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1

Baroreflex function in streptozotocin (STZ) induced diabetic rats  

Microsoft Academic Search

To determine whether the renal sympatho-inhibition and bradycardia in responses to acute increases in arterial pressure are altered in the diabetic state, the renal nerve discharge and heart rate were measured in streptozotocin (STZ) induced diabetic (DIA) rats. Integrated renal sympathetic nerve activity and heart rate were measured before and during an acute increase in blood pressure in anesthetized (Inactin

Kaushik P. Patel; Ping L. Zhang

1995-01-01

2

Berberine chloride improved synaptic plasticity in STZ induced diabetic rats.  

PubMed

Previous studies indicated that diabetes affects synaptic transmission in the hippocampus, leading to impairments of synaptic plasticity and defects in learning and memory. Although berberine treatment ameliorates memory impairment and improves synaptic plasticity in streptozotocin (STZ) induced diabetic rats, it is not clear if the effects are pre- or post-synaptic or both. The aim of this study was to evaluate the effects of berberine chloride on short-term plasticity in inhibitory interneurons in the dentate gyrus of STZ-induced diabetic rats. Experimental groups included: The control, control berberine treated (100 mg/kg), diabetic and diabetic berberine treated (50,100 mg/kg/day for 12 weeks) groups. The paired pulse paradigm was used to stimulate the perforant pathway and field excitatory post-synaptic potentials (fEPSP) were recorded in dentate gyrus (DG). In comparison with control, paired pulse facilitation in the diabetic group was significantly increased (P?diabetes berberine treated (50 and 100 mg/kg) groups as compared to the control group. The present results suggest that the pre-synaptic component of synaptic plasticity in the dentate gyrus is affected under diabetic conditions and that berberine prevents this effect. PMID:23640014

Moghaddam, Hamid Kalalian; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Goshadrou, Fatemeh; Ronaghi, Abdolaziz

2013-09-01

3

Effects of streptozotocin (STZ)-induced diabetes and insulin replacement on rat ventral prostate  

Microsoft Academic Search

BackgroundDiabetes mellitus due to insulin deficiency has adverse effect on all organ systems including reproductive organs. Streptozotocin (STZ)-induced diabetes in rats provides a relevant model to study reproductive dysfunction under diabetic conditions, as they exhibit a number of deficits in reproductive function that resemble those seen in humans. The present investigation was designed to delineate the impact of STZ-induced diabetes

E. Suthagar; S. Soudamani; S. Yuvaraj; A. Ismail Khan; M. M. Aruldhas; K. Balasubramanian

2009-01-01

4

Effects of voluntary exercise on heart function in streptozotocin (STZ) - induced diabetic rat  

Microsoft Academic Search

Exercise training improves cardiac performance and has been utilized as an effective adjunct to pharmacotherapy in the management of diabetes mellitus. The aims of this study were to characterize voluntary exercise habits in streptozotocin (STZ)-induced diabetic rats and investigate whether attained levels of voluntary exercise induce effects on diabetic heart function. Diabetes was induced by a single intraperitoneal injection of

M Ljubisavijevic

5

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.

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

2014-01-01

6

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

7

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).

2013-01-01

8

Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ-induced diabetic rats.  

PubMed

Diabetes mellitus increases the risk of central nervous system (CNS) disorders such as stroke, seizures, dementia, and cognitive impairment. Berberine, a natural isoquinoline alkaloid, is reported to exhibit beneficial effect in various neurodegenerative and neuropsychiatric disorders. Moreover, astrocytes are proving critical for normal CNS function, and alterations in their activity and impaired oxidative stress could contribute to diabetes-related cognitive dysfunction. Metabolic and oxidative insults often cause rapid changes in glial cells. Key indicators of this response are increased synthesis of glial fibrillary acidic protein (GFAP) as an astrocytic marker. Therefore, we examined the effects of berberine on glial reactivity of hippocampus in streptozotocin (STZ)-induced diabetic rats, using GFAP immunohistochemistry. Lipid peroxidation, superoxide dismutase (SOD) activity, and nitrite levels were assessed as the parameters of oxidative stress. Eight weeks after diabetes induction, we observed increased numbers of GFAP(+) astrocytes immunostaining associated with increased lipid peroxidation, decreased superoxide dismutase activity, and elevated nitrite levels in the hippocampus of STZ-diabetic rats. In contrast, chronic treatment with berberine (50 and 100 mg/kg p.o. once daily) lowered hyperglycemia, reduced oxidative stress, and prevented the upregulation of GFAP in the brain of diabetic rats. In conclusion, the present study demonstrated that the treatment with berberine resulted in an obvious reduction of oxidative stress and GFAP-immunoreactive astrocytes in the hippocampus of STZ-induced diabetic rats. PMID:24113841

Moghaddam, Hamid Kalalian; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Khaksari, Mehdi; Norouzi, Pirasteh; Ahooie, Malihea; Mahboobi, Fatemeh

2014-04-01

9

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

PubMed

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

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

2012-09-01

10

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

Microsoft Academic Search

This study examined the influence of two intensities of exercise on ventricular myocyte shortening and intracellular calcium\\u000a in the streptozotocin (STZ)-induced diabetic rat. Animals were divided into four groups: control sedentary (CS), diabetic\\u000a sedentary (DS), diabetic light exercise (DLE; 5 × 30 min\\/week, 9 m\\/min) and diabetic moderate exercise (DME; 5 × 30 min\\/week,\\u000a 18 m\\/min) and the exercise programme started 2 months after STZ treatment. Time to peak

Frank Christopher Howarth; F. A. Almugaddum; M. A. Qureshi; M. Ljubisavijevic

2008-01-01

11

Anti-diabetic and antihyperlipidemic effect of allopolyherbal formulation in OGTT and STZ-induced diabetic rat model.  

PubMed

The present study was undertaken to evaluate the antidiabetic and antihyperlipidemic activities of Allopolyherbal formulation (APHF) consisting of combinations of three well known medicinal plants used in traditional medicines (Trigonella foenum graceum, Momordica charantia, Aegle marmelos) and synthetic oral hypoglycaemic drug (Glipizide-GL). The optimized combination of lyophilized hydro-alcoholic extracts of drugs was 2:2:1 using OGTT model. The optimized PHF was simultaneously administered with GL and optimized using OGTT model in diabetic rats and further studied in STZ-induced diabetic rats for 21 days. The results (serum glucose level, lipid profile, hepatic enzymes and body weight) were compared with the standard drug GL (10 mg/kg body wt). The optimized APHF (500+5 mg/kg body wt) has shown significant antihyperglycemic and antihyperlipidemic activities. The results were comparable with the standard; even better than the GL (10 mg/kg body wt) alone. The proposed hypothesis has reduced the no. of drug components from eight to three and dose almost 50% of both PHF and GL which fulfil the FDA requirements for export. Thus the developed APHF will be an ideal alternative for the existing hypoglycemic formulations in the market with an additional advantage of hypolipidemic effect and minimizing the cardiovascular risk factors associated with diabetes. PMID:24377129

Manik, Swati; Gauttam, Vinod; Kalia, A N

2013-09-01

12

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

Microsoft Academic Search

Thirty streptozotocin (STZ)-induced diabetic of Wistar Albino rats were divided into five groups. The rat groups received different food (natural diet or high fat content diet) supplemented with 10% or 15% of samh seeds for 6weeks. At the end of the study, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phophatase (ALP) and lactate dehydrogenase (LDH) enzymes have been measured in

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

2010-01-01

13

Potential nephrotoxic effects produced by steroidal saponins from hydro alcoholic extract of Tribulus terrestris in STZ-induced diabetic rats.  

PubMed

Chronic hyperglycemia leads to the development of microvascular complications like diabetic nephropathy. The present study investigated the potential effects of the hydroalcoholic extract of Tribulus terrestris, a plant of Zygophyllaceae family, on the renal complications in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by administering STZ (90?mg/kg) to the 2-days old neonates. After 6 weeks of induction, diabetic rats were treated with 50?mg/kg hydroalcoholic extract of T. terrestris for 8 weeks. The anti-hyperglycaemic nature was confirmed by reduction in blood glucose and improvement in insulin levels. Diabetic renal injury associated with decrease in total proteins and albumin levels was observed to be improved by T. terrestris extract. Glomerular filtration rate along with inflammatory and growth factors, adiponectin and erythropoietin were also improved by the treatment, though the findings were not significant. However, the beneficial antidiabetic effects of T. terrestris extract in plasma were not observed in kidney histopathology. This was confirmed by the quantitative estimation of unhydrolyzed fraction of saponins (major component: protodioscin) in plasma and kidney samples of normal and diabetic rats. Hence, it can be concluded that 8 weeks treatment with T. terrestris extract produces potential toxic effects in kidney, which are independent of its anti-diabetic action. PMID:23594260

Gandhi, Sonia; Srinivasan, B P; Akarte, Atul S

2013-09-01

14

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

PubMed

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

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

2008-03-01

15

Effects of cilostazol on the peripheral nerve function and structure in STZ-induced diabetic rats  

Microsoft Academic Search

We examined the effect of cilostazol (CZ), antiplatelet agent and potent vasoactive compound, which has an inhibitory effect on tissue phosphodiesterase, on peripheral nerve in streptozotocin-induced diabetic rats. Diabetic rats were fed for 12 weeks with a chow containing 0.01% or 0.03% CZ (ww) and the results were compared with untreated diabetic rats. The 0.03% CZ treatment significantly improved motor

Kenji Uehara; Kazuhiro Sugimoto; Ryu-ichi Wada; Tomohiro Yoshikawa; Keiko Marukawa; Yoshinobu Yasuda; Yukio Kimura; Soroku Yagihashi

1997-01-01

16

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.

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

2014-01-01

17

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.

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

2012-01-01

18

Deterioration of bone quality by streptozotocin (STZ)-induced type 2 diabetes mellitus in rats.  

PubMed

Patients with diabetes mellitus (DM) have various skeletal disorders and bone quality can be impaired in DM leading to fractures. Wistar albino male rats (270-300 g; n?=?16) were assigned randomly to nondiabetic and diabetic rats (single dose intravenous injection of 45 mg/kg streptozotocin). All rats in each group were perpetuated for 8 weeks, and blood glucose levels as well as body weights were measured once weekly. Biomechanical measurements were performed at the mid-diaphysis of the left femur with tensile test. Extrinsic and intrinsic properties were measured or calculated. Bone mineral density (BMD) was also evaluated and measured by dual-energy X-ray absorptiometry. Cross-sectional area of the femoral shaft was evaluated by computerized tomography. Blood glucose levels in diabetic rats were significantly increased compared to that of the nondiabetic rats, while the body and femur weights were decreased (P?diabetic rats (P?>?0.05). The maximum load, ultimate stress, and toughness endpoints in diabetic rats were significantly decreased compared to that of the nondiabetics (P?diabetic rats with regard to the displacement and stiffness (P?>?0.05). Femurs of diabetic rats had less absorbed energy than that in nondiabetics (P?diabetic rats than that in nondiabetics, while the elastic modulus was higher (P?>?0.05). The bone quality of rats is decreased by streptozotocin-induced type 2 diabetes mellitus. PMID:20446056

Erdal, Nurten; Gürgül, Serkan; Kavak, Servet; Yildiz, Altan; Emre, Mustafa

2011-06-01

19

Deterioration of Bone Quality by Streptozotocin (STZ)Induced Type 2 Diabetes Mellitus in Rats  

Microsoft Academic Search

Patients with diabetes mellitus (DM) have various skeletal disorders and bone quality can be impaired in DM leading to fractures.\\u000a Wistar albino male rats (270–300 g; n?=?16) were assigned randomly to nondiabetic and diabetic rats (single dose intravenous injection of 45 mg\\/kg streptozotocin).\\u000a All rats in each group were perpetuated for 8 weeks, and blood glucose levels as well as body weights were

Nurten Erdal; Serkan Gürgül; Servet Kavak; Altan Yildiz; Mustafa Emre

2011-01-01

20

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

Microsoft Academic Search

Adult male Sprague-Dawley rats injected with 45 mg STZ\\/kg rapidly developed the classical symptoms of diabetes which persisted throughout the 90 day test period. Serum ketone concentrations in control and STZ-treated rats were within normal limits. Diabetic animals exhibited depressed cytochrome P-450 content as well as decreased activities of benzphetamine N-demethylase, styrene oxide hydrolase, UDP-glucuronosyltransferase toward 1-naphthol and testosterone, and

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

1986-01-01

21

Endothelin antagonism normalizes VEGF signaling and cardiac function in STZ-induced diabetic rat hearts.  

PubMed

Abnormal alterations in cardiac expression of vascular endothelial growth factor (VEGF) as well as its receptors and impairment in the development of coronary collaterals have recently been reported in diabetic subjects. However, the presence of pharmacological intervention on these defects in diabetes remains unsettled. Here, we studied the effect of endothelin (ET) receptor blockade on cardiac VEGF signaling pathways and cardiac function in Sprague-Dawley rats 5 wk after induction of type I diabetes with streptozotocin (65 mg/kg ip) in comparison with age-matched control rats. After streptozotocin (1 wk), some diabetic rats were treated with the ET receptor antagonist SB-209670 (1 mg/day) for 4 wk. VEGF, its receptors, and its angiogenic signaling molecules [phosphorylated Akt and endothelial nitric-oxide synthase (eNOS)] were analyzed by Western blot, ELISA, real-time PCR, and immunohistochemistry, and cardiac function was evaluated by echocardiography. Coronary capillary morphology was assessed by lectin and enzymatic double staining. We found significant decreases in cardiac expression of VEGF, its receptors, phosphorylation of Akt and eNOS, and coronary capillary density in diabetic rats compared with controls. Treatment of diabetic rats with SB-209670 reversed these alterations to the control levels and ameliorated impairment of cardiac function. From a molecular point of view, the present study is the first to indicate the potential usefulness of an ET receptor antagonist in the treatment of cardiac dysfunction in type I diabetes. PMID:17148754

Jesmin, Subrina; Zaedi, Sohel; Shimojo, Nobutake; Iemitsu, Motoyuki; Masuzawa, Koichi; Yamaguchi, Naoto; Mowa, Chishimba N; Maeda, Seiji; Hattori, Yuichi; Miyauchi, Takashi

2007-04-01

22

Calcineurin and Akt expression in hypertrophied bladder in STZ-induced diabetic rat  

PubMed Central

Diabetes causes significant increases in bladder weight but the natural history and underlying mechanisms are not known. In this study, we observed the temporal changes of detrusor muscle cells (DMC) and the calcineurin (Cn) and Akt expressions in detrusor muscle in the diabetic rat. Male Sprague–Dawley rats were divided into 3 groups: streptozotocin-induced diabetics, 5% sucrose-induced diuretics, and age-matched controls. The bladders were removed 1, 2, or 9 weeks after disease induction and the extent of hypertrophy was examined by bladder weights and cross sectional area of DMC. Cn and Akt expression were evaluated by immunoblotting. Both diabetes and diuresis caused significant increases in bladder weight. The mean cross sectional areas of DMC were increased in both diabetic and diuretic animals 1, 2, or 9 weeks after disease induction. The expression levels of both the catalytic A (CnA) and regulatory B (CnB) subunits of Cn were increased at 1 and 2 weeks, but not at 9 weeks. Expression of Akt was similar among control, diabetic, and diuretic rat bladder at all time points. In conclusion, diabetes and diuresis induce similar hypertrophy of detrusor muscle during the first 9 weeks, indicating that bladder hypertrophy in the early stage of diabetes is in response to the presence of increased urine output in diabetes. Our results suggest that the Cn, but not the Akt signaling pathway may be involved in the development of bladder hypertrophy.

