Changes in Pore Size and Anionic Sites of the Glomerular Basement Membrane in Streptozotocin-Induced Diabetic Rats and Their Prevention by Insulin Treatment  

Microsoft Academic Search

Background\\/Aim: The present study was conducted to elucidate the mechanism(s) of the development of early diabetic nephropathy, examining ultrastructural changes employing electron microscopy, especially changes in pore size of the glomerular basement membrane (GBM) of streptozotocin (STZ)-induced diabetics rats. Methods: Urinary albumin excretion rate (UAE), pore size of the lamina densa of the GBM visualized directly by the tissue negative

Sho Isogai; Kosei Mogami; Noriko Shiina; Gen Yoshino

1999-01-01

85

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

PubMed Central

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.

Arokiyaraj, S; Balamurugan, R; Augustian, P

2011-01-01

86

Gender difference and change of ?1-adrenoceptors in the distal mesenteric arteries of streptozotocin-induced diabetic rats  

PubMed Central

Background The purpose of this study was to evaluate the gender-related changes in the function and distribution of ?1-adrenoceptors in the distal mesenteric artery of streptozotocin (STZ)-induced diabetic rats at the level of ?1-adrenoceptor subtypes. Methods Diabetes was induced by intravenous injection of STZ in a dose of 60 mg/kg through the tail vein in 8 week-old male or female Sprague-Dawley rats (n = 13/group). Age-matched normal rats (n = 15) were used as a control group. Four weeks after STZ injection, the change in mean arterial pressure caused by a 45° tilting was recorded. The ?1-adrenoceptor subtypes mediating contractions of the distal mesenteric artery were investigated using the agonist, phenylephrine as well as subtype-selective antagonists including prazocin, 5-methylurapidil, and BMY 7378. The expression of ?1-adrenoceptor subtypes of each artery was examined by immunofluorescence staining and western blotting using subtype selective antibodies. Results Compared with normal male rats, the contractile response to phenylephrine was decreased in the distal mesenteric artery in normal female rats. Moreover, a decrease in contractile force was observed in STZ-induced diabetic rats compared with age-matched controls. Western blotting revealed that there was the difference between normal male and female rats in manifestation of the ?1D-adrenoceptor. In STZ-induced male and female diabetic rats, all ?1-adrenoceptor subtypes were decreased in distal mesenteric arteries, compared with normal rats. Conclusions There was the gender-related functional difference of ?1-adrenoceptors in normal rats. In both male and female rats, diabetes decreased the contractile response in mesenteric arteries, which might be caused by the overall change in ?1-adrenoceptor.

Park, Sang-Hyun; Oh, Ah-Young; Gil, Nam-Su; Huh, Jin; Lee, Jong-Hwan

2011-01-01

87

Differential Distribution of Insulin-Like Growth Factor1 and Insulin-Like Growth Factor Binding Proteins in Experimental Diabetic Rat Kidney  

Microsoft Academic Search

Insulin-like growth factor-1 (IGF-1) is a peptide growth factor, and its activity is modulated by interaction with the family of IGF binding proteins (IGFBP-1 to 6). IGF-1 is detected in rat kidney and has metabolic and growth effects. To explore the possible involvement of IGFBPs in glomerular hypertrophy in streptozotocin (STZ)-induced diabetic rat, the immunolocalization of IGF-1 and IGFBPs were

Nobuyuki Miyatake; Kenichi Shikata; Jun Wada; Hikaru Sugimoto; Shin-Ichiro Takahashi; Hirofumi Makino

1999-01-01

88

Polyphenol extracts from Hibiscus sabdariffa Linnaeus attenuate nephropathy in experimental type 1 diabetes.  

PubMed

Diabetic nephropathy progressed to end-stage renal disease (ESRD) is found in type 1 or type 2 diabetes. Oxidative stress is one of the precipitation factors in diabetic nephropathy. Previously, Hibiscus sabdariffa Linnaeus and its polyphenol extracts were found to possess antioxidative effects. This study is aimed to investigate the effect of Hibiscus sabdariffa L. polyphenol extract (HPE) in streptozotocin (STZ) induced diabetic nephropathy. The results show that HPE reduced kidney mass induced by STZ significantly, as well as improving hydropic change of renal proximal convoluted tubules in the rats. HPE also significantly reduced serum triglyceride, total cholesterol and LDL in STZ induced rats. Treatment with HPE significantly increased the activity of catalase and glutathione and reduced lipid peroxidation (thiobarbituric acid-reactive substances, TBARS). The findings of this research show the beneficial effects of HPE on STZ induced diabetic nephropathy including pathology, serum lipid profile and oxidative marker in kidney. PMID:19219995

Lee, Wen-Chin; Wang, Chau-Jong; Chen, Yu-Hsin; Hsu, Jen-Dong; Cheng, Su-Ya; Chen, Hong-Chen; Lee, Huei-Jane

2009-03-25

89

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

PubMed Central

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.

2011-01-01

90

Protective effects of D-limonene on lipid peroxidation and antioxidant enzymes in streptozotocin-induced diabetic rats.  

PubMed

The aim of this study was to evaluate the protective effects of D-limonene on the levels of lipid peroxidation by-products and antioxidant defence systems in the plasma and tissues of normal and streptozotocin (STZ)-induced diabetes rats. The experimental diabetes was induced in rats by a single dose of STZ (40 mg/kg i.p.) injection, and treatment with D-limonene was continued for 45 days. After the treatment period, oxidative stress parameters such as lipid peroxidation by-products; enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase; non-enzymic antioxidants including reduced glutathione, Vitamins C and E were measured in the plasma and tissues of experimental rats. An increase in the levels of lipid peroxidation by-products and significant decrease in antioxidant enzymes were observed in untreated diabetic rats. Administration of D-limonene to diabetic rats for 45 days caused a significant reduction in the levels of lipid peroxidation by-products and an increase in the activities of antioxidant enzymes, when compared with the untreated diabetic group. There was no significant difference in normal treated groups, when compared with normal rats. Biochemical observations were substantiated with the help of histopathological examinations through its antioxidant properties and thereby conferred protection against STZ-induced diabetic rats. The result of this study indicates that D-limonene has antioxidant potential in addition to its antidiabetic effect in experimental diabetes. PMID:22998493

Murali, Ramakrishnan; Karthikeyan, Arumugam; Saravanan, Ramalingam

2012-10-25

91

Inhibition of peripheral NPY Y1 and Y2 receptors ameliorates the aberrant baroreceptor reflex sensitivity in streptozotocin induced diabetic rats.  

PubMed

Neuropeptide Y (NPY), a sympathetic neurotransmitter, is highly associated with baroreflex dysfunction and multiple cardiac diseases such as diabetic myocardiopathy. In the present study, we aimed to explore the role of peripheral NPY Y1 receptor (Y1R) and Y2 receptor (Y2R), which are dominantly present in peripheral cardiovascular control, in baroreflex sensitivity (BRS) of streptozotocin (STZ)-induced diabetic rats. Peripheral Y1R and Y2R were antagonized by specific antagonists (BIBP 3226 and BIIE 0246, respectively) from subcutaneously implanted ALZET mini-osmotic pump in STZ-induced diabetic rats for 4 weeks. Then baseline systolic blood pressure, heart rate, cardiac function, BRS, plasma NPY and lipid levels were evaluated. We found that STZ led to increased plasma NPY and lipid level. And the STZ-increased lipid levels were reduced by BIBP 3226 and BIIE 0246. BIBP 3226 ameliorated the aberrant BRS, but had little effect on the impaired cardiac function of the STZ rats. BIIE 0246 alleviated sodium nitroprusside (SNP)-induced but not phenylephrine (PE)-induced aberrant barore?ex control of heart rate in the STZ rats. In addition, BIIE 0246 alleviated the bradycardia, but further impaired cardiac contractility in the STZ rats. These results suggest that peripheral Y1R and Y2R play different roles in STZ-induced impairment of BRS. PMID:23963068

Niu, Hui-Fang; Xu, Ling; Yan, Yan; Xie, Fang; Yang, Bao-Feng; Ai, Jing

2013-08-25

92

Antidiabetic activity of ?-sitosterol isolated from Lippia nodiflora L. in streptozotocin induced diabetic rats.  

PubMed

Lippia nodiflora L. (Verbenaceae) is a creeping perennial herb widely used in traditional system of medicine to treat ulcers, bronchitis and heart diseases; it also possesses antidiabetic property. In the present study, ?-sitosterol isolated from Lippia nodiflora was screened for its antidiabetic property in streptozotocin (STZ) induced diabetic rats. Insulin secretion in response to glucose was evaluated in isolated rat islets. Oral administration of ?-sitosterol (20 mg/kg body weight) once daily for 21 days in STZ-induced diabetic rats resulted in a significant decrease in blood glucose and glycosylated hemoglobin with a significant increase in plasma insulin level, body weight and food intake. Furthermore ?-sitosterol showed antihyperlipidemic activity as evidenced by significant decrease in serum total cholesterol, triglycerides and very low density lipoprotein-cholesterol levels coupled with elevation of high density lipoprotein-cholesterol levels in treated rats. A significant decrease in the activities of alanine aminotransaminase, aspartate aminotransaminase, alkaline phosphatase and acid phosphatase in ?-sitosterol treated rats when compared to diabetic control rats indicated its protective role against liver damage. ?-Sitosterol increased insulin secretion in response to glucose. Immunohistochemical study of pancreas also confirmed the biochemical findings. These results indicated that ?-sitosterol, the compound isolated from L. nodiflora, possessed antihyperglycemic activity. PMID:21658378

Balamurugan, Rangachari; Duraipandiyan, Veeramuthu; Ignacimuthu, Savarimuthu

2011-06-07

93

Chemical sympathectomy further increases muscle protein degradation of acutely diabetic rats.  

PubMed

The present work investigated the role of the sympathetic nervous system (SNS) in the control of protein degradation in skeletal muscles from rats with streptozotocin (STZ)-induced diabetes. Diabetes (1, 3, and 5 days after STZ) induced a significant increase in the norepinephrine content of soleus and EDL muscles, but it did not affect plasma catecholamine levels. Chemical sympathectomy induced by guanethidine (100 mg/kg body weight, for 1 or 2 days) reduced muscle norepinephrine content to negligible levels (less than 5%), decreased plasma epinephrine concentration, and further increased the high rate of protein degradation in muscles from acutely diabetic rats. The rise in the rate of proteolysis (nmol.mg wet wt(-1).2h(-1)) in soleus from 1-day diabetic sympathectomized rats was associated with increased activities of lysosomal (0.127 +/- 0.008 vs. 0.086 +/- 0.013 in diabetic control) and ubiquitin (Ub)-proteasome-dependent proteolytic pathways (0.154 +/- 0.007 vs. 0.121 +/- 0.006 in diabetic control). Increases in Ca2+-dependent (0.180 +/- 0.007 vs. 0.121 +/- 0.011 in diabetic control) and Ub-proteasome-dependent proteolytic systems (0.092 +/- 0.003 vs. 0.060 +/- 0.002 in diabetic control) were observed in EDL from 1-day diabetic sympathectomized rats. The lower phosphorylation levels of AKT and Foxo3a in EDL muscles from 3-day diabetic rats were further decreased by sympathectomy. The data suggest that the SNS exerts acute inhibitory control of skeletal muscle proteolysis during the early stages of diabetes in rats, probably involving the AKT/Foxo signaling pathway. PMID:18663737

Baviera, Amanda Martins; Zanon, Neusa Maria; Navegantes, Luiz Carlos C; Migliorini, Renato Hélios; Kettelhut, Isis C

2008-08-01

94

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

PubMed Central

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.

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

2013-01-01

95

Effect of Commiphora mukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats  

PubMed Central

Objective To study the antioxidant efficacy of Commiphora mukul (C. mukul) gum resin ethanolic extract in streptozotocin (STZ) induced diabetic rats. Methods The male Wistar albino rats were randomly divided into four groups of eight animals each: Control group (C), CM-treated control group (C+CMEE), Diabetic control group (D), CM- treated diabetic group (D+CMEE). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg/ bwt). After being confirmed the diabetic rats were treated with C. mukul gum resin ethanolic extract (CMEE) for 60 days. The biochemical estimations like antioxidant, oxidative stress marker enzymes and hepatic marker enzymes of tissues were performed. Results The diabetic rats showed increased level of enzymatic activities aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) in liver and kidney and oxidative markers like lipid peroxidation (LPO) and protein oxidation (PO) in pancreas and heart. Antioxidant enzyme activities were significantly decreased in the pancreas and heart compared to control group. Administration of CMEE (200 mg/kg bw) to diabetic rats for 60 days significantly reversed the above parameters towards normalcy. Conclusions In conclusion, our data indicate the preventive role of C. mukul against STZ-induced diabetic oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of diabetes and aggravated antioxidant status.

Ramesh, B; Karuna, R; Sreenivasa, Reddy S; Haritha, K; Sai, Mangala D; Sasi, Bhusana Rao B; Saralakumari, D

2012-01-01

96

Potential of Nonoral ?-Lipoic Acid Aqueous Formulations to Reduce Ocular Microvascular Complications in a Streptozotocin-Induced Diabetic Rat Model.  

PubMed

Abstract Purpose: ?-Lipoic acid (LA) aqueous formulations were studied for nonoral administration, including intravitreal and intraperitoneal preparations and topical eyedrops. The potential retinoprotective effects of these LA preparations were also evaluated in streptozotocin (STZ)-induced diabetic rats for screening better delivery systems of LA. Methods: Four LA liquid preparations were prepared and investigated. The short-term accelerated stabilities of LA preparations were investigated at 3 temperatures: 50°C, 70°C, and 90°C. The time courses of LA degradation in the preparations were determined by high-performance liquid chromatography. Furthermore, the potential therapeutic effects of LA preparations in a STZ-induced diabetic rat model were assessed by vitreous fluorophotometry to evaluate the fluorescein leakage from ocular vascular vessels into the vitreous. Capillary lesion in the retina was also examined using hematoxylin-eosin-stained microsections. Results: LA in an aqueous solution was rapidly degraded with the activation energy of 10.4 kcal/mol. The 3 LA preparations had shelf lives of ?1 month at 25°C. These formulations significantly reduced the vitreous fluorescein level in STZ-induced diabetic rats as evaluated by the fluorescein leakage after tail vein injection. Capillary lesions in the retina of the diabetic rats were remarkably reduced by nonoral administration, particularly the intraperitoneal injection (30?mg/kg/day). Conclusions: LA could be developed as aqueous preparations with suitable stability for short-term use in nonoral administration. LA preparations could be administered intravitreally or intraperitoneally to reduce ocular microvascular complications, such as retinopathy, in diabetic patients. PMID:23848951

Chen, Chen-Ling; Cheng, Wen-Sheng; Chen, Jiin-Long; Chiang, Chiao-Hsi

2013-07-13

97

Influence of rutin treatment on biochemical alterations in experimental diabetes.  

PubMed

Dietary antioxidant compounds such as flavonoids may offer some protection against early-stage diabetes mellitus and its complications. Abnormalities in both glucose metabolism and lipid profile constitute one of the most common complications in diabetes mellitus. The present study aimed to evaluate the effect of rutin, through biochemical parameters, on experimental streptozotocin (STZ)-induced diabetes in rats. Male Wistar rats were divided into four groups: untreated controls (GI); normal rats receiving rutin (GII); untreated diabetics (GIII); diabetic rats receiving rutin (GIV). STZ was injected at a single dose of 60 mg kg(-1) to induce diabetes mellitus. The diabetes resulted in increased serum glucose, cholesterol, triacylglycerols and lipoproteins (LDL and VLDL-cholesterol) but decresed serum HDL-cholesterol and insulin. Rutin (50 mg kg(-1)) reduced (p<0.05) blood glucose and improved the lipid profile in STZ-induced diabetic rats. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities were significantly augmented in serum of STZ-diabetic rats, while these activities were diminished in hepatic and cardiac tissues compared with the control group. Rutin prevents changes in the activities of ALT, AST and LDH in the serum, liver and heart, indicating the protective effect of rutin against the hepatic and cardiac toxicity caused by STZ. Rutin was associated with markedly decreased hepatic and cardiac levels of tryacylglycerols and elevated glycogen. These results suggest that rutin can improve hyperglycemia and dyslipidemia while inhibiting the progression of liver and heart dysfunction in STZ-induced diabetic rats. PMID:19932588

Fernandes, Ana Angélica Henrique; Novelli, Ethel Lourenzi Barbosa; Okoshi, Katashi; Okoshi, Marina Politi; Di Muzio, Bruno Paulino; Guimarães, Julliano F Campos; Fernandes Junior, Ary

2009-10-27

98

Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats  

PubMed Central

Background and Objective: Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of naringenin was investigated on aortic reactivity of streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Male diabetic rats (n=32) were divided into control, naringenin-treated control, diabetic, and naringenin-treated diabetic groups of eight animals each. The latter group received naringenin for 5 weeks at a dose of 10 mg/kg/day after diabetes induction. The contractile responses to potassium chloride (KCl) and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Meanwhile, participation of nitric oxide (NO) and endothelial vasodilator factors in response to ACh were evaluated using N (G)-nitro-l-arginine methyl ester (L-NAME) and indomethacin (INDO), respectively. Results: Maximum contractile response of endothelium-intact rings to KCl and PE was significantly (P<0.05) lower in naringenin-treated diabetic rats as compared to untreated diabetics. Endothelium-dependent relaxation to ACh was significantly (P<0.05-0.01) higher in naringenin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N (G)-nitro-l-arginine methyl ester (L-NAME) significantly (P<0.001) attenuated the observed response. Conclusion: Chronic treatment of diabetic rats with naringenin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and endothelium integrity is necessary for this beneficial effect.

Fallahi, Faramarz; Roghani, Mehrdad; Moghadami, Sanaz

2012-01-01

99

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

PubMed Central

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.

Singh, Rambir; Bhardwaj, Priyanka; Sharma, Poonam

2013-01-01

100

Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.  

PubMed

The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes. The increase in brain CK possibly expresses alterations in energy production. The decrease in CK activity caused by V and T treatment in diabetic rats suggests that both agents tend to normalize energy consumption. It is also possible that V and T-induced hypoglycemic effects cause metabolic alterations in brain. PMID:18038759

Lemberg, A; Fernández, M A; Ouviña, G; Rodríguez, R R; Peredo, H A; Susemihl, C; Villarreal, I; Filinger, E J

2007-12-01

101

Comparison of antinociceptive and antidiabetic effects of sertraline and amitriptyline on streptozotocin-induced diabetic rats.  

PubMed

Antidepressants (ADs) are frequently used for the treatment of persistent pain associated with diabetic neuropathy. The aim of this study is to investigate the antinociceptive effects of sertraline (Ser) and amitriptyline (Ami) in diabetic rats, and additionally monitoring their effects on grip strength, blood glucose and percentage glycosylated hemoglobin (GHb%) levels. Streptozotocin (STZ; 55 mg/kg, intraperitoneal [ip]) was injected in rats to induce diabetes. After 7 days, Ser (30 mg/kg) or Ami (15 mg/kg) was administered in diabetic rats orally. After 28 days drug treatment, the antinociceptive effects were evaluated using hot plate test both in diabetic and non-diabetic rats. The effects of these drugs on grip strength, blood glucose and GHb% were also measured. Ser and Ami showed antinociceptive effects in diabetic and non-diabetic rats. Both the drugs increased the grip strength reduction in STZ-induced diabetic rats. Ser reduces and Ami increases the serum glucose levels in diabetic and normal rats. Administration of Ami per se increased GHb% levels, while Ser per se has no effects. The effects of Ser (30 mg/kg, per os [po]) on glucose, GHb% and antinociceptive action on hot plate test showed an association between improved blood glucose levels and analgesia. However, the results of Ami treatment are controversial and needs further studies. PMID:20194573

Mahmood, Danish; Akhtar, M; Vohora, Divya; Khanam, Razia

2010-03-01

102

Altered MicroRNA Expression Profiles in Retinas with Diabetic Retinopathy  

Microsoft Academic Search

Rats with streptozotocin (STZ)-induced diabetes were studied in order to identify abnormal microRNA (miRNA) expression profiles in diabetic retinopathy (DR) and to ascertain miRNAs associated with DR. Histopathologically, we observed characteristic features of DR in rats at 10 weeks after STZ injection. Investigation of miRNA expression profiles in the retinas of control and diabetic rats using miRNA microarrays revealed that

Jin-hui Wu; Yu Gao; An-jing Ren; Shi-hong Zhao; Ming Zhong; Ya-jun Peng; Wei Shen; Ming Jing; Lin Liu

2012-01-01

103

Hypolipidaemic activity of Helicteres isora L. bark extracts in streptozotocin induced diabetic rats.  

PubMed

In this study, the hypolipidaemic effect of an aqueous extract of the bark of Helicteres isora was investigated in streptozotocin (STZ)-induced diabetic rats. Administration of the bark extract of Helicteres isora (100 and 200 mg/kgb.w.) for 21 days resulted in significant reduction in serum and tissue cholesterol, phospholipids, free fatty acids and triglycerides in STZ diabetic rats. In addition to that, significant (p<0.05) decrease in high-density lipoprotein (HDL) whereas significant increase (p<0.05) low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) were observed in STZ diabetic rats, which were normalized after 21 days of bark extract treatment. The bark extract at a dose of 200 mg/kgb.w. showed much significant hypolipidaemic effect than at the dose of 100 mg/kgb.w. PMID:18191354

Kumar, G; Murugesan, A G

2007-11-22

104

Effect of iridoid glucoside on plasma lipid profile, tissue fatty acid changes, inflammatory cytokines, and GLUT4 expression in skeletal muscle of streptozotocin-induced diabetic rats.  

PubMed

The present study was designed to examine the antihyperlipidaemic potential of iridoid glucoside isolated from Vitex negundo leaves in STZ-induced diabetic rats. The levels of cholesterol (TC), triglycerides, lipoproteins, free fatty acids, phospholipids, fatty acid composition, proinflammatory cytokines, muscle glycogen content, and glucose transporter 4 (GLUT4) expression were estimated in control and diabetic rats. Oral administration of iridoid glucoside at a dose of 50 mg/kg body weight per day to STZ-induced diabetic rats for a period of 30 days resulted in a significant reduction in plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids, and phospholipids. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low density lipoprotein- and very low density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with iridoid glucoside. The fatty acid composition of the liver and kidney was analyzed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was also restored upon treatment with iridoid glucoside. Moreover, the elevated plasma levels of proinflammatory cytokines and decreased levels of muscle glycogen and GLUT4 expression in the skeletal muscle of diabetic rats were reinstated to their normal levels via enhanced secretion of insulin from the remnant ? cells of pancreas by the administration of iridoid glucoside. The effect produced by iridoid glucoside on various parameters was comparable with that of glibenclamide, a well-known antihyperglycemic drug. PMID:23625195

Sundaram, Ramalingam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

2013-04-27

105

The augmentation of pituitary adenylate cyclase-activating polypeptide (PACAP) in streptozotocin-induced diabetic rats.  

PubMed

Pituitary adenylate cyclase activating polypeptide (PACAP), which was isolated from ovine hypothalamic extract, has been shown to have a physiological role in the regulation of insulin or islet functions. In streptozotocin (STZ)-induced diabetic rats, we examined the content of PACAP immunoreactivity and gene expression of three specific receptors. Four weeks after administration of STZ (50 mg/kg), plasma glucose levels increased 3.3-fold, and plasma insulin levels decreased to one-tenth as compared with the control. The content of PACAP immunoreactivity in the pancreas potently increased by 30%, but the content of vasoactive intestinal polypeptide (VIP) immunoreactivity was not changed. In the other tissues, the content of PACAP immunoreactivity did not significantly change except in the hypothalamus, which showed a 10% increment. In the expression level of PACAP/VIP receptors, semi-quantitative RT-PCR analysis revealed that VIP1/PACAP receptor mRNA significantly increased as compared with the other two types of receptors in the pancreas of STZ-induced diabetic rats. These findings suggest that PACAP and VIP1/PACAP receptor might be involved in the pathophysiology of diabetes mellitus. PMID:9864055

Tamakawa, H; Miyata, A; Satoh, K; Miyake, Y; Matsuo, H; Arimura, A; Kangawa, K

1998-01-01

106

In vivo antioxidant and hypolipidemic effect OF Cardiospermum halicacabum leaf extract in streptozotocin-induced diabetic rats.  

PubMed

In this study we investigated the antioxidant and antihyperlipidemic of an ethanolic leaf extract of Cardiospermum halicacabum (CHE) in plasma and tissues of streptozotocin (STZ)-induced diabetic rats. The plasma and tissue concentrations of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide were significantly elevated in STZ diabetic rats. CHE administration decreased TBARS and lipid hydroperoxide levels. The plasma vitamin E level increased and the vitamin C level decreased. The reduced glutathione level significantly decreased in plasma and tissues, as did the activities of enzymatic antioxidants. The enzymatic and non enzymatic alterations reversed toward normalcy after treatment with CHE. STZ-induced diabetic rats showed significant increases in plasma total cholesterol, phospholipids, triglycerides, and free fatty acids, which returned to near normalcy in CHE-treated animals. Plasma LDL-C and VLDL-C increased and HDL-C decreased and both reverted to near normalcy following CHE treatment. We conclude that CHE possesses antioxidant and hypolipidemic effects in diabetic rats, which may be due to the presence of flavonoids, such as apigenin and luteolin in the extract. PMID:20853595

Veeramani, Chinnaveeramani; Pushpavalli, Ganesan; Pugalendi, Kodukkur Viswanathan

2010-01-01

107

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

PubMed

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

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

2013-04-06

108

Antiarrhythmic effects and ionic mechanisms of allicin on myocardial injury of diabetic rats induced by streptozotocin.  

PubMed

The aim of this study was to evaluate the antiarrhythmic effect of allicin (AL) on streptozotocin (STZ)-induced diabetic rats and explore the possible mechanisms. Hyperglycemia was induced in rats by single intraperitoneal injection of STZ (40 mg/kg). Three days after STZ treatment, the hyperglycemic rats (plasma glucose levels?16.7 mM) were administered with AL (4, 8, and 16 mg/kg) by intraperitoneal injection daily for 28 days. The fasting blood glucose levels were measured on every seventh day during the 28 days of treatment. The body weight and blood glucose levels were detected after 28 days. Antiarrhythmic effect of AL was observed in the diabetic rats induced by BaCl2. To determine the ionic mechanism in rat ventricular myocytes of AL, action potential duration (APD), L-type calcium current (ICa-L), and inward rectifier potassium current (IK1) were recorded by the whole cell-patch clamp technique. The expressions of L-type calcium channel protein ?1C mRNA and cell potassium channels protein Kir2.1 mRNA were studied by RT-PCR. AL normalized the RR interval and QT interval in diabetic rats. AL obviously delayed the onset of ventricular arrhythmia and reduced the score of arrhythmia induced by BaCl2. Electrophysiological experiment revealed that AL could shorten APD through inhibition of ICa-L and enhancement of IK1. RT-PCR analysis indicated that long-term treatment with AL could decrease the expression of ?1C mRNA and increase the expression of Kir2.1 mRNA. AL has antiarrhythmic effect in STZ-induced diabetic rats. It is tempting for the application of AL to be a useful therapeutic approach in diabetes with ventricular arrhythmia. PMID:23604291

Huang, Wei; Wang, Ye; Cao, Yong-Gang; Qi, Han-Ping; Li, Lei; Bai, Bing; Liu, Yang; Sun, Hong-Li

2013-04-20

109

Diabetes impairs synaptic plasticity in the superior cervical ganglion: possible role for BDNF and oxidative stress.  

PubMed

The majority of diabetics develop serious disorders of the autonomic nervous system; however, there is no clear understanding on the causes of these complications. In this study, we examined the effect of streptozocin (STZ)-induced diabetes on activity-dependent synaptic plasticity, associated levels of brain-derived neurotrophic factor (BDNF) and antioxidant biomarkers in the rat sympathetic superior cervical ganglion. Diabetes (STZ-induced) was achieved by a single intraperitoneal injection of streptozocin (55 mg/kg).Compound action potentials were recorded from isolated ganglia before (basal) and after repetitive stimulation, or trains of paired pulses to express ganglionic long-term potentiation (gLTP) or long-term depression (gLTD). The input/output curves of ganglia from STZ-treated animals showed a marked rightward shift along most stimulus intensities, compared to those of ganglia from control animals, indicating impaired basal synaptic transmission in ganglia from STZ-induced diabetic animals. Repetitive stimulation induced robust gLTP and gLTD in ganglia isolated from control animals; the same protocols failed to induce gLTP or gLTD in ganglia from STZ-induced diabetic animals, indicating impairment of activity-dependent synaptic plasticity in these animals. Molecular analysis revealed significant reduction in the levels of BDNF and the ratio of glutathione/oxidized glutathione. Additionally, the activity of glutathione peroxidase, glutathione reductase, catalase, and the levels of thiobarbituric acid-reactive substances were increased in ganglia from STZ-treated animals. In conclusion, impaired basal synaptic transmission and synaptic plasticity are associated with reduced BDNF and altered oxidative stress biomarkers in the sympathetic ganglia from STZ-induced diabetic animals, suggesting a possible correlation of these factors with the manifestations of STZ-induced diabetes in the peripheral nervous system. PMID:23832486

Alzoubi, K H; Khabour, O F; Alhaidar, I A; Aleisa, A M; Alkadhi, K A

2013-07-06

110

Phosphatidylinositol-3-kinase is involved in the antihyperglycemic effect induced by resveratrol in streptozotocin-induced diabetic rats.  

PubMed

Resveratrol, a polyphenolic substance found in grape skin, is proposed to account in part for the protective effect of red wine in the cardiovascular system. The aim of the present study is to investigate the action and possible mechanisms of resveratrol-produced regulation of plasma glucose in normal and diabetic rats including the animal model of streptozotocin (STZ)-induced and nicotinamide-STZ-induced (NA-STZ), and insulin-resistant diabetic rats. Resveratrol (p.o.) produced a hypoglycemic effect in a dose-dependent manner in normal and diabetic rats, and the insulin level was increased following resveratrol treatment in normal and NA-STZ diabetic rats. In insulin-deficient STZ-diabetic rats, resveratrol significantly lowered the plasma glucose 90 min after oral treatment, and the hypoglycemic effect was abolished by phosphatidyl-3-kinase (PI3K) inhibitors (LY294002 and wortmannin) which also inhibited resveratrol-induced Akt phosphorylation in soleus muscle of STZ-diabetic rats. The change in the protein expression level of glucose transporter subtype 4 (GLUT4) in the soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats treated with resveratrol (3 mg/kg, p.o.) for 7 days was examined. Resveratrol normalized hepatic PEPCK expression and increased GLUT4 expression in the soleus muscle of STZ-diabetic rats. The results indicate that the mechanisms contributing to the hypoglycemic effect of resveratrol include insulin-dependent and insulin-independent pathway, and PI3K-Akt-signaling was involved in the latter mechanism to enhance glucose uptake in skeletal muscle. PMID:17346750

Chi, Tzong-Cherng; Chen, Win-Pin; Chi, Tsung-Li; Kuo, Tzong-Fu; Lee, Shoei-Sheng; Cheng, Juei-Tang; Su, Ming-Jai

2007-02-09

111

The effects of vanadium (V) absorbed by Coprinus comatus on bone in streptozotocin-induced diabetic rats.  

PubMed

The purpose of this study was to evaluate the effects of vanadium absorbed by Coprinus comatus (VACC) treatment on bone in streptozotocin (STZ)-induced diabetic rats. Forty-five Wistar female rats used were divided into three groups: (1) normal rats (control), (2) diabetic rats, and (3) diabetic rats treated with VACC. Normal and diabetic rats were given physiological saline, and VACC-treated rats were administered VACC intragastrically at doses of 0.18 mg vanadium/kg body weight once daily. Treatments were performed over a 12-week period. At sacrifice, one tibia and one femur were removed, subjected to micro computed tomography (micro-CT) for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. Another femoral was used for mechanical testing. In addition, bone samples were collected to evaluate the content of mineral substances in bones. Treatment with VACC increased trabecular bone volume fraction in diabetic rats. Vanadium-treated animals had significant increases in ultimate load, trabecular thickness, and osteoblast surface. However, vanadium treatment did not seem to affect bone stiffness, bone energy absorption, trabecular separation, and osteoclast number. P levels in the femurs of diabetic rats treated with VACC were significantly higher than those of diabetic animals. Ca levels in diabetic and diabetic rats treated with vanadium showed no obvious changes. In conclusion, our results provide an important proof of concept that VACC may represent a powerful approach to treating or reversing diabetic osteopathy in humans. PMID:20734239

Pei, Yi; Fu, Qin

2010-08-24

112

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

PubMed Central

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.

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

2013-01-01

113

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

PubMed

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

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

2013-06-01

114

Anti-diabetic effects of sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate in streptozotocin-induced diabetic rats.  

PubMed

The evaluation of the anti-diabetic effects of an organic vanadium(V) complex in streptozotocin (STZ)-induced diabetic rats was investigated. The STZ-induced diabetic rats were orally administrated with sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate (V5dipic-NH(2)), a vanadium(V) coordination compound. The compound was administered through drinking water at a concentration of 0.1mg/mL for 20 days, and then the concentration was increased to 0.3mg/mL for the following 20 days. At the end of the experiment, V5dipic-NH(2) statistically significantly reduced the levels of blood glucose (P<0.01), serum total cholesterol (P<0.01), triglycerides (P<0.01) and the activities of serum aspartate amino transferase (P<0.05) and alkaline phosphatase (P<0.01) compared to untreated diabetic animals. After treatment with 0.3mg/mL V5dipic-NH(2), the oral glucose tolerance was improved in diabetic animals (P<0.01). In addition, the daily intake of elemental vanadium was markedly decreased in V5dipic-NH(2)-treated diabetic rats compared to vanadyl sulfate (VOSO(4))-treated diabetic rats, which suggested that the anti-diabetic activity of the element vanadium was elevated after being modified with an organic ligand. These results suggested that V5dipic-NH(2), as an organic vanadium compound, is more effective than inorganic vanadium salt at alleviating the symptoms of diabetes. PMID:19203797

Li, Ming; Smee, Jason J; Ding, Wenjun; Crans, Debbie C

2008-11-28

115

Hypoglycemic effect of Mucuna pruriens seed extract on normal and streptozotocin-diabetic rats.  

PubMed

The hypoglycemic effect of the aqueous extract of the seeds of Mucuna pruriens was investigated in normal, glucose load conditions and streptozotocin (STZ)-induced diabetic rats. In normal rats, the aqueous extract of the seeds of Mucuna pririens (100 and 200 mg/kg body weight) significantly (P<0.001) reduced the blood glucose levels after an oral glucose load from 127.5+/-3.2 to 75.6+/-4.8 mg% 2 h after oral administration of seed extract. It also significantly lowered the blood glucose in STZ diabetic rats from 240.5+/-7.2 to 90.6+/-5.6 mg% after 21 days of daily oral administration of the extract (P<0.001). Thus, this study shows that M. pruriens has an anti-hyperglycemic action and it could be a source of hypoglycemic compounds. PMID:18672037

Bhaskar, Anusha; Vidhya, V G; Ramya, M

2008-07-10

116

Antidiabetic effect of secoisolariciresinol diglucoside in streptozotocin-induced diabetic rats.  

PubMed

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia. Its complications such as neuropathy, cardiopathy, nephropathy, and micro and macro vascular diseases are believed to be due to the increase in oxidative stress and decrease in the level of antioxidants. The aim of this study was to determine the antihyperglycemic activity of synthetic Secoisolariciresinol diglucoside (SDG) in streptozotocin (STZ)-induced diabetic rats. The synthetic SDG in a single-dose (20 mg/kg b.w.) two-day study showed dose-dependent reduction in glucose levels with maximum effect of 64.62% at 48 h post drug treatment (p<0.05), which is comparable to that of the standard drug tolbutamide (20 mg/kg b.w.). In a multi-dose fourteen-day study, lower doses of SDG (5 and 10 mg/kg b.w.) exhibited moderate reduction in glucose levels, lipid profile, restoration of antioxidant enzymes and improvement of the insulin and c-peptide levels which shows the regeneration of ?-cell which secretes insulin. Altered levels of lipids and enzymatic antioxidants were also restored by the SDG to the considerable levels in diabetic rats. Results of the present investigation suggest that diabetes is associated with an increase in oxidative stress as shown by increase in serum malondialdehyde (MDA), decreased levels of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH). Also, diabetes is associated with an increase in serum total cholesterol as well as triglycerides levels and decrease in insulin and c-peptide levels. SDG is effective in retarding the development of diabetic complications. We propose that synthetic SDG exerts anti hyperglycemic effect by preventing the liver from peroxidation damage through inhibition of ROS level mediated increased level of enzymatic and non-enzymatic antioxidants. And, also maintaining tissue function which results in improving the sensitivity and response of target cells in STZ-induced diabetic rats to insulin. PMID:23271000

Moree, Sadiq S; Kavishankar, G B; Rajesha, J

2012-12-25

117

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

PubMed

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 D(2) 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 A(1) and apoB(100)), and endothelial dysfunction parameters. Histomorphological studies also confirmed biochemical findings. Our results showed that FIIc has protective effect on hyperglycemia-induced atherosclerosis. PMID:21584267

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

2011-04-07

118

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

PubMed Central

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.

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

2011-01-01

119

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

PubMed Central

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.

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

120

The stem bark extracts of Cenostigma macrophyllum attenuates tactile allodynia in streptozotocin-induced diabetic rats.  

