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1

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

PubMed Central

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

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

2014-01-01

2

Protective Effect of Agaricus brasiliensis on STZ-Induced Diabetic Neuropathic Pain in Rats  

PubMed Central

Objective. The present investigation examined the neuroprotective effect of Agaricus brasiliensis (AbS) against STZ-induced diabetic neuropathic pain in laboratory rats. STZ-induced diabetic rats were administered orally with AbS. Body weight, serum glucose, and behavioral parameters were measured before and at the end of the experiment to see the effect of AbS on these parameters. After 6 weeks of treatments, all animals were sacrificed to study various biochemical parameters. Treatment with AbS 80?mg/kg in diabetic animals showed significant increase in body weight, pain threshold, and paw withdrawal threshold and significant decrease in serum glucose, LPO and NO level, Na-K-ATPase level, and TNF-? and IL-1? level as compared to vehicle treated diabetic animals in dose and time dependent manner. AbS can offer pain relief in PDN. This may be of potential benefit in clinical practice for the management of diabetic neuropathy. PMID:24527050

Ji, Weifeng; Huang, Haiying; Chao, Ji; Lu, Wuchao; Guo, Jianyou

2014-01-01

3

Effect of arctiin on glomerular filtration barrier damage in STZ-induced diabetic nephropathy rats.  

PubMed

Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permeability of glomerular basement membrane plays an important role in DN pathogenesis. This study was performed to assess the effect of arctiin, the lignan constituent from Arctium lappa L., on metabolic profile and aggravation of renal lesions in a rat model of streptozotocin (STZ)-induced DN. STZ-induced diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via intraperitoneal injection for 8 weeks. Blood glucose and 24-h urinary albumin content were measured, and kidney histopathological changes were monitored. RT-PCR and immunohistochemistry were used to detect the mRNA and protein levels of nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats, respectively. Treatment with arctiin significantly decreased the levels of 24-h urinary albumin, prevented the sclerosis of glomeruli and effectively restored the glomerular filtration barrier damage by up-regulating the expression of nephrin and podocin and down-regulating HPSE level. Our studies suggest that arctiin might be beneficial for DN. The effects of arctiin on attenuating albuminuria and glomerulosclerosis are possibly mediated by regulating the expression of nephrin and podocin and HPSE in STZ-induced diabetic rats. PMID:23147865

Ma, Song-Tao; Liu, Dong-lian; Deng, Jing-jing; Niu, Rui; Liu, Rui-bin

2013-10-01

4

Antidiabetic and antihyperlipidemic activity of Piper longum root aqueous extract in STZ induced diabetic rats  

PubMed Central

Background The available drugs for diabetes, Insulin or Oral hypoglycemic agents have one or more side effects. Search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic and antihyperlipidemic effects of Piper longum root aqueous extract (PlrAqe) in streptozotocin (STZ) induced diabetic rats. Methods Diabetes was induced in male Wister albino rats by intraperitoneal administration of STZ (50 mg/kg.b.w). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The activities of liver and kidney functional markers were measured. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by DMRT. Results During the short term study the aqueous extract at a dosage of 200 mg/kg.b.w was found to possess significant antidiabetic activity after 6 h of the treatment. The administration of aqueous extract at the same dose for 30 days in STZ induced diabetic rats resulted in a significant decrease in FBG levels with the corrections of diabetic dyslipidemia compared to untreated diabetic rats. There was a significant decrease in the activities of liver and renal functional markers in diabetic treated rats compared to untreated diabetic rats indicating the protective role of the aqueous extract against liver and kidney damage and its non-toxic property. Conclusions From the above results it is concluded that the plant extract is capable of managing hyperglycemia and complications of diabetes in STZ induced diabetic rats. Hence this plant may be considered as one of the potential sources for the isolation of new oral anti hypoglycemic agent(s). PMID:23414307

2013-01-01

5

Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats.  

PubMed

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T(1) (AT(1)) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP. PMID:20446791

Kanter, Mehmet; Sen, Saniye; Donmez, Salim; Aktas, Cevat; Ustundag, Sedat; Erboga, Mustafa

2010-05-01

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. PMID:22301628

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. PMID:21792366

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

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

PubMed Central

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

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

2014-01-01

9

Effects of varying intensity exercise on shortening and intracellular calcium in ventricular myocytes from streptozotocin (STZ)-induced diabetic rats.  

PubMed

This study examined the influence of two intensities of exercise on ventricular myocyte shortening and intracellular calcium in the streptozotocin (STZ)-induced diabetic rat. Animals were divided into four groups: control sedentary (CS), diabetic sedentary (DS), diabetic light exercise (DLE; 5 x 30 min/week, 9 m/min) and diabetic moderate exercise (DME; 5 x 30 min/week, 18 m/min) and the exercise programme started 2 months after STZ treatment. Time to peak (TPK) shortening was prolonged in myocytes from DS (112.1 +/- 2.5 ms) compared to CS (98.1 +/- 2.1 ms) rats and was not additionally altered by either light (117.0 +/- 2.1 ms) or moderate (115.4 +/- 2.0 ms) exercise. TPK of the Ca(2+) transient was not significantly altered by STZ treatment (69.4 +/- 2.4 ms) but was prolonged by light (79.8 +/- 3.5 ms) and moderate (76.6 +/- 2.9 ms) exercise compared to CS (65.5 +/- 2.7 ms). Data from this study suggest that the chosen intensities of exercise were ineffective in modulating the dynamics of cardiac muscle contraction and reversing the deleterious effects of diabetes on heart-muscle contraction. PMID:18553174

Howarth, Frank Christopher; Almugaddum, F A; Qureshi, M A; Ljubisavljevic, M; Ljubisavijevic, M

2008-10-01

10

Effect of Urtica dioica L. (Urticaceae) on testicular tissue in STZ-induced diabetic rats.  

PubMed

Urtica dioica L. (Stinging nettle) has already been known for a long time as a medicinal plant in the world. This histopathological and morphometrical study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on testis of streptozotocin-induced diabetic rats. Eighteen male Wistar rats were allocated to equally normal, diabetic and treatment groups. Hyperglycemia was induced by Streptozotocin (80 mg kg(-1)) in animals of diabetic and treatment groups. One week after STZ injection (80 mg kg(-1)), the rats of treatment group received the extract of U. dioica (100 mg/kg/day) IP for 28 days. After 5 weeks of study, all the rats were sacrificed and testes were removed and fixed in bouin and after tissue processing stained with H and E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization and decrease in sperm concentration in seminiferous tubules were seen in diabetic and treatment groups group in comparison with control. External Seminiferous Tubular Diameter (STD) and Seminiferous Epithelial Height (SEH) significantly reduced (p < 0.05) in the diabetic rats compared with controls and these parameters in the treatment group were similar to diabetics animals. This study showed that hydroalcoholic extract of Urtica dioica leaves, after induction of diabetes; has no treatment effect on seminiferous tubules alterations in streptozotocin-induced diabetic rats. PMID:22545354

Ghafari, S; Balajadeh, B Kabiri; Golalipour, M J

2011-08-15

11

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

PubMed

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

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

2014-12-01

12

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

PubMed

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

Sato, K; Fujita, S; Iemitsu, M

2014-09-01

13

Effect of Pimpinellatirupatiensison Oxidative Enzymes in STZ-induced Diabetic Rat Kidney  

PubMed Central

The present study was aimed to evaluate the therapeutic potential of Pimpinellatirupatiensis(Pt) by assaying the activities of selective mitochondrial enzymes in streptozotocin induced diabetic rats. Diabetic rats showed a significant (p < 0.01) reduction in the activities of oxidative enzymes Succinate dehydrogenase (SDH), Malate dehydrogenase (MDH), Glutamate dehydrogenase (GDH) and isocitrate dehydrogenase (ICDH). Lactate dehydrogenase (LDH) activity was significantly (p < 0.01) increased in diabetic rats. The daily oral treatment of Pimpinellatirupatiensisethyl alcohol extract (750 mg/kg body weight/day) to diabetic rats for 30 days reversed the above changes in a significant (p < 0.01) manner. From our observations, we conclude that administration of Pt altered the activities of oxidative enzymes, thereby suggesting its role in mitochondrial energy production. The obtained results were compared with Glibenclamide, a standard anti diabetic drug. Thus, the modulatory effects of Pt on altering these enzymes activities afford a promise for widespread use for treatment of diabetes in the future. PMID:24250450

RajeswaraReddy, Saddala; Lavany, Thopireddy; Narasimhulu, Ganapathi; SathyaveluReddy, Kesireddy

2012-01-01

14

Methoxy VO–salen Stimulates Pancreatic ? Cell Survival by Upregulation of eNOS and Downregulation of Apoptosis in STZ-induced Diabetic Rats  

Microsoft Academic Search

The present study was designed to investigate the effect of MetVO–salen in ameliorating diabetes and oxidative stress in the\\u000a pancreas of diabetic rats. Streptozotocin (STZ)-induced diabetic rats were treated with MetVO–salen complex intraperitonially\\u000a (0.3 and 0.6 mg\\/kg) thrice a week and continued for 8 weeks. Total cholesterol, high-density lipoprotein (HDL) cholesterol,\\u000a triglycerides in serum, and blood glucose were estimated. Furthermore, oxidative stress

Souvik Roy; Anil Kumar Mondru; Sudheer Kumar Dontamalla; Ram Prasad Vaddepalli; Santanu Sannigrahi; Prabhakar Reddy Veerareddy

15

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

PubMed Central

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

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

2013-01-01

16

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

PubMed

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

Singh, Jyotsna; Kakkar, Poonam

2013-12-01

17

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

PubMed Central

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

2013-01-01

18

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

PubMed

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

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

2014-07-01

19

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. PMID:23691525

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

2013-01-01

20

Comparing the Effects of Ginger and Glibenclamide on Dihydroxybenzoic Metabolites Produced in Stz-Induced Diabetic Rats  

PubMed Central

Background: The aim of the present study was to investigate the effect of ginger and glibenclamide on oxidative stress markers. Oxidative stress is caused by an unbalance between a relative overload of oxidants and depletion of antioxidants, as implicated in the pathogenesis of several chronic diseases, including atherosclerosis and diabetes mellitus. Regarding the role of oxidative stress in the pathogenesis of diabetes mellitus, we investigated the effect of ginger and glibenclamide in diabetic rats induced bystreptozocin (STZ). Objectives: This study assessed the effects of ginger and glibenclamide on dihydroxybenzoic acid metabolites in diabetic rats. Materials and Methods: In this study 30 Wistar strain male rats were divided into five groups: Group 1: Normal control receiving normal saline (0.9 0/0), Group 2: control DMSO (Dimethyl sulfoxide) (as solvent of glibenclamide), Group 3: Diabetic control receiving Streptozocin (STZ ) (50 mg/kg) ,Group 4: diabetic+ Ginger Extract: this group received ginger ethanolic extract (200 mg/kg) via IP (Intraperitoneally) injection for 30 days, and Group 5 diabetic rats received glibenclamide (0.5 m/kg). Production of hydroxyl radicals was examined in the diabetic rats induced by streptozocin. Hydroxyl radicals were generated in plasma of the hyperglycemic rats, and were quantitatively assayed by trapping hydroxyl radicals with salicylic acid so as to produce 2,3-and 2,5-dihydroxybenzoic acid. Results: Production of hydroxyl radicals increased; therefore, by using salicylic acid, hydroxyl radicals were trapped and 2,3dihydroxybenzoic acid and 2,5dihydroxybenzoic acid metabolites were formed then measured by HPLC and spectrophotometer. Rats receiving ginger extract and glibenclamide showed decreased level of metabolites compared to the diabetic controls (P <0/001). This means that antioxidants act as scavenger of free radicals. Conclusions: Comparative effect of ginger and glibenclamide also showed that glibenclamide has antioxidant effect as a scavenger of free radical, but ginger is more capable of eliminating them. PMID:24719624

Ahmadi, Ramesh; Pishghadam, Saeede; Mollaamine, Fatemeh; Zand Monfared, Mohammad Reza

2013-01-01

21

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

2013-07-01

22

Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation  

PubMed Central

Background Diabetes in humans induces chronic complications such as cardiovascular damage, cataracts and retinopathy, nephropathy and polyneuropathy. The most common animal model of human diabetes is streptozotocin (STZ)-induced diabetes in the rat. The present study investigated the effects of Nigella sativa hydroalcholic extract on glucose concentrations in streptozotocin (STZ) diabetic rats. Methods In this study Twenty-five Wister-Albino rats (aged 8-9 weeks and weighing 200-250 g) were tested. Rats were divided into five experimental groups (control, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with hydroalcholic extract of Nigella Sativa (NS) (5 mg/kg B.W, IP), treated STZ-diabetic with hydroalcholic extract of NS (10 mg/kg B.W., IP) and treated STZ-diabetic with hydroalcholic extract of NS (20 mg/kg B.W., IP and 32 days were evaluated to assess its effect on fasting blood glucose (FBG), and in different groups fasting blood glucose (FBG) and body weight (BW) were measured in the particular days (1, 16 and 32). At the end of the study, the animals were fasted overnight, anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for obtaining tissues samples (liver, pancreases). The number of islets and cells were counted and the islet diameters were determined by calibrated micrometer. The glycogen content in the liver was examined by Periodic Acid-Schiff (PAS) staining. Results Treatment with NS (5 mg/kg b.w.) markedly increased BW gain and the FBG level was significantly (p<0.001) reduced when compared to the control. Histopathological examination showed that the NS (5 mg/kg b.w.) partially recovered hepatic glycogen content and protected the great deal of the pancreatic islet cells. The number of islets, cells and islets diameter were found statistically significant when compared to the control (p<0.01, p<0.05). Conclusions Higher doses of NS did not exhibit any therapeutic effect. These results showed that hydroalcholic extract of NS at low doses has hypoglycemic effect and ameliorative effect on regeneration of pancreatic islets and may be used as a therapeutic agent in the management of diabetes mellitus. The hypoglycemic effect observed could be due to amelioration of ?-cell, thus leading to increased insulin levels. Consequently, N. sativa may prove clinically useful in the treatment of diabetics and in the protection of ?-cells against streptozotocin. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1845133011104231 PMID:23947821

2013-01-01

23

Determination of Micronutrients and Oxidative Stress Status in the Blood of STZ-Induced Experimental Diabetic Rat Models.  

PubMed

This study aims to research the effect of streptozotocin (STZ) at different doses on the serum micronutrients and oxidative stress status in diabetic rat models. Twenty male rats averaged 250 g and 3-4 months old were used as experimental models. They were put in four groups composed of five rats each. Diabetic was induced by administering STZ 55 and 65 mg/kg intraperitonally. The serum micronutrients including minerals and vitamins (Cu, Zn, Mg, Fe, vitamins D, E, and C) and oxidative stress (malondialdehyde, MDA) were determined. Cu, Zn, and Vitamin D3 levels were found to increase significantly in STZ groups (p < 0.005). Retinol levels decreased significantly in STZ groups (p < 0.005). In the groups administered 55 mg/kg STZ ferrum and vitamin C levels were found significantly lower than the other groups (p < 0.005). In the group given 65 mg/kg STZ ?-tocopherol levels were highest (p < 0.005) among other groups. There was not any difference between the groups for MDA, Cu/Zn, and Mg. For both doses, oxidative stress status was not significantly affected within 48 h of the application, however, some micronutritents were affected significantly. PMID:24817639

Ragbetli, Cennet; Dede, Semiha; Tanritanir, Pinar; Yoruk, Ibrahim Hakki; Ragbetli, Murat Cetin

2014-11-01

24

Aqueous extract of unfermented honeybush (Cyclopia maculata) attenuates STZ-induced diabetes and ?-cell cytotoxicity.  

PubMed

New strategies, which include ?-cell protection, are required in the treatment of T2D, as current drugs demonstrate little or no capacity to directly protect the vulnerable ?-cell against diabetes-induced cytotoxicity. In this study we investigated the ameliorative effect of pre-treatment with an aqueous extract of unfermented Cyclopia maculata (honeybush) on STZ-induced diabetes and pancreatic ?-cell cytotoxicity in Wistar rats after demonstrating a protective effect in vitro in RIN-5F cells. The amelioration of STZ-induced diabetes was seen in the reduction of the area under the curve, determined by the oral glucose tolerance test, as well as fasting glucose levels in extract-treated rats. Pre-treatment with extract also improved serum triglyceride levels and the glucose-to-insulin ratio. Pre-treatment with the extract or the drug, metformin, increased the ?-cell area in islets, with a concomitant increase in ?-cell proliferation at the higher extract dose (300 mg/kg/d), but not the lower dose (30 mg/kg/d). Subsequently, the in vitro tritiated thymidine incorporation assay showed that the extract was not mitogenic in RIN-5F cells. STZ-induced elevation of plasma nitrite levels was reduced in extract-treated rats, but no changes were observed in their serum catalase, serum glutathione, liver lipid peroxidation and liver nitrotyrosine levels. Pre-treating the rats with extract ameliorated the diabetic effect of STZ in Wistar rats, with evidence of pancreatic ?-cells protection, attributed to the presence of high levels of antioxidants such as the xanthones, mangiferin and isomangiferin. PMID:24853761

Chellan, Nireshni; Joubert, Elizabeth; Strijdom, Hans; Roux, Candice; Louw, Johan; Muller, Christo J F

2014-06-01

25

Modulation of GLUT4 expression by oral administration of Mg(2+) to control sugar levels in STZ-induced diabetic rats.  

PubMed

It has been previously shown that oral magnesium administration decreases the levels of glucose in the plasma. However, the mechanisms are not fully understood. The aim of this study was to determine the potential role of GLUT4 on plasma glucose levels by orally administering magnesium sulfate to diabetic rats. Animals were distributed among 4 groups (n = 10 rats per group): one group served as the non-diabetic control, while the other groups had diabetes induced by streptozotocin (intraperitoneal (i.p.) injection). The diabetic rats were either given insulin by i.p. injection (2.5 U·(kg body mass)(-1)·day(-1)), or magnesium sulfate in their drinking water (10 g·L(-1)). After 8 weeks of treatment, we conducted an i.p. glucose tolerance test (IPGTT), measured blood glucose and plasma magnesium levels, and performed in-vitro and in-vivo insulin level measurements by radioimmunoassay. Gastrocnemius (leg) muscles were isolated for the measurement of GLU4 mRNA expression using real-time PCR. Administration of magnesium sulfate improved IPGTT and lowered blood glucose levels almost to the normal range. However, the insulin levels were not changed in either of the in-vitro or in-vivo studies. The expression of GLU4 mRNA increased 23% and 10% in diabetic magnesium-treated and insulin-treated groups, respectively. Our findings suggest that magnesium lowers blood glucose levels via increased GLU4 mRNA expression, independent to insulin secretion. PMID:24821133

Solaimani, Haniah; Soltani, Nepton; MaleKzadeh, Kianoosh; Sohrabipour, Shahla; Zhang, Nina; Nasri, Sema; Wang, Qinghua

2014-06-01

26

Acute and Chronic Regulation of the Renal Na+\\/H+ Exchanger NHE3 in Rats with STZ-Induced Diabetes mellitus  

Microsoft Academic Search

Background: Early stages of diabetic nephropathy are characterized by alterations of glomerular filtration, increased tubular sodium and water reabsorption, and systemic volume expansion, which may be a major cause for the development of hypertension. As a significant fraction of renal salt and water transport is mediated by the proximal tubular Na+\\/H+ exchanger NHE3, we investigated its regulation in rats with

Jelena Klisic; Vera Nief; Livia Reyes; Patrice M. Ambühl

2006-01-01

27

Antidiabetic and antioxidant effect of Semecarpus anacardium Linn. nut milk extract in a high-fat diet STZ-induced type 2 diabetic rat model.  

PubMed

Semecarpus anacardium commonly known as marking nut has been used in the Siddha system of medicine against various ailments. The antidiabetic and antioxidant potential of the drug was evaluated in Type 2 diabetic rats induced by feeding a high-fat diet (HFD) for 2 weeks followed by single intraperitoneal injection of streptozotocin (STZ) 35 mg/kg body weight. Three days after STZ induction, the hyperglycemic rats were treated with Semecarpus anacardium nut milk extract (SA) orally at a dosage of 200 mg/kg body weight daily for 30 days. Metformin (500 mg/kg body weight, orally) was used as a reference drug. The fasting blood glucose, insulin, Hb, HbA1c levels, and HOMA-IR and HOMA-? were measured, and also the levels of lipid peroxidation and antioxidant enzymes were observed. SA significantly (p < .05) reduced and normalized blood glucose levels and also decreased the levels of HbA1c as compared with that of HFD STZ control group. SA treatment also significantly (p < .05) increased the levels of antioxidant enzymes while decreasing the levels of lipid peroxidation. The potential antihyperglycemic action and antioxidant role might be due to the presence of flavonoids in the drug. PMID:22432800

Khan, Haseena Banu Hedayathullah; Vinayagam, Kaladevi Siddhi; Sekar, Ashwini; Palanivelu, Shanthi; Panchanadham, Sachdanandam

2012-03-01

28

The Effects of Exercise Training on Indices of Cardiovascular Autonomic Neuropathy in STZ-Induced Type 1 Diabetic Rats Treated with Insulin.  

E-print Network

??This study investigated whether regular aerobic exercise training could prevent the dysregulation of autonomic cardiovascular (CV) control in a streptozotocin (STZ)-diabetes model designed to represent… (more)

Grise, Kenneth N

2012-01-01

29

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. PMID:23423956

Lee, Hye-Jin

2013-01-01

30

Hypoglycemic Effect of Sargassum ringgoldianum Extract in STZ-induced Diabetic Mice  

PubMed Central

This study was designed to investigate whether Sargassum ringgoldianum extract may inhibit ?-glucosidase and ?-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. The IC50 values of Sargassum ringgoldianum extract against ?-glucosidase and ?-amylase were 0.12 mg/mL and 0.18 mg/mL, respectively, which evidenced higher activities than those of acarbose. The blood glucose levels of the Sargassum ringgoldianum extract administered group were significantly lower compared to the control group in the streptozotocin-induced diabetic mice. Moreover, the area under the two-hour blood glucose response curve was significantly reduced and the absorption of dietary carbohydrates was delayed after administration of Sargassum ringgoldianum extract in the diabetic mice. Therefore, these results indicated that Sargassum ringgoldianum extract may help decrease the postprandial blood glucose level via inhibiting ?-glucosidase. PMID:24471057

Lee, Chae-Won; Han, Ji-Sook

2012-01-01

31

Immunosuppressive Effect of Compound K on Islet Transplantation in an STZ-Induced Diabetic Mouse Model.  

PubMed

Islet transplantation is a therapeutic option for type 1 diabetes, but its long-term success is limited by islet allograft survival. Many factors imperil islet survival, especially the adverse effects and toxicity due to clinical immunosuppressants. Compound (Cpd) K is a synthesized analog of highly unsaturated fatty acids from Isatis tinctoria L. (Cruciferae). Here we investigated the therapeutic effect of Cpd K in diabetic mice and found that it significantly prolonged islet allograft survival with minimal adverse effects after 10 days. Furthermore, it reduced the proportion of CD4(+) and CD8(+) T cells in spleen and lymph nodes, inhibited inflammatory cell infiltration in allografts, suppressed serum interleukin-2 and interferon-? secretion, and increased transforming growth factor-? and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin had a synergistic effect. Cpd K suppressed proliferation of naïve T cells by inducing T-cell anergy and promoting the generation of regulatory T cells. In addition, nuclear factor-?B signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effect on islet transplantation. PMID:24834979

Ma, Peng-Fei; Jiang, Jie; Gao, Chang; Cheng, Pan-Pan; Li, Jia-Li; Huang, Xin; Lin, Ying-Ying; Li, Qing; Peng, Yuan-Zheng; Cai, Mei-Chun; Shao, Wei; Zhu, Qi; Han, Sai; Qin, Qing; Xia, Jun-Jie; Qi, Zhong-Quan

2014-10-01

32

Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats.  

PubMed

Recent evidence indicates that severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease pathology. It has been reported that naringenin (NAR), derived from citrus aurantium, exhibits antioxidant potential and protects the brain against neurodegeneration. The current study was designed to further investigate the protective effect of the NAR on neurodegeneration in a rat model of AD induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ), and to determine whether this neuroprotective effect was associated with brain insulin signaling. Rats were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with NAR (25, 50 mg, 100 mg/kg, respectively) for 3 weeks. The ICV-STZ injected rats did not have elevated blood glucose levels. 21 days following ICV-STZ injection, rats treated with NAR had better learning and memory performance in the Morris water maze test compared with rats treated with saline. We demonstrated that NAR increased the mRNA expression of INS and INSR in cerebral cortex and hippocampus. In addition, NAR reversed ICV-STZ induced Tau hyper-phosphorylation in both hippocampus and cerebral cortex through downregulation of glycogen synthase kinase-3? (GSK-3?) activity, a key kinase in the insulin signaling. Brain levels of Abeta, which were elevated in ICV-STZ rats, were significantly reduced in NAR-treated rats via upregulation of insulin degrading enzyme. These effects were mediated by increased insulin and insulin receptors expression in the brain, suggesting that insulin sensitizer agents might have therapeutic efficacy in early AD. PMID:24337945

Yang, Wenqing; Ma, Jing; Liu, Zheng; Lu, Yongliang; Hu, Bin; Yu, Huarong

2014-05-01

33

Antihyperglycemic Effect of Mangiferin in Streptozotocin Induced Diabetic Rats  

Microsoft Academic Search

The study was undertaken to evaluate the antihyperglycemic potential of mangiferin purified from methano- lic root extract of Salacia chinensis (S. chinensis )i nc ontrol and streptozotocin (STZ)-induced diabetic rats. The mangiferin was administered orally at a dose of 40 mg\\/kg weight per day (30 days) to STZ-induced diabetic rats. The mangiferin treated diabetic rats significantly decreased the level of

Periyar Selvam Sellamuthu; Balu Periamallipatti Muniappan; Sathiya Moorthi Perumal; Murugesan Kandasamy

2009-01-01

34

Evaluation of the Effects of STZ-Induced Diabetes on In Vitro Fertilization and Early Embryogenesis Processes  

PubMed Central

The aim of this study was to investigate the effects of experimentally induced diabetes on (a) germ cells, (b) in vitro fertilization (IVF) success rate, and (c) gap junction and cell adhesion molecule gene and protein expressions during the early blastocyst period. Germ cells were obtained from healthy and diabetic rats, analyzed for number, motility, and morphology, and used for IVF. After reaching the early blastocyst stage, the expressions of genes encoding gap junction proteins and cell adhesion molecules were analyzed by quantitative RT-PCR. Histomorphologically and immunohistochemically analyses were also performed. Diabetes significantly affected sperm number and motility and the development of oocytes. Gene expressions of ?-catenin and connexin family members and protein expressions of E-cadherin and connexin-43 significantly decreased in groups including germ cells isolated from diabetic rats. Connective tissue growth factor expression increased in groups that included sperm cells isolated from diabetic male rats, whereas mucin-1 expression increased in the group that included oocytes isolated from diabetic female rats paired with sperm cells isolated from healthy male rats. In summary, experimentally induced diabetes was found to influence gap junctions, cell adhesion molecules, and associated proteins which all have important roles in germ cell maturation, fertilization, and development. PMID:23671879

Aktug, Huseyin; Uysal, Aysegul; Oltulu, Fatih; Yavasoglu, Altug; Akarca, Saadet Ozen; Kosova, Buket

2013-01-01

35

Evaluation of the Effects of STZ-Induced Diabetes on In Vitro Fertilization and Early Embryogenesis Processes.  

PubMed

The aim of this study was to investigate the effects of experimentally induced diabetes on (a) germ cells, (b) in vitro fertilization (IVF) success rate, and (c) gap junction and cell adhesion molecule gene and protein expressions during the early blastocyst period. Germ cells were obtained from healthy and diabetic rats, analyzed for number, motility, and morphology, and used for IVF. After reaching the early blastocyst stage, the expressions of genes encoding gap junction proteins and cell adhesion molecules were analyzed by quantitative RT-PCR. Histomorphologically and immunohistochemically analyses were also performed. Diabetes significantly affected sperm number and motility and the development of oocytes. Gene expressions of ? -catenin and connexin family members and protein expressions of E-cadherin and connexin-43 significantly decreased in groups including germ cells isolated from diabetic rats. Connective tissue growth factor expression increased in groups that included sperm cells isolated from diabetic male rats, whereas mucin-1 expression increased in the group that included oocytes isolated from diabetic female rats paired with sperm cells isolated from healthy male rats. In summary, experimentally induced diabetes was found to influence gap junctions, cell adhesion molecules, and associated proteins which all have important roles in germ cell maturation, fertilization, and development. PMID:23671879

Aktu?, Hüseyin; Bozok Çetinta?, Vildan; Uysal, Ay?egül; Oltulu, Fatih; Yava?o?lu, Altu?; Akarca, Saadet Özen; Kosova, Buket

2013-01-01

36

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

PubMed Central

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

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

2014-01-01

37

In vivo hypoglycaemic effect and inhibitory mechanism of the branch bark extract of the mulberry on STZ-induced diabetic mice.  

PubMed

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

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

2014-01-01

38

Anti-diabetic activity of cassava cross-linked octenyl succinic maltodextrin in STZ-induced diabetic mice.  

PubMed

The effect of cassava cross-linked octenyl succinic maltodextrin (CCOMD) on diabetic mice was investigated in this study. For CCOMD-L (low dose) and CCOMD-H (high dose) groups, the body weights were recovered by 14.9% and 18.5%, respectively, which were significantly higher than that of model control group. It was also found that the blood glucose and insulin levels were ameliorated in the diabetic mice by the CCOMD diet. Moreover, the CCOMD diet decreased the plasma total cholesterol level (8.1-9.1%) and LDL cholesterol level (28.9-39.4%), and improved the plasma HDL cholesterol level (13.8-15.3%) and intestine short chain fatty acid content. The results indicated that CCOMD administration may be helpful for treating and preventing hyperlipidemia and hyperglycemia in diabetes. PMID:24296405

Wang, Li; Zheng, Maoqiang; Wang, Yingyao; Zhang, Ying; Qian, Haifeng; Zhang, Hui; Qi, Xiguang

2014-03-01

39

Beneficial effect of flax seeds in streptozotocin (STZ) induced diabetic mice: isolation of active fraction having islet regenerative and glucosidase inhibitory properties.  

PubMed

Diabetes mellitus is a metabolic disorder that affects millions of people worldwide. Present study highlights the antidiabetogenic property of Linum usitassimum active fraction (LU6) in streptozotocin (STZ) induced diabetic Swiss mice. Treatment with LU6 fraction showed improved glucose utilization with increase in liver glucose-6-phosphate dehydrogenase enzyme activity and normal glycogenesis in hepatic and muscle tissues. Reduction in pancreatic and intestinal glucosidase inhibitory activity was observed with LU6 treatment, indicating beneficial effects in reducing postprandial hyperglycemia (PPHG). Normalization of plasma insulin and C-peptide levels were observed in diabetic mice, indicating endogenous insulin secretion after the treatment with LU6. The histochemical and immunohistochemical analysis on pancreatic islets suggests the role of LU6 fraction in islet regeneration and insulin secretion as evident in increase functional pancreatic islets producing insulin. Furthermore, significant insulin producing islet formation was also observed in in vitro PANC-1 cells after LU6 treatment, indicating the cellular aggregates to be newly formed islets. This suggests the potential of LU6 fraction in the formation of new islets in vitro, as well as in vivo. Thus, LU6 can be used as a neutraceutical-based first-line treatment for diabetes. PMID:23656171

Dusane, Menakshi Bhat; Joshi, Bimba N

2013-05-01

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

Biochemical effects of Citrullus colocynthis in normal and diabetic rats  

Microsoft Academic Search

Diabetes mellitus is one of the most common endocrine diseases. In UAE many traditional plants such as the Citrullus colocynthis (Handal) are used as antidiabetic remedies. The aim of this study was to examine the effect of the aqueous extract of the seed of C. colocynthis on the biochemical parameters of normal and streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was

Fatma Al-Ghaithi; Mamdouh R. El-Ridi; Ernest Adeghate; Mohamed H. Amiri

2004-01-01

42

Erythropoietin and its carbamylated derivative prevent the development of experimental diabetic autonomic neuropathy in STZ-induced diabetic NOD-SCID mice.  