Liu, Guiming; Li, Mei; Daneshgari, Firouz

2014-01-01

23

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

PubMed

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

She, Shaoyi; Liu, Weijuan; Li, Tong; Hong, Yingkai

2014-04-23

24

Myocardial Capillary Net And Blood Constituents In Streptozotocin (Stz)Induced Diabetic Rats  

Microsoft Academic Search

Type 1 diabetes was induced in Wistar rats by injection of streptozotocin (STZ). Changes in the myocardial capillary network\\u000a were examined using the doublestaining enzymatic method for alkaline phosphatase (AP) and dipeptidylpeptidase IV (DPPIV) This\\u000a method allows the identification of the arteriolar (AP-containing) and the venular (DPPIV-containing) portions of the capillary\\u000a network. In addition, blood plasma was analysed. The AP-

Tomiyasu Koyama; Akira Taka

25

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

PubMed

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

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

2012-01-01

26

Expression changes of thrombospondin-1 and neuropeptide Y in myocardium of STZ-induced rats  

Microsoft Academic Search

Diabetic cardiomyopathy was the most dangerous diabetic complication facing diabetics, with its exact mechanisms remaining obscure. Our study was conducted to investigate the expression of thrombospondin-1 (TSP-1) and neuropeptide Y (NPY) in myocardium of streptozotocin (STZ)-induced diabetic rats. We employed streptozotocin (STZ)-induced diabetic rats to study the alteration of the TSP-1 and NPY expression in the left ventricle myocardium in

Xiao-Ming Zhang; Fang Shen; Zhen-Yu Xv; Zhi-Yu Yan; Shu Han

2005-01-01

27

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.

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

2013-01-01

28

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

Microsoft Academic Search

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

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

2010-01-01

29

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

PubMed Central

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

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

2013-01-01

30

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

PubMed Central

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

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

2009-01-01

31

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 28days. 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

32

Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats.  

PubMed

Atorvastatin, a lipid lowering agent, possesses various pleiotropic vasculoprotective effects, but its role in coronary angiogenesis is still controversial. Our objective was to study the effects of atorvastatin on the angiogenic responsiveness of coronary endothelial cells (cEC) from normal and diabetic rats. Male Wistar rats were distributed among 9 groups; (i) normal rats, (ii) 30 day diabetic rats, (iii) 60 day diabetic rats, (iv) normal rats administered a low dose of atorvastatin (1 mg/kg body mass, per oral (p.o.), for 15 days); (v) 30 day diabetic rats administered a low dose of atorvastatin; (vi) 60 day diabetic rats administered a low dose of atorvastatin; (vii) normal rats administered a high dose of atorvastatin (5 mg/kg, p.o., for 15 days); (viii) 30 day diabetic rats administered a high dose of atorvastatin; (ix) 60 day diabetic rats administered a high dose of atorvastatin. Each group was further divided into 2 subgroups, (i) sham ischemia-reperfusion and (ii) rats hearts that underwent ischemia-reperfusion. Angiogenic responsiveness the and nitric oxide (NO) releasing properties of the subgroups of cECs were studied using a chorioallantoic membrane assay and the Griess method, respectively. Atorvastatin treatment significantly increased VEGF-induced angiogenic responsiveness and the NO-releasing properties of cECs from all of the subgroups, compared with their respective non-treated subgroups except for the late-phase diabetic rat hearts that underwent ischemia-reperfusion, and the high dose of atorvastatin treatment groups. These effects of atorvastatin were significantly inhibited by pretreatment of cECs with l-NAME, wortmannin, and chelerythrine. Thus, treatment with a low dose of atorvastatin improves the angiogenic responsiveness of the cECs from normal and diabetic rats, in the presence of VEGF, via activation of eNOS-NO release. PMID:24708217

Chaudagar, Kiranj K; Mehta, Anita A

2014-04-01

33

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.

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

2013-01-01

34

The PI3K/Akt and MAPK-ERK1/2 pathways are altered in STZ induced diabetic rat placentas.  

PubMed

Diabetic pregnancy is associated with complications such as early and late embryonic death, fetal growth disorders, placental abnormalities, and embryonal-placental metabolic disorders. Excessive apoptosis and/or changes of proliferation mechanisms are seen as a major event in the pathogenesis of diabetes-induced embryonic death, placental weight and structural anomalies. Akt and ERK1/2 proteins are important for placental and fetal development associated with cellular proliferation and differentiation mechanisms. The mechanism underlying the placental growth regulatory effects of hyperglycemia have not been elucidated. Moreover, it is still not determined how Akt and ERK1/2 proteins related proliferation and apoptosis mechanisms are influenced by Streptozotocin (STZ) induced diabetic rat placental development. The aim of this study was to investigate the expression levels and spatio-temporal immunolocalizations of Akt, p-Akt, ERK1/2 and p-ERK1/2 proteins in normal and STZ-treated diabetic rat placental development. In order to compose the diabetic group, pregnant females were injected with a single dose of 40mg/kg STZ intraperitonally seven days before their sacrifice at 12th, 14th, 16th, 18th and 20th day of their gestation. We found that maternal diabetic environment led to a decrease in ERK1/2 and Akt phosphorylation during rat placental development. It could be said that MAPK-ERK1/2 and PI3K/Akt cell signaling pathways are affected from hyperglycemic conditions in rat placentas. In conclusion, hyperglycemia-induced placental and embryonal developmental abnormalities could be associated with reduction of Akt and ERK1/2 phosphorylation. PMID:24346807

Ozmen, Asli; Unek, Gozde; Kipmen-Korgun, Dijle; Korgun, Emin Turkay

2014-06-01

35

Effect of PUFA-rich plant oil on risk factors of STZ-induced diabetes in Wistar rats.  

PubMed

Objective This study has been focused on the effect of an n-6 polyunsaturated fatty acid (PUFA) rich plant oil on oxidation and glycooxidation stress markers as well as on antioxidant enzyme activities in male Wistar rats with streptozotocin-induced diabetes. Methods The non-diabetic and diabetic groups of Wistar rats were administered plant oil at concentrations of 100 and 500 mg/kg body weight and controls without plant oil. The parameters of glycaemic control, lipid profile, total antioxidant status, antioxidant enzyme activities, together with oxidative and glycooxidative stress markers were measured in the blood. Results The intake of the plant oil did not significantly influence the parameters of glycaemic control and significantly increased the levels of all lipid profile parameters in the diabetic rats. Plant oil administration significantly decreased the total antioxidant status and glutathione peroxidase activity and the activity of Cu/Zn superoxide dismutase was significantly increased. The plant oil also increased the levels of lipoperoxides and advanced the glycation end products. Discussion These results suggest that the plant oil with high concentrations of n-6 PUFA - linoleic acid, acts prooxidatively when administered to the rats. PMID:24533892

Kopál, Martin; Ondrejovi?ová, Iveta; Deáková, Zuzana; Uli?ná, Olga; Van?ová, Olga; Dura?ková, Zdenka; Muchová, Jana

2014-05-28

36

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

2013-01-01

37

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

PubMed Central

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

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

2014-01-01

38

Thyroid Hormone T3 Counteracts STZ Induced Diabetes in Mouse  

PubMed Central

This study intended to demonstrate that the thyroid hormone T3 counteracts the onset of a Streptozotocin (STZ) induced diabetes in wild type mice. To test our hypothesis diabetes has been induced in Balb/c male mice by multiple low dose Streptozotocin injection; and a group of mice was contemporaneously injected with T3. After 48 h mice were tested for glucose tolerance test, insulin serum levels and then sacrified. Whole pancreata were utilized for morphological and biochemical analyses, while protein extracts and RNA were utilized for expression analyses of specific molecules. The results showed that islets from T3 treated mice were comparable to age- and sex-matched control, untreated mice in number, shape, dimension, consistency, ultrastructure, insulin and glucagon levels, Tunel positivity and caspases activation, while all the cited parameters and molecules were altered by STZ alone. The T3-induced pro survival effect was associated with a strong increase in phosphorylated Akt. Moreover, T3 administration prevented the STZ-dependent alterations in glucose blood level, both during fasting and after glucose challenge, as well as in insulin serum level. In conclusion we demonstrated that T3 could act as a protective factor against STZ induced diabetes.

Madaro, Luca; Ranieri, Danilo; Lupoi, Lorenzo; Stigliano, Antonio; Torrisi, Maria Rosaria; Bouche, Marina; Toscano, Vincenzo; Misiti, Silvia

2011-01-01

39

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

Microsoft Academic Search

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

Pitchai Daisy; James Eliza; Khanzan Abdul Majeed Mohamed Farook

2009-01-01

40

Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training.  

PubMed

Skeletal muscle atrophy is associated with type-1 diabetes. Skeletal muscle is the source of pro- and anti-inflammatory cytokines that can mediate muscle hypertrophy and atrophy, while resistance exercise can modulate both muscle mass and muscle cytokine expression. This study determined the effects of a 5-week resistance exercise training regimen on the expression of muscle cytokines in healthy and streptozotocin-induced diabetic rats, with special emphasis on interleukin-15 (IL-15), a muscle-derived cytokine proposed to be involved in muscle hypertrophy or responses to stress. Induction of diabetes reduced muscle weight in both the fast flexor hallucis longus (FHL) and slow soleus muscles, while resistance training preserved FHL muscle weight in diabetic rats. IL-15 protein content was increased by training in both FHL and soleus muscles, as well as serum, in normal and diabetic rats. With regard to proinflammatory cytokines, muscle IL-6 levels were increased in diabetic rats, while training decreased muscle IL-6 levels in diabetic rats; training had no effect on FHL muscle IL-6 levels in healthy rats. Also, tumor necrosis factor-alpha (TNF-?) and IL-1? levels were increased by diabetes, but not changed by training. In conclusion, we found that in diabetic rats, resistance training increased muscle and serum IL-15 levels, decreased muscle IL-6 levels, and preserved FHL muscle mass. PMID:24006180

Molanouri Shamsi, M; Hassan, Z H; Gharakhanlou, R; Quinn, L S; Azadmanesh, K; Baghersad, L; Isanejad, A; Mahdavi, M

2014-05-01

41

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

Microsoft Academic Search

The anti-diabetic effect of the drug Semecarpus anacardium Linn nut milk extract (SA) was studied in male Sprague Dawley rats. The rats were divided into seven groups of six animals\\u000a each. Type 2 diabetes mellitus was induced in rats by feeding them with a high fat diet for 2 weeks followed by intraperitoneal\\u000a injection of 35 mg\\/kg\\/body weight (b. wt.) of streptozotocin.

Haseena Banu Hedayathullah Khan; Kaladevi Siddhi Vinayagam; Shanthi Palanivelu; Sachdanandam Panchanatham

42

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

Microsoft Academic Search

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

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

43

Protective effect and potential mechanism of Ginkgo biloba extract EGb 761 on STZ-induced neuropathic pain in rats.  

PubMed

Diabetes induced neuropathic pain is recognized as one of the most difficult types of pain to treat with conventional analgaesics. EGb 761 is a standardized extract of Ginkgo biloba that has analgaesic and antiinflammatory properties and modulatory effects on key pain-related molecules. We examined the effect of EGb 761 on streptozotocin (STZ)-induced neuropathic pain behaviours and assessed its mechanism of action. Streptozotocin (20?mg/kg i.p for 5?days) was administered to induce experimental diabetes. Pain hypersensitivity to radiant heat was measured using the Dynamic Plantar Aesthesiometer to test the pain threshold. Diabetic rats exhibited mechanical allodynia and thermal hyperanalgaesia after the third week of STZ injection and concomitantly increased thiobarbituric acid reactive substance and nitric oxide concentration. The antioxidant enzymes level of superoxide dismutase and catalase was markedly reduced in STZ-diabetic rats (p?STZ-induced thermal hyperanalgaesia and mechanical allodynia. Moreover, it reduced oxidonitrosative stress and concomitantly restored the level of antioxidant enzymes (p?diabetic rats. These results suggest that EGb 761 attenuated STZ-induced neuropathic pain behaviours by inhibiting oxidative and nitrosative stress and may constitute a new approach for treatment of painful diabetic neuropathy. PMID:22422566

Taliyan, Rajeev; Sharma, P L

2012-12-01

44

Insulin resistance occurres in parallel with sensory neuropathy in STZ-induced diabetes in rats; differential response to early vs late insulin supplementation  

Microsoft Academic Search

Objective: We investigated whether progressive sensory neuropathy was accompanied by changes in whole body insulin sensitivity in rats made diabetic by streptozotocin (STZ). The effects of early and late insulin supplementation were also studied. Materials\\/Methods: The STZ-treated rats failed to gain weight and exhibited stable hyperglycaemia and low plasma insulin levels with a decrease in nerve conduction velocity (NCV) measured

Zoltan Szilvássy; Joseph Nemeth; Péter Kovács; György Paragh; Réka Sári; László Vígh; Barna Peitl

45

Co-administration of Grape Seed Extract and Exercise Training Improves Endothelial Dysfunction of Coronary Vascular Bed of STZ-Induced Diabetic Rats  

PubMed Central

Background One of the known complications of diabetes mellitus is vascular dysfunction. Inability of the coronary vascular response to cardiac hyperactivity might cause a higher incidence of ischemic heart disease in diabetic subjects. It has been indicated that regular exercise training and antioxidants could prevent diabetic cardiovascular problems enhanced by vascular damage. Objectives The aim of this study was to determine the effects of grape seed extract (as antioxidant), with and without exercise training on coronary vascular function in streptozotocin induced diabetic rats. Materials and Methods Fifty male Wistar rats weighing 200 – 232 grams were randomly divided into five groups of 10 rats each: sedentary control, sedentary diabetic, trained diabetic, grape seed extract (200 mg/kg) treated sedentary diabetic and, grape seed extract treated trained diabetic. Diabetes was induced by one intraperitoneal injection of streptozotocin. After eight weeks, coronary vascular responses to vasoactive agents were determined. Results The endothelium dependent vasorelaxation to acetylcholine was reduced significantly in diabetic animals; exercise training or grape seed extract administration partially improves this response. However, exercise training in combination with grape seed extract restores endothelial function completely. The endothelium independent vasorelaxation to sodium nitroprusside was improved by combination of exercise training and grape seed extract. On the other hand, the basal perfusion pressure and vasoconstrictive response to phenylephrine did not change significantly. Conclusions The data indicated that co-administration of grape seed extract and exercise training had more significant effects than exercise training or grape seed extract alone; this may constitute a convenient and inexpensive therapeutic approach to diabetic vascular complications.