PubMed

Abstract Context. Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae- Caesalpinioideae) is popularly known as "caneleiro". Previous studies showed antioxidant action and analgesic effects of the ethanol extract from the leaves of C. macrophyllum. The phytochemical evaluation of the stem bark revealed the presence of antinociceptive compounds. Objective: To investigate the antinociceptive actions of the ethanol extract and ethyl acetate fraction from C. macrophyllum stem bark in streptozotocin (STZ)-induced diabetic rats and the involvement of opioid and nitrergic mechanisms. Materials and methods: STZ-rats received the ethanol extract (E.EtOH 200 and 300?mg/kg, p.o.) during 5 weeks. In acute experiments, untreated diabetic rats were treated with the ethyl acetate fraction (F.EtOAc 250 and 500?mg/kg, p.o.), on the 28th day of diabetes induction when the opioid and nitrergic mechanisms were investigated. The mechanical nociceptive threshold (MNT) was determined by application of von Frey filaments. Results: Data show that STZ-induced diabetic rats developed a significant tactile allodynia during 5 weeks. Diabetic rats that received E.EtOH (200 and 300?mg/kg) and F.EtOAc (250 and 500?mg/kg) had a pain threshold higher than those in the STZ-vehicle group. F.EtOAc effects were inhibited by pretreatment with naloxone and were not influenced by .-arginine. Discussion and conclusion: The results suggest that the ethanol extract and ethyl acetate fraction of C. macrophyllum presented antinociceptive activity. Thus, F.EtOAc may be exerting its effect by affecting the opioid system, but nitrergic mechanisms are not detectable. The observed activity may be due to its gallic acid, lupeol and bergenin content. PMID:23844576

Piaulino, Celyane Alves; Carvalho, Fernanda Cerqueira Barroso; Almeida, Buana Carvalho; Chaves, Mariana Helena; Almeida, Fernanda Regina Castro; Brito, Salete Maria Rocha Cipriano

2013-07-11

121

Evaluation of the hypoglycemic and hypolipidemic effects of an ethylacetate fraction of Artocarpus heterophyllus (jak) leaves in streptozotocin-induced diabetic rats  

PubMed Central

Aqueous extracts of mature leaves of Artocarpus heterophyllus (jak) are used by traditional medical practitioners in Sri Lanka and India for the treatment of diabetes. This study was conducted to investigate the hypoglycemic and hypolipidemic effects of an ethylacetate (EA) fraction of the mature leaves of A. heterophyllus in a streptozotocin (STZ) induced diabetic rat model. In normoglycemic rats, administration of a single dose (20 mg/kg) of the EA fraction resulted in a significant (P < 0.05) reduction in the fasting blood glucose concentration and a significant improvement in glucose tolerance (P < 0.05), compared to the controls. In STZ-induced diabetic rats, chronic administration of the EA fraction of A. heterophyllus leaves daily for 5 weeks resulted in a significant lowering of serum glucose, cholesterol and triglyceride (TG) levels. Compared to control diabetic rats, the extract-treated rats had 39% less serum glucose, 23% lower serum total cholesterol and 40% lower serum TG levels and 11% higher body weight at the end of the fifth week. The percentage reductions in the serum parameters mediated by the test fraction were comparable with those produced by glibenclamide (0.6 mg/kg), the reference drug used in this study. It can be concluded that the EA fraction of A. heterophyllus leaves contains one or more hypoglycemic and hypolipidemic principles which have the potential to be developed further for the treatment of diabetes specifically associated with a hyperlipidemic state.

Chackrewarthy, S.; Thabrew, M. I.; Weerasuriya, M. K. B.; Jayasekera, S.

2010-01-01

122

Hypoglycemic effect of Rehmannie Radix Preparata (Sookjihwang) extract in streptozotocin-induced diabetic rats  

PubMed Central

Rhemannie Radix Preparata (RRP) has been previously employed in traditional oriental medicine as a treatment for diabetic thirst and improving blood flow. The aim of this study was to evaluate its hypoglycemic control by assaying the activities of key enzymes of carbohydrate metabolism in streptozotocin-(STZ)-induced diabetic rats. Further, RRP extracts were prepared in water (RRPW), in 50% ethanol (RRP50), and in 100% ethanol (RRP100), respectively, and compared for their actions in diabetic rats. The oral treatment of RRP (5 mg/kg b.w./d) to diabetic rats for 21 days resulted in a significant decline in blood glucose by 67% compared to diabetic control rats (P < 0.05). The altered activities of glucokinase, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and acetyl CoA carboxylase (ACC) in the livers of diabetic rats were reversed significantly to near-normal levels by the administration of RRP (P < 0.05). Among the three RRP extracts, RRP100 was the most effective in terms of hypoglycemic action. However, the administration of RRP to diabetic rats did not improve insulin production. The modulatory effects of RRP100 on the attenuation of carbohydrate enzyme activities appear to hold promise for widespread use for the treatment of diabetes in the future.

Kang, Shin-Jyung; Bao, Cun Liu; Park, Soojin

2010-01-01

123

Effects of Crataegus microphylla on vascular dysfunction in streptozotocin-induced diabetic rats.  

PubMed

Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65?mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4?weeks of diabetes, CM extract (100?mg/kg) was administrated to diabetic rats for 4?weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5) ?M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-? and IL-6 and by preventing lipid peroxidation. PMID:22585450

Topal, Gökçe; Koç, Ebru; Karaca, Cetin; Altu?, Tuncay; Ergin, Bülent; Demirci, Cihan; Meliko?lu, Gülay; Meriçli, Ali H; Kucur, Mine; Ozdemir, Osman; Uyde? Do?an, B Sönmez

2012-05-14

124

Effects of pancreatic transplantation on osteopenia in streptozotocin-induced non-insulin-dependent diabetic rats.  

PubMed

The effect of pancreatic transplantation on mineral homeostasis and the histomorphometric changes were studied in streptozotocin (STZ)-induced non-insulin-dependent diabetic rat. Although the fasting blood-glucose levels in diabetic rat were similar to those in controls, intravenous glucose tolerance tests (ivGTT) showed diabetic patterns in the diabetic rat. Serum ALP was found to be significantly higher, but bony ALP (calvarium) and circulating 1;25(OH)D were markedly decreased, in diabetic rat. The histomorphometric study showed a decreased relative osteoid volume (ROV), a decreased total osteoid volume (TOV), and an increased inert surface of the osteoid. Tetracycline (TC) labeling failed to be acquired in diabetic rat. These findings indicated that long-term insulin deficiency may be related to a lack in the maturity of the bone matrix and reduced turn-over. Transplanted rat showed a normal response to ivGTT and increased bony ALP. Histologically, ROV and TOV increased together, with acquired TC double labeling lines. These results indicated that diabetic osteopenia can be reversed by pancreatic transplantation. PMID:7852784

Kato, H; Nozawa, M

1994-11-01

125

Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction  

PubMed Central

Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function is associated with reduced endoneural blood flow (EBF) which may contribute to nerve dysfunction.We examined whether diabetes-induced reductions in sciatic nerve conduction velocity and EBF were associated with impaired endothelium-dependent dilation in adjacent arterioles. We measured motor nerve conduction velocity (MNCV) in the sciatic nerve using a non-invasive procedure, and sciatic nerve nutritive blood flow using microelectrode polarography and hydrogen clearance. In vitro videomicroscopy was used to quantify arteriolar diameter responses to dilator agonists in arterioles overlying the sciatic nerve.MNCV and EBF in 4-week-STZ-induced diabetic rats were decreased by 22% and 49% respectively. Arterioles were constricted with U46619 and dilation to acetylcholine (ACh), aprikalim, or sodium nitroprusside (SNP) examined. All agonists elicited dose-dependent dilation in control and diabetic rats, although ACh-induced dilation was significantly reduced in diabetic rats. Treating vessels from normal or diabetic rats with indomethacin (INDO) alone did not significantly affect ACh-induced relaxation. However, ACh-induced vasodilation was significantly reduced by treatment with KCl or N?-nitro-L-arginine (LNNA) alone. Combining LNNA and KCl further reduced ACh-induced dilation in these vessels.Diabetes causes vasodilator dysfunction in a microvascular bed that provides circulation to the sciatic nerve. These studies imply that ACh-induced dilation in these vessels is mediated by multiple mechanisms that may include the endothelial-dependent production of nitric oxide and endothelial-derived hyperpolarizing factor. This impaired vascular response is associated with neural dysfunction.

Terata, K; Coppey, L J; Davidson, E P; Dunlap, J A; Gutterman, D D; Yorek, M A

1999-01-01

126

Effect of dragon fruit extract on oxidative stress and aortic stiffness in streptozotocin-induced diabetes in rats.  

PubMed

Cardiovascular complications are consistently observed in diabetic patients across all age groups. The objective of the present study was to investigate the effect of aqueous extract of the fruit pulp of Hylocereus undatus (DFE) on aortic stiffness and oxidative stress in streptozotocin (STZ)-induced diabetes in rats. Twenty-four male, Sprague-Dawley rats were randomized into four groups: I (control), II (diabetic), III (DFE, 250 mg/kg) and IV (DFE 500 mg/kg). Diabetes was induced in groups II, III and IV by intraperitoneal (i.p.) injection of STZ (40 mg/kg). After confirmation of diabetes, group III and IV received DFE for 5 weeks. Pulse wave velocity (PWV) was used as a marker of aortic stiffness and was determined at the end of 5 weeks. DFE significantly decreased (P < 0.05) the fasting blood glucose levels in diabetic rats, but not to normal levels. Systolic blood pressure, pulse pressure and PWV were significantly increased (P < 0.05) in diabetic rats at the end of 5 weeks in comparison with control group. DFE treatment significantly decreased (P < 0.05) these elevations. Oxidative damage was observed in group II after 5 weeks. Plasma malondialdehyde levels significantly decreased (P < 0.05), while superoxide dismutase and total antioxidant capacity significantly increased (P < 0.05) with DFE treatment in comparison with group II. These data demonstrate that DFE treatment was effective in controlling oxidative damage and decreasing the aortic stiffness measured by PWV in STZ-induced diabetes in rats. PMID:21808536

Anand Swarup, Kolla R L; Sattar, Munavvar A; Abdullah, Nor A; Abdulla, Mohammed H; Salman, Ibrahim M; Rathore, Hassaan A; Johns, Edward J

2010-01-01

127

Effect of dragon fruit extract on oxidative stress and aortic stiffness in streptozotocin-induced diabetes in rats  

PubMed Central

Cardiovascular complications are consistently observed in diabetic patients across all age groups. The objective of the present study was to investigate the effect of aqueous extract of the fruit pulp of Hylocereus undatus (DFE) on aortic stiffness and oxidative stress in streptozotocin (STZ)-induced diabetes in rats. Twenty-four male, Sprague-Dawley rats were randomized into four groups: I (control), II (diabetic), III (DFE, 250 mg/kg) and IV (DFE 500 mg/kg). Diabetes was induced in groups II, III and IV by intraperitoneal (i.p.) injection of STZ (40 mg/kg). After confirmation of diabetes, group III and IV received DFE for 5 weeks. Pulse wave velocity (PWV) was used as a marker of aortic stiffness and was determined at the end of 5 weeks. DFE significantly decreased (P < 0.05) the fasting blood glucose levels in diabetic rats, but not to normal levels. Systolic blood pressure, pulse pressure and PWV were significantly increased (P < 0.05) in diabetic rats at the end of 5 weeks in comparison with control group. DFE treatment significantly decreased (P < 0.05) these elevations. Oxidative damage was observed in group II after 5 weeks. Plasma malondialdehyde levels significantly decreased (P < 0.05), while superoxide dismutase and total antioxidant capacity significantly increased (P < 0.05) with DFE treatment in comparison with group II. These data demonstrate that DFE treatment was effective in controlling oxidative damage and decreasing the aortic stiffness measured by PWV in STZ-induced diabetes in rats.

Anand Swarup, Kolla R. L.; Sattar, Munavvar A.; Abdullah, Nor A.; Abdulla, Mohammed H.; Salman, Ibrahim M.; Rathore, Hassaan A.; Johns, Edward J.

2010-01-01

128

The antidiabetic effects of an herbal formula composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin-induced diabetic rats.  

PubMed

A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of ?-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry. PMID:23610602

Hu, Weicheng; Yeo, Jin-Hee; Jiang, Yunyao; Heo, Seong-Il; Wang, Myeong-Hyeon

2013-04-01

129

Transcriptomic Analysis in Diabetic Nephropathy of Streptozotocin-Induced Diabetic Rats  

PubMed Central

Diabetic nephropathy (DN) is a major complication of diabetes and is caused by an imbalance in the expression of certain genes that activate or inhibit vital cellular functions of kidney. Despite several recent advances, the pathogenesis of DN remains far from clear, suggesting the need to carry out studies identifying molecular aspects, such as gene expression, that could play a key role in the development of DN. There are several techniques to analyze transcriptome in living organisms. In this study, the suppression subtractive hybridization (SSH) method was used to generate up- and down-regulated subtracted cDNA libraries in the kidney of streptozotocin (STZ)-induced diabetic rats. Northern-blot analysis was used to confirm differential expression ratios from the obtained SSH clones to identify genes related to DN. 400 unique SSH clones were randomly chosen from the two subtraction libraries (200 of each) and verified as differentially expressed. According to blast screening and functional annotation, 20.2% and 20.9% of genes were related to metabolism proteins, 9% and 3.6% to transporters and channels, 16% and 6.3% to transcription factors, 19% and 17.2% to hypothetical proteins, and finally 24.1 and 17.2% to unknown genes, from the down- and up-regulated libraries, respectively. The down- and up-regulated cDNA libraries differentially expressed in the kidney of STZ diabetic rats have been successfully constructed and some identified genes could be highly important in DN.

Lomas-Soria, Consuelo; Ramos-Gomez, Minerva; Guevara-Olvera, Lorenzo; Guevara-Gonzalez, Ramon; Torres-Pacheco, Irineo; Gallegos-Corona, Marco A.; Reynoso-Camacho, Rosalia

2011-01-01

130

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

PubMed Central

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.

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

2007-01-01

131

Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats  

PubMed Central

Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-? and decreased insulin growth factor (IGF)-1? in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-? and IGF-1?, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and antiapototic effects.

Georgy, Gehan S.; Nassar, Noha N.; Mansour, Hanaa A.; Abdallah, Dalaal M.

2013-01-01

132

Beneficial effect of S-allylcysteine (SAC) on blood glucose and pancreatic antioxidant system in streptozotocin diabetic rats.  

PubMed

The aim of the present study was to evaluate the possible protective effects of S-allyl cysteine (SAC) on the antioxidant defense system of pancreas in streptozotocin(STZ) induced diabetes in rats. The levels of blood glucose and TBARS in plasma and pancreas were estimated in control and experimental groups of rats. To assess the changes in the cellular antioxidant defense system, the level of reduced glutathione in plasma and pancreas and activities of superoxide dismutase and catalase were assayed in pancreatic tissue homogenate. The levels of glucose, TBARS and enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of SAC. The antidiabetic and antioxidant effect of SAC was compared with glyclazide, a well-known hypoglycemic drug. These findings suggest that SAC treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress. PMID:20839055

Saravanan, Ganapathy; Ponmurugan, Ponnusamy

2010-12-01

133

Glabridin as a major active isoflavan from Glycyrrhiza glabra (licorice) reverses learning and memory deficits in diabetic rats.  

PubMed

Cognitive impairment occurs in diabetes mellitus. Glabridin as a major active flavonoids in Glycyrrhiza glabra (licorice) improves learning and memory in mice. In the present study, we investigated the effect of chronic treatment with glabridin (5, 25 and 50 mg/kg, p.o.) on cognitive function in control and streptozotocin (STZ)-induced diabetic rats.Animals were divided into untreated control, glabridin-treated control (5, 25 and 50 mg/kg), untreated diabetic and glabridin treated diabetic (5, 25 and 50 mg/kg) groups. Treatments were begun at the onset of hyperglycemia. Passive avoidance learning (PAL) and memory was assessed 30 days later. Diabetes caused cognition deficits in the PAL and memory paradigm. While oral glabridin administration (25 and 50 mg/kg) improved learning and memory in non-diabetic rats, it reversed learning and memory deficits of diabetic rats. Low dose glabridin (5 mg/kg) did not alter cognitive function in non-diabetic and diabetic groups. Glabridin treatment partially improved the reduced body weight and hyperglycemia of diabetic rats although the differences were not significant. The combination of antioxidant, neuroprotective and anticholinesterase properties of glabridin may all be responsible for the observed effects. These results show that glabridin prevented the deleterious effects of diabetes on learning and memory in rats. Further studies are warranted for clinical use of glabridin in the management of demented diabetic patients. PMID:21616781

Hasanein, Parisa

2011-06-01

134

A stereological study of effects of aqueous extract of Tamarindus indica seeds on pancreatic islets in streptozotocin-induced diabetic rats.  

PubMed

Tamarindus indica Linn was used as a traditional medicine for the management of diabetes mellitus in human and experimental animals. This study investigated effects of aqueous extract of Tamarindus indica seeds (AETIS) against STZ-induced damages in pancreatic islands by means of stereological methods. sixty matured normoglycemic male Wistar rats, weighing 200-250 gr, were selected and randomly divided into 6 groups (n=10). Control, STZ-induced diabetic; by intraperitoneal injection of 55 mg/Kg streptozotocin, Treated control group (TC); received AETIS at a dose of 200mg/kg/day, and AETIS treated diabetic groups (TD1-3); received respectively AETIS at the dose of 50, 100,and 200 mg/kg/day by gavage from one week after induction of diabetes by STZ. After 8 weeks of experiment, stereological estimation of volume density and total volume of islets and beta cells, volume weighted mean islets volume, mass of beta cells, islets, and pancreas and total number of islets were done. Volume density and total volume of islets, volume weighted mean islets volume, volume density islets/pancreas, volume density beta cells/islet, mass of islets and pancreas of treated diabetic groups (TD1-3) were significantly higher than untreated diabetic group (P<0.001), and in TD3 group these values were comparable to controls. Although total volume and mass of beta cells in TD1-3 were significantly higher than D group but they were significantly lower than control group (P>0.05). Total number of islets, pancreas wet weight and volume did not show any significant changes between control and experimental groups (P>0.05). Results suggested that AETIS partially restores pancreatic beta cells and repairs STZ-induced damages in rats. PMID:20884458

Hamidreza, Hamidreza; Heidari, Zahra; Shahraki, Mohammadreza; Moudi, Bita

2010-10-01

135

Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats  

Microsoft Academic Search

We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF),\\u000a tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase\\/extracellular\\u000a signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats\\u000a with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague–Dawley rats were divided into the

Chang-Hun Chae; Sung-Lim Jung; Sang-Hyun An; Chan-Kyoung Jung; Sang-Nam Nam; Hyun-Tae Kim

2011-01-01

136

Dietary ?-3 polyunsaturated fatty acids improves learning performance of diabetic rats by regulating the neuron excitability.  

PubMed

Previous research has demonstrated that diabetes induced learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids (PUFA), have been shown to enhance learning and memory and prevent memory deficits in various experimental conditions. Sprague-Dawley rats were used in the present study to investigate the effect of fish oil supplementation on spatial learning and memory of streptozotocin (STZ)-induced diabetic rats with the Morris Water Maze. The excitability of CA1 pyramidal neurons and the related ionic currents was also examined. Diabetes impaired spatial learning and memory of rats. Diabetes decreased the sodium currents and increased the potassium currents, and further led to the reduction of excitability of CA1 pyramidal neurons, effects which may contribute to the behavioral deficits. Fish oil dietary supplementation decreased the transient currents and Kv4.2 expression in the hippocampus and partially improved learning performance of diabetic rats. The results of the present study suggested that sodium and potassium currents contributed to the inhibitory effect of diabetes on neuron excitability, further influencing learning and memory processing. Dietary fish oil may modulate the membrane excitability and is a possible strategy for preventing the impairments of diabetes on hippocampal function. PMID:22516014

Yang, R-H; Wang, F; Hou, X-H; Cao, Z-P; Wang, B; Xu, X-N; Hu, S-J

2012-04-16

137

Protective effects of enalapril in streptozotocin-induced diabetic rat: studies of DNA damage, apoptosis and expression of CCN2 in the heart, kidney and liver.  

PubMed

Diabetes mellitus is characterized by hyperglycemia, which induces oxidative stress and perturbs a number of pathways, leading to tissue injury. One of the pathological responses to tissue injury is the development of fibrosis and cell death. Enalapril is a non-thiol angiotensin-converting enzyme inhibitor that is commonly used in the treatment of diabetes-associated hypertension. The present study examines the possible beneficial effects of enalapril on the development of diabetes associated fibrosis and DNA damage in rats. Sprague-Dawley rats (250 ± 10 g) were used in the study. Enalapril (10 mg kg(-1) per oral) was administered for four consecutive weeks to the streptozotocin (STZ)-induced diabetic rats. After 4 weeks, all the animals were sacrificed and comet assay (normal and modified) was performed to detect the normal as well as oxidative DNA damage. Expression of profibrotic marker CCN2 and fibrosis was examined in the heart, kidney and liver of diabetic rats. Enalapril treatment significantly restored the malondialdehyde and glutathione content as well as the DNA damage in the heart, kidney and liver of diabetic rat. Significant decrease in the expression of CCN2 was observed in the heart, kidney and liver of diabetic rat receiving enalapril treatment as compared with the diabetic group. Further, the enalapril treatment led to significant decrease in the fibrosis and CCN2 expression in the diabetic group as compared with control. The results of the present study clearly demonstrate that enalapril ameliorates the DNA damage, cell death and expression of CCN2 in the heart, kidney and liver of the STZ-induced diabetic rat. PMID:21416479

Kushwaha, S; Vikram, A; Jena, G B

2011-03-18

138

Inhibitory effect of glimepiride on nicotinamide-streptozotocin induced nuclear damages and sperm abnormality in diabetic Wistar rats.  

PubMed

The generation of reactive oxygen species in diabetes is considered to be the major cause for the mutation related defects such as cancer, infertility etc. Glimepiride (Gmp) is a third generation antidiabetic sulphonylurea known to possess the antioxidant effect in streptozotocin (STZ) induced diabetes. In this study, the anti-mutagenic activity of Gmp (0.175, 17.5 and 175 mg/kg, po daily for 4 weeks) was evaluated against the nicotinamide (NA-230 mg/kg) and STZ (65 mg/kg) induced somatic and germinal cells defect using bone marrow micronucleus (MN) test and sperm abnormality test respectively in male Wistar rats. Administration of Gmp at 175 mg prevented the NA-STZ induced increased frequency of MN in polychromatic and normochromatic erythrocytes. The treatment with Gmp also decreased the sperm shape abnormality and enhanced the sperm count besides improving the antioxidant status in the diabetic rats. However, the other doses of Gmp (0.175 and 17.5 mg) did not produce significant change in the MN frequency and sperm abnormality although Gmp at 17.5 mg showed significant antidiabetic effect in the hyperglycemic animals. The results indicated that Gmp inhibited the NA-STZ mediated changes in the MN frequency and sperm abnormality and enhanced the antioxidant defense. The observations suggest that the antioxidant property of Gmp could have contributed for its ability to decrease the NA-STZ mediated defects in somatic and germinal cells. PMID:20112807

Rabbani, Syed Imam; Devi, Kshama; Khanam, Salma

2009-10-01

139

Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats  

Microsoft Academic Search

Leaves of Piper betle (Piperaceae) possess several bioactivities and are used in traditional medicinal systems. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study therefore, was to investigate the antidiabetic activity of Piper betle leaves. This was tested in normoglycaemic and strepozotocin (STZ)-induced diabetic rats using oral administration of hot water extract (HWE)

L. S. R. Arambewela; L. D. A. M. Arawwawala; W. D. Ratnasooriya

2005-01-01

140

Partial preservation of pancreatic ?-cells by vanadian: Evidence for long-term amelioration of diabetes  

Microsoft Academic Search

Streptozotocin (STZ)-diabetic rats treated with vanadium can remain euglycemic for up to 20 weeks following withdrawal from vanadium treatment. In this study, we examined the effects of short-term vanadium treatment in preventing or reversing the STZ-induced diabetic state. Male Wistar rats were untreated (D) or treated (DT) with vanadyl sulfate for 1 week before administering STZ. Treatment was subsequently maintained

M. C. Cam; W. M. Li; J. H. McNeill

1997-01-01

141

Terminalia arjuna improves cardiovascular autonomic neuropathy in streptozotocin-induced diabetic rats.  

PubMed

The present study was designed to examine the therapeutic potential of Terminalia arjuna bark extract in improving cardiovascular autonomic neuropathy in Streptozotocin (STZ)-induced diabetic Wistar Albino rats. The baroreflex was evaluated by measuring the changes in heart rate with changes in arterial blood pressure induced by bolus injections of phenylephrine (vasoconstrictor) and sodium nitroprusside (vasodilator). T. arjuna bark extract, Rosuvastatin and Insulin were tested/administered therapeutically in rat model of uncontrolled diabetes. After 8 weeks of STZ administration, the reflex bradycardia and tachycardia response to hypertension and hypotension, respectively, were impaired in the diabetic group. The reflex bradycardia improved significantly after 1 month treatment of T. arjuna while the reflex tachycardia could not improve. The decreased body weight, heart rate, blood pressure and raised blood sugar in diabetic rats were not improved by T. arjuna therapy. Rosuvastatin treatment exerted similar effects while Insulin improved all the parameters. Further T. arjuna, Rosuvastatin and Insulin significantly reduced oxidative stress and inflammatory cytokine levels in diabetic rats. Results suggest that T. arjuna bark extract improves the altered baroreflex sensitivity in diabetic rats possibly through maintaining endogenous antioxidant enzyme activities and decreasing cytokine levels. PMID:23001577

Khaliq, Farah; Parveen, Adila; Singh, Savita; Hussain, M Eijaz; Fahim, M

2013-03-01

142

Antihyperglycaemic and antioxidant effect of hyponidd, an ayurvedic herbomineral formulation in streptozotocin-induced diabetic rats.  

PubMed

Hyponidd is a herbomineral formulation composed of the extracts of ten medicinal plants ( Momordica charantia, Melia azadirachta, Pterocarpus marsupium, Tinospora cordifolia , Gymnema sylvestre, Enicostemma littorale, Emblica officinalis, Eugenia jambolana, Cassia auriculata and Curcuma longa). We have investigated hyponidd for its possible antihyperglycaemic and antioxidant effect in diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg kg(-1) body weight). Oral administration of hyponidd (100 mg kg(-1) and 200 mg kg(-1)) for 45 days resulted in significant lowered levels of blood glucose and significant increased levels of hepatic glycogen and total haemoglobin. An oral glucose tolerance test was also performed in experimental diabetic rats in which there was a significant improvement in blood glucose tolerance in the rats treated with hyponidd. Hyponidd administration also decreased levels of glycosylated haemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and alpha-tocopherol in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of hyponidd. The effect of hyponidd at a dose of 200 mg kg(-1) was more effective than glibenclamide (600 microg kg(-1)) in restoring the values to near normal. The results showed that hyponidd exhibits antihyperglycaemic and antioxidant activity in STZ-induced diabetic rats. PMID:15525451

Babu, P Subash; Stanely Mainzen Prince, P

2004-11-01

143

The antioxidant activity of copper(II) (3,5-diisopropyl salicylate)4 and its protective effect against streptozotocin-induced diabetes mellitus in rats.  

PubMed

Oxidative stress has been suggested as a potential contributor to the development of diabetic complications. In this study, we investigated the protective effect of a strong antioxidant copper complex against streptozotocin (STZ)-induced diabetes in animals. Out of four copper complexes used, copper(II) (3,5-diisopropyl salicylate)4 (Cu(II)DIPS) was found to be the most potent antioxidant-copper complex. Pretreatment with Cu(II)DIPS (5 mg/kg) twice a week prior to the injection of streptozotocin (50 mg/kg) has reduced the level of hyperglycemia by 34 % and the mortality rate by 29 %. Injection of the same dosage of the ligand 3,5-diisopropyl salicylate has no effect on streptozotocin-induced hyperglycemia. The same copper complex has neither hypoglycemic activity when injected in normal rats nor antidiabetic activity when injected in STZ-induced diabetic rats. The protective effect of Cu(II)DIPS could be related to its strong antioxidant activity compared to other copper complexes median effective concentration (MEC)?=?23.84 ?g/ml and to Trolox MEC?=?29.30 ?g/ml. In addition, it reduced serum 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage, by 29 %. This effect may explain why it was not effective against diabetic rats, when ? Langerhans cells were already destroyed. Similar protective activities were reported by other antioxidants like Trolox. PMID:23677849

Qazzaz, Munir; Abdul-Ghani, Rula; Metani, Munther; Husein, Rateb; Abu-Hijleh, Abdul-Latif; Abdul-Ghani, Abdul-Salam

2013-05-17

144

Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis  

PubMed Central

Background Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. Methods This study was designed to examine the effect of long-acting calcium channel blocker (CCB), Azelnidipine (AZL) on contractile dysfunction, intracellular calcium (Ca2+) cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ). Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-relengthening (TR90), maximal velocity of shortening/relengthening (± dL/dt) and intracellular Ca2+ fluorescence. Results Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD), calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. Conclusion Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property.

2011-01-01

145

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

PubMed Central

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.

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

2012-01-01

146

Hypoglycemic activity of a polyphenolic oligomer-rich extract of Cinnamomum parthenoxylon bark in normal and streptozotocin-induced diabetic rats.  

PubMed

Cinnamon bark has been reported to be effective in the alleviation of diabetes through its antioxidant and insulin-potentiating activities. The water-soluble polyphenolic oligomers found in cinnamon are thought to be responsible for this biological activity. In this study, the hypoglycemic activity of a polyphenolic oligomer-rich extract from the barks of Cinnamomum parthenoxylon (Jack) Nees was studied in normal, transiently hyperglycemic, and streptozotocin (STZ)-induced diabetic rats. Oral administration of the extract at doses of 100, 200, and 300 mg/kg body wt. caused significant changes in body weight loss and fasting blood glucose levels of normal rats. In STZ-induced diabetic rats, after administration of the extract at doses of 100, 200, and 300 mg/kg body wt. over 14 days, the blood glucose levels were decreased by 11.1%, 22.5%, and 38.7%, respectively, and the plasma insulin levels were significantly increased over pre-treatment levels. In an oral glucose tolerance test, the extract produced a significant decrease in glycemia 90 min after the glucose pulse. These results suggest that Cinnamomum parthenoxylon polyphenolic oligomer-rich extract could be potentially useful for post-prandial hyperglycemia treatment. PMID:19464860

Jia, Q; Liu, X; Wu, X; Wang, R; Hu, X; Li, Y; Huang, C

2009-05-22

147

Effects of Persea americana Mill (Lauraceae) ["Avocado"] ethanolic leaf extract on blood glucose and kidney function in streptozotocin-induced diabetic rats and on kidney cell lines of the proximal (LLCPK1) and distal tubules (MDBK).  

PubMed

Extracts of Persea americana Mill (Lauraceae) ("Avocado") have been traditionally used to treat hypertension and diabetes mellitus. Accordingly, we studied the hypoglycaemic and renal function effects of P. americana leaf ethanolic extracts (PAE) in STZ-induced diabetic rats. Oral glucose tolerance responses to various doses of PAE were monitored in fasted rats following a glucose load. Rats treated with deionized water or standard hypoglycaemic drugs acted as untreated and treated positive controls, respectively. Acute renal effects of PAE were investigated in anesthetized rats challenged with 0.077 M NaCl after a 3.5-h equilibration for 4 h comprising 1 h control, 1.5 h treatment and 1.5 h recovery periods. PAE was added to the infusate during the treatment period. Hepatic glycogen concentration was measured after 6 weeks of daily treatment with PAE. PAE induced dose-dependent hypoglycaemic responses in STZ-induced diabetic rats while subchronic PAE treatment additionally increased hepatic glycogen concentrations. Acute PAE infusion decreased urine flow and electrolyte excretion rates, whilst subchronic treatment reduced plasma creatinine and urea concentrations. These results indicate not only the basis of the ethnomedicinal use of P. americana leaf extract in diabetes management, but also of need for further studies to identify and evaluate the safety of PAE's bioactive compounds. PMID:18389095

Gondwe, M; Kamadyaapa, D R; Tufts, M A; Chuturgoon, A A; Ojewole, J A O; Musabayane, C T

148

Mechanisms of the antihyperglycemic activity of Retama raetam in streptozotocin-induced diabetic rats.  

PubMed

Retama raetam (RR) fruits are used in Saudi traditional medicine for the treatment of diabetes. Current study aimed at evaluating the potential and mechanisms of the antidiabetic activity of the RR methanolic extract in streptozotocin-induced diabetic rats. Oral LD(50) of the extract was found to be 1995 mg/kg. The extract was administered once orally to STZ-diabetic rats at three dose levels; 100, 250 or 500 mg/kg/day for 4 consecutive weeks. RR extract at 250 or 500 mg/kg significantly lowered blood glucose levels at the 3rd and 1st week of treatment, respectively. Meanwhile, oral glucose tolerance test indicated that the same two doses significantly lowered glucose levels at 30 and 60 min after glucose challenge. Administration of RR extract at 500 mg/kg/day for 4 consecutive weeks significantly increased serum insulin level. In vitro studies indicated that the extract significantly inhibits glucose absorption by rat isolated intestine. The extract neither altered glucose uptake by rat isolated psoas muscle nor the activity of hepatic microsomal glucose-6-phosphatase. In conclusion, the methanolic extract of RR improves STZ-induced diabetes in rats. This can be attributed, at least partly, to stimulating pancreatic insulin release and reducing intestinal glucose absorption. PMID:20538037

Algandaby, Mardi M; Alghamdi, Hassan A; Ashour, Osama M; Abdel-Naim, Ashraf B; Ghareib, Salah A; Abdel-Sattar, Essam A; Hajar, Abdulrahman S

2010-06-09

149

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

SciTech Connect

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.

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

1991-01-01

150

Changes in superoxide dismutase mRNA expression by streptozotocin-induced diabetes.  

PubMed Central

1. Experiments were designed to investigate the involvement of superoxide anions in the attenuated endothelium-dependent relaxation of the rat aorta from streptozotocin (STZ)-induced diabetic rats. 2. The endothelium-dependent relaxation responses to acetylcholine (ACh, 10(-7) M) in helical strips of the aorta precontracted with noradrenaline (NA, 5 x 10(-3) approximately 3 x 10(-7) M) were significantly decreased in STZ-induced diabetic rats. The recovery phase of the relaxation after single administration of ACh in the STZ-induced diabetic rats was more rapid than those in control vessels. 3. Preincubation of aortic strips with superoxide dismutase (SOD, 60 u ml-1) normalized the recovery phase of the relaxation of diabetic aorta after single administration of ACh, whereas catalase (150 u ml-1) or indomethacin (10(-5) M) had no effects on the relaxation. 4. SOD (180 u ml-1) caused relaxation in NA precontracted aortic strips and the degree of the SOD-induced relaxation was significantly greater in diabetic aorta as compared with age-matched control vessels. 5. When the changes in mRNA expressions of Mn-SOD or Cu-Zn-SOD were observed, Mn-SOD mRNA expression was markedly decreased, and Cu-Zn-SOD was slightly decreased in diabetic aorta. 6. These results suggest that the rapid destruction of NO by superoxide anions may occur in the STZ-induced diabetic rats, and this may be due to a decrease in mRNA expression of Mn-SOD or Cu-Zn-SOD. Images Figure 4

Kamata, K.; Kobayashi, T.

1996-01-01

151

Effects of Selenium Supplementation on Antioxidant Defense and Glucose Homeostasis in Experimental Diabetes Mellitus  

Microsoft Academic Search

The objective of this study was to investigate the effects of different forms of Se supplementation on the antioxidant defense\\u000a and glucose homeostasis in experimental diabetes. Sodium selenate (SS) or selenomethionine (SM) were administered (2 ?mol\\u000a Se kg?1 day?1) via orogastric route to streptozotocine (STZ)-induced diabetic rats in addition to basal diet for 12 weeks. Glucose levels\\u000a in whole blood, glutathione peroxidase

Zubeyde Erbayraktar; Osman Y?lmaz; Ay?egul Temiz Artmann; Ruksan Cehreli; Canan Coker

2007-01-01

152

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

PubMed Central

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.

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

2013-01-01

153

Evaluation of Antidiabetic Activity of Hydroalcoholic Extract of Cestrum nocturnum Leaves in Streptozotocin-Induced Diabetic Rats  

PubMed Central

Objective. To investigate antidiabetic activity of hydroalcoholic extract of Cestrum nocturnum leaves in Wistar rats. Method. Cestrum nocturnum leaves extract in hydroalcoholic solution were prepared by Soxhletation method and stored in refrigerator at 4°C for two days before use. Wistar rats were made diabetic by a single dose of streptozotocin (150?mg/kg i.p.). Hydroalcoholic leaves extract of Cestrum nocturnum was screened for antidiabetic activity and given to the STZ-induced diabetic rats at a concentration of 200?mg/kg and 400?mg/kg of body weight in different groups of 6 diabetic rats each orally once a day for 15 days. Metformin is also given to another group to support the result at a dose of 10?mg/kg of body weight orally once a day for 15 days. Blood glucose levels and body weights of rats were measured on 0, 5, 7, and 15th days. Results. Oral administration of the extracts for 15 days caused a significant (P < 0.01) reduction in blood glucose levels in diabetic rats. The body weight of diabetic animals was also improved after daily administration of extracts. The extract also improved other altered biochemical parameters associated with diabetes. Also the changes in food intake, water intake, and weight of internal organs were also restored to normal by the prolonged effect of extract treatment.

Kamboj, Anil; Kumar, Sunil; Kumar, Vipin

2013-01-01

154

Beneficial effects of ginger (Zingiber officinale) on carbohydrate metabolism in streptozotocin-induced diabetic rats.  