PubMed

Autonomic neuropathy is a significant diabetic complication resulting in increased morbidity and mortality. Studies of autopsied diabetic patients and several rodent models demonstrate that the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in prevertebral ganglia is the occurrence of synaptic pathology resulting in distinctive dystrophic neurites ("neuritic dystrophy"). Our prior studies show that neuritic dystrophy is reversed by exogenous IGF-I administration without altering the metabolic severity of diabetes, i.e. functioning as a neurotrophic substance. The description of erythropoietin (EPO) synergy with IGF-I function and the recent discovery of EPO's multifaceted neuroprotective role suggested it might substitute for IGF-I in treatment of diabetic autonomic neuropathy. Our current studies demonstrate EPO receptor (EPO-R) mRNA in a cDNA set prepared from NGF-maintained rat sympathetic neuron cultures which decreased with NGF deprivation, a result which demonstrates clearly that sympathetic neurons express EPO-R, a result confirmed by immunohistochemistry. Treatment of STZ-diabetic NOD-SCID mice have demonstrated a dramatic preventative effect of EPO and carbamylated EPO (CEPO, which is neuroprotective but not hematopoietic) on the development of neuritic dystrophy. Neither EPO nor CEPO had a demonstrable effect on the metabolic severity of diabetes. Our results coupled with reported salutary effects of EPO on postural hypotension in a few clinical studies of EPO-treated anemic diabetic and non-diabetic patients may reflect a primary neurotrophic effect of EPO on the sympathetic autonomic nervous system, rather than a primary hematopoietic effect. These findings may represent a major clinical advance since EPO has been widely and safely used in anemic patients due to a variety of clinical conditions. PMID:17967455

Schmidt, Robert E; Green, Karen G; Feng, Dongyan; Dorsey, Denise A; Parvin, Curtis A; Lee, Jin-Moo; Xiao, Qinlgi; Brines, Michael

2008-01-01

43

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

Microsoft Academic Search

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

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

2006-01-01

44

Dark-Cycle Video Surveillance of Sexual Performances of Normal and Diabetic Rats  

Microsoft Academic Search

Clinically, a 59% prevalence of impotence was reported among diabetic male patients. Neurological, vascular, endocrinologic and psychological factors are probably involved. Previous reports with the rat model found deterioration of sexual behavior and reproductive function caused by streptozotocin (STZ)- induced diabetes. The purpose of the present study was to develop the dark-cycle video recording methodology for the observation of rat

Yat-Ching Tong; Ying-Cho Hung; Shinn-Nan Lin; Juei-Tang Cheng

1996-01-01

45

Normalization of Retinal Blood Flow in Diabetic Rats With Primary Intervention Using Insulin Pumps  

Microsoft Academic Search

Purpose. Prior results have demonstrated a significant reduction in retinal blood flow in strep- tozotocin (STZ)-induced diabetic rats. These studies were extended to investigate whether retinal blood flow changes, in the diabetic rat model, could be prevented with strict glycemic control using insulin pumps. Retinal blood flow changes also were measured during hyperoxia and after intravitreal histamine infusion to validate

Allen C. Clermont; Mariel Brittis; Teruo Shiba; Terence McGovem; George L. King; Sven-Erik Bursell

46

Phosphatidylinositol3-kinase is involved in the antihyperglycemic effect induced by resveratrol in streptozotocin-induced diabetic rats  

Microsoft Academic Search

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),

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

2007-01-01

47

Effect of Potent Ethyl Acetate Fraction of Stereospermum suaveolens Extract in Streptozotocin-Induced Diabetic Rats  

PubMed Central

To evaluate the antihyperglycemic effect of ethyl acetate fraction of ethanol extract of Stereospermum suaveolens in streptozotocin-(STZ-) induced diabetic rats by acute and subacute models. In this paper, various fractions of ethanol extract of Stereospermum suaveolens were prepared and their effects on blood glucose levels in STZ-induced diabetic rats were studied after a single oral administration (200?mg/kg). Administration of the ethyl acetate fraction at 200?mg/kg once daily for 14 days to STZ-induced diabetic rats was also carried out. The parameters such as the fasting blood glucose, hepatic glycogen content, and pancreatic antioxidant levels were monitored. In the acute study, the ethyl acetate fraction is the most potent in reducing the fasting serum glucose levels of the STZ-induced diabetic rats. The 14-day repeated oral administration of the ethyl acetate fraction significantly reduced the fasting blood glucose and pancreatic TBARS level and significantly increased the liver glycogen, pancreatic superoxide dismutase, and catalase activities as well as reduced glutathione levels. The histopathological studies during the subacute treatment have been shown to ameliorate the STZ-induced histological damage of pancreas. This paper concludes that the ethyl acetate fraction from ethanol extract of Stereospermum suaveolens possesses potent antihyperglycemic and antioxidant properties, thereby substantiating the use of plant in the indigenous system of medicine. PMID:22593683

Balasubramanian, T.; Chatterjee, Tapan Kumar; Senthilkumar, G. P.; Mani, Tamizh

2012-01-01

48

Nesfatin-1 Stimulates Fatty-Acid Oxidation by Activating AMP-Activated Protein Kinase in STZ-Induced Type 2 Diabetic Mice  

PubMed Central

Nesfatin-1 is an anorexigenic peptide involved in energy homeostasis. Recently, nesfatin-1 was reported to decrease blood glucose level and improve insulin sensitivity in high-fat diet-fed rats. However, little information is known about the influence of nesfatin-1 on lipid metabolism either in physiological or diabetic condition. This study undertook whether nesfatin-1 was involved in the pathophysiology in Streptozotocin-induced type 2 diabetic mice (T2DM), which was induced by a combination of high-calorie diet and two low-doses Streptozotocin. We observed that plasma nesfatin-1 was significantly increased while expression of nesfatin-1 neurons were decreased in hypothalamus in diabetes group compared to only high-calorie diet control group; intravenous injection of nesfatin-1 decreased 0–1h, 0–2h, 0–3h cumulative food intake in T2DM, but 0–24h total food intake had no difference between groups. Body weight and plasma FFA were normalized after nesfatin-1(10 µg/Kg) administration for 6 days. These results suggested that nesfatin-1 improved lipid disorder in T2DM. It was found that blood glucose and insulin resistance coefficient decreased with treatment of nesfatin-1 (both in 1 µg/Kg and 10 µg/Kg doses) in diabetes mice. For further understanding the role of nesfatin-1 on lipid metabolism, we detected p-AMPK and p-ACC of skeletal muscle in T2DM using western blotting. The expression of p-AMPK and p-ACC increased when nesfatin-1 was given with doses 1 µg/Kg but not in doses 10 µg/Kg. Taken together, nesfatin-1 participated in the development of T2DM and stimulated free fatty acid utilization via AMPK-ACC pathway in skeletal muscle in T2DM. PMID:24391760

Xu, Huan; Wang, Peng-fei; Cai, Gui-ju; Song, Hai-feng; Wang, Chang-chen; Dong, Zhao-tong; Ju, Yan-jiao; Jiang, Zheng-yao

2013-01-01

49

Beta Cell Protective Effects of Sodium Tungstate in Streptozotocin-Induced Diabetic Rats: Glycemic Control, Blockage of Oxidative Stress and Beta Cell Histochemistry  

Microsoft Academic Search

Background: Diabetes is a major public health problem. The development of new therapies that are able to improve glycemia management and even to cure diabetes is of great interest. In this study, protective effects of sodium tungstate against STZ-induced beta-cell damages were investigated. Methods: Sixty rats were divided into six groups: control, diabetic, sodium tungstate treated diabetic rats from one

Zahra Heidari; Mehdi Harati; Hamid Reza Mahmoudzadeh-Sagheb; Bita Moudi

2008-01-01

50

Elevated Expression of Liver X Receptor Alpha (LXR?) in Myocardium of Streptozotocin-Induced Diabetic Rats  

Microsoft Academic Search

The present study was designed to investigate the myocardial expression of liver X receptor alpha (LXR?) in a streptozotocin\\u000a (STZ)-induced diabetic rat model. Immunohistochemical staining, quantitative real-time RT-PCR, and Western blot analysis were\\u000a used to determine the expression of LXR? in the myocardium of STZ-induced diabetic rats. The myocardial expression of LXR?\\u000a target genes, long-chain acyl-CoA synthetase 3 (ACSL3), fatty

Yongxia Cheng; Guibo Liu; Qian Pan; Sufen Guo; Xianghong Yang

51

Reduced conduction reserve in the diabetic rat heart: role of iPLA2 activation in the response to ischemia.  

PubMed

Hearts from streptozotocin (STZ)-induced diabetic rats have previously been shown to have impaired intercellular electrical coupling, due to reorganization (lateralization) of connexin43 proteins. Due to the resulting reduction in conduction reserve, conduction velocity in diabetic hearts is more sensitive to conditions that reduce cellular excitability or intercellular electrical coupling. Diabetes is a known risk factor for cardiac ischemia, a condition associated with both reduced cellular excitability and reduced intercellular coupling. Activation of Ca(2+)-independent phospholipase A(2) (iPLA(2)) is known to be part of the response to acute ischemia and may contribute to the intercellular uncoupling by causing increased levels of arachidonic acid and lysophosphatidyl choline. Normally perfused diabetic hearts are known to exhibit increased iPLA(2) activity and may thus be particularly sensitive to further activation of these enzymes. In this study, we used voltage-sensitive dye mapping to assess changes in conduction velocity in response to acute global ischemia in Langendorff-perfused STZ-induced diabetic hearts. Conduction slowing in response to ischemia was significantly larger in STZ-induced diabetic hearts compared with healthy controls. Similarly, slowing of conduction velocity in response to acidosis was also more pronounced in STZ-induced diabetic hearts. Inhibition of iPLA(2) activity using bromoenol lactone (BEL; 10 ?M) had no effect on the response to ischemia in healthy control hearts. However, in STZ-induced diabetic hearts, BEL significantly reduced the amount of conduction slowing observed beginning 5 min after the onset of ischemia. BEL treatment also significantly increased the time to onset of sustained arrhythmias in STZ-induced diabetic hearts but had no effect on the time to arrhythmia in healthy control hearts. Thus, our results suggest that iPLA(2) activation in response to acute ischemia in STZ-induced diabetic hearts is more pronounced than in control hearts and that this response is a significant contributor to arrhythmogenic conduction slowing. PMID:21037228

Rahnema, Parisa; Shimoni, Yakhin; Nygren, Anders

2011-01-01

52

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

53

Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats.  

PubMed

Previous studies demonstrated anti-diabetic effects of berberine. However, the facts that berberine had low bioavailability and poor absorption through the gut wall indicated that berberine might exert its antihyperglycaemic effect in the intestinal tract before absorption. The purpose of this study was to investigate whether berberine attenuates disaccharidase activities and beta-glucuronidase activity in the small intestine of streptozotocin (STZ)-induced diabetic rats. Two groups of STZ-induced diabetic rats were treated with protamine zinc insulin (10 U/Kg) subcutaneously twice daily and berberine (100 mg/Kg) orally once daily for 4 weeks, respectively. Both age-matched normal rats and diabetic control rats received physiological saline only. Fasting blood glucose levels, body weight, intestinal disaccharidase and beta-glucuronidase activities in duodenum, jejunum and ileum were assessed for changes. Our findings suggested that berberine treatment significantly decreases the activities of intestinal disaccharidases and beta-glucuronidase in STZ-induced diabetic rats. The results demonstrated that the inhibitory effect on intestinal disaccharidases and beta-glucuronidase of berberine might be one of the mechanisms for berberine as an antihyperglycaemic agent. PMID:18557425

Liu, Li; Deng, Yuanxiong; Yu, Sen; Lu, Shousi; Xie, Lin; Liu, Xiaodong

2008-05-01

54

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

Microsoft Academic Search

Plants with antidiabetic activities provide important source for the development of new drugs in the management of diabetes mellitus. The main aim of this study was to evaluate the protective effect of aqueous extract (AE) of Pimpinella tirupatiensis (Pt) tuberous root on cardiac oxidative stress and lipid peroxidation (LPO) in non-diabetic and streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in

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

55

Date Fruit Extract Is a Neuroprotective Agent in Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats: A Multimodal Analysis  

PubMed Central

Background. To study the effects of an aqueous extract of date fruit (Phoenix dactylifera L. Arecaceae) diet on diabetic polyneuropathy (DPN) in streptozotocin- (STZ-) induced diabetic rats. Methods. The effects of a date fruit extract (DFE) diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with a nondiabetic control group, diabetic control group (sham), and vehicle group with respect to the following parameters: open field behavioral test, motor nerve conduction velocity (MNCV), and morphological observations. Results. In the model of STZ-induced of diabetic neuropathy, chronic treatment for 6 weeks with DFE counteracted the impairment of the explorative activity of the rats in an open field behavioral test and of the conduction velocity of the sciatic nerve (MNCV). In addition, pretreatment with DFE significantly reversed each nerve diameter reduction in diabetic rats. Conclusion. DFE treatment shows efficacy for preventing diabetic deterioration and for improving pathological parameters of diabetic neuropathy in rats, as compared with control groups. PMID:22191015

Zangiabadi, Nasser; Asadi-Shekaari, Majid; Sheibani, Vahid; Jafari, Mandana; Shabani, Mohammad; Asadi, Ali Reza; Tajadini, Hale; Jarahi, Morteza

2011-01-01

56

Extract of Adenanthera pavonina L. seed reduces development of diabetic nephropathy in streptozotocin-induced diabetic rats  

PubMed Central

Objective: The aim of the present study was to investigate the renal protective effect of Adenanthera pavonina (A. pavonina) seed aqueous extract (APSAE), in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: The renal protective effect of A. pavonina seed aqueous extract (APSAE) was studied in STZ-induced diabetic rats. APSAE (50, 100 and 200 mg/kg per day) was given daily to diabetic rats for 13 weeks. Blood glucose, serum parameters such as albumin, creatinine, total protein, urea, lipid profile, glycated haemoglobin (HbA1c), and urine parameters such as urine protein and albumin were examined. Kidney histopathology was also done. Results: After 13 weeks of treatment, in STZ-induced diabetic rats, severe hyperglycemia was developed, with marked increase in proteinuria and albuminuria. However, APSAE treatment significantly reduced proteinuria, albuminuria, lipid levels, and HbA1c deposition in diabetic rats. Conclusion: These results suggested that APSAE has reduced development of diabetic nephropathy in streptozotocin-induced diabetic rats and could have beneficial effect in reducing the progression of diabetic nephropathy. PMID:25050253

Pandhare, Ramdas; Sangameswaran, Balakrishnan

2012-01-01

57

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

58

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

PubMed Central

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

2012-01-01

59

Changes of endothelin in streptozotocin-induced diabetic rats: effects of an angiotensin converting enzyme inhibitor, enalapril maleate  

Microsoft Academic Search

Endothelin-1 (ET-1) concentrations are increased in patients with diabetes mellitus, particularly those with diabetic retinopathy, or essential hypertension. We hypothesized that ET-1 might participate in the develop- ment and progression of diabetic microangiopathy. In this study, the effects of the angiotensin converting enzyme (ACE) inhibitor, enalapril maleate, on diabetic angiopathy were examined in streptozotocin (STZ)-induced diabetic (STZ-DM) rats by monitoring

Y Itoh; S Imamura; K Yamamoto; Y Ono; M Nagata; T Kobayashi; T Kato; M Tomita; A Nakai; M Itoh; A Nagasaka

2002-01-01

60

The effects of chronic L-arginine treatment on vascular responsiveness of streptozotocin-diabetic rats  

Microsoft Academic Search

In this study, the protective effects of L-arginine treatment in vivo on vascular reactivity of streptozotocin (STZ)-induced 12-week-old diabetic rats were examined. Loss of weight, polydipsia, polyphagia, hyperglycemia, hypoinsulinemia, and elevated levels of plasma cholesterol and triglyceride were observed in diabetic rats. L-arginine treatment (1 mg\\/mL in drinking water) did not significantly affect these metabolic and biochemical abnormalities. Plasma malondialdehyde

A. Tanju Özçelikay; Aydin Tay; Deniz Dinçer; Suna Meral; Nuray Yildizo?lu-Ari; V. Melih Altan

1999-01-01

61

N-3 Fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring  

Microsoft Academic Search

Objective:We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring.Design:Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21

A Yessoufou; N Soulaimann; S A Merzouk; K Moutairou; H Ahissou; J Prost; A M Simonin; H Merzouk; A Hichami; N A Khan

2006-01-01

62

The Effect of Nimodipine on Calcium Homeostasis and Pain Sensitivity in Diabetic Rats  

Microsoft Academic Search

Summary  1. The pathogenesis of diabetic neuropathy is a complex phenomenon, the mechanisms of which are not fully understood. Our previous studies have shown that the intracellular calcium signaling is impaired in primary and secondary nociceptive neurons in rats with streptozotocin (STZ)-induced diabetes. Here, we investigated the effect of prolonged treatment with the L-type calcium channel blocker nimodipine on diabetes-induced changes

L. Shutov; I. Kruglikov; O. Gryshchenko; E. Khomula; V. Viatchenko-Karpinski; P. Belan; N. Voitenko

2006-01-01

63

Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats.  

PubMed

Plasma arginine vasopressin (AVP) is known to be elevated in patients with uncontrolled insulin-dependent diabetes mellitus who have plasma hyperosmolality with hyperglycaemia. Although osmotic stimuli cause an increase in nitric oxide synthase (NOS) activity as well as synthesis of AVP and oxytocin in the paraventricular (PVN) and supraoptic nuclei (SON), it is not known whether NOS activity in the hypothalamus changes in the diabetic patients who have plasma hyperosmolality with hyperglycaemia caused by insulin deficiency. Expression of the neuronal (n) NOS gene in the PVN and SON in streptozotocin (STZ)-induced diabetic rats was investigated by using in situ hybridization histochemistry and NADPH-diaphorase histochemical staining. Four weeks after intraperitoneal (i. p.) administration of STZ, male Wistar rats developed hyperglycaemia and plasma hyperosmolality. The expression of nNOS gene and NADPH-diaphorase staining in the PVN and SON remarkably increased in STZ-induced diabetic rats compared to control rats. Three weeks after administration of STZ, the diabetic rats were subcutaneously treated with insulin for 1 week, which resulted in significant suppression of the induction of nNOS, AVP and oxytocin gene expression in the PVN and SON. Furthermore, the induction of nNOS gene expression in the PVN and SON was suppressed in STZ-induced diabetic rats treated with phlorizin and diet to normalize hyperglycaemia without insulin treatment. These results suggest that upregulation of nNOS gene expression as well as AVP and oxytocin gene expression in the PVN and SON in STZ-induced diabetic rats may be associated with hyperglycaemia and plamsa hyperosmolality. PMID:9662044

Serino, R; Ueta, Y; Tokunaga, M; Hara, Y; Nomura, M; Kabashima, N; Shibuya, I; Hattori, Y; Yamashita, H

1998-06-01

64

Antihyperglycemic and antihyperlipidemic effects of n-hexane fraction from the hydro-methanolic extract of sepals of Salmalia malabarica in streptozotocin-induced diabetic rats.  

PubMed

Bio-efficacy of n-hexane fraction of sepal of Salmalia malabarica was evaluated covering the biochemical sensors for the management of hyperglycemic and hyperlipidemic effects. Evaluation of n-hexane fraction of Salmalia malabarica (SMH) from hydro-methanolic (2:3) extract at the dose of 0.1 gm/kg body weight twice a day were investigated in normal and streptozotocin (STZ) induced diabetic rats. Normal and STZ-induced diabetic rats were divided into five groups. The effect of the fraction on fasting blood glucose (FBG), serum insulin, hemoglobin, glycated hemoglobin, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc), phospholipids, free fatty acids, urea, uric acid, creatinine, albumin and transaminases were investigated in STZ-induced diabetic rat. A significant reduction of FBG level was observed after SMH treatment in STZ-induced diabetic rat. Treatment of diabetic rats with n-hexane fraction of this plant restored the levels of the above biochemical sensors significantly (p<0.001) in respect to the control. Histological studies of pancreas showed a qualitative diminution in the area of the islet's of Langerhans in diabetic group which was recovered by said fraction. Phytochemical screening of the fraction revealed the presence of flavonoids, terpenoids and steroids. PMID:22732718

De, Debasis; Ali, Kazi Monjur; Chatterjee, Kausik; Bera, Tushar Kanti; Ghosh, Debidas

2012-01-01

65

Mangiferin protects the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats  

Microsoft Academic Search

The role of oxidative stress in streptozotocin (STZ)-induced toxicity and its prevention by a xanthone glucoside, mangiferin was investigated. To induce diabetes mellitus, adult male Wistar rats were injected STZ intravenously at 55 mg\\/kg body weight. The effect of mangiferin (10 and 20 mg\\/kg, i.p., 28 days) was investigated in STZ-induced diabetic male rats. Insulin-treated rats (6 U\\/kg, i.p., 28

S Muruganandan; S Gupta; M Kataria; J Lal; P. K Gupta

2002-01-01

66

Voltage-dependence of contraction in streptozotocin-induced diabetic myocytes  

Microsoft Academic Search

Cardiac contractile dysfunction is frequently reported in human patients and experimental animals with type-1 diabetes mellitus. The aim of this study was to investigate the voltage-dependence of contraction in ventricular myocytes from the streptozotocin (STZ)-induced diabetic rat. STZ-induced diabetes was characterised by hyperglycaemia and hypoinsulinaemia. Other characteristics included reduced body and heart weight and raised blood osmolarity. Isolated ventricular myocytes

N. K. Bracken; A. J. Woodall; F. C. Howarth; J. Singh

2004-01-01

67

Anti-depressant effect of hesperidin in diabetic rats.  

PubMed

This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain. PMID:25358020

El-Marasy, Salma A; Abdallah, Heba M I; El-Shenawy, Siham M; El-Khatib, Aiman S; El-Shabrawy, Osama A; Kenawy, Sanaa A

2014-11-01

68

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

2013-01-01

69

Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats  

PubMed Central

The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats. PMID:23407749

Pandhare, Ramdas B.; Sangameswaran, B.; Mohite, Popat B.; Khanage, Shantaram G.

2011-01-01

70

Inhibitory Effect of r-Hirudin Variant III on Streptozotocin-Induced Diabetic Cataracts in Rats  

PubMed Central

The in vivo inhibitory effect of r-hirudin variant III (rHV3) on streptozotocin (STZ)-induced diabetic cataracts in rats was investigated. SD-rats were firstly made diabetic by a single intraperitoneal injection of 2% (W/V) STZ (65?mg/kg). Two weeks later, cataract formation was examined by slit lamp microscope, and the cataracted animals were randomly grouped. The animals in the treated groups received rHV3 drops administration to the eyes with various doses. After 4 weeks treatment, the animals were sacrificed to evaluate the biochemical changes of aldose reductase (AR), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels in the eye lens. Meanwhile, the cataract progression was monitored by slit lamp microscope. As a result, rHV3 drops treatment significantly increased the activities of SOD and GSH-Px in the lens in a dose-dependent manner, whereas AR activity and MDA level in the lens were dramatically decreased. Also, the morphological observation further confirmed the inhibition of the development of STZ-induced diabetic cataracts by the rHV3 drops treatment. Thus, our data suggest that rHV3 drops are pharmacologically effective for the protection against STZ-induced diabetic cataracts in rats. PMID:24391466

Gong, Xiaojian; Zhang, Qiuyan; Tan, Shuhua

2013-01-01

71

Effect of an antidiabetic extract of Catharanthus roseus on enzymic activities in streptozotocin induced diabetic rats  

Microsoft Academic Search

Hypoglycemic activity was detected in dichloromethane:methanol extract (1:1) of leaves and twigs of Catharanthus roseus (family Apocynaceae), a traditionally used medicinal plant, using streptozotocin (STZ) induced diabetic rat model. Extract at dose 500 mg\\/kg given orally for 7 and 15 days showed 48.6 and 57.6% hypoglycemic activity, respectively. Prior treatment at the same dose for 30 days provided complete protection

Som Nath Singh; Praveen Vats; Shoba Suri; Radhey Shyam; M. M. L Kumria; S Ranganathan; K Sridharan

2001-01-01

72

Comparative effects of Citrullus colocynthis, sunflower and olive oil-enriched diet in streptozotocin-induced diabetes in rats.  

PubMed

Citrullus colocynthis (colocynth) seeds are traditionally used as antidiabetic medication in Mediterranean countries. The present study evaluated the differential effects of diets enriched with C. colocynthis, sunflower or olive oils on the pancreatic beta-cell mass in streptozotocin (STZ)-induced diabetes in rats. STZ injection induced rapid hyperglycaemia in all animals. However, 2 months later, hyperglycaemia was significantly less pronounced in the rats fed a C. colocynthis oil-enriched diet compared with other rat groups (7.9mM versus 12mM and 16mM with colocynth versus olive and sunflower oils, respectively). Assessment of insulin sensitivity using the homoeostasis model assessment (HOMA) method also indicated less insulin resistance in the rats fed a C. colocynthis oil-enriched diet versus the other rats. Finally, 2 months after STZ injection, the pancreatic beta-cell mass was similar in both the STZ-treated rats fed the colocynth oil-enriched diet and their controls fed the same diet. In contrast, the pancreatic beta-cell mass remained lower in the STZ-induced diabetic rats fed with olive oil- and sunflower oil-enriched diets compared with the C. colocynthis group. We conclude that C. colocynthis oil supplementation may have a beneficial effect by partly preserving or restoring pancreatic beta-cell mass in the STZ-induced diabetes rat model. PMID:19264524

Sebbagh, N; Cruciani-Guglielmacci, C; Ouali, F; Berthault, M-F; Rouch, C; Sari, D Chabane; Magnan, C

2009-06-01

73

Comparative effects of Citrullus colocynthis, sunflower and olive oil-enriched diet in streptozotocin-induced diabetes in rats  

Microsoft Academic Search

Citrullus colocynthis (colocynth) seeds are traditionally used as antidiabetic medication in Mediterranean countries. The present study evaluated the differential effects of diets enriched with C. colocynthis, sunflower or olive oils on the pancreatic ?-cell mass in streptozotocin (STZ)-induced diabetes in rats. STZ injection induced rapid hyperglycaemia in all animals. However, 2months later, hyperglycaemia was significantly less pronounced in the rats fed

N. Sebbagh; C. Cruciani-Guglielmacci; F. Ouali; M.-F. Berthault; C. Rouch; D. Chabane Sari; C. Magnan

2009-01-01

74

Renoprotective effect of atorvastatin on STZ-diabetic rats through attenuating kidney-associated dysmetabolism.  

PubMed

Atorvastatin (AT) has been alternatively used for managing diabetic complications in clinic. However, AT-related therapeutic potentiality remains relatively unexplored, especially in diabetic nephropathy. This study aimed to investigate the underlying potentiality that AT exerted on anti-diabetic nephropathy role against streptozotocin (STZ)-induced kidney injury in rats. STZ-diabetic rats were intragastrically administered with AT (10, 20 mg/kg/d) for consecutive 8 weeks. The effects of AT on body weight, levels of blood glucose, lipometabolism, redox state, cellular metabolism, regulator factor and kidney morphological changes were monitored by routine measurement, biochemistry assay, PT-PCR analysis, ultrastructural and pathological observations, respectively. Compared with the diabetic nephropathy rats, AT elevated the body weight of diabetic nephropathy rats (P<0.01), effectively reduced the blood glucose level (P<0.01), increased the levels of insulin and high-density lipoprotein cholesterol (HDL-C) in plasma (P<0.01), and decreased the 24 h urine protein content and serum concentrations of low-density lipoprotein cholesterol (LDL-C) (P<0.01). Meanwhile, increase in kidney tissue, the intrarenal activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced, while the malonaldehyde (MDA) content was reduced (P<0.01). In addition, the expression of transforming growth factor beta 1 (TGF-?1) mRNA in kidney tissue was notably down-regulated (P<0.01). Furthermore, AT contributed to alleviating STZ-induced nephritic damages in rats. These results demonstrate that atorvastatin exerts the effective protective role against kidney injuries of STZ-induced diabetic nephropathy rat, which the underlying mechanisms are associated with ameliorating glyco, lipometabolism, enhancing antioxidant ability, and mitigating renal damage. PMID:25008071

Zhou, Suxian; Zhao, Ping; Li, Yingfang; Deng, Tingting; Tian, Lihua; Li, Hao

2014-10-01

75

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

PubMed Central

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

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

2014-01-01

76

Protective effects of Phyllanthus amarus aqueous extract against renal oxidative stress in Streptozotocin -induced diabetic rats  

PubMed Central

Aim and Objectives: In the present study, we have evaluated the antihyperglycemic, hypolipidemic and antioxidant activities of aqueous extract of Phyllanthus amarus (PAAEt) in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: PAAEt was administered at 200 mg/kg body weight/day to normal treated (NT-group) and STZ-induced diabetic treated rats (DT-group) by gavage for eight weeks. During the experimental period, blood was collected from fasted rats at 10 days intervals and plasma glucose level was estimated. The plasma lipid profile was estimated at the end of experimental period. After the treatment, period kidney lipid peroxidation (LPO), protein oxidation and reduced glutathione (GSH) were estimated and antioxidant enzymes viz., glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) were also assayed. Results: The significant decrease in the body weight, hyperglycemia and hyperlipidemia observed in STZ-induced diabetic rats (D-group) were rectified with PAAEt treatment in diabetic treated group (DT-group). D-group rats showed increased renal oxidative stress with increased LPO and protein oxidation. DT-group showed a significant decrease in renal LPO, protein oxidation and a significant increase in GSH content and GR, GPx and GST activities when compared with D-group. The activities of SOD and CAT decreased significantly in D-group, but were normalized in DT-group. Normal rats treated with PAAEt (NT-rats) showed a significant decrease in lipid profile, renal LPO and protein oxidation, with significant increase in renal GSH and activities of antioxidant enzymes compared to normal rats (N-group). Conclusion: Our results demonstrated that PAAEt with its antidiabetic, hypolipidemic and antioxidant properties could be a potential herbal medicine in treating diabetes and renal problems. PMID:21844996

Karuna, R.; Bharathi, Vijaya G.; Reddy, Sreenivasa S.; Ramesh, B.; Saralakumari, D.

2011-01-01

77

Vascular Dysfunction in Streptozotocin-Induced Experimental Diabetes Strictly Depends on Insulin Deficiency  

Microsoft Academic Search

Objective: In previous studies we and others have shown that streptozotocin (STZ)-induced diabetes in rats is associated with vascular oxidative stress and dysfunction. In the present study, we sought to determine whether vascular dysfunction and oxidative stress strictly depend on insulin deficiency. Methods: The effects of insulin (2.5 U\\/day s.c., 2 weeks) therapy on vascular disorders in STZ-induced (60 mg\\/kg

Matthias Oelze; Maike Knorr; Swenja Schuhmacher; Tjebo Heeren; Christian Otto; Eberhard Schulz; Kurt Reifenberg; Philip Wenzel; Thomas Münzel; Andreas Daiber

2011-01-01

78

The effects of dexpanthenol in streptozotocin-induced diabetic rats: Histological, histochemical and immunological evidences.  

PubMed

This study was designed to investigate the effects of Dexpanthenol (Dxp) on liver and pancreas histology and cytokine levels in streptozotocine (STZ)-induced diabetic rats. Twenty-four Wistar albino male rats were divided into four groups: control, Dxp, STZ-induced diabetic (STZ) and diabetic treatment with Dexpanthenol (STZ-Dxp) groups. Experimental diabetes was induced by single dose STZ (50 mg/kg) intraperitoneally (i.p.). After administration of STZ, the STZ-Dxp group began to receive a 300 mg/kg/day i.p. dose of Dxp for 6 weeks. Liver and pancreas tissues of the control group were in normal morphology. Liver tissue of STZ group showed vacuolisation of hepatocytes in the liver parenchyma with enlargement of sinusoidal spaces and increasing amounts of connective tissue in the portal area. Pancreatic section of STZ group displayed ?-cells with of cytoplasmic mass, reduction of islet size, and atrophy. The STZ-Dxp group that received Dxp treatment exhibit partially normal hepatic parenchyma. Histochemical examinations revealed that the diabetes-induced glycogen depletion markedly improved with the Dxp treatment (p?0.001). The severity of degenerative alteration was lessened by Dxp supplementation in the STZ-Dxp group. Induction of STZ presented a significant increase both in interleukin-1? (IL-1?) (p=0.033) and monocyte chemotactic protein-1 (MCP-1) (p=0.011) levels, when compared with the control rats. DXP-treated diabetic rats' IL-1? and MCP-1 levels were similar to control value. This evidence suggests that Dxp is effective in reducing STZ-induced, diabetic-related complications and may be beneficial for the treatment of diabetic patients. PMID:24733664

Gulle, K; Ceri, N G; Akpolat, M; Arasli, M; Demirci, B

2014-10-01

79

Slowing of motor nerve conduction velocity in streptozotocin-induced diabetic rats is preceded by impaired vasodilation in arterioles that overlie the sciatic nerve.  

PubMed

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 in arterioles that provide circulation to the region of the sciatic nerve is associated with reduced endoneural blood flow (EBF) and that these defects precede slowing of motor nerve conduction velocity, and thereby may contribute to nerve dysfunction. As early as three days after the induction of diabetes endoneural blood flow was reduced in the STZ-induced diabetic rat. Furthermore, after 1 week of diabetes acetylcholine-induced vasodilation was found to be impaired. This was accompanied by an increase in the superoxide level in arterioles that provide circulation to the region of the sciatic nerve as well as changes in the level of other markers of oxidative stress including an increase in serum levels of thiobarbituric acid reactive substances and a decrease in lens glutathione level. In contrast to the vascular related changes that occur within 1 week of diabetes, motor nerve conduction velocity and sciatic nerve Na+/K+ ATPase activity were significantly reduced following 2 and 4 weeks of diabetes, respectively. These studies demonstrate that changes in vascular function in the STZ-induced diabetic rat precede the slowing of motor nerve conduction velocity (MNCV) and are accompanied by an increase in superoxide levels in arterioles that provide circulation to the region of the sciatic nerve. PMID:11469397

Coppey, L J; Davidson, E P; Dunlap, J A; Lund, D D; Yorek, M A

2000-01-01

80

Slowing of Motor Nerve Conduction Velocity in Streptozotocin-induced Diabetic Rats is Preceded by Impaired Vasodilation in Arterioles that Overlie the Sciatic Nerve  

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 in arterioles that provide circulation to the region of the sciatic nerve is associated with reduced endoneural blood flow (EBF) and that these defects precede slowing of motor nerve conduction velocity, and thereby may contribute to nerve dysfunction. As early as three days after the induction of diabetes endoneural blood flow was reduced in the STZ-induced diabetic rat. Furthermore, after 1 week of diabetes acetylcholine- induced vasodilation was found to be impaired. This was accompanied by an increase in the superoxide level in arterioles that provide circulation to the region of the sciatic nerve as well as changes in the level of other markers of oxidative stress including an increase in serum levels of thiobarbituric acid reactive substances and a decrease in lens glutathione level. In contrast to the vascular related changes that occur within 1 week of diabetes, motor nerve conduction velocity and sciatic nerve Na+/k+ ATPase activity were significantly reduced following 2 and 4 weeks of diabetes, respectively. These studies demonstrate that changes in vascular function in the STZ-induced diabetic rat precede the slowing of motor nerve conduction velocity (MNCV) and are accompanied by an increase in superoxide levels in arterioles that provide circulation to the region of the sciatic nerve. PMID:11469397

Coppey, Lawrence J.; Davidson, Eric P.; Dunlap, Joyce A.; Lund, Donald D.

2000-01-01

81

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

PubMed

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

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

2014-01-01

82

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. PMID:23569798

Arokiyaraj, S; Balamurugan, R; Augustian, P

2011-01-01

83

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

PubMed

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

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

2014-06-01

84

Expression of hexokinase isoforms in the dorsal root ganglion of the adult rat and effect of experimental diabetes  

Microsoft Academic Search

The effect of streptozotocin (STZ)-induced diabetes on expression and activity of hexokinase, the first enzyme and rate-limiting step in glycolysis, was studied in sensory neurons of lumbar dorsal root ganglia (DRG). The DRG and sciatic nerve of adult rats expressed the hexokinase I isoform only. Immunofluorescent staining of lumbar DRG demonstrated that small–medium neurons and satellite cells exhibited high levels

Natalie J. Gardiner; Zuocheng Wang; Claire Luke; Angela Gott; Sally A. Price; Paul Fernyhough

2007-01-01

85

Beneficial Effects of Rutin and Vitamin C Coadministration in a Streptozotocin-Induced Diabetes Rat Model of Kidney Nephrotoxicity  

Microsoft Academic Search

The aim of this study was to examine the possible antinephrotoxic activity of rutin (vitamin P) and vitamin C in kidney of streptozotocin (STZ)-induced diabetic rats. Oral administration on rutin (100 mg\\/kg), vitamin C (200 mg\\/day) and their combination (50 and 100 mg\\/kg) for 5 weeks on body and kidney weights and the levels of serum glucose, insulin and creatinine

Mohammed A. Alsaif

2009-01-01

86

Biochemical effects of Citrullus colocynthis in normal and diabetic rats.  

PubMed

Diabetes mellitus is one of the most common endocrine diseases. In UAE many traditional plants such as the Citrullus colocynthis (Handal) are used as antidiabetic remedies. The aim of this study was to examine the effect of the aqueous extract of the seed of C. colocynthis on the biochemical parameters of normal and streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal (60 mg/kg body wt1) injection of STZ. Normal and diabetic rats were fed with the plant extract daily by oral intubation for 2 weeks. Blood sample were collected at the beginning and end of the experiment for the measurement of biochemical parameters. The plasma level of alanine aminotranferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), lactic dehydrogenase (LDH) increased significantly after the onset of diabetes. Oral administration of the plant extract reduced the plasma level of AST and LDH significantly. However, the plant extract failed to reduce the increased blood level of GGT and ALP in diabetic rats. Blood urea nitrogen (BUN) increased significantly after the onset of diabetes. No significant difference was observed in the blood creatinine, K+, Na+, Ca2+ and P levels of normal and diabetic rats. The plant extract did not have any effect on BUN level, however, it caused an increase in the level of K+, Na+ in diabetic rats. In conclusion, oral administration of the aqueous extract of the C. colocynthis can ameliorate some of the toxic effects of streptozotocin. PMID:15362497

Al-Ghaithi, Fatma; El-Ridi, Mamdouh R; Adeghate, Ernest; Amiri, Mohamed H

2004-06-01

87

Protective Effects of Fufang Xueshuantong on Diabetic Retinopathy in Rats  

PubMed Central

The aim of this study was to evaluate the protective effects of Fufang Xueshuantong (FXT) on diabetic retinopathy in rats induced by streptozotocin (STZ). Diabetes was induced in Sprague-Dawley rats by a single injection of 60?mg/kg STZ. One week after STZ, FXT 0.525?g/kg or 1.05?g/kg was administrated to the rats by intragastric gavage (ig) once daily consecutively for 24 weeks. The control rats and untreated STZ rats received vehicle the same way. At the end of the experiment, the erythrocyte aggregation and blood viscosity were assayed. The retina vessel morphology was observed in retinal digestive preparations. Expression of occludin and intercellular adhesion molecule-1 (ICAM-1) in retina was measured by western blotting. Expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in retina was detected by immunohistochemistry. The activity of aldose reductase in retina was investigated with a NADPH oxidation method. The results showed that, in STZ rats, there were distinct lesions in retinal vessel, including decrease of pericytes and increase of acellular capillaries, together with dilatation of retinal veins. The expression of VEGF and ICAM-1 increased, while the expression of PEDF and occludin decreased. The activity of aldose reductase elevated, and the whole blood viscosity, plasma viscosity, and erythrocyte aggregation also increased after STZ stimulation. FXT 0.525?g/kg and 1.05?g/kg demonstrated significant protective effects against STZ induced microvessel lesion in the retina with increased pericytes and reduced acellular capillaries. FXT also reduced the expression of VEGF and ICAM-1 and enhanced the expression of PEDF and occludin in STZ insulted rats. The activity of aldose reductase, the whole blood viscosity, plasma viscosity, and erythrocyte aggregation also decreased after FXT treatment. The results demonstrated that FXT has protective effect on STZ induced diabetic retinopathy in rats. PMID:24204392

Duan, Huihui; Huang, Jianmei; Li, Wei; Tang, Minke

2013-01-01

88

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

PubMed

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

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

2014-11-01

89

Effect of vitamin D3 on behavioural and biochemical parameters in diabetes type 1-induced rats.  