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

2013-01-01

46

Total Glucosides of Paeony Attenuate Renal Tubulointerstitial Injury in STZ-Induced Diabetic Rats: Role of Toll-Like Receptor 2.  

PubMed

Accumulating evidence suggested that macrophages induce tubulointerstitial injury. Total glucosides of paeony (TGP), extracted from Paeonia lactiflora, has presented anti-inflammatory activities in diabetic kidney disease. This research will investigate the protective effect of TGP on renal tubulointerstitium and its mechanism in streptozotocin-induced diabetic rats. TGP was administered orally at a dose of 50, 100, and 200 mg·kg(-1)·d(-1) for 8 weeks. Tubulointerstitial injury was quantified, followed by immunohistochemistry analysis of renal ?-smooth muscle actin (?-SMA), E-cadherin (E-cad) expression, nuclear factor kappa B (NF-?B)-p-p-65(+), Toll-like receptor (TLR)2(+), and ED-1(+) cell infiltration in renal tubulointerstitium. Renal TLR2(+) macrophages were detected by double immunohistochemical staining. Western blotting was used to detect the TLR2 expression. Histologically, there was marked accumulation of TLR2(+), NF-?B-p-p-65(+), ED-1(+) cells, and ED-1(+)TLR2(+) cells (macrophages) in the diabetic kidney and TGP treatment could alleviate it. Accompanying with that, the tubulointerstitial injury was ameliorated, ?-SMA expression was lower, and E-cad expression was higher compared with the diabetic rats. Western blot analysis showed that the expression of TLR2 protein was significantly increased in the kidney of the diabetic rats, whereas TGP treatment reduced it. Our study showed that TGP could prevent renal tubulointerstitium injury in diabetic rats through a mechanism that may be at least partly correlated with suppression of increased macrophage infiltration and the expression of TLR2. PMID:24739281

Zhang, Wei; Zhao, Li; Su, Shuang-Quan; Xu, Xing-Xin; Wu, Yong-Gui

2014-05-20

47

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

48

Brazilin augments cellular immunity in multiple low dose streptozotocin (MLD-STZ) induced type I diabetic mice  

Microsoft Academic Search

Brazilin, an active principle ofCaesalprenia sappan, was examined for its immunopotentiating effects in multiple low dose streptozotocin (MLD-STZ) induced type diabetic mice.\\u000a Brazilin was intraperitoneally administered for 5 consecutive days to MLD-STZ induced type I diabetic mice. Delayed type hypersensitivity,\\u000a Con A-induced proliferation of splenocytes and mixed lymphocyte reaction, which had been decreased in diabetic mice, were\\u000a significantly recovered by

Kyoung-Mee Yang; Sun-Duck Jeon; Dhong-Soo So; Chang-Kiu Moon

2000-01-01

49

Evaluation of hypoglycaemic and hypolipidaemic effects of aqueous ethanolic extracts of Treculia africana Decne and Bryophyllum pinnatum Lam. and their mixture on streptozotocin (STZ)-induced diabetic rats  

Microsoft Academic Search

The plants Treculia africana and Bryophyllum pinnatum are ethnobotanically used in the treatment of various diseases including diabetes and heart diseases. Diabetes mellitus is a disease characterized by hyperglycaemia, and hyperlipidaemia which leads to an increased risk of atherosclerosis and other cardiovascular diseases. The effects of aqueous ethanol (80%) extracts of T. africana leaves and B. pinnatum plants and their

50

IL-32? overexpression accelerates streptozotocin (STZ)-induced type 1 diabetes.  

PubMed

Interleukin-32 (IL-32) is a cytokine produced by T lymphocytes, natural killer (NK) cells, monocytes and epithelial cells. There are five splicing variants (?, ?, ?, ?, and ?) and IL-32? is the most active isoform. We generated human IL-32? transgenic (IL-32? TG) mice, displaying a high level of IL-32? expression in the pancreas. We investigated the effect of IL-32? on streptozotocin (STZ)-induced type 1 diabetes model using IL-32? TG mice. After a suboptimal diabetogenic dose of STZ administration, IL-32? TG mice showed significantly increased blood glucose level comparing with that of wild type (WT) mice at day 5. Inflammatory cytokines levels such as, IL-6, TNF?, IFN? and IL-1?, in pancreas and liver lysates were accessed by a specific cytokine ELISA. The proinflammatory cytokines were significantly enhanced in the pancreas of IL-32? TG mice comparing to that of WT mice whereas those cytokines levels in liver of IL-32? TG and WT mice were not changed by STZ. These data indicate that the overexpression of IL-32? contributes to initial islet ?-cells injury and inflammation in pancreas and aggravates STZ-induced type 1 diabetes. PMID:25022955

Jhun, Hyunjhung; Choi, Jida; Hong, Jaewoo; Lee, Siyoung; Kwak, Areum; Kim, Eunsom; Jo, Seunghyun; Ryoo, Soyoon; Lim, Yoojung; Yoon, Do-Young; Hong, Jin Tae; Kim, Tae Sung; Lee, Youngmin; Song, Keeho; Kim, Soohyun

2014-09-01

51

Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary, hypothalamus and cerebellum of streptozotocin (STZ)-induced diabetic rats.  

PubMed

Poorly controlled type1 diabetes is associated with hormonal imbalances and increased cell death in different tissues, including the pituitary, hypothalamus and cerebellum. In the pituitary, lactotrophs are the cell population with the greatest increase in cell death, whereas in the hypothalamus and cerebellum astrocytes are most highly affected. Insulin treatment can delay, but does not prevent, diabetic complications. As ghrelin and growth hormone (GH) secretagogues are reported to prevent apoptosis in different tissues, and to modulate glucose homeostasis, a combined hormonal treatment may be beneficial. Hence, we analyzed the effect of insulin and GH-releasing peptide 6 (GHRP-6) on diabetes-induced apoptosis in the pituitary, hypothalamus and cerebellum of diabetic rats. Adult male Wistar rats were made diabetic by streptozotocin injection (65 mg/kg ip) and divided into four groups from diabetes onset: those receiving a daily sc injection of saline (1 ml/kg/day), GHRP-6 (150 ?g/kg/day), insulin (1-8U/day) or insulin plus GHRP-6 for 8 weeks. Control non-diabetic rats received saline (1 ml/kg/day). Diabetes increased cell death in the pituitary, hypothalamus and cerebellum (P<0.05). In the pituitary, insulin treatment prevented diabetes-induced apoptosis (P<0.01), as well as the decline in prolactin and GH mRNA levels (P<0.05). In the hypothalamus, neither insulin nor GHRP-6 decreased diabetes-induced cell death. However, the combined treatment of insulin+GHRP-6 prevented the diabetes induced-decrease in glial fibrillary acidic protein (GFAP) levels (P<0.05). In the cerebellum, although insulin treatment increased GFAP levels (P<0.01), only the combined treatment of insulin+ GHRP-6 decreased diabetes-induced apoptosis (P<0.05). In conclusion, insulin and GHRP-6 exert tissue specific effects in STZ-diabetic rats and act synergistically on some processes. Indeed, insulin treatment does not seem to be effective on preventing some of the diabetes-induced alterations in the central nervous system. PMID:21352888

Granado, Miriam; García-Cáceres, Cristina; Tuda, María; Frago, Laura M; Chowen, Julie A; Argente, Jesús

2011-04-30

52

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

PubMed Central

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

2014-01-01

53

Impairment of baroreflex control of heart rate and structural changes of cardiac ganglia in conscious streptozotocin (STZ)-induced diabetic mice  

Microsoft Academic Search

Baroreflex control of heart rate (HR) is impaired in human diabetes mellitus and in large experimental models. However, baroreflex impairment in diabetic mouse models and diabetes-induced remodeling of baroreflex circuitry are not well studied. We examined the impairment of baroreflex control of heart rate (HR) and assessed structural remodeling of cardiac ganglia in the streptozotocin (STZ)-induced diabetic mouse model. FVB

Min Lin; Jing Ai; Scott W. Harden; Chenghui Huang; Lihua Li; Robert D. Wurster

2010-01-01

54

High Pancreatic n-3 Fatty Acids Prevent STZ-Induced Diabetes in Fat-1 Mice: Inflammatory Pathway Inhibition  

PubMed Central

OBJECTIVE Because of confounding factors, the effects of dietary n-3 polyunsaturated fatty acids (PUFA) on type 1 diabetes remain to be clarified. We therefore evaluated whether fat-1 transgenic mice, a well-controlled experimental model endogenously synthesizing n-3 PUFA, were protected against streptozotocin (STZ)-induced diabetes. We then aimed to elucidate the in vivo response at the pancreatic level. RESEARCH DESIGN AND METHODS ?-Cell destruction was produced by multiple low-doses STZ (MLD-STZ). Blood glucose level, plasma insulin level, and plasma lipid analysis were then performed. Pancreatic mRNA expression of cytokines, the monocyte chemoattractant protein, and GLUT2 were evaluated as well as pancreas nuclear factor (NF)-?B p65 and inhibitor of ?B (I?B) protein expression. Insulin and cleaved caspase-3 immunostaining and lipidomic analysis were performed in the pancreas. RESULTS STZ-induced fat-1 mice did not develop hyperglycemia compared with wild-type mice, and ?-cell destruction was prevented as evidenced by lack of histological pancreatic damage or reduced insulin level. The prevention of ?-cell destruction was associated with no proinflammatory cytokine induction (tumor necrosis factor-?, interleukin-1?, inducible nitric oxide synthase) in the pancreas, a decreased NF-?B, and increased I?B pancreatic protein expression. In the fat-1–treated mice, proinflammatory arachidonic-derived mediators as prostaglandin E2 and 12-hydroxyeicosatetraenoic acid were decreased and the anti-inflammatory lipoxin A4 was detected. Moreover, the 18-hydroxyeicosapentaenoic acid, precursor of the anti-inflammatory resolvin E1, was highly increased. CONCLUSIONS Collectively, these findings indicate that fat-1 mice were protected against MLD-STZ–induced diabetes and pointed out for the first time in vivo the beneficial effects of n-3 PUFA at the pancreatic level, on each step of the development of the pathology—inflammation, ?-cell damage—through cytokine response and lipid mediator production.

Bellenger, Jerome; Bellenger, Sandrine; Bataille, Amandine; Massey, Karen A.; Nicolaou, Anna; Rialland, Mickael; Tessier, Christian; Kang, Jing X.; Narce, Michel

2011-01-01

55

Reversal of neurobehavioral and neurochemical alterations in STZ-induced diabetic rats by FeTMPyP, a peroxynitrite decomposition catalyst and 1,5-Isoquinolinediol a poly(ADP-ribose) polymerase inhibitor.  

PubMed

Objective: In this study, we have evaluated the involvement of nitrosative stress and poly-ADP ribosyl polymerase (PARP) in diabetes induced neurobehavioral and neurochemical changes using pharmacological agents peroxynitrite decomposition catalyst (FeTMPyP) and a PARP inhibitor (1,5-Isoquinolinediol) in diabetic brains. Methods: The extent of neurobehavioral changes was assessed by functional observation battery, motor coordination activity (rota rod performance) and passive avoidance test. Neurochemical changes were assessed by measuring nicotinamide adenine dinucleotide (NAD), malondialdehyde, acetylcholinesterase, neurotransmitters (GABA and glutamate) levels in the hippocampus. GABA and glutamate were measured by high-performance liquid chromatography with electrochemical detection method. Results: Two weeks' treatment with FeTMPyP (3 mg/kg, i.p.) and 1,5-Isoquinolinediol (3 mg/kg, i.p.) improved the cognitive deficits in diabetic rats as observed in passive avoidance test. Both the agents inhibited lipid peroxidation and improves the acetylcholinesterase level in the hippocampus. 1,5-Isoquinolinediol treatment also improves the NAD, neurotransmitter level in the hippocampus. Discussion: These results suggest that peroxynitrite decomposition catalyst and PARP inhibitor have beneficial effects in neurobehavioral alterations induced by diabetes. Improvement in neurobehavioral alteration may be attributed to reversal of neurotransmitter homeostasis deficits. PMID:24620961

Jangra, Ashok; Datusalia, Ashok Kumar; Sharma, Shyam Sunder

2014-07-01

56

Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary, hypothalamus and cerebellum of streptozotocin (STZ)-induced diabetic rats  

Microsoft Academic Search

Poorly controlled type1 diabetes is associated with hormonal imbalances and increased cell death in different tissues, including the pituitary, hypothalamus and cerebellum. In the pituitary, lactotrophs are the cell population with the greatest increase in cell death, whereas in the hypothalamus and cerebellum astrocytes are most highly affected. Insulin treatment can delay, but does not prevent, diabetic complications. As ghrelin

Miriam Granado; Cristina García-Cáceres; María Tuda; Laura M. Frago; Julie A. Chowen; Jesús Argente

2011-01-01

57

Effects of thyroid hormone on the sorbitol pathway in streptozotocin-induced diabetic rats  

Microsoft Academic Search

Sorbitol accumulation plays an important role in diabetic complications involving the kidney, nerves, retina, lens and cardiac muscle. To investigate the influence of thyroid hormone on the sorbitol pathway, we studied the effects of thyroid hormone on polyol metabolism in normal and diabetic rats. Rats were divided into three groups: controls, streptozotocin (STZ)-induced diabetic euthyroid rats (DM) and STZ-induced diabetic

Rikio Shinohara; Toshiki Mano; Akio Nagasaka; Yoshikuni Sawai; Keiko Uchimura; Ritsuko Hayashi; Nobuki Hayakawa; Mutsuko Nagata; Masaki Makino; Hiroaki Kakizawa; Yasutoshi Itoh; Akira Nakai; Mitsuyasu Itoh

1998-01-01

58

Antidiabetic Activity of the Orally Effective Vanadyl-Poly (?-Glutamic Acid) Complex in Streptozotocin(STZ)-induced Type 1 Diabetic Mice  

Microsoft Academic Search

Newly synthesized vanadyl-poly(?-glutamic acid) complex (VO-?-PGA) with a VO(O4) coordination mode was found to have potent antidiabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice (STZ-mice), compared with that of a solution containing only vanadyl sulfate, VOSO 4. This was the first example of orally active vanadyl complex of ?-PGA for treating STZ-mice. To better define its efficacy, we examined

Subarna Karmaker; Tapan Kumar Saha; Hiromu Sakurai

2008-01-01

59

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.