PubMed

Zingiber officinale (ZO), commonly known as ginger, has been traditionally used in the treatment of diabetes mellitus. Several studies have reported the hypoglycaemic properties of ginger in animal models. The present study evaluated the antihyperglycaemic effect of its aqueous extract administered orally (daily) in three different doses (100, 300, 500 mg/kg body weight) for a period of 30 d to streptozotocin (STZ)-induced diabetic rats. A dose-dependent antihyperglycaemic effect revealed a decrease of plasma glucose levels by 38 and 68 % on the 15th and 30th day, respectively, after the rats were given 500 mg/kg. The 500 mg/kg ZO significantly (P<0·05) decreased kidney weight (% body weight) in ZO-treated diabetic rats v. control rats, although the decrease in liver weight (% body weight) was not statistically significant. Kidney glycogen content increased significantly (P<0·05) while liver and skeletal muscle glycogen content decreased significantly (P<0·05) in diabetic controls v. normal controls. ZO (500 mg/kg) also significantly decreased kidney glycogen (P<0·05) and increased liver and skeletal muscle glycogen in STZ-diabetic rats when compared to diabetic controls. Activities of glucokinase, phosphofructokinase and pyruvate kinase in diabetic controls were decreased by 94, 53 and 61 %, respectively, when compared to normal controls; and ZO significantly increased (P<0·05) those enzymes' activities in STZ-diabetic rats. Therefore, the present study showed that ginger is a potential phytomedicine for the treatment of diabetes through its effects on the activities of glycolytic enzymes. PMID:22152092

Abdulrazaq, Nafiu Bidemi; Cho, Maung Maung; Win, Ni Ni; Zaman, Rahela; Rahman, Mohammad Tariqur

2011-12-12

155

Aminoguanidine prevents arterial stiffening and cardiac hypertrophy in streptozotocin-induced diabetes in rats  

PubMed Central

The formation of advanced glycation endproducts (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study was to examine the role of aminoguanidine (AG), an inhibitor of AGEs formation, in the prevention of arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) induced diabetes in rats. Diabetes was induced in animals by a single tail vein injection with 65?mg?kg?1 STZ. After confirmation of the development of hyperglycemia (2 days later), rats were treated for 8 weeks with AG (daily peritoneal injections of 50?mg?kg?1) and compared with the age-matched untreated diabetic controls. After exposure to AG, the STZ-diabetic rats showed no alterations in cardiac output, aortic pressure profiles, total peripheral resistance, and aortic characteristic impedance. By contrast, treatment of this experimental diabetes with AG resulted in a significant increase in wave transit time (?), from 20.4±0.6 to 24.7±0.5?ms (P<0.05) and a decrease in wave reflection factor (Rf), from 0.78±0.04 to 0.53±0.02 (P<0.05). The decreased Rf associated with the increased ? suggest that AG may retard the diabetes-induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, the diminished ratio of left ventricular weight to body weight suggests that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. Glycation-derived modification on aortic collagen was also found to be enhanced in rats with diabetes (+65.3%, P<0.05) and the advanced glycation process was retarded by AG treatment. We conclude that long-term administration of AG to the STZ-treated rats imparts significant protection against the diabetes-derived deterioration in vascular dynamics, at least partly through inhibition of the AGEs accumulation on collagen in the arterial wall.

Chang, Kuo-Chu; Hsu, Kwan-Lih; Tseng, Chuen-Den; Lin, Yue-Der; Cho, Yi-Li; Tseng, Yung-Zu

2006-01-01

156

White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats.  

PubMed

Agaricus bisporus (white button mushroom; WBM) contains high levels of dietary fibers and antioxidants including vitamin C, D, and B(12); folates; and polyphenols that may provide beneficial effects on cardiovascular and diabetic diseases. The objective of this study was to examine the hypothesis that intake of the fruiting bodies of WBM regulates anticholesterolemic and antiglycemic responses in rats fed a hypercholesterolemic diet (0.5% cholesterol; 14% fat) and rats with type 2 diabetes induced by injection of streptozotocin (STZ) (50 mg/kg body weight), respectively. The STZ-induced diabetic male Sprague-Dawley rats fed the Agaricus bisporus powder (ABP; 200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose and triglyceride (TG) concentrations (24.7% and 39.1%, respectively), liver enzyme activities, alanine aminotransferase and aspartate aminotransferase (11.7% and 15.7%, respectively), and liver weight gain (P < .05). In hypercholesterolemic rats, oral feeding of ABP for 4 weeks resulted in a significant decrease in plasma total cholesterol (TC) and low-density lipoprotein (LDL) (22.8% and 33.1%, respectively) (P < .05). A similar significant decrease in hepatic cholesterol and TG concentrations was observed (36.2% and 20.8%, respectively) (P < .05). Decrease in TC, LDL, and TG concentrations was accompanied by a significant increase in plasma high-density lipoprotein concentrations. It was concluded that A bisporus mushroom had both hypoglycemic and hypolipidemic activity in rats. PMID:20116660

Jeong, Sang Chul; Jeong, Yong Tae; Yang, Byung Keun; Islam, Rezuanul; Koyyalamudi, Sundar Rao; Pang, Gerald; Cho, Kai Yip; Song, Chi Hyun

2010-01-01

157

Early Visual Deficits in Streptozotocin-Induced Diabetic Long Evans Rats  

PubMed Central

Purpose. Although diabetic retinopathy (DR) is clinically diagnosed based on vascular pathology, diabetic patients with angiographically normal retinas have been found to exhibit subtle defects in vision. This has led to the theory that diabetes-associated metabolic abnormalities directly impair neural retinal function before the development of vasculopathy, thereby resulting in visual deficits. In this study, we sought to delineate the temporal relationship between retinal dysfunction and visual deficits in a rat model of Type 1 diabetes. Moreover, we investigated the relative contribution of retinal dysfunction versus diabetes-induced lens opacity, to the visual deficits found in early-stage DR. Methods. Pigmented Long Evans rats were rendered diabetic with streptozotocin (STZ). Control and diabetic rats were assessed across 12 weeks of hyperglycemia for visual function with optokinetic tracking weekly visual acuity and monthly contrast sensitivity, retinal function with dark-adapted electroretinograms (monthly electroretinograms [ERGs]), and cataract formation with slit lamp exam (biweekly). Results. Diabetic rats exhibited significantly reduced visual function and delayed ERG responses by 1 month post-STZ. Significant cataracts did not develop until 6 weeks post-STZ. Moreover, increases in lens opacity (r = ?0.728) and ERG implicit times (r = ?0.615 for rod-dominated response and r = ?0.322 for rod/cone mixed response) showed significant correlations with reductions in visual acuity in diabetic rats. Conclusions. STZ-induced hyperglycemia reduces visual function, affecting both visual acuity and contrast sensitivity. The data suggest that visual defects found in early-stage DR may initially involve abnormalities of the neural retina and worsen with later development of cataracts.

Aung, Moe H.; Kim, Moon K.; Olson, Darin E.; Thule, Peter M.; Pardue, Machelle T.

2013-01-01

158

Influence of vanadium supplementation on oxidative stress factors in the muscle of STZ-diabetic rats.  

PubMed

In recent years, the role of free radical damage consequent to oxidative stress is widely discussed in diabetic complications. In this aspect, the protection of cell integrity by trace elements is a topic to be investigated. Vanadium is a trace element believed to be important for normal cell function and development. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the muscle tissue of diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) to male Swiss albino rats. The rats were randomly divided into 4 groups: Group I, control; Group II, vanadyl sulfate control; Group III, STZ-diabetic untreated; Group IV, STZ-diabetic treated with vanadyl sulfate. Vanadyl sulfate (100 mg/kg) was given daily by gavage for 60 days. At the last day of the experiment, rats were killed, muscle tissues were taken, homogenized in cold saline to make a 10% (w/v) homogenate. Body weights and blood glucose levels were estimated at 0, 30 and 60th days. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), as well as carbonic anhydrase (CA), myeloperoxidase (MPO) activities and protein carbonyl content (PCC) were determined in muscle tissue. Vanadyl sulfate administration improved the loss in body weight due to STZ-induced diabetes and decreased the rise in blood glucose levels. It was shown that vanadium supplementation to diabetic rats significantly decrease serum antioxidant enzyme levels, which were significantly raised by diabetes in muscle tissue showing that this trace element could be used as preventive for diabetic complications. PMID:21479831

Kurt, Ozlem; Ozden, Tugba Yilmaz; Ozsoy, Nurten; Tunali, Sevim; Can, Ayse; Akev, Nuriye; Yanardag, Refiye

2011-04-10

159

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

PubMed

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

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

2010-02-12

160

Anti-diabetic activity of methanol/methylene chloride stem bark extracts of Terminalia superba and Canarium schweinfurthii on streptozotocin-induced diabetic rats.  

PubMed

Stem bark extracts of Terminalia superba Engl. and Diels and Canarium schweinfurthii Engl. are used in Africa for the treatment of various ailments, including diabetes mellitus. The anti-diabetic effects of the methanol/methylene chloride extracts of the stem barks on streptozotocin (STZ)-induced diabetes were evaluated on male rats. Through the subcutaneous route, diabetes was induced using 60 mg/mL of streptozotocin. After 2 days, the rats received, by gavage, 150 mg/kg and 300 mg/kg of extract daily for 14 days. At 300 mg/kg, the two extracts (Terminalia superba and Canarium schweinfurthii), significantly showed at least 67.1% and 69.9% reduction in blood glucose level, respectively, while insulin (three units) given subcutaneously and once daily, had 76.8% reduction compared to diabetic untreated control rats. Similarly, the weight gains were 6.6% and 4.9%, respectively, and were comparable to the normal rats, whereas, diabetic untreated rats lost 14.1% body weight. Still with the same dose, there was 68.5% and 58.5% (p < 0.001) significant decrease in food consumption and 79.7% and 64.0% (p < 0.001) in fluid intake by diabetic rats treated with the respective plant extracts. The insulin-treated rats showed 56.4% and 75.8% decrease in food and fluid intake compared to an augmentation for diabetic control rats, 43.0% and 383.8%, respectively, at the end of the second week of experimentation. These results showed that the plant extracts can reverse hyperglycemia, polyphagia and polydipsia provoked by streptozotocin, and thus, they have anti-diabetic properties. PMID:16271836

Kamtchouing, P; Kahpui, S M; Dzeufiet, P-D Djomeni; Tédong, L; Asongalem, E A; Dimo, T

2005-11-04

161

Antidiabetic and antiacetylcholinesterase effects of ethyl acetate fraction of Chaenomeles sinensis (Thouin) Koehne fruits in streptozotocin-induced diabetic rats.  

PubMed

The present study was intended to examine the effects of the supplementation of active ?-glucosidase, ?-amylase and lipase inhibitory ethyl acetate (CSE) fraction from the fruits of Chaenomeles sinensis (Thouin) Koehne on blood glucose (BG), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransaminase (AST), acetylcholinesterase (AChE) and antioxidant levels. The diabetic rats were treated orally with CSE at the doses of 50 and 100 mg/kg bw for 14 days. BG, TC, TG, HDL-C, ALT, AST and AChE levels were significantly reduced; on the other hand antioxidant levels were significantly increased in the treated groups. These observations suggest protective effects of CSE against STZ-induced diabetic dementia model. PMID:21764274

Sancheti, Sandesh; Sancheti, Shruti; Seo, Sung-Yum

2011-07-20

162

Crocin Improved Learning and Memory Impairments in Streptozotocin-Induced Diabetic Rats  

PubMed Central

Objective(s): Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (IP) injection of streptozotocin (STZ, 45 mg/kg). Transfer latency (TL) paradigm in elevated plus-maze (EPM) was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC) and malondialdehyde (MDA), blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. Results: STZ increased acquisition transfer latency (TL1) and retention transfer latency (TL2), and MDA, decreased transfer latency shortening (TLs) and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. Conclusion: The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments.

Tamaddonfard, Esmaeal; Farshid, Amir Abbas; Asri-Rezaee, Siamak; Javadi, Shahram; Khosravi, Voria; Rahman, Bentolhoda; Mirfakhraee, Zahra

2013-01-01

163

Crocin improved learning and memory impairments in streptozotocin-induced diabetic rats.  

PubMed

Objective(s): Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (IP) injection of streptozotocin (STZ, 45 mg/kg). Transfer latency (TL) paradigm in elevated plus-maze (EPM) was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC) and malondialdehyde (MDA), blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. Results: STZ increased acquisition transfer latency (TL1) and retention transfer latency (TL2), and MDA, decreased transfer latency shortening (TLs) and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. Conclusion: The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments. PMID:23638297

Tamaddonfard, Esmaeal; Farshid, Amir Abbas; Asri-Rezaee, Siamak; Javadi, Shahram; Khosravi, Voria; Rahman, Bentolhoda; Mirfakhraee, Zahra

2013-01-01

164

Amadori-glycated phosphatidylethanolamine, a potential marker for hyperglycemia, in streptozotocin-induced diabetic rats.  

PubMed

It has been demonstrated in vivo that lipid glycation products such as Amadori-glycated phosphatidylethanolamine (Amadori-PE) accumulate in the plasma of diabetic humans and animals, but how lipid glycation products are formed under hyperglycemic conditions are not clear. We sought to clarify the occurrence of lipid glycation and its relationships with lipid peroxidation and protein glycation during the development of hyperglycemia using the streptozotocin (STZ)-induced diabetic rat model. A significant increase in Amadori-PE was observed in STZ rats 7 days after STZ treatment, and Amadori-PE (especially 18:0-20:4 Amadori-PE) was found at high levels in the blood and in organs that are strongly affected by diabetes, such as the kidney. Significant changes in Amadori-PE appeared to occur prior to changes in levels of oxidized lipids, which increased after 21-28 days. In addition, accumulation of N?-(carboxymethyl)lysine (CML), a protein glycation product, proceeded somewhat more slowly and moderately than that of Amadori-PE, suggesting that Amadori-PE and CML are early and advanced glycation products, respectively. Our results suggest that Amadori-PE may be a useful predictive marker for hyperglycemia, particularly in the early stages of diabetes. Similar speculations have been made from previous human studies, but this study provides a direct evidence to support the speculations in rat study. PMID:21732214

Sookwong, Phumon; Nakagawa, Kiyotaka; Fujita, Ikuko; Shoji, Naoki; Miyazawa, Teruo

2011-07-06

165

Efficacy of biodegradable curcumin nanoparticles in delaying cataract in diabetic rat model.  

PubMed

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

Grama, Charitra N; Suryanarayana, Palla; Patil, Madhoosudan A; Raghu, Ganugula; Balakrishna, Nagalla; Kumar, M N V Ravi; Reddy, Geereddy Bhanuprakash

2013-10-14

166

Hypoglycemic dipeptide cyclo (His-Pro) significantly altered plasma proteome in streptozocin-induced diabetic rats and genetically-diabetic (ob/ob) mice.  

PubMed

The proteins in plasma perform many important functions in the body, and the protein profiles of the plasma vary under different physiological and pathological conditions. In an attempt to identify novel marker proteins for diabetes prognosis, we examined the effect of hypoglycemic dipeptide cyclo (His-Pro) (CHP) on the differential regulation of plasma proteins in streptozocin-induced diabetic rats and genetically-diabetic (ob/ob) mice. The orally-administrated CHP produced an excellent hypoglycemic effect in both animal models, lowering the average plasma glucose level by over 50 %. In the 2-DE analysis of the plasma, a total of 23 spots among 500 visualized spots were found to be differentially regulated, and they were identified by MALDI/TOF mass spectrometry. These proteins include the down-regulation of Apo E and the up-regulation of FGA, Apo A-I, Apo A-IV, and A1M in STZ-induced diabetic rats. Moreover, CHP significantly reduced the plasma protein levels of FGB, FGC, F12, C1QTNF5, and SPA3K, as well as increased the abundance of A1M, A2M, Apo E, and TTR in genetically-diabetic mice. In conclusion, alteration in the regulation of these proteins indicates that this treatment may be successful in overcoming the diabetic state. The present proteomic data can serve as the basis for the development of specific evidence-based interventions allowing for the prevention and treatment of diabetes. PMID:23086277

Choi, Song Ah; Yun, Jong Won; Park, Hee Sung; Choi, Jang Won

2012-10-20

167

Mitochondria-targeted antioxidant peptide SS31 protects the retinas of diabetic rats.  

PubMed

Oxidative stress is one of the main contributors in the pathogenesis of diabetic retinopathy. The aim of this study is to investigate the effects of SS31 which is a mitochondria-targeted antioxidant peptide on the retinas of streptozotocin (STZ)-induced diabetic rats. Two weeks after induction of diabetes, SS31 (3 mg/kg) or the same volume of normal saline (N.S) was injected subcutaneously into the back of diabetic rats every day. Four months later, the integrity of inner blood retinal barrier (iBRB) was measured by Evans blue perfusion. The expression and distribution of claudin-5, occludin, acrolein, 8-OHdG and nitrotyrosine in the rat retinas were detected by immunofluorescent staining. Retinal ultrastructures were observed by transmission electron microscopy. The protein level of VEGFR2, Trx-2, Bcl-2, Bax, caspase-3, p53, and NF-?B in the rat retinas were assayed by western blot. Four months after subcutaneous injection, the diabetic rats treated with SS31 had better structures of retinal ganglion cells, thinner capillary basement membrane, less iBRB leakage, more uniform staining of claudin-5 and occludin in the retinal vessels, lower levels of acrolein, 8-OHdG, nitrotyrosine, Bax, caspase-3, p53, and NF-?B, and higher levels of Trx-2 and Bcl-2 in the retinas than those treated with N.S. In conclusion, SS31 could protect the retinal structures and inhibit the breakdown of iBRB by reducing oxidative damage, increasing Trx-2 and Bcl-2 expression, and decreasing p53, NF-?B, Bax, caspase-3, and VEGFR2 expression in the retinas of diabetic rats. SS31 could be a potential new treatment for diabetic retinopathy and other oxidative stress-related diseases. PMID:23745582

Huang, J; Li, X; Li, M; Li, J; Xiao, W; Ma, W; Chen, X; Liang, X; Tang, S; Luo, Y

2013-07-01

168

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

PubMed

The hypoglycemic activity of a purified extract from prickly pear cactus (Opuntia fuliginosa) 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. The blood glucose response to administered glucose also showed that the rats receiving the combination treatment of insulin and Opuntia extract for 7 weeks followed by Opuntia extract alone were capable of rapidly returning blood glucose to the levels of the nondiabetic rats. Although the mechanism of action is unknown, the magnitude of the glucose control by the small amount of Opuntia extract required (1 mg/kg body weight per day) preclude a predominant role for dietary fiber. These very encouraging results for diabetes control by the purified extract of this Opuntia cactus make the need for clinical studies in humans evident. PMID:9121164

Trejo-González, A; Gabriel-Ortiz, G; Puebla-Pérez, A M; Huízar-Contreras, M D; Munguía-Mazariegos, M R; Mejía-Arreguín, S; Calva, E

1996-12-01

169

Glutamine Supplementation Stimulates Protein-Synthetic and Inhibits Protein-Degradative Signaling Pathways in Skeletal Muscle of Diabetic Rats  

PubMed Central

In this study, we investigated the effect of glutamine (Gln) supplementation on the signaling pathways regulating protein synthesis and protein degradation in the skeletal muscle of rats with streptozotocin (STZ)-induced diabetes. The expression levels of key regulatory proteins in the synthetic pathways (Akt, mTOR, GSK3 and 4E-BP1) and the degradation pathways (MuRF-1 and MAFbx) were determined using real-time PCR and Western blotting in four groups of male Wistar rats; 1) control, non-supplemented with glutamine; 2) control, supplemented with glutamine; 3) diabetic, non-supplemented with glutamine; and 4) diabetic, supplemented with glutamine. Diabetes was induced by the intravenous injection of 65 mg/kg bw STZ in citrate buffer (pH 4.2); the non-diabetic controls received only citrate buffer. After 48 hours, diabetes was confirmed in the STZ-treated animals by the determination of blood glucose levels above 200 mg/dL. Starting on that day, a solution of 1 g/kg bw Gln in phosphate buffered saline (PBS) was administered daily via gavage for 15 days to groups 2 and 4. Groups 1 and 3 received only PBS for the same duration. The rats were euthanized, and the soleus muscles were removed and homogenized in extraction buffer for the subsequent measurement of protein and mRNA levels. The results demonstrated a significant decrease in the muscle Gln content in the diabetic rats, and this level increased toward the control value in the diabetic rats receiving Gln. In addition, the diabetic rats exhibited a reduced mRNA expression of regulatory proteins in the protein synthesis pathway and increased expression of those associated with protein degradation. A reduction in the skeletal muscle mass in the diabetic rats was observed and was alleviated partially with Gln supplementation. The data suggest that glutamine supplementation is potentially useful for slowing the progression of muscle atrophy in patients with diabetes.

Lambertucci, Adriana C.; Lambertucci, Rafael H.; Hirabara, Sandro M.; Curi, Rui; Moriscot, Anselmo S.; Alba-Loureiro, Tatiana C.; Guimaraes-Ferreira, Lucas; Levada-Pires, Adriana C.; Vasconcelos, Diogo A. A.; Sellitti, Donald F.; Pithon-Curi, Tania C.

2012-01-01

170

Antihyperalgesic effects of cizolirtine in diabetic rats: behavioral and biochemical studies.  

PubMed

Although clinically well controlled at the metabolic level, type I diabetes resulting from an insufficient insulin secretion remains the cause of severe complications. In particular, diabetes can be associated with neuropathic pain which fails to be treated by classical analgesics. In this study, we investigated the efficacy of a novel non opioid analgesic, cizolirtine, to reduce mechanical hyperalgesia associated with streptozotocin (STZ)-induced diabetes, in the rat. Cizolirtine was compared to paroxetine, an antidepressant drug with proven efficacy to relieve painful diabetic neuropathy. Under acute conditions, cizolirtine (30 and 80 mg/kgi.p.) significantly increased paw withdrawal and vocalization thresholds in the paw pressure test in diabetic rats displaying mechanical hyperalgesia. The antihyperalgesic effects of cizolirtine persisted under chronic treatment conditions, since pre-diabetes thresholds were recovered after a two week-treatment with the drug (3 mg/kg/day, s.c.). In this respect, cizolirtine was as efficient as paroxetine (5 mg/kg per day, s.c.) which, however, was inactive under acute treatment conditions. Measurements of the spinal release of calcitonin gene-related peptide (CGRP) through intrathecal perfusion under halothane-anesthesia showed that acute administration of cizolirtine (80 mg/kg, i.p.) significantly diminished (-36%) the peptide outflow in diabetic rats suffering from neuropathic pain. This effect as well as the antihyperalgesic effect of cizolirtine were prevented by the alpha(2)-adrenoreceptor antagonist idazoxan (2 mg/kg, i.p.). These data suggest that the antihyperalgesic effect of cizolirtine in diabetic rats suffering from neuropathic pain implies an alpha(2)-adrenoceptor-dependent presynaptic inhibition of CGRP-containing primary afferent fibers. PMID:15275748

Aubel, Bertrand; Kayser, Valérie; Mauborgne, Annie; Farré, Antonio; Hamon, Michel; Bourgoin, Sylvie

2004-07-01

171

Protective role of glibenclamide against nicotinamide-streptozotocin induced nuclear damage in diabetic Wistar rats  

PubMed Central

Objective: To evaluate the protective effect of glibenclamide against the experimental diabetes-induced nuclear damage in Wistar rats. Materials and Methods: The anti-mutagenic effect of glibenclamide (0.5, 5 and 50 mg/kg, p.o daily for 4 weeks) was evaluated against the nicotinamide (NA)-streptozotocin (STZ) induced type-2 diabetes mellitus using bone marrow micronucleus and sperm abnormalities tests. The antioxidant status was tested by estimating the serum levels of lipid peroxidation (LPO), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Results: The results indicated that glibenclamide at 50 mg/kg decreased the frequency of micronuclei in erythrocytes (P < 0.05) and sperm shape abnormality (P < 0.01) besides enhancing the antioxidant status (P < 0.05) in the diabetic rats. However, glibenclamide treatment did not enhance the polychromatic and normochromatic erythrocytes (P/N) ratio and sperm count in the diabetic condition. Conclusion: The observations indicate that the glibenclamide has anti-mutagenic potential which could be related to the antioxidant effect and might also possess anti-proliferative property.

Rabbani, Syed Imam; Devi, Kshama; Khanam, Salma

2010-01-01

172

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

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.

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

173

Prevention of diabetes-induced myocardial dysfunction in rats using the juice of the Emblica officinalis fruit  

PubMed Central

Normalization of hyperglycemia, hyperlipidemia and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. The present study investigated the effects of the fruit juice obtained from Emblica officinalis on myocardial dysfunction in diabetic rats. Diabetes was induced by streptozotocin (STZ), and the rats were treated with E officinalis fruit juice for eight weeks. Injection of STZ produced loss of body weight, polydypsia, polyphagia, hyperglycemia, hypoinsulinemia and dyslipidemia. It also produced hypertension, bradycardia, hypertrophy and myocardial functional alterations associated with an increase in serum lactate dehydrogenase and creatinine kinase-MB levels. Treatment with the fruit juice not only prevented STZ-induced loss of body weight, increases in water and food intake, increases in serum glucose levels and disturbed lipid profile, but also an increase in serum lactate dehydrogenase and creatinine kinase-MB levels, and increased myocardial hypertrophy and cardiomyopathy. There was an increase in the area under the curve (AUC) for glucose, and a decrease in AUCinsulin was observed in diabetic rats; treatment decreased AUCglucose but not AUCinsulin or hyperinsulinemia. There was a decrease in antioxidant enzyme levels (in superoxide dismutase, reduced glutathione and catalase) in diabetic hearts, which could be improved by treatment with fruit juice. The present data suggest that fruit juice may be beneficial for the treatment of myocardial damage associated with type 1 diabetes mellitus. The activity of E officinalis fruit juice can be attributed to the concentration of polyphenol present.

Patel, Snehal S; Goyal, Ramesh K

2011-01-01

174

Prevention of diabetes-induced myocardial dysfunction in rats using the juice of the Emblica officinalis fruit.  

PubMed

Normalization of hyperglycemia, hyperlipidemia and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. The present study investigated the effects of the fruit juice obtained from Emblica officinalis on myocardial dysfunction in diabetic rats. Diabetes was induced by streptozotocin (STZ), and the rats were treated with E officinalis fruit juice for eight weeks. Injection of STZ produced loss of body weight, polydypsia, polyphagia, hyperglycemia, hypoinsulinemia and dyslipidemia. It also produced hypertension, bradycardia, hypertrophy and myocardial functional alterations associated with an increase in serum lactate dehydrogenase and creatinine kinase-MB levels. Treatment with the fruit juice not only prevented STZ-induced loss of body weight, increases in water and food intake, increases in serum glucose levels and disturbed lipid profile, but also an increase in serum lactate dehydrogenase and creatinine kinase-MB levels, and increased myocardial hypertrophy and cardiomyopathy. There was an increase in the area under the curve (AUC) for glucose, and a decrease in AUC(insulin) was observed in diabetic rats; treatment decreased AUC(glucose) but not AUC(insulin) or hyperinsulinemia. There was a decrease in antioxidant enzyme levels (in superoxide dismutase, reduced glutathione and catalase) in diabetic hearts, which could be improved by treatment with fruit juice. The present data suggest that fruit juice may be beneficial for the treatment of myocardial damage associated with type 1 diabetes mellitus. The activity of E officinalis fruit juice can be attributed to the concentration of polyphenol present. PMID:22065939

Patel, Snehal S; Goyal, Ramesh K

2011-01-01

175

Protective Effects of Green Tea Extract against Hepatic Tissue Injury in Streptozotocin-Induced Diabetic Rats  

PubMed Central

Although diabetic hepatopathy is potentially less common, it may be appropriate for addition to the list of target organ conditions related to diabetes. This study was designed to evaluate the hepatoprotective properties of green tea extract (GTE) in STZ-induced diabetes in rats. Wistar rats were made diabetic through single injection of STZ (75?mg/kg i.p.). The rats were randomly divided into four groups of 10 animals each: Group 1, healthy control; Group 2, nondiabetics treated with GTE administered orally (1.5%, w/v); Group 3, diabetics; Group 4, diabetics treated with GTE (1.5%, w/v) for 8 weeks. Serum biomarkers were assessed to determine hepatic injury. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were measured to assess free radical activity in the liver tissue. Hepatic antioxidant activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were also determined. The biochemical findings were matched with histopathological verifications. Liver MDA content and serum levels of ALT, AST, ALP, and bilirubin in Group 3 significantly increased compared to Group 1 (P < 0.05) and significantly decreased in Group 4 compared to Group 3 (P < 0.05). Serum albumin level and GSH, SOD, CAT, and GSH-Px contents of the liver in Group 3 were significantly decreased compared to Group 1 (P < 0.05) and were significantly increased in Group 4 compared to Group 3 (P < 0.05). Histopathologically, the changes were in the same direction with biochemical findings. This study proved the hepatoprotective activity of GTE in experimentally induced diabetic rats.

Abolfathi, Ali Akbar; Mohajeri, Daryoush; Rezaie, Ali; Nazeri, Mehrdad

2012-01-01

176

Acetyl l-carnitine corrects the altered peripheral nerve function of experimental diabetes  

Microsoft Academic Search

Acetyl-l-carnitine (ALC) has been shown to facilitate the repair of transected sciatic nerves. The effect of ALC (50 mg\\/kg\\/d) on the diminished nerve conduction velocity (NCV) of rats with streptozotocin (STZ)-induced hyperglycemia of 3 weeks' duration was evaluated. The aldose reductase inhibitor, sorbinil, which is reported to normalize the impaired NCV associated with experimental diabetes, was used as a positive

S. Lowitt; J. I. Malone; A. F. Salem; J. Korthals; S. Benford

1995-01-01

177

Alteration of alpha(1A)-adrenoceptor gene expression in the prostate of streptozotocin-induced diabetic rats.  

PubMed

Diabetes-associated alterations in prostate alpha(1A)-adrenoceptor (alpha(1A)-AR) gene expression were studied using a streptozotocin (STZ) induced diabetic rat model. Male Wistar rats were divided into four groups: group I animals were vehicle-treated normal rats; group II consisted of vehicle-treated, STZ-diabetic rats; group III represented insulin-treated, STZ-diabetic rats (0.5 IU/kg three times daily for 4 days), and group IV animals were phlorizin-treated, STZ-diabetic rats (1 mg/kg three times daily for 4 days). The expression of mRNA that encoded protein of alpha(1A)-AR in the rat prostate was studied using reverse transcription combined with polymerase chain reaction. The alpha(1A)-AR protein expression in the prostate was studied by Western blotting analysis with a polyclonal antiserum. A 2.51 +/- 0.21-fold increase in the mRNA level of alpha(1A)-AR was observed in the prostate of diabetic rats (n = 8, p < 0.05). Similarly, there was a 2.23 +/- 0.10-fold increase in the alpha(1A)-AR protein level (n = 8, p < 0.05). Both insulin and phlorizin treatments restored the normal levels of mRNA and protein expression. In conclusion, the gene expression of alpha(1A)-AR is increased in the prostate of diabetic rats. Hyperglycemia plays a major role in this alteration. PMID:12784082

Tong, Yat-Ching; Liu, I-Min; Cheng, Juei-Tang

2003-07-01

178

Effect of Scoparia dulcis extract on insulin receptors in streptozotocin induced diabetic rats: studies on insulin binding to erythrocytes.  

PubMed

We investigated the insulin-receptor-binding effect of Scoparia dulcis plant extract in streptozotocin (STZ)-induced male Wistar rats, using circulating erythrocytes (ER) as a model system. An aqueous extract of S dulcis plant (SPEt) (200 mg/kg body weight) was administered orally. We measured blood levels of glucose and plasma insulin and the binding of insulin to cell-membrane ER receptors. Glibenclamide was used as standard reference drug. The mean specific binding of insulin to ER was significantly lower in diabetic control rats (DC) (55.0 +/- 2.8%) than in SPEt-treated (70.0 +/- 3.5%)- and glibenclamide-treated (65.0 +/- 3.3%) diabetic rats, resulting in a significant decrease in plasma insulin. Scatchard plot analysis demonstrated that the decrease in insulin binding was accounted for by a lower number of insulin receptor sites per cell in DC rats when compared with SPEt- and glibenclamide-treated rats. High-affinity (Kd1), low-affinity (Kd2), and kinetic analysis revealed an increase in the average receptor affinity in ER from SPEt and glibenclamide treated diabetic rats having 2.5 +/- 0.15 x 10(10) M(-1) (Kd1); 17.0 +/- 1.0 x 10(-8) M(-1) (Kd2), and 2.0 +/- 0.1 x 10(-10) M(-1) (Kd1); 12.3 +/- 0.9 x 10(-8) M(-1) (Kd2) compared with 1.0 +/- 0.08 x 10(-10) M(-1) (Kd1); 2.7 +/- 0.25 x 10(-8) M(-1) (Kd2) in DC rats. The results suggest an acute alteration in the number of insulin receptors on ER membranes in STZ-induced diabetic rats. Treatment with SPEt and glibenclamide significantly improved specific insulin binding, with receptor number and affinity binding (p < 0.001) reaching almost normal non-diabetic levels. The data presented here show that SPEt and glibenclamide increase total ER membrane insulin binding sites with a concomitant significant increase in plasma insulin. PMID:15803960

Pari, Leelavinothan; Latha, Muniappan; Rao, Chippada Appa

2004-01-01

179

Impaired molecular regenerative responses in sensory neurones of diabetic rats: gene expression changes in dorsal root ganglia after sciatic nerve crush.  

PubMed

This study investigated changes in gene expression in lumbar dorsal root ganglia (DRG), contralateral and ipsilateral to a sciatic nerve crush in control and streptozotocin (STZ)-induced diabetic rats. After 10 weeks of diabetes, the left sciatic nerves of all rats were crushed at mid-thigh level, and the rats were maintained for a further 2 weeks. Northern blots, with internal standards, were made from L4 and L5 (pooled) DRG on each side to compare RNA hybrids from ganglia attached to crushed nerves with those attached to intact nerves. The expression of growth-associated proteins, GAP-43 and Talpha1 alpha-tubulin mRNA in DRG, was stimulated (all P < 0.05) by crush injury in control and diabetic rats. Steady-state expression of transcripts for neurofilament (NF) proteins (NF-L, NF-H) and the high-affinity NGF receptor, trkA was decreased by diabetes in the contralateral ganglia to the crush (all P < 0.05). Crush injury further decreased expression of these transcripts in both control and diabetic rats (all P < 0.05). This reduced expression of mRNA coding for both growth-associated proteins, and neurofilament proteins in ganglia of diabetic rats could participate in the reduced competence of the regenerative response to nerve crush. PMID:9392496

Mohiuddin, L; Tomlinson, D R

1997-12-01

180

Decrease of heatstroke-induced multiorgan dysfunction by whole body cooling in streptozotocin-induced diabetic rats.  

PubMed

The present study was conducted to assess the effects of whole body cooling on multiorgan dysfunction that occurred during heatstroke in streptozotocin (STZ)-induced diabetic rats. The rats were randomly divided into four groups: [1] the normal control, [2] diabetic control, [3] diabetic heatstroke, and [4] diabetic heatstroke-whole body cooling (WBC). They were exposed to ambient temperature of 43 degrees C for exactly 58 min to induce heatstroke. When the diabetic heatstroke rats underwent heat stress, their survival time values were found to be 11-13 min. Immediately after the onset of heatstroke, resuscitation with body cooling greatly improved survival (221-257 min). Compared with the diabetic (STZ-treated) controls, the diabetic-heatstroke rats displayed higher levels of body temperature, intracranial pressure, serum nitric oxide metabolite, tumor necrosis factor-alpha and dihydroxybenzoic acid, blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and brain levels of local blood flow, and partial pressure of oxygen were all significantly lower during heatstroke. The cerebrovascular, renal, and hepatic dysfunction, the increased levels of nitric oxide metabolites, tumor necrosis factor-alpha, and dihydroxybenzoic acid in the serum during heatstroke were significantly reduced by WBC. Although the serum interleukin-10 maintained at a negligible levels before heat stress, they were significantly elevated by WBC in diabetic-heatstroke rats. The data demonstrate that heatstroke-induced multiorgan dysfunction in streptozotocin-induced diabetic rats can be decreased by WBC. PMID:19764353

Hsu, Chuan-Chih; Niu, Chiang-Shan; Lin, Mao-Tsun

2009-02-28

181

Hypolipidemic and hypoglycemic effects of Orostachys japonicus A. Berger extracts in streptozotocin-induced diabetic rats  

PubMed Central

The hypolipidemic and hypoglycemic effects of two dietary dosages (0.1% and 0.5%) of water and 80% ethanol extracts from hot-air dried Orostachys japonicus A. Berger were evaluated in the serum and organ tissues of streptozotocin-induced diabetic rats. The STZ-induced diabetic groups supplemented with the O. japonicus extracts showed significantly higher body weight compared to a diabetic control group at the end of experiment. The extracts exhibited substantial hypoglycemic effects by significant reductions of fasting blood glucose levels at all time points tested compared to the initial stage before treatment of the extracts. Declines of serum and hepatic triglyceride levels were greater than declines of total cholesterol in the groups treated with the 0.5% O. japonicus extract (DBW2 and DBE2) when compared to the DBC group. Hepatic glycogen content was higher in the groups treated with O. japonicus extract, while lipid peroxide content was decreased in these treated groups compared to the DBC group. Hepatic antioxidant activity was significantly increased in the groups supplemented with the O. japonicus ethanol extract. The hypolipidemic and hypoglycemic effects of the O. japonicus ethanol extract were significantly greater than the effects of the water extract. Based on this study, it seems that O. japonicus ethanol extract, due to its higher phenolic and flavonoid components than the water extract, may control blood glucose and alleviate hyperlipidemia in diabetes.