PubMed

Diabetes is associated with long-term complications in the brain and reduced cognitive ability. Vitamin D3 (VD3 ) appears to be involved in the amelioration of hyperglycaemia in streptozotocin (STZ)-induced diabetic rats. Our aim was to analyse the potential of VD3 in avoiding brain damage through evaluation of acetylcholinesterase (AChE), Na(+) K(+) -adenosine triphosphatase (ATPase) and delta aminolevulinate dehydratase (?-ALA-D) activities and thiobarbituric acid reactive substance (TBARS) levels from cerebral cortex, as well as memory in STZ-induced diabetic rats. Animals were divided into eight groups (n = 5): control/saline, control/metformin (Metf), control/VD3 , control/Metf?+?VD3 , diabetic/saline, diabetic/Metf, diabetic/VD3 and diabetic/Metf?+?VD3 . Thirty days after treatment, animals were submitted to contextual fear-conditioning and open-field behavioural tests, after which they were sacrificed and the cerebral cortex was dissected. Our results demonstrate a significant memory deficit, an increase in AChE activity and TBARS levels and a decrease in ?-ALA-D and Na(+) K(+) -ATPase activities in diabetic rats when compared with the controls. Treatment of diabetic rats with Metf and VD3 prevented the increase in AChE activity when compared with the diabetic/saline group. In treated diabetic rats, the decrease in Na(+) K(+) -ATPase was reverted when compared with non-treated rats, but the increase in ?-ALA-D activity was not. VD3 prevented diabetes-induced TBARS level and improved memory. Our results show that VD3 can avoid cognitive deficit through prevention of changes in important enzymes such as Na(+) K(+) -ATPase and AChE in cerebral cortex in type 1 diabetic rats. PMID:24947461

Calgaroto, Nicéia Spanholi; Thomé, Gustavo Roberto; da Costa, Pauline; Baldissareli, Jucimara; Hussein, Fátima Abdala; Schmatz, Roberta; Rubin, Maribel A; Signor, Cristiane; Ribeiro, Daniela Aymone; Carvalho, Fabiano Barbosa; de Oliveira, Lizielle Souza; Pereira, Luciane Belmonte; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

2014-08-01

90

4-phenylbutyric acid attenuates endoplasmic reticulum stress-mediated pancreatic ?-cell apoptosis in rats with streptozotocin-induced diabetes.  

PubMed

Endoplasmic reticulum stress (ERS) plays an important role in diabetes mellitus (DM), but the association between DM and ERS is unknown. We have previously shown that streptozotocin (STZ)-induced diabetes in rats is characterized by increased levels of ERS markers. Here, we tested whether the chemical chaperone 4-phenylbutyric acid (4-PBA) ameliorated ERS-associated apoptosis in pancreatic ?-cells in rats with STZ-induced diabetes. Male Sprague-Dawley rats were divided into 3 groups: control group, DM group, and DM model plus 4-PBA treatment group (4-PBA group). DM model rats were induced by injection of STZ (60 mg/kg) intraperitoneally, and 4-PBA was administered daily by gavage at a dose of 500 mg/kg body weight for 20 days. ?-cell apoptosis was higher in the DM group than in the control group. Moreover, the expression of caspase-3, Bax, and the ERS indicators Bip and CHOP was markedly elevated in the pancreas of rats in the DM group, whereas the expression of Bcl-2 was lower in these rats (P < 0.05). Blood glucose concentration in diabetic rats gradually decreased with 4-PBA treatment but remained higher at the end of the experiment compared to the concentration in control rats. Consistent with this, 4-PBA raised the fasting insulin level in diabetic rats; it also suppressed the expression of caspase-3, Bax, and ERS indicators but enhanced the expression of Bcl-2. In conclusion, 4-PBA protects pancreatic ?-cells from apoptosis in STZ-induced diabetes by attenuating the severity of ERS. PMID:24347242

Zhu, Min; Guo, Mei; Fei, Li; Pan, Xiao-Qin; Liu, Qian-Qi

2014-09-01

91

Pharmacological evaluation of "sugar remedy," a polyherbal formulation, on streptozotocin-induced diabetic mellitus in rats.  

PubMed

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

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

2014-07-01

92

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

PubMed Central

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

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

2013-01-01

93

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

PubMed Central

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

2013-01-01

94

Hypoglycemic Activity of Fumaria parviflora in Streptozotocin-Induced Diabetic Rats  

PubMed Central

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

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

2013-01-01

95

Leptin deficiency is involved in the cognitive impairment of streptozocin-induced diabetic rats undergoing cardiopulmonary bypass  

PubMed Central

Several lines of evidence have demonstrated that leptin is probably involved in the cognitive impairment which induced by a single injection of streptozocin (STZ). However, there is little literature reporting the relationship between cognitive impairment and cardiopulmonary bypass (CPB). This study aimed to investigate the role of leptin in the cognitive impairment of STZ-induced diabetic rats undergoing CPB. Wistar rats received 2 h of CPB exposure 1 month after a single intraperitoneal injection of 60 mg/kg of STZ or the vehicle. Behavioral results of rats in Morris water maze were recorded. After that, rat hippocampi were harvested for measuring leptin, tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?). Besides, we observed intracerebroventricular injection of leptin on the cognitive impairment of diabetic-rats undergoing CPB and measured behavioral performance and hippocampal TNF-? and IL-1? levels. Rats undergoing CPB significantly aggravates STZ-induced an increase of the latency to the platform and a decrease of the proportion of time spent in the target quadrant of rats in Morris water maze test. Additionally, the expression of leptin significantly decreased, while TNF-? and IL-1? levels significantly increased. Moreover, intracerebroventricular injection of leptin has a therapeutic effect for cognitive impairment of diabetic rats undergoing CPB. Leptin deficiency in hippocampus is probably involved in the cognitive impairment of streptozocin-induced diabetic rats undergoing cardiopulmonary bypass. PMID:25356111

Yang, Chun; Zhu, Bin; Hua, Fei

2014-01-01

96

The role of arginase I in diabetes-induced retinal vascular dysfunction in mouse and rat models of diabetes  

PubMed Central

Aims/hypothesis A reduction in retinal blood flow occurs early in diabetes and is likely to be involved in the development of diabetic retinopathy. We hypothesise that activation of the arginase pathway could have a role in the vascular dysfunction of diabetic retinopathy. Methods Experiments were performed using a mouse and rat model of streptozotocin (STZ)-induced diabetes for in vivo and ex vivo analysis of retinal vascular function. For in vivo studies, mice were infused with the endothelial-dependent vasodilator acetylcholine (ACh) or the endothelial-independent vasodilator sodium nitroprusside (SNP), and vasodilation was assessed using a fundus microscope. Ex vivo assays included pressurised vessel myography, western blotting and arginase activity measurements. Results ACh-induced retinal vasodilation was markedly impaired in diabetic mice (40% of control values), whereas SNP-induced dilation was not altered. The diabetes-induced vascular dysfunction was markedly blunted in mice lacking one copy of the gene encoding arginase I and in mice treated with the arginase inhibitor 2(S)-amino-6-boronohexanoic acid. Ex vivo studies performed using pressure myography and central retinal arteries isolated from rats with STZ-induced diabetes showed a similar impairment of endothelial-dependent vasodilation that was partially blunted by pretreatment of the isolated vessels with another arginase inhibitor, (S)-2-boronoethyl-l-cysteine. The diabetes-induced vascular alterations were associated with significant increases in both arginase I protein levels and total arginase activity. Conclusions/interpretation These results indicate that, in the mouse and rat model, diabetes-induced increases in arginase I were involved in the diabetes-induced impairment of retinal blood flow by a mechanism involving vascular endothelial cell dysfunction. PMID:23232640

Elms, S. C.; Toque, H. A.; Rojas, M.; Xu, Z.; Caldwell, R. B.

2012-01-01

97

Antioxidant protective effect of glibenclamide and metformin in combination with honey in pancreas of streptozotocin-induced diabetic rats.  

PubMed

Hyperglycemia exerts toxic effects on the pancreatic beta-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage. PMID:20559501

Erejuwa, Omotayo Owomofoyon; Sulaiman, Siti Amrah; Wahab, Mohd Suhaimi Abdul; Salam, Sirajudeen Kuttulebbai Nainamohammed; Salleh, Md Salzihan Md; Gurtu, Sunil

2010-01-01

98

Antioxidant Protective Effect of Glibenclamide and Metformin in Combination with Honey in Pancreas of Streptozotocin-Induced Diabetic Rats  

PubMed Central

Hyperglycemia exerts toxic effects on the pancreatic ?-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage. PMID:20559501

Erejuwa, Omotayo Owomofoyon; Sulaiman, Siti Amrah; Wahab, Mohd Suhaimi Abdul; Salam, Sirajudeen Kuttulebbai Nainamohammed; Salleh, Md Salzihan Md; Gurtu, Sunil

2010-01-01

99

Effect of early insulin therapy on nuclear factor ?B and cytokine gene expressions in the liver and skeletal muscle of high-fat diet, streptozotocin-treated diabetic rats  

Microsoft Academic Search

To clarify the effect of early insulin therapy on nuclear factor ?B (NF?B) pathway and inflammatory cytokine responses in\\u000a the liver and skeletal muscle in type 2 diabetes. High-fat diet and low dose streptozotocin (STZ) induced diabetic rats were\\u000a given NPH insulin or gliclazide for 3 weeks initiated at the 3rd day after STZ injection as early treatment and NPH

Y. Bi; W. P. Sun; X. Chen; M. Li; H. Liang; M. Y. Cai; Y. H. Zhu; X. Y. He; F. Xu; J. P. Weng

2008-01-01

100

Protective effect of potato peel powder in ameliorating oxidative stress in streptozotocin diabetic rats.  

PubMed

The potential of dietary potato peel (PP) powder in ameliorating oxidative stress (OS) and hyperglycemia was investigated in streptozotocin (STZ)-induced diabetic rats. In a 4-week feeding trial, incorporation of potato peel powder (5 and 10%) in the diet of diabetic rats was found to significantly reduce the plasma glucose level and also reduce drastically the polyuria of STZ diabetic rats. The total food intake was significantly reduced in the diabetic rats fed 10% PP powder compared to the control diabetic rats. However, the body weight gain over 28 days was nearly four times greater in PP powder supplemented diabetic rats (both at 5 and 10%) compared to the control diabetic rats. PP powder in the diet also decreased the elevated activities of serum transaminases (ALT and AST) and nearly normalized the hepatic MDA and GSH levels as well as the activities of specific antioxidant enzymes in liver of diabetic rats. The result of these studies clearly establishes the modulatory propensity of PP against diabetes induced alterations. Considering that potato peels are discarded as waste and not effectively utilized, these results suggest the possibility that PP waste could be effectively used as an ingredient in health and functional food to ameliorate certain disease states such as diabetes. PMID:16021831

Singh, Nandita; Kamath, Vasudeva; Rajini, P S

2005-06-01

101

Decreased cholinergic receptor expression in the striatum: motor function deficit in hypoglycemic and diabetic rats.  

PubMed

Hypoglycemic brain injury is a common and serious complication of insulin therapy associated with diabetes. This study evaluated the effect of insulin-induced hypoglycemia and STZ-induced diabetes on striatal cholinergic receptors and enzyme expression and on motor function. Cholinergic enzymes: AChE and ChAT gene expression, radioreceptor binding assay and immunohistochemistry of muscarinic M1, M3 receptors and ?7nAChR were carried out. Motor performance on grid walk test was analysed. AChE and ChAT expression significantly downregulated in hypoglycemic and diabetic rats. Total muscarinic and Muscarinic M3 receptor binding decreased in hypoglycemic rats compared to diabetic rats whereas muscarinic M1 receptor binding increased in hypoglycemic rats compared to diabetic rats. Real-time PCR analysis and confocal imaging of muscarinic M1, M3 receptors confirmed the changes in muscarinic receptor binding in hypoglycemic and diabetic rats. In hypoglycemic rats, ?7nAChR expression significantly up regulated compared to diabetic rats. Grid walk test demonstrated the impairment in motor function and coordination in hypoglycemic and hyperglycemic rats. Neurochemical changes along with the behavioral data implicate a role for impaired striatal cholinergic receptor function inducing motor function deficit induced by hypo and hyperglycemia. Hypoglycemia exacerbated the neurobehavioral deficit in diabetes which has clinical significance in the treatment of diabetes. PMID:21796364

Sherin, A; Peeyush, K T; Jayanarayanan, S; Amee, K K; Paulose, C S

2012-01-01

102

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. PMID:24174814

Singh, Rambir; Bhardwaj, Priyanka; Sharma, Poonam

2013-01-01

103

Antidiabetic and hypolipidemic activities of Kigelia pinnata flowers extract in streptozotocin induced diabetic rats  

PubMed Central

Objective To evaluate antidiabetic and hypolipidemic activities of Kigelia pinnata methanolic flowers extract in streptozotocin (STZ) induced diabetic wistar rat. Methods Rats were made diabetic by a single dose of STZ at 60 mg/kg body weight i.p. The blood glucose level was checked before and 72 h after STZ injection to confirm the development of diabetes. The flower extract and glibenclamide were administered orally at the doses of 250 and 500 mg/kg body weight for 21 days. Results Daily oral treatment with the extract and standard drug for 21 days significantly reduced blood glucose, serum cholesterol and triglycerides levels. High density lipoprotein-cholesterol level was found to be improved (P<0.01) as compared to diabetic control group. Conclusions It is concluded that Kigellia pinnata flowers extract have significant antidiabetic and hypolipidemic effect. PMID:23569967

Kumar, S; Kumar, V; Prakash, OM

2012-01-01

104

MiR-29b Protects Dorsal Root Ganglia Neurons from Diabetic Rat.  

PubMed

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

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

2014-11-01

105

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

2008-02-28

106

Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat.  

PubMed

This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls (n = 12), (2) nondiabetic controls administered losartan (70-80 mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan (n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan (n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 +/- 0.21 g) than in the controls (1.37 +/- 0.14 g; P <.05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 +/- 0.22, 1.73 +/- 0.13, and 1.51 +/- 0.14 g, respectively; P <.05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 +/- 436, 596 +/- 323, 567 +/- 349, and 159 +/- 28 pg/mL; P <.001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 +/- 12 vs 117 +/- 16 nmol/mL/min; P <.05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor-blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous. PMID:14532904

Natif, Noam; Sclarovsky-Benjaminov, Fabiana; Van Dijk, David Jonathan; Sulkes, Jacklin; Gafter, Uzi; Boner, Geoffrey; Erman, Arie

2003-09-01

107

Effect of Diashis, a polyherbal formulation, in streptozotocin-induced diabetic male albino rats  

PubMed Central

This study focuses on the effect of ‘Diashis’, a polyherbal formulation composed of eight medicinal plants for the management of streptozotocin (STZ)-induced diabetes in rats. As oxidative stress is one of the consequences of diabetes, the activities of hepatic antioxidant enzymes and metabolic enzymes were evaluated. Treatment with ‘Diashis’ in STZ-induced diabetic rats resulted in a significant (P < 0.01) recovery in the activities of hepatic hexokinase, glucose-6-phosphate dehydrogenase, and glucose-6-phosphatase along with correction in the levels of fasting blood glucose, glycated hemoglobin, and liver and skeletal muscle glycogen. The oxidative stress status in the liver was corrected by ‘Diashis’ which was highlighted by the recovery in the activities of catalase, peroxidase, and glutathione-S-transferase along with the correction in the quantity of thiobarbituric acid-reactive substances and conjugated diene. ‘Diashis’ was not found to have any metabolic toxicity. The antidiabetic effects of ‘Diashis’ were compared with those of the antidiabetic drug, ‘Glibenclamide’. PMID:20532093

Bera, Tushar K.; De, Debasis; Chatterjee, Kausik; Ali, Kazi M.; Ghosh, Debidas

2010-01-01

108

Antidiabetic effect of Phlomis anisodonta: Effects on hepatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes  

Microsoft Academic Search

The present study investigated the effects of aerial parts of Phlomis anisodonta methanolic extract (PAE) on streptozotocin (STZ)-induced diabetic rats by measuring fasting blood glucose, serum insulin, change in body weight, ferric reducing antioxidant power (FRAP), lipid peroxidation (LPO), and liver antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Male Wistar rats were randomly divided into

Parisa Sarkhail; Somayeh Rahmanipour; Sedigheh Fadyevatan; Azaadeh Mohammadirad; Gholamreza Dehghan; Gholamreza Amin; Abbas Shafiee; Mohammad Abdollahi

2007-01-01

109

Effects of 20-hydroxyecdysone on improving memory deficits in streptozotocin-induced type 1 diabetes mellitus in rat.  

PubMed

We investigate the effects of 20-hydroxyecdysone (20E) on improving memory deficits in the current study by using an animal model of type 1 diabetes mellitus in rats. Animals in control group went on a normal diet. Rats that developed diabetes were divided into 4 groups, including STZ-induced diabetic group which was treated with saline and three 20E groups received different 20E concentrations for 12 weeks. Spatial memory performance was measured in rats by the Morris water maze. The level of nuclear factor-?B (NF-?B) in the brain was determined by real-time quantitative PCR. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were analyzed by real-time quantitative PCR and spectrophotometry. The concentrations of brain-derived neurotrophic factor (BDNF) in the brain were detected by ELISA. Compared with the control group, rats in the STZ-induced diabetic group that developed type 1 diabetes exhibited significant memory loss. In addition to the hippocampus CA1 area that displayed severe damage, significantly higher expression levels of NF-?B were observed in these rats. Furthermore, the expression levels of SOD, catalase, GSH-Px GR and BDNF were significantly decreased in rats with diabetes. By contrast, the treatment with 20E, especially at higher concentrations, reversed the above-mentioned conditions caused by diabetes. The results suggest that the 20E has a protective role in counteracting memory deficits in rats with diabetes of rat, possibly through enhancing the antioxidative ability in the brain. PMID:24997424

Xia, Xichao; Zhang, Qingyuan; Liu, Rongzhi; Wang, Zhongxiao; Tang, Nianya; Liu, Fei; Huang, Guosheng; Jiang, Xiao; Gui, Gaixia; Wang, Lijuan; Sun, Xiuli

2014-10-01

110

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

PubMed Central

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

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

2013-01-01

111

Effects of aminoguanidine and tolrestat on the development of ocular and renal structural changes in experimental diabetic rats.  

PubMed

Studies that researched the role of aminoguanidine and tolestat in the prevention of diabetic retinopathy and nephropathy resulted in conflicting data. We investigated the effects of these agents in the prevention of ocular and renal changes in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ in 30 rats. Ten rats that were not given STZ served as non-diabetic control (Group 1). Ten STZ-diabetic rats that were not given any treatment served as diabetic control (Group 2). Groups 3 and 4 were composed of STZ-induced diabetic rats (10 each) that were given tolrestat and aminoguanidine respectively. Eyes and kidneys were examined at the 24th week under electronmicroscopy. Cataract was observed in all six of the surviving rats in Groups 2 and 4, and in one of 6 surviving rats in group 3. Cataract development was lower in Group 3 than Groups 2 and 4. All retinal samples obtained from group 2 demonstrated a number of structural abnormalities, whereas there were no significant ultrastructural changes in groups 3 and 4. Groups 2 and 3 demonstrated mesangial proliferation and expansion, diffuse glomerular basement membrane (GBM) thickening, and focal GBM thickening in the bulb form. Group 4 demonstrated a normally appearing mesangial space, minimal diffuse but no focal GBM thickening. The urinary albumin excretion (UAE) was lower in Group 4 than the other groups. In conclusion, our results suggest that aminoguanidine may be an important agent for the prevention of renal changes, whereas tolrestat may be effective for the prevention of ocular changes in diabetes mellitus. PMID:11874446

Azal, O; Yönem, A; Güler, S; Cakir, B; Baydar, A; Corakçi, A; Kutlu, M

2002-01-01

112

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

PubMed Central

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

2014-01-01

113

Relationship between the Level of Hippocampal Leptin Receptor Gene Expression and Learning Performance in Diabetic Rats.  

PubMed

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

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

2014-11-01

114

Antidiabetic effect of plumbagin isolated from Plumbago zeylanica L. root and its effect on GLUT4 translocation in streptozotocin-induced diabetic rats.  

PubMed

Plumbago zeylanica L. root is widely used in Indian medicine to treat diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of plumbagin isolated from P. zeylanica L. root and its effect on GLUT4 translocation in STZ-induced diabetic rats. Plumbagin (15 and 30 mg/kg b wt) was orally administered to STZ-induced diabetic rats for 28 days. An oral glucose tolerance test was performed on 21st day. The effect of plumbagin on body weight, blood glucose, plasma insulin, total protein, urea, creatinine, liver glycogen, plasma enzymes (SGOT, SGPT and ALP) and carbohydrate metabolism enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase) were investigated. GLUT4 mRNA and protein expression in skeletal muscles were also studied. Plumbagin significantly reduced the blood glucose and significantly altered all other biochemical parameters to near normal. Further, plumbagin increased the activity of hexokinase and decreased the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase significantly in treated diabetic rats. Enhanced GLUT4 mRNA and protein expression were observed in diabetic rats after treatment with plumbagin. The results indicated that plumbagin enhanced GLUT4 translocation and contributed to glucose homeostasis. It could be further probed for use as a drug to treat diabetes. PMID:22960630

Sunil, Christudas; Duraipandiyan, Veeramuthu; Agastian, Paul; Ignacimuthu, Savarimuthu

2012-12-01

115

Neuroprotective effect of RYGB in Zucker fatty diabetic rats  

PubMed Central

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

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

2014-01-01

116

Anti-diabetic effect of sorghum extract on hepatic gluconeogenesis of streptozotocin-induced diabetic rats  

PubMed Central

Background It has been suggested that Sorghum, a rich source of phytochemicals, has a hypoglycemic effect, but the mechanism is unknown. We investigated the effects of oral administration of sorghum extract (SE) on hepatic gluconeogenesis and the glucose uptake of muscle in streptozotocin-induced diabetic rats for six weeks. Methods Male Wistar rats were divided in five groups (n=5 per group): normal control (NC), rats with STZ-induced diabetic mellitus (DM), diabetic rats administrated 0.4 g/kg body weight of SE (DM-SE 0.4) and 0.6 g/kg body weight of SE (DM-SE 0.6), and diabetic rats administrated 0.7 mg/kg body weight of glibenclamide (DM-G). Results Administration of SE and G reduced the concentration of triglycerides, total and LDL-cholesterol and glucose, and the area under the curve of glucose during intraperitoneal glucose tolerance tests down to the levels observed in non-diabetic rats. In addition, administration of 0.4 and 0.6 g/kg SE and 0.7 mg/kg glibenclamide (G) significantly reduced the expression of phosphoenolpyruvate carboxykinase and the phosphor-p38/p38 ratio, while increased phosphor adenosine monophosphate activated protein kinase (AMPK)/AMPK ratio, but the glucose transporter 4 translocation and the phosphor-Akt/Akt ratio was significantly increased only by administration of G. Conclusions These results indicate that the hypoglycemic effect of SE was related to hepatic gluconeogenesis but not the glucose uptake of skeletal muscle, and the effect was similar to that of anti-diabetic medication. PMID:23186010

2012-01-01

117

Decrease of PPAR? in Type-1-Like Diabetic Rat for Higher Mortality after Spinal Cord Injury  

PubMed Central

Changes in the peroxisome proliferator-activated receptors-? (PPAR?) expression in rats after spinal cord injury (SCI) have been previously reported. Diabetic animals show a higher mortality after SCI. However, the relationship between the progress of diabetes and PPAR? in SCI remains unknown. In the present study, we used compressive SCI in streptozotocin-(STZ-) induced diabetic rats. GW0742, a PPAR? agonist, was used to evaluate its merit in STZ rats after SCI. Changes in PPAR? expression were detected by Western blot. Survival rates were also estimated. A lower expression of PPAR? in spinal cords of STZ-diabetic rats was observed. In addition, the survival times in two-week induction diabetes were longer than those in eight-week induction group, which is consistent with the expression of PPAR? in the spinal cord. Moreover, GW0742 significantly increased the survival time of STZ rats. Furthermore, their motor function and pain response were attenuated by GSK0660, a selective PPAR? antagonist, but were enhanced by GW0742. In conclusion, the data suggest that higher mortality rate in STZ-diabetic rats with SCI is associated with the decrease of PPAR? expression. Thus, change of PPAR? expression with the progress of diabetes seems responsible for the higher mortality rate after SCI. PMID:24817882

Tsai, Cheng-Chia; Lee, Kung-Shing; Chen, Sheng-Hsien; Chen, Li-Jen; Liu, Keng-Fan; Cheng, Juei-Tang

2014-01-01

118

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. PMID:23840309

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

2013-01-01

119

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. PMID:22272082

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

120

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. PMID:10516670

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

1999-01-01

121

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

PubMed

1. 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. 2. 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. 3. 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 Nomega-nitro-L-arginine (LNNA) alone. Combining LNNA and KCl further reduced ACh-induced dilation in these vessels. 4. 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. PMID:10516670

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

1999-10-01

122

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

123

Selenium-vitamin E combination and melatonin modulates diabetes-induced blood oxidative damage and fetal outcomes in pregnant rats.  

PubMed

Oxidative stress is considered to be the main cause of diabetic complications. In the current study, we investigated the effect of selenium-vitamin E combination and melatonin on lipid peroxidation (LPO) and scavenging enzyme activity in the blood of streptozocin (STZ)-induced diabetic pregnant rats. Forty female Wistar rats were randomly divided into five groups. The first and second groups were used as the non-pregnant control and pregnant control groups, respectively. The third group was the pregnant diabetic group. Vitamin E plus selenium and melatonin were administered to the diabetic pregnant rats consisting fourth and fifth groups, respectively. Diabetes was induced on day 0 of the study by STZ. Blood samples were taken from all animals on the 20th day of pregnancy. LPO level was higher in diabetic pregnant rats than in control, although superoxide dismutase, catalase, and glutathione peroxidase activities were lower in diabetic pregnant animals than in control. LPO levels were lower both in the two treatment groups than in the diabetic pregnant rats, whereas selenium-vitamin E combination and melatonin caused a significant increase in the activities of these antioxidant enzymes (p<0.01). In conclusion, vitamin E plus selenium seems to be a more potent antioxidant compared to melatonin in diabetic pregnant rats. Melatonin did not significantly affect the elevated glucose concentration of diabetic pregnant treated with melatonin group. Vitamin E plus selenium may play a role in preventing diabetes-related diseases of pregnant subjects. PMID:21240568

Guney, Mehmet; Erdemoglu, Evrim; Mungan, Tamer

2011-11-01

124

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

PubMed Central

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

Singh, Ajay Kumar; Singh, Jyoti

2010-01-01

125

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 Central

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

2013-01-01

126

Berberine ameliorates renal injury by regulating G proteins-AC- cAMP signaling in diabetic rats with nephropathy.  

PubMed

Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to glomerulus and glomerular mesangial cells (MCs) proliferation play a critical role in the pathogenesis of DN. The current studies were undertaken to investigate the protective effects and the possible molecular mechanism of berberine on streptozotocin (STZ)-induced DN rats. Male Wistar rats were randomly assigned to normal control and DN groups of comparable age. Three DN groups received 50, 100 and 200 mg/kg of berberine for 8 weeks via daily intragastrically, respectively. The G proteins-adenylyl cyclase (AC)-cAMP signaling pathway and glomerular MCs proliferation were examined in STZ-induced diabetic rat kidney. Enhanced MCs proliferation and remarkable renal injury were concomitant with activation of G?i and inhibition of G?s and cAMP in DN model group. Berberine treatment for 8 weeks abolished the above changes by upregulating the expression of G?s protein and downregulating the expression of G?i protein, increasing cAMP level, and inhibiting MCs proliferation compared with model group. Taken together, for the first time, these results demonstrated that berberine can relieve renal injury in DN rats through mediating G proteins-AC-cAMP signaling pathway and inhibiting the abnormal proliferation of MCs by increasing cAMP level, suggesting that berberine could be a potential therapeutic agent for the treatment of DN. PMID:23266672

Tang, Li Qin; Wang, Feng Ling; Zhu, Ling Na; Lv, Fei; Liu, Sheng; Zhang, Shan Tang

2013-06-01

127

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

Microsoft Academic Search

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

M. Shahidul Islam; Haymie Choi; Du Toit Loots

2008-01-01

128

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

PubMed Central

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

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

2013-01-01

129

Effects of warfarin and L-carnitine on hemostatic function and oxidative stress in streptozotocin-induced diabetic rats.  

PubMed

Diabetes mellitus (DM) is a complex progressive disease characterized by hyperglycemia and a high risk of atherothrombotic disorders affecting the coronary, cerebral, and peripheral arterial trees. Oxidative stress is reported in diabetic patients. We investigated the hemostatic functions and oxidative stress in streptozotocin (STZ)-induced diabetic rats and the effects of warfarin and L-carnitine on those parameters. Forty male Sprague-Dawley rats were divided into four groups: control, DM, and DM received warfarin or L-carnitine. In all rats, blood glucose, insulin, hemoglobin A1c (HbA1c), fibrinogen, factor VII (FVII), plasminogen activator inhibitor-1 (PAI-1), fibrin degradation products (FDP), protein C, antithrombin III (ATIII), malondialdehydes (MDA), and antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione) were measured. Also, prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation time, and platelet aggregation were evaluated. In diabetic rats, plasma glucose, HbA1c, MDA, fibrinogen, FVII, FDP, PAI-1, and platelet aggregation increased while insulin, PT, aPTT, coagulation time, protein C, ATIII, and antioxidants decreased. Warfarin administration to diabetic rats decreased FVII and FDP and increased PT, aPTT, and coagulation time with no effect on MDA, antioxidants, PAI-1, protein C, ATIII, and platelet aggregation. On the other hand, L-carnitine decreased fibrinogen, FVII, FDP, PAI-1, MDA, and platelet aggregation and increased PT, aPTT, coagulation time, protein C, ATIII, and antioxidants in diabetic rats. Therefore, we concluded that hyperglycemia plays an important role in hypercoagulation state and oxidative stress in STZ-induced DM. While L-carnitine improves oxidative stress and decreases the hypercoagulation state in DM, warfarin normalizes the hypercoagulation state with no effect on oxidative stress. PMID:24671746

ElGendy, Ahmed A; Abbas, Amr M

2014-06-01

130

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

PubMed Central

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

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

2014-01-01

131

Cardiopulmonary Profile in Streptozotocin-Induced Type 1 Diabetic Rats during Systemic Endotoxemia  

PubMed Central

This study was designed to determine the severity of cardiopulmonary dysfunction during systemic endotoxemia in type 1 diabetes. Thirty-two adult male Wistar rats were randomly assigned to a control group or to a group treated with streptozotocin (STZ) to create an animal model of type 1 diabetes. Survival time and cardiovascular parameters were continually monitored in urethane anaesthetized animals receiving intravenous infusion of endotoxin (lipopolysaccharide (LPS)) or saline. We also determined arterial blood gases, lung injury, and tumor necrosis factor-alpha (TNF-?) levels in serum and bronchoalveolar lavage fluid. Before LPS administration, the mean arterial pressure in STZ rats was significantly higher than that in normal rats. After LPS injection, the heart rate drop significantly in STZ rats than that in the control group. Also, the increased levels of TNF-? in serum and lavage fluid after LPS treatment were significantly higher in STZ rats than those in normal rats. Survival time in STZ rats was shorter than that in normal rats after LPS application. Albumin content, wet/dry weight ratio of lung, and lung injury were indistinguishable between STZ and normal rats. These results indicate that the cardiopulmonary change which occurs during LPS-induced endotoxemia is minor in STZ-induced diabetic rats. PMID:23671873

Hung, Ching-Hsia; Chang, Che-Ning; Chen, Yu-Wen; Chen, Yu-Chung; Tzeng, Jann-Inn; Wang, Jhi-Joung

2013-01-01

132

Short-term effects of vanadate treatment in diabetic rats  

SciTech Connect

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

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

1991-03-11

133

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

PubMed Central

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

2013-01-01

134

Expression and Activity of SGLT2 in Diabetes Induced by Streptozotocin: Relationship with the Lipid Environment  

Microsoft Academic Search

Background\\/Aims: Diabetes mellitus may impact on the regulation of renal Na+-glucose cotransporter type 2 (SGLT2), however, previous studies have yielded conflicting results on the effects of streptozotocin (STZ)-induced diabetes on SGLT-mediated glucose transport. Methods: Diabetes was induced in male Wistar rats. The studies were performed at 3 (D3), 7 (D7) and 14 (D14) days after a single i.p. injection of

María F. Albertoni Borghese; Mónica P. Majowicz; María C. Ortiz; María del Rosario Passalacqua; Norma B. Sterin Speziale; Norberto A. Vidal

2009-01-01

135

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

PubMed

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

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

2013-08-01

136

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

PubMed Central

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

Kim, Si Oh

2013-01-01

137

Streptozotocin-induced diabetic pregnant rats exhibit signs and symptoms mimicking preeclampsia.  

PubMed

The number of patients with hypertension, obesity, diabetes, and hyperlipidemia is increasing. This tendency is observed in pregnant women, in whom many obstetrical and perinatal complications occur. The prevention of these abnormalities is important in reducing perinatal mortality and the risk of coronary disease. We established a pregnant rat model with diabetes and signs and symptoms mimicking preeclampsia. On day 6 of pregnancy, streptozotocin (STZ) or citrate buffer was injected into the tail vein. After STZ administration, plasma glucose was increased within 48 hours and sustained at a high level until day 20 of pregnancy, and plasma insulin was decreased. Fetuses from STZ-treated mothers were growth-restricted, and plasma glucose was 6-fold higher in fetuses of STZ-treated versus control rats. The systolic blood pressure, urinary protein, and hematocrit were increased significantly in STZ-treated rats. Total cholesterol and triglycerides were also elevated in STZ-treated rats, but plasma leptin levels were decreased. The STZ-induced diabetic pregnant rat model exhibited preeclampsia, hemoconcentration, hyperlipidemia, hypoleptinemia, and intrauterine growth restriction. This model closely mimics the features of human pregnancy complicated by diabetes and is useful for the basic study of the pathophysiology of pregnancy with diabetes. PMID:10909994

Ishihara, G; Hiramatsu, Y; Masuyama, H; Kudo, T

2000-07-01

138

The Role of Cutaneous Innervation in the Sensory Abnormalities Associated with Diabetic Neuropathy  

E-print Network

type 1 etiology. In several strains of rats, STZ-induced diabetes causes mechanical, thermal, and chemogenic hyperalgesia as well as tactile and thermal allodynia (Calcutt 2004). Hyperalgesia also develops in genetic rat models of type 1 and type 2... of diabetes, such as the autoimmune-initiated BioBreeding diabetic rats (Gabra et al. 2005), Zucker diabetic fatty rats (Zhuang et al. 1997; Piercy et al. 1999; Li et al. 2006), and the Otsuka Long-Evans Tokushima fatty rat (Kamenov et al. 2006...

Johnson, Megan Sarah

2008-05-05

139

Distribution of free amino acids in streptozotocin-induced diabetic pregnant rats, their placentae and fetuses.  