Lee, Chae-Won; Han, Ji-Sook

2012-01-01

60

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

Microsoft Academic Search

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

Sandhya L Sitasawad; Yogita Shewade; Ramesh Bhonde

2000-01-01

61

Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat  

Microsoft Academic Search

This study investigated the beneficial effects and mechanism of action of the juice of Momordica charantia in streptozotocin (STZ)-induced diabetes mellitus in rats. Diabetes mellitus was associated with significant (p p M. charantia juice by STZ-induced diabetic rats partially reversed all the diabetes-induced effects measured. Daily oral administration of M. charantia juice to STZ-induced diabetic rates significantly (p +- and

I. Ahmed; E. Adeghate; E. Cummings; A. K. Sharma; J. Singh

2004-01-01

62

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.

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

2013-01-01

63

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

PubMed Central

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

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

2012-01-01

64

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

PubMed

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

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

2013-04-01

65

Effects of Fomes fomentarius supplementation on antioxidant enzyme activities, blood glucose, and lipid profile in streptozotocin-induced diabetic rats  

Microsoft Academic Search

The effect of water extract of Fomes fomentarius (WEFF) on hepatic antioxidant enzyme activities, blood glucose, and lipid profile in streptozotocin (STZ)-induced diabetic rats was examined. Male Sprague-Dawley rats were divided into nondiabetic, diabetic, and diabetic WEFF-supplemented groups. Water extract of Ffomentarius (100 mg\\/kg BW) was orally administered once a day for 2 weeks.Administering WEFF to STZ-induced diabetic rats lowered

Jeong-Sook Lee

2005-01-01

66

Effects of Streptozotocin-Induced Diabetes on Kv Channels in Rat Small Coronary Smooth Muscle Cells  

Microsoft Academic Search

Diabetes impairs endothelium dependent vasodilation, but the mechanism of endothelium independent dilation is not well understood. In the present study, we examined the effect of streptozotocin (STZ)-induced diabetes on the vasomotor of small coronary artery and the activity of voltage-dependent K + channel of vascular smooth muscle cells in STZ rat using the videomicroscopy and patch clamp method. STZ-induced diabetes

Qiang Chai; Zhixiang Liu; Lianbi Chen

2005-01-01

67

Anti-hyperglycemic and anti-oxidative activities of ginseng polysaccharides in STZ-induced diabetic mice.  

PubMed

Neutral (WGPN) and acidic (WGPA) polysaccharides were fractionated from ginseng polysaccharide. WGPN and WGPA decreased fasting blood glucose by different manners of administration. Intra-gastric administration of WGPA showed a marked hypoglycemic effect, which may be related to its anti-oxidative activity. The results indicated that WGPA may have anti-diabetic potential. PMID:24671219

Sun, Chengxin; Chen, Yan; Li, Xinzhi; Tai, Guihua; Fan, Yuying; Zhou, Yifa

2014-04-23

68

Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced diabetic nephropathy.  

PubMed

A range of in vitro, experimental and clinical intervention studies have implicated an important role for hyperglycaemia-induced activation of the renin-angiotensin system (RAS) in the development and progression of diabetic nephropathy (DN). Blockade of RAS by angiotensin converting enzyme (ACE) inhibitors is an effective strategy in treating diabetic kidney diseases. However, few studies demonstrate the mechanism by which hyperglycaemia up-regulates the expression of ACE gene. Our previous studies have identified a novel curcumin analogue, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66), which could inhibit the high glucose (HG)-induced phosphorylation of mitogen-activated protein kinases in mouse macrophages. In this study, we found that the renal protection of C66 in diabetic mice was associated with mitogen-activated protein kinase (MAPK) inactivation and ACE/angiotensin II (Ang II) down-regulation. Generally, MAPKs have been considered as a downstream signalling of Ang II and a mediator for Ang II-induced pathophysiological actions. However, using C66 and specific inhibitors as small molecule probes, in vitro experiments demonstrate that the MAPK signalling pathway regulates ACE expression under HG stimulation, which contributes to renal Ang II activation and the development of DN. This study indicates that C66 is a potential candidate of DN therapeutic agents, and more importantly, that reduction in ACE expression by MAPKs inhibition seems to be an alternative strategy for the treatment of DN. PMID:24330074

Pan, Yong; Huang, Yi; Wang, Zhe; Fang, Qilu; Sun, Yusheng; Tong, Chao; Peng, Kesong; Wang, Yangwei; Miao, Lining; Cai, Lu; Zhao, Yunjie; Liang, Guang

2014-02-01

69

Viscoelastic Behavior of Small Intestine in Streptozotocin-Induced Diabetic Rats  

Microsoft Academic Search

Diabetes is associated with remodeling of the morphology and elastic properties of the small intestine. This study aims to study remodeling of the viscoelastic (time-dependent) properties of the small intestine during experimental diabetes. Stress relaxation tests were performed on the duodenum, jejunum, and ileum in 10 nondiabetic and 28 streptozotocin (STZ) -induced diabetic rats. The rats were made diabetic by

Jingbo Zhao; Donghua Liao; Jian Yang; Hans Gregersen

2003-01-01

70

Erythropoietin and its Carbamylated Derivative Prevent the Development of Experimental Diabetic Autonomic Neuropathy in STZ-Induced Diabetic NOD-SCID Mice  

PubMed Central

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.

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

2008-01-01

71

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

72

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

PubMed Central

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

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

2014-01-01

73

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

PubMed Central

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

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

2013-01-01

74

Pharmacodynamic interaction of Momordica charantia with rosiglitazone in rats  

Microsoft Academic Search

The present study was undertaken to determine the interaction of rosiglitazone, a PPAR-? agonist with methanolic extract of Momordica charantia L (MC), an herbal drug used widely as an antidiabetic agent. The pharmacodynamic interaction was evaluated in oral glucose tolerance test, streptozotocin (STZ) induced diabetes in adult rats and STZ induced diabetes in neonatal rats. Rosiglitazone was given orally at

Susan Nancy Nivitabishekam; Mohammed Asad; V. Satya Prasad

2009-01-01

75

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

76

Rutin improves the antioxidant status in streptozotocin-induced diabetic rat tissues  

Microsoft Academic Search

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

N. Kamalakkannan; P Stanely Mainzen Prince

2006-01-01

77

Nicorandil improves diabetes and rat islet beta-cell damage induced by streptozotocin in vivo and in vitro  

Microsoft Academic Search

Objective: N-(2-hydroxyethyl)-nicotinamide nitrate (nicorandil) is a unique anti-anginal agent, reported to act as both an ATP-sensitive Kþ channel opener (PCO) and a nitric oxide donor. It also has an anti-oxidant action. We examined the effects of nicorandil on streptozotocin (STZ)-induced islet b-cell damage both in vivo and in vitro. Design and methods: STZ-induced diabetic Brown Norway rats (STZ-DM) were fed

K Kasono; T Yasu; A Kakehashi; N Kinoshita; H Tamemoto; K Namai; R Ohno; H Ueba; M Kuroki; S Ishikawa; M Kawakami

2004-01-01

78

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.

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

2012-01-01

79

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

PubMed

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

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

2008-01-01

80

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

Microsoft Academic Search

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:

Mohamed D Morsy; Waleed N Hassan; Sherif I Zalat

2010-01-01

81

Antihyperglycemic Effect of Ginkgo biloba Extract in Streptozotocin-Induced Diabetes in Rats  

PubMed Central

The Ginkgo biloba extract (GBE) has been reported to have a wide range of health benefits in traditional Chinese medicine. The aim of this study was to evaluate the antihyperglycemic effects of GBE on streptozotocin- (STZ-) induced diabetes in rats. Diabetes was induced in male Wistar rats by the administration of STZ (60?mg/kg b.w.) intraperitoneally. GBE (100, 200, and 300?mg/kg b.w.) was administered orally once a day for a period of 30 days. Body weight and blood glucose levels were determined in different experimental days. Serum lipid profile and antioxidant enzymes in hepatic and pancreatic tissue were measured at the end of the experimental period. Significant decreases in body weight and antioxidant ability and increases in blood glucose, lipid profile, and lipid peroxidation were observed in STZ-induced diabetic rats. The administration of GBE and glibenclamide daily for 30 days in STZ-induced diabetic rats reversed the above parameters significantly. GBE possesses antihyperglycemic, antioxidant, and antihyperlipidemia activities in STZ-induced chronic diabetic rats, which promisingly support the use of GBE as a food supplement or an adjunct treatment for diabetics.

Cheng, Daye; Liang, Bin; Li, Yunhui

2013-01-01

82

Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide bioavailability in diabetic rat aortas  

Microsoft Academic Search

The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w\\/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg?1 body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin

Ajay Machha; Francis I. Achike; Ali Mohd Mustafa; Mohd Rais Mustafa

2007-01-01

83

Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats  

Microsoft Academic Search

Momordica charantia (karela) is commonly used as an antidiabetic and antihyperglycemic agent in Asian, Oriental and Latin American countries. This study was undertaken to investigate the effects of long term feeding (10 weeks) of M. charantia fruit extract on blood plasma and tissue lipid profiles in normal and streptozotocin (STZ) -induced Type 1 diabetic rats. The results show that there

I. Ahmed; M. S. Lakhani; M. Gillett; A. John; H. Raza

2001-01-01

84

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.

Pandhare, Ramdas; Sangameswaran, Balakrishnan

2012-01-01

85

Protective effect of high-dose thiamine (B 1 ) on rat detrusor contractility in streptozotocin-induced diabetes mellitus  

Microsoft Academic Search

We investigated the effect of thiamine (B1) treatment on bladder dysfunction in streptozotocin (STZ)-induced diabetic rats.\\u000a A total of 40 rats were randomly divided into four groups: a control group, a group given thiamine only, a diabetic group\\u000a and a diabetic group given thiamine therapy. Diabetes was induced in the rats by 65 mg\\/kg STZ via an intraperitoneal injection.\\u000a Thiamine

A. Yenilmez; M. Özçifçi; Y. Aydin; M. Turgut; K. Uzuner; A. Erkul

2006-01-01

86

Efficacy of ethanolic extract of ginger on kidney lipid metabolic profiles in diabetic rats  

Microsoft Academic Search

The present study was carried out to investigate the antihyperglycemic and hypolipidemic effect of ginger in streptozotocin\\u000a (STZ)-induced diabetic rats. Forty two male wistar rats were divided into seven groups and treatment was given as stated in\\u000a experimental protocol. The two doses (100 mg\\/kg and 200 mg\\/kg bw) of ginger on blood glucose levels in diabetic rats were\\u000a studied and the levels

Shanmugam Kondeti Ramudu; K. Mallikarjuna; Sathyavelu Reddy Kesireddy

87

Generation of Nitric Oxide from Streptozotocin (STZ) in the Presence of Copper(II) plus Ascorbate: Implication for the Development of STZ-Induced Diabetes  

Microsoft Academic Search

Streptozotocin (STZ) is widely used as a strong inducer of insulin-dependent diabetes in experimental animals. Although nitric oxide (NO) generation from STZ has been proposed to be responsible for the toxicity of pancreatic B-cells, the mechanism is yet unknown. We found that STZ generates NO in the presence of Cu(II) plus ascorbate. In addition, nicotinamide, which is an antidiabetic agent

Akihiro Tsuji; Hiromu Sakurai

1998-01-01

88

Nicorandil attenuates endothelial VCAM?1 expression via thioredoxin production in diabetic rats induced by streptozotocin.  

PubMed

The anti?angina agent nicorandil has been reported to be beneficial even in patients who have angina with diabetes. However, the mechanism underlying the effect of nicorandil in patients with diabetes remains to be elucidated. In this study, the protective effect of nicorandil on thioredoxin (TRX) protein was investigated, as TRX is a multifunctional endogenous redox regulator that protects cells against various types of cellular and tissue stress. This study was conducted to examine whether nicorandil induces the expression of TRX for the protection against diabetic damage in the vascular tissue of rats. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (STZ) (fasting glucose levels in STZ?induced rats were >14 mmol/l). Diabetic rats were divided into a diabetic control and a nicorandil?treated group. Nicorandil was administered at a dosage of 15 mg/kg/day by gavage feeding. After five weeks of nicorandil administration, blood samples were obtained from the angular vein to measure levels of stress markers, serum superoxide dismutase and malondialdehyde, using the ELISA. The expression of TRX in STZ?induced rat vascular tissue was analyzed by immunohistochemistry, quantitative polymerase chain reaction (qPCR) and western blot analysis. The oral administration of nicorandil induced TRX protein and mRNA expression in the vascular tissue of STZ?induced diabetic rats. In the diabetic control group, the levels of stress were markedly higher than those in the nicorandil?treated group, indicating that nicorandil reduces oxidative stress in serum. In addition to inducing TRX expression, nicorandil attenuated the expression of the vascular cell adhesion molecule?1 (VCAM?1) in diabetic rat vascular endothelial cells. In conclusion, nicorandil attenuates the formation of reactive oxygen species and induces TRX protein expression, consequently resulting in the suppression of VCAM?1 secretion in the vascular endothelial cells of STZ?induced diabetic rats. PMID:24676284

Liu, Lihua; Liu, Yun; Qi, Benling; Wu, Qinqin; Li, Yuanyuan; Wang, Zhaohui

2014-06-01

89

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

Microsoft Academic Search

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

Mamiko Hie; Masumi Shimono; Kayoko Fujii; Ikuyo Tsukamoto

2007-01-01

90

Expression of basic fibroblast growth factor, protein kinase C and members of the apoptotic pathway in skeletal muscle of streptozotocin-induced diabetic rats.  

PubMed

This study investigated the potential mechanisms that may underlie diabetes induced amyoatrophy. Sprague-Dawley rats were either injected intraperiotneally with STZ (test group; N=8) to induce diabetic-like symptoms (blood glucose level ?16.65mmol/L) or with buffer (control group; N=8). Differences in muscle structure between the STZ-induced diabetic and control groups were evaluated by histochemistry. Protein and mRNA levels of basic FGF (bFGF), bax, bcl-2, and caspase 3 in skeletal muscle were compared between the 2 groups using immunohistochemistry and quantitative PCR, respectively. Serum level of insulin and protein kinase C (PKC) were measured by competitive RIA and ELISA, respectively. Unlike control animals, the skeletal muscle fibers from STZ-induced diabetic animals were broken and pyknotic, the sarcomeric structure disrupted, and mild hyperplasia of interstitial adipose tissues was detected. The serum level of PKC was higher (P=0.003) and the protein and mRNA levels of bFGF in skeletal muscle were lower (P=0.001) in STZ-induced diabetic versus control animals. Protein and mRNA levels of the apoptosis promoting genes caspase-3 and bax were higher in skeletal muscle from STZ-induced diabetic rats as compared to control animals (P<0.001 and P=0.037, respectively), while mRNA and protein levels of bcl-2, an inhibitor of apoptosis, was lower in STZ-induced diabetic rats versus control animals (P=0.026). Increasing apoptosis in skeletal muscle from STZ-induced diabetic rats was further demonstrated by TNNEL assay. Our findings suggest that enhanced PKC levels, reduction of bFGF expression, and increased in apoptosis might be associated with the development of diabetes-induced myoatrophy. PMID:24008114

Xiang, Jingyan; Zhao, Yuwu; Chen, Jingjiong; Zhou, Jian

2014-02-01

91

Protective effects of chronic melatonin treatment against renal injury in streptozotocin-induced diabetic rats.  