Lee, Soo Jung; Zhang, Gui Fang

2011-01-01

182

Advanced Glycation End Products in Extracellular Matrix Proteins Contribute to the Failure of Sensory Nerve Regeneration in Diabetes  

PubMed Central

OBJECTIVE The goal of this study was to characterize glycation adducts formed in both in vivo extracellular matrix (ECM) proteins of endoneurium from streptozotocin (STZ)-induced diabetic rats and in vitro by glycation of laminin and fibronectin with methylglyoxal and glucose. We also investigated the impact of advanced glycation end product (AGE) residue content of ECM on neurite outgrowth from sensory neurons. RESEARCH DESIGN AND METHODS Glycation, oxidation, and nitration adducts of ECM proteins extracted from the endoneurium of control and STZ-induced diabetic rat sciatic nerve (3–24 weeks post-STZ) and of laminin and fibronectin that had been glycated using glucose or methylglyoxal were examined by liquid chromatography with tandem mass spectrometry. Methylglyoxal-glycated or unmodified ECM proteins were used as substrata for dissociated rat sensory neurons as in vitro models of regeneration. RESULTS STZ-induced diabetes produced a significant increase in early glycation N?-fructosyl-lysine and AGE residue contents of endoneurial ECM. Glycation of laminin and fibronectin by methylglyoxal and glucose increased glycation adduct residue contents with methylglyoxal-derived hydroimidazolone and N?-fructosyl-lysine, respectively, of greatest quantitative importance. Glycation of laminin caused a significant decrease in both neurotrophin-stimulated and preconditioned sensory neurite outgrowth. This decrease was prevented by aminoguanidine. Glycation of fibronectin also decreased preconditioned neurite outgrowth, which was prevented by aminoguanidine and nerve growth factor. CONCLUSIONS Early glycation and AGE residue content of endoneurial ECM proteins increase markedly in STZ-induced diabetes. Glycation of laminin and fibronectin causes a reduction in neurotrophin-stimulated neurite outgrowth and preconditioned neurite outgrowth. This may provide a mechanism for the failure of collateral sprouting and axonal regeneration in diabetic neuropathy.

Duran-Jimenez, Beatriz; Dobler, Darin; Moffatt, Sarah; Rabbani, Naila; Streuli, Charles H.; Thornalley, Paul J.; Tomlinson, David R.; Gardiner, Natalie J.

2009-01-01

183

Effects of Combined Epidermal Growth Factor and Gastrin on PDX1 Expression in Experimental Type 1 Diabetic Rats.  

PubMed

INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. METHODS:: Rat diabetes was induced by intraperitoneal injection of STZ. The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. Serum levels of C-peptide and insulin were analyzed using radioimmunoassay kits. RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo. PMID:21804373

Yu, Haiying; Sun, Zhonghua; Cui, Junsheng; Song, Guohua; Wang, Fuqing; Gao, Fenglan; Liu, Xiaobin; Wang, Xinrui; Ni, Jinsong

2011-07-28

184

Antidiabetic effects of scoparic acid D isolated from Scoparia dulcis in rats with streptozotocin-induced diabetes.  

PubMed

We evaluated the antihyperglycaemic effect of scoparic acid D (SAD), a diterpenoid isolated from the ethanol extract of Scoparia dulcis in streptozotocin (STZ)-induced diabetic male Wistar rats. SAD was administered orally at a dose of 10, 20 and 40 mg kg(-1) bodyweight for 15 days. At the end of the experimental period, the SAD-treated STZ diabetic rats showed decreased levels of glucose as compared with diabetic control rats. The improvement in blood glucose levels of SAD-treated rats was associated with a significant increase in plasma insulin levels. SAD at a dose of 20 mg kg(-1) bodyweight exhibited a significant effect when compared with other doses. Further, the effect of SAD was tested on STZ-treated rat insulinoma cell lines (RINm5F cells) and isolated islets in vitro. SAD at a dose of 20 microg mL(-1) evoked two-fold stimulation of insulin secretion from isolated islets, indicating its insulin secretagogue activity. Further, SAD protected STZ-mediated cytotoxicity and nitric oxide (NO) production in RINm5F cells. The present study thus confirms the antihyperglycaemic effect of SAD and also demonstrated the consistently strong cytoprotective properties of SAD. PMID:19606382

Latha, Muniappan; Pari, Leelavinothan; Ramkumar, Kunga Mohan; Rajaguru, Palanisamy; Suresh, Thangaraj; Dhanabal, Thangavel; Sitasawad, Sandhya; Bhonde, Ramesh

2009-01-01

185

Expression of endothelin receptor subtypes and their messenger RNAs in diabetic rat prostate: effect of insulin treatment.  

PubMed

Streptozotocin (STZ)-induced diabetes causes an upregulation in the expression of endothelin (ET) receptors in the rat prostate (Eur J Pharmacol 310:197, 1996). We examined the effects of insulin treatment, started 8 weeks after the induction of diabetes, on the expression and distribution of ET receptors and their respective mRNAs in the rat prostate. The densities, pharmacological properties and distribution of ET receptors in the rat prostate were examined using radioligand receptor binding and autoradiographic studies, and gene expression of ET receptors was evaluated utilizing the reverse transcription-polymerase chain reaction (RT-PCR). STZ-injected rats had smaller prostates and reduced serum testosterone levels than control and insulin treated diabetic animals. ET receptor density was shown to be significantly higher in the prostate from diabetic rats than those from either control or insulin treated diabetic animals. The pharmacological profile of prostatic ET receptors was similar in all groups (approximately 80% ET(A); 20% ET(B) subtype). ET receptors were predominantly localized to the prostatic stroma. Induction of diabetes increased the expression of mRNA levels of ET(A) and ET receptors, and insulin treatment reversed this upregulation to control levels. These results indicate that (1) ET receptor subtypes are expressed in the rat prostate as transcription and translation products; (2) insulin can normalize the diabetes-induced upregulation in the expression of ET receptors and their respective mRNAs; and (3) diabetes-induced regression of the prostate may involve an alteration in ET receptors. PMID:10976752

Saito, M; Wada, Y; Ikeda, K; Wang, Z; Foster, H E; Smith, S D; Weiss, R M; Latifpour, J

2000-07-01

186

Streptozotocin-induced insulin deficiency leads to development of behavioral deficits in rats.  

PubMed

Diabetes mellitus is one of the most common serious metabolic disorders in humans that develops due to diminished production of insulin (type I) or resistance to its effect (type II and gestational). The present study was designed to determine the neuropsychological deficits produced following streptozotocin-induced diabetes in rats. Rats were made diabetic by the intra-peritoneal administration of 60 mg/kg streptozotocin (STZ) which induces type-1 diabetes by the destruction "?-cells" of pancreas. Body weight, food and water intake was monitored daily. Open field test (OFT) model, forced swim test (FST) and Morris water maze (MWM) model were performed for the evaluation of ambulation, depression-like symptoms and memory effects, respectively. After 10 days of diabetes induction the exploratory activity of rats was monitored by OFT while depression-like symptoms and memory effects in rats were analyzed by FST and MWM. Results showed that there was no significant effect of STZ-induced diabetes on body weight but food and water intake of STZ-induced diabetic rats was significantly increased. Exploratory activity was significantly decreased and short-term and long-term memory was significantly impaired while the depression-like symptoms was significantly increased in STZ diabetic rats. Thus, it may be suggested that STZ-induced diabetes alters the brain functions and may play an important role in the pathophysiology of certain behavioral deficits like depression, impaired learning and memory functions related to diabetes. This finding may be of relevance in the pathophysiology and in the clinical picture, which could be related to an altered brain serotonin metabolism and neurotransmission and may possibly be related to neuropsychiatric disorders in diabetic patients. PMID:22878975

Haider, Saida; Ahmed, Saara; Tabassum, Saiqa; Memon, Zahida; Ikram, Mehwish; Haleem, Darakhshan J

2012-08-10

187

Comparison of effects of vanadium absorbed by Coprinus comatus with those of inorganic vanadium on bone in streptozotocin-diabetic rats.  

PubMed

The purpose of this study was to compare the effect of vanadium absorbed by Coprinus comatus (VACC) with inorganic vanadium (vanadium nitrate, IV) in preventing diabetes-related osteopenia in streptozotocin-diabetic rats. Sixty Wistar female rats used were divided into four groups: (1) normal rats (control), (2) diabetic rats, (3) diabetic rats treated with VACC, and (4) diabetic rats treated with vanadium nitrate. A standardized type 1-like diabetes model was induced by injection of streptozotocin. After the rats were treated orally with VACC and IV respectively, plasma glucose, body weights, micro-CT, biomechanical testing, and histomorphometry were examined. In addition, bone samples were obtained to evaluate the content of mineral substances in bones. Treatments were performed over a 12-week period. Both VACC and IV have a positive effect on plasma glucose and body weights of STZ-induced diabetic rats. However, treatment with IV only caused a 39.6 % decrease in glucose levels and a 14.6 % increase in body weights, whereas VACC decreased plasma glucose and increased body weights by up to 52.2 and 24.5 %, respectively. At the same time, VACC significantly improved trabecular microstructure and mechanical strength, while IV did not exhibit desirable such effects. Also, bone Ca and bone P were not significantly increased by IV. These results indicated that both VACC and IV have hypoglycemic activity on diabetic rats, while IV did not improve bone properties. In conclusion, this study suggests that VACC improves diabetes-related bone dysfunction, primarily by improving the diabetic states. PMID:22549703

Wang, Guangbin; He, Ming; Yi, Pei; Wang, Jiashi; Li, Bin; Li, Jianjun; Fu, Yonghui; Bai, Lunhao; Fu, Qin

2012-05-03

188

ELEVATED LIPID PEROXIDATION AND DNA OXIDATION IN NERVE FROM DIABETIC RATS: EFFECTS OF ALDOSE REDUCTASE INHIBITION, INSULIN AND NEUROTROPHIC FACTORS  

PubMed Central

We investigated the effect of treatment with an aldose reductase inhibitor, insulin or select neurotrophic factors on the generation of oxidative damage in peripheral nerve. Rats were either treated with streptozotocin (STZ) to induce insulin-deficient diabetes or fed with a diet containing 40% D-galactose to promote hexose metabolism by aldose reductase. Initial time-course studies showed that lipid peroxidation and DNA oxidation were significantly elevated in sciatic nerve after 1 week or 2 weeks of STZ-induced diabetes, respectively, and that both remained elevated after 12 weeks of diabetes. The increase in nerve lipid peroxidation was completely prevented or reversed by treatment with the aldose reductase inhibitor, ICI 222155, or by insulin, but not by the neurotrophic factors, prosaptide TX14(A) or neurotrophin-3. The increase in nerve DNA oxidation was significantly prevented by insulin treatment. In contrast, up to 16 weeks of galactose feeding did not alter nerve lipid peroxidation or protein oxidation, despite evidence of ongoing nerve conduction deficits. These observations demonstrate that nerve oxidative damage develops early after the onset of insulin-deficient diabetes and that it is not induced by increased hexose metabolism by aldose reductase per se, but rather is a downstream consequence of flux through this enzyme. Furthermore, the beneficial effect of prosaptide TX14(A) and neurotrophin-3 on nerve function and structure in diabetic rats are not due to amelioration of increased lipid peroxidation.

Cunha, Joice M.; Jolivalt, Corinne G.; Ramos, Khara M.; Gregory, Joshua A.; Calcutt, Nigel A.; Mizisin, Andrew P.

2008-01-01

189

Diabetic mice are protected from normally lethal nephrotoxicity of S-1,2-dichlorovinyl- l-cysteine (DCVC): role of nephrogenic tissue repair  

Microsoft Academic Search

Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg\\/kg, ip) of S-1,2-dichlorovinyl-l-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is

Ankur V. Dnyanmote; Sharmilee P. Sawant; Edward A. Lock; John R. Latendresse; Alan A. Warbritton; Harihara M.. Mehendale

2006-01-01

190

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

PubMed

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

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

2012-10-11

191

The gastroduodenal branch of the common hepatic vagus regulates voluntary lard intake, fat deposition, and plasma metabolites in streptozotocin-diabetic rats.  

PubMed

The common hepatic branch of the vagus nerve negatively regulates lard intake in rats with streptozotocin (STZ)-induced, insulin-dependent diabetes. However, this branch consists of two subbranches: the hepatic branch proper, which serves the liver, and the gastroduodenal branch, which serves the distal stomach, pancreas, and duodenum. The aim of this study was to determine whether the gastroduodenal branch specifically regulates voluntary lard intake. We performed a gastroduodenal branch vagotomy (GV) on nondiabetic, STZ-diabetic, and STZ-diabetic insulin-treated groups of rats and compared them with sham-operated counterparts. All rats had high steady-state corticosterone levels to maximize lard intake. Five days after surgery, all rats were provided with the choice of chow or lard to eat for another 5 days. STZ-diabetes resulted in a reduction in lard intake that was partially rescued by either GV or insulin treatment. Patterns of white adipose tissue (WAT) deposition differed after GV- and insulin-induced lard intake, with subcutaneous WAT increasing exclusively after the former and mesenteric WAT increasing exclusively in the latter. GV also prevented the insulin-induced reduction in the STZ-elevated plasma glucagon, triglycerides, free fatty acids, and total ketone bodies but did not alter the effect of insulin-induced reduction of plasma glucose levels. These data suggest that the gastroduodenal branch of the vagus inhibits lard intake and regulates WAT deposition and plasma metabolite levels in STZ-diabetic rats. PMID:17971508

Warne, James P; Foster, Michelle T; Horneman, Hart F; Pecoraro, Norman C; de Jong, Hanna K; Ginsberg, Abigail B; Akana, Susan F; Dallman, Mary F

2007-10-30

192

Mg2+-induced adenosine-receptor mediated relaxations in mesenteric vascular beds of diabetic rats.  

PubMed

Our previous studies showed that the magnesium Mg2+-induced relaxations were completely dependent on concentration of nitric oxide (NO) in non-diabetic rat mesenteric vascular beds, in diabetic rats other mechanisms may be involved. The present study was designed to determine the role of adenosine receptor in Mg2+-induced relaxation in streptozotocin (STZ)-induced diabetic rats vessels. Diabetes was induced by the intravenous injection of 60 mg/kg STZ. Eight weeks after diabetes induction, superior mesenteric arteries were isolated and perfused according to the McGregor method. Prepared vascular beds were constricted with phenylephrine to induce 70-75% of maximal constriction (0.001 M). Mg2+ at concentrations of 10(-4) to 10(-1) M were added into the medium and perfusion pressure was recorded. Theophylline (1 mM), and 3,7- dimethyl-1- propargylxanthine (0.01 ?M) were added into medium 20 min before phenylephrine administration. In the presence of theophylline, vasorelaxation induced by high dose of Mg2+ (from 0.03 to 0.1 M) was totally suppressed. In presence of N(?)-nitro-L-arginine methyl ester (L-NAME), the response of Mg2+ was completely inhibited at low dose of Mg2+. But, Mg2+-induced relaxation in the presence of adenosine A2a receptor blocker was significantly suppressed in high dose of Mg2+. Mg2+-induced relaxation in the presence of an A2a receptor blocker was not suppressed either by denudation of endothelium or presence of L-NAME. From the results of this study it may be concluded that Mg2+-induced relaxation at high concentrations is mediated by adenosine A2a receptors, but at low concentrations Mg2+-induced relaxation is dependent on NO. PMID:23255667

Tavasoli, Roya A; Soltani, Nepton; Keshavarz, Mansoor; Shorabipour, Shahla

2012-12-01

193

Effect of S-allylcysteine, a sulphur containing amino acid on iron metabolism in streptozotocin induced diabetic rats.  

PubMed

It is suggested that iron may play a role in the pathogenesis of diabetes. Iron is not only chaperoned through its essential functional pathways, but it also causes damage to biological systems by catalyzing the production of reactive oxygen species. So, the parenchymal tissues of several organs are subject to cell injury and functional insufficiency due to excess deposition of iron. The present study investigated the effects of S-allylcysteine (SAC), a sulphur containing amino acid derived from garlic on the changes in iron metabolism induced by oxidative stress in tissues, as well as on serum biochemical parameters of streptozotocin (STZ)-induced diabetic rats. SAC was administered orally for 45days to control and experimental diabetic rats. The effects of SAC on glucose, insulin, serum iron, ferritin, transferrin, serum bilirubin, heart heme oxygenase activity (HO) and ?-aminolevulinicacid dehydratase activity (?-ALA-D) in liver and kidneys were studied. The levels of glucose, iron, ferritin, bilirubin and HO in liver were increased significantly (p<0.05) whereas the levels of insulin, transferrin and ?-ALA-D in tissues were decreased in diabetic rats. Administration of SAC to diabetic rats showed a decrease in blood glucose, iron, ferritin, bilirubin and HO. In addition, the levels of insulin, transferrin and ?-ALA-D activity in tissues were increased in SAC treated diabetic rats. These findings suggest that S-allylcysteine could have a protective effect against alterations in oxidative stress induced iron metabolism in the diabetic state which was evidenced by the capacity of this natural antioxidant to modulate parameters of iron metabolism. PMID:22981633

Saravanan, Ganapathy; Ponmurugan, Ponnusamy; Begum, Mustapha Shabana

2012-09-13

194

Zinc supplementation inhibits the increase in osteoclastogenesis and decrease in osteoblastogenesis in streptozotocin-induced diabetic rats.  

PubMed

Zinc (Zn) has been shown to stimulate bone formation and inhibit osteoclastic bone resorption and osteoclastogenesis. However, the effects of Zn on bone metabolism in diabetic animals remain to be clarified in vivo. Here, the effects of Zn supplementation on bone metabolism, including osteoclastogenesis and osteoblastogenesis, were investigated using streptozotocine (STZ)-induced diabetic rats. Zn-supplemented water (7.5mg/L) was given for 1 week to diabetic rats injected with STZ (30mg/kg body weight) 1 week earlier. The Zn supplement prevented a decrease in the activity and mRNA of alkaline phosphatase (ALP), osteocalcin mRNA, and hydroxyproline and calcium levels, and an increase in the activity and mRNA of tartrate-resistant acid phosphatase (TRAP) and cathepsin K in the proximal tibia of diabetic rats. Histological analysis revealed that the Zn supplement inhibited the diabetes-induced increase and decrease in the number of osteoclasts and osteoblasts, respectively, in the metaphysis of the proximal tibia. The increase in mRNA levels of receptor for activation of NF-?B (RANK), c-fos, c-jun, TRAP, and cathepsin K and decrease in the expression of Runx2, Dlx5, osterix, ALP, osteocalcin, and collagen were prevented by the supplement. The decrease in ?-catenin, phosphorylated GSK3?, phosphorylated Akt, insulin-like growth factor 1 (IGF-1), and IGF-1 receptor (IGF-1R) protein levels in diabetic rats was also inhibited, although Zn did not affect the diabetes-increased gene and protein expression of Sost and Dkk1. These results suggested that Zn prevented the diabetes-induced increase in osteoclastogenesis and decrease in osteoblastogenesis by inhibiting RANK expression and stimulating IGF-1/IGF-1R/Akt/GSK3?/?-catenin signaling, respectively. PMID:23735664

Iitsuka, Natsumi; Hie, Mamiko; Tsukamoto, Ikuyo

2013-06-02

195

Inhibitory effects of isorhamnetin-3-O-beta-D-glucoside from Salicornia herbacea on rat lens aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues.  

PubMed

The inhibitory effects of compounds from Salicornia herbacea (Chenopodiaceae) on rat lens aldose reductase (RLAR) and sorbitol accumulation in streptozotocin-induced diabetic rat tissues were investigated. The various fractions from the MeOH extract of S. herbacea were tested for their effects on RLAR in vitro. Among them, the EtOAc fraction was found to exhibit a potent RLAR inhibition (IC(50)=0.75 microg/ml), from which an active principle as a potent AR inhibitor was isolated and its chemical structure was elucidated as isorhamnetin-3-O-beta-D-glucoside (1) by spectral analysis. Compound 1 exhibited a potent RLAR inhibition in vitro, its IC(50) being 1.4 microM. Compound 1, when administered orally at 25 mg/kg in streptozotocin (STZ)-induced diabetic rats, caused not only a significant inhibition of serum glucose concentration but also sorbitol accumulation in the lenses, red blood cells (RBC), and sciatic nerves. These results indicate that compound 1 from S. herbacea is a leading compound for further study as a new drug for the prevention and/or treatment of diabetes and its complications. PMID:15863906

Lee, Yeon Sil; Lee, Sanghyun; Lee, Hye Seung; Kim, Bak-Kwang; Ohuchi, Kazuo; Shin, Kuk Hyun

2005-05-01

196

Silymarin regulates the cytochrome P450 3A2 and glutathione peroxides in the liver of streptozotocin-induced diabetic rats.  

PubMed

This study aimed to investigate the protective and regulatory effects of silymarin (SMN) and melatonin (MEL) on streptozotocin (STZ)-induced diabetic changes in cytochrome P450 3A2 (CYP 3A2) and glutathione peroxidase (GPX) expression and antioxidant status in the liver. Male Wistar rats were divided into five groups, including: control (C), untreated diabetic animals (D), SMN-treated diabetics (S, 50 mg/kg, orally), MEL-treated diabetics (M, 10 mg/kg, i.p.), and SMN plus MEL-treated diabetics (S+M). Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). The blood glucose level, daily urinary volume and body weight changes were measured. After the 28 days treatment period, antioxidant status was analyzed by means of the determination of malondialdehyde (MDA) content, nitric oxide (NO) and total thiol molecules (TTM) levels in the liver. The glycogen depletion in the liver was examined by histochemical staining. The CYP 3A2 and GPX expression at mRNA level was determined using RT-PCT technique. SMN and MEL both individually or in combination prevented from diabetes-induced weight loss and lowered daily urinary volume significantly (p<0.05). None of the test compounds could lower the blood glucose level significantly (p>0.05). Both SMN and MEL could convert the diabetes induced elevated levels of MDA and NO and the diabetes-reduced TTM content to the control level. Moreover, the diabetes-up regulated CYP 3A2 and down regulated GPX, returned to normal values after SMN treatment. Histochemical and histopathological examinations revealed that the diabetes-induced glycogen-depletion and single cell necrosis markedly improved with the SMN and SMN plus MEL treatment. Our data suggest that the STZ-induced diabetes in addition of disturbing the antioxidant status, alters the expression levels of CYP 3A2 and GPX. Moreover, the SMN and SMN plus MEL treatment was able to normalize both the antioxidant status and the expression of CYP 3A2 and GPX in the liver of diabetic rats. PMID:22445624

Malekinejad, H; Rezabakhsh, A; Rahmani, F; Hobbenaghi, R

2012-03-24

197

Impaired protein quality control system underlies mitochondrial dysfunction in skeletal muscle of streptozotocin-induced diabetic rats.  

PubMed

Hyperglycaemia-related mitochondrial impairment is suggested as a contributor to skeletal muscle dysfunction. Aiming a better understanding of the molecular mechanisms that underlie mitochondrial dysfunction in type 1 diabetic skeletal muscle, the role of the protein quality control system in mitochondria functionality was studied in intermyofibrillar mitochondria that were isolated from gastrocnemius muscle of streptozotocin (STZ)-induced diabetic rats. Hyperglycaemic rats showed more mitochondria but with lower ATP production ability, which was related with increased carbonylated protein levels and lower mitochondrial proteolytic activity assessed by zymography. LC-MS/MS analysis of the zymogram bands with proteolytic activity allowed the identification of an AAA protease, Lon protease; the metalloproteases PreP, LAP-3 and MIP; and cathepsin D. The content and activity of the Lon protease was lower in the STZ animals, as well as the expression of the m-AAA protease paraplegin, evaluated by western blotting. Data indicated that in muscle from diabetic rats the mitochondrial protein quality control system was compromised, which was evidenced by the decreased activity of AAA proteases, and was accompanied by the accumulation of oxidatively modified proteins, thereby causing adverse effects on mitochondrial functionality. PMID:22542900

Padrão, Ana Isabel; Carvalho, Tiago; Vitorino, Rui; Alves, Renato M P; Caseiro, Armando; Duarte, José Alberto; Ferreira, Rita; Amado, Francisco

2012-04-21

198

The effects of the melatonin treatment on the oxidative stress and apoptosis in diabetic eye and brain.  

PubMed

Oxidative stress plays an important role in the development of complications in diabetes mellitus. Antioxidant therapy has been thought to decrease oxidative stress. The objective of the present study was to explore the effects of melatonin (MLT) on oxidative stress in diabetic rat eye and brain tissue by using immunohistochemical methods. Diabetes was induced by streptozotocin, (STZ, 55 mg/kg/i.p) in adult rats. MLT was given 10 mg/kg/i.p once a day for 2 weeks beginning from the sixth week. Six weeks later, rats were divided into three groups: control (CR), STZ-induced diabetic (STZ), and STZ-induced diabetic group received melatonin (STZ+MLT). Although no significant difference was observed with respect to antioxidant status, NOS activity tended to be higher in the untreated diabetic rats than in the treated rats. It was observed that MLT treatment improved the histopathological changes including apoptosis and oxidative stress in brain and eye in diabetic rat. PMID:22654617

Gürp?nar, Tu?ba; Ekerbiçer, Nuran; Uysal, Nazan; Barut, Turgay; Tarakç?, Figen; Tuglu, M Ibrahim

2012-05-01

199

Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats.  

PubMed

Persistent hyperglycemia is associated with chronic oxidative stress which contributes to the development and progression of diabetes-associated complications. The sensitivity of pancreatic ?-cells to oxidative stress has been attributed to their low content of antioxidants compared with other tissues. Bioactive compounds with potent antidiabetic properties have been shown to ameliorate hyperglycemia mediated oxidative stress. Recently, we have reported that oral administration of fisetin (10 mg/Kg b.w.), a bioflavonoid found to be present in strawberries, persimmon, to STZ-induced experimental diabetic rats significantly improved normoglycemia. The present study was aimed to evaluate the antioxidant potential of fisetin in both in vitro and in vivo. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Fisetin was administered orally for 30 days. At the end of the study, all animals were killed. Blood samples were collected for the biochemical estimations. The antioxidant status was evaluated. Histological examinations were performed on pancreatic tissues. Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1? (plasma), serum nitric oxide (NO) with an elevation in plasma insulin. The treatment also improved the antioxidant status in pancreas as well as plasma of diabetic rats indicating the antioxidant potential of fisetin. In addition, the results of DPPH and ABTS assays substantiate the free radical scavenging activity of fisetin. Histological studies of the pancreas also evidenced the tissue protective nature of fisetin. It is concluded that, fisetin possesses antioxidant and anti-inflammatory property and may be considered as an adjunct for the treatment of diabetes. PMID:23277230

Prasath, Gopalan Sriram; Sundaram, Chinnakrishnan Shanmuga; Subramanian, Sorimuthu Pillai

2013-01-01

200

The effects of resveratrol on cyclooxygenase-1 and cyclooxygenase-2 mRNA and protein levels in diabetic rat kidneys.  

PubMed

Cyclooxygenase (COX), which have the isoforms of COX-1 and COX-2, is the key enzyme of prostaglandins biosynthesis. Especially, COX-2 is induced in inflammatory disease such as Diabetes Mellitus (DM). Resveratrol (RSV), a natural antioxidant, has a beneficial role in prevention of inflammatory disease. We investigated the changes of COX-1 and COX-2 mRNA expression and protein level in diabetic rat kidney after RSV treatment. Three months-old, 44 Wistar albino male rats, which were divided into six groups such as control group, sodium citrate buffer (sham control) group, diabetic group (DM), Dimethyl Sulfoxide induced control group, RSV treated sham control group (RSV) and RSV treated diabetic group (DM + RSV) were used for the study. Experimental diabetes was induced by intraperitoneal injection of 55 mg/kg Streptozotocin. After the induction of chronic diabetes 10 mg/kg per day RSV was administered intraperitoneally for 4 weeks. In this study. RSV has no significant effect on COX-1 mRNA expression in diabetic rat kidney (P > 0.05). Immunohistochemical study showed that COX-1 expression was slightly inhibited in RSV group and was not significantly supressed in DM + RSV group. When comparing control and treated groups, there were no significant differences in COX-2 mRNA or protein levels (P > 0.05). In conclusion, our results indicate that resveratrol do not significantly affect COX gene and protein expression. Therefore, different therapy strategies such as combination with other antidiabetic drugs may tried in STZ induced animal model for reducing diabetic symptoms and altering COX-1 and COX-2 mRNA or protein levels. PMID:19693696

Yar, Atiye Seda; Menevse, Sevda; Alp, Ebru; Helvacioglu, Fatma; Take, Gulnur

2009-08-20

201

Protective Effect of Proanthocyanidin against Diabetic Oxidative Stress  

PubMed Central

We investigated the antidiabetic potential of proanthocyanidin and its oligomeric form in STZ-induced diabetic model rats and db/db type 2 diabetic mice. Proanthocyanidin ameliorated the diabetic condition by significant decreases of serum glucose, glycosylated protein, and serum urea nitrogen as well as decreases of urinary protein and renal-AGE in STZ-induced diabetic rats and decrease of serum glucose as well as significant decrease of glycosylated protein in db/db type 2 diabetic mice. The suppression of ROS generation and elevation of the GSH/GSSG ratio were also observed in the groups administered proanthocyanidin. Moreover, proanthocyanidin, especially its oligomeric form, affected the inflammatory process with the regulation of related protein expression, iNOS, COX-2 and upstream regulators, NF-?B, and the I?B-?. In addition, it had a marked effect on hyperlipidemia through lowering significant levels of triglycerides, total cholesterol, and NEFA. Moreover, expressions in the liver of SREBP-1 and SREBP-2 were downregulated by the administration of proanthocyanidins. The protective effect against hyperglycemia and hyperlipidemia in type 1 and 2 diabetic models was significantly strong in the groups administered the oligomeric rather than polymeric form. This suggests that oligomers act as a regulator in inflammatory reactions caused by oxidative stress in diabetes.

Yokozawa, Takako; Cho, Eun Ju; Park, Chan Hum; Kim, Ji Hyun

2012-01-01

202

Microemulsions for oral delivery of insulin: design, development and evaluation in streptozotocin induced diabetic rats.  

PubMed

Insulin loaded microemulsions were developed adopting a low shear reverse micellar approach using didoceyldimethylammonium bromide (DMAB) as the surfactant, propylene glycol (PG) as the co-surfactant, triacetin (TA) as the oil phase and insulin solution as the aqueous phase. A ternary phase diagram was constructed based on multiple cloud point titration to highlight the reverse micellar region. The droplet sizes of the microemulsions were 161.7±24.7nm with PDI of 0.447±0.076 and insulin entrapment of ?85%. Transmission electron microscopy (TEM) revealed the spherical nature and size homogeneity of the microemulsion droplets. The conformational stability of the entrapped insulin within microemulsions was confirmed by fluorescence spectroscopy and circular dichroism. The microemulsions displayed a 10-fold enhancement in bioavailability compared with plain insulin solution administered per oral in healthy rats. The short-term in vivo efficacy in STZ induced diabetic rats provided the proof of concept by a modest glucose reduction at a dose of 20IU/kg. Together this preliminary data indicate the promise of microemulsions for oral delivery of insulin. PMID:20655382

Sharma, G; Wilson, K; van der Walle, C F; Sattar, N; Petrie, J R; Ravi Kumar, M N V

2010-07-22

203

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

SciTech Connect

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.

Pleta, M.; Chan, T.

1987-05-01

204

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

PubMed Central

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.

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

2012-01-01

205

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

PubMed

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

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

206

Efficacy of asiatic acid, a pentacyclic triterpene on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats.  

PubMed

Asiatic acid (AA), a triterpenoid derivative of Centella asiatica, has shown significant biological effects of antioxidant and anti-inflammatory activities. Aim of this investigation was to evaluate the antihyperglycemic effect of AA on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. To induce diabetes mellitus, rats were injected with streptozotocin intraperitoneally at a single dose of 40 mg/kg b.w. Diabetic rats showed significant (p<0.05) increased in plasma glucose, glycosylated hemoglobin and significant (p<0.05) decreased in circulating insulin and hemoglobin. The altered activities of key enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase of carbohydrate metabolism significantly (p<0.05) increased whereas hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and glycogen content significantly (p<0.05) decreased in the liver of diabetic rats and also increased activities of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). Oral administration of AA (5, 10 and 20 mg/kg b.w.) and glibenclamide (600 ?g/kg b.w.) to diabetic rats for 45 days prevented the above alteration and reverted to near normalcy. Protection of body weight loss of diabetic rats by AA was also observed. No significant effect was observed in normal rats treated with AA (20 mg/kg b.w.). In this search, AA found to be potential bioactive compound to regulate the carbohydrate metabolism by modulating the key regulatory enzymes in diabetic rats. These findings merit further research in this field. PMID:23102509

Ramachandran, Vinayagam; Saravanan, Ramalingam

2012-10-25

207

Upregulation of PPAR? by Aegle marmelos ameliorates insulin resistance and ?-cell dysfunction in high fat diet fed-streptozotocin induced type 2 diabetic rats.  

PubMed

The global epidemic of type 2 diabetes demands the rapid evaluation of new and accessible interventions. This study investigated whether Aegle marmelos fruit aqueous extract (AMF; 250, 500 and 1000?mg/kg) improves insulin resistance, dyslipidemia and ?-cell dysfunction in high fat diet fed-streptozotocin (HFD-STZ)-induced diabetic rats by modulating peroxisome proliferator-activated receptor-? (PPAR?) expression. The serum levels of glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of ?-cell function (HOMA-B), lipid profile, TNF-? and IL-6 were evaluated. Further, the TBARS level and SOD activity in pancreatic tissue and PPAR? protein expression in liver were assessed. In addition, histopathological and ultrastructural studies were performed to validate the effect of AMF on ?-cells. The HFD-STZ treated rats showed a significant increase in the serum levels of glucose, insulin, HOMA-IR, TNF-?, IL-6, dyslipidemia with a concomitant decrease in HOMA-B and PPAR? expression. Treatment with AMF for 21?days in diabetic rats positively modulated the altered parameters in a dose-dependent manner. Furthermore, AMF prevented inflammatory changes and ?-cell damage along with a reduction in mitochondrial and endoplasmic reticulum swelling. These findings suggest that the protective effect of AMF in type 2 diabetic rats is due to the preservation of ?-cell function and insulin-sensitivity through increased PPAR? expression. PMID:21351301

Sharma, Ashok Kumar; Bharti, Saurabh; Goyal, Sameer; Arora, Sachin; Nepal, Saroj; Kishore, Kamal; Joshi, Sujata; Kumari, Santosh; Arya, Dharamvir Singh

2011-02-24

208

Esculetin induced changes in Mmp13 and Bmp6 gene expression and histone H3 modifications attenuate development of glomerulosclerosis in diabetic rats.  

PubMed

Esculetin, an antioxidant, has been used in the treatment of a variety of diseases. This study aimed to investigate the protective effect of esculetin in attenuating streptozotocin (STZ)-induced type I diabetic nephropathy and to understand the molecular mechanism involved in it. Sprague-Dawley rats were rendered diabetic using a single dose of STZ (55?mg/kg, i.p.). Protein expression of PPAR? and transforming growth factor-?1 (TGF-?1) was detected by immunoblotting and immunohistochemistry respectively. RNA expression levels of Mmp13 and Bmp6 were detected by RT-PCR analysis. In diabetic rats, esculetin treatment resulted in a significant decrease in blood glucose, blood urea nitrogen, and plasma creatinine and increase in plasma albumin levels. Esculetin treatment attenuates the downregulation of PPAR? in diabetic kidney, which in turn blocks the TGF-?1-mediated fibronectin expression. In addition, it attenuates the decrease in mono-methylation (K4) and acetylation of histone H3 in diabetic kidney. RT-PCR analysis revealed that esculetin treatment provides protection by decreasing antifibrotic Bmp6 and increasing fibrogenic Mmp13 mRNA expression in diabetic kidney. This is the first report to show that protection observed by esculetin treatment involves alteration in mRNA expression of Mmp13 and Bmp6 genes either directly via altered histone H3 modifications or indirectly by inhibiting the PPAR?/TGF-?1 pathway. PMID:21450970

Surse, Vivek Madhukar; Gupta, Jeena; Tikoo, Kulbhushan

2011-06-09

209

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

PubMed Central

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.

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

2013-01-01

210

Synthesis, characterization and anti-diabetic therapeutic potential of a new benzyl acid-derivatized kojic acid vanadyl complex.  

PubMed

Vanadium complexes are potent hypoglycemic agents and of great potential for therapeutical treatment of diabetes. In the present work, a novel vanadium compound, bis ((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl benzoatato) oxovanadium (IV) (BBOV) has been synthesized. Treatment of STZ-induced diabetic rats with BBOV restored the blood glucose to normal level and ameliorated glucose tolerance. The hypoglycemic effect of BBOV is similar to that of bis (maltolato) oxovanadium but is less toxic in median lethal dose. Overall, the present work will provide useful information for further development of new anti-diabetic vanadium compounds. PMID:23015214

Wei, Yong-Biao; Yang, Xiao-Da

2012-09-27

211

Chronic endothelin-A receptor antagonism is as protective as angiotensin converting enzyme inhibition against cardiac dysfunction in diabetic rats  

PubMed Central

Background and purpose: Diabetes mellitus is associated with a specific cardiomyopathy. We compared the cardioprotective effects of an endothelin-A receptor blocker (ETA-RB) with those of an angiotensin-converting enzyme inhibitor (ACE-I) in rats with streptozotocin (STZ)-induced diabetes. Experimental approach: Diabetic rats were left untreated or received either the ETA-RB atrasentan or the ACE-I ramipril (each 3?mg kg?1 per day) orally for 8 weeks. Isolated isovolumic heart function was studied during normoxia and in response to ischaemia-reperfusion. Cardiac fibrosis, tissue oxidative stress and tissue nitric oxide synthase (NOS) activity were determined. Key results: Basal left ventricular systolic contractility was lower in diabetic compared to nondiabetic hearts and ETA-RB or ACE-I treatment significantly antagonised the decline. Following 15?min of no-flow ischaemia, reperfusion systolic function was depressed and left-ventricular end-diastolic pressure (LVEDP) was elevated in diabetic hearts. ETA-RB or ACE-I treatment significantly improved recovery of reperfusion systolic and diastolic function, without differences between groups. Hydroxyproline (an index of tissue fibrosis) and malondialdehyde (a measure of tissue oxidative stress) were elevated at the end of reperfusion in diabetic, compared to nondiabetic hearts. Either treatment reduced hydroxyproline and malondialdehyde to control level. Constitutive NOS activity was similar in nondiabetic and diabetic hearts and unaffected by ETA-RB or ACE-I treatment. Conclusions and implications: These results suggest that in experimental type 1 diabetes ETA-RB is as effective as an ACE-I in ameliorating myocardial functions during normoxia and ischaemia-reperfusion. Combining the two treatments neither afforded additive effects, nor diminished any protection effect seen with either drug.