PubMed

Amino acid levels in the non-pregnant streptozotocin (STZ)-induced diabetic rat have been shown to be abnormal. Our preliminary studies showed that placental transport, fetal serum levels and tissue uptake of the non-metabolizable amino acid alpha-amino isobutyric acid (AIB) were decreased in STZ-diabetic pregnant rats. In the present experiments, amino acid concentrations were measured in maternal (MS) and fetal (FS) sera and placentae (PL) by high performance liquid chromatography (HPLC) after triple extraction in 80% ethanol. Control (C), STZ-diabetic (D) and insulin-treated diabetic (DI) animals were studied at 22 days gestation. Pregnant diabetic rats had low serum levels of Gln, Lys, and Ser and insulin treatment corrected Gln and Ser but not Lys levels. Branched-chain amino acids did not show the large elevation characteristic of the non-pregnant diabetic rat. Placental levels of Tau, Gln, HPr, Thr and Lys were depressed in the diabetic animals and insulin treatment only partially improved these amino acid profiles. Placental amino acid levels did not always reflect maternal serum levels. Serum levels of most amino acids were lower in the fetus of the diabetic rat than in the fetus of the control rat. The notable exception was Ala which was higher in the fetuses of the diabetic animals. Insulin treatment of the mother did not correct many of the fetal amino acid levels even though maternal and fetal serum glucose levels at the time of autopsy were normal. The ability to maintain normal serum levels of many amino acids is impaired in the fetus of the diabetic rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2182503

Copeland, A D; Hendrich, C E; Porterfield, S P

1990-02-01

140

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

PubMed

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

Hasanein, Parisa; Fazeli, Farzaneh

2014-12-01

141

Investigation of hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats  

PubMed Central

Objective To investigate the hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark (AETPB) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity was studied in rats after the oral administration of AETPB to determine the dose to assess hypoglycemic activity. In rats, diabetes was induced by injection of STZ (60 mg/kg, i.p.) and diabetes was confirmed 72 h after induction, and then allowed for 14 days to stabilize blood glucose level. In diabetic rats, AETPB was orally given for 28 days and its effect on blood glucose and body weight was determined on a weekly basis. At the end of the experimental day, fasting blood sample was collected to estimate the haemoglobin (Hb), glycosylated haemoglobin (HbA1c), serum creatinine, urea, serum glutamate-pyruvate transaminase (SGPT), serum glutamate-oxaloacetate transaminase (SGOT) and insulin levels. The liver and kidney were collected to determine antioxidants levels in diabetic rats. Results Oral administration of AETPB did not exhibit toxicity and death at a dose of 2?000 mg/kg. AETPB treated diabetic rats significantly (P<0.001, P<0.01 and P<0.05) reduced elevated blood glucose, HbA1c, creatinine, urea, SGPT and SGOT levels when compared with diabetic control rats. The body weight, Hb, insulin and total protein levels were significantly (P<0.001, P<0.01 and P<0.05) increased in diabetic rats treated with AETPB compared to diabetic control rats. In diabetic rats, AETPB treatment significantly reversed abnormal status of antioxidants and lipid profile levels towards near normal levels compared to diabetic control rats. Conclusions Present study results confirm that AETPB possesses significant hypoglycemic, hypolipidemic and antioxidant activities in diabetic condition. PMID:23569911

Ramachandran, Subramaniam; Rajasekaran, Aiyalu; Manisenthilkumar, KT

2012-01-01

142

Diazoxide Reduces Status Epilepticus Neuron Damage in Diabetes  

Microsoft Academic Search

Diabetic hyperglycemia is associated with seizure severity and may aggravate brain damage after status epilepticus. Our earlier\\u000a studies suggest the involvement of ATP-sensitive potassium channels (KATP) in glucose-related neuroexcitability. We aimed to determine whether KATP agonist protects against status epilepticus-induced brain damage. Adult male Sprague–Dawley rats were divided into two groups:\\u000a the streptozotocin (STZ)-induced diabetes (STZ) group and the normal

Chin-Wei Huang; Sheng-Nan Wu; Juei-Tang Cheng; Jing-Jane Tsai; Chao-Ching Huang

2010-01-01

143

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

PubMed Central

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

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

2014-01-01

144

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

Microsoft Academic Search

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

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

2009-01-01

145

Effect of curcumin on hyperglycemia-induced vascular endothelial growth factor expression in streptozotocin-induced diabetic rat retina.  

PubMed

Diabetic retinopathy is one of the most devastating microvascular complications of long standing type 1 and type 2 diabetes. Neovascularization stimulated by hyperglycemia-mediated induction of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis. Various small molecules have been investigated for their ability to inhibit angiogenesis. In this study, we evaluated whether curcumin and its dietary source turmeric can inhibit VEGF expression in strepotzotocin (STZ)-induced diabetic rat retina. Diabetes was induced in 3-month-old male WNIN rats by a single intraperitoneal injection of STZ. After induction, one group of diabetic rats were fed only the AIN-93 diet and the rest of the groups were fed with AIN-93 diet containing 0.002% or 0.01% curcumin or 0.5% turmeric for a period of 8 weeks. The control rats received sham injection and fed on the AIN-93 diet. At the end of 8 weeks animals were sacrificed and retina was dissected. The VEGF expression was analyzed by both real time PCR and immunoblotting. There was an increase in VEGF expression in diabetic retina as compared to control retina at both transcript and protein level. Notably, feeding of curcumin and turmeric to diabetic rats inhibited expression of VEGF. This study highlights the importance of biologically active compounds derived from dietary agents that could be explored further for the prevention and/or treatment of diabetic retinopathy. PMID:17662242

Mrudula, T; Suryanarayana, P; Srinivas, P N B S; Reddy, G Bhanuprakash

2007-09-21

146

Thyroid hormones-mediated effects of insulin on antioxidant enzymes from diabetic rat hearts.  

PubMed

Free radicals, oxidative stress, and antioxidants have become commonly used terms in modern discussion of disease mechanisms. Accumulation of evidence suggests that toxic oxygen-derived reactive free radicals (superoxide, peroxide and hydroxyl radicals) play a crucial role in etiology of diabetes and its complication. Thus, it was aimed to determine the role of thyroid hormones in reversal of antioxidatant enzyme activities and lipid peroxidation alterations observed in experimentally induced diabetic rat hearts. The present study investigates the antioxidant enzyme activities such as SOD, CAT, GSH-Px and lipid peroxidation products in cardiac tissues of streptozotosin (STZ)-induced diabetic rats before and after thyroidectomy. Our results showed that CAT, GPx enzyme activities and FOX, MDA levels were increased (p<0.05) during diabetes, hypothyroidism and hypothyroidism with diabetes, which can be regulated in different percentages with treatment of insulin and various doses of thyroid hormone ((p<0.05). In conclusion, in this study, the possible contribution of thyroid hormones to the insulin effect of normalizing the induced diabetic changes in cardiac tissue and serum of rat has been seen (Tab. 5, Ref. 32). PMID:23514549

Kosova, F; Altan, N; Sepici, A; Engin, A; Kocamanoglu, N

2013-01-01

147

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

PubMed Central

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

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

2015-01-01

148

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

PubMed Central

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

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

2014-01-01

149

Effects of Phenolic Compounds of Fermented Thai Indigenous Plants on Oxidative Stress in Streptozotocin-Induced Diabetic Rats  

PubMed Central

We investigated the effects of antioxidant activity of fermentation product (FP) of five Thai indigenous products on oxidative stress in Wistar rats with streptozotocin (STZ)-induced diabetes type II. The rats were fed with placebo and with the FP (2 and 6?mL/kg body weight/day) for 6 weeks. Rutin, pyrogallol and gallic acid were main compounds found in the FP. Plasma glucose levels in diabetic rats receiving the higher dose of the FP increased less when compared to the diabetic control group as well as the group receiving the lower FP dose (13.1%, 29%, and 21.1%), respectively. A significant dose-dependent decrease in plasma levels of thiobarbituric acid reactive substance (P < .05) was observed. In addition, the doses of 2 and 6?mL FP/kg/day decreased the levels of erythrocyte ROS in diabetic rats during the experiment, but no difference was observed when compared to the untreated diabetic rat group. Results imply that FP decreased the diabetes-associated oxidative stress to a large extent through the inhibition of lipid peroxidation. The FP also improved the abnormal glucose metabolism slightly but the difference was not statistically significant. Thus, FP may be a potential therapeutic agent by reducing injury caused by oxidative stress associated with diabetes. PMID:21423638

Chaiyasut, Chaiyavat; Kusirisin, Winthana; Lailerd, Narissara; Lerttrakarnnon, Peerasak; Suttajit, Maitree; Srichairatanakool, Somdet

2011-01-01

150

The Impact of Low-Dose Insulin on Peripheral Nerve Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats  

PubMed Central

Background The precise mechanisms of the neuroprotective effects of insulin in streptozotocin (STZ)-induced diabetic animals remain unknown, but altered peripheral nerve insulin receptor signaling due to insulin deficiency might be one cause. Methodology and Principal Findings Diabetes was induced in 10-week-old, male Wistar rats by injecting them with STZ (45 mg/kg). They were assigned to one group that received half of an insulin implant (?1 U/day; I-group, n?=?11) or another that remained untreated (U-group, n?=?10) for 6 weeks. The controls were age- and sex-matched, non-diabetic Wistar rats (C-group, n?=?12). Low-dose insulin did not change haemoglobin A1c, which increased by 136% in the U-group compared with the C-group. Thermal hypoalgesia and mechanical hyperalgesia developed in the U-group, but not in the I-group. Sensory and motor nerve conduction velocities decreased in the U-group, whereas sensory nerve conduction velocity increased by 7% (p?=?0.0351) in the I-group compared with the U-group. Western blots showed unaltered total insulin receptor (IR), but a 31% decrease and 3.1- and 4.0-fold increases in phosphorylated IR, p44, and p42 MAPK protein levels, respectively, in sciatic nerves from the U-group compared with the C-group. Phosphorylated p44/42 MAPK protein decreased to control levels in the I-group (p<0.0001). Conclusions and Significance Low-dose insulin deactivated p44/42 MAPK and ameliorated peripheral sensory nerve dysfunction in rats with STZ-induced diabetes. These findings support the notion that insulin deficiency per se introduces impaired insulin receptor signaling in type 1 diabetic neuropathy. PMID:24023699

Sugimoto, Kazuhiro; Baba, Masayuki; Suzuki, Susumu; Yagihashi, Soroku

2013-01-01

151

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

PubMed Central

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

2014-01-01

152

Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats.  

PubMed

Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas. PMID:20398890

Erejuwa, O O; Sulaiman, S A; Wahab, M S; Sirajudeen, K N S; Salleh, M S Md; Gurtu, S

2010-09-01

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. PMID:24151502

Kamboj, Anil; Kumar, Sunil; Kumar, Vipin

2013-01-01

154

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. PMID:24167738

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

2013-01-01

155

Protective nature of mangiferin on oxidative stress and antioxidant status in tissues of streptozotocin-induced diabetic rats.  

PubMed

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

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

2013-01-01

156

The effects of the water-extraction of Astragali Radix and Lycopi herba on the Pathway of TGF-smads-UPP in a rat model of Diabetic Nephropathy  

PubMed Central

Background: Astragali Radix and Lycopi Herba were widely used in clinical practice for treating the diabetic nephropathy (DN), but their therapeutic mechanisms were not clear. Objective: To observe the effects of the water-extraction of Astragali Radix and Lycopi Herba on the signaling pathway of TGF-Smads-UPP in streptozotocin (STZ)-induced DN. Materials and Methods: Sprague-Dawley (SD) rats were randomly divided into the normal control (NC) group and the model group. The NC group was fed with a standard diet and the other five diabetic groups received a high-fat diet. After 4 weeks, five diabetic groups were treated with STZ (30mg/kg i.p.). The NC group rats were treated with citrate buffer. Tail random blood glucose (RBG) was measured 72h later using a strip-operated blood glucose sensor and monitored every 2 weeks until drug intervention. Rats with RBG levels less than 16.7mmol/L were excluded from the diabetic groups. At the end of 4 weeks after STZ injection, 24h microalbuminuria was collected and detected. The microalbuminuria was measured by radioimmunoassay (RIA). The blood glucose was tested using a blood glucose meter. The kidney was dissected from each SD rat. Proteins and mRNA of TGF-?1, Smads and Smurf were tested by western-blot and real-time PCR analysis, and 26S proteasome activity was measured by an ELISA kit. Results: The water-extraction of Astragali Radix and Lycopi Herba significantly lowered fasting glucose and urine albumin in diabetic rats through inhibition of TGF-?1 mRNA and protein expression in the STZ-induced diabetic rats, and regulation of the Smad3, Smad7, Smurf1, Smurf2 mRNA and protein expression, as well as elevated 26S proteasome activity to play control effect in DN. Conclusion: 0.9 g/ml water-extraction of Astragali Radix and Lycopi Herba group has significant therapeutic effects on the STZ-induced diabetic rats, and this regulation depends on TGF-Smads-UPP signaling pathway.

Fu, Xiao; Song, Bing; Tian, Guo-wei; Li, Jing-Lin

2014-01-01

157

Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats  

PubMed Central

Bone marrow stem cells participate in tissue repair processes and may have a role in wound healing. Diabetes is characterised by delayed and poor wound healing. We investigated the potential of bone marrow-derived mesenchymal stromal cells (BMSCs) to promote healing of fascial wounds in diabetic rats. After manifestation of streptozotocin (STZ)-induced diabetic state for 5 weeks in male adult Sprague–Dawley rats, healing of fascial wounds was severely compromised. Compromised wound healing in diabetic rats was characterised by excessive polymorphonuclear cell infiltration, lack of granulation tissue formation, deficit of collagen and growth factor [transforming growth factor (TGF-?), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor PDGF-BB and keratinocyte growth factor (KGF)] expression in the wound tissue and significant decrease in biomechanical strength of wounds. Treatment with BMSC systemically or locally at the wound site improved the wound-breaking strength (WBS) of fascial wounds. The improvement in WBS was associated with an immediate and significant increase in collagen levels (types I–V) in the wound bed. In addition, treatment with BMSCs increased the expression of growth factors critical to proper repair and regeneration of the damaged tissue moderately (TGF-?, KGF) to markedly (EGF, VEGF, PDGF-BB). These data suggest that cell therapy with BMSCs has the potential to augment healing of the diabetic wounds. PMID:18593394

Kwon, David S; Gao, Xiaohua; Liu, Yong Bo; Dulchavsky, Deborah S; Danyluk, Andrew L; Bansal, Mona; Chopp, Michael; McIntosh, Kevin; Arbab, Ali S; Dulchavsky, Scott A; Gautam, Subhash C

2013-01-01

158

Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats  

PubMed Central

Background: Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. Objective: This study was undertaken to examine the effects of gallic acid in myocardial dysfunctions associated with type-1 diabetes. Materials and Methods: Diabetes was induced by single intravenous injection of streptozotocin (STZ, 50 mg/kg i.v.). Gallic acid was administered daily at three different doses (100, 50, and 25 mg/kg p.o.) for 8 weeks at the end of which blood samples were collected and analyzed for various biochemical parameters. Results: Injection of STZ produced significant loss of body weight (BW), polyphagia, polydypsia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypertension, bradycardia, and myocardial functional alterations. Treatment with gallic acid significantly lowered fasting glucose, the AUCglucose level in a dose-dependent manner; however, the insulin level was not increased significantly at same the dose and prevented loss of BW, polyphagia, and polydypsia in diabetic rats. It also prevented STZ-induced hyperlipidemia, hypertension, bradycardia, structural alterations in cardiac tissue such as increase in force of contraction, left ventricular weight to body weight ratio, collagen content, protein content, serum lactate dehydrogenase, and creatinine kinase levels in a dose-dependent manner. Further, treatment also produced reduction in lipid peroxidation and increase in antioxidant parameters in heart of diabetic rats. Conclusion: The results of this study suggest that gallic acid to be beneficial for the treatment of myocardial damage associated with type-1 diabetes. PMID:22224046

Patel, Snehal S.; Goyal, Ramesh K.

2011-01-01

159

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. PMID:23372054

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

2013-01-01

160

Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism  

Microsoft Academic Search

This paper explores the role of endothelins (ETs) in diabetes-induced testicular damage by investigating, in a temporal manner,\\u000a testes from streptozotocin (STZ)-induced diabetic rats. Testicular and epididymal weights and testicular morphology were assessed.\\u000a Cell death was evaluated by light microscopy using conventional staining and morphology, and by apoptotic cell staining using\\u000a the Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling (TUNEL) technique.

Lu Cai; Shali Chen; Terry Evans; Diana Xi Deng; Kallol Mukherjee; Subrata Chakrabarti

2000-01-01

161

Streptozotocin induced diabetic retinopathy in rat and the expression of vascular endothelial growth factor and its receptor  

PubMed Central

AIM To establish the rat model of streptozotocin (STZ)-induced diabetic retinopathy (DR), which is the most common cause of visual loss and blindness in patients with diabetes, and observe the gene expression of vascular endothelial growth factor (VEGF) and its receptors during the development of DR. METHODS A rat model of diabetes was established by intraperitoneal injection of STZ. The diabetic rats were housed for 2, 3 and 4 months after the development of diabetes. Retinal histopathological observation was performed. The retinal vessels were observed by immunofluorescence staining by CD31. The mRNA expression of VEGF, VEGF receptor 1 and 2 (VEGFR1/2) in rat retina was detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis. RESULTS Retinal histopathological observation showed the morphological changes of inner nuclear layer (INL) and outer nuclear layer (ONL) at any time-point, and also demonstrated the increased new vessels at both 3, 4 months after the development of diabetes. The CD31 staining results showed that the number of vessels was increased in the retinas of diabetic rats at both 3 and 4 months after the development of diabetes. As compared to the normal rats, the mRNA expression of VEGF was increased in retinas of diabetic rats at 3 months after the development of diabetes, while VEGFR1 and VEGFR2 mRNA expression was increased at 2, 3 and 4 months after the development of diabetes. CONCLUSION Taken together, our results demonstrated that DR was occurred at 3 months after the development of diabetes, and the mRNA expression of VEGF, VEGFR1 and VEGFR2 were increased in the process of DR. The present study further evidenced the involvement of VEGF and its receptors in the process of DR. PMID:24195027

Gong, Chen-Yuan; Lu, Bin; Hu, Qian-Wen; Ji, Li-Li

2013-01-01

162

Improvement of renal oxidative stress markers after ozone administration in diabetic nephropathy in rats  

PubMed Central

Background Several complications of diabetes mellitus (DM) e.g. nephropathy (DN) have been linked to oxidative stress. Ozone, by means of oxidative preconditioning, may exert its protective effects on DN. Aim The aim of the present work is to study the possible role of ozone therapy in ameliorating oxidative stress and inducing renal antioxidant defence in streptozotocin (STZ)-induced diabetic rats. Methods Six groups (n = 10) of male Sprague Dawley rats were used as follows: Group C: Control group. Group O: Ozone group, in which animals received ozone intraperitoneally (i.p.) (1.1 mg/kg). Group D: Diabetic group, in which DM was induced by single i.p. injections of streptozotocin (STZ). Group DI: Similar to group D but animals also received subcutaneous (SC) insulin (0.75 IU/100 gm BW.). Group DO: In which diabetic rats received the same dose of ozone, 48 h after induction of diabetes. Group DIO, in which diabetic rats received the same doses of insulin and ozone, respectively. All animals received daily treatment for six weeks. At the end of the study period (6 weeks), blood pressure, blood glycosylated hemoglobin (HbA1c), serum creatinine, blood urea nitrogen (BUN), kidney tissue levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx), aldose reductase (AR) activities and malondialdehyde (MDA) concentration were measured. Results Induction of DM in rats significantly elevated blood pressure, HbA1c, BUN, creatinine and renal tissue levels of MDA and AR while significantly reducing SOD, CAT and GPx activities. Either Insulin or ozone therapy significantly reversed the effects of DM on all parameters; in combination (DIO group), they caused significant improvements in all parameters in comparison to each alone. Conclusions Ozone administration in conjunction with insulin in DM rats reduces oxidative stress markers and improves renal antioxidant enzyme activity which highlights its potential uses in the regimen for treatment of diabetic patients. PMID:20465785

2010-01-01

163

Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats  

PubMed Central

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

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

2014-01-01

164

Attenuation of Biochemical Parameters in Streptozotocin-induced Diabetic Rats by Oral Administration of Extracts and Fractions of Cephalotaxus sinensis  

PubMed Central

Cephalotaxus sinensis (C. sinensis) large size, evergreen tree common in China and utilized for numerous effective pharmacological applications in Chinese traditional medicine. The hepato-renal effects of C. sinensis were evaluated in vivo using Streptozotocin (STZ)-induced diabetic rats as an tentative model. Animals were orally treated with 80% EtOH extract (aq.EE), H2O extract (WtE) and ethylacetate (EaF)/butanol fractions (BtF) of C. sinensis (200 mg/kg, b.w.) for 28 days whereas control received vehicle merely. The degree of fortification was measured by using biochemical parameters like serum transaminases (ALT and AST), alkaline phosphatase (ALP), creatinine, urea and urine sugar. Meanwhile, the histopathological studies were conducted out to support the above parameters. Administration of C. sinensis aq.EE/BtF (p<0.05) and EaF (p<0.01) patently prevented STZ-induced elevation levels of serum ALT, AST, ALP, creatinine, urea, urine sugar and increase body weight respectively, which were comparable with the standard drug tolbutamide, while WtE did not show any significant effect (p>0.05). Phytochemical studies revealed the presence of saponins, terpenes, sterols and flavonoids in C. sinensis which could be responsible for the possible hepato-renal protective action. The results sustain the fact that the extract/fractions of C. sinensis have an immense potential to be developed further into a phytomedicine. PMID:18231626

Saeed, Muhammad K.; Deng, Yulin; Dai, Rongji

2008-01-01

165

Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats.  

PubMed

Effect of metformin treatment on blood pressure, endothelial function and oxidative stress in streptozotocin (STZ)-induced diabetes in rats was studied. In vitro effect of metformin on vascular reactivity to various agonist in the presence of metformin in untreated nondiabetic and STZ-diabetic rats were also studied. Sprague-Dawley rats were randomized into nondiabetic and STZ-diabetic groups. Rats were further randomized to receive metformin (150 mg/kg) or vehicle for 4 weeks. Metformin treatment reduced blood pressure without having any significant effect on blood glucose level in STZ-diabetic rats. Enhanced phenylephrine (PE)-induced contraction and impaired acetylcholine (Ach)-induced relaxation in STZ-diabetic rats were restored to normal by metformin treatment. Enhanced Ach-induced relaxation in metformin-treated STZ-diabetic rats was blocked due to pretreatment with 100 microM of Nomega-nitro-L-arginine-methyl ester (L-NAME) or 10 microM of methylene blue but not 10 microM of indomethacin. Metformin treatment significantly increased antioxidant enzymes and reduced lipid peroxidation in STZ-diabetic rats. In vitro studies in aortic rings of untreated nondiabetic and STZ-diabetic rats showed that the presence of higher concentration of metformin (1 mM and 10 mM) significantly reduced PE-induced contraction and increased Ach-induced relaxation. Metformin per se relaxed precontracted aortic rings of untreated nondiabetic and STZ-diabetic rats in a dose-dependent manner. Pretreatment with L-NAME or removal of endothelium blocked metformin-induced relaxation at lower concentration (up to 30 microM) but not at higher concentration (above 30 microM). Metformin-induced relaxation was blocked in the presence of 1 mM of 4-aminopyridine, or 1 mM of tetraethylammonium but not in the presence of 100 microM of barium ion or 10 microM of glybenclamide. The restored endothelial function along with direct effect of metformin on aortic rings and reduced oxidative stress contributes to reduced blood pressure in STZ-diabetic rats. From the present study, it can be concluded that metformin administration to STZ-diabetic rats lowers blood pressure, and restores endothelial function. PMID:16318863

Majithiya, Jayesh B; Balaraman, R

2006-04-25

166

Effects of nimesulide, a selective COX-2 inhibitor, on cardiovascular function in 2 rat models of diabetes.  

PubMed

Cyclooxygenase-2 (COX-2) has been found to be activated in diabetes. We investigated whether nimesulide (selective COX-2 inhibitor) alters cardiovascular responses to adrenaline in 2 rat models of diabetes. Wistar rats (5-week old) were continuously fed a normal or high-fructose diet (60% of caloric intake). At week 2, half of the rats in each diet regimen were given streptozotocin (STZ) (60 mg/kg, intravenously). At week 6, cardiovascular effects of adrenaline (6 and 16 × 10 mol·kg·min, intravenously) were measured in 4 groups of thiobutabarbital-anesthetized rats (control, fructose, STZ, and fructose-streptozotocin [F-STZ]) before and after the injection of nimesulide (3 mg/kg, intravenously). Both the STZ and F-STZ groups exhibited hyperglycemia and significantly (P < 0.05) reduced left ventricular contractility, mean arterial pressure, arterial and venous resistance, and mean circulatory filling pressure (index of venous tone) responses to adrenaline, relative to the control and fructose groups. Nimesulide did not affect responses in the control and fructose groups but increased the venous and, to a less extent, arterial constriction to adrenaline in both the groups of diabetic rats. The cardiac contractile responses, however, were not altered after nimesulide treatment. The results show that nimesulide partially restored arterial and venous constriction to adrenaline in rats with STZ- and F-STZ-induced diabetes. PMID:24621649

Leung, Joanne Y T; Pang, Catherine C Y

2014-07-01

167

Role of nitric oxide in intrarenal hemodynamics in experimental diabetes mellitus in rats.  

PubMed

The role of nitric oxide (NO) in the regulation of the intrarenal microcirculation in streptozotocin (STZ)-induced diabetes mellitus in rats is not clear. We examined renal cortical and papillary hemodynamics in STZ rats and determined the effects of systemic inhibition and stimulation of NO synthesis. Renal blood flow in cortical (QCC), and inner medullary ascending (QAV) and descending (QDV) vasa recta capillaries was measured by fluorescence videomicroscopy in STZ Munich-Wistar rats and nondiabetic control rats. Ten days after STZ injection (80 mg/kg ip), basal QCC and QDV were significantly greater in STZ rats (n = 16) compared with control rats (n = 15). Infusion of N(G)-monomethyl-L-arginine (L-NMMA, 15 mg/kg bolus, 500 microg. min(-1). kg(-1) iv) decreased Q(CC) (-41%), QAV (-38%), and QDV (-37%) in control rats (n = 6) and to a significantly greater magnitude than in STZ rats (n = 7), Q(CC) (-14%), QAV (-20%), and QDV (-25%). Coinfusion of L-arginine (L-Arg, 1 mg. kg(-1). min(-1) iv) with L-NMMA increased Q(CC) to a significantly greater extent (P < 0.01) in control rats compared with STZ rats. In subsequent studies, infusion of L-Arg alone increased QCC (+50%), QAV (+16%), and QDV (+11%) in control rats (n = 5) but had no effect in STZ rats (n = 5). These results show that the response of renal cortical and papillary capillary blood flow to both inhibition and stimulation of NO synthesis is attenuated in the early onset of STZ-diabetes mellitus rats compared with control rats. PMID:10484489

Pflueger, A C; Larson, T S; Hagl, S; Knox, F G

1999-09-01

168

Effect of propionate on in vivo carbohydrate metabolism in streptozocin-induced diabetic rats.  

PubMed

Undigested carbohydrates and some dietary fibers are fermented in the large intestine to form short-chain fatty acids (SCFA), including acetate, propionate, and butyrate. It has been suggested that some of the beneficial effects of high-carbohydrate, high-fiber diets on carbohydrate and lipid metabolism are mediated by the metabolism of SCFA in the liver. Propionate has been shown in vitro to decrease glucose production in rat hepatocytes. The aim of the present study was to investigate the effects of propionate on carbohydrate metabolism in normal and streptozocin (STZ)-induced diabetic male Sprague-Dawley rats. Rats were fed a high-fat diet with or without sodium propionate supplementation (either 0.5% or 5% wt/wt) for 4 weeks. At the completion of the feeding period, body weight and liver glycogen concentrations were significantly decreased in STZ-diabetic rats and were unaffected by propionate supplementation. Although STZ-diabetic animals had elevated fasting plasma glucose, cholesterol, and triglyceride levels relative to nondiabetic rats, propionate supplementation had no significant effect on these parameters in either group. Basal and insulin-stimulated carbohydrate metabolism were assessed using the euglycemic clamp technique in overnight-fasted animals with 3(H)-6-glucose infusion. As expected, basal hepatic glucose production (HGP) was higher and the metabolic clearance rate of glucose (MCR) was lower in STZ-diabetic rats. High-dose insulin infusion (3 mU.kg-1.min-1) suppressed HGP in nondiabetic and diabetic animals and increased the MCR in nondiabetic animals. However, propionate supplementation did not alter basal or insulin-stimulated HGP or the MCR in either nondiabetic or diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8201962

Cameron-Smith, D; Collier, G R; O'Dea, K

1994-06-01

169

Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats.  

PubMed

The purpose of the study was to evaluate the effects of hesperetin (Hsp) on diabetes-induced retinal oxidative stress, neuroinflammation and apoptosis in rats. The Hsp treatment (100 mg/kg body weight) was carried for twenty four weeks in STZ-induced diabetic rats and evaluated for antioxidant (Superoxide dismutase; SOD, Catalase; CAT and glutathione; GSH) enzymes, inflammatory cytokines (TNF-?, IL-1?), caspase-3, glial fibrillary acidic protein (GFAP) and aquaporin-4(AQP4) expression. Histological changes were evaluated by light and transmission electron microscopic (LM and TEM) studies. Retinal GSH levels and anti-oxidant enzymes (SOD and CAT) activity were significantly decreased in diabetic group as compared to normal group. However, in Hsp-treated rats, retinal GSH levels were restored close to normal levels and positive modulation of anti-oxidant enzyme activity was observed. Diabetic retinae showed significantly increased expression of Pro-inflammatory cytokines (TNF-? and IL-1?) as compared to normal retinae. While Hsp-treated retinae showed significantly lower levels of cytokines as compared to diabetic retinae. Diabetic retinae showed increased caspase-3, GFAP and AQP4 expression. However, Hsp-treated retinae showed inhibitory effect on caspase-3, GFAP and AQP4 expression. LM images showed edematous Müller cell endfeet, and also degenerated photoreceptor layer; however, protective effect of Hsp was seen on Müller cell processes and photoreceptors. TEM study showed increased basement membrane (BM) thickness in diabetic retina, while relatively thin BM was recorded in Hsp-treated retina. It can be postulated that dietary flavanoids, like Hsp, can be effective for the prevention of diabetes induced neurovascular complications such as diabetic retinopathy. PMID:23376836

Kumar, Binit; Gupta, Suresh Kumar; Srinivasan, B P; Nag, Tapas Chandra; Srivastava, Sushma; Saxena, Rohit; Jha, Kumar Abhiram

2013-05-01

170

Multiple Antioxidants Improve Cardiac Complications and Inhibit Cardiac Cell Death in Streptozotocin-Induced Diabetic Rats  

PubMed Central

Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. Since diabetic cardiomyopathy is now known to have a high prevalence in the asymptomatic diabetic patient, prevention at the earliest stage of development by existing molecules would be appropriate in order to prevent the progression of heart failure. In this study, we investigated the protective role of multiple antioxidants (MA), on cardiac dysfunction and cardiac cell apoptosis in streptozotocin (STZ)-induced diabetic rat. Diabetic cardiomyopathy in STZ-treated animals was characterized by declined systolic, diastolic myocardial performance, oxidative stress and apoptosis in cardiac cells. Diabetic rats on supplementation with MA showed decreased oxidative stress evaluated by the content of reduced levels of lipid per-oxidation and decreased activity of catalase with down-regulation of heme-oxygenase-1 mRNA. Supplementation with MA also resulted in a normalized lipid profile and decreased levels of pro-inflammatory transcription factor NF-kappaB as well as cytokines such as TNF-?, IFN-?, TGF-?, and IL-10. MA was found to decrease the expression of ROS-generating enzymes like xanthine oxidase, monoamine oxidase-A along with 5-Lipoxygenase mRNA and/or protein expression. Further, left ventricular function, measured by a microtip pressure transducer, was re-established as evidenced by increase in ±dp/dtmax, heart rate, decreased blood pressure, systolic and diastolic pressure as well as decrease in the TUNEL positive cardiac cells with increased Bcl-2/Bax ratio. In addition, MA supplementation decreased cell death and activation of NF-kappaB in cardiac H9c2 cells. Based on our results, we conclude that MA supplementation significantly attenuated cardiac dysfunction in diabetic rats; hence MA supplementation may have important clinical implications in terms of prevention and management of diabetic cardiomyopathy. PMID:23843977

Kumar, Santosh; Prasad, Sahdeo; Sitasawad, Sandhya L.

2013-01-01

171

Ruscogenin ameliorates diabetic nephropathy by its anti-inflammatory and anti-fibrotic effects in streptozotocin-induced diabetic rat  

PubMed Central

Background Ruscogenin is a major steroid sapogenin in the traditional Chinese herb Ophiopogon japonicus that have multiple bioactivities. Recent studies have demonstrated that ruscogenin is involved in down-regulation of intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-?B (NF-?B) activation in anti-inflammatory pathways. We hypothesized that ruscogenin protects against diabetic nephropathy (DN) by inhibiting NF-?B-mediated inflammatory pathway. To test this hypothesis, the present study was to examine the effects of ruscogenin in rats with streptozotocin (STZ)-induced DN. Methods Diabetes was induced with STZ (60 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats in the treatment group were orally dosed with 0.3, 1.0 or 3.0 mg/kg ruscogenin for 8 weeks. The normal rats were chosen as nondiabetic control group. The rats were sacrificed 10 weeks after induction of diabetes. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for pathology histology, immunohistochemistry, and Western blot analyses. Results Ruscogenin administration did not lower the levels of plasma glucose and glycosylated hemoglobin in STZ-diabetic rats. Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, blood urea nitrogen and proteinuria, along with marked elevation in the ratio of kidney weight to body weight, that were reversed by ruscogenin. Ruscogenin treatment was found to markedly improve histological architecture in the diabetic kidney. Renal NF-?B activity, as wells as protein expression and infiltration of macrophages were increased in diabetic kidneys, accompanied by an increase in protein content of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in kidney tissues. All of the above abnormalities were reversed by ruscogenin treatment, which also decreased the expression of transforming growth factor-?1 and fibronectin in the diabetic kidneys. Conclusions Our data demonstrated that ruscogenin suppressed the inflammation and ameliorated the structural and functional abnormalities of the diabetic kidney in rats might be associated with inhibition of NF-?B mediated inflammatory genes expression. PMID:24666993

2014-01-01

172

Comparative Proteomics Study of Streptozotocin-induced Diabetic Nephropathy in Rats Kidneys Transfected with Adenovirus-mediated Fibromodulin Gene  

PubMed Central

Background Transforming Growth Factor-beta (TGF-?) activation appears to be crucial for tissue injury in Diabetic Nephropathy (DN). Fibromodulin, the small leucine-rich proteoglycan, has been proposed to be the potent TGF-? modulator. In this study, the therapeutic effects of fibromodulin in the kidneys of streptozotocin (STZ)-induced diabetic rats were investigated. Methods Diabetic rats received intraperitoneal (IP) injections of recombinant adenovirus expression vectors (RAd5) containing fibromodulin (RAd-FMOD) and were killed after 10 weeks. Proteins were isolated from the rat kidney and separated using two-dimensional gel electrophoresis. The differentially expressed proteins were analyzed using Matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Results Ten spots were identified using MALDI-TOF-MS. The identified proteins were primarily responsible for cell metabolism, cytoskeleton formation, and oxidative stress. RAd-FMOD treatment markedly attenuated the albuminuria in diabetic rats. Conclusion Taken together, these results provide a valuable clue in exploring the mechanism underlying the therapeutic effects of fibromodulin in diabetic nephropathy suggesting that it can be a potential agent in the treatment of this disease. PMID:24834312

Maleki, Akram; Ramazani, Ali; Foroutan, Maryam; Biglari, Alireza; Ranjzad, Parisa; Mellati, Ali Awsat

2014-01-01

173

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. PMID:22956978

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

2012-01-01

174

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

PubMed

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

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

2014-11-01

175

Sequential alterations of glucocorticoid receptors in the hippocampus of STZ-treated type 1 diabetic rats  

PubMed Central

Type 1 diabetes is a common metabolic disorder accompanied by increased blood glucose levels along with glucocorticoid and cognitive deficits. The disease is also thought to be associated with environmental changes in brain and constantly induces oxidative stress in patients. Therefore, glucocorticoid-mediated negative feedback mechanisms involving the glucocorticoid receptor (GR) binding site are very important to understand the development of this disease. Many researchers have used streptozotocin (STZ)-treated diabetic animals to study changes in GR expression in the brain. However, few scientists have evaluated the hyperglycemic period following STZ exposure. In the present study, we found GR expression in the hippocampus varied based on the period after STZ administration for up to 4 weeks. We performed immunohistochemistry and Western blotting to validate the sequential alterations of GR expression in the hippocampus of STZ-treated type 1 diabetic rats. GR protein expression increased significantly until week 3 but decreased at week 4 following STZ administration. GR expression after 70 mg/kg STZ administration was highest at 3 weeks post-treatment and decreased thereafter. Although STZ-induced increase in GR expression in diabetic animals has been described, our data indicate that researchers should consider the sequential GR expression changes during the hyperglycemic period following STZ exposure. PMID:23820217

Shin, Jae Hoon; Seong, Je Kyung

2014-01-01

176

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. PMID:21994524

Lee, Soo Jung; Zhang, Gui Fang

2011-01-01

177

Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.  