PubMed

The aim of this study was to investigate the effects of melatonin as an antioxidant, on prevention and treatment of streptozotocin (STZ)-induced diabetic renal injury in rats. Male Wistar rats were divided into four groups: (1) untreated, (2) melatonin-treated, (3) untreated diabetic (UD), (4) melatonin-treated diabetic (MD). Experimental diabetes was induced by single dose (60 mg/kg, i.p.) STZ injection. For 3 days prior to administration of STZ, melatonin was injected (200 microg/kg/day, i.p.); these injections were continued until the end of the study (4 weeks). Malondialdehyde (MDA) levels as a marker of lipid peroxidation were significantly increased in the renal homogenates of UD animals and decreased after melatonin administration. The activity of the antioxidative enzyme glutathione peroxidase (GSH-Px) was significantly reduced in UD rats. Melatonin treatment reversed STZ-induced reduction of GSH-Px activity without having an effect on blood glucose. Upon histopathological examination, it was observed that the melatonin treatment prevented the renal morphological damage caused by diabetes. Upon immunohistochemical investigation, glomerular anti-laminin beta1 staining decreased in MD rats. Additionally, no tubular anti-IGF-1 staining was observed in melatonin-treated rats. In conclusion, chronically administered melatonin reduced renal injury in STZ-induced diabetic rats and thus it may provide a useful therapeutic option in humans to reduce oxidative stress and the associated renal injury in patients with diabetes mellitus. PMID:12932206

Cam, Meryem; Yavuz, Ozlem; Guven, Aysel; Ercan, Feriha; Bukan, Neslihan; Ustündag, Nil

2003-10-01

92

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

Microsoft Academic Search

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

Ranganathan Babujanarthanam; Purushothaman Kavitha; Moses Rajasekara Pandian

93

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

94

Antihyperlipidemic effect of Eugenia jambolana seed kernel on streptozotocin-induced diabetes in rats  

Microsoft Academic Search

Abnormalities in lipid profile are one of the most common complications in diabetes mellitus, which is found in about 40% of diabetics. In the present study, anti-hyperlipidemic efficacy of Eugenia jambolana seed kernel (EJs-kernel) was evaluated in streptozotocin (STZ)-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide. The effect of oral administration of ethanolic extract of

Kasiappan Ravi; Subbaih Rajasekaran; Sorimuthu Subramanian

2005-01-01

95

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

96

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

PubMed

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

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

2014-04-01

97

Mechanism of exocrine pancreatic insufficiency in streptozotocin-induced diabetes mellitus in rat: Effect of cholecystokinin-octapeptide  

Microsoft Academic Search

This study investigated the effects of cholecystokinin-octapeptide (CCK-8) on pancreatic juice flow and its contents, and on cytosolic calcium (Ca2+) and magnesium (Mg2+) levels in streptozotocin (STZ)-induced diabetic rats compared to healthy age-matched controls. Animals were rendered diabetic by a single injection of STZ (60 mg kg–1, I.P.). Age-matched control rats obtained an equivalent volume of citrate buffer. Seven weeks

R. Patel; M. D. Yago; M. Mañas; E. M. Victoria; A. Shervington; J. Singh

2004-01-01

98

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

Microsoft Academic Search

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

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

2007-01-01

99

Treadmill exercise inhibits apoptotic neuronal cell death with suppressed vascular endothelial growth factor expression in the retinas of the diabetic rats  

PubMed Central

Diabetic retinopathy is one of the most important microvascular complications in diabetes, and it is the major cause of visual loss. Physical exercise is known to ameliorate the symptoms of metabolic syndromes such as diabetic mellitus. In the present study, we investigated the effects of treadmill exercise on vascular endothelial growth factor (VEGF) expression and apoptotic cell death in the retinas of streptozotocin (STZ)-induced diabetic rats. The male Sprague-Dawley rats were randomly divided into three groups (n = 10 in each group): control group, STZ-induce diabetes group, STZ-induced diabetes and treadmill exercise group. To induce diabetes in the experimental animals, a single intraperitioneal injection of STZ (50 mg/kg) was given to each animal. The rats in the exercise group were forced to run on a motorized treadmill for 30 min once a day during 1 week starting 6 weeks after STZ injection. In the present results, VEGF expression in the retinas was increased by induction of diabetes. The numbers of caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the retinas were also enhanced by induction of diabetes. Treadmill exercise significantly decreased VEGF expression and suppressed the number of TUNEL-positive and caspase-3-positive cells in the retinas of diabetic rats. In the present study, we have shown that treadmill exercise might alleviate the progression of diabetic retinopathy through suppressing VEGF expression and apoptotic cell death in the retinas of the diabetic rats.

Ji, Eun-Sang; Ko, Il-Gyu; Cho, Jung-Wan; Davis, Ronald W.; Hwang, Gwang-Yon; Jee, Yong-Seok; Lim, Baek-Vin

2013-01-01

100

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

PubMed Central

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

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

2014-01-01

101

Hypoglycemic activity of Urtica pilulifera in streptozotocin-diabetic rats.  

PubMed

The hypoglycemic activity of lectin isolated from Urtica pilulifera L. seeds (Urticaceae) was investigated in streptozotocin (STZ) induced diabetic rats. Significant hypoglycemic effect was found at the dose of 100 mg/kg after i.p. administration for 30 days. Blood glucose (BG) level, food and fluid intake, body weight (BW) loss and histopathologic findings of the normal and diabetic animals were evaluated. The group treated with UPSL (U. pilulifera seed lectin) was also compared against glipizide (oral antidiabetic agent, Carlo-Erba) as a standard. PMID:12648821

Kavalali, G; Tuncel, H; Göksel, S; Hatemi, H H

2003-02-01

102

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

PubMed

The antihyperglycemic effect of a water extract (WE) and an alkali extract (AE) of the Fomitopsis pinicola fruit body was studied in streptozotocin (STZ)-induced diabetic rats. The STZ-induced diabetes mellitus (DM) control group lost a significant amount of body weight, whereas the normal control group (NC) gained weight; however, the DM-AE group gained a significant amount of weight, with weight gain approaching normal. Feed intake by the DM-AE group was also similar to the NC group. The liver and kidney weights per body weight increased with the STZ treatment; however, the weights were lower in the F. pinicola-treated groups and nearly normalized in the DM-AE group. The weights of the heart, lungs, and spleen were not influenced by the STZ treatment. Blood glucose levels of F. pinicola-treated DM groups were significantly lower than that of the DM group. In particular, STZ-induced hyperglycemia was remarkably inhibited by the AE-supplemented diet. Serum insulin levels were decreased with STZ injection; however, the decreased levels were almost restored to the NC level with F. pinicola supplementation. The increased serum fructosamine levels associated with hyperglycemia were decreased with the F. pinicola treatment. Cells of the pericentral regions were found to have significant swelling, and some necrotic cells were observed in the pancreas of DM animals; however, pancreatic tissue damage by STZ in the F. pinicola-supplemented diet groups was ameliorated. In this study, the AE from F. pinicola showed the highest antidiabetic effect among the treatments. These results indicate that constituents of F. pinicola may regulate hyperglycemia via either increased insulin secretion during recovery or the prevention of STZ-induced pancreatic damage. This is the first report of antihyperglycemic effects of F. pinicola in STZ-induced DM rats. PMID:18800901

Lee, Sang-Il; Kim, Jeong-Sook; Oh, Sung-Hee; Park, Kun-Young; Lee, Hyun-Goo; Kim, Soon-Dong

2008-09-01

103

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.

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

2011-01-01

104

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

PubMed

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

105

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

Microsoft Academic Search

The present study was designed to investigate the hypoglycemic and hypolipidemic activities of the semi–purified fractions of an ethanolic leaf extract of Averrhoa bilimbi (ABe) in high fat diet (HFD)–streptozotocin (STZ)–induced diabetic rats. Male Sprague–Dawley rats aged 10 weeks (200–250 g) were fed with a high fat diet obtained from Glen Forrest stock feeders (Western Australia) for 2 weeks prior

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

2005-01-01

106

Impaired duodenal bicarbonate secretion in diabetic rats. Salutary effect of nitric oxide synthase inhibitor  

Microsoft Academic Search

We previously reported the impaired HCO3? secretion and the increased mucosal susceptibility to acid in the duodenum of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated the salutary effect of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) on these changes and compared it with those of insulin. Animals were injected streptozotocin (STZ: 70 mg\\/kg, ip) and used after

K Takeuchi; T Hirata; R Korolkiewicz; Y Sugawa; M Kubomi

1997-01-01

107

Role of inducible nitric oxide synthase in induction of RhoA expression in hearts from diabetic rats  

Microsoft Academic Search

Aims Recent studies from our laboratory demonstrated that increased expression of the small GTP- binding protein RhoA and activation of the RhoA\\/rho kinase (ROCK) pathway play an important role in the contractile dysfunction associated with diabetic cardiomyopathy in hearts from streptozotocin (STZ)-induced diabetic rats. Nitric oxide (NO) has been reported to be a positive regulator of RhoA expression in vascular

Hesham Soliman; Graham P. Craig; Prabhakar Nagareddy; Violet G. Yuen; Guorong Lin; Ujendra Kumar; John H. McNeill; Kathleen M. MacLeod

2008-01-01

108

Alleviation of Oxidative Damage in Multiple Tissues in Rats with Streptozotocin-Induced Diabetes by Rice Bran Oil Supplementation  

Microsoft Academic Search

The possibility of 8-hydroxy-2'-deoxyguanosine (8-OHdG) serving as a sensitive biomarker of oxidative DNA damage and oxidative stress was investigated. Reactive oxygen species (ROS) have been reported to be a cause of diabetes induced by chemicals such as streptozotocin (STZ) in experimental animals. In this study, we examined oxidative DNA damage in multiple tissues in rats with STZ-induced diabetes by measuring

Rong-Hong Hsieh; Li-Ming Lien; Shyh-Hsiang Lin; Chia-Wen Chen; Huei-Ju Cheng; Hsing-Hsien Cheng

2005-01-01

109

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

110

Protective Effects of Simvastatin, a Lipid Lowering Agent, against Oxidative Damage in Experimental Diabetic Rats  

PubMed Central

The present study was undertaken to evaluate the possible protective effects of simvastatin (SMV) against oxidative stress in streptozotocin- (STZ)-induced diabetic rats. Diabetes was induced experimentally in rats by i.p. injection of STZ in a dose of 60?mg/kg bwt. After 5 weeks of STZ injection, there were apparent reductions in the animal body weight and significant increase in blood glucose, HbA1c, urea, creatinine, AST, ALT, and lipid profiles with a concomitant decrease in total hemoglobin, plasma glutathione and vitamin C as compared to the control group. The treatment with SMV at a dose (10?mg/kg, orally) normalized all the above-mentioned biochemical parameters in STZ-induced diabetic rats. In vitro studies confirmed the free radical scavenging and antioxidant activity of SMV. Therefore, the present results revealed that SMV has a protective effect against STZ-induced oxidative damage by scavenging the free radicals generation and restoring the enzymatic and nonenzymatic antioxidant systems.

Mohamadin, Ahmed M.; Elberry, Ahmed A.; Abdel Gawad, Hala S.; Morsy, Gehan M.; Al-Abbasi, Fahad A.

2011-01-01

111

Influence of umbelliferone on membrane-bound ATPases in streptozotocin-induced diabetic rats.  

PubMed

The activities of membrane-bound ATPases are altered both in erythrocytes and tissues of streptozotocin (STZ)-induced diabetic rats and diabetic patients. Umbelliferone (UMB), a natural antioxidant, is a benzopyrone occurring in nature, and it is present in the fruits of golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). Earlier we evaluated and reported the effect of UMB on plasma insulin and glucose, and this study was designed to evaluate the effect of umbelliferone on membrane-bound ATPases in erythrocytes and tissues (liver, kidney and heart) of STZ-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180-200 g, were made diabetic by an intraperitonial administration of STZ (40 mg/kg). Normal and diabetic rats were treated with UMB dissolved in 10% dimethyl sulfoxide (DMSO) and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In our study, diabetic rats had increased level of blood glucose and lipid peroxidation markers, and decreased level of plasma insulin and decreased activities of total ATPases, (Na(+)+K(+))-ATPase, low affinity Ca(2+)-ATPase and Mg(2+)-ATPase in erythrocytes and tissues. Restoration of plasma insulin and glucose by UMB and glibenclamide seemed to have reversed insulin, glucose and lipid peroxidation markers, and diabetes-induced alterations in the activities of membrane-bound ATPases. Thus, our results show that the normalization of membrane-bound ATPases in various tissues, is due to improved glycemic control and antioxidant activity by UMB. PMID:17652835

Ramesh, Balakrishnan; Pugalendi, Kodukkur V

2007-01-01

112

Treatment with AT 1 receptor blocker restores diabetes-induced alterations in intracellular Ca 2+ transients and contractile function of rat myocardium  

Microsoft Academic Search

We investigated the effect of treatment with an angiotensin II receptor blocker, candesartan-cilexetil, on the mechanical and electrophysiological properties of cardiomyocytes isolated from streptozotocin-induced diabetic (STZ) rats. Contractile activity and electrophysiological properties were measured in papillary muscle and ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 5mg\\/kg\\/day candesartan-cilexetil for 4 weeks. Alterations in the kinetics of contractile

Semir Ozdemir; Mehmet Ugur; Hakan Gürdal; Belma Turan

2005-01-01

113

Protective effects of the volatile oil of Nigella sativa seeds on ?-cell damage in streptozotocin-induced diabetic rats: a light and electron microscopic study  

Microsoft Academic Search

The aim of this study was to evaluate the possible protective effects of the volatile oil of Nigella sativa (NS) seeds on insulin immunoreactivity and ultrastructural changes of pancreatic ?-cells in STZ-induced diabetic rats. STZ\\u000a was injected intraperitoneally at a single dose of 50 mg\\/kg to induce diabetes. The rats in NS treated groups were given NS\\u000a (0.2 ml\\/kg) once a day

Mehmet Kanter; Meryem Akpolat; Cevat Aktas

2009-01-01

114

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

115

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.