Wolkart, G; Pang, X; Stessel, H; Kirchengast, M; Brunner, F

2007-01-01

212

Carbamylated erythropoietin attenuates cardiomyopathy via PI3K/Akt activation in rats with diabetic cardiomyopathy  

PubMed Central

The aim of the present study was to investigate the protective effect of carbamylated erythropoietin (CEPO) against cardiomyopathy in high-fat, high-carbohydrate diet-fed rats with streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM). Healthy male Wistar rats were fed a high-fat, high-carbohydrate diet for four weeks, and then were injected with STZ twice (50 mg/kg, intraperitoneally). Once DCM was confirmed, the rats were divided randomly into the following groups: DCM without treatment, CEPO treatment at different dosages (500, 1,000 or 2,000 IU/kg) or recombinant human erythropoietin (rhEPO) treatment (1,000 IU/kg), for a four-week short intervention or an eight-week long intervention protocol. Healthy rats were used as normal controls. Venous blood samples were drawn for routine hematological examinations, and heart tissues were collected for histological analysis, as well as the determination of myocardial apoptosis and phosphatidylinositol-3-kinase (PI3K)/Akt signaling. CEPO treatment had no significant effect on the erythrocyte or hemoglobin levels in the rats with DCM; however, it reduced myocardial cell apoptosis in the rats and protected the cellular ultrastructure. In addition, CEPO treatment inhibited caspase-3 and increased Bcl-xl protein expression (P<0.05). It also increased PI3K (p85) and Akt1 expression at the mRNA and protein levels in the hearts of the rats with DCM, with a dose-response relationship. An eight-week treatment using CEPO, in comparison with a four-week protocol, marginally increased PI3K (p85) and Akt1 expression, and did not demonstrate significant benefit. The study indicated that CEPO protects against DCM, without markedly affecting erythropoiesis, and that the activation of PI3K/Akt may be a key mechanism in the protection conferred by CEPO.

HE, HONGYING; QIAO, XIAOYU; WU, SUISHENG

2013-01-01

213

Renal (pro)renin receptor contributes to development of diabetic kidney disease through TGF?1-CTGF signaling cascade  

PubMed Central

SUMMARY Transforming growth factor ?1 (TGF?1) and connective tissue growth factor (CTGF) are expressed in renal glomeruli and contribute to development of diabetic nephropathy. Recently we demonstrated that (pro)renin receptor (PRR) is upregulated in the kidneys of streptozocin (STZ)-induced diabetes rat model. We hypothesized that in the presence of hyperglycemia, increased renal PRR expression contributes to enhanced TGF?1-CTGF signaling activity, leading to development of diabetic kidney disease.In vivo and in vitro studies were conducted in Sprague-Dawley rats and rat mesangial cells (RMCs). PRR blockade was achieved in vivo by treating STZ induced diabetes rats with the handle region peptide (HRP) of prorenin and in vitro by HRP or PRR siRNA in RMCs. Angiotensin AT1 receptor blockade was achieved by Valsartan treatment.Results showed that expression of PRR, TGF?1 and CTGF were upregulated in diabetic kidneys and RMCs exposed to high glucose. Glucose exposure also induced PRR phosphorylation, a process that was inhibited by HRP, Valsartan or PRR siRNA. HRP and Valsartan significantly attenuated renal TGF?1 and CTGF expression in diabetic animals and high glucose treated RMCs. Similar results were observed in high glucose exposed RMCs in response to PRR siRNA. TGF? receptor blockade decreased CTGF expression in RMCs. Combined administration of Valsartan and PRR siRNA demonstrated further reduction of TGF?1 and CTGF expression in RMCs.In conclusion, PRR contributes to kidney disease in diabetes through enhanced TGF?1-CTGF signaling cascade.

Huang, Jiqian; Matavelli, Luis C.; Siragy, Helmy M.

2011-01-01

214

Ameliorative potential of S-allylcysteine: effect on lipid profile and changes in tissue fatty acid composition in experimental diabetes.  

PubMed

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 S-allylcysteine (SAC) in STZ induced diabetic rats. The levels of blood glucose, cholesterol (TC), triglycerides (TG), free fatty acids, phospholipids and fatty acid composition were estimated in the liver and kidneys of control and experimental groups of rats. Oral administration of SAC at a dose of 150 mg/kg bodyweight per day to STZ-induced diabetic rats for a period of 45 days resulted in a significant reduction in fasting blood glucose, TC, TG, free fatty acids, phospholipids, LDL-C, VLDL-C and elevation of HDL-C in comparison with diabetic control group. Oral administration of SAC 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 SAC was compared with glyclazide; a well-known antihyperglycemic drug. The result of the present study indicates that SAC showed an antihyperlipidemic effect in addition to its antidiabetic effect in experimental diabetes. PMID:21216577

Saravanan, Ganapathy; Ponmurugan, Ponnusamy

2011-01-08

215

Insulin administration abrogates perturbation of methyl group and homocysteine metabolism in streptozotocin-treated type 1 diabetic rats.  

PubMed

Modifications in methyl group and homocysteine metabolism are associated with a number of pathologies, including vascular disease, cancer, and neural tube defects. A diabetic state is known to alter both methyl group and homocysteine metabolism, and glycine N-methyltransferase (GNMT) is a major regulatory protein that controls the supply and utilization of methyl groups. We have shown previously that diabetes induces GNMT expression and reduces plasma homocysteine pools by stimulating both its catabolism and folate-independent remethylation. This study was conducted to determine whether insulin plays a role in the control of homocysteine concentrations and GNMT as well as other key regulatory proteins. Male Sprague-Dawley rats were randomly assigned to one of three groups: control, streptozotocin (STZ)-induced diabetic (60 mg/kg body wt), and insulin-treated diabetic (1.0 U bid). After 5 days, rats were anesthetized (ketamine-xylazine) for procurement of blood and tissues. A 1.5-fold elevation in hepatic GNMT activity and hypohomocysteinemia in diabetic rats was completely prevented by insulin treatment. Additionally, diabetes-mediated alterations in methionine synthase, phosphatidylethanolamine N-methyltransferase, and DNA methylation were also prevented by insulin. We hypothesize that the concentration of blood glucose may represent a regulatory signal to modify GNMT and homocysteine. In support of this, blood glucose concentrations were negatively correlated with total plasma homocysteine (r = -0.75, P < 0.001) and positively correlated with GNMT activity (r = 0.77, P < 0.001). Future research will focus on further elucidating the role of glucose or insulin as a signal for regulating homocysteine and methyl group metabolism. PMID:21730260

Nieman, Kristin M; Schalinske, Kevin L

2011-07-05

216

Increase of angiotensin-converting enzyme activity and peripheral sympathetic dysfunction could contribute to hypertension development in streptozotocin-induced diabetic rats.  

PubMed

Diabetes augments the risk of hypertension. Although several factors have been implicated in the development of such hypertensive state, we designed this study to investigate blood pressure development, the activity of angiotensin-converting enzyme (ACE) in blood as well as sympathetic neurotransmission in the vas deferens of diabetic rats. We used streptozotocin (STZ)-induced diabetic rats (60 mg/kg) in order to evaluate the systolic blood pressure (SBP), ACE activity and peripheral sympathetic neurotransmission. We observed the following changes of parameters: increase of SBP, decrease of heart rate, augmentation of plasma ACE activity, enhancement of phasic and tonic vas deferens contractions elicited by electrical stimulation at 5 Hz, increase of maximal response to noradrenaline (NA) and decrease of adenosine triphosphate (ATP)-elicited contraction of vasa deferentia. The results reveal that in the development of hypertension in diabetic rats, augmentation of circulating ACE activity precedes the sympathetic dysfunction. Additionally, it seems that the purinergic and noradrenergic neurotransmission is compromised. PMID:23975725

Musial, Diego C; da Silva Júnior, Edilson D; da Silva, Regiane M; Miranda-Ferreira, Regiane; Lima-Landman, M Teresa R; Jurkiewicz, Aron; García, Antonio G; Jurkiewicz, Neide H

2013-08-22

217

Antidiabetic effect of S-allylcysteine: Effect on plasma and tissue glycoproteins in experimental diabetes.  

PubMed

The present study was conducted to investigate the effect of S-allylcysteine (SAC) on dearrangement in glycoprotein levels in the streptozotocin induced diabetic model. SAC (150 mg/kg b.w./day) was administered orally for 45 days to normal and diabetic rats. STZ-induced diabetic rats showed significant increase in blood glucose and glycoprotein components such as hexose, hexosamine, fucose and sialic acid in plasma, liver and kidneys of diabetic rats. Oral administration of SAC to diabetic rats for a period of 45 days normalized all the above-mentioned biochemical parameters. The antihyperglycemic effect of SAC was compared with glyclazide, a well-known antihyperglycemic drug. The present study indicates that SAC possesses a significantly beneficial effect on the glycoprotein moiety in addition to its antidiabetic effect. PMID:20576413

Saravanan, G; Ponmurugan, P; Senthil Kumar, G P; Rajarajan, T

2010-06-23

218

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

PubMed Central

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.

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

2013-01-01

219

Protective role of Scoparia dulcis plant extract on brain antioxidant status and lipidperoxidation in STZ diabetic male Wistar rats  

PubMed Central

Background The aim of the study was to investigate the effect of aqueous extract of Scoparia dulcis on the occurrence of oxidative stress in the brain of rats during diabetes by measuring the extent of oxidative damage as well as the status of the antioxidant defense system. Methods Aqueous extract of Scoparia dulcis plant was administered orally (200 mg/kg body weight) and the effect of extract on blood glucose, plasma insulin and the levels of thiobarbituric acid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) were estimated in streptozotocin (STZ) induced diabetic rats. Glibenclamide was used as standard reference drug. Results A significant increase in the activities of plasma insulin, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione was observed in brain on treatment with 200 mg/kg body weight of Scoparia dulcis plant extract (SPEt) and glibenclamide for 6 weeks. Both the treated groups showed significant decrease in TBARS and hydroperoxides formation in brain, suggesting its role in protection against lipidperoxidation induced membrane damage. Conclusions Since the study of induction of the antioxidant enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of the medicinal plant, these findings suggest a possible antiperoxidative role for Scoparia dulcis plant extract. Hence, in addition to antidiabetic effect, Scoparia dulcis possess antioxidant potential that may be used for therapeutic purposes.

Pari, Leelavinothan; Latha, Muniappan

2004-01-01

220

Alkaline, Endo III and FPG modified comet assay as biomarkers for the detection of oxidative DNA damage in rats with experimentally induced diabetes.  

PubMed

Increased production of reactive oxygen species under diabetic condition underlines the higher oxidatively damaged DNA in different tissues. However, it is practically difficult to assess the oxidatively damaged DNA in different internal organs. Therefore, the present study was aimed to evaluate the extent of oxidative stress-induced DNA damage in different organs with the progression of diabetes. Diabetic and control Sprague Dawley rats were sacrificed in time-dependent manner and the lung, liver, heart, aorta, kidney, pancreas and peripheral blood lymphocytes (PBL) were analyzed for both alkaline and modified comet assay with endonuclease-III (Endo III) and formamidopyrimidine-DNA glycosylase (FPG) (hereafter called modified comet assay) for the detection of oxidative DNA damage. The statistically significant increase in olive tail moment (OTM) was found in all the tested tissues. The extent of DNA damage was increased with the progression of diabetes as revealed by the parameter of OTM in alkaline and modified comet assay. Further, the positive correlations were observed between OTM of the lung, liver, heart, aorta, kidney and pancreas with PBL of diabetic rat in the alkaline and modified comet assay. Moreover, significant increase in the 8-oxodG positive nuclei in the lung, liver, heart, aorta, kidney and pancreas was observed in 4th and 8th week diabetic rat as compared to control. Results of the present study clearly indicated the suitability of alkaline and modified comet assay for the detection of multi-organ oxidative DNA damage in streptozotocin (STZ)-induced diabetic rat and showed that damaged DNA of PBL can be used as a suitable biomarker to assess the internal organs response to DNA damage in diabetes. PMID:22015262

Kushwaha, S; Vikram, A; Trivedi, P P; Jena, G B

2011-10-12

221

Effects of ghrelin on gastric distention sensitive neurons in the arcuate nucleus of hypothalamus and gastric motility in diabetic rats.  

PubMed

This study was performed to observe the effects of ghrelin on the activity of gastric distention (GD) sensitive neurons in the arcuate nucleus of hypothalamus (Arc) and on gastric motility in vivo in streptozocin (STZ) induced diabetes mellitus (DM) rats. Electrophysiological results showed that ghrelin could excite GD-excitatory (GD-E) neurons and inhibit GD-inhibitory (GD-I) neurons in the Arc. However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of ghrelin on GD-E neurons was much weaker in DM rats. Gastric motility research in vivo showed that microinjection of ghrelin into the Arc could significantly promote gastric motility and it showed a dose-dependent manner. The effect of ghrelin promoting gastric motility in DM rats was weaker than that in normal rats. The effects induced by ghrelin could be blocked by growth hormone secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163. RIA and real-time PCR data showed that the levels of ghrelin in the plasma, stomach and ghrelin mRNA in the Arc increased at first but decreased later and the expression of GHSR-1a mRNA in the Arc maintained a low level in DM rats. The present findings indicate that ghrelin could regulate the activity of GD sensitive neurons and gastric motility via ghrelin receptors in the Arc. The reduced effects of promoting gastric motility induced by ghrelin could be connected with the decreased expression of ghrelin receptors in the Arc in diabetes. Our data provide new experimental evidence for the role of ghrelin in gastric motility disorder in diabetes. PMID:23965296

Xu, Luo; Qu, Zhuling; Guo, Feifei; Pang, Mingjie; Gao, Shengli; Zhu, Hai; Gu, Fang; Sun, Xiangrong

2013-08-18

222

17ss-Estradiol Antagonizes the Down-Regulation of ER?/NOS-3 Signaling in Vascular Endothelial Dysfunction of Female Diabetic Rats  

PubMed Central

Previous studies indicated that estrogen could improve endothelial function. However, whether estrogen protects vascular complications of diabetes has yet to be clarified. The study was designed to investigate the action of 17ß-estradiol on vascular endothelium in streptozotocin (STZ)-induced diabetic rats. Ovariectomized female Sprague-Dawley rats were administered with streptozotocin to produce an ovariectomized-diabetic (OVS) model which manifested as dysfunction of aortic dilation and contraction ability. Meanwhile, OVS animals with 17ß-estradiol supplementation significantly improved aortic function. Accordingly, nitric oxide synthase-3 (NOS-3), Akt, PI3K and estrogen receptor ? (ER?) protein expression in aorta declined in the OVS group. Such effects were partially restored by estrogen replacement. The presence of 17ß-estradiol similarly counteracted the reduction of cyclic guanosine monophosphate (cGMP), the enhanced expression of inducible NOS (NOS-2) and NO metabolites (nitrite and nitrate), as well as the increase of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1), which is an index of arterial compliance. 17ß-estradiol could also decrease ROS production in vascular endothelium. In EA hy 926 cells we found that ER antagonist, wortmannin and Akt inhibitor could block improvement effects of 17ß-estradiol. These results strongly suggest that functional impairment of the ER?/NOS-3 signaling network in OVS animals was partially restored by 17ß-estradiol administration, which provides experimental support for estrogen recruitment to improve vascular outcomes in female diabetes after endogenous hormone depletion.

Meng, Guoliang; Xiao, Yujiao; Zhang, Wen; Wang, Zhuoying; Xie, Liping; Liu, Zhen; Lu, Hui; Ji, Yong

2012-01-01

223

How obesity causes diabetes in Zucker diabetic fatty rats  

Microsoft Academic Search

The mechanisms of adipogenic diabetes in Zucker diabetic fatty (ZDF) rats, a model of obesity complicated by diabetes, are reviewed. In ZDF rats, a mutation in the leptin receptor, OB-R, is associated with leptin resistance, obesity, and increased fat content of islets. Exaggerated nitric oxide (NO) generation, attributed to high intracellular levels of long-chain fatty acids, impairs ?-cell function and

Roger H. Unger

1997-01-01

224

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

PubMed Central

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.

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

2010-01-01

225

Streptozotocin, Type I Diabetes Severity and Bone  

PubMed Central

As many as 50% of adults with type I (T1) diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ)-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2). An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

2009-01-01

226

Anti-diabetic activity of the semi-purified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin-induced diabetic rats.  

PubMed

The present study was designed to investigate the hypoglycemic and hypolipidemic activities of the semi-purified fractions of an ethanolic leaf extract of Averrhoa bilimbi (ABe) in high fat diet (HFD)-streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats aged 10 weeks (200-250 g) were fed with a high fat diet obtained from Glen Forrest stock feeders (Western Australia) for 2 weeks prior to intraperitoneal injection with streptozotocin (STZ, 50 mg/kg). The leaves of A.bilimbi were exhaustively extracted with 80% ethanol, concentrated at 40 degrees C using a rotavapor and partitioned successively with butanol, ethylacetate and hexane to get aqueous (AF), butanol (BuF), ethylacetate (EF), and hexane fractions (HF). The fractions were freeze-dried to obtain powders of each. To investigate the effect of long term administration of the hypoglycemic fractions, diabetic animals were treated with vehicle (distilled water), AF (125 mg/kg), or BuF (125 mg/kg), twice a day for 14 days. The long term administration of AF and BuF at a dose of 125 mg/kg significantly (P < 0.05) lowered blood glucose and triglyceride concentrations when compared to the vehicle. The hepatic glycogen content was significantly higher (P < 0.05) in AF-treated rats when compared to diabetic control, however no change was found in the BuF-treated rats. Moreover, AF as well as BuF did not cause any significant change in the total cholesterol and HDL-cholesterol. There was also no difference in liver thiobarbituric acid reactive substances (TBARS) and cytochrome P450 values between AF, BuF and vehicle-treated control rats. In conclusion, the results indicate that AF is more potent than BuF in the amelioration of hyperglycemia and hyperlipidemia in HFD fed-STZ diabetic rats. Hence, AF is a potential source for the isolation of active principle(s) for oral anti-diabetic therapy. PMID:15808883

Tan, Benny Kwong Huat; Tan, Chee Hong; Pushparaj, Peter Natesan

2005-04-29

227

Nifedipine versus fosinopril in uninephrectomized diabetic rats  

Microsoft Academic Search

Nifedipine versus fosinopril in uninephrectomized diabetic rats. Antihypertensive agents have been shown to exert inequivalent effects on glomerular injury in experimental renal disease models. To compare the consequences of dissimilar antihypertensive regimens on the development of diabetic glomerulopathy, studies were performed in three groups of uninephrectomized moderately hyperglycemic diabetic rats. One group (DM) received no therapy except insulin. The remaining

Sharon Anderson; Helmut G Rennke; Barry M Brenner; Miguel A Zayas; Helen M Lafferty; Julia L Troy; Deborah J Sandstrom

1992-01-01

228

Effective control of blood glucose status and toxicity in streptozotocin-induced diabetic rats by orally administration of vanadate in an herbal decoction.  

PubMed

Vanadium compounds have been well recognized for hypoglycemic effects, but questions remain on gastrointestinal disturbance and possible tissue vanadium accumulation thus slowing the acceptance of vanadium compounds as diabetic therapeutic agents. Our intestinal permeability and toxicity studies of vanadium compounds have suggested that the co-administration of vanadate with Salvia miltiorrhiza Bunge decoction could benefit the therapeutic use of hypoglycemic vanadium compounds. In the present paper, we tested the hypoglycemic effects of vanadate ingested in an aqueous extract of S. Bunge using a streptozocin (STZ)-induced diabetic rat model. Oral administration of vanadate in S. Bunge herbal decoction produced a stable (free of hypoglycemic shock) and long-lasting ( approximately 70day) control of blood glucose status. Effective protection of animal organs from hyperglycemic damage was also observed. As expected, the herbal extract significantly alleviated vanadium toxicity, i.e. GI stress and metal accumulation. In addition, the result suggesting that vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of the pancreatic beta-cells which initially survived STZ-toxicity. These studies provide new insight into the therapeutic treatment of diabetics with vanadium compounds. PMID:18601969

Zhang, L; Zhang, Y; Xia, Q; Zhao, X M; Cai, H X; Li, D W; Yang, X D; Wang, K; Xia, Z L

2008-06-11

229

Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier Through Differential Regulation of VEGF-A and Its Receptors in Early Diabetic Rat Retinas  

PubMed Central

OBJECTIVE To elucidate the mechanism of the unique beneficial effect of intravitreal steroid therapy on diabetic macular edema, we investigated the effect of locally administered triamcinolone acetonide (TA) on the expression of vascular endothelial growth factor (VEGF)-A and its receptors in retinas of rats with streptozotocin (STZ)-induced diabetes. We then correlated the expression of these proteins with breakdown of the blood-retinal barrier (BRB). RESEARCH DESIGN AND METHODS Thirty-two eyes of 16 diabetic and nondiabetic rats were divided into four groups. TA was injected into the vitreous of the right eye, and saline was injected into the left eye (control) 3.5 weeks after induction of diabetes. Retinas were harvested 48 h following treatment. mRNA and protein expression of VEGF-A, VEGF-A receptor 1 (fms-like tyrosine kinase [FLT]-1), and VEGF-A receptor 2 (fetal liver kinase [FLK]-1) were determined by real-time RT-PCR and immunohistochemistry. BRB permeability was quantitated by measuring extravasated endogenous albumin and retinal thickness. RESULTS Diabetes-induced retinal thickness and albumin extravasation were significantly reduced in TA-treated diabetic retinas to a level similar to that in sham-treated nondiabetic eyes. A close correlation between albumin leakage and increased expression of both Vegf-a and Flk-1 was noted in the diabetic retinas. TA downregulated the expression of Vegf-a and Flk-1 but upregulated the expression of Flt-1. TA did not alter the expression of these genes in nondiabetic retinas. CONCLUSIONS Intravitreal injection of TA stabilizes the BRB in association with regulation of Vegf-a, Flk-1, and Flt-1 expression in retinas in the early stages of diabetes.

Zhang, Xinyuan; Bao, Shisan; Lai, Donna; Rapkins, Robert W.; Gillies, Mark C.

2008-01-01

230

Retinal Not Systemic Oxidative and Inflammatory Stress Correlated with VEGF Expression in Rodent Models of Insulin Resistance and Diabetes  

PubMed Central

Purpose. To correlate changes between VEGF expression with systemic and retinal oxidative stress and inflammation in rodent models of obesity induced insulin resistance and diabetes. Methods. Retinal VEGF mRNA and protein levels were assessed by RT-PCR and VEGF ELISA, respectively. Urinary 8-hydroxydeoxyguanosine (8-OHdG), blood levels of C-reactive protein (CRP), malondialdehyde (MDA), and CD11b/c positive cell ratio were used as systemic inflammatory markers. Retinal expression of Nox2, Nox4, and p47phox mRNA levels were measured as oxidative stress markers. TNF-?, inter-cellular adhesion molecule-1 (ICAM-1), IL1?, and activation of nuclear factor ?B (NF-?B) were used as retinal inflammatory markers. Results. Retinal VEGF mRNA and protein expression increased in Zucker diabetic fatty (ZDFfa/fa) rats and streptozotosin (STZ) induced diabetic Sprague-Dawley rats, after two months of disease, but not in Zucker fatty (ZF) rats. Systemic markers of oxidative stress and inflammation were elevated in insulin resistant and diabetic rats. Some oxidative stress and inflammatory markers (TNF-?, IL-6, ICAM-1, and IL1-?) were upregulated in the retina of ZDFfa/fa and STZ diabetic rats after 4 months of disease. In contrast, activation of NF-?B in the retina was observed in high fat fed nondiabetic and diabetic cis-NF-?BEGFP mice, ZF, ZDFfa/fa, and STZ-induced diabetic rats. Conclusions. Only persistent hyperglycemia and diabetes increased retinal VEGF expression. Some markers of inflammation and oxidative stress were elevated in the retina and systemic circulation of obese and insulin resistant rodents with and without diabetes. Induction of VEGF and its associated retinal pathologies by diabetes requires chronic hyperglycemia and factors in addition to inflammation and oxidative stress.

Mima, Akira; Qi, Weier; Hiraoka-Yamomoto, Junko; Park, Kyoungmin; Matsumoto, Motonobu; Kitada, Munehiro; Li, Qian; Mizutani, Koji; Yu, Edward; Shimada, Takeshi; Lee, Jongsoon; Shoelson, Steven E.; Jobin, Christian; Rask-Madsen, Christian; King, George L.

2012-01-01

231

Simvastatin treatment inhibits hypoxia inducible factor 1-alpha-(HIF-1alpha)-prolyl-4-hydroxylase 3 (PHD-3) and increases angiogenesis after myocardial infarction in streptozotocin-induced diabetic rat.  

PubMed

BACKGROUND: Statins (HMG-CoA reductase inhibitors), are known to improve cardiac function in diabetes-induced cardiovascular disease. We investigated the mechanism by which statins ameliorate cardiac function after myocardial infarction (MI). Simvastatin (S) increased tube formation and migration of HUVEC in vitro. We examined the role of simvastatin on cardiac function in streptozotocin (STZ) induced diabetic rats subjected to MI. METHODS: Rats were randomly assigned to 1) Control (non-diabetic) Sham (CS); 2) Control (non-diabetic) MI (CMI); 3) Control Statin treated Sham (CSS); 4) Control Statin treated MI (CSMI); 5) Diabetic Sham (DS); 6) Diabetic MI (DMI); 7) Diabetic Statin treated Sham (DSS); 8) Diabetic Statin treated MI (DSMI). Two weeks after STZ/saline injection Simvastatin (1mg/kg.b.wt) was gavaged for 15days (d). MI was induced 30 d after treatment by permanent LAD ligation. RESULTS: The S treated MI groups exhibited increased arteriolar density (23±0.6 vs. 14.8±0.4 counts/mm(2), DSMI vs. DMI) and reduced fibrosis at 30d post-MI. VEGF measurement by ELISA after 4d post-MI showed increased expression in DSMI group compared to DMI group. Western blot analysis showed decreased Prolyl-4-Hydroxylase 3 (PHD-3) in DSMI group as compared to DMI group. Echocardiographic analysis 4weeks after post-MI showed significant improvement in ejection fraction (50.11±1.83 vs. 32.46±2.19%; DSMI vs. DMI) and fractional shortening (26.77±1.12 vs.16.36±1.22%; DSMI vs. DMI) in both statin-treated MI groups regardless of diabetic status. CONCLUSION: These results suggest that statin therapy mitigates impairment of angiogenesis and myocardial dysfunction following MI in the diabetic rat through PHD3 inhibition. PMID:23590933

Thirunavukkarasu, Mahesh; Selvaraju, Vaithinathan; Dunna, Nageswara Rao; Foye, Jocelyn L C; Joshi, Mandip; Otani, Hajime; Maulik, Nilanjana

2013-04-13

232

Antihyperglycaemic effect of Mangifera indica in rat.  

PubMed

The leaves of Mangifera indica are used as an antidiabetic agent in Nigerian folk medicine. To determine whether or not there is a scientific basis for this use, the effect of the aqueous extract of the leaves on blood glucose level was assessed in normoglycaemic, glucose - induced hyperglycaemic and streptozotocin (STZ)-induced diabetic rats. The aqueous extract given orally (1 g/kg) did not alter the blood glucose levels in either normoglycaemic or STZ-induced diabetic rats. In glucose - induced hyperglycaemia, however, antidiabetic activity was seen when the extract and glucose were administered simultaneously and also when the extract was given to the rats 60 min before the glucose. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity. This action may be due to an intestinal reduction of the absorption of glucose. However, other different mechanisms of action cannot be excluded. PMID:10479762

Aderibigbe, A O; Emudianughe, T S; Lawal, B A

1999-09-01

233

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

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.

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

234

Gadd45?: A Novel Diabetes-Associated Gene Potentially Linking Diabetic Cardiomyopathy and Baroreflex Dysfunction  

PubMed Central

Both diabetic cardiomyopathy (DCM) and baroreflex dysfunction independently contribute to sudden cardiac death (SCD), however the inherent connections between them under diabetic state remains unclear. As microRNAs (miRNAs) have been reported to participate in various physiological and pathological processes, we presume they may also be involved in DCM and DM-induced impairment of baroreflex sensitivity. Two sets of gene expression profiles data from streptozotocin (STZ)-induced diabetic heart and diabetic dorsal root ganglia (DDRG) were retrieved from GEO and ArrayExpress. Co-differentially-expressed genes in diabetic heart and DDRG were identified by t test and intersection analysis. Human Protein Reference Database (HPRD) was applied to find direct interacting proteins of Gadd45?. Differentially-expressed miRNAs in left ventricle from 4-week STZ-induced diabetic rats were screened by miRNA microarray. Expression of miR-499 and its regulating effect on Gadd45? were then verified by quantitative real-time PCR (qRT-PCR), western blot, computational predication, and dual-luciferase reporter analysis. Four co-differentially-expressed genes in DCM and DDRG were identified. Among these genes, Gadd45? has 16 direct interacting proteins and 11 of them are documentedly associated with DM. Accompanied with significantly increased miR-499 expression, Gadd45? expression was increased at mRNA level but decreased at protein level in both diabetic heart and nucleus ambiguous. Furthermore, miR-499 was confirmed negatively regulating Gadd45? by targeting its 3?UTR. Collectively, reduced Gadd45? protein expression by forced miR-499 expression indicated it's a diabetes-associated gene which might potentially be involved in both DCM and DM-induced baroreflex dysfunction.

Xie, Fang; Sun, Lihua; Su, Xiaolin; Wang, Ying; Wei, Ran; Zhang, Rong; Li, Xia; Yang, Baofeng; Ai, Jing

2012-01-01

235

Effects of telmisartan or amlodipine monotherapy versus telmisartan/amlodipine combination therapy on vascular dysfunction and oxidative stress in diabetic rats.  

PubMed

Our previous studies identified potent antioxidant effects and improvement of vascular function by telmisartan therapy in experimental diabetes and nitrate tolerance. The present study compared the beneficial effects of single telmisartan or amlodipine versus telmisartan/amlodipine combination therapy (T+A) in streptozotocin (STZ)-induced type 1 diabetic rats. Male Wistar rats were injected once with STZ (60 mg/kg, i.v.) and 1 week later the drugs (telmisartan, amlodipine, or T+A) were administrated orally by a special diet (2.5-5 mg?kg(-1)?day(-1)) for another 7 weeks. We only observed a marginal beneficial on-top effect of T+A therapy over the single drug regimen that was most evident in the improvement of endothelial function (acetylcholine response) and less pronounced in the reduction of whole blood, vascular and cardiac oxidative stress (blood leukocyte oxidative burst, aortic dihydroethidine and 3-nitrotyrosine staining, as well as cardiac NADPH oxidase activity and uncoupling of endothelial nitric oxide synthase) in diabetic rats. These effects on oxidative stress parameters were paralleled by those on the expression pattern of NADPH oxidase and nitric oxide synthase isoforms. In addition, development of mild hypotension in the T+A-treated rats was observed. Reasons for this moderate synergistic effect of T+A therapy may be related to the potent beneficial effects of telmisartan alone and the fact that amlodipine and telmisartan share similar pathways to improve endothelial function. Moreover, hypotension in the T+A-treated rats could partially antagonize the beneficial additive effects by counter-regulatory mechanisms (e.g., activation of the renin-angiotensin-aldosterone system). PMID:23443495

Mollnau, Hanke; Oelze, Matthias; Zinßius, Elena; Hausding, Michael; Wu, Zhixiong; Knorr, Maike; Ghaemi Kerahrodi, Jasmin; Kröller-Schön, Swenja; Jansen, Thomas; Teutsch, Christine; Foster, Carolyn; Li, Huige; Wenzel, Philip; Schulz, Eberhard; Münzel, Thomas; Daiber, Andreas

2013-02-27

236

A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat.  

PubMed

The Zucker fatty (ZF) rat harboring a missense mutation (fatty, fa) in the leptin receptor gene (Lepr) develops obesity without diabetes; Zucker diabetic fatty (ZDF) rats derived from the ZF strain exhibit obesity with diabetes and are widely used for research on type 2 diabetes (T2D). Here we establish a novel diabetic strain derived from normoglycemic ZF rats. In our ZF rat colony, we incidentally found fa/fa homozygous male rats having reproductive ability, which is generally absent in these animals. During maintenance of this strain by mating fa/fa males and fa/+ heterozygous females, we further identified fa/fa male rats exhibiting diabetes. We then performed selective breeding using the fa/fa male rats that exhibited relatively high blood glucose levels at 10 weeks of age, resulting in establishment of a diabetic strain that we designated Hos:ZFDM-Lepr(fa) (ZFDM). These fa/fa male rats developed diabetes as early as 10 weeks of age, reaching 100% incidence by 21 weeks of age, while none of the fa/+ male rats developed diabetes. The phenotypic characteristics of this diabetic strain are distinct from those of normoglycemic ZF rats. ZFDM rat strain having high reproductive efficiency should serve as a more useful animal model of T2D. PMID:23671847

Yokoi, Norihide; Hoshino, Masayuki; Hidaka, Shihomi; Yoshida, Eri; Beppu, Masayuki; Hoshikawa, Ritsuko; Sudo, Katsuko; Kawada, Akihiko; Takagi, Sadaaki; Seino, Susumu

2013-02-26

237

A new salicylic acid-derivatized kojic acid vanadyl complex: synthesis, characterization and anti-diabetic therapeutic potential.  

PubMed

The molecular mechanisms of vanadium toxicity suggest that incorporation of antioxidant groups in the structure of vanadium complexes could be a preferable strategy in designing novel hypoglycemic vanadium complexes with proper efficacy and safety. By conjugating a pyrone skeleton to provide a coordination group and antioxidative motifs, we synthesized a novel complex of bis ((5-hydroxy-4-oxo-4H-pyran-2-yl) methyl 2-hydroxy- benzoatato) oxovanadium (IV) (BSOV). Evaluation of the anti-diabetic effects of BSOV using streptozotocin (STZ)-induced diabetic rats with bis (maltolato) oxovanadium (BMOV) as a positive control showed that BSOV effectively lowered blood glucose level, ameliorated damages of hepatic and renal function in diabetic rats and improved lipid metabolism. The signs of potential alteration of renal function caused by BSOV and BMOV were observed and are discussed. Overall, the experimental results suggest BSOV as a potent hypoglycemic agent and further studies using this strategy for anti-diabetic agents. PMID:21726771

Wei, Yongbiao; Zhang, Chengyue; Zhao, Pan; Yang, Xiaoda; Wang, Kui

2011-05-27

238

Induction of diabetes by Streptozotocin in rats  

Microsoft Academic Search

The objective of this study is to induce experimental diabetes mellitus by Streptozotocin in normal adult Wistar rats via\\u000a comparison of changes in body weight, consumption of food and water, volume of urine and levels of glucose, insulin and C-peptide\\u000a in serum, between normal and diabetic rats. Intra-venous injection of 60mg\\/kg dose of Streptozotocin in adult wistar rats,\\u000a makes pancreas

A. Akbarzadeh; D. Norouzian; M. R. Mehrabi; Sh. Jamshidi; A. Farhangi; A. Allah Verdi; S. M. A. Mofidian; B. Lame Rad

2007-01-01

239

Soybeans ameliolate diabetic nephropathy in rats.  

PubMed

Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. Soybeans have been shown to reduce urinary albumin excretion and total cholesterol in non-diabetic patients with nephrotic syndrome. However, reports focusing specifically on diabetic nephropathy are scarce and the available results are inconsistent. It was reported that soybean consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas it was found to elicit an increase in urinary protein excretion when soybeans were consumed by type 2 diabetic patients. This study aims to investigate the effects of soybean in diabetic nephropathy, particularly the effects of consuming soybeans on the histopathology of diabetic nephropathy, using aquaporin (AQP) and osteopontin (OPN) expression as diagnostic markers. Male Sprague-Dawley rats were assigned to one of three groups: control, diabetic with red chow diet and diabetic with soybean diet. For histological examination, the expression of OPN and AQP, renal function and hemoglobin A1c were evaluated at the end of the study. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group given a soybean diet. OPN and AQP expression were suppressed in the kidney specimens of diabetic rats with the soybean diet. In conclusion, soybeans may prevent the weight loss and morphological disruption of the kidney associated with diabetes mellitus. Soybeans also may improve glycemic control. It seems likely that long-term control of blood glucose levels using a soybean diet could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented. PMID:18955330

Choi, Young Eun; Ahn, Soo Kyung; Lee, Won Taek; Lee, Jong Eun; Park, Seung Hwa; Yoon, Bang Bu; Park, Kyung Ah

2008-03-20

240

Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation.  

PubMed

Hyperuricemia, hyperlipidemia and inflammation are associated with diabetic nephropathy. The NLRP3 inflammasome-mediated inflammation is recently recognized in the development of kidney injury. Urate and lipid are considered as danger signals in the NLRP3 inflammasome activation. Although dietary flavonoid quercetin and allopurinol alleviate hyperuricemia, dyslipidmia and inflammation, their nephroprotective effects are currently unknown. In this study, we used streptozotocin (STZ)-induced diabetic nephropathy model with hyperuricemia and dyslipidemia in rats, and found over-expression of renal inflammasome components NLRP3, apoptosis-associated speck-like protein and Caspase-1, resulting in elevation of IL-1? and IL-18, with subsequently deteriorated renal injury. These findings demonstrated the possible association between renal NLRP3 inflammasome activation and lipid accumulation to superimpose causes of nephrotoxicity in STZ-treated rats. The treatment of quercetin and allopurinol regulated renal urate transport-related proteins to reduce hyperuricemia, and lipid metabolism-related genes to alleviate kidney lipid accumulation in STZ-treated rats. Furthermore, quercetin and allopurinol were found to suppress renal NLRP3 inflammasome activation, at least partly, via their anti-hyperuricemic and anti-dyslipidemic effects, resulting in the amelioration of STZ-induced the superimposed nephrotoxicity in rats. These results may provide a basis for the prevention of diabetes-associated nephrotoxicity with urate-lowering agents such as quercetin and allopurinol. PMID:22701621

Wang, Chuang; Pan, Ying; Zhang, Qing-Yu; Wang, Fu-Meng; Kong, Ling-Dong

2012-06-11

241

Salutary effect of Cassia auriculata L. Leaves on hyperglycemia-induced atherosclerotic environment in streptozotocin rats.  