PubMed

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. PMID:22761931

Banki, Nora F; Ver, Agota; Wagner, Laszlo J; Vannay, Adam; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya-Nagy; Kenesei, Eva; Rosta, Klara; Reusz, Gyorgy; Szabo, Attila J; Tulassay, Tivadar; Baylis, Chris; Fekete, Andrea

2012-01-01

178

Aldosterone Antagonists in Monotherapy Are Protective against Streptozotocin-Induced Diabetic Nephropathy in Rats  

PubMed Central

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. PMID:22761931

Banki, Nora F.; Ver, Agota; Wagner, Laszlo J.; Vannay, Adam; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya-Nagy; Kenesei, Eva; Rosta, Klara; Reusz, Gyorgy; Szabo, Attila J.; Tulassay, Tivadar; Baylis, Chris; Fekete, Andrea

2012-01-01

179

Elevated expression of alphaA- and alphaB-crystallins in streptozotocin-induced diabetic rat.  

PubMed

alpha-Crystallin, a predominant protein of the ocular lens, is composed of two subunits, alphaA and alphaB. Of these, alphaB-crystallin has been shown to present widely in non-lenticular tissues while alphaA-crystallin is largely lens-specific. Although, expression of alphaB-crystallin is elevated under various stress and pathological conditions, yet its physiological significance remained unknown. Some studies suggest that the expression of alphaB-crystallin gene is related to oxidative stress. Persistent hyperglycemia during uncontrolled diabetes is known to cause oxidative stress, which has been implicated in various secondary complications of diabetes. Hence, expression of alphaA- and alphaB-crystallins in various tissues of streptozotocin (STZ)-induced diabetic Wistar-NIN rats was investigated by RT-PCR and immunoblotting. While expression of alphaB-crystallin was noted in the wide range of tissues examined in the study, alphaA-crystallin expression was detected only in lens and retina. Interestingly, alphaB-crystallin expression was elevated in lens, heart, muscle, and brain, but decreased in adipose tissue of diabetic rats compared to control rats. alphaA-Crystallin expression was increased in retina of diabetic rat. Increased oxidative stress appears to be a major stimulus for the enhanced expression of alphaA- and alphaB-crystallins in the tissues of diabetic rats and elevated expression of alpha-crystallin may have a protective role against metabolic stress. Interestingly, feeding of curcumin, a dietary antioxidant, to diabetic rats attenuated the enhanced expression of alphaB-crystallin. The results indicate that elevated expression of alpha-crystallins in some tissues may have implications in pathophysiology of diabetic complications. PMID:16309625

Kumar, P Anil; Haseeb, Abdul; Suryanarayana, P; Ehtesham, Nasreen Z; Reddy, G Bhanuprakash

2005-12-15

180

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

PubMed Central

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

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

2014-01-01

181

In vitro toxicity and antidiabetic activity of a newly developed polyherbal formulation (MAC-ST/001) in streptozotocin-induced diabetic Wistar rats.  

PubMed

The present study was designed to investigate the hypoglycemic effect of an aqueous extract of MAC-ST/001 (a new polyherbal formulation) which was given once daily to rats at different doses. The animals were divided into diabetic and nondiabetic control groups. The duration of each experiment lasted from 1 week to 1 month, and the results were compared with that of the standard hypoglycemic drug glibenclamide (10 mg/kg), which was given once daily. In this study, biochemical and histopathological parameters were studied in streptozotacin (STZ) (single intraperitoneal injection of 55 mg/kg)-induced diabetic rats. The diabetic rats showed a significant (p?diabetes. Cytotoxicity of MAC-ST/001 formulation was also studied on C2C12, 3T3-L1, and HepG2 cells through MTT assay. Histological examination of the liver and pancreas of normal control, diabetic control, and drug-treated rats revealed significant results. Finally, it was concluded that administration of this MAC-ST/001 extract reversed most blood and tissue changes caused by STZ-induced diabetes in rats. PMID:23053765

Yadav, Deepak; Chaudhary, Anis Ahmad; Garg, Veena; Anwar, Mohammad Faiyaz; Rahman, Md Mahfooz-ur; Jamil, Sayed Sakir; Khan, Haider Ali; Asif, Mohd

2013-06-01

182

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

PubMed

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

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

2014-01-01

183

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. PMID:19720799

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

2009-01-01

184

Therapeutic effects of globular adiponectin in diabetic rats with nonalcoholic fatty liver disease  

PubMed Central

AIM: To explore the therapeutic role of globular adiponectin (gAd) in high-fat diet/streptozotocin (STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease (NAFLD). METHODS: Seven rats were fed a basic diet (normal control group; NC) during the experiment. Experimental rats (14 rats) were given a high-fat diet for 4 wk and were then injected with STZ to induce type 2 diabetes mellitus (T2DM) and NAFLD. Half of the T2DM/NAFLD rats were randomly injected intraperitoneally with gAd for 7 d (gAd-treated group), while the other 7 rats (T2DM/NAFLD group) received 0.9% saline. Plasma biochemical parameters and insulin concentrations were measured. Liver histopathology was examined by hematoxylin-eosin staining. Insulin receptor expression in the liver was analyzed by immunohistochemical staining, Western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. RESULTS: Compared to the control group, the T2DM/NAFLD group had increased levels of glucolipid and decreased levels of insulin. Plasma glucose and lipid levels were decreased in the gAd-treated group, while serum insulin levels increased. The expression of insulin receptor in the T2DM/NAFLD group increased compared with the NC group, and gAd downregulated insulin receptor expression in the livers of T2DM/NAFLD rats. Steatosis of the liver was alleviated in the gAd-treated group compared to the T2DM/NAFLD group (NAS 1.39 ± 0.51 vs 1.92 ± 0.51, P < 0.05). CONCLUSION: Globular adiponectin exerts beneficial effects in T2DM rats with NAFLD by promoting insulin secretion, mediating glucolipid metabolism, regulating insulin receptor expression and alleviating hepatic steatosis. PMID:25356056

Ma, Hong; Cui, Fan; Dong, Jing-Jing; You, Guo-Ping; Yang, Xiang-Jiu; Lu, Hua-Dong; Huang, Yan-Ling

2014-01-01

185

Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats.  

PubMed

Berberine (BBR), an effective compound of Chinese traditional herbal medicine, has preventive effects on diabetes and its complications. In this study, we investigated the therapeutic effects and underlying molecular mechanisms of BBR in rats with high-fat diet and streptozotocin (STZ)-induced diabetic nephropathy model. BBR (50, 100, 200 mg/kg/d) were orally administered to male Sprague-Dawley rats after STZ injection and conducted for 8 weeks. Renal damage was evaluated by kidney weight to body weight ratio (KW/BW), urine microalbumin (UMAlb), urine protein for 24 h (UP24 h), urine creatinine (UCr), and histological examination. Type IV collagen and transforming growth factor-beta1 (TGF-?1) were detected by immunohistochemistry and ultrastructure of glomeruli was observed. Fasting blood glucose (FBG),serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c) in serum and G protein-coupled receptor kinases (GRKs), cAMP in kidney were measured. Remarkable renal damage, hyperglycemia and hyperlipidemia were observed in DN rats. BBR could restore renal functional parameters, suppress alterations in histological and ultrastructural changes in the kidney tissues, improve glucose and lipid metabolism disorders, and increase cAMP levels compared with those of DN model group. Furthermore, BBR down-regulated total protein expression of GRK2, GRK3 and up-regulated expression of GRK6 of renal cortex in DN rats, but had a slight effects on GRK4 and GRK5. These studies demonstrate, for the first time, that BBR exerts renoprotection in high-fat diet and STZ-induced DN rats by modulating the proteins expression of GRKs in G protein- AC-cAMP signaling pathway. PMID:23196710

Wang, Feng Ling; Tang, Li Qin; Yang, Feng; Zhu, Ling Na; Cai, Ming; Wei, Wei

2013-03-01

186

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

2013-01-01

187

Antioxidant effects of maslinic acid in livers, hearts and kidneys of streptozotocin-induced diabetic rats: effects on kidney function.  

PubMed

Studies indicate that hyperglycemia-induced oxidative stress triggers the development of microvascular and macrovascular complications in diabetes. Accordingly, we hypothesized that maslinic acid (MA) prevents these complications due to its antioxidant properties. We, therefore, investigated the effects of 5-week MA treatment of streptozotocin (STZ)-induced diabetic rats on anti-oxidative status of cardiac, hepatic and renal tissues as well as on kidney function. Proximal tubular effects of MA were studied in anesthetized rats challenged with hypotonic saline after a 3.5?h equilibration for 4 h of 1 h control, 1.5?h treatment and 1.5?h recovery periods using lithium clearance. MA was added to the infusate during the treatment period. Oral glucose tolerance responses to MA were monitored in rats given a glucose load after an 18?h fast. Compared with untreated diabetic rats, MA-treated diabetic animals exhibited significantly low malondialdehyde (MDA, a marker of lipid peroxidation) and increased the activity of antioxidant enzymes; superoxide dismutase and glutathione peroxidase in hepatic, cardiac and renal tissues. The expressions of gastrocnemius muscle GLUT4 and kidney GLUT1 and GLUT2 were assessed to elucidate the mechanism of the hypoglycemic effects of MA. MA-treatment diminished the expression of GLUT1 and GLUT2 in diabetic kidney and reduced glycemia values of diabetic rats. MA administration increased urinary Na+ outputs and additionally the FENa indicating that at least part of the overall reduction in Na+ reabsorption occurred in the proximal tubules. These results suggest antioxidant effects of MA can ameliorate oxidative stress and improve kidney function in diabetes mellitus. PMID:24344651

Mkhwanazi, Blessing N; Serumula, Metse R; Myburg, Rene B; Van Heerden, Fanie R; Musabayane, Cephas T

2014-04-01

188

Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNF? related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats.  

PubMed

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

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

2014-01-01

189

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

PubMed Central

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

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

2014-01-01

190

Effect of the Combination of Gelam Honey and Ginger on Oxidative Stress and Metabolic Profile in Streptozotocin-Induced Diabetic Sprague-Dawley Rats  

PubMed Central

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

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

2014-01-01

191

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

2013-10-01

192

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

PubMed Central

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

2014-01-01

193

The effect of nimodipine on calcium homeostasis and pain sensitivity in diabetic rats.  

PubMed

1. The pathogenesis of diabetic neuropathy is a complex phenomenon, the mechanisms of which are not fully understood. Our previous studies have shown that the intracellular calcium signaling is impaired in primary and secondary nociceptive neurons in rats with streptozotocin (STZ)-induced diabetes. Here, we investigated the effect of prolonged treatment with the L-type calcium channel blocker nimodipine on diabetes-induced changes in neuronal calcium signaling and pain sensitivity. 2. Diabetes was induced in young rats (21 p.d.) by a streptozotocin injection. After 3 weeks of diabetes development, the rats were treated with nimodipine for another 3 weeks. The effect of nimodipine treatment on calcium homeostasis in nociceptive dorsal root ganglion neurons (DRG) and substantia gelatinosa (SG) neurons of the spinal cord slices was examined with fluorescent imaging technique. 3. Nimodipine treatment was not able to normalize elevated resting intracellular calcium ([Ca(2+)]( i )) levels in small DRG neurons. However, it was able to restore impaired Ca(2+) release from the ER, induced by either activation of ryanodine receptors or by receptor-independent mechanism in both DRG and SG neurons. 4. The beneficiary effects of nimodipine treatment on [Ca(2+)]( i ) signaling were paralleled with the reversal of diabetes-induced thermal hypoalgesia and normalization of the acute phase of the response to formalin injection. Nimodipine treatment was also able to shorten the duration of the tonic phase of formalin response to the control values. 5. To separate vasodilating effect of nimodipine Biessels et al., (Brain Res. 1035:86-93) from its effect on neuronal Ca(2+) channels, a group of STZ-diabetic rats was treated with vasodilator - enalapril. Enalapril treatment also have some beneficial effect on normalizing Ca(2+) release from the ER, however, it was far less explicit than the normalizing effect of nimodipine. Effect of enalapril treatment on nociceptive behavioral responses was also much less pronounced. It partially reversed diabetes-induced thermal hypoalgesia, but did not change the characteristics of the response to formalin injection. 6. The results of this study suggest that chronic nimodipine treatment may be effective in restoring diabetes-impaired neuronal calcium homeostasis as well as reduction of diabetes-induced thermal hypoalgesia and noxious stimuli responses. The nimodipine effect is mediated through a direct neuronal action combined with some vascular mechanism. PMID:16838100

Shutov, L; Kruglikov, I; Gryshchenko, O; Khomula, E; Viatchenko-Karpinski, V; Belan, P; Voitenko, N

2006-01-01

194

The Effects of the Melatonin Treatment on the Oxidative Stress and Apoptosis in Diabetic Eye and Brain  

PubMed Central

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

Gurp?nar, Tugba; Ekerbicer, Nuran; Uysal, Nazan; Barut, Turgay; Tarakc?, Figen; Tuglu, M. Ibrahim

2012-01-01

195

S-allylcysteine Improves Streptozotocin-Induced Alterations of Blood Glucose, Liver Cytochrome P450 2E1, Plasma Antioxidant System, and Adipocytes Hormones in Diabetic Rats  

PubMed Central

Background: S-allylcysteine, a garlic derivative, could have a protective effect against pathogenesis of diabetes mellitus. Objectives: Sustained free radical generation and oxidative damage to system leads to the final conclusion phase of diabetes and also it coexists with a constant diminution in the antioxidant status.The present study aims to evaluate the therapeutic effects of S-allylcysteine (SAC) against adipocytes hormones and antioxidant defense systems of plasma and erythrocytes of treptozotocin (STZ) induced diabetes in rats. Materials and Methods: Diabetic rats were administered SAC (150 mg/kg b.w) orally for 45 days. At 46th day, the rats were anesthetized, and blood and liver sample were collected for analyzing glucose, plasma insulin, CYP2E1 activity, Thiobarbituric acid reactive substances (TBARS), hydroperoxide, enzymatic and nonenzymatic antioxidants, reduced glutathione (GSH), ceruloplasmin, plasma leptin, and adiponectin. Results; The levels of glucose, CYP2E1 activity, Thiobarbituric acid reactive substances (TBARS), hydroperoxide, and ceruloplasmin were increased significantly; whereas, the levels of plasma insulin, reduced glutathione, enzymatic and nonenzymatic antioxidants, leptin and adiponectin were decreased in experimental diabetic rats. Administration of SAC to diabetic rats led to a decrease in the levels of glucose, CYP2E1 activity, TBARS, and ceruloplasmin. In addition, the levels of plasma insulin, enzymatic and nonenzymatic antioxidants leptin and adiponectin were increased in SAC treated diabetic rats. Gliclazide, a standard drug for diabetes, was used for the comparative purpose. Conclusions: The results of the present investigation suggest that SAC could be used as a food supplement in the treatment of diabetes characterized by provoked antioxidant status, altered blood glucose, and hormones level. PMID:24719626

Saravanan, Ganapathy; Ponmurugan, Ponnusamy

2013-01-01

196

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

PubMed Central

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

2013-01-01

197

Catalase inhibition in diabetic rats potentiates DNA damage and apoptotic cell death setting the stage for cardiomyopathy.  

PubMed

Diabetes is a risk factor for cardiovascular disease that has a multifactorial etiology, with oxidative stress as an important component. Our previous observation of a significant diabetes-related increase in rat cardiac catalase (CAT) activity suggested that CAT could play a major role in delaying the development of diabetic cardiomyopathy. Thus, in the present work, we examined the effects of the daily administration of the CAT inhibitor, 3-amino-1,2,4-triazole (1 mg/g), on the hearts of streptozotocin (STZ)-induced diabetic rats. Administration of CAT inhibitor was started from the 15th day after the last STZ treatment (40 mg/kg/5 days), and maintained until the end of the 4th or 6th weeks of diabetes. Compared to untreated diabetic rats, at the end of the observation period, CAT inhibition lowered the induced level of cardiac CAT activity to the basal level and decreased CAT protein expression, mediated through a decline in the nuclear factor erythroid-derived 2-like 2 /nuclear factor-kappa B p65 (Nrf2/NF-?B p65) subunit ratio. The perturbed antioxidant defenses resulting from CAT inhibition promoted increased H2O2 production (P?diabetes-promoted cardiac dysfunction and cardiomyopathy. PMID:25298180

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

2014-12-01

198

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

PubMed

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

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

2013-01-01

199

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. PMID:23637830

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

2013-01-01

200

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

2011-10-01

201

Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats.  

PubMed

Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, B(max) showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes. PMID:20513244

Kumar, T Peeyush; Antony, Sherin; Gireesh, G; George, Naijil; Paulose, C S

2010-01-01

202

Reduced hepatic LDL-receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase and sterol carrier protein-2 expression is associated with pregnancy loss in the diabetic rat.  

PubMed

Hepatic low density lipoprotein receptor (LDLR), 3-hydroxy-3-methylglutaryl coenyzme A reductase (HMGR), cholesterol 7?-hydroxylase, and sterol carrier protein-2 are important proteins associated with the uptake, synthesis, degradation and transport of cellular cholesterol. Since cholesterol is critically important for steroid hormone synthesis and is an essential component in membrane biosynthesis, this study investigated whether these proteins are altered in the normal pregnant and streptozotocin (STZ)-induced diabetic pregnant rat. The goal of these experiments was to determine whether diabetic reproductive dysfunction is associated with a significant change in maternal cholesterol homeostasis. Diabetic animals were grouped based on their ability or inability to maintain pregnancy up to day 15 post-conception. LDLR and HMGR mRNA levels were significantly reduced in animals which did not maintain pregnancy whereas diabetic animals with fetuses had normal LDLR and HMGR mRNA levels. Hepatic LDLR, HMGR, and SCP2 protein levels were examined in normal pregnant and diabetic pregnant animals by Western blot analysis. SCP2 levels were reduced in all diabetic animals, particularly in the diabetic animals which lost their fetuses. The decline in SCP2 was associated with an increase in sterol carrier protein-X (SCPx), a protein related to SCP2. SCPx has been shown to have thiolytic activity and is thought to have a role in ?-oxidation of fatty acids. HMGR was also significantly reduced in diabetic animals which lost their fetuses. Cholesterol 7?-hydroxylase mRNA was slightly, but not significantly, reduced in all diabetic animals. Serum very low density lipoprotein (VLDL) +LDL cholesterol increased significantly in the STZ-treated diabetic rats while the HDL cholesterol levels declined in these animals. Reduced hepatic LDLR and HMGR mRNA levels were consistently associated with reduced serum progesterone and an inability to maintain pregnancy. The results of this study suggest that the maintenance of maternal cholesterol metabolism is a critical factor directly associated with successful pregnancy outcome in the diabetic rat. PMID:21153157

McLean, M P; Zhao, Z; Ness, G C

1995-10-01

203

Diabetes-induced abnormalities in ER calcium mobilization in primary and secondary nociceptive neurons.  

PubMed

Development of diabetic sensory polyneuropathy is associated with alterations in intracellular calcium homeostasis in primary and secondary nociceptive neurons. We have shown previously that in a model of streptozotocin (STZ)-induced diabetes, the calcium signal is prolonged and calcium release from ryanodine-sensitive calcium stores down-regulated in neurons of the nociceptive system. The aim of the present study was a more detailed characterization of calcium homeostasis in primary (dorsal root ganglia, DRG) and secondary (dorsal horn, DH) nociceptive neurons in STZ-induced diabetes. Fluorescence video-imaging was used to measure free cytosolic [Ca2+] ([Ca2+]i) in lumbar nociceptive neurons of control and streptozotocin-diabetic rats. Resting [Ca2+]i rose progressively in these neurons with the duration of diabetes and calcium mobilization from the endoplasmic reticulum (ER) decreased during diabetes. The amplitude of calcium release from both ryanodine- and IP3-sensitive calcium stores induced by caffeine, ionomycin, ATP or glutamate was significantly (P<0.01) lower in DRG and DH neurons from 6-week STZ-diabetic rats. Diabetes-induced changes in the calcium homeostasis were similar in DRG and DH neurons indicating that they might be general for many types of neurons from the central and peripheral nervous systems. PMID:15048576

Kruglikov, I; Gryshchenko, O; Shutov, L; Kostyuk, E; Kostyuk, P; Voitenko, N

2004-07-01

204

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. PMID:23633838

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

2013-01-01

205

Caffeic acid phenethyl amide improves glucose homeostasis and attenuates the progression of vascular dysfunction in Streptozotocin-induced diabetic rats  

PubMed Central

Background Glucose intolerance and cardiovascular complications are major symptoms in patients with diabetes. Many therapies have proven beneficial in treating diabetes in animals by protecting the cardiovascular system and increasing glucose utilization. In this study, we evaluated the effects of caffeic acid phenethyl amide (CAPA) on glucose homeostasis and vascular function in streptozotocin (STZ)-induced type 1 diabetic rats. Methods Diabetes (blood glucose levels > 350 mg/dL), was induced in Wistar rats by a single intravenous injection of 60 mg/kg STZ. Hypoglycemic effects were then assessed in normal and type 1 diabetic rats. In addition, coronary blood flow in Langendorff-perfused hearts was evaluated in the presence or absence of nitric oxide synthase (NOS) inhibitor. The thoracic aorta was used to measure vascular response to phenylephrine. Finally, the effect of chronic treatment of CAPA and insulin on coronary artery flow and vascular response to phenylephrine were analyzed in diabetic rats. Results Oral administration of 0.1 mg/kg CAPA decreased plasma glucose in normal (32.9 ± 2.3% decrease, P < 0.05) and diabetic rats (11.8 ± 5.5% decrease, P < 0.05). In normal and diabetic rat hearts, 1–10 ?M CAPA increased coronary flow rate, and this increase was abolished by 10 ?M NOS inhibitor. In the thoracic aorta, the concentration/response curve of phenylephrine was right-shifted by administration of 100 ?M CAPA. Coronary flow rate was reduced to 7.2 ± 0.2 mL/min at 8 weeks after STZ-induction. However, 4 weeks of treatment with CAPA (3 mg/kg, intraperitoneal, twice daily) started at 4 weeks after STZ induction increased flow rate to 11.2 ± 0.5 mL/min (P < 0.05). In addition, the contractile response induced by 1 ?M phenylephrine increased from 6.8 ± 0.6 mN to 11.4 ± 0.4 mN (P < 0.05) and 14.9 ± 1.4 mN (P < 0.05) by insulin (1 IU/kg, intraperitoneal) or CAPA treatment, respectively. Conclusions CAPA induced hypoglycemic activity, increased coronary blood flow and vascular response to phenylephrine in type 1 diabetic rats. The increase in coronary blood flow may result from endothelial NOS activation. However, the detailed cellular mechanisms need to be further evaluated. PMID:23829275

2013-01-01

206

Codelivery of a tea extract prevents morbidity and mortality associated with oral vanadate therapy in streptozotocin-induced diabetic rats.  

PubMed

Oral administration of vanadate has a strong hypoglycemic effect but results in toxic side effects like life-threatening diarrhea. Tea is known to have potent antidiarrhea effects. We investigated the potential of suspending the vanadate in a tea decoction to reduce the diarrheatic action of vanadate. A concentrated extract of Lichee black tea was, therefore, added to sodium orthovanadate. Streptozotocin (STZ)-induced diabetic rats were orally gavaged with vanadate suspended in water or in the tea decoction, or with the tea extract alone. Blood glucose levels were assessed daily over 11 weeks with levels greater than 10 mmol/L warranting therapeutic intervention. Both the vanadate/water and vanadate/tea solutions acutely reduced blood glucose. The tea extract alone had no effect. The majority of vanadate/water-treated rats developed diarrhea and mortality rates approached 40%. Vanadate/tea-treated diabetic rats experienced no diarrhea or mortality and liver and kidney analyses (plasma ALT and creatinine, blood urea nitrogen [BUN], and urine-specific gravity) were normal. Animals treated with vanadate/tea retained blood glucose levels less than 10 mmol/L for an average of 24 consecutive days without subsequent treatments. Cataract formation was completely prevented. The mechanism of action of vanadate may have involved beta-cell stimulation because vanadate/tea-treated diabetic rats exhibited normal plasma insulin levels. In summary, because of its long-lasting effects, oral administration, and lack of side effects, vanadate/tea represents a potentially important alternative therapy for an insulin-deficient diabetic state. PMID:15334376

Clark, Tod A; Heyliger, Clayton E; Edel, Andrea L; Goel, Danny P; Pierce, Grant N

2004-09-01

207

Susceptibility to myocardial ischemia reperfusion injury at early stage of type 1 diabetes in rats  

PubMed Central

Background Large body of evidences accumulated in clinical and epidemiological studies indicate that hearts of diabetic subjects are more sensitive to ischemia reperfusion injury (IRI), which results in a higher rate of mortality at post-operation than that of non-diabetes. However, experimental results are equivocal and point to either increased or decreased susceptibility of the diabetic hearts to IRI, especially at the early stage of the disease. The present study was designed to test the hypothesis that the duration/severity of the indexed ischemia is a major determinant of the vulnerability to myocardial IRI at early stage of diabetes. Methods Four weeks streptozotocin (STZ)-induced diabetic (D) and non-diabetic (C) Sprague–Dawley rats were randomly assigned to receive 30 or 45 min of left anterior descending artery ligation followed by 2 or 3 hours of reperfusion, respectively. Cardiac function was recorded by using Pressure-Volume (PV) conduction system. Myocardial infarct size was determined with triphenyltetrazolium chloride staining. Plasma Creatine kinase-MB (CK-MB), Lactate dehydrogenase (LDH) release, myocardial nitric oxide(NO) content and nitrotyrosine formation, 15-F2t-Isoprostane and plasma superoxide dismutase (SOD) were measured with colorimetric assays. Cardiomyocyte apoptosis was assessed by TUNEL staining. Myocardial TNF?, Caspase-3, STAT3, Akt, and GSK-3? were determined by Western blotting. Results Prolongation of ischemia but not reperfusion from 30 min to 45 min significantly increased infarct size in D compared to C rats (P?rats (P?Diabetic hearts, even at early stage of the disease are more sensitive to IRI, and this increased severity of post-ischemic myocardial injury depends more on the duration of ischemia than that of reperfusion. PMID:24041262

2013-01-01

208

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

PubMed Central

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

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

2014-01-01

209

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

2013-10-01

210

Effects of glutamine supplementation on oxidative stress-related gene expression and antioxidant properties in rats with streptozotocin-induced type 2 diabetes.  

PubMed

There are close links among hyperglycaemia, oxidative stress and diabetic complications. Glutamine (GLN) is an amino acid with immunomodulatory properties. The present study investigated the effect of dietary GLN on oxidative stress-relative gene expressions and tissue oxidative damage in diabetes. There were one normal control (NC) and two diabetic groups in the present study. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin (STZ). Rats in the NC group were fed a regular chow diet. In the two diabetic groups, one group (diabetes mellitus, DM) was fed a common semi-purified diet while the other group received a diet in which part of the casein was replaced by GLN (DM-GLN). GLN provided 25% of total amino acid N. The experimental groups were fed the respective diets for 8 weeks, and then the rats were killed for further analysis. The results showed that blood thioredoxin-interacting protein (Txnip) mRNA expression in the diabetic groups was higher than that in the NC group. Compared with the DM group, the DM-GLN group had lower glutamine fructose-6-phosphate transaminase 1, a receptor of advanced glycation end products, and Txnip gene expressions in blood mononuclear cells. The total antioxidant capacity was lower and antioxidant enzyme activities were altered by the diabetic condition. GLN supplementation increased antioxidant capacity and normalised antioxidant enzyme activities. Also, the renal nitrotyrosine level and Txnip mRNA expression were lower when GLN was administered. These results suggest that dietary GLN supplementation decreases oxidative stress-related gene expression, increases the antioxidant potential and may consequently attenuate renal oxidative damage in rats with STZ-induced diabetes. PMID:22129885

Tsai, Pei-Hsuan; Liu, Jun-Jen; Yeh, Chui-Li; Chiu, Wan-Chun; Yeh, Sung-Ling

2012-04-01

211

Diabetic Complications in Obese Type 2 Diabetic Rat Models  

PubMed Central

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

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

2014-01-01

212

The cardioprotective effect of an aqueous extract of fermented rooibos (Aspalathus linearis) on cultured cardiomyocytes derived from diabetic rats.  

PubMed

Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle that contributes to cardiovascular deaths in the diabetic population. Excessive generation of free radicals has been directly implicated in the pathogenesis of DCM. The use of antioxidants, through dietary supplementation, to combat increased cellular oxidative stress has gained popularity worldwide. Aspalathus linearis (rooibos) is a popular herbal tea that contains a novel antioxidant, aspalathin. Literature has reported on the antidiabetic, anti-inflammatory and free radical scavenging effects of rooibos. However, its protective effect against DCM has not been established. Therefore, this study investigated whether chronic exposure to an aqueous extract of fermented rooibos (FRE) has an ex vivo cardioprotective effect on hearts obtained from streptozotocin (STZ) induced diabetic rats. Adult Wistar rats were injected with 40 mg/kg of STZ. Two weeks after STZ injection, cardiomyocytes were isolated and cultured. Cultured cardiomyocytes were treated with FRE (1 and 10 ?g/ml), vitamin E (50 ?g/ml), and n-acetyl cysteine (1mM) for 6h, before exposure to either hydrogen peroxide (H2O2) or an ischemic solution. Cardiomyocytes exposed to H2O2 or an ischemic solution showed a decrease in metabolic activity and glutathione content with a concomitant increase in apoptosis and intracellular reactive oxygen species. Pretreatment with FRE was able to combat these effects and the observed amelioration was better than the known antioxidant vitamin E. This study provides evidence that an aqueous extract of fermented rooibos protects cardiomyocytes, derived from diabetic rats, against experimentally induced oxidative stress and ischemia. PMID:24268738

Dludla, P V; Muller, C J F; Louw, J; Joubert, E; Salie, R; Opoku, A R; Johnson, R

2014-04-15

213

Effect of diabetes on the levels of two forms of Met-enkephalin in plasma and peripheral tissues of the rat.  

PubMed

Levels of native and cryptic or peptidase-derivable (after being digested with trypsin and carboxypeptidase) Met-enkephalin were measured by a specific radioimmunoassay method in plasma, anterior and neurointermediate lobes of pituitary and various peripheral tissues of streptozotocin (STZ) diabetic rats. The results show that the highest concentration of native and cryptic Met-enkephalin were found in the neurointermediate lobe of pituitary. Streptozotocine-induced diabetes alters the concentration of either or both forms of Met-enkephalin in plasma, the anterior and neurointermediate lobes of the pituitary, heart, lung, spleen, liver, seminal vesicle, vas deferens, kidney, bladder detrusor, and duodenum. One of the most pronounced effects of diabetes observed in this study is seen in the seminal vesicles where native Met-enkephalin was depleted to less than 10% of the control value. The uneven distribution of Met-enkephalin in peripheral tissues may suggest that these tissues process and/or metabolize Met-enkephalin to different degrees. Our data also suggest that STZ-induced diabetes alters the enkephalinergic activity in some of these tissues. It is suggested that some of the peripheral pathophysiological symptoms associated with diabetes may be attributed, in part, to altered activity of enkephalinergic systems. PMID:1738434

Kolta, M G; Pierzchala, K; Houdi, A A; Van Loon, G R

1992-01-01

214

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

PubMed Central

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

2013-01-01

215

Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress.  

PubMed

Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain. Repeated treatment with cannabis extract significantly relieved mechanical allodynia and restored the physiological thermal pain perception in streptozotocin (STZ)-induced diabetic rats without affecting hyperglycemia. In addition, the results showed that eCBD increased the reduced glutathione (GSH) content in the liver leading to a restoration of the defence mechanism and significantly decreased the liver lipid peroxidation suggesting that eCBD provides protection against oxidative damage in STZ-induced diabetes that also strongly contributes to the development of neuropathy. Finally, the nerve growth factor content in the sciatic nerve of diabetic rats was restored to normal following the repeated treatment with eCBD, suggesting that the extract was able to prevent the nerve damage caused by the reduced support of this neurotrophin. These findings highlighted the beneficial effects of cannabis extract treatment in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and a specific action upon nerve growth factor. PMID:19441010

Comelli, Francesca; Bettoni, Isabella; Colleoni, Mariapia; Giagnoni, Gabriella; Costa, Barbara

2009-12-01

216

Differing effects of water-soluble and fat-soluble extracts from Japanese radish (Raphanus sativus) sprouts on carbohydrate and lipid metabolism in normal and streptozotocin-induced diabetic rats.  