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

2011-01-01

116

Preferential Elevation of Protein Kinase C Isoform betaII and Diacylglycerol Levels in the Aorta and Heart of Diabetic Rats: Differential Reversibility to Glycemic Control by Islet Cell Transplantation  

Microsoft Academic Search

In the present study, we have measured protein kinase C (PKC) specific activities and total diacylglycerol (DAG) level in the aorta and heart of rats, which showed that after 2 weeks of streptozotocin (STZ)-induced diabetes, membranous PKC specific activity and total DAG content were increased significantly by 88% and 40% in the aorta and by 21% and 72% in the

Toyoshi Inoguchi; Ruggero Battan; Eugene Handler; J. Richard Sportsman; William Heath; George L. King

1992-01-01

117

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

PubMed Central

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

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

2011-01-01

118

Reducing effect of matrix metalloproteinase inhibitors on serum triacylglycerol in streptozotocin-induced diabetic rats and Zucker fa/fa rats.  

PubMed

In the course of the investigation of effects of newly synthesized matrix metalloproteinase inhibitors (MMPIs), FYK-1388, FYK-1352 and F61-1008, which have strong and broad matrix metalloproteinase (MMP) inhibitory activity, on wound healing in streptozotocin (STZ)-induced diabetic rats, strong reducing effects on serum triacylglycerol (TG) have been found. Namely, when examined using breaking wound strength as an index, MMPIs did not significantly facilitate wound healing in STZ-induced diabetic rats. Unexpectedly, however, the treatment of STZ-induced diabetic rats with MMPIs markedly lowered the serum level of TG without changing the blood glucose level. Among these compounds tested, FYK-1388 was the most effective, and the compound reduced serum concentrations of TG and cholesterol and levels of very low-density lipoprotein (VLDL)-TG and low density lipoprotein (LDL)-cholesterol in a dose-dependent manner. FYK-1388 did not affect serum levels of free fatty acids, high-density lipoprotein (HDL)-cholesterol, aspartate aminotransferase and alanine aminotransferase, mass of body fat, liver weights, and hepatic contents of TG and cholesterol. Moreover, treatment of Zucker fa/fa rats with FYK-1388 lowered serum levels of TG and cholesterol without changing blood levels of glucose and insulin. Since the structures of these MMPIs markedly differ from those of the hypotriglyceridemic drugs that are used clinically, it seems plausible that these MMPIs could be used as a new type of hypotriglyceridemic drug. PMID:17666804

Morikawa, Tadanori; Toyama, Tomoaki; Kudo, Naomi; Kawashima, Yoichi

2007-08-01

119

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

PubMed

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

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

2009-07-01

120

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

2014-01-01

121

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

PubMed Central

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.

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

2014-01-01

122

Effects of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat  

Microsoft Academic Search

An investigation was made of the effect of Momordica charantia fruit juice on the distribution and number of ?, ? and ? cells in the pancreas of streptozotocin (STZ)-induced diabetic rats using immunohistochemical methods. The results indicated that there was a significant (Student's t-test, P<0.004) increase in the number of ? cells in M. charantia-treated animals when compared with untreated

I Ahmed; E Adeghate; A. K Sharma; D. J Pallot; J Singh

1998-01-01

123

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

PubMed Central

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

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

2014-01-01

124

Tissue specific expression and immunohistochemical localization of glutathione S-transferase in streptozotocin induced diabetic rats: Modulation by Momordica charantia (karela) extract  

Microsoft Academic Search

In streptozotocin (STZ)-induced diabetes, destruction of pancreatic beta-cell causes an acute shortage of insulin. Increased oxidative stress is believed to be one of the main factors in the etiology and complications of diabetes. In this study we have reported hyperglycemia and glutathione-associated oxidative stress in rats one week after treatment with STZ. In our previous studies, we have reported oxidative

Haider Raza; Ijaz Ahmed; Annie John

2004-01-01

125

Bitter melon extracts in diabetic and normal rats favorably influence blood glucose and blood pressure regulation.  

PubMed

Bitter melon (BM) was tested in normal and streptozotocin (STZ)-induced diabetic rats. First, normal and diabetic Wistar rats were given four test extracts (EX-1-EX-4) of a wild-genotype BM or metformin by intubation. Second, normal Sprague-Dawley rats were divided into control and three test groups given for 52 days one of three BM preparations in food: Chinese or Indian commercial preparations or EX-4 from experiment I. In experiment I, extracts of BM administered at 50 mg/kg of body weight in normal rats reduced blood sugar for 4 hours without, unlike metformin, inducing hypoglycemia. In STZ-induced diabetic rats, two extracts administered at 250 mg/kg decreased glucose levels to values comparable to metformin at 150 mg/kg. At 4 hours, EX-1 and EX-4 significantly reduced blood glucose 67% and 63%, respectively, compared with metformin's 54%. In experiment II, all test groups had lowered systolic, but not diastolic, blood pressure. The China and EX-4 arms had significantly lowered serum glucose levels compared with the control. In the glucose tolerance test, only EX-4 had significantly lowered glucose levels. Only EX-4 had significantly lowered angiotensin converting enzyme (ACE) activity. All active arms showed significance in the losartan challenge (the renin-angiotensin system [RAS]), with the greatest effect in the EX-4 group. In the N(?)-nitro-l-arginine-methyl ester challenge, only EX-4 exhibited a significant impact on the nitric oxide system, suggesting higher activity in this group. In the STZ-induced diabetic rat model, wild-type BM powerfully lowered glucose levels, and, in healthy adult rats, wild-type BM exhibited beneficial effects in the regulation of blood glucose, in RAS and ACE inhibition, and in nitric oxide generation. PMID:21861717

Clouatre, Dallas L; Rao, Sadanand N; Preuss, Harry G

2011-12-01

126

Ethanol extract of Butea monosperma bark modulates dyslipidemia in streptozotocin-induced diabetic rats.  

PubMed

Abstract Context: Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus (DM). The availability of multiple lipid-lowering drugs and supplements provides new opportunities for patients to regulate lipid levels. Objective: The present study was designed to evaluate the effect of Butea monosperma Lam. (Fabaceae) bark extract in diabetes-induced dyslipidemia. Materials and methods: A daily dose of B. monosperma bark extract (BMBE, 500?mg/kg body weight) was given orally to streptozotocin (STZ)-induced diabetic rats for 60?d. Several indices such as blood glucose, insulin, glycosylated hemoglobin, TC, TG, high-density lipoprotein-cholesterol (HDL-C), apo A1, apo B, activities of lipogenic enzymes in tissues, liver function tests, and histopathology of liver were analyzed to assess the modulation of STZ-induced diabetic dyslipidemia by B. monosperma bark. Results: BMBE significantly reduced blood glucose (40.79%) and increased plasma insulin (37.5%) levels in diabetic rats. Altered levels of serum lipids, lipoproteins, and activities of lipogenic enzymes in tissues were partially restored upon the administration of BMBE in diabetic rats. Liver function tests and histopathological examination revealed that consumption of BMBE at a dose of 500?mg/kg body weight had no toxic effects in experimental rats. Conclusion: The findings suggest that BMBE supplementation could ameliorate dyslipidemia in DM. PMID:24617860

Divya, B T; Mini, S

2014-08-01

127

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

PubMed Central

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

2011-01-01

128

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

Microsoft Academic Search

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

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

1999-01-01

129

Postprandial Hyperlipidemia in Streptozotocin-Induced Diabetic Rats Is Due to Abnormal Increase in Intestinal Acyl Coenzyme A:Cholesterol Acyltransferase Activity  

Microsoft Academic Search

Postprandial hyperlipidemia (PH) is recognized as a significant risk factor for cardiovascular disease. The present study, involving rats with streptozotocin (STZ)-induced diabetes, was performed to establish a PH model and to examine the relation between small intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and serum lipid levels in the postprandial state. The small intestinal ACAT activities in normal rats during the

Jun Kusunoki; Katsumi Aragane; Tetsuya Kitamine; Hideki Kozono; Kyoko Kano; Kouji Fujinami; Kazuhiro Kojima; Tsuyoshi Chiwata; Yasuo Sekine

2010-01-01

130

Effects of diabetes on ryanodine receptor Ca release channel (RyR2) and Ca2+ homeostasis in rat heart.  

PubMed

The defects identified in the mechanical activity of the hearts from type 1 diabetic animals include alteration of Ca2+ signaling via changes in critical processes that regulate intracellular Ca2+ concentration. These defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channel (RyR2). The present study was designed to determine whether the properties of the Ca2+ sparks might provide insight into the role of RyR2 in the altered Ca2+ signaling in cardiomyocytes from diabetic animals when they were analyzed together with Ca2+ transients. Basal Ca2+ level as well as Ca2+-spark frequency of cardiomyoctes isolated from 5-week streptozotocin (STZ)-induced diabetic rats significantly increased with respect to aged-matched control rats. Ca2+ transients exhibited significantly reduced amplitude and prolonged time courses as well as depressed Ca2+ loading of sarcoplasmic reticulum in diabetic rats. Spatio-temporal properties of the Ca2+ sparks in cardiomyocytes isolated from diabetic rats were also significantly altered to being almost parallel to the changes of Ca2+ transients. In addition, RyR2 from diabetic rat hearts were hyperphosphorylated and protein levels of both RyR2 and FKBP12.6 depleted. These data show that STZ-induced diabetic rat hearts exhibit altered local Ca2+ signaling with increased basal Ca2+ level. PMID:16249429

Yaras, Nazmi; Ugur, Mehmet; Ozdemir, Semir; Gurdal, Hakan; Purali, Nuhan; Lacampagne, Alain; Vassort, Guy; Turan, Belma

2005-11-01

131

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.

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

2013-01-01

132

Antihyperglycemic effect of black tea ( Camellia sinensis) in rat  

Microsoft Academic Search

Investigations were carried out to evaluate the effect of the hot water extract of black tea (Camellia sinensis (L.) O. Kuntze (Theaceae) on streptozotocin (STZ)-induced diabetes in rats. The extract significantly reduced the blood glucose level and was found to possess both preventive and curative effects on experimentally produced diabetes in rats. The study reveals that, like green tea, black

A. Gomes; J. R. Vedasiromoni; M. Das; R. M. Sharma; D. K. Ganguly

1995-01-01

133

Investigation of Antidiabetic, Antihyperlipidemic, and In Vivo Antioxidant Properties of Sphaeranthus indicus Linn. in Type 1 Diabetic Rats: An Identification of Possible Biomarkers  

PubMed Central

The present investigation was aimed to study the antidiabetic, antihyperlipidemic, and in vivo antioxidant properties of the root of Sphaeranthus indicus Linn. in streptozotocin- (STZ-) induced type 1 diabetic rats. Administration of ethanolic extract of Sphaeranthus indicus root (EESIR) 100 and 200?mg/kg to the STZ-induced diabetic rats showed significant (P < .01) reduction in blood glucose and increase in body weight compared to diabetic control rats. Both the doses of EESIR-treated diabetic rats showed significant (P < .01) alteration in elevated lipid profile levels than diabetic control rats. The EESIR treatment in diabetic rats produced significant increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and decrease in thiobarbituric acid reactive substances (TBARS) levels than diabetic control rats. Administration of EESIR 200?mg/kg produced significant (P < .01) higher antioxidant activity than EESIR 100?mg/kg. The high performance liquid chromatography (HPLC) analysis of EESIR revealed the presence of biomarkers gallic acid and quercetin. In conclusion, EESIR possess antidiabetic, antihyperlipidemic, and in vivo antioxidant activity in type 1 diabetic rats. Its antioxidant and lipid lowering effect will help to prevent diabetic complications, and these actions are possibly due to presence of above biomarkers.

Ramachandran, S.; Asokkumar, K.; Uma Maheswari, M.; Ravi, T. K.; Sivashanmugam, A. T.; Saravanan, S.; Rajasekaran, A.; Dharman, J.

2011-01-01

134

Effect of testosterone and frequent low-dose sildenafil/tadalafil on cavernous tissue oxidative stress of aged diabetic rats.  

PubMed

This study aimed to assess the effect of testosterone (T) administration and chronic low-dose sildenafil/tadalafil on cavernous tissue oxidative stress (OS) of aged diabetic rats. In all, 140 Sprague-Dawley aged rats were subdivided into the following: controls; streptozotocin (STZ)-induced diabetic rats; diabetic rats injected with T every 4 weeks; diabetic rats on sildenafil orally daily; diabetic rats on T and daily sildenafil; diabetic rats on tadalafil orally every other day; diabetic rats on T and tadalafil; diabetic rats on alternate sildenafil/tadalafil; and diabetic rats on alternate sildenafil/tadalafil with T. After 12 weeks, the rats were euthanised where in dissected cavernous tissues malondialdehyde (MAD), glutathione peroxidase (GPx) and cGMP (cyclic guanosine monophosphate) were estimated. Compared with controls, aged diabetic rats demonstrated significant increase in cavernous tissue MDA and significant decrease in GPx and cGMP where diabetic rats injected with T had marked improvement of these parameters. Diabetic rats on sildenafil, tadalafil or alternate sildenafil/tadalafil demonstrated significant increased cavernous tissue GPx, cGMP and decreased cavernous MDA that was further improved when supplemented with T. It is concluded that frequent low-dose use of sildenafil and/or tadalafil supplemented with T has a marked impact on ameliorating cavernous OS in aged diabetic rats. PMID:22489795

Mostafa, T; Rashed, L; Kotb, K; Taymour, M

2012-12-01

135

Rosiglitazone is effective to improve renal damage in type-1-like diabetic rats.  

PubMed

A marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats) showing diabetic nephropathy. It has been documented that klotho is the target gene of PPAR?. However, the effect of PPAR? agonist on klotho expression in kidney of STZ rats remains obscure. Thus, we used rosiglitazone (TZD) as PPAR? agonist to investigate the effect on renal dysfunction in STZ rats. Treatment of TZD reversed the lower levels of PPAR?, klotho, and FGFR1 expressions in kidneys of STZ rats without the correction of hyperglycemia. Also, renal functions and structural defeats were improved by TZD treatment. Taken together, oral administration of TZD may improve STZ-induced diabetic nephropathy due to restoration of the expression of klotho axis through an increase in PPAR? expression without changing blood glucose in rats. PMID:24136780

Huang, K-C; Cherng, Y-G; Chen, L-J; Hsu, C-T; Cheng, J-T

2014-04-01

136

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

PubMed

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

137

Lack of Nitric Oxide Mediation of Flow-Dependent Arteriolar Dilation in Type I Diabetes Is Restored by Sepiapterin  

Microsoft Academic Search

The mechanisms leading to microangiopathy in diabetes mellitus have still not been clearly elucidated. We hypothesized that type I diabetes mellitus affects the endothelium and alters flow-dependent dilation of arterioles, an important mechanism involved in local regulation of blood flow. Isolated, pressurized gracilis muscle arterioles (inside diameter approximately 150 ?m at 80 mm Hg) from rats with streptozotocin (STZ)-induced diabetes

Zsolt Bagi; Akos Koller

2003-01-01

138

Effects of N-adamantyl-4-methylthiazol-2-amine on hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats.  