PubMed

Diabetes mellitus is very often associated with dyslipidemia, increased oxidative stress and endothelial dysfunction that could develop atherosclerosis and consequently cardiovascular diseases. Medicinal plants with reputed traditional use to treat diabetes and cardiovascular diseases might provide valuable drugs. Therefore, the present study was designed to evaluate anti-atherosclerotic potential of aqueous extract of Cassia auriculata L. leaves in streptozotocin (STZ)-induced diabetic rats. The rats were rendered diabetic by STZ (45 mg/kg, ip). Diabetic rats were orally administered C. auriculata leaf extract at 400 mg/kg dose daily for 21 days. The supplementation of extract to the diabetic rats produced significant reduction in fasting blood glucose along with significant reversal in altered serum lipid profile and apolipoprotein B. Lipid peroxidation was found to be significantly suppressed in extract-fed diabetic rats. The significant reduction in serum levels of oxidized low-density lipoprotein, soluble vascular cell adhesion molecule and plasma fibrinogen with a concomitant elevation in serum nitric oxide was observed in diabetic rats following treatment with extract. Histopathological examination of heart myocardium of extract-treated diabetic rats revealed reversal of fatty change toward normal. These results suggest that C. auriculata aqueous leaf extract exhibits anti-atherosclerotic role in the diabetic state and it indicates toward the notion that extract may help to prevent the progression of cardiovascular diseases. PMID:21800129

Gupta, Shipra; Sharma, Suman Bala; Singh, Usha Rani; Bansal, Surendra Kumar

2011-12-01

242

Antidepressant effect of taurine in diabetic rats.  

PubMed

Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals. PMID:22302366

Caletti, Greice; Olguins, Danielly B; Pedrollo, Elis F; Barros, Helena M T; Gomez, Rosane

2012-10-01

243

Total parenteral nutrition in diabetic rats  

SciTech Connect

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.

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

1986-03-01

244

Fibronectin Facilitates Corneal Epithelial Wound Healing in Diabetic Rats  

Microsoft Academic Search

To determine whether the effect of fibronectin on corneal epithelial healing occurs in eyes affected by diabetes, the effect of fibronectin on the rates at which corneal epithelial wounds healed was compared in diabetic and normal rats. Streptozotocin was used to induce diabetes in rats. Two weeks after treatment, the whole corneal epithelium of diabetic and untreated rats was debrided.

MASATSUGU NAKAMURA; NORIAKI SATO; TAI-ICHIRO CHIKAMA; YASUSHI HASEGAWA; TERUO NISHIDA

1997-01-01

245

Neurobiological effects of pulsed magnetic field on diabetes-induced neuropathy.  

PubMed

In the clinic, although several pharmacological agents or surgical procedures are used to treat diabetes and diabetes-induced neuropathic pain, their success has been limited. Therefore, development of different alternatives in treatments is very important. The purpose of this study was to determine the efficacy of pulsed magnetic field (PMF) in improving signs and symptoms of diabetic neuropathy. In this study, the effects of PMF treatment were investigated in Streptozotocin (STZ)-induced acute and chronic diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels and body weights. After STZ administration to rats, blood glucose level elevated and body weight decreased. Although PMF treatment did not affect changes in body weight, the blood glucose levels of PMF-treated diabetic rats exhibited a decrease during the treatments. Diabetic animals displayed marked decrease in mechanical thresholds and thermal latencies. While treatment of PMF partially restored the mechanical thresholds and thermal latency in acute diabetic rats, PMF caused a corrective effect on only mechanical threshold of chronic diabetic rats. These results suggested that treatment of PMF can potentially ameliorate the painful symptoms of diabetes, such as hyperalgesia and allodynia, by partially preventing the hyperglycemia. PMID:19593780

Mert, Tufan; Gunay, Ismail; Ocal, Isil

2010-01-01

246

Effects of aspartame on diabetic rats and diabetic patients.  

PubMed

The effects of aspartame (L-aspartyl-L-phenylalanine methyl ester) on plasma glucose and insulin levels were investigated in diabetic rats and patients with non-insulin-dependent diabetes mellitus. The oral administration of 0.45 mg aspartame per 100g body weight, which is equivalent to 150 mg of glucose in sweetness, to streptozotocin-induced diabetic rats had no effect on the plasma glucose or insulin levels. Also, 225 mg oral aspartame loading, which is equivalent to 75 g of glucose in sweetness, to patients with non-insulin-dependent diabetes mellitus did not increase plasma glucose or insulin levels, although 75 g of oral glucose loading increased plasma glucose and insulin levels in diabetic patients as expected. Aspartame ingestion for three days at a dose of 24-48 mg per day and the intake of snacks flavored with 240 mg of aspartame also did not increase fasting plasma glucose levels. These results suggest that acute administration of aspartame has no influence on plasma glucose or insulin levels in diabetic rats and patients with non-insulin-dependent diabetes mellitus. PMID:3908628

Shigeta, H; Yoshida, T; Nakai, M; Mori, H; Kano, Y; Nishioka, H; Kajiyama, S; Kitagawa, Y; Kanatsuna, T; Kondo, M

1985-10-01

247

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

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

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

2013-01-18

248

Skeletal changes in type-2 diabetic Goto-Kakizaki rats  

Microsoft Academic Search

We characterized appendicular and axial bones in rats with type-2 diabetes in five female Goto-Kakizaki (GK) rats, a strain developed from the Wistar rat showing spontaneous type-2 diabetes, and five age- and sex-matched non- diabetic Wistar rats. The humerus, tibia, metatarsals and vertebral bodies were analysed by peripheral quantitative computerized tomography (pQCT). In diabetic rats, the height of the vertebral

T Ahmad; C Ohlsson; M Sääf; C-G Östenson; A Kreicbergs

2003-01-01

249

Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes  

PubMed Central

We examined the impact of early diabetes on the circulating and kidney renin-angiotensin system (RAS) in male and female mRen2.Lewis (mRen2) hypertensive rats. Diabetes (DB) was induced by streptozotocin (STZ; 65 mg/kg) at 11 wk of age for 4 wk without insulin replacement. Systolic blood pressures were not increased in DB males or females compared with controls (CON). Circulating angiotensin-converting enzyme 2 (ACE2) increased ninefold (P < 0.05) in DB females and threefold (P < 0.05) in DB males, but circulating ACE and ANG II were higher in the DB groups. Serum C-reactive protein was elevated in DB females but not DB males, and the vascular responses to acetylcholine and estradiol were attenuated in the DB females. Proteinuria, albuminuria, and angiotensinogen excretion increased to a similar extent in both DB females and males. Glomerular VEGF expression also increased to a similar extent in both DB groups. Renal inflammation (CD68+cells) increased only in DB females although males exhibited greater inflammation that was not different with DB. Cortical ACE2 did not change in DB females but was reduced (30%) in DB males. Renal neprilysin activity (>75%, P < 0.05) was markedly reduced in the DB females to that in the DB and CON males. ACE activity was significantly lower in both female (75%, P < 0.05) and male (50%; P < 0.05) DB groups, while cortical ANG II and Ang-(1-7) levels were unchanged. In conclusion, female mRen2 rats are not protected from vascular damage, renal inflammation, and kidney injury in early STZ-induced diabetes despite a marked increase in circulating ACE2 and significantly reduced ACE within the kidney.

Yamaleyeva, Liliya M.; Gilliam-Davis, Shea; Almeida, Igor; Brosnihan, K. Bridget; Lindsey, Sarah H.

2012-01-01

250

Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes.  

PubMed

We examined the impact of early diabetes on the circulating and kidney renin-angiotensin system (RAS) in male and female mRen2.Lewis (mRen2) hypertensive rats. Diabetes (DB) was induced by streptozotocin (STZ; 65 mg/kg) at 11 wk of age for 4 wk without insulin replacement. Systolic blood pressures were not increased in DB males or females compared with controls (CON). Circulating angiotensin-converting enzyme 2 (ACE2) increased ninefold (P < 0.05) in DB females and threefold (P < 0.05) in DB males, but circulating ACE and ANG II were higher in the DB groups. Serum C-reactive protein was elevated in DB females but not DB males, and the vascular responses to acetylcholine and estradiol were attenuated in the DB females. Proteinuria, albuminuria, and angiotensinogen excretion increased to a similar extent in both DB females and males. Glomerular VEGF expression also increased to a similar extent in both DB groups. Renal inflammation (CD68(+)cells) increased only in DB females although males exhibited greater inflammation that was not different with DB. Cortical ACE2 did not change in DB females but was reduced (30%) in DB males. Renal neprilysin activity (>75%, P < 0.05) was markedly reduced in the DB females to that in the DB and CON males. ACE activity was significantly lower in both female (75%, P < 0.05) and male (50%; P < 0.05) DB groups, while cortical ANG II and Ang-(1-7) levels were unchanged. In conclusion, female mRen2 rats are not protected from vascular damage, renal inflammation, and kidney injury in early STZ-induced diabetes despite a marked increase in circulating ACE2 and significantly reduced ACE within the kidney. PMID:22378820

Yamaleyeva, Liliya M; Gilliam-Davis, Shea; Almeida, Igor; Brosnihan, K Bridget; Lindsey, Sarah H; Chappell, Mark C

2012-02-29

251

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

PubMed

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

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

2013-08-03

252

Antiallodynic Effects of Electroacupuncture Combined with MK-801 Treatment through the Regulation of p35/p25 in Experimental Diabetic Neuropathy  

PubMed Central

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.

Hwang, Hye Suk; Yang, Eun Jin; Lee, Sang Min; Lee, Soon Cheol

2011-01-01

253

The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in streptozotocin-induced diabetic rats  

Microsoft Academic Search

This study aimed to investigate the effect of the Rho-kinase inhibitor fasudil on the development of diabetic nephropathy and clarify a contribution of the Rho\\/Rho-kinase pathway to the pathogenesis of diabetic nephropathy. Diabetes was induced in male Sprague–Dawley rats with an intraperitoneal injection of streptozotocin. Animals were then divided into the following 4 groups; normal control rats, diabetic rats, diabetic

Atsushi Gojo; Kazunori Utsunomiya; Kanta Taniguchi; Tamotsu Yokota; Shoh Ishizawa; Yasushi Kanazawa; Hideaki Kurata; Naoko Tajima

2007-01-01

254

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

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.

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

2013-01-01

255

Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats.  

PubMed

We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague-Dawley rats were divided into the following four groups: (1) normal control group (NCG; n?=?8), (2) normal exercise group (NEG; n?=?8), (3) diabetes control group (DCG; n?=?8), and (4) diabetes exercise group (DEG; n?=?8). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg dissolved in 0.05 M citrate buffer, pH 4.5). Rats were subjected to treadmill exercise 5 days a week for 6 weeks. The protein level of NGF significantly increased in the NEG and DEG (p?diabetic rats. PMID:21207218

Chae, Chang-Hun; Jung, Sung-Lim; An, Sang-Hyun; Jung, Chan-Kyoung; Nam, Sang-Nam; Kim, Hyun-Tae

2011-01-05

256

Curcumin Alleviates Diabetic Cardiomyopathy in Experimental Diabetic Rats  

PubMed Central

Objectives Diabetic cardiomyopathy (DCM), characterized by myocardial structural and functional changes, is an independent cardiomyopathy that develops in diabetic individuals. The present study was sought to investigate the effect of curcumin on modulating DCM and the mechanisms involved. Methods An experimental diabetic rat model was induced by low dose of streptozoticin(STZ) combined with high energy intake on rats. Curcumin was orally administrated at a dose of 100 or 200 mg·kg?1·d?1, respectively. Cardiac function was evaluated by serial echocardiography. Myocardial ultrastructure, fibrosis area and apoptosis were assessed by histopathologic analyses. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. Inflammatory factors were detected by ELISA, and interrelated proteins were measured by western blot. Results Rats with DCM showed declined systolic myocardial performance associated with myocardial hypertrophy and fibrosis, which were accompanied with metabolism abnormalities, aberrant myocardial enzymes, increased AGEs (advanced glycation end products) accumulation and RAGE (receptor for AGEs) expression, elevated markers of oxidative stress (MDA, SOD, the ratio of NADP+/NADPH, Rac1 activity, NADPH oxidase subunits expression of gp91phox and p47phox ), raised inflammatory factor (TNF-? and IL-1?), enhanced apoptotic cell death (ratio of bax/bcl-2, caspase-3 activity and TUNEL), diminished Akt and GSK-3? phosphorylation. Remarkably, curcumin attenuated myocardial dysfunction, cardiac fibrosis, AGEs accumulation, oxidative stress, inflammation and apoptosis in the heart of diabetic rats. The inhibited phosphorylation of Akt and GSK-3? was also restored by curcumin treatment. Conclusions Taken together, these results suggest that curcumin may have great therapeutic potential in the treatment of DCM, and perhaps other cardiovascular disorders, by attenuating fibrosis, oxidative stress, inflammation and cell death. Furthermore, Akt/GSK-3? signaling pathway may be involved in mediating these effects.

Cai, Fei; Xiang, Jizhou; Zha, Wenliang; Fan, Dan; Guo, Shuang; Ming, Zhangyin; Liu, Chao

2012-01-01

257

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema.  

PubMed

Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema. In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC(50) of 230 nM; rat IC(50) of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats. PMID:23337801

Inoue, Takayuki; Morita, Masataka; Tojo, Takashi; Yoshihara, Kousei; Nagashima, Akira; Moritomo, Ayako; Ohkubo, Mitsuru; Miyake, Hiroshi

2012-12-29

258

Cerebral lesions in rats with streptozotocin-induced diabetes  

Microsoft Academic Search

We studied cerebral lesions in the streptozotocin-diabetic rat, an established model of diabetic retinopathy. A group of diabetic rats all had cerebral lesions, but showed no gross abnormalities of the brain or signs of effects on the central nervous system. Light and electron microscopy of horizontal brain sections stained by a variety of methods showed focal accumulation of collagen fibrils

Noritsugu Mukai; Sadao Hori; Marsha Pomeroy

1980-01-01

259

Hyaluronan Facilitates Corneal Epithelial Wound Healing in Diabetic Rats  

Microsoft Academic Search

We investigated the effect of hyaluronan on corneal epithelial wound healing in rats affected by diabetes. Furthermore, because hyaluronan is thought to affect corneal epithelial wound healing through the mechanism of binding of hyaluronan to provisional fibronectin in the wounded area, we compared the localization of fibronectin immunohistochemically during corneal epithelial wound healing in diabetic and non-diabetic rats. Streptozotocin was

MASATSUGU NAKAMURA; NORIAKI SATO; TAI-ICHIRO CHIKAMA; YASUSHI HASEGAWA; TERUO NISHIDA

1997-01-01

260

Melatonin and taurine reduce early glomerulopathy in diabetic rats  

Microsoft Academic Search

Oxidative stress occurs in diabetic patients and experimental models of diabetes. We examined whether two antioxidants, melatonin and taurine, can ameliorate diabetic nephropathy. Enhanced expression of glomerular TGF-?1 and fibronectin mRNAs and proteinuria were employed as indices of diabetic nephropathy. Experimental diabetes was induced by intravenous injection of streptozotocin 50 mg\\/kg. Two days after streptozotocin, diabetic rats were assigned to

Hunjoo Ha; Mi-Ra Yu; Kyung Hwan Kim

1999-01-01

261

Influence of fluoride on streptozotocin induced diabetic nephrotoxicity in mice: Protective role of Asian ginseng (Panax ginseng) & banaba (Lagerstroemia speciosa) on mitochondrial oxidative stress  

PubMed Central

Background & objectives: Chronic fluoride intoxication through drinking water is a serious health problem. Patients with diabetes are known to have impaired renal function and elimination of fluoride from the body is mainly done through kidney. Fluoride toxicity in diabetes patients may aggravate complications. In this study, the influence of fluoride was assessed on streptozotocin (STZ) induced diabetes in mice as also the efficacy/protective effective of oral supplementation of ginseng (GE) and banaba leaf extracts (BLE). Methods: The efficacy of plant extracts, GE and BLE at doses of 50, 150, 250 mg/kg b.w./day alone and in combination, was tested for a period of 15 days on fluoride treated STZ induced diabetic animals. Results: Fluoride exposure to mice with STZ-induced diabetes produced significant changes in OSI (organo-somatic index), fluoride content, blood glucose, urea, serum creatinine and oxidative stress indices in kidney tissues with evident histological alterations. Among the antioxidant treatments, combination therapy of GE and BLE at 150 mg/kg b.w. significantly normalized the impaired biochemical variables in kidney tissues of fluoride toxicated diabetic mice. Interpretations & conclusions: High fluoride uptake was found to be diabetogenic and further aggravated the renal oxidative damage and thereby the toxicity in mice with STZ induced diabetes mice. GE and BLE exposure individually or in combination at a dose of 150 mg/kg b.w./day for 15 days exhibited protective effects on fluoride toxicated STZ induced nephrotoxicity in mice.

Basha, Mahaboob P.; Saumya, S.M.

2013-01-01

262

Renal protective effect of xiao-chai-hu-tang on diabetic nephropathy of type 1-diabetic mice.  

PubMed

Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese medicine formula consisting of seven medicinal plants, is used in the treatment of various diseases. We show here that XCHT could protect type-1 diabetic mice against diabetic nephropathy, using streptozotocin (STZ)-induced diabetic mice and high-glucose (HG)-exposed rat mesangial cell (RMC) as models. Following 4 weeks of oral administration with XCHT, renal functions and renal hypertrophy significantly improved in the STZ-diabetic mice, while serum glucose was only moderately reduced compared to vehicle treatment. Treatment with XCHT in the STZ-diabetic mice and HG-exposed RMC resulted in a decrease in expression levels of TGF-?1, fibronectin, and collagen IV, with concomitant increase in BMP-7 expression. Data from DPPH assay, DHE stain, and CM-H(2)DCFDA analysis indicated that XCHT could scavenge free radicals and inhibit high-glucose-induced ROS in RMCs. Taken together, these results suggest that treatment with XCHT can improve renal functions in STZ-diabetic mice, an effect that is potentially mediated through decreasing oxidative stress and production of TGF-?1, fibronectin, and collagen IV in the kidney during development of diabetic nephropathy. XCHT, therefore merits further investigation for application to improve renal functions in diabetic disorders. PMID:22474533

Lin, Chun-Ching; Lin, Liang-Tzung; Yen, Ming-Hong; Cheng, Juei-Tang; Hsing, Chung-Hsi; Yeh, Ching-Hua

2012-03-07

263

Luminescence experiments involved in the mechanism of streptozotocin diabetes and cataract formation.  

PubMed

Streptozotocin (STZ)-induced diabetes is linked to excessive nitric oxide (NO), and possibly peroxynitrite (OONO(-)) and/or other nitrogen oxides, e.g. nitrogen trioxide (N(2)O(3)), which damages DNA of pancreatic beta cells, causing death and loss of insulin. Simultaneous injection of carboxy-PTIO (CPTIO) and STZ prevents diabetes and cataract formation in rats, whereas 4-hydroxy-Tempo (4HT) does not. CPTIO oxidizes nitric oxide to nitrite, which prevents production of the diabetogenic toxin. Peroxynitrite may not be involved, since 4HT (converts O(2)(-) to H(2)O(2)) injected with STZ produces diabetes. All six of the control rats injected with STZ became diabetic and developed cataracts after 3 months. Eight rats injected with STZ and CPTIO were non-diabetic with no cataracts up to a year. This work establishes the idea that excessive nitric oxide is a primary initiator in STZ diabetes. Luminescence experiments using OONO(-) generation from SIN-1 with L-012 indicates that 4HT is an effective inhibitor, while CPTIO is ineffective. Experiments with dilute solutions of nitrogen trioxide added to ladder or plasmid DNA reveal extensive nicking of DNA, thereby raising the possibility that other oxides of nitrogen could be involved with the damage to DNA. It can be concluded that diabetes can be prevented by oxidizing excessive NO from STZ. PMID:18651583

Van Dyke, Knox; Ghareeb, Erica; Van Dyke, Mark; Sosa, Arturo; Hoeldtke, Robert D; Van Thiel, David H

264

Decreased O-GlcNAcylation of the key proteins in kinase and redox signalling pathways is a novel mechanism of the beneficial effect of ?-lipoic acid in diabetic liver.  

PubMed

The present study aimed to investigate the effects of the treatment with a-lipoic acid (LA), a naturally occurring compound possessing antioxidant activity, on liver oxidant stress in a rat model of streptozotocin (STZ)-induced diabetes by examining potential mechanistic points that influence changes in the expression of antioxidant enzymes such as catalase (CAT) and CuZn/Mn superoxide dismutase(s) (SOD). LA was administered for 4 weeks by daily intraperitoneal injections (10 mg/kg) to STZ-induced diabetic rats, starting from the last STZ treatment. LA administration practically normalised the activities of the indicators of hepatocellular injury, alanine and aspartate aminotransferases, and lowered oxidative stress, as observed by the thiobarbituric acid-reactive substance assay, restored the reduced glutathione:glutathione disulphide ratio and increased the protein sulfhydryl group content. The lower level of DNA damage detected by the comet assay revealed that LA reduced cytotoxic signalling, exerting a hepatoprotective effect. The LA-treated diabetic rats displayed restored specific enzymatic activities of CAT, CuZnSOD and MnSOD. Quantitative real-time PCR analysis showed that LA restored CAT gene expression to its physiological level and increased CuZnSOD gene expression, but the gene expression of MnSOD remained at the diabetic level. Although the amounts of CAT and CuZnSOD protein expression returned to the control levels, the protein expression of MnSOD was elevated. These results suggested that LA administration affected CAT and CuZnSOD expression mainly at the transcriptional level, and MnSOD expression at the post-transcriptional level. The observed LA-promoted decrease in the O-GlcNAcylation of extracellular signal-regulated kinase, protein 38 kinase, NF-kB, CCAAT/enhancer-binding protein and the antioxidative enzymes themselves in diabetic rats suggests that the regulatory mechanisms that supported the changes in antioxidative enzyme expression were also influenced by post-translational mechanisms. PMID:23312093

Dini?, Svetlana; Arambaši?, Jelena; Mihailovi?, Mirjana; Uskokovi?, Aleksandra; Grdovi?, Nevena; Markovi?, Jelena; Karadži?, Borivoje; Poznanovi?, Goran; Vidakovi?, Melita

2013-01-14

265

Vanadyl sulfate protects against streptozotocin-induced morphological and biochemical changes in rat aorta.  

PubMed

The aim of this study was to investigate the protective effects of vanadyl sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats, morphologically and biochemically. The animals were made diabetic by an intraperitoneal injection of streptozotocin (65 mg/kg) and vanadyl sulfate (100 mg/kg) that was given every day for 60 days by gavage technique to rats. Under the light and transmission electron microscopes, hypertrophy of the vessel wall, focal disruption in the elastic lamellae, an increase in thickness of total aortic wall, tunica intima, subendothelial space and adventitial layer, and a disorganization in smooth muscular cells of the tunica media were observed in diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly increased and the aorta glutathione (GSH) levels were significantly reduced in STZ diabetic rats. In diabetic rats administered vanadyl sulfate for 60 days, aorta LPO levels significantly decreased and the aorta GSH level significantly increased. In conclusion, in vivo treatment with vanadyl sulfate of diabetic rats prevented the morphological and biochemical changes observed in thoracic aorta of diabetic animals. PMID:16892454

Akgün-Dar, Kadriye; Bolkent, Sehnaz; Yanardag, Refiye; Tunali, Sevim

266

Carbonylation Contributes to SERCA2a Activity Loss and Diastolic Dysfunction in a Rat Model of Type 1 Diabetes  

PubMed Central

OBJECTIVE Approximately 25% of children and adolescents with type 1 diabetes will develop diastolic dysfunction. This defect, which is characterized by an increase in time to cardiac relaxation, results in part from a reduction in the activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), the ATP-driven pump that translocates Ca2+ from the cytoplasm to the lumen of the sarcoplasmic reticulum. To date, mechanisms responsible for SERCA2a activity loss remain incompletely characterized. RESEARCH DESIGN AND METHODS The streptozotocin (STZ)-induced murine model of type 1 diabetes, in combination with echocardiography, high-speed video detection, confocal microscopy, ATPase and Ca2+ uptake assays, Western blots, mass spectrometry, and site-directed mutagenesis, were used to assess whether modification by reactive carbonyl species (RCS) contributes to SERCA2a activity loss. RESULTS After 6–7 weeks of diabetes, cardiac and myocyte relaxation times were prolonged. Total ventricular SERCA2a protein remained unchanged, but its ability to hydrolyze ATP and transport Ca2+ was significantly reduced. Western blots and mass spectroscopic analyses revealed carbonyl adducts on select basic residues of SERCA2a. Mutating affected residues to mimic physio-chemical changes induced on them by RCS reduced SERCA2a activity. Preincubating with the RCS, methylglyoxal (MGO) likewise reduced SERCA2a activity. Mutating an impacted residue to chemically inert glutamine did not alter SERCA2a activity, but it blunted MGO's effect. Treating STZ-induced diabetic animals with the RCS scavenger, pyridoxamine, blunted SERCA2a activity loss and minimized diastolic dysfunction. CONCLUSIONS These data identify carbonylation as a novel mechanism that contributes to SERCA2a activity loss and diastolic dysfunction during type 1 diabetes.

Shao, Chun Hong; Capek, Haley L.; Patel, Kaushik P.; Wang, Mu; Tang, Kang; DeSouza, Cyrus; Nagai, Ryoji; Mayhan, William; Periasamy, Muthu; Bidasee, Keshore R.

2011-01-01

267

Low Dose Poly I:C Prevents Diabetes in the Diabetes Prone BB Rat  

Microsoft Academic Search

Poly I:C, an inducer of IFN-? and other cytokines, has been used to study the development of diabetes in both the BioBreeding (BB) diabetes prone rat and non-obese diabetic (NOD) mouse animal models of insulin-dependent diabetes mellitus (IDDM). Surprisingly, poly I:C accelerates the disease in the BB rat while inhibiting it in the NOD mouse. Since cytokines can have dose

Douglas O Sobel; Deepshika Goyal; Behrouz Ahvazi; Ji-Won Yoon; Young Hwa Chung; Adam Bagg; David M Harlan

1998-01-01

268

Low-dose poly(ADP-ribose) polymerase inhibitor-containing combination therapies reverse early peripheral diabetic neuropathy.  

PubMed

Poly(ADP-ribose) polymerase (PARP) inhibition has recently been identified as a novel approach to treatment of experimental peripheral diabetic neuropathy (PDN). However, long-term inhibition of PARP, an enzyme involved in DNA repair, can potentially result in premature aging, loss of genome stability, and other side effects. This study evaluated potential synergistic interactions between low doses of the potent and specific PARP inhibitor 1,5-isoquinolinediol (ISO) and one of two vasodilators, the ACE inhibitor lisinopril (LIS) and the beta2-adrenoceptor agonist salbutamol (SAL) in the model of early PDN. Control and streptozotocin (STZ)-induced diabetic rats were treated with either ISO plus LIS or ISO plus SAL for 2 weeks after an initial 2 weeks without treatment. ISO (intraperitoneally) and LIS and SAL (both in the drinking water) were used in subtherapeutic doses, resulting in a minor correction of diabetes-associated sciatic motor and hind-limb digital sensory nerve conduction deficits when administered as monotherapies. Both combination treatments corrected endoneurial blood flow and vascular conductance deficits in STZ-induced diabetic rats. ISO plus SAL corrected all other changes of PDN, i.e., motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) deficits as well as thermal and mechanical hyperalgesia. With ISO plus LIS, no significant correction of MNCV was observed, and the effect on thermal hyperalgesia was quite modest. SNCV and mechanical hyperalgesia were corrected. In vitro studies in human endothelial and Schwann cells showed early accumulation of poly(ADP-ribosyl)ated proteins (Western blot analysis) in response to high glucose, thus suggesting the importance of PARP activation in human PDN. In conclusion, low-dose PARP inhibitor-containing combination therapies may constitute a new approach for treatment of PDN. PMID:15855340

Li, Fei; Drel, Viktor R; Szabó, Csaba; Stevens, Martin J; Obrosova, Irina G

2005-05-01

269

Selective nitrergic neurodegeneration in diabetes mellitus-a nitric oxide-dependent phenomenon  

PubMed Central

In vitro and in vivo studies have demonstrated a dysfunctional nitrergic system in diabetes mellitus, thus explaining the origin of diabetic impotence. However, the mechanism of this nitrergic defect is not understood.In the penises of streptozotocin (STZ)-induced diabetic rats, here, we show by immunohistochemistry that nitrergic nerves undergo selective degeneration since the noradrenergic nerves which have an anti-erectile function in the penis remained intact.Nitrergic relaxation responses in vitro and erectile responses to cavernous nerve stimulation in vivo were attenuated in these animals, whereas noradrenergic responses were enhanced.Activity and protein amount of neuronal nitric oxide synthase (nNOS) were also reduced in the penile tissue of diabetic rats.We, thus, hypothesized that NO in the nitrergic nerves may be involved in the nitrergic nerve damage, since only the nerves which contain neuronal NO synthase underwent degeneration.We administered an inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (L-NAME), in the drinking water of rats for up to 12 weeks following the establishment of diabetes with STZ.Here we demonstrate that this compound protected the nitrergic nerves from morphological and functional impairment. Our results show that selective nitrergic degeneration in diabetes is NO-dependent and suggest that inhibition of NO synthase is neuroprotective in this condition.

Cellek, Selim; Rodrigo, Jose; Lobos, Edgar; Fernandez, Patricia; Serrano, Julia; Moncada, Salvador

1999-01-01

270

Prevention of albuminuria by captopril in diabetic rats.  

PubMed

1. Streptozotocin diabetic rats were treated with captopril (50 mg l), an angiotensin converting enzyme-inhibitor, in drinking water for 20 weeks. 2. Systolic blood pressure and 24-hr urinary excretions of heparan sulfate and albumin were done at 2, 8, 16 and 20 weeks. 3. At the end of 20 weeks, all rats were killed, kidneys removed and glomeruli isolated. 4. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of 35S-sulfate. 5. Captopril significantly lowered blood pressure in diabetic rats 8 weeks after treatment. 6. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from nondiabetic rats. 7. Further characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. 8. Therapy with captopril normalized not only glomerular synthesis and content but also various fractions of heparan sulfate in diabetic rats. 9. Excretions of heparan sulfate and albumin were significantly higher in diabetic than in nondiabetic rats. 10. Captopril therapy did significantly lower but not normalize both these excretions in diabetic rats. 11. The data suggest that catopril therapy improves albuminuria through preservation of glomerular heparan sulfate and prevention of its urinary loss in diabetic rats. PMID:2055428

Reddi, A S

1991-01-01

271

Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: Effect of secoisolariciresinol diglucoside (SDG)  

Microsoft Academic Search

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant activity and has been shown to prevent hypercholesterolemic atherosclerosis. An investigation was made of the effects of SDG on the development of diabetes in diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes [insulin dependent diabetes mellitus (IDDM)] to determine if this type of diabetes is due to

Kailash Prasad

2000-01-01

272

Antihyperglycemic activity of Prunella vulgaris L. in streptozotocin-induced diabetic mice  

Microsoft Academic Search

Prunella vulgaris L. (Labiatae) has been reported to have a wide range of health benefits in oriental medicine. This study for the first time is to examine the antihyperglycemic effects of P. vulgaris in streptozotocin (STZ) - induced diabetic ICR mice (STZ diabetic mice). The effects of P. vulgaris L. aqueous-ethanol extract (PVE) on blood glucose, exogenous insulin sensitivity and

Jie Zheng; Jiguo He; Baoping Ji; Ye Li; Xiaofeng Zhang

2007-01-01

273

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

PubMed

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 2weeks. 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 11weeks 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

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

2013-07-02

274

[Treatment of diabetes in experimental animals by metallocomplexes].  

PubMed

The number of patients suffered from diabetes mellitus has increased over the decades probably because of both lifestyle- and diet-changes. There are two types of diabetes mellitus. Type 1 diabetes mellitus is due to the autoimmune-mediated destruction of pancreatic B cells, which results in absolute insulin deficiency, thus the patients require insulin injections. Type 2 diabetes mellitus is due to the insulin resistance and abnormal insulin secretion, thus the patients require exercise, diet control and/or oral hypoglycemic medicines. Each treatment, however, has some problems involving physical and mental burden, and formation of self-antibodies for insulin injections, and the severe side effects and discontinuation of insulin synthesis in the pancreas for hypoglycemic medicines. To overcome these important problems and find the replacements for the insulin injections and synthetic medicines, we attempted to develop new antidiabetic metallocomplexes with novel structures and mechanisms. In 1990, we first presented orally active vanadyl (+4 oxidation state of oxo-vanadium) complexes including vanadyl-cysteine methyl ester complex, which normalized hyperglycemia in the streptozocin (STZ)-induced type 1 diabetic rats. Based on these findings, we have developed a wide variety of vanadyl complexes with different coordination environments around vanadyl ion. Following the study, we also challenged to develop orally active zinc complexes since 2002. This review focuses on our recent development of vanadyl and zinc complexes for anti-diabetic and anti-metabolic syndromes, together with the propose for the possible action mechanism of these complexes in adipocytes. PMID:18311049

Sakurai, Hiromu

2008-03-01

275

Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes  

PubMed Central

Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation.

Choi, Ran; Kim, Bo Hwan; Naowaboot, Jarinyaporn; Lee, Mi Young; Hyun, Mi Ri; Cho, Eun Ju; Lee, Eun Soo; Lee, Eun Young; Yang, Young Chul

2011-01-01

276

Increased degradation of dermal collagen in diabetic rats.  

PubMed

The effect of alloxan induced diabetes on the dermal collagen content of albino rats was studied in relation to few lysosomal enzymes. Diabetes decreased the dermal collagen content. The specific activities of the lysosomal enzymes studied in the diabetic rat skin were elevated. It has been established that lysosomal enzymes degrade the connective tissue components. Thus, it may be suggested that the increase in the lysosomal enzymes studied should have facilitated the decrease in dermal collagen content of diabetic rats by increasing the degradation of dermal collagen. PMID:1816088

Rajkumar, L; Srinivasan, N; Balasubramanian, K; Govindarajulu, P

1991-11-01

277

Oxidative and nitrosative stress in brain mitochondria of diabetic rats  

Microsoft Academic Search

Diabetic encephalopathy, characterized by impaired cog- nitive functions and neurochemical and structural abnor- malities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochon- dria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue

R Mastrocola; F Restivo; O Danni; E Brignardello; M Aragno; G Boccuzzi

2005-01-01

278

Liver Glycogen of Alloxan-Diabetic Rats under Different Conditions  

Microsoft Academic Search

IT is generally agreed that a low glycogen level in liver and muscle is a characteristic of pancreatic diabetes. Considerable importance is attached to this phenomenon in the pathology of diabetes. A similar condition has been observed in alloxan-diabetic rats by Lackey, Bunde, Gill and Harris1.

E. Tuerkischer; E. Wertheimer

1946-01-01

279

Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model  

PubMed Central

Spontaneously Diabetic Torii Leprfa (SDT fatty) rat, established by introducing the fa allele of the Zucker fatty rat into SDT rat genome, is a new model of obese type 2 diabetes. Both male and female SDT fatty rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT fatty rats were seen at younger ages compared to those in the SDT rats. In this paper, we overview pathophysiological features in SDT fatty rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT fatty rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT fatty rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT fatty rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.

Kemmochi, Yusuke; Fukui, Kenji; Maki, Mimi; Kimura, Shuichi; Ishii, Yukihito; Sasase, Tomohiko; Miyajima, Katsuhiro; Ohta, Takeshi

2013-01-01

280

Effects of bis(?-furancarboxylato)oxovanadium(IV) on non-diabetic and streptozotocin-diabetic rats  

Microsoft Academic Search

BackgroundBis(?-furancarboxylato)oxovanadium(IV) (BFOV), a new orally active anti-diabetic vanadium complex with organic agent, has been synthesized and characterized. The current study examined the stability in aqueous solution and effects of the complex on carbohydrate and lipid metabolism in non-diabetic and streptozotocin-induced diabetic rats.