PubMed

We have shown previously that Japanese radish (Raphanus sativus) sprouts (JRS) improve blood glucose levels in diabetic rats. In this study, we investigated the components in JRS that caused this hypoglycemic effect, by examining the effects of water-soluble (WSE) and fat-soluble (FSE) extracts of JRS on diabetes markers in normal (NM) and streptozotocin (STZ)-induced diabetic (DM) rats. The NM and DM rats were divided into a control group and 2 test groups (WSE (2.2%) or FSE (0.2%)), with the rats (n = 6/group) then being maintained for 3 wk on either a control diet or one of the test diets; this was followed by the measurement of serum concentrations of glucose, insulin, glycoalbumin, fructosamine, ketone bodies, and lipids (cholesterol and triglyceride) and liver concentrations of lipids (total lipid, total cholesterol, and triglyceride). The FSE suppressed insulin secretion and improved lipid metabolism in the NM rats. The effect of WSE was different from that of the FSE as it decreased blood glucose levels without increasing insulin secretion and also lowered glycoalbumin and fructosamine levels in the DM rats. Therefore, the WSE have potential as functional food components with the hypoglycemic effect. PMID:17874832

Taniguchi, Hironobu; Muroi, Rieko; Kobayashi-Hattori, Kazuo; Uda, Yasushi; Oishi, Yuichi; Takita, Toshichika

2007-06-01

217

Roles of the co-culture of human umbilical cord Wharton's jelly-derived mesenchymal stem cells with rat pancreatic cells in the treatment of rats with diabetes mellitus  

PubMed Central

The aim of the present study was to investigate the roles of the co-culture of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hUC-MSCs) with rat pancreatic cells in the treatment of rats with diabetes mellitus. hUC-MSCs were isolated and passaged, followed by Transwell co-culture with rat pancreatic cells. The induced islet-like cell clusters were transplanted into the renal capsule in rats with streptozotocin (STZ)-induced diabetes mellitus. The effects of co-culture on blood glucose levels in rats were observed. The isolated hUC-MSCs expressed the specific surface markers, including cluster of differentiation 44 (CD44) (91.4%), CD29 (91.3%) and CD105 (99.2%). Following co-culture with hUC-MSCs for 7 and 10 days, the rat pancreatic cells were strongly stained by pancreatic and duodenal homeobox-1 and human insulin. The insulin and C-peptide concentrations were increased significantly compared to the pure culture group. One week following the transplantation of induced islet-like cells into the renal capsule, the blood glucose level of rats in the STZ experimental group was significantly lower than that of the STZ control group. There were notable 5-bromo-2?-deoxyuridine-positive nuclei and insulin-positive cytoplasm in the renal capsule following cell transplantation. Therefore, co-culture of hUC-MSCs with rat pancreatic cells can lower the blood glucose levels in rats with diabetes mellitus. PMID:25289028

WANG, GUANGYU; LI, YONG; WANG, YU; DONG, YU; WANG, FU-SHENG; DING, YI; KANG, YUDONG; XU, XUYING

2014-01-01

218

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

SciTech Connect

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

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

2010-11-15

219

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. PMID:18174522

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

2008-01-01

220

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. PMID:19495918

2009-01-01

221

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

PubMed

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

Masjedi, Fatemeh; Gol, Ali; Dabiri, Shahriar

2013-01-01

222

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

PubMed Central

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

Masjedi, Fatemeh; Gol, Ali; Dabiri, Shahriar

2013-01-01

223

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

PubMed

This study was designed to investigate the effects of Cd exposure on the glycogen localization in the placenta and in fetal and maternal livers in streptozotocin (STZ)-induced-diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200-220 g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups (control, Cd treated, STZ treated, and Cd+STZ treated). The Cd-treated group was injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl, starting at the onset of pregnancy throughout the experiment. Diabetes was induced on d 13 of pregnancy by a single intraperitoneal injection of STZ in the STZ-treated group. In addition to the daily injection of Cd, a single intraperitoneal injection of STZ was also given on d 13 of pregnancy in the Cd+STZ-treated group. The rats received the last injection 24 h before being sacrificed and 10 randomly selected rats in each group were sacrificed on d 15 and d 20 of pregnancy. Blood samples were taken for determination of the serum glucose and insulin levels. Fetal and maternal livers of sacrificed rats in all groups were harvested on d 15 and d 20 of pregnancy, whereas placentas were harvested only on d 20 of pregnancy for histochemical examination. Although both Cd and STZ caused hyperglycemia and decreased insulin secretion, Cd-alone treatment increased the glycogen content only in the placental labyrinth, whereas STZ-alone treatment increased the glycogen content only in the maternal part of the placenta. Increased glycogen localization was observed in both the placental labyrinth and the maternal part of placenta when Cd and STZ were given together. Fetal and maternal livers of control and other treatment groups were not different regarding the glycogen content on d 15 or d 20 of pregnancy. It was concluded that Cd exposure during pregnancy might produce a glycogen localization in the placenta of diabetic rats. However, the function and the mechanisms of increased glycogen contents in the placenta of Cd-exposed pregnant diabetic rats remain unclear and further studies are needed. PMID:14716101

Yoruk, Mecit; Kanter, Mehmet; Meral, Ismail; Agaoglu, Zahid

2003-01-01

224

Combined Renin Inhibition/(Pro)Renin Receptor Blockade in Diabetic Retinopathy- A Study in Transgenic (mREN2)27 Rats  

PubMed Central

Dysfunction of renin-angiotensin system (RAS) contributes to the pathogenesis of diabetic retinopathy (DR). Prorenin, the precursor of renin is highly elevated in ocular fluid of diabetic patients with proliferative retinopathy. Prorenin may exert local effects in the eye by binding to the so-called (pro)renin receptor ((P)RR). Here we investigated the combined effects of the renin inhibitor aliskiren and the putative (P)RR blocker handle-region peptide (HRP) on diabetic retinopathy in streptozotocin (STZ)-induced diabetic transgenic (mRen2)27 rats (a model with high plasma prorenin levels) as well as prorenin stimulated cytokine expression in cultured Müller cells. Adult (mRen2)27 rats were randomly divided into the following groups: (1) non-diabetic; (2) diabetic treated with vehicle; (3) diabetic treated with aliskiren (10 mg/kg per day); and (4) diabetic treated with aliskiren+HRP (1 mg/kg per day). Age-matched non-diabetic wildtype Sprague-Dawley rats were used as control. Drugs were administered by osmotic minipumps for three weeks. Transgenic (mRen2)27 rat retinas showed increased apoptotic cell death of both inner retinal neurons and photoreceptors, increased loss of capillaries, as well as increased expression of inflammatory cytokines. These pathological changes were further exacerbated by diabetes. Aliskiren treatment of diabetic (mRen2)27 rats prevented retinal gliosis, and reduced retinal apoptotic cell death, acellular capillaries and the expression of inflammatory cytokines. HRP on top of aliskiren did not provide additional protection. In cultured Müller cells, prorenin significantly increased the expression levels of IL-1? and TNF-?, and this was completely blocked by aliskiren or HRP, their combination, (P)RR siRNA and the AT1R blocker losartan, suggesting that these effects entirely depended on Ang II generation by (P)RR-bound prorenin. In conclusion, the lack of effect of HRP on top of aliskiren, and the Ang II-dependency of the ocular effects of prorenin in vitro, argue against the combined application of (P)RR blockade and renin inhibition in diabetic retinopathy. PMID:24968134

Batenburg, Wendy W.; Verma, Amrisha; Wang, Yunyang; Zhu, Ping; van den Heuvel, Mieke; van Veghel, Richard; Danser, A. H. Jan; Li, Qiuhong

2014-01-01

225

Antidiabetic effect of Korean traditional Baechu (Chinese cabbage) kimchi in a type 2 diabetes model of rats.  

PubMed

The present study was conducted to examine the antidiabetic effects of two dietary dosages (0.5% and 2.0%) of freeze-dried Korean traditional Baechu (Chinese cabbage) kimchi in a high-fat (HF) diet-fed, streptozotocin (STZ)-induced type 2 diabetes (T2D) rat model. Five-week-old male Sprague-Dawley rats were fed HF diet for 2 weeks and then randomly divided into four groups of eight animals: normal control (NC), diabetic control (DBC), kimchi low (KML) (0.5%), and kimchi high (KMH) (2.0%) groups. Diabetes was induced by an intraperitoneal injection of STZ (40 mg/kg of body weight) in all groups except the NC group. After 4 weeks of feeding of experimental diets, serum insulin concentrations and Homeostatic Model Assessment pancreatic beta-cell function were increased and blood glycated hemoglobin was decreased in the kimchi-fed groups compared to the DBC group, while a significant (P < .05) difference was observed only in the KMH group for serum insulin concentration. Lower fasting blood glucose and better glucose tolerance were observed in the KMH group compared to the DBC and KML groups; however, differences were not significant. Food intake, body weight gain, Homeostatic Model Assessment insulin resistance index, and serum lipid profiles were not significantly influenced by kimchi-containing diets. Data of this study suggest that dietary Baechu kimchi has some antidiabetic effects even when fed with a HF-containing diet. Better results are possible if it is consumed with normal or low-fat rather than HF-containing diet. PMID:19459728

Islam, Md Shahidul; Choi, Haymie

2009-04-01

226

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

227

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.  

PubMed

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 (1g/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-1alpha (p-IRE1alpha), 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 kappaB (NF-kappaB) 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-kappaB activity, the expression of p-IRE1alpha, 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. PMID:20399799

Luo, Zhi-Feng; Feng, Bing; Mu, Jiao; Qi, Wei; Zeng, Wei; Guo, Yan-Hong; Pang, Qi; Ye, Zi-Lin; Liu, Li; Yuan, Fa-Huan

2010-07-01

228

[Adipocyte insulin binding and glucose transport in normal pregnancy and streptozotocin-induced diabetic pregnancy in the rat: evidence for a postreceptor abnormality in insulin action].  

PubMed

To investigate the effect of pregnancy on the course of streptozotocin (STZ) induced diabetes, insulin binding to receptors and glucose transport activity were studied in isolated adipocytes from normal nonpregnant, normal pregnant, STZ-treated nonpregnant and STZ-treated pregnant rats. Experimental diabetes was induced by the administration of 40 mg/kg of STZ, and those exhibiting blood sugar concentrations between 150 and 250 mg/100 ml (198.8 +/- 6.4 mg/100 ml, mean +/- SEM) 7 days after treatment, were then used for the experiments as diabetic animals. Rats were mated at least 10 days after STZ administration. All studies were performed on gestational day 19. Fetuses of the diabetic mothers tended to be heavier than those of the control rats (2.49 +/- 0.31 vs. 2.38 +/- 0.22 g, mean +/- SD), but the difference was not statistically significant. Placental weights were significantly greater in the diabetics than in the controls (0.60 +/- 0.12 vs. 0.48 +/- 0.097 g, mean /+- SD, p less than 0.05). Insulin binding to receptors at an insulin concentration of 0.2 ng/ml was increased by 21% in the STZ-treated nonpregnant group as compared with the untreated non-pregnant group, by 32% in the STZ-treated pregnant group as compared with the untreated pregnant group due to increased receptor affinity without increasing the receptor number. However, no change in insulin binding was detected between the normal nonpregnant and normal pregnant, STZ-treated nonpregnant and STZ-treated pregnant groups. Glucose transport activity was decreased in adipocytes from the normal pregnant group as compared with that of the normal nonpregnant group. The effect was also observed between adipocytes from the sTZ-treated pregnant group and from the STZ-treated nonpregnant group. Adipocytes from rats belonging to either the normal pregnant group or the STZ-treated nonpregnant group showed a similar decrease in glucose transport activity, suggesting an equal effect of pregnancy and mild diabetes on glucose transport. Furthermore, adipocytes from the STZ-treated pregnant group showed the lowest transport activity of the four groups studied, suggesting an additive effect of pregnancy and diabetes on glucose transport activity. In conclusion, although insulin action in isolated adipocytes is reduced by pregnancy whether diabetes is induced or not, insulin binding to receptors is not changed by pregnancy. Thus, the effect on insulin action in adipocytes from diabetic rats as well as normal rats might lie at a site distal to the receptor. Insulin action in isolated adipocytes is reduced additively by pregnancy and diabetes. PMID:6687055

Shimizu, K; Toyoda, N; Morikawa, F; Sugiyama, Y

1983-12-20

229

Protective action of Citrullus colocynthis seed extracts against the deleterious effect of streptozotocin on both in vitro glucose-stimulated insulin release from rat pancreatic islets and in vivo glucose homeostasis  

PubMed Central

Citrullus colocynthis extracts improve glucose homeostasis in alloxan- or streptozotocin (STZ)-induced diabetic rats. Little is known, however, regarding the protective effect of these extracts against the ?-cytotoxic action of STZ. In the present study, an H2O-methanol extract was found to suppress the inhibition of glucose-stimulated insulin secretion by STZ in rat-isolated pancreatic islets. Similarly, when an aqueous extract from Citrullus colocynthis seeds was injected daily for 21 days prior to STZ administration, the perturbation of glucose homeostasis otherwise generated by the ?-cytotoxic agent was minimized in rats. PMID:24648906

BENARIBA, NABILA; BELLAKDHAR, WAFAA; DJAZIRI, RABEH; HUPKENS, EMELINE; LOUCHAMI, KARIM; MALAISSE, WILLY J.

2013-01-01

230

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

PubMed Central

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

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

2014-01-01

231

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. PMID:23227140

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

2012-01-01

232

Ethanol extract of Dendrobium chrysotoxum Lindl ameliorates diabetic retinopathy and its mechanism.  

PubMed

Diabetic retinopathy (DR) is the most common and serious complication of diabetes mellitus (DM). The present study investigates the amelioration of ethanol extract of Dendrobium chrysotoxum Lindl (DC) on streptozotocin (STZ)-induced DR and its engaged mechanism. Retinal immunofluorescence staining with cluster of differentiation 31 (CD31) demonstrated that DC (30-300 mg/kg) decreased the increased retinal vessels in STZ-induced diabetic rats. Retinal histopathological observation also showed that retinal vessels were decreased in DC-treated diabetic rats. DC decreased the increased retinal mRNA expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in diabetic rats, and DC also decreased the elevated serum VEGF level. Immunohistochemical staining further evidenced that DC decreased VEGF and VEGFR2 expression in retinas. Retinal mRNA expression of matrix metalloproteinase (MMP) 2/9 was decreased in DC (300 mg/kg)-treated diabetic rats. Serum levels of MMP 2/9, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) A/B, insulin-like growth factor 1 (IGF-1), interleukin 1? (IL-1?), and IL-6 were all decreased in DC-treated diabetic rats. In addition, DC decreased the increased phosphorylation of p65 and the increased expression of intercellular adhesion molecule-1 (ICAM-1). In conclusion, DC can alleviate retinal angiogenesis during the process of DR via inhibiting the expression of VEGF/VEGFR2, and some other pro-angiogenic factors such as MMP 2/9, PDGF A/B, bFGF, IGF-1. In addition, DC can also ameliorate retinal inflammation via inhibiting NF?B signaling pathway. PMID:24846859

Gong, Chen-Yuan; Yu, Zeng-Yang; Lu, Bin; Yang, Li; Sheng, Yu-Chen; Fan, Yuan-Min; Ji, Li-Li; Wang, Zheng-Tao

2014-09-01

233

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

PubMed Central

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

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

2014-01-01

234

Arginine metabolism in enterocytes of diabetic rats  

E-print Network

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

Morrow, Natalie Anne

2012-06-07

235

Reversibility of Diabetic Cardiomyopathy with Insulin in Rats  

Microsoft Academic Search

SUMMARY Diabetes appears to cause a cardiomyopathy independent of atherosclerotic coronary artery disease and hypertension. Left ventricular papillary muscle function studies in rats made severely diabetic with streptozotocin have shown a slowing of relaxation and a depression of shortening velocity. However, the effects of insulin therapy on the myocardial mechanics of diabetic rats have not been studied. Therefore, rats diabetic

FREDERICK S. FEIN; JOHN E. STROBECK; ASHWANI MALHOTRA; JAMES SCHEUER; EDMUND H. SONNENBLICK

2009-01-01

236

Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats  

Microsoft Academic Search

This study investigated the hypoglycemic and antioxidant effects of Flax and Pumpkin seeds mixture on the kidney of alloxan-induced diabetic rats. Animals were allocated into three groups of six rats each: a control group (CD), a diabetic group (DD) and diabetic rats fed with Flax and Pumpkin seeds mixture (DMS) group. The DD rats showed a significant increase of glycemia

Mohamed Makni; Mediha Sefi; Hamadi Fetoui; El Mouldi Garoui; Nabil K. Gargouri; Tahia Boudawara; Najiba Zeghal

2010-01-01

237

Testicular lesions of streptozotocin diabetic rats.  

PubMed

Diabetes was induced in adult male albino rats by a single intravenous injection of streptozotocin (75 mg/kg body weight). The diabetes was allowed to stabilize for at least 15 days, whereafter the testicular and seminal vesicle histology was studied at various time intervals. Reduction in testis weights and tubule diameters was significant after 2 weeks of diabetes. The changes in seminiferous tubules ranged from premature sloughing of epithelium to total cessation of spermatogenesis. The testicular histology of diabetic animals frequently greatly simulated the situation described following hypophysectomy. By subjective visual assessment the number of Leydig cells was found to be normal or reduced in all of the diabetic animals. Diabetes was also demonstrated to induce seminal vesicle atrophy, which did not show any correlation with the degree of testicular lesions. The possible etiology of testicular damage in diabetic animals is discussed. PMID:130334

Oksanen, A

1975-01-01

238

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. PMID:23209733

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

2012-01-01

239

Quercetin and Allopurinol Ameliorate Kidney Injury in STZ-Treated Rats with Regulation of Renal NLRP3 Inflammasome Activation and Lipid Accumulation  

PubMed Central

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

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

2012-01-01

240

Oxidative-Nitrosative Stress and Poly(ADP-Ribose) Polymerase (PARP) Activation in Experimental Diabetic Neuropathy  

PubMed Central

Poly(ADP-ribose) polymerase (PARP) activation, an important factor in the pathogenesis of diabetes complications, is considered a downstream effector of oxidative-nitrosative stress. However, some recent findings suggest that it is not necessarily the case and that PARP activation may precede and contribute to free radical and oxidant-induced injury. This study evaluated the effect of PARP inhibition on oxidative-nitrosative stress in diabetic peripheral nerve, vasa nervorum, aorta, and high glucose–exposed human Schwann cells. In vivo experiments were performed in control rats and streptozocin (STZ)-induced diabetic rats treated with and without the PARP inhibitor 3-aminobenzamide (ABA) (30 mg · kg?1 · day?1 i.p. for 2 weeks after 2 weeks of untreated diabetes). Human Schwann cells (HSC) (passages 7–10; ScienCell Research Labs) were cultured in 5.5 or 30 mmol/l glucose with and without 5 mmol/l ABA. Diabetes-induced increase in peripheral nerve nitrotyrosine immunoreactivity, epineurial vessel superoxide and nitrotyrosine immunoreactivities, and aortic superoxide production was reduced by ABA. PARP-1 (Western blot analysis) was abundantly expressed in HSC, and its expression was not affected by high glucose or ABA treatment. High-glucose–induced superoxide production and overexpression of nitrosylated and poly(ADP-ribosyl)ated protein, chemically reduced amino acid-(4)-hydroxynonenal adducts, and inducible nitric oxide synthase were decreased by ABA. We concluded that PARP activation contributes to superoxide anion radical and peroxynitrite formation in peripheral nerve, vasa nervorum, and aorta of STZ-induced diabetic rats and high-glucose–exposed HSC. The relations between oxidative-nitrosative stress and PARP activation in diabetes are bi-rather than unidirectional, and PARP activation cannot only result from but also lead to free radical and oxidant generation. PMID:16306359

Obrosova, Irina G.; Drel, Viktor R.; Pacher, Pal; Ilnytska, Olga; Wang, Zhong Q.; Stevens, Martin J.; Yorek, Mark A.

2008-01-01

241

Pharmacokinetics and Pharmacodynamics of Gliclazide from Immediate and Modified Release Formulation Tablets in Rats  

PubMed Central

The objective of the study was to compare pharmacokinetic and pharmacodynamic parameters of gliclazide after administration of immediate (IR) and modified release (MR) tablets. The experiment included rats with both normoglycemia and streptozocin (STZ)-induced hyperglycemia. Several MR formulations were designed and in-vitro drug release profile was assessed by a dissolution test. For the further in-vivo study the most suitable formulation was chosen. For pharmacokinetic analysis concentrations of gliclazide in plasma were determined by a validated high performance liquid chromatography (HPLC) method with UV detection. Pharmacodynamic efficacy of the drug was evaluated by measuring blood glucose concentrations. Gliclazide bioavailability was totally different for two formulations in both healthy and diabetic rats based on area under the curve (AUC), time to peak concentration (tmax) and peak concentration (Cmax). Reduction of blood glucose level was significantly higher after the administration of IR than MR formulation. The highest pharmacodynamic efficacy of gliclazide was observed in the normal animals group after administration of the IR tablets, while hypoglycemic effect of the drug was diminished in animals with induced diabetes. Our study suggested that results of reduction in blood glucose level for STZ-induced groups were not comparable with pharmacodynamic effect for normal group. It may be assumed that a decrease in glycemia in healthy subjects might not be a suitable factor for characterizing anti-diabetic drugs. PMID:24734054

Resztak, M; Hermann, TW; Sawicki, W; Danielak, DZ

2014-01-01

242

Effects of streptozotocin-induced diabetes in pregnant rats on placental transport and tissue uptake of alpha-amino-isobutyric acid.  

PubMed

Placental transport and tissue uptake of amino acids were studied in streptozotocin (STZ)-induced diabetic rats by using the non-metabolizable amino acid [U-14C]-alpha-amino-isobutyric acid (AIB). Fifteen minutes prior to autopsy, animals of each group, control (C), diabetic (D), diabetic-insulin treated (DI) and diabetic-T4 followed by 3-5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT) treated (DTD), received an injection of the [U-14C]-AIB SC. Disintegrations per minute (DPM) were measured in serum and tissues subsequent to autopsy. There were no differences in maternal serum DPM/ml among groups. Fetal serum DPM, however, were lower in D and DTD groups than in the C group. The whole fetal tissue homogenate radioactivity was lower in the D, DTD, and DI groups than in the C group. In general, more AIB was taken up by fetal tissues of C than D animals. Maternal liver AIB uptake was reduced in D, DI, and DTD from C animals and net placental transport of AIB was less in D and DTD than C animals. Fetal liver protein concentrations were depressed in D and DTD animals from C and DI, but fetal brain protein concentrations showed no significant differences. Furthermore, the lower organ and fetal body weights of the D and DTD groups compared with the C and DI groups support the proposal that fetal anabolism is impaired. Maternal and fetal serum T4 concentrations were lower in D and DTD than in C and DI animals. Insulin therapy improved serum T4 levels in both mother and fetuses. It did not, however, correct all other measured parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3557285

Copeland, A D; Porterfield, S P

1987-02-01

243

Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: the relation is revisited.  

PubMed

Poly(ADP-ribose) polymerase (PARP) activation, an important factor in the pathogenesis of diabetes complications, is considered a downstream effector of oxidative-nitrosative stress. However, some recent findings suggest that it is not necessarily the case and that PARP activation may precede and contribute to free radical and oxidant-induced injury. This study evaluated the effect of PARP inhibition on oxidative-nitrosative stress in diabetic peripheral nerve, vasa nervorum, aorta, and high glucose-exposed human Schwann cells. In vivo experiments were performed in control rats and streptozocin (STZ)-induced diabetic rats treated with and without the PARP inhibitor 3-aminobenzamide (ABA) (30 mg . kg(-1) . day(-1) i.p. for 2 weeks after 2 weeks of untreated diabetes). Human Schwann cells (HSC) (passages 7-10; ScienCell Research Labs) were cultured in 5.5 or 30 mmol/l glucose with and without 5 mmol/l ABA. Diabetes-induced increase in peripheral nerve nitrotyrosine immunoreactivity, epineurial vessel superoxide and nitrotyrosine immunoreactivities, and aortic superoxide production was reduced by ABA. PARP-1 (Western blot analysis) was abundantly expressed in HSC, and its expression was not affected by high glucose or ABA treatment. High-glucose-induced superoxide production and overexpression of nitrosylated and poly(ADP-ribosyl)ated protein, chemically reduced amino acid-(4)-hydroxynonenal adducts, and inducible nitric oxide synthase were decreased by ABA. We concluded that PARP activation contributes to superoxide anion radical and peroxynitrite formation in peripheral nerve, vasa nervorum, and aorta of STZ-induced diabetic rats and high- glucose-exposed HSC. The relations between oxidative-nitrosative stress and PARP activation in diabetes are bi- rather than unidirectional, and PARP activation cannot only result from but also lead to free radical and oxidant generation. PMID:16306359

Obrosova, Irina G; Drel, Viktor R; Pacher, Pal; Ilnytska, Olga; Wang, Zhong Q; Stevens, Martin J; Yorek, Mark A

2005-12-01

244

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

PubMed Central

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

2014-01-01

245

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

2013-09-01

246

Intestinal absorption of cephalexin in diabetes mellitus model rats  

Microsoft Academic Search

We investigated the intestinal absorption and pharmacokinetics of cephalexin, as well as the intestinal H+\\/oligopeptide transporter PEPT1 mRNA and protein levels in type 1 and type 2 diabetic rats. Cephalexin disappearance from the duodenum loop was significantly lower in streptozotocin-induced type 1 diabetic rats and higher in hyperinsulinemic type 2 diabetic GK and Zucker-fa\\/fa (Zucker) rats, than in control rats.

Kazuhiro Watanabe; Kazuaya Terada; Juichi Sato

2003-01-01

247

Increased myocardial short-range forces in a rodent model of diabetes reflect elevated content of ? myosin heavy chain.  

PubMed

Diastolic dysfunction is a clinically significant problem for patients with diabetes and often reflects increased ventricular stiffness. Attached cross-bridges contribute to myocardial stiffness and produce short-range forces, but it is not yet known whether these forces are altered in diabetes. In this study, we tested the hypothesis that cross-bridge-based short-range forces are increased in the streptozotocin (STZ) induced rat model of type 1 diabetes. Chemically permeabilized myocardial preparations were obtained from 12week old rats that had been injected with STZ or vehicle 4weeks earlier, and activated in solutions with pCa (=-log10[Ca(2+)]) values ranging from 9.0 to 4.5. The short-range forces elicited by controlled length changes were ?67% greater in the samples from the diabetic rats than in the control preparations. This change was mostly due to an increased elastic limit (the length change at the peak short-range force) as opposed to increased passive muscle stiffness. The STZ-induced increase in short-ranges forces is thus unlikely to reflect changes to titin and/or collagen filaments. Gel electrophoresis showed that STZ increased the relative expression of ? myosin heavy chain. This molecular mechanism can explain the increased short-ranges forces observed in the diabetic tissue if ? myosin molecules remain bound between the filaments for longer durations than ? molecules during imposed movements. These results suggest that interventions that decrease myosin attachment times may be useful treatments for diastolic dysfunction associated with diabetes. PMID:24012810

Chung, Charles S; Mitov, Mihail I; Callahan, Leigh Ann; Campbell, Kenneth S

2014-06-15

248

Ciliary neurotrophic factor activates NF-?B to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents  

PubMed Central

Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether the NF-?B signal transduction pathway was mobilized by CNTF. Neurite outgrowth of sensory neurons derived from streptozotocin (STZ)-induced diabetic rats was reduced compared to neurons from control rats and exposure to CNTF for 24 h enhanced neurite outgrowth. CNTF also activated NF-?B, as assessed by Western blotting for the NF-?B p50 subunit and reporter assays for NF-?B promoter activity. Conversely, blockade of NF-?B signaling using SN50 peptide inhibited CNTF-mediated neurite outgrowth. Studies in mice with STZ-induced diabetes demonstrated that systemic therapy with CNTF prevented functional and structural indices of peripheral neuropathy along with deficiencies in dorsal root ganglion (DRG) NF-?B p50 expression and DNA binding activity. DRG neurons derived from STZ-diabetic mice also exhibited deficiencies in maximal oxygen consumption rate and associated spare respiratory capacity that were corrected by exposure to CNTF for 24 h in an NF-?B-dependent manner. We propose that the ability of CNTF to enhance axon regeneration and protect peripheral nerve from structural and functional indices of diabetic peripheral neuropathy is associated with targeting of mitochondrial function, in part via NF-?B activation, and improvement of cellular bioenergetics. PMID:23022047

Saleh, Ali; Roy Chowdhury, Subir K.; Smith, Darrel R.; Balakrishnan, Savitha; Tessler, Lori; Martens, Corina; Morrow, Dwane; Schartner, Emily; Frizzi, Katie E.; Calcutt, Nigel A.; Fernyhough, Paul

2012-01-01

249

Effects of cadmium exposure on morphological aspects of pancreas, weights of fetus and placenta in streptozotocin-induced diabetic pregnant rats.  

PubMed

This study was designed to evaluate the effects of Cd exposure on morphological aspects of beta-cell and weights of fetus and placenta in streptozotocin (STZ)-induced diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200-220 g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups (control, Cd treated, STZ treated, and Cd+STZ treated). The Cd-treated group was injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl, starting at the onset of pregnancy throughout the experiment. Diabetes was induced on the 13th d of pregnancy by a single intraperitoneal injection of STZ in STZ-treated group. In addition to the daily injection of Cd, a single intraperitoneal injection of STZ was also given on the 13th d of pregnancy in the Cd+STZ-treated group. The rats received the last injection 24 h before being sacrificed and 10 randomly selected rats in each group were sacrificed on the 15th and 20th d of pregnancy. Blood samples were taken for the determination of the serum glucose and insulin levels. Maternal pancreases, fetuses, and placentas of sacrificed rats in all groups were harvested (fetal pancreas was also harvested only on the 20th d of pregnancy) for morphological and immunohistochemical examinations. Cd exposure alone caused a degeneration, necrosis, and weak degranulation, but Cd exposure with STZ caused a severe degeneration, necrosis, and degranulation in the beta-cells of the pancreatic islets. No morphological or immunohistochemical differences were found in beta-cells of fetal pancreatic islets of control or other treatment groups. Cd exposure alone also decreased the fetal and placental weights. The administration of STZ alone, on the other hand, increased the placental weight. Cd, STZ, and Cd+STZ administration increased the glucose and decreased the insulin level. The increase in glucose and decrease in insulin levels were higher when Cd and STZ were given together. All of these changes were more severe on the 20th d than those on the 15th d of the pregnancy. It is concluded that Cd exposure during pregnancy may reduce the birth and placental weights and produce necrosis, degeneration, and degranulation in beta-cells of pancreatic islets, causing an increase in the serum glucose level. These changes might be severe in diabetic pregnant mothers. PMID:12835501

Kanter, Mehmet; Yoruk, Mecit; Koc, Ahmet; Meral, Ismail; Karaca, Turan

2003-01-01

250

Activation of spinal GABAB receptors normalizes N-methyl-D-aspartate receptor in diabetic neuropathy.  

PubMed

N-methyl-D-aspartate receptor (NMDAR) activity is increased, while GABAB receptor is downregulated in the spinal cord dorsal horn in diabetic neuropathy. In this study, we determined the interaction of NMDARs and GABAB receptors in streptozotocin (STZ)-induced diabetic neuropathy. The paw withdrawal threshold (PWT) was significantly lower in STZ-treated rats than in vehicle-treated rats. Intrathecal injection of baclofen, a GABAB receptor agonist, significantly increased the PWT in STZ-treated rats, an effect that was abolished by pre-administration of the GABAB receptor specific antagonist CGP55845. Spinal NR2B, an NMDA receptor subunit, protein and mRNA expression levels were significantly higher in STZ-treated rats than in vehicle-treated rats. Intrathecal baclofen significantly reduced the NR2B protein and mRNA expression levels in STZ-treated rats. Intrathecal administration of CGP55845 eliminated baclofen-induced reduction of NR2B protein and mRNA levels in STZ-treated rats. In addition, the phosphorylated cAMP response element-binding (CREB) protein level was significantly higher in the spinal cord dorsal horn in STZ-treated rats compared with vehicle-treated rats. Intrathecal injection of baclofen significantly decreased phosphorylated CREB protein level in STZ-treated rats; an effect was blocked by CGP55845. These data suggest that activation of GABAB receptors in the spinal cord dorsal horn normalizes NMDAR expression level in diabetic neuropathic pain. PMID:24787504

Bai, Hui-Ping; Liu, Peng; Wu, Yu-Ming; Guo, Wen-Ya; Guo, Yue-Xian; Wang, Xiu-Li

2014-06-15

251

Antioxidant effect of vanadate on experimental diabetic rats  

Microsoft Academic Search

Summary  The activities of enzymes involved in cellular defence mechanisms such as superoxide dismutase, catalase, glutathione peroxidase\\u000a and glutathione level have been found to be altered in experimental diabetes. Rats were made diabetic by a single i.v. injection\\u000a of streptozotocin (55 mg\\/kg body weight) in citrate buffer. After the onset of diabetes, the diabetic rats were treated with\\u000a sodium orthovanadate (0.3

Natesanpillai Sekar; Anumanthan Kanthasamy; Samuel William; Natarajan Balasubramaniyan; Saminathan Govindasamy

1990-01-01

252

Antidiabetic influence of quercetin in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The effect of feeding quercetin at the level of 1 g per kilogram of diet was studied in rats with streptozotocin-induced diabetes. The study involved a comparison between a starch-fed diabetic group and quercetin-fed diabetic group. The rats were examined for diet intake, water intake, gain in body weight, urine output, urine sugar, and fasting blood sugar. Diabetic status in

A. K Shetty; R Rashmi; M. G. R Rajan; K Sambaiah; P. V Salimath

2004-01-01

253

Antidiabetic effects of quercetin in streptozocin-induced diabetic rats  

Microsoft Academic Search

Effects of the intraperitoneal injection of quercetin in streptozocin-induced diabetic and normal rats were investigated and compared. Although quercetin had no effect on plasma glucose level of normal animals, it significantly and dose-dependently decreased the plasma glucose level of streptozocin-induced diabetic rats. Glucose tolerance tests of the diabetic animals approached those of normal rats, their plasma cholesterol and triglycerides were

Mahmood Vessal; Mina Hemmati; Mohammad Vasei

2003-01-01

254

Ovary Cells Apoptosis in Opium-Addicted Diabetic and Non-Diabetic Rats  

PubMed Central

Background Apoptosis is a physiological mechanism of cell death and it can be triggered by a variety of internal and external stimuli. It has been indicated that some opium derivatives develop cell apoptosis. Objectives The aim of this investigation was to evaluate the effect of opium addiction on ovary cell apoptosis in diabetic and non-diabetic Wistar rats. Materials and Methods This experimental study was done on control, control-addicted, diabetic and diabetic-addicted rats. DNA fragmentation as a biomarker of apoptosis was determined by the TUNEL assay. Results The blood glucose concentration in diabetic-addicted and diabetic rats was increased when compared to control (P < 0.001). There was no significant difference between weights of control, control-addicted (non-diabetic) and diabetic-addicted groups during this study. The results of this study indicated that apoptosis in addicted and diabetic-addicted ovary cells was significantly higher than in diabetic group, and also apoptosis in addicted group was significantly more than the control rats. In addition, we found that ovary cells apoptosis of diabetic rats were significantly less than in control group. Conclusions Overall, these findings suggest that opium-addiction could play an important role in ovary cell apoptosis and could be very harmful for the reproductive system. Also, ovary cells of non-diabetic rats are more susceptible to opium-induced apoptosis than those of diabetic. PMID:24971264

Asadikaram, Gholamreza; Asiabanha, Majid; Sirati Sabet, Majid

2013-01-01

255

Protective effect of magnesium and metformin on endometrium and ovary in experimental diabetes mellitus.  

PubMed

We evaluated the effect of magnesium and metformin on streptozotocin (STZ)-induced diabetes mellitus (DM) in non-pregnant female rats. The study comprised four groups, each consisting of eight, non-pregnant, adult Wistar female rats with a weight range of 170-250 g, maintained under the usual laboratory conditions. One group of female rats was the control group that received no treatment. To induce DM, the other three groups of animals received streptozotocin (STZ), 60 mg/kg i.p. (in a single dose). The first STZ group received no additional treatment. The second group received MgCl2 1 mmol/kg/day i.p. daily, for eight weeks. The third group received daily metformin, 100 mg/kg/day per os (endogastric probe), for eight weeks. Blood glucose, total plasma magnesium concentrations, and oxidative status were determined prior to, 24 hours and eight weeks after administration of the STZ. After eight weeks of treatment, the animals were anesthetized and sacrificed. The uterus and ovaries were removed and examined under optical microscopy. The data obtained were analyzed statistically using the ANOVA test. The results showed that the number of atretic ovarian follicles was 84%higher in the STZ-induced diabetes group compared to the control group (p<0.01). The number of atretic follicles found in the group receiving daily MgCl2 was 32% higher compared to the untreated control group (p<0.05). The number of atretic follicles was increased by only 27% in the metformin-treated group, as compared with the untreated control group.. The STZ-induced diabetes group presented an endometrial epithelial atrophy not seen in the control group. MgCl2 administration attenuated the degree of endometrial atrophy, there being an endometrial epithelial thickness of 19.43 ± 0.51 ?m in the STZ+MgCl2 group (p<0.05), as compared to a thickness of 13.51 ± 0.27 ?m in the STZ only-treated diabetic group. PMID:25118888

Gales, Cristina; Zamfir, Carmen; Radulescu, Doina; Stoica, Bogdan; Nechifor, Mihai

2014-05-01

256

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

257

Increased accumulation of sorbitol in offspring of manifest diabetic rats.  