PubMed

Thiazole derivatives are attractive candidates for drug development because they can be efficiently synthesized and are active against a number of diseases and conditions, including diabetes. In our present study, we investigated the anti-inflammatory and antioxidant properties of N-adamantyl-4-methylthiazol-2-amine (KHG26693), a new thiazole derivative, in a streptozotocin (STZ)-induced model of diabetes mellitus. STZ-induced diabetic rats were intraperitoneally administered KHG26693 (3mg/kg-body weight/day) for 4 weeks. KHG26693 administration significantly decreased blood glucose, triglycerides, and cholesterol and increased insulin. KHG26693 also suppressed several inflammatory responses in STZ-induced diabetic rats, as evidenced by decreased levels of serum tumor necrosis factor-?, interleukin-1?, and nitric oxide. Additionally, KHG26693 significantly modulated hepatic lipid peroxidation, catalase and superoxide dismutase activity, and the nonenzymatic antioxidant status (e.g., vitamins C and E), and reduced the glutathione content. These anti-inflammatory/antioxidative actions occurred as a result of the downregulation of inducible nitric oxide synthase and nuclear factor-kappa B. Taken together, our results suggest that KHG26693 successfully reduces the production of oxidative stress in STZ-induced diabetic rats by regulating the oxidation-reduction system, specifically increasing antioxidant capacity. Furthermore, KHG26693 treatment significantly reverted the key enzymes of glucose metabolism, such as glucokinase, glucose-6-phosphatase, glycogen synthase, glycogen phosphorylase, and fructose-1,6-bisphosphatase, to near-normal levels in liver tissues. These results indicate that KHG26693 normalizes disturbed glucose metabolism by enhancing glucose utilization and decreasing liver glucose production via insulin release, suggesting the possibility of future diabetes treatments. PMID:24797782

Yang, Seung-Ju; Je Lee, Woo; Kim, Eun-A; Dal Nam, Kee; Hahn, Hoh-Gyu; Young Choi, Soo; Cho, Sung-Woo

2014-08-01

139

Proximal skeletal muscle alterations in streptozotocin-diabetic rats: a histochemical and morphometric analysis.  

PubMed

The response of rat quadriceps muscle fibers to chronic streptozotocin (STZ) diabetes was studied. Transverse sections of rectus femoris muscle from diabetic and weight-matched control rats were assayed for myofibrilar adenosine triphosphatase (ATPase) and nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR). A quantitative analysis was carried out by an automatic interactive analysis system focused on the fiber type size and distribution. STZ-induced diabetes caused important effects in this muscle, with changes in the distribution of oxidative enzyme reactions, type I fiber hypertrophy, and type II fiber atrophy, which was greater in type IIB than in type IIA. It is concluded that hypoinsulinism produces morphological alterations in proximal skeletal muscle fibers that are similar to those of neurogenic myopathy. Thus the pathological changes in these mammalian muscle fibers could explain the clinical syndrome seen in diabetic patients called "diabetic symmetrical proximal motor neuropathy," perhaps the least understood of the major neuropathic complications of diabetes. PMID:1829578

Medina-Sanchez, M; Rodriguez-Sanchez, C; Vega-Alvarez, J A; Menedez-Pelaez, A; Perez-Casas, A

1991-05-01

140

A histological and immunohistochemical study of beta cells in streptozotocin diabetic rats treated with caffeine.  

PubMed

In this study, the histological, immunohistochemical, morphometric, and biochemical changes to pancreatic beta-cells in STZ-induced diabetes were evaluated in rats treated with different doses of caffeine. Fifty adult male Wistar albino rats were divided into five groups: the nondiabetic control group, the diabetic untreated group, and three diabetic groups treated with different doses of caffeine (10, 50, and 100 mg/kg/day). Blood glucose and serum insulin levels were measured. The pancreata were collected and processed into paraffin sections. They were stained using hematoxylin and eosin (H&E) and Masson trichrome stains. The insulin expression in beta-cells was assessed using immunohistochemistry. Morphometrically, the percentage area of anti-insulin antibody reaction, the percentage of beta-cells per total islet cell number, and the average area of the islets were determined. STZ-induced degenerative changes in beta-cells led to decreases in the number of functioning beta-cells and insulin immunoreactivity and to increases in the number of collagen fibers in the islets. In STZ-treated rats, caffeine significantly decreased blood glucose concentration while increasing blood insulin levels at the highest applied dose. It also induced a significant increase in the number of immunoreactive beta-cells. In conclusion, caffeine may have a protective role in the biochemical and microscopic changes in pancreatic beta-cells in diabetes induced in rats through STZ administration. PMID:24802960

Abunasef, Siham K; Amin, Hanan A; Abdel-Hamid, Ghada A

2014-01-01

141

Hemodynamic alterations in chronically conscious unrestrained diabetic rats  

SciTech Connect

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

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

1987-05-01

142

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.

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

2012-01-01

143

Oral Lactobacillus reuteri GMN-32 treatment reduces blood glucose concentrations and promotes cardiac function in rats with streptozotocin-induced diabetes mellitus.  

PubMed

Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 10? colony-forming units (cfu)/d) and 3040 mg/l (with 10? cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats. PMID:24001238

Lin, Chih-Hsueh; Lin, Cheng-Chieh; Shibu, Marthandam Asokan; Liu, Chiu-Shong; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Hsieh, Cheng-Hong; Chen, Yi-Hsing; Huang, Chih-Yang

2014-02-01

144

Influence of umbelliferone on glycoprotein components in diabetic rats.  

PubMed

ABSTRACT Umbelliferone (7-hydroxycoumarin), a derivative of coumarin, is benzopyrone in nature, and it is present in the fruits of golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). The present study was designed with the objective of evaluating the effect of umbelliferone (UMB) on glycemic control and glycoprotein components in the plasma and tissues (liver, kidney, heart, and brain) of streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180 to 200 g, were induced diabetes by administration of STZ (40 mg/kg b.w.) intraperitoneally. The normal and diabetic rats were treated with UMB dissolved in 10% dimethyl sulfoxide (DMSO) for 45 days. In our study, diabetic rats had decreased plasma insulin and elevated blood glucose, sialic acid, total hoxoses, fucose, and hexosamines in the plasma and tissues. Treatment with UMB brought the levels of glucose, sialic acid, total hoxoses, fucose, and hexosamines to near-normal level. Thus, our results show that treatment with UMB has improved glycemic control and thereby reduced the formation of glycoprotein components. This leads to the normalization of circulatory and tissue sialic acid, fucose, hexoses, and hexosamines in STZ-diabetic rats, which reflects a protective effect of UMB from the risk of diabetic complications. PMID:20020964

Ramesh, B; Pugalendi, K V

2007-01-01

145

Sodium tungstate attenuate oxidative stress in brain tissue of streptozotocin-induced diabetic rats.  

PubMed

High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms. PMID:19834650

Nakhaee, Alireza; Bokaeian, Mohammad; Akbarzadeh, Azim; Hashemi, Mohammad

2010-08-01

146

Amino acid supplementation counteracts metabolic and functional damage in the diabetic rat heart.  

PubMed

We aimed to assess whether a specific mixture of amino acid (AA) supplements counteracts the metabolic and functional changes in the streptozotocin (STZ)-induced diabetic rat heart model. Adult male Wistar rats were divided into 6 groups (n = 10 each) and treated for 43 days: nondiabetic controls, nondiabetic rats given an AA mixture (0.1 g/kg per day), diabetic rats (induced with 65 mg/kg STZ given intraperitoneally), diabetic rats given AAs, diabetic rats given insulin (5 IU/day given subcutaneously), and diabetic rats given insulin plus AAs. During treatment, glycemia and insulinemia levels were measured in all groups. Changes in enzyme (reduced nicotinamide adenine dinucleotide-dehydrogenase, cytochrome c oxidase) activities and myosin heavy chain (MHC) composition were measured in the left ventricle. In 5 rats contractile function was assessed by measuring maximal shortening velocity of skinned ventricular trabeculae and the expression of translational regulator mammalian target of rapamycin (mTOR) was also found. STZ-induced diabetes was associated with reduced myocardial contractility, overall loss of oxidative capacity, a shift toward a slower MHC phenotype, and decreased mTOR tissue content. All of these changes appeared to be reversible with insulin. AA supplements partially restored the myocardial and oxidative dysfunction and also increased mTOR tissue content. The combination of insulin and AAs did not have a synergistic effect on either enzymatic or functional profiles. We conclude that AA supplements may contribute to restoring the oxidative and contractile dysfunction of diabetic rat hearts, probably through an mTOR-insulin independent mechanism. PMID:18514627

Pellegrino, Maria Antonietta; Patrini, Cesare; Pasini, Evasio; Brocca, Lorenza; Flati, Vincenzo; Corsetti, Giovanni; D'Antona, Giuseppe

2008-06-01

147

Effect of bitter melon ( Momordica Charantia) fruit juice on the hepatic cytochrome P450-dependent monooxygenases and glutathione S-transferases in streptozotocin-induced diabetic rats  

Microsoft Academic Search

Bitter melon (Momordica charantia), commonly known as karela, has been reported to have hypoglycemic, antiviral, antidiabetic, and antitumor activities. In the present study, we have investigated the effects of oral feeding of karela fruit juice on the hepatic cytochrome P450 (CYP) and glutathione S-transferase (GST) drug-metabolizing enzymes in the streptozotocin (STZ)-induced diabetic rat. Hepatic CYP contents, ethoxycoumarin-O-deethylase (ECOD), ethoxyresorufin-O-deethylase (EROD),

Haider Raza; Ijaz Ahmed; Mohammad S. Lakhani; Ashutosh K. Sharma; David Pallot; William Montague

1996-01-01

148

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

149

Protective effects of thymoquinone on streptozotocin-induced diabetic nephropathy  

Microsoft Academic Search

The aim of this study was designed to investigate the possible beneficial effects of the thymoquinone (TQ) in streptozotocine\\u000a (STZ)-induced diabetes in rats. The rats were randomly allotted into one of three experimental groups: A (control), B (diabetic\\u000a untreated), and C (diabetic treated with TQ); each group contain ten animals. B and C groups received STZ. Diabetes was induced\\u000a in

Mehmet Kanter

2009-01-01

150

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

PubMed Central

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

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

2013-01-01

151

The diabetes-induced functional and distributional changes of the alpha 1-adrenoceptor of the abdominal aorta and distal mesenteric artery from streptozotocin-induced diabetic rats  

PubMed Central

Background The aim of this study was to evaluate the effect of diabetes on the function and distribution of vascular ?1-adrenoceptors in the abdominal aorta and distal mesenteric artery from streptozotocin (STZ)-induced diabetic rats at the level of the ?1-adrenoceptor subtypes. Methods Diabetes was induced by a single intravenous injection of STZ (60 mg/kg) in 8 week-old male Sprague-Dawley rats (n = 11). Age-matched normal rats (n = 14) were used as a control group. Four weeks after STZ injection, the tilting-induced change of the mean arterial pressure was recorded. The ?1-adrenoceptor subtypes mediating the contractions of the distal mesenteric artery and abdominal aorta were investigated using the agonist phenylephrine and subtype-selective antagonists that included prazocin, 5-methylurapidil and BMY 7378. The expressions of the ?1-adrenoceptor subtypes of each artery were examined by immunofluorescence staining using the subtype selective antibodies. Results The recovery of the mean arterial pressure was delayed after positional change in the diabetic rats. Compared with that of the normal rats, the contractile response to phenylephrine was increased in the abdominal aortas and it was decreased in the distal mesenteric arteries in the diabetic rats. In addition, compared with the normal rats, the fluorescent intensity of all the ?1-adrenoceptor subtypes was increased in the abdominal aortas and it was decreased in the mesenteric arteries of the diabetic rats. Conclusions Diabetes increased the contractility of the abdominal aorta in response to phenylephrine, yet diabetes decreased that of the mesenteric arteries in the STZ-induced diabetic rats. Those results are mainly based on the overall change of the ?1-adrenoceptor, and not on the change of the specific ?1-adrenoceptor subtypes.

Lee, Jong-Hwan; Park, Sang-Hyun; Huh, Jin

2011-01-01

152

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

153

Altered expression of mitofusin 2 in penile tissues of diabetic rats.  

PubMed

Diabetic erectile dysfunction (ED) is a common complication in diabetes mellitus, and the efficacy of first-line therapies is not satisfactory. Recent studies revealed that corporal apoptosis was responsible for the nonresponsiveness of severe ED to phosphodiesterase type 5 inhibitors. Mitofusin 2 (Mfn2) is a versatile protein, regulating mitochondrial morphology and playing an important role in apoptosis. Several studies showed that expression of Mfn2 was decreased in STZ-induced diabetic rats' kidney, myocardium and retina, which was associated with diabetic nephropathy, cardiomyopathy and retinopathy respectively. In this study, our aim was to explore the expression of Mfn2 and apoptosis in diabetic rats' penes. We found that erectile function (ICP/MAP) elicited by electrical stimulation of cavernous nerve was markedly impaired in diabetic rats compared with the normal rats. The mRNA and protein levels of Mfn2 were found to be significantly reduced in diabetic rats' penile tissues. Compared with normal rats, the content of smooth muscle and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were dramatically decreased, and penile apoptotic index and expression of activated-caspase-3 were dramatically increased in diabetic rats. This data indicated that repression of Mfn2 in diabetic rats' penes might be associated with excessive apoptosis in diabetes-induced severe ED. PMID:23682852

Yang, J; Wang, T; Zhang, Y; Li, R; Wang, S; Xu, H; Liu, J; Ye, Z

2014-06-01

154

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

PubMed Central

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

Singh, Rambir; Bhardwaj, Priyanka; Sharma, Poonam

2013-01-01

155

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats.  

PubMed

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-?) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-? expression and inhibited the nuclear transcription factor-kappa B (NF-?B) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-?), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1?) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-? pathway. PMID:24848621

Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

2014-08-15

156

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.