Li H. Gao; Wei P. Liu; Bo L. Wang; Ling Li; Ming J. Xie; Yan R. Li; Zhi H. Chen; Xi Z. Chen

2006-01-01

281

AntiDiabetic Activity of Terminalia Catappa Linn. Leaf Extracts in Alloxan-Induced Diabetic Rats  

Microsoft Academic Search

In view of suggested anti diabetic potential, effect of aqueous and cold extracts of Terminalia Catappa Linn (Combretaceae) leaves, on fasting blood sugar levels and serum biochemical analysis in alloxan- induced diabetic rats was investigated. All the extracts of Terminalia Catappa produced a significant anti diabetic activity at dose levels of 1\\/5 th of their lethal doses. Concurrent histological studies

SYED MANSOOR AHMED; VRUSHABENDRA SWAMY BM; P GOPKUMAR; R DHANAPAL

282

Amelioration of diabetic dyslipidemia by macrocyclic binuclear oxovanadium complex on streptozotocin induced diabetic rats  

Microsoft Academic Search

Diabetic dyslipidemia, the main causative factor for the progression of vascular complications in diabetes, is caused due to hyperglycemia and excess mobilisation of fatty acids. Recently we have reported on a novel macrocyclic binuclear oxovanadium (MBOV) complex synthesized by us with significant hypoglycemic efficacy and without any apparent toxicity on streptozotocin induced diabetic rats. In the present study, streptozotocin induced

Balasubramanian Ramachandran; Sorimuthu Subramanian

2005-01-01

283

Suppression of XBP1S Mediates High Glucose-Induced Oxidative Stress and Extracellular Matrix Synthesis in Renal Mesangial Cell and Kidney of Diabetic Rats  

PubMed Central

Recent evidences suggest that endoplasmic reticulum (ER) stress was involved in multi pathological conditions, including diabetic nephropathy (DN). X-box binding protein 1(XBP1), as a key mediator of ER stress, has been proved having the capability of preventing oxidative stress. In this study, we investigated the effects of spliced XBP1 (XBP1S), the dominant active form of XBP1, on high glucose (HG)-induced reactive oxygen species (ROS) production and extracellular matrix (ECM) synthesis in cultured renal mesangial cells (MCs) and renal cortex of STZ-induced diabetic rats. Real time PCR and Western blot were used to evaluate the mRNA and protein levels respectively. Transfection of recombinant adenovirus vector carrying XBP1S gene (Ad-XBP1S) was used to upregulate XBP1S expression. XBP1S siRNA was used to knockdown XBP1S expression. ROS level was detected by dihydroethidium (DHE) fluorescent probe assay. The results showed that HG treatment significantly reduced XBP1S protein and mRNA level in the cultured MCs while no obvious change was observed in unspliced XBP1 (XBP1U). In the mean time, the ROS production, collagen IV and fibronectin expressions were increased. Diphenylene-chloride iodonium (DPI), a NADPH oxidase inhibtor, prevented HG-induced increases in ROS as well as collagen IV and fibronectin expressions. Transfection of Ad-XBP1S reversed HG-induced ROS production and ECM expressions. Knockdown intrinsic XBP1S expression induced increases in ROS production and ECM expressions. Supplementation of supreoxide reversed the inhibitory effect of Ad-XBP1S transfection on ECM synthesis. P47phox was increased in HG-treated MCs. Ad-XBP1S transfection reversed HG-induced p47phox increase while XBP1S knockdown upregulated p47phox expression. In the renal cortex of diabetic rats, the expression of XBP1S was reduced while p47phox, collagen IV and fibronectin expression were elevated. These results suggested that XBP1S pathway of ER stress was involved in HG-induced oxidative stress and ECM synthesis. A downstream target of XBP1S in regulating ROS formation might be NADPH oxidase.

Ni, Jun; Wang, Zhen; Shen, Yang; Zhou, Li; Huang, Yu; Wang, Jun; Xue, Hong; Zhang, Wei; Lu, Limin

2013-01-01

284

Immunological evidence for increased oxidative stress in diabetic rats  

Microsoft Academic Search

Summary   The role of oxidative stress in aging and diabetes mellitus is currently under discussion. We previously showed age-dependent\\u000a accumulations of fluorescent protein adducts with lipoperoxidative aldehydes, (malondialdehyde (MDA), and hydroxynonenal (HNE))\\u000a in rat skin collagen with diabetic BB rats exhibiting faster accumulation. Modified proteins have been shown to be immunogenic:\\u000a antibody titres against rat serum albumin modified by MDA

N. Traverso; S. Menini; L. Cosso; P. Odetti; E. Albano; M. A. Pronzato; U. M. Marinari

1998-01-01

285

Erythrocyte flow in choriocapillaris of normal and diabetic rats  

Microsoft Academic Search

The choriocapillaris is a unique capillary bed that provides nutrients to the retinal photoreceptors. It changes anatomically in diabetes, but the impact of these changes on blood flow is unknown. In this study hemodynamic parameters in individual choriocapillaris vessels were compared in normal and diabetic rats. Three groups were studied: normal buffer-injected control rats, streptozotocin (STZ)-injected mildly hyperglycemic (STZ-MH) rats,

Rod D. Braun; Christopher A. Wienczewski; Asad Abbas

2009-01-01

286

Hypoinsulinemia may mediate the lowering of self-stimulation thresholds by food restriction and streptozotocin-induced diabetes  

Microsoft Academic Search

Streptozotocin (STZ)-induced diabetes and chronic food restriction have both been reported to lower thresholds for lateral hypothalamic self-stimulation (LHSS). In view of recent evidence that insulin regulates monoamine transporter gene expression in brain, it is possible that the hypoinsulinemia that is common to diabetes and food restriction mediates the enhancement of brain stimulation reward. Two experiments were conducted to test

Kenneth D Carr; Gye-Young Kim; Soledad Cabeza de Vaca

2000-01-01

287

Pharmacokinetics of oltipraz in diabetic rats with liver cirrhosis  

PubMed Central

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.

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

2009-01-01

288

Forced-exercise delays neuropathic pain in experimental diabetes: effects on voltage-activated calcium channels.  

PubMed

Physical exercise produces a variety of psychophysical effects, including altered pain perception. Elevated levels of centrally produced endorphins or endocannabinoids are implicated as mediators of exercise-induced analgesia. The effect of exercise on the development and persistence of disease-associated acute/chronic pain remains unclear. In this study, we quantified the physiological consequence of forced-exercise on the development of diabetes-associated neuropathic pain. Euglycemic control or streptozotocin (STZ)-induced diabetic adult male rats were subdivided into sedentary or forced-exercised (2-10 weeks, treadmill) subgroups and assessed for changes in tactile responsiveness. Two weeks following STZ-treatment, sedentary rats developed a marked and sustained hypersensitivity to von Frey tactile stimulation. By comparison, STZ-treated diabetic rats undergoing forced-exercise exhibited a 4-week delay in the onset of tactile hypersensitivity that was independent of glucose control. Exercise-facilitated analgesia in diabetic rats was reversed, in a dose-dependent manner, by naloxone. Small-diameter (< 30 ?m) DRG neurons harvested from STZ-treated tactile hypersensitive diabetic rats exhibited an enhanced (2.5-fold) rightward (depolarizing) shift in peak high-voltage activated (HVA) Ca(2+) current density with a concomitant appearance of a low-voltage activated (LVA) Ca(2+) current component. LVA Ca(2+) currents present in DRG neurons from hypersensitive diabetic rats exhibited a marked depolarizing shift in steady-state inactivation. Forced-exercise attenuated diabetes-associated changes in HVA Ca(2+) current density while preventing the depolarizing shift in steady-state inactivation of LVA Ca(2+) currents. Forced-exercise markedly delays the onset of diabetes-associated neuropathic pain, in part, by attenuating associated changes in HVA and LVA Ca(2+) channel function within small-diameter DRG neurons possibly by altering opioidergic tone. PMID:21554321

Shankarappa, Sahadev A; Piedras-Rentería, Erika S; Stubbs, Evan B

2011-06-02

289

Lipid glycation and protein glycation in diabetes and atherosclerosis.  

PubMed

Recent instrumental analyses using a hybrid quadrupole/linear ion trap spectrometer in LC-MS/MS have demonstrated that the Maillard reaction progresses not only on proteins but also on amino residues of membrane lipids such as phosphatidylethanolamine (PE), thus forming Amadori-PE (deoxy-D: -fructosyl PE) as the principal products. The plasma Amadori-PE level is 0.08 mol% of the total PE in healthy subjects and 0.15-0.29 mol% in diabetic patients. Pyridoxal 5'-phosphate and pyridoxal are the most effective lipid glycation inhibitors, and the PE-pyridoxal 5'-phosphate adduct is detectable in human red blood cells. These findings are beneficial for developing a potential clinical marker for glycemic control as well as potential compounds to prevent the pathogenesis of diabetic complications and atherosclerosis. Glucose and other aldehydes, such as glyoxal, methylglyoxal, and glycolaldehyde, react with the amino residues of proteins to form Amadori products and Heynes rearrangement products. Because several advanced glycation end-product (AGE) inhibitors such as pyridoxamine and benfotiamine inhibit the development of retinopathy and neuropathy in streptozotocin (STZ)-induced diabetic rats, AGEs may play a role in the development of diabetic complications. In the present review, we describe the recent progress and future applications of the Maillard reaction research regarding lipid and protein modifications in diabetes and atherosclerosis. PMID:20957396

Miyazawa, Teruo; Nakagawa, Kiyotaka; Shimasaki, Satoko; Nagai, Ryoji

2010-10-19

290

HYPOGLYCEMIC ACTIVITY OF CAMEL MILK IN STREPTOZOTOCIN INDUCED DIABETIC RATS  

Microsoft Academic Search

Oral hypoglycemic activity of camel milk in streptozotocin (50 mg\\/kg, I.P.) induced diabetic rats was investigated in this controlled study. These rats were maintained on normal diet of wheat dalia and in addition to that they were offered raw camel milk (Group I), raw cattle milk (Group II), water (Group III) and untreated control rats on normal diet (Group IV)

R. P. Agrawal; D. K. Kochar; M. S. Sahani; F. C. Tuteja; S. K. Ghorui

2004-01-01

291

Calcitriol improves streptozotocin-induced diabetes and recovers bone mineral density in diabetic rats.  

PubMed

Vitamin D analogs exert a preventative effect on experimental diabetes, but whether or not they are able to halt progress of established diabetes is not yet known. Moreover, it is widely accepted that diabetes may induce osteoporosis, but the efficacy of vitamin D on diabetic osteoporosis is not clear. In order to help clarify these issues, we have tested the efficacy of calcitriol streptozotocin-induced diabetes. Streptozotocin (60 mg/Kg body weight) was injected in 3-month-old Wistar rats, randomly distributed into two groups: vehicle (olive oil) treated diabetic rats (D) and diabetic rats treated with 1.25-(OH)2D3 250 mg, three times a week (DT). Control animals (C) were treated with vehicle alone. The experiment lasted 8 weeks. The histology of the pancreata was evaluated. Blood glucose and calcium and phosphate in serum and urine were measured. Finally, bone mineral density (BMD) of tibia and lumbar vertebrae were evaluated. After 8 weeks, diabetes persisted in 85% of the diabetic rats (D group), but in only 45% of vitamin D-treated group (DT). At the end of the experiment, DT animals were separated into two groups, those still remaining diabetic (DT-NR) and reversed animals (DT-R). Moreover, bone loss was observed in diabetic animals (D), whereas BMD of DT-R rats showed similar values to those of controls (C). Our results suggest that 1.25(OH)2D3 improves diabetes and, as such, may recover BMD in streptozotocin-induced diabetic rats. PMID:15654497

Del Pino-Montes, J; Benito, G E; Fernández-Salazar, M P; Coveñas, R; Calvo, J J; Bouillon, R; Quesada, J M

2004-08-24

292

The anti-diabetic effects and pharmacokinetic profiles of bis(maltolato)oxovanadium in non-diabetic and diabetic rats.  

PubMed

The purpose of this study was to evaluate the anti-diabetic effects and pharmacokinetics of bis(maltolato)oxovanadium (BMOV) in rats. The anti-diabetic study was carried out in non-diabetic and diabetic rats by single-dose subcutaneous and intragastric administration. Pharmacokinetic investigation was performed using non-diabetic rats. Results showed that BMOV significantly decreased plasma glucose levels in diabetic rats at all given doses, and restored hyperglycaemic values to normal values after subcutaneous injections at doses of 4 and 8 mg vanadium (V)/kg or after intragastric administration at doses of 14 and 28 mgV/kg, respectively, but did not affect the plasma glucose level in non-diabetic rats. BMOV could be rapidly absorbed, slowly eliminated from plasma, widely distributed in various tissues and accumulated to a greater extent in the femur tissue. The average absolute bioavailability for intragastric administration at a single dose of 3, 6 and 12 mgV/kg was 28.1%, 33.7% and 21.4%, respectively. The presence of the peak vanadium level in the plasma was not coincident with that of the maximum effect of lowering plasma glucose levels. In conclusion, at the present dosing levels and administration routes, BMOV was effective in lowering plasma glucose levels in diabetic rats. BMOV has a promising outlook as an oral glucose-lowering drug. PMID:18088510

Zhang, Shuang-Qing; Zhong, Xu-Ying; Chen, Guo-Hua; Lu, Wan-Liang; Zhang, Qiang

2008-01-01

293

Standardized Aqueous Tribulus terristris (Nerunjil) Extract Attenuates Hyperalgesia in Experimentally Induced Diabetic Neuropathic Pain Model: Role of Oxidative Stress and Inflammatory Mediators.  

PubMed

The present study aimed to evaluate standardized aqueous Tribulus terristris (nerunjil) extract on the pain threshold response in streptozotocin (STZ)-induced diabetic neuropathic pain model in rats. After a single injection of STZ (40?mg/kg; i.p.), Wistar male rats were tested by the thermal and chemical-induced pain models. Diabetic rats exhibited significant hyperalgesia, and these rats were left untreated for the first four weeks. Thereafter, treatment was initiated and continued up to week-8. All the rats except the vehicle-treated group received insulin 5?IU/kg/day to maintain plasma glucose levels. Treatment with nerunjil (100 and 300?mg/kg; p.o.) for 4?weeks significantly attenuated the nociception in behavioural models. Nerunjil also inhibited the tumour necrosis factor-? and interleukin-1 beta levels. The effect of nerunjil (300?mg/kg) is comparable to the standard drug Pregabalin (100?mg/kg). Nerunjil increased the superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and decreased the lipid peroxide levels in dose-dependent manner. Insulin alone-treated rats failed to attenuate hyperalgesic response. In comparison to insulin alone-treated rats, nerunjil exhibited significant increase in the pain threshold response. It could be concluded that in controlled diabetic states, nerunjil attenuated the neuropathic pain through modulation of oxidative stress and inflammatory cytokine release. Copyright © 2012 John Wiley & Sons, Ltd. PMID:23280817

Ranjithkumar, Ravichandran; Prathab Balaji, S; Balaji, Bhaskar; Ramesh, R V; Ramanathan, Muthiah

2012-12-27

294

Gamma interferon prevents diabetes in the BB rat.  

PubMed Central

The BB rat model of human insulin-dependent diabetes mellitus (IDDM) spontaneously develops diabetes through an autoimmune process. Gamma interferon (IFN-gamma) is thought to play an important pathogenic role. This study examined if IFN-gamma administration can, paradoxically, prevent diabetes in BB rats. Diabetes-prone BB rats were initially injected intraperitoneally with murine recombinant IFN-gamma (rIFN-gamma) at doses of 0.5 x 10(4) to 40 x 10(4) U three times a week for 6 weeks beginning at 35 days of age. The effects of altering the duration of treatment (2 to 6 weeks) and the age at which injections were initiated (45 through 65 days) were also assessed. rIFN-gamma administration prevented the development of diabetes in a dose-dependent manner. The optimal treatment condition resulted in a 9.1% incidence of diabetes versus a 90% incidence in control rats. This diabetes-sparing effect was long lasting and continued to 7 months of age. A 4- to 6-week course resulted in maximal inhibition. Treatment initiated as late as 55 days of age, when insulitis is already present, was effective in preventing diabetes. Islet inflammation was dramatically lower in rIFN-gamma- versus saline-injected rats (P < 0.01). Total leukocyte count and subpopulations of peripheral mononuclear cells were unaltered by rIFN-gamma. In summary, rIFN-gamma paradoxically and potently prevents diabetes in BB rats in a dose-dependent fashion by inhibiting islet inflammation. This diabetes-sparing effect occurs even when injections are initiated after evidence of the diabetic process is already present.

Sobel, D O; Newsome, J

1997-01-01

295

Chronic cobalt treatment decreases hyperglycemia in streptozotocin-diabetic rats.  

PubMed

Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 +/- 2 gm) compared to controls (482 +/- 3 gm). Body weight was further reduced by cobalt treatment (290 +/- 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 +/- 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 +/- 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose. PMID:16802070

Vasudevan, Harish; McNeill, John H

2006-06-27

296

High rat food vitamin E content improves nerve function in streptozotocin-diabetic rats  

Microsoft Academic Search

Antioxidants can improve nerve dysfunction in hyperglycaemic rats. We evaluated whether the standard supplementation of rat food with vitamin E (normally added for preservation purposes) or high-dose vitamin E treatment improves nerve conduction in maturing streptozotocin-diabetic rats, a model widely used to study diabetic neuropathy. Hyperglycaemic rats received food containing 25 mg\\/kg (non-supplemented), 70 mg\\/kg (standard food) or 12 g\\/kg

P. Sytze van Dam; Bert Bravenboer; B. Sweder van Asbeck; Joannes J. M Marx; Willem Hendrik Gispen

1999-01-01

297

Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion.  

PubMed

Oxidative stress due to excessive reactive oxygen species (ROS) and depleted antioxidants such as glutathione (GSH) can give rise to apoptotic cell death in acutely diabetic hearts and lead to heart disease. At present, the source of these cardiac ROS or the subcellular site of cardiac GSH loss [i.e., cytosolic (cGSH) or mitochondrial (mGSH) GSH] has not been completely elucidated. With the use of rotenone (an inhibitor of the electron transport chain) to decrease the excessive ROS in acute streptozotocin (STZ)-induced diabetic rat heart, the mitochondrial origin of ROS was established. Furthermore, mitochondrial damage, as evidenced by loss of membrane potential, increases in oxidative stress, and reduction in mGSH was associated with increased apoptosis via increases in caspase-9 and -3 activities in acutely diabetic hearts. To validate the role of mGSH in regulating cardiac apoptosis, L-buthionine-sulfoximine (BSO; 10 mmol/kg ip), which blocks GSH synthesis, or diethyl maleate (DEM; 4 mmol/kg ip), which inactivates preformed GSH, was administered in diabetic rats for 4 days after STZ administration. Although both BSO and DEM lowered cGSH, they were ineffective in reducing mGSH or augmenting cardiomyocyte apoptosis. To circumvent the lack of mGSH depletion, BSO and DEM were coadministered in diabetic rats. In this setting, mGSH was undetectable and cardiac apoptosis was further aggravated compared with the untreated diabetic group. In a separate group, GSH supplementation induced a robust amplification of mGSH in diabetic rat hearts and prevented apoptosis. Our data suggest for the first time that mGSH is crucial for modulating the cell suicide program in short-term diabetic rat hearts. PMID:15805231

Ghosh, Sanjoy; Pulinilkunnil, Thomas; Yuen, Gloria; Kewalramani, Girish; An, Ding; Qi, Dake; Abrahani, Ashraf; Rodrigues, Brian

2005-04-01

298

Role of 20-hydroxyeicosatetraenoic acid in altering vascular reactivity in diabetes  

PubMed Central

Summary This study examined the role of 20-hydroxyeicosatetraenoic (20-HETE) in altering vascular function in streptozotocin (STZ)-induced diabetic rats. The expression of CYP4A protein and the formation of 20-HETE were elevated in the kidney, but not in the renal or mesenteric vasculature, of diabetic animals. The vasoconstrictor responses to norepinephrine (NE), endothelin-1 (ET-1), and angiotensin II (Ang II) were significantly enhanced in the isolated perfused mesenteric vascular bed and renal artery segments of diabetic rats. Chronic treatment of the diabetic rats with 1-aminobenzotriazole (ABT, 50 mg kg?1 alt?1 diem) or N-hydroxy-N?-(4-butyl-2-methylphenyl) formamidine (HET0016, 2.5 mg kg?1 day?1) attenuated the responses to these vasoconstrictors in both vascular beds. The synthesis of 20-HETE in renal microsomes was reduced by >80% confirming that the doses of ABT and HET0016 were sufficient to achieve system blockade. Addition of HET0016 (1 ?M) in vitro also normalized the enhanced vascular responsiveness of renal and mesenteric vessels obtained from diabetic animals to NE and inhibited the formation of 20-HETE by >90% while having no effect on the formation of epoxides. Vasodilator responses to carbachol and histamine were reduced in the mesenteric vasculature, but not in renal arteries, of diabetic rats. Treatment of the diabetic animals with HET0016 improved vasodilator responses in both vascular beds. Vascular sensitivity to exogenous 20-HETE was elevated in the mesenteric bed of diabetic animals compared to controls. These results suggest that 20-HETE contributes to the elevation in vascular reactivity in diabetic animals. This effect is not due to increased vascular expression of CYP4A but may be related to either enhanced agonist-induced release of substrate (arachidonic acid) by the CaMKII/Ras-GTPase system and/or elevated vascular responsiveness to 20-HETE.

Yousif, M. H. M.; Dunn, K. M. J.; Dahly-Vernon, A. J.; Akhtar, S.; Roman, R. J.

2009-01-01

299

Combined effects of streptozotocin-diabetes and ionizing radiation on nephropathy in the rat  

Microsoft Academic Search

The individual effects of radiation and diabetes on nephropathy in the rat are well-documented; however, the combined effects of these factors on nephropathy have not been adequately studied. The combined effect of radiation and diabetes on nephropathy is a significant problem in view of human populations at risk; diabetic radiation workers and diabetic radiotherapy patients. Streptozotocin-diabetic and control rats were

Claycamp

1982-01-01

300

Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice  

Microsoft Academic Search

Diabetic nephropathy involves a renal inflammatory response induced by the diabetic milieu. Macrophages accumulate in diabetic kidneys in association with the local upregulation of monocyte chemoattractant protein-1 (MCP-1); however, the contribution of macrophages to renal injury and the importance of MCP-1 to their accrual are unclear. Therefore, we examined the progression of streptozotocin (STZ)-induced diabetic nephropathy in mice deficient in

F Y Chow; D J Nikolic-Paterson; E Ozols; R C Atkins; B J Rollin; G H Tesch

2006-01-01

301

Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis  

Microsoft Academic Search

Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis.BackgroundTo elucidate the molecular mechanism of diabetic nephropathy, a high-density DNA filter array was employed to survey the gene expression profile of streptozotocin-induced diabetic CD-1 (ICR) mouse kidneys.MethodsTen-week-old CD-1 male mice were divided into four groups: (1) control, (2) unilaterally nephrectomized (UX) mice, (3) streptozotocin (STZ)-induced diabetic (STZ) mice, and (4)

Jun Wada; Hong Zhang; Yoshinori Tsuchiyama; Keita Hiragushi; Kazuyuki Hida; Kenichi Shikata; Yashpal S. Kanwar; Hirofumi Makino

2001-01-01

302

Renal ACE and ACE2 Expression in Early Diabetic Rats  

Microsoft Academic Search

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.

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

2008-01-01

303

Effect of cobalt on the liver glycogen content in the streptozotocin-induced diabetic rats  

Microsoft Academic Search

Cobalt decreases blood glucose in diabetic rats but the mechanisms involved are unclear. To determine the contribution of glycogen metabolism to glycemia-lowering effect, glycogen contents of liver and muscle in the streptozotocin-induced diabetic rats were determined. The liver glycogen was depleted in diabetic rats. But when cobalt was administered to the rats, the glycogen returned to the level of healthy

Yasutomo Nomura; Shin-ichiro Okamoto; Mitsuru Sakamoto; Zhonggang Feng; Takao Nakamura

2005-01-01

304

Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats.  

PubMed

Spontaneously diabetic BB rats were sham operated (SO) or ovariectomized (OVX) within days after onset and studied after 4, 8, and 12 weeks. Analyses included histomorphometry of proximal tibial metaphyses, biochemical analyses of humeri, DXA analyses, and biomechanical testing of femora. In SO diabetic rats, no osteoblasts, osteoid tissue, or osteoclasts were present on the trabecular bone surface, but trabecular bone volume (TBV) remained normal compared with control BB rats. The concentration of IGF-I per dry weight of humerus was decreased after 12 weeks of diabetes, whereas the concentrations of calcium and osteocalcin did not change. DXA analysis showed normal bone mineral density (BMD) at both diaphyseal and metaphyseal femoral areas. On biomechanical testing, angular deformation, energy absorption, and torsional strength of the femora were decreased after 8-12 weeks of diabetes, but stiffness was normal. Ovariectomy in diabetic rats caused a decrease in femoral BMD especially at the metaphysis, and there was a trend toward decreased TBV in the tibial metaphysis; TBV loss was less marked than in control OVX rats, however. The increase in BMD at the femoral diaphysis, measured after 12 weeks of OVX in control rats, was absent in diabetic rats. Multiple-regression analysis indicated that the presence of diabetes but not ovariectomy, weight, and mineral content correlated with decreased energy absorption, angular deformation, and strength of the femora. The data infer that the (near) absence of unmineralized bone matrix in severely diabetic rats alters bone microarchitecture and ultimately results in brittle bones, which is not predicted by BMC or BMD measurements. PMID:7817814

Verhaeghe, J; Suiker, A M; Einhorn, T A; Geusens, P; Visser, W J; Van Herck, E; Van Bree, R; Magitsky, S; Bouillon, R

1994-10-01

305

Diabetes downregulates BK?1 potassium channel subunit in retinal arteriolar smooth muscle  

PubMed Central

Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased retinal arteriolar tone during diabetes remain unclear. Normally, local Ca2+ release events (Ca2+-sparks), trigger the activation of large-conductance Ca2+-activated K+(BK)-channels which hyperpolarize and relax vascular smooth muscle cells (VSMCs), thereby causing vasodilatation. In the present study, we examined BK channel function in retinal VSMCs from streptozotocin(STZ)-induced diabetic rats. The BK channel inhibitor, Penitrem A, constricted non-diabetic retinal arterioles (pressurized to 70mmHg) by 28%. The BK current evoked by caffeine was dramatically reduced in retinal arterioles from diabetic animals even though caffeine-evoked [Ca2+]i release was unaffected. Spontaneous BK currents were smaller in diabetic cells, but the amplitude of Ca2+-sparks was larger. The amplitudes of BK currents elicited by depolarizing voltage steps were similar in control and diabetic arterioles and mRNA expression of the pore-forming BK? subunit was unchanged. The Ca2+-sensitivity of single BK channels from diabetic retinal VSMCs was markedly reduced. The BK?1 subunit confers Ca2+-sensitivity to BK channel complexes and both transcript and protein levels for BK?1 were appreciably lower in diabetic retinal arterioles. The mean open times and the sensitivity of BK channels to tamoxifen were decreased in diabetic cells, consistent with a downregulation of BK?1 subunits. The potency of blockade by Pen A was lower for BK channels from diabetic animals. Thus, changes in the molecular composition of BK channels could account for retinal hypoperfusion in early diabetes, an idea having wider implications for the pathogenesis of diabetic hypertension.

McGahon, MK; Dash, DP; Arora, A; Wall, N; Dawicki, J; Simpson, DA; Scholfield, CN; McGeown, JG; Curtis, TM

2008-01-01

306

The effects of vanadium treatment on bone in diabetic and non-diabetic rats  

Microsoft Academic Search

Vanadium-based drugs lower glucose by enhancing the effects of insulin. Oral vanadium drugs are being tested for the treatment of diabetes. Vanadium accumulates in bone, though it is not known if incorporated vanadium affects bone quality. Nine- to 12-month-old control and streptozotocin-induced diabetic female Wistar rats were given bis(ethylmaltolato)oxovanadium(IV) (BEOV), a vanadium-based anti-diabetic drug, in drinking water for 12 weeks.

D. M. Facchini; V. G. Yuen; M. L. Battell; J. H. McNeill; M. D. Grynpas

2006-01-01

307

Effect of eplerenone, enalapril and their combination treatment on diabetic nephropathy in type II diabetic rats  

Microsoft Academic Search

Background. Recent data suggest that aldosterone antag- onists have beneficial effects on diabetic nephropathy. In this study, we investigated the dose-dependent effect of eplerenone and a combined treatment with eplerenone and enalapril compared with each drug alone on renal function in type II diabetic rats. To further explore the molecular mechanism of action of combination therapy, we also per- formed

Young Sun Kang; Gang Jee Ko; Hwa Lee; Hye Kyoung Song; Sang Youb Han; Kum Hyun Han; Hyoung Kyu Kim; Jee Young Han; Dae Ryong Cha

308

Arginase Promotes Skeletal Muscle Arteriolar Endothelial Dysfunction in Diabetic Rats  

PubMed Central

Endothelial dysfunction is a characteristic feature in diabetes that contributes to the development of vascular disease. Recently, arginase has been implicated in triggering endothelial dysfunction in diabetic patients and animals by competing with endothelial nitric oxide synthase for substrate l-arginine. While most studies have focused on the coronary circulation and large conduit blood vessels, the role of arginase in mediating diabetic endothelial dysfunction in other vascular beds has not been fully investigated. In the present study, we determined whether arginase contributes to endothelial dysfunction in skeletal muscle arterioles of diabetic rats. Diabetes was induced in male Sprague Dawley rats by streptozotocin injection. Four weeks after streptozotocin administration, blood glucose, glycated hemoglobin, and vascular arginase activity were significantly increased. In addition, a significant increase in arginase I and II mRNA expression was detected in gracilis muscle arterioles of diabetic rats compared to age-matched, vehicle control animals. To examine endothelial function, first-order gracilis muscle arterioles were isolated, cannulated in a pressure myograph system, exposed to graded levels of luminal flow, and internal vessel diameter measured. Increases in luminal flow (0–50??L/min) caused progressive vasodilation in arterioles isolated from control, normoglycemic animals. However, flow-induced vasodilation was absent in arterioles obtained from streptozotocin-treated rats. Acute in vitro pretreatment of blood vessels with the arginase inhibitors N?-hydroxy-nor-l-arginine or S-(2-boronoethyl)-l-cysteine restored flow-induced responses in arterioles from diabetic rats and abolished differences between diabetic and control animals. Similarly, acute in vitro pretreatment with l-arginine returned flow-mediated vasodilation in vessels from diabetic animals to that of control rats. In contrast, d-arginine failed to restore flow-induced dilation in arterioles isolated from diabetic animals. Administration of sodium nitroprusside resulted in a similar degree of dilation in arterioles isolated from control or diabetic rats. In conclusion, the present study identifies arginase as an essential mediator of skeletal muscle arteriolar endothelial dysfunction in diabetes. The ability of arginase to induce endothelial dysfunction in skeletal muscle arterioles may further compromise glucose utilization and facilitate the development of hypertension in diabetes.

Johnson, Fruzsina K.; Johnson, Robert A.; Peyton, Kelly J.; Shebib, Ahmad R.; Durante, William

2013-01-01

309

Cognitive Dysfunction Associated with Diabetic Ketoacidosis in Rats  

PubMed Central

Background Type 1 diabetes mellitus in children may be associated with neurocognitive deficits of unclear cause. A recent retrospective study in children suggested possible associations between diabetic ketoacidosis (DKA) and decreased memory. The current investigation was undertaken to determine whether cognitive deficits could be detected after a single episode of DKA in an animal model. Methods Streptozotocin was used to induce diabetes in juvenile rats, and rats were then treated with subcutaneous insulin injections. In one group, insulin was subsequently withdrawn to allow development of DKA, which was then treated with insulin and saline. After recovery from DKA, subcutaneous insulin injections were re-started. In the diabetes control group, rats continued to receive subcutaneous insulin and underwent sham procedures identical to the DKA group. One week after recovery, cognitive function was tested using the Morris Water Maze, a procedure that requires rats to locate a hidden platform in a water pool using visual cues. During a 10 day period, mean time to locate the platform (latency) during 4 trials per day was recorded. Results Comparison of latency curves demonstrated longer mean latency times on days 7 and 8 in the DKA group indicating delayed learning compared to diabetic controls. Conclusions These data demonstrate that a single DKA episode results in measurable deficits in learning in rats, consistent with findings that DKA may contribute to neurocognitive deficits in children with type 1 diabetes.

Glaser, Nicole; Anderson, Steve; Leong, Wesley; Tancredi, Daniel; O'Donnell, Martha

2012-01-01

310

Intervention of D-glucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat  

SciTech Connect

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.

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

311

Altered microRNA expression profiles in retinas with diabetic retinopathy.  

PubMed

Rats with streptozotocin (STZ)-induced diabetes were studied in order to identify abnormal microRNA (miRNA) expression profiles in diabetic retinopathy (DR) and to ascertain miRNAs associated with DR. Histopathologically, we observed characteristic features of DR in rats at 10 weeks after STZ injection. Investigation of miRNA expression profiles in the retinas of control and diabetic rats using miRNA microarrays revealed that many miRNAs were abnormally expressed in DR. On the basis of their fold changes and probability values, a total of 37 miRNAs were selected for further validation by real-time PCR analysis. The results showed that 11 miRNAs were significantly upregulated and 6 miRNAs were notably downregulated in DR. Furthermore, these changes in retinal miRNA expression levels paralleled the course of DR. Levels of miR-182, miR-96, miR-183, miR-211, miR-204, and miR-124 were significantly increased during the progress of DR, whereas miR-10b, miR-10a, miR-219-2-3p, miR-144, miR-338, and miR-199a-3p were significantly decreased. Our data indicate that the aberrant miRNA expression profiles in DR are associated with the development of DR. Modulation of retinal miRNA expression levels may provide a potential therapeutic strategy for DRs. PMID:22156553

Wu, Jin-hui; Gao, Yu; Ren, An-jing; Zhao, Shi-hong; Zhong, Ming; Peng, Ya-jun; Shen, Wei; Jing, Ming; Liu, Lin

2011-12-07

312

Cardioprotective Effect of Sodium Ferulate in Diabetic Rats  

PubMed Central

Reactive oxygen species (ROS) play important roles in the occurrence and development in diabetic cardiomyopathy (DC). Ferulic acid is one of the ubiquitous compounds in diet. Sodium ferulate (SF) is its sodium salt. SF has potent free radical scavenging activity and can effectively scavenge ROS. The study investigated the effect of SF on cardioprotection in diabetic rats. The diabetic rats induced by streptozotocin (STZ) were treated with SF (110mg/kg) by gavage per day for 12 weeks. Results showed that the levels of nitric oxide (NO) and superoxide dismutase (SOD) activity in plasma and myocardium in SF-treated group were significantly higher than those in diabetic control group. The levels of malondialdehyde (MDA) in plasma and myocardium in SF-treated group were significantly lower than those in diabetic control group. Expression of connective tissue growth factor (CTGF) in myocardium in SF-treated group was apparently lower than that in diabetic control group. Compared with normal control group, electron micrographs of myocardium in diabetic control group showed apparently abnormality, while that was significantly ameliorated in SF-treated group. The study demonstrated that SF has a cardioprotective effect via increasing SOD activity and NO levels in plasma and myocardium, inhibiting oxidative stress in plasma and myocardium, and inhibiting the expression of CTGF in myocardium in diabetes rats.

Xu, Xiaohong; Xiao, Haijuan; Zhao, Jiangpei; Zhao, Tongfeng

2012-01-01

313

Anti-diabetic activity of Bauhinia forficata decoction in streptozotocin-diabetic rats.  

PubMed

The effects of using Bauhinia forficata leaf decoction (150 g leaf/l water; 35.2+/-7.8 ml/100 g body weight mean daily dose) as a drinking-water substitute for about 1 month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats were investigated. The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum triglycerides and cholesterol, plasma glucose, urinary glucose and urea, and the weight of epididymal and retroperitoneal adipose tissue and soleus and extensor digitorum longus muscles. The STZ-diabetic rats treated with decoction showed a significant reduction in serum and urinary glucose and urinary urea as compared to the STZ-diabetic control, no difference being seen between decoction-treated and -untreated non-diabetic rats. The other physico-metabolic factors showed no changes in treated STZ-diabetic rats. The improvement in carbohydrate metabolism seen in the rats treated with Bauhinia forficata decoction does not appear to be linked to the inhibition of glycogenolysis or the stimulation of glycogenesis nor does it appear to act in a way similar to insulin or the sulfonylureas, although it may act by the inhibition of neoglycogenesis in a manner similar to that of the biguanides. PMID:12065150

Pepato, M T; Keller, E H; Baviera, A M; Kettelhut, I C; Vendramini, R C; Brunetti, I L

2002-07-01

314

Diabetes mellitus in sand rats (Psammomys obesus). Metabolic pattern during development of the diabetic syndrome.  

PubMed

It has been reported that sand rats, naturally feeding on low-caloric-value plants containing a high concentration of salt, become obese and develop hyperglycemia when fed on a standard laboratory diet. The aim of this study was to examine the long-term effects of a synthetic-chow diet on the metabolic pattern of the diabetic syndrome in a large group of sand rats. While a few animals had a fulminant reaction with markedly decreased glucose tolerance, low plasma insulin levels, and death within 3-4 wk, most sand rats developed obesity and elevated plasma insulin levels. From the third month and forward, 40% of sand rats presented with a diabetic syndrome with hyperinsulinemia, hyperglycemia, markedly decreased glucose tolerance, and insulin resistance. This diabetic syndrome can be compared with maturity-onset (type II) diabetes. When this synthetic-chow diet was given for more than 6 mo, the majority of animals lost considerable weight and showed a major depletion of fat stores. Serum immunoreactive insulin levels fell, while blood glucose rose to above 500 mg/dl with glycosuria and ketonuria. The elevated triglyceride content of plasma and the lipid deposits in the liver were greatly augmented, and no glycogen was present. Animals developed frank insulin-dependent diabetes, and diabetic animals not treated with insulin died in diabetic coma with presumed ketoacidosis. The disease was essentially confined to sand rats showing abnormal glucose tolerance, even before eating laboratory chow. This observation suggests a genetic factor. Thus, the sand rat appears to be a potentially interesting model for investigation of both maturity-onset and insulin-dependent diabetes. PMID:6373452

Marquié, G; Duhault, J; Jacotot, B

1984-05-01

315

Carvacrol attenuates diabetes-associated cognitive deficits in rats.  

PubMed

Carvacrol (CAR), a naturally occurring phenolic monoterpene, has been demonstrated to possess various biological actions. The present study was designed to investigate the neuroprotective effect of CAR on diabetes-associated cognitive deficit (DACD) in a rat model of diabetes and exploring its potential molecular mechanism. Diabetic rats were treated with CAR by the doses of 25, 50, and 100 mg/kg for 7 weeks. Morris water maze was used for behavioral evaluation of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of oxidative stress (MDA, SOD, and GSH), NF-?B p65 unit, TNF-?, IL-1?, and caspase-3. After 7 weeks of streptozotocin injection, the rats produced remarkable increase in escape latency, coupled with increased oxidative stress (increased MDA level and decreased SOD as well as reduced GSH), NF-?B p65 unit, TNF-?, IL-1?, and caspase-3 in different regions of diabetic rat brain. Interestingly, coadministration of CAR significantly and dose-dependently prevented behavioral, biochemical, and molecular changes associated with diabetes. In summary, our findings provide the first evidence that CAR can remarkably attenuate DACD and suggest the involvement of oxidative stress, inflammation, and apoptotic cascades in the development of cognitive impairment caused by diabetes. The pharmacological effect of CAR suggests that it may be used as a promising agent for the treatment of conventional antihyperglycemic regiments as well as DACD. PMID:23877802

Deng, Wenjing; Lu, Hong; Teng, Junfang

2013-07-23

316

Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity  

SciTech Connect

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.