PubMed

The effects of maternal diabetes on somatic development and activity of the polyol pathway were investigated during early and late gestation in a rat model for diabetic pregnancy. We studied embryo-fetal growth, mortality, and malformation rate in the offspring of nondiabetic rats and in the offspring of diabetic rats either treated with an aldose reductase inhibitor during gestation or left untreated. The numbers of embryo-fetal resorptions and malformations were significantly increased in the diabetic groups compared with the controls despite maternal treatment with the aldose reductase inhibitor. The sorbitol content of embryos and membranes from the diabetic rats in early gestation was increased 3-5 times over the control values. Similarly, elevated sorbitol levels were observed in the fetal livers and placentas of the diabetic rats in late gestation. Administration of the aldose reductase inhibitor to the pregnant diabetic rats normalized the sorbitol levels in the embryos and their membranes, whereas the sorbitol contents of the fetal livers and placentas were significantly lowered but not completely corrected. Furthermore, in the diabetic groups, no differences in sorbitol levels could be demonstrated between malformed and nonmalformed offspring. The results of this study suggest that enhanced polyol metabolism leading to increased sorbitol accumulation is present in the embryos of diabetic mothers as early as organogenesis. This accumulation is apparently not a major factor in the early developmental disturbances (e.g., growth perturbations and congenital malformations) of diabetic pregnancy. PMID:3770312

Eriksson, U J; Naeser, P; Brolin, S E

1986-12-01

258

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 2 weeks. Peripheral administration of NaHS (an exogenous donor of H2S) and L-cysteine (an endogenous donor of H2S) dose-dependently increased flinching behavior in diabetic and non-diabetic rats. Contrariwise, hydroxylamine (HA, a CBS inhibitor) and DL-propargylglycine (PPG, a CSE inhibitor) decreased formalin-induced nociceptive behavior in both experimental groups. In addition, an ineffective dose of HA and PPG partially prevented the L-cysteine-induced hyperalgesia in diabetic and non-diabetic rats. Interestingly, HA and PPG were three order of magnitude more potent in diabetic rats respect to non-diabetic rats, whereas NaHS was ten times more potent in the streptozotocin-diabetic group. Nine to 11 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, subcutaneous administration of PPG or HA reduced tactile allodynia in diabetic rats. Paradoxically, H2S levels were decreased in nerve sciatic, dorsal root ganglion and spinal cord, but not paw nor blood plasma, during diabetes-associated peripheral neuropathy development. Collectively, results suggest that H2S synthesized by CBS and CSE participate in formalin-induced nociception in diabetic and non-diabetic rats, as well as; in tactile allodynia in streptozotocin-injected rats. In addition, data seems to indicate that diabetic rats are more sensible to H2S-induced hyperalgesia than normoglycemic rats. PMID:23830907

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

2013-10-10

259

Improvement of diabetic complication by hydrangea dulcis folium in streptozotocin-induced diabetic rats.  

PubMed

The improvement of diabetic complications such as lipid lowering and anti-oxidative potential of Hydrangea Dulcis Folium (HDF) was studied in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into 3 groups after induction of streptozotocin (STZ)-diabetes: normal control; diabetic control; diabetic-HDF supplement (hot water extract 40 g/kg diet); and fed experimental diets for 3 weeks. Serum glucose and insulin concentrations, serum lipid profile, intraperitoneal glucose tolerance test, and liver cytosolic antioxidant enzyme levels were measured. The HDF supplement significantly decreased serum glucose concentration, increased insulin level, and improved glucose homeostasis in diabetic control rats. The total cholesterol and triglyceride concentrations in the serum and liver were markedly reduced by HDF treatment in STZ-diabetic rats. Moreover, low density lipoprotein (LDL)-, VLDL-, and high density lipoprotein (HDL)-cholesterol levels were ameliorated in HDF supplemented diabetic rats. Decreased fecal excretions of cholesterol, triglyceride, and bile acid in diabetic rats were significantly increased by HDF consumption. HDF supplement reversed the effects of the oxidative stress system of liver in diabetic rats. Lipid peroxidation of diabetic rats, assessed by thiobarbituric acid reactive substance (TBARS), as well as superoxide dismutase (SOD) activities were significantly increased, and glutathione contents were decreased in diabetic rats. HDF supplement reverted these parameters to near normal value. Our data suggest that HDF supplement could be used to improve the glucose and lipid metabolism as well as to reduce the imbalance between the generation of reactive oxygen species (ROS) and the scavenging enzyme activity in preventing diabetic complications. PMID:19122300

Kim, Hye Kyung; Kim, Mi Jeong; Lyu, Eun Soon; Shin, Dong-Hoon

2009-01-01

260

Mechanism of placental glycogen deposition in diabetes in the rat  

Microsoft Academic Search

Summary  The metabolic basis for glycogen accumulation in the placenta of rats with diabetes induced by streptozotocin on day 12 of pregnancy was studied on days 15 and 20. On day 15 glycogen content of the placenta was 1.5-fold higher in the diabetic than in the control rats and this difference increased to > fivefold on day 20 of gestation whether

V. Barash; A. Gutman; E. Shafrir

1983-01-01

261

The impact of type I diabetes on rat liver ?-glutamyltranspeptidase  

Microsoft Academic Search

The impact of type 1 diabetes mellitus on liver ?-glutamyltranspeptidase, a premalignant marker, was studied. Diabetes was induced in male Sprague Dawley and Fischer 344 rats by administration of Streptozotocin, which produced a stable and moderately severe diabetic state. In liver homogenates, ?-glutamyltranspeptidase was increased over control levels: 1.2, 8.1 and 13,2 fold in Strague-Dawley rats; 4.8, 58.4 and 84.7

Susan J. Hemmings; Robert D. Pekush

1994-01-01

262

Short and long term effects of antihypertensive therapy in the diabetic rat  

Microsoft Academic Search

Short and long term effects of antihypertensive therapy in the diabetic rat. To compare the impact of differing antihypertensive regimens on the development of renal injury, studies were performed in three groups of moderately hyperglycemic diabetic rats, and one group of non-diabetic control (C) rats. One diabetic group (DM) received no therapy except insulin. The remaining diabetic groups received insulin

Sharon Anderson; Helmut G Rennke; Diego L Garcia; Barry M Brenner; Susan L Riley; Deborah J Sandstrom

1989-01-01

263

Activation profile of dorsal root ganglia Iba-1 (+) macrophages varies with the type of lesion in rats.  

PubMed

The interactions between neurons, immune and immune-like glial cells can initiate the abnormal processes that underlie neuropathic pain. In the peripheral nervous system the resident macrophages may play an important role. In this study we investigated in experimental adult Sprague-Dawley rats how Iba-1 (ionized calcium binding adaptor molecule 1) (+) resident macrophages in the dorsal root ganglion (DRG) are activated after a spinal nerve ligation (SNL) or streptozotocin (STZ)-induced diabetes. The activation profile was defined by comparing the responses of resident macrophages against microglia in the spinal cord as they share a common origin. After SNL, the Iba-1 (+) macrophages in L5 DRG reached their activation peak 5 days later, clustered as satellite cells around large A-neurons, expressed the MHC-II marker, but did not show p-p38 and p-ERK1/2 activation and did not secrete IL-18. After STZ-induced diabetes, the Iba-1 (+) macrophages reached their activation peak 1 week later in L4 and L5 DRG, remained scattered between neurons, expressed the MHC-II marker only in L5 DRG, did not show p-p38 and p-ERK1/2 activation and did not secrete any of the investigated cytokines/chemokines. These responses suggest that depending on the type of lesion DRG Iba-1 (+) resident macrophages have different activation mechanisms, which are dissimilar to those in microglia. PMID:23701965

Ton, Bich-Hoai Thi; Chen, Qingmin; Gaina, Gisela; Tucureanu, Catalin; Georgescu, Adriana; Strungaru, Carmen; Flonta, Maria-Luiza; Sah, Dinah; Ristoiu, Violeta

2013-10-01

264

Mangiferin mitigates diabetic cardiomyopathy in streptozotocin-diabetic rats.  

PubMed

The purpose of this study was to investigate the cardioprotective effect of mangiferin on diabetic cardiomyopathy (DCM). The DCM model was induced by a high-fat diet and a low dose of streptozotocin. We evaluated the characteristics of DCM by serial echocardiography, electron microscopy, histopathologic analysis of cardiomyocyte fibrosis area, and Western blot analysis of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. Rats with DCM showed severe left ventricular dysfunction and cardiac fibrosis. Mangiferin mitigated DCM and prevented the accumulation of myocardial collagen. These anatomic findings were accompanied by significant improvements in cardiac function. Based on these results, we conclude that mangiferin has a therapeutic effect on DCM and improves cardiac function. PMID:23984905

Hou, Jun; Zheng, Dezhi; Zhong, Guocheng; Hu, Yonghe

2013-09-01

265

Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats.  

PubMed

This study investigated the hypoglycemic and antioxidant effects of Flax and Pumpkin seeds mixture on the kidney of alloxan-induced diabetic rats. Animals were allocated into three groups of six rats each: a control group (CD), a diabetic group (DD) and diabetic rats fed with Flax and Pumpkin seeds mixture (DMS) group. The DD rats showed a significant increase of glycemia and lipid parameters such as total lipid, total cholesterol and triglycerides levels compared to those of the control group (CD). In addition, plasma and kidney malonaldialdehyde levels (MDA) were significantly increased compared to (CD) group. Antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD) and non-enzymatic levels of reduced glutathione (GSH) significantly decreased in the plasma and kidney of diabetic rats compared to those of controls. Diet supplemented with Flax and Pumpkin seeds mixture ameliorated the antioxidant enzymes activities observed in diabetic rats and significantly decreased MDA levels. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In DMS rats, these histopathological changes were less prominent. Our results suggest that Flax and Pumpkin seeds mixture supplemented in diet of diabetic rats may be helpful to prevent diabetes and its complications. PMID:20570704

Makni, Mohamed; Sefi, Mediha; Fetoui, Hamadi; Garoui, El Mouldi; Gargouri, Nabil K; Boudawara, Tahia; Zeghal, Najiba

2010-01-01

266

Characterization of diabetic neuropathy in the zucker diabetic sprague-dawley rat: a new animal model for type 2 diabetes.  

PubMed

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

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

2014-01-01

267

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

PubMed Central

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

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

2014-01-01

268

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment  

Microsoft Academic Search

Summary  Kidney weight and glomerular volume have been studied in groups of insulin-treated streptozotocin diabetic rats maintained at high, or nearly normal plasma glucose levels. Kidney weight and glomerular volume in these groups were compared to a non-diabetic control group. — Rats with nearly normal plasma glucose levels (95±35 to 182±20 mg\\/100ml) had the same kidney weight as the non-diabetic controls,

R. Rasch

1979-01-01

269

ACE inhibitor or angiotensin II receptor antagonist attenuates diabetic neuropathy in streptozotocin-induced diabetic rats.  

PubMed

ACE inhibition and/or blocking of the angiotensin II receptor are recognized as first-line treatment for nephropathy and cardiovascular disease in diabetic patients. However, little information is available about the potential benefits of these drugs on diabetic neuropathy. We examined vascular and neural activity in streptozotocin-induced diabetic rats that were treated for 12 weeks with enalapril, an ACE inhibitor, or L-158809, an angiotensin II receptor blocker. A prevention protocol (group 1) as well as three intervention protocols (treatment was initiated after 4, 8, or 12 weeks of diabetes [groups 2, 3, and 4, respectively]) were used. Endoneurial blood flow and motor nerve conduction velocity (MNCV) were impaired in all groups of untreated diabetic rats. In group 1, treatment of diabetic rats with enalapril or L-158809 partially prevented the diabetes-induced decrease in endoneurial blood flow and MNCV. In groups 2-4, intervention with enalapril was more effective in reversing the diabetes-induced impairment in endoneurial blood flow and MNCV than L-158809. The superoxide level in the aorta and epineurial arterioles of diabetic rats was increased. Treatment of diabetic rats with enalapril or L-158809 reduced the superoxide level in the aorta in all groups but was less effective in epineurial arterioles. Acetylcholine and calcitonin gene-related peptide (CGRP) cause vasodilation in epineurial arterioles of the sciatic nerve, which was impaired by diabetes. Treatment of diabetic rats (all groups) with enalapril or L-158809 completely prevented/reversed the diabetes-induced impairment in CGRP-mediated vascular relaxation. Treatment with enalapril or L-158809 was also effective in improving impaired acetylcholine-mediated vasodilation, but the efficacy was diminished from groups 1 to 4. These studies suggest that ACE inhibitors and/or angiotensin II receptor blockers may be effective treatments for diabetes and vascular and neural dysfunction. However, the efficacy of these treatments may be dependent on when the treatment is initiated. PMID:16443766

Coppey, Lawrence J; Davidson, Eric P; Rinehart, Thomas W; Gellett, Jill S; Oltman, Christine L; Lund, Donald D; Yorek, Mark A

2006-02-01

270

Sorbitol in the accessory glands of the diabetic male rat.  

PubMed

Diabetes was induced in rats by i.v. injection of streptozotocin (60 mg/kg body weight). Diabetes was accompanied by infertility and atrophy of the male accessory glands. Blood glucose rose above 500 mg% (post-prandial) and blood testosterone decreased to 14% of the level found in normoglycemic rats. Diabetes was followed by increased levels of sorbitol in the male accessory glands, prostate, seminal vesicle and coagulating gland, and in the eyes and sciatic nerves. Insulin treatment of the diabetic rats prevented sorbitol accumulation in the above tissues. AY-22, 284, and inhibitor of aldose reductase given in the food (1 g/kg body weight/day) for 3 weeks, did not prevent sorbitol accumulation in the organs mentioned. The changes in sorbitol metabolism in the diabetic rat and their possible involvement in male fertility are discussed. PMID:7223308

Paz, G F; Drasnin, N; Homonnai, Z T

1980-01-01

271

Incretin attenuates diabetes-induced damage in rat cardiac tissue.  

PubMed

Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1 week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect. PMID:25011640

AbdElmonem Elbassuoni, Eman

2014-09-01

272

Foreign Body Response to Subcutaneous Implants in Diabetic Rats  

PubMed Central

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

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

2014-01-01

273

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment  

Microsoft Academic Search

Summary  Glomerular basement membrane thickness (GBMT) has been measured in streptozotocin diabetic rats treated with insulin. The study included 3 groups of 8 rats each: 1) a well-controlled group of diabetic rats under insulin treatment with a plasma glucose level reasonable close to normal values, 2) a poorly-controlled group also under insulin treatment with constant high plasma glucose values, and 3)

R. Rasch

1979-01-01

274

Clinical and morphological studies in streptozotocin diabetic pregnant rats.  

PubMed

Diabetes was induced in pregnant rats by administration of streptozotocin and the changes of the feto-placental unit were investigated. Dead fetuses were found in 12% of the untreated diabetic animals. In comparison to the controls, the fetal weights were significantly smaller and placental weights greater in diabetic animals. The changes were clearly characterized by the ratio fetal placental weight. Edema and cystic degeneration were characteristic of insulin treated diabetic placentas while fibrosis and ischemia were observed mainly in untreated animals. Insulin treatment resulted in hemorrhages and necrosis in the placenta of normal pregnant rats; the change is ascribed to hypoglycaemia. PMID:135471

Szalay, J; Gaál, M

1975-01-01

275

Ocular Inflammation in Uveal Tract in Aged Obese Type 2 Diabetic Rats (Spontaneously Diabetic Torii Fatty Rats)  

PubMed Central

We report uveitis observed in an obese type 2 diabetes rat model, Spontaneously Diabetic Torii Leprfa (SDT fatty) rats aged over 50 weeks. The eyes of SDT fatty rats (16 animals: 7 males and 9 females with 50 or 60 weeks of age) were examined histopathologically. Infiltration of inflammatory cells in the uveal tract was observed in 13 of 16 animals. One female showed severe inflammation affecting the entire uveal tract including the iris, ciliary body, and choroid with a variety of inflammatory cells (neutrophils, lymphocytes, and macrophages). Those changes clinically mimic the findings of diabetic iridocyclitis in diabetic patients. Uveitis associated with diabetes can occur in diabetic patients but the pathogenesis still remains unknown. Since increased extramedullary hematopoiesis in the spleen and abscess in the genital and lower urinary tracts were observed in some SDT fatty rats, increased susceptibility to infection, prolongation of inflammatory states, and disorders of the immune system were considered to be possible factors of the uveitis in aged SDT fatty rats. There have been few reports on how diabetes has influence on the development of uveitis associated with bacterial infection. The SDT fatty rat can be an animal model to investigate diabetes-associated uveitis. PMID:25295283

Kemmochi, Yusuke; Miyajima, Katsuhiro; Ohta, Takeshi; Yasui, Yuzo; Toyoda, Kaoru; Kakimoto, Kochi; Shoda, Toshiyuki

2014-01-01

276

Effector Mechanisms in Low-Dose Streptozotocin-induced Diabetes  

PubMed Central

The cellular and molecular requirements for ?-cell damages in an immune-mediated toxininduced insulin-dependent diabetes mellitus have been studied in the model of multiple low-dose streptozotocin-induced diabetes in rats and mice. It was found that strain-related susceptibility to diabetes induction correlated with a higher level of IL-2, IFN-?, and TNF-? production, whereas such differences were not observed when IL-1 and NO production by macrophages were analyzed; elimination of immunoregulatory RT6+T cells that increases IFN-? production, enhances susceptibility to MLD-STZ-induced diabetes; mercury-induced Th-2 cells downregulated the disease; IFN-?-mediated macrophage activation to produce proinflammatory cytokines rather than NO is an important event in early diabetogenic effects of invading macrophages; inhibition of IL-1 activity downregulates diabetes induction; and generation of NO in ? cells appears to be important for diabetogenic effects. Taken together, data indicate that MLD-STZ diabetes is induced by Th-1 lymphocytes that secrete soluble effector molecules that activate macrophages and promote destruction of ? cells possibly by both nitric oxide and nonnitric oxide-mediated mechanisms. PMID:9716913

Stosic-Grujicic, Stanislava; Shahin, Allen

1998-01-01

277

Early Renal Histological Changes in Alloxan-Induced Diabetic Rats  

PubMed Central

Diabetes mellitus is a progressive disease. Most investigators have focused on glomerular changes in diabetic kidney and non-glomerular alterations have been less attended. The present study has been conducted to find early non-glomerular histological changes in diabetic renal tissue. Twenty male Wistar rats weighting 200-250 g were used for the diabetic group. Diabetes mellitus was induced by single injection of Alloxan. After 8 weeks, paraffin embedded blocks of kidneys were prepared for evaluating the histological changes due to diabetes. Histological study showed the deposit of eosinophilic materials in the intermediate substantial of medulla and thickening of renal arterial wall in the kidney of 70% of diabetic rats. The average weight of kidneys increased when compared to non diabetic animals. Furthermore, the amount of blood flow in arteries of all diabetic kidneys has been enhanced. The present study demonstrates some early renal histological changes in diabetes mellitus which were earlier compared to those reported previously. Diabetic nephropathy is a progressive disease and renal care design can help better prognosis achievement. PMID:24551816

Pourghasem, Mohsen; Nasiri, Ebrahim; Shafi, Hamid

2014-01-01

278

Virus-Induced Type 1 Diabetes in the Rat  

Microsoft Academic Search

\\u000a Evidence from epidemiological studies suggests that the mechanism of type 1 diabetes (T1D ?) involves environmental factors\\u000a and viral infections, in particular. Data establishing a direct link between microbial infections and diabetes and demonstrating\\u000a how viruses lead to disease onset in humans are currently lacking. Rat models of diabetes have recently emerged as powerful\\u000a experimental tools for examining the role

Travis R. Wolter; Danny Zipris

279

Effect of renin inhibition on adipokines in diabetic rats.  

PubMed

Insulin resistance predicts development of type 2 diabetes mellitus (DM). Adipocytes release tumor Necrosis factor-alpha (TNF-?), and adiponectin. They modulate whole-body insulin sensitivity . The disturbance in the relationship between good and bad adipokines may cause insulin resistance. The renin-angiotensin aldosteron system (RAAS) plays a role in DM and the consequence of cardiovascular complications development. It is considered as a target for therapy. The present objective examined the relationship between renin angiotensin system and DM. There were, Group (1): Normal non obese rats, Group (2): Obese diabetic rats, Group (3): Obese diabetic rats with telmisartan, Group (4): Obese diabetic rats with enalapril, Group (5): Obese diabetic rats with aliskiren. There was a significant increase in serum glucose, lipid profile [triglycerides (TGs), low-density lipoprotein cholesterol (LDL), total serum cholesterol (TC)], tumor Necrosis factor-alpha (TNF-?), malondialdehyde (MDA) and a significant decrease in adiponectin associated with minor changes in superoxide dismutase (SOD) activity in the obese diabetic rats. Administration of telmisartan, enalapril and or aliskiren caused a significant improvement in serum lipid profile and adiponectin, a minor improvement in SOD activity, a decrease in TNF-? and or MDA. Renin angiotensin blockers significantly improve the metabolism and oxidative dysfunctions in Type 2 DM and aliskiren may show a promising powerful therapy. PMID:25015438

Hassanin, Amal; Malek, Hala Abdel

2014-07-01

280

Syngeneic islet transplantation into seminal vesicles of diabetic rats.  

PubMed

Pancreatic islet transplantation has been proposed as an attractive option for the treatment of type I diabetes. Transplantation into different sites has been investigated, among them those that are immuno-logically privileged (e.g., thymus, uterus, brain, anterior eye chamber, and testicle). Because of their characteristics, seminal vesicles could be considered as immunologically privileged organs, but there is no worldwide experience that can confirm it. The purpose of the present study is to assess the viability and functionality of islet transplantation into seminal vesicles of diabetic rats. One hundred ninety inbred adult male syngeneic Lewis rats were used as donors (n = 72), receptors (n = 36), and controls(n = 11). Diabetes was chemically induced through a single intraperitoneal injection of streptozotocin. Groups of 1200 purified islets were introduced in the right seminal vesicle of diabetic rats. Diabetic control rats were sham transplanted. Body weight and glycemia were monitored every 2 d. Of transplanted rats, 16.7% achieved a good function due to islet engraftment, while 30.6% achieved a partially good response, and 52.7% were considered as nonresponding. This is the first report about islet transplantation into seminal vesicles of diabetic animals. Our results indicate that islet transplantation into rat seminal vesicles is technically possible, and that islets can function normally after engraftment into the wall of the seminal vesicle. PMID:15804947

Luna, A; Julián, J F; Alba, A; Garcia-Cuyás, F; Broggi, M A; Ciancio, G; Pujol-Borrell, R; Fernández-Llamazares, J; Vives-Pi, M

2005-01-01

281

Antihyperglycemic action of sinapic acid in diabetic rats.  

PubMed

Sinapic acid is a hydroxycinnamic acid contained in plants. In an attempt to know the hyperglycemic effect of sinapic acid, this study applied streptozotocin (STZ) to induce type 1-like diabetic rats and fed fructose-rich chow to induce type 2-like diabetic rats. Sinapic acid dose-dependently reduced the hyperglycemia of STZ-diabetic rats (9.8 ± 1.8%, 11.6 ± 0.7%, and 19.4 ± 3.2% at 5 mg/kg, 10 mg/kg, and 25 mg/kg, respectively). Also, sinapic acid attenuated the postprandial plasma glucose without changing plasma insulin in rats. Repeated treatment of sinapic acid increased the gene expression of GLUT4 in soleus muscle of STZ-diabetic rats. Moreover, sinapic acid enhanced glucose uptake into isolated soleus muscle and L6 cells (337.0 ± 29.6%). Inhibition of phospholipase C (PLC) using U73122 (1.00 ± 0.02 ?g/mg protein) or protein kinase C (PKC) using chelerythrine (0.97 ± 0.02 ?g/mg protein) attenuated the sinapic acid-stimulated glucose uptake (1.63 ± 0.02 ?g/mg protein) in L6 cells. Otherwise, the reduced glucose infusion rate (GIR) in fructose-rich chow-fed rats was also raised by sinapic acid. Our results suggest that sinapic acid ameliorates hyperglycemia through PLC-PKC signals to enhance the glucose utilization in diabetic rats. PMID:24261449

Cherng, Yih-Giun; Tsai, Cheng-Chia; Chung, Hsien-Hui; Lai, Yun-Wen; Kuo, Shu-Chun; Cheng, Juei-Tang

2013-12-11

282

The protective effect of vanadium against diabetic cataracts in diabetic rat model.  

PubMed

The present study was designed to investigate the effect of vanadium in alloxan-induced diabetes and cataract in rats. Different doses of vanadium was administered once daily for 8 weeks to alloxan-induced diabetic rats. To know the mechanism of action of vanadium, lens malondialdehyde (MDA), protein carbonyl content, activity of superoxide dismutase (SOD), activities of aldose reductase (AR), and sorbitol levels were assayed, respectively. Supplementation of vanadium to alloxan-induced diabetic rats decreased the blood glucose levels due to hyperglycemia, inhibited the AR activity, and delayed cataract progression in a dose-dependent manner. The observed beneficial effects may be attributed to polyol pathway activation but not decreased oxidative stress. Overall, the results of this study demonstrate that vanadium could effectively reduce the alloxan-induced hyperglycemia and diabetic cataracts in rats. PMID:24604151

Sun, Lei; Shi, De-Jing; Gao, Xiang-Chun; Mi, Shu-Yong; Yu, Ying; Han, Qing

2014-05-01

283

Ghrelin reverses experimental diabetic neuropathy in mice  

SciTech Connect

Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

Kyoraku, Itaru; Shiomi, Kazutaka [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)] [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan)] [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Nakazato, Masamitsu, E-mail: nakazato@med.miyazaki-u.ac.jp [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)] [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)

2009-11-20

284

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. PMID:23730303

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

2013-01-01

285

Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats  

Microsoft Academic Search

The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period\\u000a of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing\\u000a the serum metabolite profile detected with combined gas chromatography\\/mass spectrometry (GC\\/MS) and liquid chromatography\\/mass\\u000a spectrometry (LC\\/MS). We found that the

Lina Åkesson; Johan Trygg; Jessica M. Fuller; Rasmus Madsen; Jon Gabrielsson; Stephen Bruce; Hans Stenlund; Terry Tupling; Ranae Pefley; Torbjörn Lundstedt; Åke Lernmark; Thomas Moritz

286

Polychromatic LED Therapy in Burn Healing of Non-diabetic and Diabetic Rats  

Microsoft Academic Search

Objective: We determined the effect of polychromatic light-emitting diodes (LED) in burn healing of non- diabetic and streptozotocin-induced diabetic rats. Background Data: LEDs were used as the light source for phototherapy. Materials and Methods: The polychromatic LED is a cluster of 25 diodes emitting photons at wavelengths of 510- 543, 594- 599, 626- 639, 640- 670, and 842- 879 nm

Farouk A. H. Al-Watban; Bernard L. Andres

2003-01-01

287

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. PMID:22266599

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

2012-01-01

288

Prevention of diabetes in rats by bone marrow transplantation.  

PubMed Central

Hyperglycemia, hypoinsulinemia and ketonemia often develop abruptly in previously normal young "BB" rats. The syndrome mimics human juvenile diabetes closely and is, thus, appropriate for assessing pancreatic transplantation. Transplantation of islet cells from closely histocompatible Wistar Furth (WF) donor resulted in permanent normoglycemia when immunosuppression with ALS was given. However, when islet cells from nondiabetic "BB" donors were transplanted to nonimmunosuppressed diabetic "BB" recipients, only transient normoglycemia followed. Transplantation of WF islets cells also failed in diabetic "BB" rats which were tolerant of WF antigens, again suggesting destruction of transplanted islet cells by the original disease process-possibly autoimmunity. Evidence for autoimmunity was strengthened by the finding that newly diabetic "BB" rats could be rendered normoglycemic by immunosuppression. Since genetic susceptibility to spontaneous autoimmune diabetes is unique to some members of the "BB" stock, an attempt was made to alter their vulnerability by modifying their cellular immune system. Accordingly, 50 million bone marrow cells from WF donors were inoculated into half the newborn members of "BB" litters, leaving the littermates as unmodified controls. Most bone marrow recipients were protected, only four of 37 (10.8%) ever becoming diabetic, while the incidence of diabetes in noninoculated littermates was 22 of 39 (56.4%). The ultimate goal in human diabetes, which also seems very likely to be an autoimmune disease, may not be replacement of destroyed islet cells but identification of potentially susceptible children and prevention of islet destruction by immunologic manipulation. Images Fig. 1. Fig. 3. Fig. 4. PMID:6791599

Alinaji; Silvers, W K; Bellgrau, D; Anderson, A O; Plotkin, S; Barker, C F

1981-01-01

289

Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.  

PubMed

We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 ?A, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 ?m(2), P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy. PMID:21641343

Jin, Heung Yong; Lee, Kyung Ae; Song, Sun Kyung; Liu, Wei Jing; Choi, Ji Hae; Song, Chang Ho; Baek, Hong Sun; Park, Tae Sun

2012-01-15

290

Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice  

Microsoft Academic Search

The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the

Seong-Il Kang; Young-Jun Jin; Hee-Chul Ko; Soo-Youn Choi; Joon-Ho Hwang; Ilson Whang; Moo-Han Kim; Hye-Sun Shin; Hyung-Bok Jeong; Se-Jae Kim

2008-01-01

291

Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes  

PubMed Central

Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6?months of age and 86% at 14?months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300?mg/dl at 120?min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of ?-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus. PMID:23691528

Okamura, Tadashi; Pei, Xiang Yuan; Miyoshi, Ichiro; Shimizu, Yukiko; Takanashi-Yanobu, Rieko; Mototani, Yasumasa; Kanai, Takao; Satoh, Jo; Kimura, Noriko; Kasai, Noriyuki

2013-01-01

292

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

293

The effects of resveratrol on flap survival in diabetic rats.  

PubMed

Resveratrol is an antioxidant agent with multiple positive impacts on the body. It is known to have anti-diabetic, anti-inflammatory, anti-carcinogenic, and neuroprotective effects. The goal of this study is to demonstrate the antioxidant and anti-diabetic effects of resveratrol on flap survival in diabetic rats. Streptozotocin-induced diabetic Sprague-Dawley albino rats were treated with 10 mg/kg resveratrol following a flap surgery. Histological findings regarding polymorphonuclear leukocyte (PMNL) density, vascular proliferation, fibroblast density, and tissue necrosis were compared between resveratrol-treated and control rats. Significantly higher PMNL density was found in the control group (p = 0.005); while vascular proliferation and the fibroblast density were higher in the resveratrol group (p = 0.004 and p = 0.021, respectively). Collagen density was also higher in the resveratrol group and the difference has statistical significance (p = 0.024). Lymphocyte density was not significantly different between groups (p = 0.061). When the necrosis in the distal areas was evaluated histologically, 20% of the resveratrol group had epidermal tissue necrosis, thus 90% of the control group had epidermal or full-layer necrosis. Resveratrol improved flap survival significantly in diabetic rats. Therefore, diabetic patients requiring complex reconstructive procedures may benefit from resveratrol; so, clinical trials are required to support this study. PMID:24308328

Ciloglu, N Sinem; Zeytin, Kayhan; Aker, Fugen

2014-08-01

294

Acetylsalicylic acid protects erectile function in diabetic rats.  

PubMed

We aimed to evaluate the effect of acetylsalicylic acid (ASA) treatment on diabetes-induced erectile dysfunction. Adult male Sprague-Dawley rats were divided into four groups as follows: (i) control (C), (ii) diabetic (D), (iii) ASA-treated control (C+ASA) and (iv) ASA-treated diabetic (D+ASA) groups. In groups 2 and 4, diabetes was induced by injection of 35 mg kg(-1) streptozotocin. ASA (100 mg kg(-1) day(-1) , orally) was administrated to rats in groups 3 and 4 for 8 weeks. Both intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) were measured in in vivo studies. In organ bath, the relaxation responses to acetylcholine (ACh), electrical field stimulation (EFS) and sodium nitroprusside were tested in corpus cavernosum (CC) strips. The mRNA expression for neuronal nitric oxide synthase (nNOS) was calculated using reverse transcription polymerase chain reaction technique. In in vivo experiments, diabetic rats displayed reduced ICP/MAP values, which were normalised with ASA treatment. The relaxant response to high-dose ACh and EFS at low frequencies (1-8 Hz) in CC strips from the D+ASA group were significantly higher when compared to the D group. Treatment with ASA normalised the raised mRNA expressions of nNOS in diabetic penile tissues. ASA may be involved in mRNA of protein synthesis of NO released from nonadrenergic and noncholinergic cavernosal nerve in diabetes. PMID:24428436

Hafez, G; Gonulalan, U; Kosan, M; Arioglu, E; Ozturk, B; Cetinkaya, M; Gur, S

2014-11-01

295

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. PMID:23579598

Shin, Joo Young; Sohn, Joonhong

2013-01-01

296

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. PMID:22110373

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

2011-01-01

297

Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function  

PubMed Central

Behavioral impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45 mg/kg body weight; intraperitoneally). Motor function alterations were studied using Rotarod test (motor coordination) and grip strength (muscle activity) at 2nd, 4th, 6th, 8th, 10th, and 12th week post-diabetic confirmation. Scenario of glial (astroglia and microglia) activation, cell death and glutamate transportation was gaged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labeling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioral alterations following STZ-induced diabetes.

Nagayach, Aarti; Patro, Nisha; Patro, Ishan

2014-01-01

298

MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy  

PubMed Central

Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which can result in cardiac hypertrophy and subsequent heart failure, associated with pyroptosis, the pro-inflammatory programmed cell death. MicroRNAs (miRNAs), small endogenous non-coding RNAs, have been shown to be involved in diabetic cardiomyopathy. However, whether miRNAs regulate pyroptosis in diabetic cardiomyopathy remains unknown. Our study revealed that mir-30d expression was substantially increased in streptozotocin (STZ)-induced diabetic rats and in high-glucose-treated cardiomyocytes as well. Upregulation of mir-30d promoted cardiomyocyte pyroptosis in diabetic cardiomyopathy; conversely, knockdown of mir-30d attenuated it. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic property of mir-30d, we found that forced expression of mir-30d upregulated caspase-1 and pro-inflammatory cytokines IL-1? and IL-18. Moreover, mir-30d directly repressed foxo3a expression and its downstream protein, apoptosis repressor with caspase recruitment domain (ARC). Furthermore, silencing ARC by siRNA mimicked the action of mir-30d: upregulating caspase-1 and inducing pyroptosis. These findings promoted us to propose a new signaling pathway leading to cardiomyocyte pyroptosis under hyperglycemic conditions: mir-30d??foxo3a?? ARC??caspase-1??IL-1?, IL-18??pyroptosis?. Therefore, mir-30d may be a promising therapeutic target for the management of diabetic cardiomyopathy. PMID:25341033

Li, X; Du, N; Zhang, Q; Li, J; Chen, X; Liu, X; Hu, Y; Qin, W; Shen, N; Xu, C; Fang, Z; Wei, Y; Wang, R; Du, Z; Zhang, Y; Lu, Y

2014-01-01

299

MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy.  

PubMed

Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which can result in cardiac hypertrophy and subsequent heart failure, associated with pyroptosis, the pro-inflammatory programmed cell death. MicroRNAs (miRNAs), small endogenous non-coding RNAs, have been shown to be involved in diabetic cardiomyopathy. However, whether miRNAs regulate pyroptosis in diabetic cardiomyopathy remains unknown. Our study revealed that mir-30d expression was substantially increased in streptozotocin (STZ)-induced diabetic rats and in high-glucose-treated cardiomyocytes as well. Upregulation of mir-30d promoted cardiomyocyte pyroptosis in diabetic cardiomyopathy; conversely, knockdown of mir-30d attenuated it. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic property of mir-30d, we found that forced expression of mir-30d upregulated caspase-1 and pro-inflammatory cytokines IL-1? and IL-18. Moreover, mir-30d directly repressed foxo3a expression and its downstream protein, apoptosis repressor with caspase recruitment domain (ARC). Furthermore, silencing ARC by siRNA mimicked the action of mir-30d: upregulating caspase-1 and inducing pyroptosis. These findings promoted us to propose a new signaling pathway leading to cardiomyocyte pyroptosis under hyperglycemic conditions: mir-30d??foxo3a?? ARC??caspase-1??IL-1?, IL-18??pyroptosis?. Therefore, mir-30d may be a promising therapeutic target for the management of diabetic cardiomyopathy. PMID:25341033

Li, X; Du, N; Zhang, Q; Li, J; Chen, X; Liu, X; Hu, Y; Qin, W; Shen, N; Xu, C; Fang, Z; Wei, Y; Wang, R; Du, Z; Zhang, Y; Lu, Y

2014-01-01

300

Treatment with a melanocortin agonist improves abnormal lipid metabolism in streptozotocin-induced diabetic mice  

Microsoft Academic Search

Impairments in leptin–melanocortin signaling are associated with insulin-deficient diabetes and leptin treatment has been shown to be effective in reversing hyperglycemia in animal models of type 1 diabetes. Therefore, we hypothesized that enhanced central melanocortin signaling reverses the metabolic impairments associated with type 1 diabetes. To address this hypothesis, streptozotocin (STZ)-induced diabetic mice were treated with daily intracerebroventricular injection of

Arnold Leckstrom; Pei San Lew; Nicole J. Poritsanos; Tooru M. Mizuno

2011-01-01

301

Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats.  

PubMed

The present study was designed to investigate the antihyperglycemic effect of Umbelliferone (UMB) in normal and streptozotocin (STZ)-diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180-200 g, by administration of STZ (40 mg/kg of body weight) intraperitoneally. Diabetic rats showed an increase in levels of blood glucose and glycosylated hemoglobin (HbA(1c)) and activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase, and a decrease in levels of plasma insulin, hemoglobin (Hb), and liver glycogen and activities of glucokinase and glucose-6-phosphate dehydrogenase. Intraperitoneal administration of UMB (10, 20, and 30 mg/kg of body weight) and glibenclamide (600 micro g/kg of body weight) in 10% dimethyl sulfoxide dissolved in water, for 45 days, produced significantly decreased levels of blood glucose and HbA(1c) and activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase, while elevating levels of plasma insulin, Hb, and liver glycogen and activities of glucokinase and glucose-6-phosphate dehydrogenase to near normal levels in STZ-diabetic rats when compared with normal control rats. Normal rats treated with UMB (30 mg/kg of body weight) also showed a significant effect on glycemic control. Thus, our results show that UMB at 30 mg/kg of body weight possesses a promising antihyperglycemic effect that is comparable with glibenclamide. PMID:17201645

Ramesh, B; Pugalendi, K V

2006-01-01

302

Albumin permeation of new vessels is increased in diabetic rats  

SciTech Connect

/sup 125/I-bovine serum albumin (BSA) permeation of the vasculature of 3-wk-old granulation tissue (induced by subcutaneous implantation of polyester fabric) formed in the diabetic milieu was assessed in female BB/W, spontaneously diabetic rats and in male, Sprague-Dawley rats with streptozocin-induced diabetes as well as in corresponding nondiabetic controls. Albumin permeation of new granulation tissue vessels was markedly increased in both groups of diabetic animals relative to that of nondiabetic controls, while albumin permeation of vessels in most other tissues did not differ for controls and diabetics. These observations indicate that the functional integrity of new vessels formed in the diabetic milieu is impaired: (1) to a greater extent than that of older vessels formed before induction of diabetes and (2) relative to new vessels in nondiabetics. The implication of these observations is that molecular constituents of vessels synthesized in the diabetic milieu are quantitatively and/or qualitatively abnormal and/or their incorporation into vessels is defective.

Kilzer, P.; Chang, K.; Marvel, J.; Rowold, E.; Jaudes, P.; Ullensvang, S.; Kilo, C.; Williamson, J.R.

1985-04-01

303

Protein turnover in adipose tissue from fasted or diabetic rats  

NASA Technical Reports Server (NTRS)

Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

Tischler, Marc E.; Ost, Alan H.; Coffman, Julia

1986-01-01

304

Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model  

PubMed Central

The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n = 10), OLETF rats as diabetic control group (n = 10), and OLETF rats treated with taurine group (n = 10). We treated taurine (200?mg/kg/day) for 20 weeks and treated high glucose (HG, 30?mM) with or without taurine (30?mM) in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS) levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model. PMID:24707287

Lee, Eun Soo; Hyun, Miri; Kim, Hong Min; Choi, Yoon Jung; Lee, Eun Young; Yadav, Dhananjay; Chung, Choon Hee

2014-01-01

305

Oxidative damage in pregnant diabetic rats and their embryos.  

PubMed

Free radical mechanisms may be involved in the teratogenesis of diabetes. The contribution of oxidative stress in diabetic complications was investigated from the standpoint of oxidative damage to DNA, lipids, and proteins in the livers and embryos of pregnant diabetic rats. Diabetes was induced prior to pregnancy by the administration of streptozotocin (45 mg/kg). Two groups of diabetic rats were studied, one without any supplementation (D) and another treated during pregnancy with vitamin E (150 mg/d by gavage) (D + E). A control group was also included (C). The percentage of malformations in D rats were 44%, higher than the values observed in C (7%) and D + E (12%) animals. D Group rats showed a higher concentration of thiobarbituric acid reactive substances in the mother's liver, however, treatment with vitamin E decreased this by 58%. The levels of protein carbonyls in the liver of C, D, and D + E groups were similar. The "total levels" of the DNA adducts measured, both in liver and embryos C groups were similar to the D groups. Treatment of D groups with vitamin E reduced the levels by 17% in the liver and by 25% in the embryos. In terms of the "total levels" of DNA adducts, the embryos in diabetic pregnancy appear to be under less oxidative stress when compared with the livers of their mothers. Graziewicz et al. (Free Radical Biology & Medicine, 28:75-83, 1999) suggested "that Fapyadenine is a toxic lesion that moderately arrests DNA synthesis depending on the neighboring nucleotide sequence and interactions with the active site of DNA polymerase." Thus the increased levels of Fapyadenine in the diabetic livers and embryos may similarly arrest DNA polymerase, and in the case of this occurring in the embryos, contribute to the congenital malformations. It is now critical to probe the molecular mechanisms of the oxidative stress-associated development of diabetic congenital malformations. PMID:11121718

Viana, M; Aruoma, O I; Herrera, E; Bonet, B

2000-12-01

306

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

307

Inner Retinal Oxygen Delivery and Metabolism in Streptozotocin Diabetic Rats  

PubMed Central

Purpose. The purpose of the study is to report global measurements of inner retinal oxygen delivery (DO2_IR) and oxygen metabolism (MO2_IR) in streptozotocin (STZ) diabetic rats. Methods. Phosphorescence lifetime and blood flow imaging were performed in rats 4 (STZ/4wk; n = 10) and 6 (STZ/6wk; n = 10) weeks following injection of STZ to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F). DO2_IR and MO2_IR were calculated from measurements of F and O2A and of F and the arteriovenous oxygen content difference, respectively. Data in STZ rats were compared to those in healthy control rats (n = 10). Results. Measurements of O2A and O2V were not significantly different among STZ/4wk, STZ/6wk, and control rats (P ? 0.28). Likewise, F was similar among all groups of rats (P = 0.81). DO2_IR measurements were 941 ± 231, 956 ± 232, and 973 ± 243 nL O2/min in control, STZ/4wk, and STZ/6wk rats, respectively (P = 0.95). MO2_IR measurements were 516 ± 175, 444 ± 103, and 496 ± 84 nL O2/min in control, STZ/4wk, and STZ/6wk rats, respectively (P = 0.37). Conclusions. Global inner retinal oxygen delivery and metabolism were not significantly impaired in STZ rats in early diabetes. PMID:24550355

Wanek, Justin; Teng, Pang-yu; Blair, Norman P.; Shahidi, Mahnaz

2014-01-01

308

Amelioration of diabetic nephropathy by orange peel extract in rats.  

PubMed

This study was aimed to evaluate the effect of alcoholic orange peel extract (OPE) on streptozotocin-induced diabetic nephropathy. Four weeks after the induction of diabetes, treatment with OPE (100 and 200 mg/kg) was further given for 4 weeks. Treatment with OPE 200 improved renal functions and significantly prevented the increase in creatinine, urea and blood urea nitrogen levels. Histological analysis of the kidneys revealed that tubulointerstitial fibrosis index was significantly decreased in OPE 200-treated group. The results indicated the prevention of diabetic nephropathy in rats by OPE treatment and suggest OPE as a potential treatment option. PMID:25103218

Parkar, Nishad; Addepalli, Veeranjaneyulu

2014-12-01

309

Microarray analysis of thioacetamide-treated type 1 diabetic rats  

SciTech Connect

It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats.

Devi, Sachin S. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Ave, Sugar Hall 306, Monroe, LA 71209-0470 (United States); Mehendale, Harihara M. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Ave, Sugar Hall 306, Monroe, LA 71209-0470 (United States)]. E-mail: mehendale@ulm.edu

2006-04-01

310

Oxidative stress and diabetes in pregnant rats  

Microsoft Academic Search

A considerable amount of clinical and experimental evidence now exists suggesting the involvement of free radical-mediated oxidative processes in the pathogenesis of diabetic complications. If the diabetic state is associated with a generalized increase in oxidative stress, it might well be reflected in the alterations in embryonic and fetal development during pregnancy. In the present study, incidence of the malformed

Débora Cristina Damasceno; Gustavo Tadeu Volpato; Iracema de Mattos Paranhos Calderon; Marilza Vieira Cunha Rudge

2002-01-01

311

Overexpression of GLUT3 placental glucose transporter in diabetic rats.  

PubMed Central

The localization of the two major placental glucose transporter isoforms, GLUT1 and GLUT3 was studied in 20-d pregnant rats. Immunocytochemical studies revealed that GLUT1 protein is expressed ubiquitously in the junctional zone (maternal side) and the labyrinthine zone (fetal side) of the placenta. In contrast, expression of GLUT3 protein is restricted to the labyrinthine zone, specialized in nutrient transfer. After 19-d maternal insulinopenic diabetes (streptozotocin), placental GLUT3 mRNA and protein levels were increased four-to-fivefold compared to nondiabetic rats, whereas GLUT1 mRNA and protein levels remained unmodified. Placental 2-deoxyglucose uptake and glycogen concentration were also increased fivefold in diabetic rats. These data suggest that GLUT3 plays a major role in placental glucose uptake and metabolism. The role of hyperglycemia in the regulation of GLUT3 expression was assessed by lowering the glycemia of diabetic pregnant rats. After a 5-d phlorizin infusion to pregnant diabetic rats, placental GLUT3 mRNA and protein levels returned to levels similar to those observed in nondiabetic rats. Furthermore, a short-term hyperglycemia (12 h), achieved by performing hyperglycemic clamps induced a fourfold increase in placental GLUT3 mRNA and protein with no concomitant change in GLUT1 expression. This study provides the first evidence that placental GLUT3 mRNA and protein expression can be stimulated in vivo under hyperglycemic conditions. Thus, GLUT3 transporter isoform appears to be highly sensitive to ambient glucose levels and may play a pivotal role in the severe alterations of placental function observed in diabetic pregnancies. Images PMID:7615800

Boileau, P; Mrejen, C; Girard, J; Hauguel-de Mouzon, S

1995-01-01

312

Effects of garlic extract treatment in normal and streptozotocin diabetic rats infected with Candida albicans  

Microsoft Academic Search

The anti-candidial effect of garlic extract (Allium sativum L.) was investigated in normal and streptozotocin-induced diabetic\\u000a rats. Diabetes was induced after a single intraperitoneal injection of streptozotocin (60 mg\\/kg). Rats were divided into six\\u000a groups with fifteen rats in each group: (1) Normal control rats (2) Control rats + C. albicans (3) Control rats + garlic extract\\u000a + C. albicans

M. Bokaeian; A. Nakhaee; Bita Moodi; A. Farhangi; Azim Akbarzadeh

2010-01-01

313

Mechanism of placental glycogen deposition in diabetes in the rat.  

PubMed

The metabolic basis for glycogen accumulation in the placenta of rats with diabetes induced by streptozotocin on day 12 of pregnancy was studied on days 15 and 20. On day 15 glycogen content of the placenta was 1.5-fold higher in the diabetic than in the control rats and this difference increased to greater than fivefold on day 20 of gestation whether calculated per g tissue or per total placenta. Accumulation of glycogen was associated with increased specific activities of both glycogen synthase and phosphorylase. The activities of these enzymes regulating synthase and phosphorylase activities and the activity of acid alpha-glucosidase were not significantly affected by diabetes. Glucose-6-phosphate concentration of the placenta was 67 and 23 nmol/g in diabetic and control rats, respectively. Incubation of placental homogenates with glucose increased the rate of inactivation of phosphorylase and activation of glycogen synthase. These results indicate that the enhanced glucogenesis in diabetes is not due to changes in the activities of these enzymes, as measured in vitro under standard conditions. The factors promoting glycogen accumulation in vivo are related to the abundance of glucose and glucose-6-phosphate as substrates for glycogen synthesis, which may also cause an increase in the activity ratio glycogen synthase a/phosphorylase a. In addition, the high intracellular glucose-6-phosphate concentration is likely to enable glycogen synthase b to contribute to glycogen synthesis. PMID:6402409

Barash, V; Gutman, A; Shafrir, E

1983-01-01

314

Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats.  

PubMed

We have examined the progression of vascular and neural deficits in Zucker rats, Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8 to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 wk of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 wk of age. All ZDF diabetic rats became hyperglycemic by 8 wk of age. Through their life span, serum free fatty acids and triglycerides levels were significantly higher in Zucker and ZDF diabetic rats compared with age-matched lean ZDF rats. After 24 and 28 wk of age, endoneurial blood flow was significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction velocity was significantly decreased after 12-14 wk of age in ZDF diabetic rats and at 32 wk of age in Zucker rats. ACh-mediated vascular relaxation of epineurial arterioles of the sciatic nerve was impaired after 8-10 wk of age in ZDF diabetic rats and after approximately 16 wk of age in Zucker rats. In contrast, vascular relaxation mediated by calcitonin gene-related peptide was impaired significantly after 28 wk of age in ZDF diabetic rats but not impaired in Zucker rats up to 40 wk of age. Markers of oxidative stress were differentially elevated in ZDF diabetic rats and Zucker rats. These data indicate that vascular and neural dysfunction develops in both Zucker and ZDF diabetic rats but at different rates, which may be the result of hyperglycemia. PMID:15727946

Oltman, Christine L; Coppey, Lawrence J; Gellett, Jill S; Davidson, Eric P; Lund, Donald D; Yorek, Mark A

2005-07-01

315

Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice  

PubMed Central

Islet transplantation is an effective method to obtain long-term glycemic control for patients with type 1 diabetes, yet its widespread use is limited by an inadequate supply of donor islets. The hormone leptin has profound glucose-lowering and insulin-sensitizing action in type 1 diabetic rodent models. We hypothesized that leptin administration could reduce the dose of transplanted islets required to achieve metabolic control in a mouse model of type 1 diabetes. We first performed a leptin dose-response study in C57Bl/6 mice with streptozotocin (STZ)-induced diabetes to determine a leptin dose insufficient to reverse hyperglycemia. Subsequently, we compared the ability of suboptimal islet transplants of 50 or 125 syngeneic islets to achieve glycemic control in STZ-induced diabetic C57Bl/6 mice treated with or without this dose of leptin. The dose-response study revealed that leptin reverses STZ-induced diabetes in a dose-dependent manner. Supraphysiological leptin levels were necessary to restore euglycemia but simultaneously increased risk of hypoglycemia, and also lost efficacy after 12 days of administration. In contrast, 1 µg/day leptin only modestly reduced blood glucose but maintained efficacy throughout the study duration. We then administered 1 µg/day leptin to diabetic mice that underwent transplantation of 50 or 125 islets. Although these islet doses were insufficient to ameliorate hyperglycemia alone, coadministration of leptin with islet transplantation robustly improved control of glucose and lipid metabolism, without increasing circulating insulin levels. This study reveals that low-dose leptin administration can reduce the number of transplanted islets required to achieve metabolic control in STZ-induced diabetic mice. PMID:23656888

Denroche, Heather C.; Quong, Whitney L.; Bruin, Jennifer E.; Tuduri, Eva; Asadi, Ali; Glavas, Maria M.; Fox, Jessica K.; Kieffer, Timothy J.

2013-01-01

316

Effect of polyherbal mixtures on the treatment of diabetes.  

PubMed

The study focuses on polyherbal antidiabetic formulations of different plants used in the treatment of diabetes mixed in different concentrations. In the present study eleven medicinal plants with proven antidiabetic and related beneficial effects were selected for the preparation of five mixtures. The efficacy of prepared mixtures has been tested on streptozotocin- (STZ-) induced diabetic rats and compared with a commercially available drug glibenclamide. The mixtures at the dose levels of 400?mg/kg b.w. produced a significant decrease in blood glucose level by 69.6%, 70.97%, 64.45%, 71.82%, and 64.44% after 21?days of treatment. The elevated level of SGPT, SGOT, and ALP in the diabetic controlled group reflected the significant alteration of liver function by STZ induction and was found to be equipotent to glibenclamide in restoration of the elevated enzyme levels to normal. The elevated lipid levels (triglyceride and total cholesterol) were restored to near normal by these mixtures for all the estimated parameters. The results of the mixtures on treated group were found to restore the glycemic level to the near normal level thereby indicating antihyperglycemic activity of the formulated mixtures. PMID:23691349

Panda, Aparajeya; Jena, Somanatha; Sahu, Pramod Kumar; Nayak, Sanghamitra; Padhi, Payodhar

2013-01-01

317

Diabetes alters aromatase enzyme levels in gonadal tissues of rats.  

PubMed

Diabetes mellitus (DM) is associated with increased risk of reproductive problems. Estrogens have important roles in reproductive processes in both genders. Aromatase catalyzes the conversion of androgens to estrogens and is expressed in a variety of tissues. Although it is known that insulin regulate the activity of aromatase, there are few data about the effects of diabetes on this enzyme. The aim of the present study was to investigate the effects of experimental diabetes on aromatase expression levels in ovary, testis, uterus, and vas deferens tissues of female and male rats. Rats were injected with streptozotocin to induce diabetes. At the end of 4 and 12 weeks, tissue homogenates were prepared and evaluated for aromatase proteins by western blot. Uterus and vas deferens smooth muscle responses were also evaluated. Aromatase expression levels in ovary were significantly decreased both in 4 and 12 weeks of diabetes. In testis, enzyme levels were not altered at 4 weeks, but significantly decreased at 12 weeks of diabetes. In uterus and vas deferens tissues, no significant differences were observed at aromatase immunoreactivity but uterus and vas deferens smooth muscle responses were altered. These results indicated for the first time that DM altered the expression levels of aromatase both in ovary and testis but did not affect enzyme levels in uterus and vas deferens tissues. Altered smooth muscle responses did not correlate with tissue aromatase levels. Altogether, these findings lead us to suggest that aromatase might be an important target molecule in sexual dysfunction seen in DM. PMID:20428845

Burul-Bozkurt, N; Pekiner, C; Kelicen, P

2010-07-01

318

Temporal course of streptozotocin-induced diabetic polyneuropathy in rats.  

PubMed

The temporal course of diabetic polyneuropathy in a rat model plays a critical role in studies on diabetic polyneuropathy treatment. In this study, the temporal course of neuropathic symptoms was investigated in diabetic rats induced by streptozotocin and evaluated by nerve conduction velocity and behavioral assays, including the von Frey test for mechanical allodynia and the hot plate test for hyperalgesia. The results revealed that both mechanical allodynia and heat hyperalgesia started on the 2nd week, while nerve conduction velocity significantly decreased from the 1st week. In addition, the severity of allodynia did not change after the 3rd week. Hyperalgesia and nerve conduction velocity progressively aggravated even to the 8th week. Transmission electron microscopy showed that loss of unmyelinated axons, loosening of the myelin structure, and thickening of the perineurium layer were visible from the 4th week and worsened on the 8th week. Differences in the temporal course of neuropathic symptoms are discussed. PMID:24924783

Lee, Yee-Fun; Lin, Chou-Ching K; Chen, Gin-Shin

2014-11-01

319

Anti-diabetic properties of rice-based herbal porridges in diabetic Wistar rats.  

PubMed

The present study aims to investigate anti-hyperglycaemic, anti-hyperlipidaemic and toxic effects of long-term consumption of selected green leafy porridges in a streptozotocin-induced diabetic Wistar rat model. Porridges made with Asparagus racemosus Willd. (AR), Hemidesmus indicus (L) R. Br. W. T. Aiton (HI), Scoparia dulcis L. (SD) and coconut milk porridge (CM) were incorporated into diets of diabetic Wistar rats. Diabetic control (DM) and normal control groups (NC) were provided with standard rat diet. Fasting blood glucose (FBG), HbA1c , C reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), liver enzymes and creatinine were measured. Feed and water intake among diabetic groups were significantly high when compared with those of NC (p?rats in SD (mean?=?39?±?19?g) and NC (mean?=?114?±?7?g) groups gained weight, whereas most rats in other diabetic groups lost weight. Among the diabetic groups, SD group had the lowest mean FBG, FBG increment percentage (45%) and HbA1c (5.8?±?2.1). FBG increment percentage and HbA1c of SD group were not significantly different to those of NC (38%; 4.7?±?0.7) (p?>?0.05). Among the diabetic groups, lowest TC (119?±?20.6?mg/dL) and highest HDL-C (33?±?6.3?mg/dL) were also detected in SD group. Alanine transaminase and creatinine were not significantly different (p?>?0.05) among diabetic groups but significant when compared with those of NC. When compared with those of NC, aspartate transaminase levels were significantly (p?diabetes-induced Wistar rats. PMID:24840113

Senadheera, Senadheera Pathirannehelage Anuruddhika Subhashinie; Ekanayake, Sagarika; Wanigatunge, Chandanie

2014-10-01

320

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

321

Sertoli cell function in diabetic, insulin-treated diabetic, and semi-starved rats.  

PubMed

It is well documented that long-term diabetes mellitus results in numerous deleterious consequences. However, considerable controversy exists concerning male reproductive function in diabetes. The purpose of this investigation was to study several endocrine parameters in diabetic male rats with emphasis on Sertoli cell function. Male Wistar rats were injected with streptozotocin and then either left untreated for 30 days or injected with insulin so as to prevent spillover of glucose into the urine. These two groups were compared with control animals that had only been injected with the vehicle for streptozotocin. Semi-starved control animals were included to determine if any of the potential endocrine alterations were related to body weight changes which occur in streptozotocin-injected rats. It was found that FSH, LH, PRL, and GH serum levels were reduced in diabetic animals. Only FSH was restored to normal by insulin injections. The testis, seminal vesicle, and epididymis weights were all reduced in diabetic animals. Insulin injections raised all organ weights; however, only testis weights were fully restored. Levels of epididymal ABP activity were found to be higher in diabetic animals when expressed per mg protein. Similar patterns of organ weight loss and hormonal alterations were observed in semi-starved rats. However, epididymal levels of ABP activity were unaffected by the semi-starved condition. While weight loss should be taken into consideration when interpreting cause and effect relationships in streptozotocin-treated animals, epididymal ABP levels appear to be well correlated with the altered metabolic state characteristic of diabetes. PMID:6219025

Hutson, J C; Stocco, D M; Campbell, G T; Wagoner, J

1983-02-01

322

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. PMID:21505475

Wajima, Daisuke; Nakamura, Mitsutoshi; Horiuchi, Kaoru; Takeshima, Yasuhiro; Nishimura, Fumihiko; Nakase, Hiroyuki

2011-01-01

323

Islet Remodeling in Female Mice with Spontaneous Autoimmune and Streptozotocin-Induced Diabetes  

PubMed Central

Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core. We determined how islet remodeling in autoimmune diabetes compares to streptozotocin (STZ)-induced diabetes. Islet cell mass, proliferation, and immune cell infiltration in pancreas sections from diabetic NOD mice and mice with STZ-induced diabetes was assessed using quantitative image analysis. Serial sections were stained for various beta-cell markers and Ngn3, typically restricted to embryonic tissue, was only upregulated in diabetic NOD mouse islets. Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state. Total pancreatic alpha-cell mass did not change as autoimmune diabetes developed in NOD mice despite the proportion of islet area comprised of alpha- and delta-cells increased. By contrast, alpha- and delta-cell mass was increased in mice with STZ-induced diabetes. Serum levels of glucagon reflected these changes in alpha-cell mass: glucagon levels remained constant in NOD mice over time but increased significantly in STZ-induced diabetes. Increased serum GLP-1 levels were found in both models of diabetes, likely due to alpha-cell expression of prohormone convertase 1/3. Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation. Hence, the inflammatory milieu in NOD mouse islets may restrict alpha-cell expansion highlighting important differences between these two diabetes models and raising the possibility that increased alpha-cell mass might contribute to the hyperglycemia observed in the STZ model. PMID:25101835

Plesner, Annette; ten Holder, Joris T.; Verchere, C. Bruce

2014-01-01

324

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. PMID:23569830

Ananda, Prabu K; Kumarappan, CT; Sunil, Christudas; Kalaichelvan, VK

2012-01-01

325

Hydrogen Sulfide Alleviates Diabetic Nephropathy in a Streptozotocin-induced Diabetic Rat Model.  

PubMed

Accumulating evidence has demonstrated that hydrogen sulfide (H2S) plays critical roles in the pathogenesis of chronic kidney diseases. This study was designed to investigate whether H2S has protective effects against diabetic nephropathy. Diabetic rats were induced by intraperitoneal injection of streptozotocin and administrated with H2S donor NaHS for 12 weeks. Rat glomerular mesangial cells were pretreated with NaHS or MAPK inhibitors (U0126, SP600125, and SB203580) prior to high glucose exposure, and cell proliferation was determined. Our findings suggest that H2S can improve renal function and attenuate glomerular basement membrane thickening, mesangial matrix deposition, and renal interstitial fibrosis in diabetic rats. H2S was found to reduce high glucose-induced oxidative stress by activating the Nrf2 antioxidant pathway and to exert anti-inflammatory effects by inhibiting NF-?B signaling. In addition, H2S reduced high glucose-induced mesangial cell proliferation by blockade of MAPK signaling pathways. Moreover, H2S was also found to inhibit the renin-angiotensin system in diabetic kidney. In conclusion, our study demonstrates that H2S alleviates the development of diabetic nephropathy by attenuating oxidative stress and inflammation, reducing mesangial cell proliferation, and inhibiting renin-angiotensin system activity. PMID:25164822

Zhou, Xiang; Feng, Yu; Zhan, Zhoubing; Chen, Jianchang

2014-10-17

326

Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats  

Microsoft Academic Search

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. The aim of this study was to investigate the effect of different phosphodiesterase inhibitors on lipid peroxidation and total antioxidant capacity (TAC) of plasma in streptozotocin-induced diabetic rats (Rattus norvegicus). Rats became diabetic by a single administration of streptozotocin (STZ, 45 mg\\/kg).

Elham Milani; Shekoufeh Nikfar; Reza Khorasani; Mohammad Jafar Zamani; Mohammad Abdollahi

2005-01-01

327

Antioxidant ?-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes  

Microsoft Academic Search

We have shown recently that oxidative stress by chronic hyperglycemia damages the pancreatic ?-cells of GK rats, a model of non-obese type 2 diabetes, which may worsen diabetic condition and suggested the administration of antioxidants as a supportive therapy. To determine if natural antioxidant ?-tocopherol (vitamin E) has beneficial effects on the glycemic control of type 2 diabetes, GK rats

Yu Ihara; Yuichiro Yamada; Shinya Toyokuni; Kazumasa Miyawaki; Nobuhiro Ban; Tetsuya Adachi; Akira Kuroe; Toshio Iwakura; Akira Kubota; Hiroshi Hiai; Yutaka Seino

2000-01-01

328

Hepatic insulin expression improves glycemic control in type 1 diabetic rats  

Microsoft Academic Search

Low levels of hepatic insulin production have been shown to prevent lethal ketoacidosis associated with type 1 diabetes. To assess the beneficial effects of sustained hepatic production of insulin on glycemic control in type 1 diabetes, we have employed the adenovirus-mediated gene delivery system to transfer an engineered rat preproinsulin gene to the livers of streptozotocin-induced diabetic nude rats. Hepatic

Hengjiang Dong; Núria Morral; Robert McEvoy; Marcia Meseck; Swan N. Thung; Savio L. C. Woo

2001-01-01

329

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

330

Altered responses to androgen in diabetic male rats.  

PubMed

In male rats, experimentally induced diabetes mellitus has been reported to be associated with reduced serum levels of gonadotropins and testosterone as well as decreased sex accessory organ weights. The purpose of the present study was to determine if the decreased accessory organ weights and gonadotropin levels observed in diabetic animals result from alterations in the ability of target tissues to respond to testosterone. Adult, male, Wistar rats were injected with streptozotocin (STZ) and either maintained as untreated diabetics or treated with daily injections of insulin. Semi-starved animals were included to control for any effects on the reproductive system due to body weight change alone. These three groups, plus intact controls, were maintained for 30 days with one-half of the animals from each group receiving silastic tubing implants of testosterone of various lengths. It was determined that, in uncontrolled diabetic and semi-starved animals, the serum levels of LH, FSH, and testosterone were decreased, as were the weights of seminal vesicles and ventral prostate glands. Insulin treatment restored LH, FSH, and testosterone levels to normal. Sex accessory glands exhibited slight, but significant, recovery in diabetic animals treated with insulin. Implants of testosterone that resulted in physiologic serum levels of testosterone were effective in depressing serum LH and FSH levels as well as in maintaining normal seminal vesicle and ventral prostate weights in control and semi-starved animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6432609

Jackson, F L; Hutson, J C

1984-09-01

331

The Role of Apelin in the Retina of Diabetic Rats  

PubMed Central

Purpose Apelin is a novel adipocytokine participating in diabetes, but its role in diabetic retinopathy (DR) is unknown. Our study aimed to investigate the effect of apelin on the proliferative potential in DR along with its antagonist inhibitory effects. Principal Findings Strong staining of apelin, co-localized with glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was observed in the retina of diabetic rats. Apelin, GFAP, and VEGF mRNA and protein levels were significantly increased in the sample’s retinas. Moreover, exogenous apelin promoted retinal Müller cell proliferation in vivo. Simultaneously, apelin induced GFAP and VEGF expression. F13A markedly reduced retinal gliosis caused by diabetes. Furthermore, F13A suppressed both GFAP and VEGF expression in vivo. Significance Our results strongly suggest that apelin is associated with the development of DR and contributes to changes in the retinas of diabetic rats. Apelin induced promotion of cell proliferation lends support to the possibility that apelin may play a role in the progression of DR to a proliferative phase. This possible role deserves further investigation, which may offer new perspectives in the early prevention and treatment of DR. PMID:23874984

Jiang, Yan-rong

2013-01-01

332

Antidiabetic and hypolipidemic effects of Momordica cymbalaria Hook. fruit powder in alloxan-diabetic rats  

Microsoft Academic Search

This study was undertaken to investigate the effect of Momordica cymbalaria fruit powder on blood glucose and other biochemical parameters in alloxan-induced diabetic rats. The treatment was given for 15 days. After the treatment, a significant reduction was observed in fasting blood glucose levels in the treated diabetic rats, but no hypoglycaemic activity in the treated normal rats. M. cymbalaria

B Kameswara Rao; M. M Kesavulu; R Giri; Ch Appa Rao

1999-01-01

333

Histomorphometric evaluation of new bone formation in diabetic rats submitted to insertion of temporary implants  

Microsoft Academic Search

This study aimed to quantify new bone formation in the femurs of diabetic Wistar rats. Over an eight-week period, MTI-MP® implants were evaluated in control rats and in diabetic rats. At several points during this period, various markers for bone deposit were introduced. The material was observed under fluorescent light microscopy. New bone formation in periosteal and cortical regions linked

Cyro Eduardo de Carvalho; Renato Paulo Chopard

2004-01-01

334

Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy  

Microsoft Academic Search

Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy.BackgroundType II diabetes in the Goto Kakizaki (GK) rats (derived from Wistar rats) is not associated with the development of obesity, hyperlipidemia, hypertension, or pronounced renal functional changes. The aim of this study was to investigate the effect of superimposed hypertension on renal function and morphology under conditions

Ulf Janssen; Stephen G. Riley; Athina Vassiliadou; Jürgen Floege; Aled O. Phillips

2003-01-01

335

Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist  

NASA Astrophysics Data System (ADS)

The glucagon analog [l-N?-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev

1982-02-01

336

Lutein prevents cataract development and progression in diabetic rats  

Microsoft Academic Search

Background  Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia. It is often associated with complications,\\u000a such as cataracts. Cataract, characterized by cloudiness or opacity of the eye lens, is the leading cause of blindness worldwide.\\u000a \\u000a \\u000a \\u000a Methods  The present study investigated the effect of lutein, alone or combined with insulin on the progression of eye lens opacities\\u000a in streptozotocin-diabetic rats for

Emma Arnal; María Miranda; Inmaculada Almansa; María Muriach; Jorge M. Barcia; Francisco J. Romero; Manuel Diaz-Llopis; Francisco Bosch-Morell

2009-01-01

337

Increased severity of acute Trypanosoma brucei brucei infection in rats with alloxan-induced diabetes  

E-print Network

-induced diabetes Ikechukwu Onyebuchi Igbokwea Sani Isaa Umma Kalsum Aliyub Hajja Gana Hamzab Tobias Egbe made diabetic by treatment with alloxan monohydrate (10 % solution, 100 mg/kg body weight). Ten diabetic and ten non-diabetic rats were intraperitoneally infected with the same infective doses

Paris-Sud XI, Université de

338

Blockade of Oxidative Stress by Vitamin C Ameliorates Albuminuria and Renal Sclerosis in Experimental Diabetic Rats  

PubMed Central

Purpose Oxidative stress has been suggested to play a role as a common mediator of apoptosis and kidney damage in diabetes. However, it is uncertain whether the apoptosis occurs in the kidney during the course of diabetes. We investigated the occurrence of apoptosis in the diabetic rat kidney, the role of oxidative stress and the effect of an antioxidant on apoptosis in the diabetic rat kidney. Materials and Methods Otsuka-Long-Evans-Tokushima-Fatty rats, an animal model for type 2 diabetes, were randomized into a non-treated diabetic (n = 8) and a vitamin C-treated group (n = 8). Long-Evans Tokushima Otsuka rats (n = 8 ) were used as a control. Results Apoptosis was present in the epithelial cells of the proximal tubules in diabetic rats. The number of apoptotic cells, albuminuria, proteinuria, glomerular and tubulointerstitial sclerosis, and renal malondialdehyde were significantly decreased in vitamin C-treated diabetic rats when compared to the untreated diabetic rats. The decreased slit pore density (number of slit pores per underlying glomerular basement membrane length) as assessed by electron microscopy was also significantly restored by treatment with vitamin C without significantly affecting plasma glucose in diabetic rats. Conclusion By blocking these pathophysiologic processes, a blockade of oxidative stress by vitamin C might become a useful adjunct to albuminuria and renal sclerosis in diabetic nephropathy. PMID:17963344

Lee, Eun Young; Lee, Mi Young; Hong, Soon Won; Hong, Sae Yong

2007-01-01

339

Alternanthera sessilis Red Ethyl Acetate Fraction Exhibits Antidiabetic Potential on Obese Type 2 Diabetic Rats.  

PubMed

The antidiabetic potential of Alternanthera sessilis Red was investigated using the obese type 2 diabetic rats induced by high fat diet and streptozotocin. Three fractions (hexane, ethyl acetate, and water) were obtained from the crude ethanol extract of Alternanthera sessilis Red. Alternanthera sessilis Red ethyl acetate fraction (ASEAF) was found to possess the most potent antihyperglycemic effect through oral glucose tolerance test. The ASEAF was subsequently given to the diabetic rats for two weeks. It was found that two-week administration of ASEAF reduces the fasting blood glucose level, triglyceride level, and free fatty acid level of the rats. ASEAF-treated diabetic rats showed higher pancreatic insulin content and pancreatic total superoxide dismutase activity compared to the untreated diabetic rats. Also, the insulin sensitivity indexes suggested that ASEAF ameliorates the insulin resistant state of the diabetic rats. In conclusion, ASEAF could be developed into a potential antidiabetic agent for the management of type 2 diabetes. PMID:23606892

Tan, Kok Keong; Kim, Kah Hwi

2013-01-01

340

The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats  

PubMed Central

In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were