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

317

Chlorogenic acid decreases retinal vascular hyperpermeability in diabetic rat model.  

PubMed

To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively. Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran. Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis. Expression of tight junction proteins, occludin and claudin-5, and zonula occludens protein, ZO-1 was also evaluated with immunohistochemistry and Western blot analysis. BRB breakdown and increased vascular leakage was found in diabetic rats, with increased VEGF expression and down-regulation of occludin, claudin-5, and ZO-1. CGA treatment effectively preserved the expression of occludin, and decreased VEGF levels, leading to less BRB breakdown and less vascular leakage. CGA may have a preventive role in BRB breakdown in diabetic retinopathy by preserving tight junction protein levels and low VEGF levels. PMID:23579598

Shin, Joo Young; Sohn, Joonhong; Park, Kyu Hyung

2013-03-27

318

Chlorogenic Acid Decreases Retinal Vascular Hyperpermeability in Diabetic Rat Model  

PubMed Central

To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively. Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran. Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis. Expression of tight junction proteins, occludin and claudin-5, and zonula occludens protein, ZO-1 was also evaluated with immunohistochemistry and Western blot analysis. BRB breakdown and increased vascular leakage was found in diabetic rats, with increased VEGF expression and down-regulation of occludin, claudin-5, and ZO-1. CGA treatment effectively preserved the expression of occludin, and decreased VEGF levels, leading to less BRB breakdown and less vascular leakage. CGA may have a preventive role in BRB breakdown in diabetic retinopathy by preserving tight junction protein levels and low VEGF levels.

Shin, Joo Young; Sohn, Joonhong

2013-01-01

319

Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment  

Microsoft Academic Search

Streptozotocin-diabetic rats express deficits in water maze learning and hippocampal synaptic plasticity. The present study examined whether these deficits could be prevented and\\/or reversed with insulin treatment. In addition, the water maze learning deficit in diabetic rats was further characterized. Insulin treatment was commenced at the onset of diabetes in a prevention experiment, and 10 weeks after diabetes induction in

Geert-Jan Biessels; Amer Kamal; Ivan J. A Urban; Berrie M Spruijt; D. Willem Erkelens; Willem Hendrik Gispen

1998-01-01

320

Troglitazone (CS045) ameliorates albuminuria in streptozotocin-induced diabetic rats  

Microsoft Academic Search

We studied the effect of troglitazone, a new oral antidiabetic agent that potentiates insulin action and reduces insulin resistance, on albuminuria in streptozotocin (STZ)-treated diabetic rats. Without affecting blood glucose level, blood pressure, and creatinine clearance, troglitazone treatment of diabetic rats significantly decreased the diabetes-associated albuminuria at all time points studied (4 to 12 weeks of treatment: diabetic 510 ±

Mitsuhiro Fujii; Reiji Takemura; Makiko Yamaguchi; Goji Hasegawa; Hirofumi Shigeta; Koji Nakano; Motoharu Kondo

1997-01-01

321

Effect of carnosine on erythrocyte deformability in diabetic rats.  

PubMed

It is known that oxidative stress plays an important role in the chronic complications of diabetes. Lipid peroxidation is one of the consequences of oxidative stress. Erythrocyte deformability abilities are reduced as a result of lipid peroxidation. Conversely, a decrease nitric oxide (NO) production seems to be responsible in endothelial dysfunction which occurs in diabetic vascular complications. Carnosine is a molecule with anti-oxidant properties. The aim of this study was to investigate erythrocyte deformability indices and the effects of carnosine on erythrocyte deformability in diabetes and to determine a possible relationship between carnosine and nitric oxide. Male Wistar albino rats were used in the study. Injections were administered to seven groups consisting of eight rats each. The groups were: Control, Carnosine, L-NAME (NG-nitro-L-arginine methyl ester), Diabetic, STZ (Streptozotocin) +Carnosine, STZ+L-NAME and STZ+Carnosine+L-NAME. In addition, glucose, insulin, MDA (Malondialdehyde) and NO levels were measured and erythrocyte deformability indices were calculated in all groups. Erythrocyte deformability indices and NO levels were decreased and MDA levels were found to be increased in diabetic group. It was also found that carnosine can significantly reverse erythrocyte deformability, reduce lipid peroxidation and increase NO levels in diabetes. It can be concluded that carnosine can recover from microvascular circulation problems by increasing erythrocyte deformability, can protect cells and tissues against lipid peroxidation and can be used as a multi-functional anti-oxidant in the treatment of diabetes mellitus to prevent the complications of diabetes. PMID:22946660

Yapislar, Hande; Aydogan, Sami

2012-09-05

322

Comparison of metabolic and neuropathy profiles of rats with streptozotocin-induced overt and moderate insulinopenia  

PubMed Central

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.

Romanovsky, Dmitry; Wang, Jing; Al-Chaer, Elie D.; Stimers, Joseph R.; Dobretsov, Maxim

2010-01-01

323

Increased production of active ghrelin is relevant to hyperphagia in nonobese spontaneously diabetic Torii rats  

Microsoft Academic Search

An abnormal eating behavior is often associated with diabetes mellitus in individuals. In the present study, we investigated the mechanisms underlying the relationship among uncontrolled diabetes, food intake, and the production of ghrelin, an orexigenic hormone, in spontaneous diabetic Torii (SDT) rats. Male SDT rats and age-matched control Sprague-Dawley (SD) rats were housed from 8 to 38 weeks of age.

Hiroharu Mifune; Yoshihiro Nishi; Yuji Tajiri; Taku Masuyama; Hiroshi Hosoda; Kenji Kangawa; Masayasu Kojima

324

Influence of an anti-diabetic foot ulcer formula and its component herbs on tissue and systemic glucose homeostasis.  

PubMed

Complications of diabetes impose major public health burdens worldwide. The positive effect of a Radix Astragali-based herbal preparation on healing diabetic foot ulcers in patients has been reported. Formula 1 is also referred as the 'Herbal drink to strengthen muscle and control swelling'. This formula contains six Chinese medical herbs, including Radix Astragali, Radix Rehmanniae, Rhizoma Smilacis Chinensis, Rhizoma Atractylodis Macrocephalae, Radix Polygoni Multiflori Preparata, and Radix Stephania Tetrandrae. Three of these herbs (Radix Astragali, Radix Rehmanniae, Rhizoma Atractylodis Macrocephalae) are commonly used in different anti-diabetic formulae of Chinese medicine. The objective of the current study is to use an interdisciplinary approach to test the hypothesis that Formula 1 and its components influence tissue and systemic glucose homeostasis. In vitro and in vivo models have been established including: (1) glucose absorption into intestinal brush border membrane vesicles (BBMV); (2) gluconeogenesis by H4IIE hepatoma cells; (3) glucose uptake by 3T3-L1 adipocytes and Hs68 skin fibroblasts; (4) normalization of glycaemic control in a diabetic rat model. The results of in vitro studies indicated that all herbal extracts can modify cellular glucose homeostasis. Since Formula 1 and Rhizoma Smilacis Chinensis extracts demonstrated potent effects on modifying glucose homeostasis in multiple tissues in vitro, they were further studied for their anti-diabetic activities in vivo using a streptozotocin (STZ)-induced diabetic rat model. The results showed that Formula 1 and Rhizoma Smilacis Chinensis extracts did not significantly improve oral glucose tolerance or basal glycaemia in diabetic rats. In conclusion, the anti-diabetic foot ulcer Formula 1 contains ingredients active in modifying tissue glucose homeostasis in vitro but these biological activities could not be associated with improved glycaemic control of diabetes in vivo. PMID:16891069

Chan, C M; Chan, Y W; Lau, C H; Lau, T W; Lau, K M; Lam, F C; Che, C T; Leung, P C; Fung, K P; Lau, C B S; Ho, Y Y

2006-06-27

325

Effect of bis[curcumino]oxovanadium complex on non-diabetic and streptozotocin-induced diabetic rats  

Microsoft Academic Search

The effect of the vanadium complex bis[curcumino]oxovanadium (BCOV) on blood glucose level, serum lipid levels, blood pressure and vascular reactivity were studied in non-diabetic and streptozotocin-induced diabetic (STZ-diabetic) rats and compared to that of vanadyl sulfate. Blood glucose level, serum lipid levels, and blood pressure were significantly increased in STZ-diabetic rats. Vascular reactivity to various agonists such as noradrenaline and

Jayesh B. Majithiya; R. Balaraman; Rajani Giridhar; Mange Ram Yadav

2005-01-01

326

Renoprotective effects of a selective estrogen receptor modulator, Raloxifene in an animal model of diabetic nephropathy  

PubMed Central

Background/Aims Our previous studies have shown that supplementation with 17-? estradiol (E2) from the onset of diabetes attenuates diabetic nephropathy. But, E2 is accompanied by feminizing effects as well as adverse side effects on other organs. The current study examined the renoprotective effects of a selective estrogen receptor modulator, raloxifene (RAL), in an experimental model of diabetic nephropathy. RAL activates estrogen receptors and estrogen receptor-mediated cellular events without the side effects of E2. Methods The study was performed in Sprague-Dawley non-diabetic (ND), streptozotocin (STZ)-induced diabetic (D) and STZ-induced diabetic+raloxifene (D+RAL) rats (n=6/group). Results After 12 weeks of treatment, D was associated with increased albumin excretion (UAE; ND, 4.2±0.4; ND, 41.3±9.0 mg/day), glomerulosclerosis (GSI; ND, 0.26±0.04; D, 1.86±0.80 AU), tubulointerstitial fibrosis (TIFI; ND, 0.37±0.05; D, 2.12±0.50 AU), increased collagen type I (CI; ND, 1.31±0.07; D, 4.65±0.09 ROD), collagen type IV (CIV; ND, 0.64±0.03; D, 1.37±0.11 ROD) and transforming growth factor beta protein expression (TGF-?; ND, 0.65±0.08; D, 1.25±0.10 ROD), increased density of CD68-positive cells (CD68; ND, 1.37±3.02; D, 29.2±1.74 cells/mm2) and increased plasma levels of interleukin-6 (IL-6; ND, 14.8±5.0; D, 51.3±14.0 pg/ml). Treatment with RAL partially or fully attenuated these processes (UAE, 21.0±5.0 mg/day; GSI, 0.40±0.06 AU; TIFI, 0.20±0.04 AU; CI, 2.55±0.49 ROD; CIV, 0.70±0.09 ROD; TGF-?, 0.91±0.08 ROD; CD68, 6.03±2.38 cells/mm2; IL-6, 31.2±5.0 pg/ml). Conclusions Our data indicate that treatment with RAL attenuates albuminuria and renal structural changes associated with diabetes.

Dixon, Alexis; Corinne, C. Wells; Singh, Sandhya; Babayan, Regina; Maric, Christine

2011-01-01

327

Pharmacodynamics and pharmacokinetics of the insulin-mimetic agent vanadyl acetylacetonate in non-diabetic and diabetic rats  

Microsoft Academic Search

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

Shuang-Qing Zhang; Xu-Ying Zhong; Wan-Liang Lu; Li Zheng; Xuan Zhang; Feng Sun; Gui-Ying Fu; Qiang Zhang

2005-01-01

328

Biochemical studies on the effect of medicinal plants gymnema and andrographis species on diabetes induced wistar rats  

Microsoft Academic Search

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

A. Roja Rani; K. Venkatesh; P. Chakrapani

2009-01-01

329

Morphological Changes of Gingiva in Streptozotocin Diabetic Rats  

PubMed Central

Gingivitis and periodontitis are chronic bacterial diseases of the underlying and surrounding tooth tissues. Diabetes mellitus is responsible for tooth deprivation both by decay and periodontal disease. The streptozotocin-induced diabetes results in a diabetic status in experimental animals similar to that observed in diabetes patients. The aim of the study was to investigate the relationship between the gingival lesions and the microangiopathy changes in streptozotocin-induced diabetes mellitus. Forty male Wistar rats were divided into two groups (control and experimental). Diabetes mellitus was induced by 45?mg/kg IV streptozotocin. The histological investigation of the marginal gingival and the relevant gingival papilla showed inflammation of the lamina propria and the squamous epithelium as well as marked thickness of the arteriole in the diabetic group, but no changes were observed in the control group. The results suggested a probable application of a routine gingival histological investigation in diabetic patients in order to control the progress of disease complications. It may be concluded that histological gingival investigation can be used as a routine assay for the control of the diabetic disease and prevention of its complications.

Tesseromatis, C.; Kotsiou, A.; Parara, H.; Vairaktaris, E.; Tsamouri, M.

2009-01-01

330

Changes in sodium concentration in cardiac myocytes from diabetic rats  

SciTech Connect

The effects of streptozotocin induced diabetes on rats were studied. The animals showed an increase in blood glucose concentration and a loss of weight from both the body and the heart. Loss of weight from the heart was less severe leading to an increased heart to body weight ratio. Study of element concentrations by x-ray microanalysis showed that there was an increase in intracellular Na concentration in cardiac myocytes from the diabetic animals, but no change in Mg. These results agree with studies which show changes in Na/K ATPase after the onset of diabetes.

Warley, A. (Division of Biochemistry, U.M.D.S., St. Thomas's Hospital Campus, London (England))

1991-03-01

331

Growth pattern switch of renal cells and expression of cell cycle related proteins at the early stage of diabetic nephropathy  

SciTech Connect

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}.

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

332

Ethanolic extract of Crinum asiaticum attenuates hyperglycemia-mediated oxidative stress and protects hepatocytes in alloxan induced experimental diabetic rats  

Microsoft Academic Search

The present study is to investigate the antioxidant activity in alloxan induced diabetic rats. The experimental rats were randomly divided into three groups: Group I: control; Group II: alloxan induced diabetic rats and Group III: alloxan induced diabetic rats were treated with ethanolic extract of Crinum asiaticum leaves (200mg\\/kg\\/bw). Diabetes mellitus was induced by alloxan in a single dose of

S. Indradevi; S. Ilavenil; B. Kaleeswaran; S. Srigopalram; S. Ravikumar

333

Podocyte injury promotes progressive nephropathy in zucker diabetic fatty rats.  

PubMed

The zucker diabetic fatty (ZDF-fa/fa) rat is one of the attractive models for type II diabetes based on impaired glucose tolerance caused by the inherited insulin-resistance gene fa. Characterization of nephropathy in this model may provide useful insights into the mechanism of the progression of diabetic nephropathy. The present study analyzed the pathophysiology of diabetes and nephropathy, including the process of glomerulosclerosis in this model by biochemical and morphometric analyses. In addition, we conducted studies in podocytes in culture to examine the direct effects of high glucose on podocytes. ZDF-fa/fa rats showed overt diabetes despite hyperinsulinemia as early as 3 months of age. Blood glucose levels increased further with a considerable decrease of insulin levels at 5 months. Glomerular filtration rate (GFR) was significantly elevated until 3 months, but fell to the level seen in lean rats by 7 months. Proteinuria started to rise during the period of increased GFR, and increased further after GFR had fallen to within the normal range. Renal fibronectin, collagen iv, and vascular endothelial growth factor mRNA levels were increased at 7 months. Glomerulosclerosis commenced as early as 5 months of age, and was associated with glomerular hypertrophy and mild mesangial expansion with evidence of accentuated podocyte injury, as revealed by increased expression of desmin. Electron microscopy suggested that degeneration of podocytes and the development of tuft adhesions were responsible for the glomerular sclerosis in this model. In addition, glomeruli from the diabetic rats showed up-regulation of the cyclin kinase inhibitors, p21 and p27. Further studies suggested that the increase in p27 expression was predominantly caused by podocytes, because predominant immunolocalization of p27 in podocytes in diabetic rats and high glucose medium induced cell hypertrophy accompanied by p27 up-regulation in differentiated podocyte cell lines. In conclusion, progressive diabetic nephropathy in ZDF-fa/fa rats is associated with evidence of podocyte injury. High concentrations of ambient glucose induced podocyte hypertrophy and stress in vitro, suggesting that the podocyte is a likely target of the diabetic milieu. PMID:11796823

Hoshi, Sachi; Shu, Yujing; Yoshida, Fusayo; Inagaki, Tomoko; Sonoda, Jiro; Watanabe, Teruo; Nomoto, Ken-ichi; Nagata, Michio

2002-01-01

334

Pentagastrin-Induced Gastric Acid Secretion in the Diabetic Rats: Role of Insulin  

Microsoft Academic Search

Streptozotocin-induced diabetic rats have excessively pentagastrin-simulated acid output in which insulin seems to attenuate rather than further stimulate acid output. The aim of this study was to determine the insulin impact on pentagastrin-stimulated acid output of diabetic and non-diabetic rats to resolve whether an attenuated effect does exist. Diabetic rats were induced by the streptozotocin i.v. injection four days before

Full-Young Chang; Tseng-Shing Chena; Shou-Dong Lee; Ming-Luen Doong; Guey-Hwa Yeh; Paulus S. Wang

335

Pharmacometabonomic phenotyping reveals different responses to xenobiotic intervention in rats.  

PubMed

In conventional pharmacological studies, intersubject differences within an animal strain are normally neglected, leading to variations in pharmacological outcomes in response to the same stimulus. Using two classical experimental models, the Streptozotocin (STZ)-induced diabetic model of Wistar rats and the high-energy, diet-induced obesity model of Sprague-Dawley rats, we demonstrate that the different outcomes of STZ or diet intervention are closely associated with variation in predose (baseline) urinary metabolic profiles of the rats. The pharmacometabonomic analysis of predose metabolic profiles indicates that the intersubject difference is, to a great extent, associated with gut-microbiota, which predisposes different pathophysiological outcomes upon diet alteration or chemical stimulus. We hypothesize that there may exist an important association between observations from these two models and the obese/diabetic human population in that subtle variations in metabolic phenotype may predetermine different systems' responses to xenobiotic perturbation, ultimately leading to varied pathophysiological processes. Results from two independent models also suggest that the pharmacometabonomics approach is of great importance in the study of pharmacology and clinical drug evaluations, where endogenous metabolite signatures of predose individuals should be taken into consideration to minimize intersubject difference and the resulting variation in the postdose pharmacological outcomes. PMID:17311441

Li, Houkai; Ni, Yan; Su, Mingming; Qiu, Yunping; Zhou, Mingmei; Qiu, Mingfeng; Zhao, Aihua; Zhao, Liping; Jia, Wei

2007-02-21

336

Alterations of the Renal Handling of H+ in Diabetic Rats  

Microsoft Academic Search

Renal acid excretion and proximal and distal nephron acidification were evaluated 20 days after induction of diabetes, in rats, by intraperitoneal injection of streptozotocin (45 mg\\/kg). Titratable acidity in urine was measured by microtitration and ammonium excretion (NH+4) by spectrophotometry. Proximal tubular acidification was evaluated by the kinetics of reabsorption of perfused HCO-3 Distal nephron acidification was evaluated by measuring

Guiomar Nascimento-Gomes; Frida Zaladek Gil; Margarida Mello-Aires

1997-01-01

337

Persistence of Inflammatory Response to Intense Exercise in Diabetic Rats  

PubMed Central

In this study we evaluated the onset and resolution of inflammation in control and streptozotocin-induced diabetic rats subjected to a single session of intense exercise. The following measurements were carried out prior to, immediately after, and 2 and 24 hours after exercise: plasma levels of proinflammatory cytokines (TNF-?, IL-1?, IL-6, CINC-2?/?, MIP-3?, and IL-6), immunoglobulins (IgA and IgM), acute phase proteins (CRP and C3), and creatine kinase (CK) activity. We also examined the occurrence of macrophage death by measurements of macrophages necrosis (loss of membrane integrity) and DNA fragmentation. An increase was observed in the concentration of IL-1? (3.3-fold) and TNF-? (2.0-fold) and in the proportion of necrotic macrophages (4.5-fold) in diabetic rats 24 hours after exercise, while the control group showed basal measurements. Twenty-four hours after the exercise, serum CK activity was elevated in diabetic rats but not in control animals. We concluded that lesion and inflammations resulting from intense exercise were greater and lasted longer in diabetic animals than in nondiabetic control rats.

Bortolon, Jose Ricardo; Silva Junior, Antonio Jose de Almeida; Murata, Gilson Masahiro; Newsholme, Philip; Curi, Rui; Pithon-Curi, Tania Cristina; Hatanaka, Elaine

2012-01-01

338

Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats.  

PubMed

Momordica charantia L. (MC) (Cucurbitaceae) commonly known as balsam pear, bitter gourd or karela, used in several purposes in traditional medicine is an important medicinal plant. Two sets of experiments were carried out, the first experiment indicated that the LD(50) for MC juice and alcoholic extracts were 91.9 and 362.34 mg/100g b.wt., respectively, of subcutaneously "s.c." injected mice. The toxic signs were recorded within the first 24 h post-injection. The second experiment was performed to evaluate the effect of MC juice and alcoholic extracts on blood glucose and other biochemical parameters in normal and diabetic rats. Both extracts induced a significant decrease in serum glucose levels in normal and diabetic rats. The two extracts did not show any significant effect in urea, creatinine, ALT, AST and AP in normal rat, while in diabetic rats the two extracts caused a significant decrease in serum urea, creatinine, ALT, AST, AP, cholesterol and triglyceride levels. Also, these results suggested that MC extracts possesses anti-diabetic, hepato-renal protective and hypolipidemic effect in alloxan-induced diabetic rats. Thus, MC is alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. PMID:16815658

Abd El Sattar El Batran, Seham; El-Gengaihi, Souad E; El Shabrawy, Osama A

2006-05-26

339

Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury  

SciTech Connect

Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

Zhong Qing; Terlecky, Stanley R. [Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201 (United States); Lash, Lawrence H., E-mail: l.h.lash@wayne.ed [Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201 (United States)

2009-11-15

340

Increase of cardiac M2-muscarinic receptor gene expression in type-1 but not in type-2 diabetic rats.  

PubMed

Changes of cardiac M2-muscarinic receptor (M2-mAChR) gene expression was investigated in type-1 like diabetic rats induced by intravenous injection of streptozotocin (STZ) and type-2 like diabetic rats induced by fed with fructose-rich chow. Systolic blood pressure (SBP) in STZ-diabetic rats was significantly lower than that in age-matched non-diabetic rats, while the SBP in type-2 like diabetic rats was higher than in non-diabetic rats. Also, the mRNA or protein level of cardiac M2-mAChR in STZ-diabetic rats was markedly higher than non-diabetic rats, but it was not observed in type-2 like diabetic rats as compared to age-matched non-diabetic rats. Arecaidine propargyl ester (APE), the agonist of M2-mAChR, produced a marked reduction of heart rate in STZ-diabetic rats but made less influence on heart rate in fructose-fed rats or non-diabetic rats. The results suggest that cardiac M2-mAChR gene expression is raised in type-1 like diabetic rats but not in type-2 like diabetic rats, this difference mainly due to hyperglycemia, for the production of hypotension in diabetic disorders. PMID:18603373

Lee, Liang-Ming; Chang, Cheng Kuei; Cheng, Kai-Chun; Kou, Dai-Huang; Liu, I-Min; Cheng, Juei-Tang

2008-06-05

341

Altered fatty acid desaturation and microsomal fatty acid composition in the streptozotocin diabetic rat  

Microsoft Academic Search

Streptozotocin diabetes in the rat diminishes the synthesis of both monounsaturated and polyunsaturated fatty acids. Rat liver\\u000a microsomal fatty acid composition and fatty acid desaturation were studied in the streptozotocin diabetic rat. The major alterations\\u000a in fatty acid composition found in the diabetic rat were decreased proportions of palmitoleic, oleic and arachidonic acids\\u000a and an increased proportion of linoleic and

Fred H. Faas; William J. Carter

1980-01-01

342

Stereological study of the diabetic heart of male rats  

PubMed Central

The present study aimed to quantitatively compare the normal and diabetic hearts of rats using stereological methods. Diabetic and control rats received streptozotocin (60 mg/kg) and no treatments, respectively. On the 56th day, the hearts were removed and their total volume was estimated using isotropic Cavalieri method. The total volume of the connective tissues and vessels, total length and diameter of the vessels, total number of cardiomyocytes nuclei, and the mean volume of the cardiomyocytes were estimated, as well. In comparison to the control animals, 60 and 43% increase was observed in the total volume of the connective tissue and microvessels of the diabetic rats, respectively (P<0.05). The percent of the vessel profiles with the diameter of 2-4 µm was decreased, while the percent of the vessel profiles with the diameter of 4.1-8 µm was increased in the diabetic hearts (P<0.05). No significant difference was found in the vessels with more than 8 µm diameters. The total number of the cardiomyocytes' nuclei and the number-weighted mean volume were respectively decreased by 37 and 64% in the diabetic group (P<0.01). A significant difference was observed between the two groups concerning the left ventricle volume to body weight ratio as an index for ventricular hypertrophy (P<0.05), while no difference was found regarding the right ventricle to body weight ratio. It can be concluded that diabetes can induce structural changes, including loss and/or atrophy of the cardiomyocytes, accompanied with increase in the connective tissue in the rats' hearts.

Noorafshan, Ali; Khazraei, Hajar; Mirkhani, Hossein

2013-01-01

343

Cilostazol minimizes venous ischemic injury in diabetic and normal rats  

PubMed Central

We evaluated the effects of cilostazol on venous infarction produced by a photothrombotic two-vein occlusion (2VO) model in diabetic and control rats. The cerebral blood flow (CBF) between the occluded veins was measured by laser Doppler flowmetry for 4?hours after 2VO. Infarct size and immunohistochemistry were evaluated 24, 48, 96, and 168?hours after 2VO. Cilostazol was administered 1?hour after 2VO, and thereafter at a continuous oral dose of 60?mg/kg per day. Cilostazol reduced the infarct size, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic and B-cell lymphoma 2-associated X protein (Bax)-positive cells, and improved the CBF in control rats. In diabetic rats, cilostazol reduced the infarct size, and the number of TUNEL-positive apoptotic and Bax-positive cells, 96 and 168?hours after 2VO, but did not improve the CBF 4?hours after 2VO. Cilostazol increased the number of B-cell lymphoma 2 (Bcl-2)-positive cells in both strains 48, 96, and 168?hours after 2VO, but did not improve vessel wall thickness or collagen deposits. Cilostazol appeared to limit venous infarcts by improving the penumbral CBF in nondiabetic rats, and inhibited pro-apoptotic changes through Bcl-2 overexpression, without improving the CBF in diabetic rats.

Wajima, Daisuke; Nakamura, Mitsutoshi; Horiuchi, Kaoru; Takeshima, Yasuhiro; Nishimura, Fumihiko; Nakase, Hiroyuki

2011-01-01

344

Effect of Biophytum sensitivum on streptozotocin and nicotinamide-induced diabetic rats  

PubMed Central

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.

Ananda, Prabu K; Kumarappan, CT; Sunil, Christudas; Kalaichelvan, VK

2012-01-01

345

Protection by vanadium, a contemporary treatment approach to both diabetes and focal cerebral ischemia in rats.  

PubMed

There is now substantial epidemiological evidence that diabetes is a risk factor for cerebrovascular disease. The protection by vanadium from focal cerebral ischemia in diabetic rats was studied in this paper. Rats with streptozotocin-induced diabetes were subjected to middle cerebral artery occlusion followed by 4 weeks of administration of 0.6 mg/ml sodium orthovanadate in drinking water. Vanadium significantly improved the outcome in diabetic rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. Vanadium reduces brain damage in streptozotocin-induced diabetic rats by imitating action of insulin. PMID:21833647

Liu, Zhenquan; Li, Pengtao; Zhao, Dan; Tang, Huiling; Guo, Jianyou

2011-08-11

346

A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats  

Microsoft Academic Search

Fasudil, a Rho-kinase inhibitor, may improve insulin signaling. However, its long-term effect on metabolic abnormalities and its preventive effect on diabetic nephropathy are still unknown. We assessed these effects of fasudil in insulin-resistant diabetic rats, comparing them with those of an angiotensin II receptor blocker, olmesartan. Male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka, non- diabetic control, rats

Yuichi Kikuchi; Muneharu Yamada; Toshihiko Imakiire; Taketoshi Kushiyama; Keishi Higashi; Naomi Hyodo; Kojiro Yamamoto; Takashi Oda; Shigenobu Suzuki; Soichiro Miura

2007-01-01

347

Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic fatty rats  

PubMed Central

The mulberry plant (Morus alba L.) contains abundant anthocyanins (ANCs), which are natural antioxidants. The aim of this study was to determine the ANC composition of Thai Morus alba L. fruits and to assess the effect of an ANC extract on blood glucose and insulin levels in male leptin receptor-deficient Zucker diabetic fatty (ZDF) rats. The major components of the ANC extract were identified by high-performance liquid chromatography-electrospray ionization-mass spectrometry. ZDF and lean rats were treated with 125 or 250 mg ANCs/kg body weight, or 1% carboxymethylcellulose (CMC) twice daily for 5 weeks. Neither ANC dose had an effect on body weight. Following 5 weeks of treatment, glucose levels were observed to increase from 105.5±8.7 to 396.25±21 mg/dl (P<0.0001) in the CMC-treated ZDF rats; however, the glucose levels were significantly lower in the rats treated with 125 or 250 mg/kg ANCs (228.25±45 and 131.75±10 mg/dl, respectively; P<0.001 versus CMC). The administration of 250 mg/kg ANCs normalized glucose levels in the ZDF rats towards those of the lean littermates. Insulin levels were decreased significantly in the ZDF rats treated with CMC or 125 mg/kg ANCs (P<0.0001), but not in the rats treated with 250 mg/kg ANCs. Histologically, 250 mg/kg ANCs was observed to prevent islet degeneration compared with the islets in CMC-treated rats. This study, demonstrated that ANCs extracted from Morus alba L. were well tolerated and exhibited effective anti-diabetic properties in ZDF rats. ANCs represent a promising class of therapeutic compounds that may be useful in the prevention of type 2 diabetes.

SARIKAPHUTI, ARIYA; NARARATWANCHAI, THAMTHIWAT; HASHIGUCHI, TERUTO; ITO, TAKASHI; THAWORANUNTA, SITA; KIKUCHI, KIYOSHI; OYAMA, YOKO; MARUYAMA, IKURO; TANCHAROEN, SALUNYA

2013-01-01

348

Intense exercise training induces adaptation in expression and responsiveness of cardiac ?-adrenoceptors in diabetic rats  

Microsoft Academic Search

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.

Solène Le Douairon Lahaye; Arlette Gratas-Delamarche; Ludivine Malardé; Sophie Vincent; Mohamed Sami Zguira; Sophie Lemoine Morel; Paul Delamarche; Hassane Zouhal; François Carré; Françoise Rannou Bekono

2010-01-01

349

Genetic and environmental influence on diabetic rat embryopathy.  

PubMed

We assessed genetic and environmental influence on fetal outcome in diabetic rat pregnancy. Crossing normal (N) and manifestly diabetic (MD) Wistar Furth (W) and Sprague-Dawley (L) females with W or L males yielded four different fetal genotypes (WW, LL, WL, and LW) in N or MD rat pregnancies for studies. We also evaluated fetal outcome in litters with enhanced or diminished severity of maternal MD state, denoted MD(+)WL and MD(-)LW. The MDWW litters had less malformations and resorptions (0 and 19%) than the MDLL litters (17 and 30%). The MDWL litters (0 and 8%) were less maldeveloped than the MDLW litters (9 and 22%), whereas the MD(+)WL (3 and 23%) and MD(-)LW (1 and 17%) litters showed increased and decreased dysmorphogenesis (compared with MDWL and MDLW litters). The pregnant MDW rats had lower serum levels of glucose, fructosamine, and branched-chain amino acids than the pregnant MDL rats, whereas the pregnant MD(+)W and MD(-)L rats had levels comparable with those of the MDL and MDW rats, respectively. The 8-iso-PGF2? levels of the malformed MDLW offspring were increased compared with the nonmalformed MDLW offspring. Diabetes decreased fetal heart Ret and increased Bmp-4 gene expression in the MDLW offspring and caused decreased GDNF and Shh expression in the malformed fetal mandible of the MDLW offspring. We conclude that the fetal genome controls the embryonic dysmorphogenesis in diabetic pregnancy by instigating a threshold level for the teratological insult and that the maternal genome controls the teratogenic insult by (dys)regulating the maternal metabolism. PMID:21119026

Ejdesjö, A; Wentzel, P; Eriksson, U J

2010-11-30

350

Rhaponticin from rhubarb rhizomes alleviates liver steatosis and improves blood glucose and lipid profiles in KK/Ay diabetic mice.  

PubMed

We isolated several stilbene compounds including rhaponticin (3',5-dihydroxy-4'-methoxystilbene 3- O-beta- D-glucopyranoside) from extracts of rhubarb rhizomes. These compounds showed significant hypoglycemic effects in streptozotocin (STZ)-induced type 1 diabetic rats and mice. In this study, we investigated the effect of rhaponticin on glucose utilization, lipid metabolism, and liver and heart function in a KK/Ay type 2 diabetic mouse model. The results showed that oral administration of rhaponticin (125 mg/kg) significantly reduced blood glucose levels and improved oral glucose tolerance of KK/Ay diabetic mice. Elevated plasma triglyceride (TG), low density lipoprotein (LDL), cholesterol (CHO), non-esterified free fatty acids (NEFA), and insulin levels were also markedly attenuated. Serum enzymatic activities of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the rhaponticin-treated group significantly decreased in comparison to the untreated model group. Livers of rhaponticin-treated mice had relatively normal cellular size and decreased fibrosis and steatosis. In addition, rhaponticin administration caused a remarkable increase in the hepatic glycogen content and a significant reduction in the hepatic triglyceride content. These results indicate that rhaponticin has a noticeable antidiabetic effect and could be potentially used as a new agent to treat type 2 diabetes mellitus and its complications. PMID:19235684

Chen, Jinlong; Ma, Mengmeng; Lu, Yanwei; Wang, Lisheng; Wu, Chutse; Duan, Haifeng

2009-02-23

351

Effect of human umbilical cord blood CD34+ progenitor cells transplantation in diabetic mice  

Microsoft Academic Search

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

Mona AbdElabry Hasein; Fadia Mostafa Attia; Mohamed Mohy Eldin Awad; Howedya Ahmed Abdelaal; Magady Elbarabary

352

Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension  

Microsoft Academic Search

Aims\\/hypothesis  Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by -tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar

F. Palm; J. Cederberg; P. Hansell; P. Liss; P.-O. Carlsson

2003-01-01

353

Protective effect of Cassia glauca Linn. on the serum glucose and hepatic enzymes level in streptozotocin induced NIDDM in rats  

PubMed Central

Objective: The objective of the present study was to investigate the hypoglycemic and hepatoprotective effect of Cassia glauca leaf extracts on normal and non insulin dependent diabetes mellitus (NIDDM) in rats. The study was further carried out to investigate the effect of different fractions of the active extract of Cassia glauca, on normal and NIDDM rats, and the effect of active fraction on the blood glucose and hepatic enzymes level. Methods: Diabetes was induced by streptozotocin (STZ) at a dose of 90mg/kg, i.p. in neonates. Different extracts of cassia glauca (100mg/kg, p.o.) were administered to the diabetic rats. Acetone extract was found to lower the serum glucose level significantly in diabetic rats. Further, the acetone extract was subjected to column chromatography and four fractions were obtained on the basis of TLC. All the four fractions (100mg/kg, p.o.) were administered to the diabetic rats. Fraction 1 (F1) caused the maximum reduction in the blood glucose level. The results of the test were compared with the standard antidiabetic drug glibenclamide (5mg/kg, p.o.). Results: Fraction 1 of acetone extract caused a significant reduction in the levels of hepatic enzyme Aspartate transaminase (AST), alanine transaminase (ALT), creatine kinase (CK), and lactate dehydrogenase (LDH) in STZ-induced diabetic rats. Conclusion: Improvement in the blood sugar level and normalization of liver functions by Cassia glauca indicates that the plant has hepatoprotective potential, along with antidiabetic activity, and it provides a scientific rationale for the use of Cassia glauca as an antidiabetic agent.

Farswan, Mamta; Mazumder, Papiya Mitra; Percha, V.

2009-01-01

354

The influence of dietary Cu and diabetes on tissue sup 67 Cu retention kinetics in rats  

SciTech Connect

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.

Uriu-Hare, J.Y.; Rucker, R.B.; Keen, C.L. (Univ. of California, Davis (United States))

1991-03-11

355

Metformin restores endothelial function in aorta of diabetic rats  

PubMed Central

BACKGROUND AND PURPOSE The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus. EXPERIMENTAL APPROACH Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high-fat diet during 4 months were treated with metformin for 4 weeks before evaluation. Systemic oxidative stress, endothelial function, insulin resistance, nitric oxide (NO) bioavailability, glycation and vascular oxidative stress were determined in the aortic rings of the different groups. A pro-inflammatory biomarker the chemokine CCL2 (monocyte chemoattractant protein-1) was also evaluated. KEY RESULTS High-fat fed GK rats with hyperlipidaemia showed increased vascular and systemic oxidative stress and impaired endothelial-dependent vasodilatation. Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta. CONCLUSION AND IMPLICATIONS Metformin restores endothelial function and significantly improves NO bioavailability, glycation and oxidative stress in normal and high-fat fed GK rats. This supports the concept of the central role of metformin as a first-line therapeutic to treat diabetic patients in order to protect against endothelial dysfunction associated with type 2 diabetes mellitus.

Sena, Cristina M; Matafome, Paulo; Louro, Teresa; Nunes, Elsa; Fernandes, Rosa; Seica, Raquel M

2011-01-01

356

Salutary Effect of Cassia auriculata L. Leaves on Hyperglycemia-Induced Atherosclerotic Environment in Streptozotocin Rats  

Microsoft Academic Search

Diabetes mellitus is very often associated with dyslipidemia, increased oxidative stress and endothelial dysfunction that\\u000a could develop atherosclerosis and consequently cardiovascular diseases. Medicinal plants with reputed traditional use to treat\\u000a diabetes and cardiovascular diseases