Kumar, S; Kumar, V; Prakash, OM

2012-01-01

157

Chronic treatment with vascular endothelial growth factor preserves agonist-evoked vascular responses in the streptozotocin-induced diabetic rat  

Microsoft Academic Search

Aims\\/hypothesis  Vascular dysfunction is a hallmark of diabetes mellitus and endothelial dysfunction is considered to be a key early component\\u000a of vascular dysfunction. Attenuated agonist-evoked responses are considered to be a barometer of endothelial\\/vascular dysfunction.\\u000a We sought to determine whether vascular endothelial growth factor (VEGF) could prevent dysfunction from developing in the\\u000a streptozotocin (STZ)-induced rat model of type 1 diabetes.\\u000a \\u000a \\u000a \\u000a Materials

S. Bardal; D. Misurski; X. Qiu; K. Desai; J. R. McNeill

2006-01-01

158

Long-term endothelin receptor blockade improves cardiovascular function in diabetes  

Microsoft Academic Search

To evaluate the potential contribution of endothelin-1 (ET-1) toward the cardiovascular complications of diabetes, the present study examined the effects of chronic ET receptor blockade with bosentan on heart function and vascular reactivity in streptozotocin (STZ)-induced diabetic rats. Wistar rats were divided into four groups: control, control bosentan-treated, diabetic, and diabetic bosentan-treated. After chronic bosentan treatment, cardiac function and vascular

Subodh Verma; Emi Arikawa; John H. McNeill

2001-01-01

159

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

PubMed

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

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

2013-09-01

160

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’.

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

2010-01-01

161

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

PubMed

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

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

2010-01-01

162

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

PubMed Central

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

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

2013-01-01

163

Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats  

PubMed Central

The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP), heart rate (HR), and baroreflex sensitivity (BRS) in STZ-induced diabetic rats. Male Wistar rats were divided into control (n = 8) and diabetic (n = 8) groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR) responses to AP changes, were evaluated at rest (R) and postexercise session (PE) on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103 ± 2 versus PE: 111 ± 3?mmHg) and HR (R: 290 ± 7 versus PE: 328 ± 10?bpm) reductions and BR dysfunction (R: ?0.70 ± 0.06 versus PE: ?1.21 ± 0.09?bpm/mmHg) was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes.

Jorge, Luciana; da Pureza, Demilto Y.; Dias, Danielle da Silva; Conti, Filipe Fernandes; Irigoyen, Maria-Claudia; De Angelis, Katia

2012-01-01

164

Protective effect of Coccinia indica on changes in the fatty acid composition in streptozotocin induced diabetic rats.  

PubMed

The present study was undertaken to investigate the effect of Coccinia indica, an indigenous plant used in Ayurvedic Medicine in India, on blood glucose, plasma insulin, cholesterol, triglycerides, free fatty acids and phospholipids and fatty acid composition of total lipids in liver, kidney and brain of normal and streptozotocin (STZ) diabetic rats. Oral administration of the ethanolic extract of Coccinia indica leaves (200 mg/kg body weight, CLEt) for 45 days to diabetic rats decreased the concentrations of blood glucose, lipids and fatty acids, viz., palmitic, stearic, and oleic acid whereas linolenic and arachidonic acid and plasma insulin were elevated. These results suggest that CLEt exhibits hypoglycaemic and hypolipidaemic effects in STZ induced diabetic rats. It also prevents the fatty acid changes produced during diabetes. The effect of CLEt at 200 mg/kg body weight was better than that of glibenclamide. PMID:12857005

Pari, L; Venkateswaran, S

2003-06-01

165

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

166

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

PubMed Central

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

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

2011-01-01

167

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.

2012-01-01

168

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.

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

2014-01-01

169

Selective Inhibition of Protein Kinase C ?2 Attenuates Inducible Nitric Oxide Synthase-Mediated Cardiovascular Abnormalities in Streptozotocin-Induced Diabetic Rats  

PubMed Central

OBJECTIVE Impaired cardiovascular function in diabetes is partially attributed to pathological overexpression of inducible nitric oxide synthase (iNOS) in cardiovascular tissues. We examined whether the hyperglycemia-induced increased expression of iNOS is protein kinase C-?2 (PKC?2) dependent and whether selective inhibition of PKC? reduces iNOS expression and corrects abnormal hemodynamic function in streptozotocin (STZ)-induced diabetic rats. RESEARCH DESIGN AND METHODS Cardiomyocytes and aortic vascular smooth muscle cells (VSMC) from nondiabetic rats were cultured in low (5.5 mmol/l) or high (25 mmol/l) glucose or mannitol (19.5 mmol/l mannitol + 5.5 mmol/l glucose) conditions in the presence of a selective PKC? inhibitor, LY333531 (20 nmol/l). Further, the in vivo effects of PKC? inhibition on iNOS-mediated cardiovascular abnormalities were tested in STZ-induced diabetic rats. RESULTS Exposure of cardiomyocytes to high glucose activated PKC?2 and increased iNOS expression that was prevented by LY333531. Similarly, treatment of VSMC with LY333531 prevented high glucose–induced activation of nuclear factor ?B, extracellular signal–related kinase, and iNOS overexpression. Suppression of PKC?2 expression by small interference RNA decreased high-glucose–induced nuclear factor ?B and extracellular signal–related kinase activation and iNOS expression in VSMC. Administration of LY333531 (1 mg/kg/day) decreased iNOS expression and formation of peroxynitrite in the heart and superior mesenteric arteries and corrected the cardiovascular abnormalities in STZ-induced diabetic rats, an action that was also observed with a selective iNOS inhibitor, L-NIL. CONCLUSIONS Collectively, these results suggest that inhibition of PKC?2 may be a useful approach for correcting abnormal hemodynamics in diabetes by preventing iNOS mediated nitrosative stress.

Nagareddy, Prabhakara Reddy; Soliman, Hesham; Lin, Guorong; Rajput, Padmesh S.; Kumar, Ujendra; McNeill, John H.; MacLeod, Kathleen M.

2009-01-01

170

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

PubMed

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

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

2014-04-01

171

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

PubMed

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

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

2014-05-15

172

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

PubMed Central

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

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

2014-01-01

173

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

PubMed

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

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

2012-08-01

174

Decreased autophosphorylation of EGF receptor in insulin-deficient diabetic rats  

SciTech Connect

The authors have previously reported that despite an increase in receptor concentration, there is a decrease in autophosphorylation and tyrosine kinase activity of the insulin receptor in insulin-deficient diabetic rats. To determine if other tyrosine kinases might be altered, they have studied the epidermal growth factor (EGF) receptor kinase in wheat germ agglutinin-purified, Triton X-100-solubilized liver membranes from streptozotocin (STZ)-induced diabetic rats and the insulin-deficient BB rat. They find that autophosphorylation of EGF receptor is decreased in proportion to the severity of the diabetic state in STZ rats with a maximal decrease of 67%. A similar decrease in autophosphorylation was observed in diabetic BB rats that was partially normalized by insulin treatment. Separation of tryptic phosphopeptides by reverse-phase high-performance liquid chromatography revealed a decrease in labeling at all sites of autophosphorylation. A parallel decrease in EGF receptor phosphorylation was also found by immunoblotting with an antiphosphotyrosine antibody. EGF receptor concentration, determined by Scatchard analysis of {sup 125}I-labeled EGF binding, was decreased by 39% in the STZ rat and 27% in the diabetic BB rat. Thus autophosphorylation of EGF receptor, like that of the insulin receptor, is decreased in insulin-deficient rat liver. In the case of EGF receptor, this is due in part to a decrease in receptor number and in part to a decrease in the specific activity of the kinase.

Okamoto, M.; Kahn, C.R.; Maron, R.; White, M.F. (Harvard Medical School, Boton, MA (USA))

1988-04-01

175

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

176

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.

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

2013-01-01

177

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

178

Corneal Complications in Streptozocin-Induced Type I Diabetic Rats  

PubMed Central

Purpose. This study seeks to characterize corneal functions and complications in a streptozocin (STZ)-induced rat model of type I diabetes mellitus (DM) and to understand the pathogenesis of diabetic keratopathy. Methods. DM was induced via STZ injection in Sprague-Dawley rats. Body weight, length, and corneal size were measured and compared with the age-matched normal controls. Corneal morphology and histology were evaluated with slit lamp, digital confocal microscopy and hematoxylin and eosin staining. Tear secretion was measured with cotton threads, and corneal sensitivity was determined with an esthesiometer. Protein expression and distribution were assessed with Western blotting and immunohistochemistry. Wound healing was determined using an in vivo corneal epithelial debridement model. Results. Compared with the normal control rats, STZ rats had reduced body weight, and body length, but minimally affected corneal size. No significant changes in ocular surface regularity, corneal thickness, and morphology were noted in diabetic corneas. STZ rats showed stronger Rose Bengal staining, decreased tear secretion, slightly attenuated sensitivity, less innervation, delayed epithelial wound healing, and impaired epidermal growth factor receptor signaling in their corneas. While the expression of adherens junction protein ?-catenin, and tight junction proteins occludin and ZO-1 was unchanged, the formation of these junctions after wound closure was delayed. Conclusions. Pathogenesis of diabetic keratopathy involves multiple tissues and/or cell types and several events including reduced tear secretion, impaired innervation, weakened cell junction, and altered wound responses. These insights may prove useful for the clinical translation of evolving strategies for the management and treatment of diabetic corneal complications.

Yin, Jia; Huang, Jenny; Chen, Cynthia; Gao, Nan; Wang, Feng

2011-01-01

179

Pharmacodynamic interaction of Momordica charantia with rosiglitazone in rats.  

PubMed

The present study was undertaken to determine the interaction of rosiglitazone, a PPAR-gamma agonist with methanolic extract of Momordica charantia L (MC), an herbal drug used widely as an antidiabetic agent. The pharmacodynamic interaction was evaluated in oral glucose tolerance test, streptozotocin (STZ) induced diabetes in adult rats and STZ induced diabetes in neonatal rats. Rosiglitazone was given orally at two different doses of 2mg/kg and 5mg/kg and MC was administered at a dose of 500 mg/kg, p.o. The serum glucose level estimation and histopathological studies of pancreas, liver and kidney were carried out. Both rosiglitazone and MC showed hypoglycaemic effect in oral glucose tolerance test. The hypoglycaemic effect observed with combination of rosiglitazone and MC was significantly more compared to either of the drugs given alone. MC also augmented the hypoglycaemic effect of rosiglitazone in both STZ induced diabetes in adult animals and STZ induced diabetes in neonatal rats. Histopathological studies revealed that administration of rosiglitazone with MC increased the volume of islet cell in pancreas and prevented the hepatic damage when compared to control. It was concluded that MC augments hypoglycaemic effect of rosiglitazone. This could be important in reducing the dose of rosiglitazone to achieve enhanced therapeutic effect with minimal adverse effects. PMID:18983991

Nivitabishekam, Susan Nancy; Asad, Mohammed; Prasad, V Satya

2009-02-12

180

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

PubMed

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

Babu, P Subash; Stanely Mainzen Prince, P

2004-11-01

181

Insulin sensitising action of chromium picolinate in various experimental models of diabetes mellitus  

Microsoft Academic Search

Although chromium is an essential element for carbohydrate and lipid metabolism, its effects in diabetic patients are still debated. We have studied the effect of 6 week treatment with chromium picolinate (8?g\\/ml in drinking water) in streptozotocin (STZ)-induced type 1 and type 2 diabetic rat models. The mechanism of anti-diabetic action of chromium picolinate was studied using C2C12 myoblasts and

Urmila A. Shinde; Geeta Sharma; Yan J. Xu; Naranjan S. Dhalla; Ramesh K. Goyal

2004-01-01

182

Pharmacognostical standardization and antidiabetic activity of Syzygium cumini (Linn.) barks (Myrtaceae) on streptozotocin-induced diabetic rats.  

PubMed

Abstract Background: The objectives of the present study were phytochemical and pharmacological screening of bark of Syzygium cumini on streptozotocin (STZ)-induced diabetic Wistar albino rats. Methods: Dose selection was made on the basis of acute oral toxicity study (300-5,000 mg/kg b.w.) as per OECD guidelines. Rats were made diabetic by a single dose of STZ at 50 mg/kg b.w. intraperitoneally. The effect of Syzygium cumini extracts (500 mg/kg) on postprandial blood glucose level was determined in fasted diabetic and normal rats. Blood glucose levels were measured at 0, 30, and 90 min after the glucose administration in the OGTT study. The bark extracts were administered orally at the dose of 500 mg/kg for 21 days in the chronic study. Glibenclamide (2.5 mg/kg) was used as a standard drug for activity comparison. Statistical analyses were performed using one-way ANOVA followed by Bonferroni's multiple comparison tests. Results: The phytochemical screening showed positive results for triterpenes/steroids, glycosides, carbohydrates, alkaloids, flavonoids, saponins, tannins and amino acids. Administration of Syzygium cumini extracts 30 min before oral glucose loading significantly suppressed (p<0.001) the rise in postprandial blood glucose levels in treated rats compared to control rats but less significant than glibenclamide. Daily, continuous oral treatment of STZ-induced diabetic with various extract of Syzygium cumini for 3 weeks resulted in significant reductions in fasting blood glucose levels compared with diabetic controls. The ethanol and aqueous extracts were most active. Conclusions: This study brings out the evidence regarding phytochemistry and pharmacological activities of Syzygium cumini. PMID:24760764

Tripathi, Akhilesh K; Kohli, Seema

2014-06-01

183

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.

Kim, Si Oh

2013-01-01

184

Antidiabetic and in vitro antioxidant potential of Hybanthus enneaspermus (Linn) F. Muell in streptozotocin-induced diabetic rats  

PubMed Central

Objective To evaluate antidiabetic and antioxidant potential of Hybanthus enneaspermus in different models. Methods The oral glucose tolerance test (OGTT) and normoglycemic effect of alcoholic extract of Hybanthus enneaspermus (AHE) were evaluated at a dose of 125, 250 and 500 mg/kg p.o. while hypoglycemic activity and effect on body weight were tested at 250 and 500 mg/kg p.o. per day for 21 days in Streptozotocin (STZ) induced diabetic rats. Further, glucose uptake by hemidiaphram was also evaluated. The total polyphenolic and flavonoid were determined and their correlation with various antioxidant assays was also determined. Results The results showed high level of phenolic content in AHE. AHE also exhibited higher total antioxidant capacity, good reducing power and a significant scavenger of reactive oxygen species like DPPH radical, nitric oxide, hydrogen peroxide and deoxyribose. Furthermore there was a significant increase in the body weight and decrease in the blood glucose level on treatment with the AHE. AHE increased glucose uptake on isolated rat hemi-diaphragm compared to control group. Conclusions AHE reduce blood glucose level in STZ-induced diabetic model. It does not show significant effect in normoglycemic study but showes significant effect in OGT. AHE has significant antioxidant activity, which may be attributed to high phenolic content.

Patel, DK; Kumar, R; Prasad, SK; Sairam, K; Hemalatha, S

2011-01-01

185

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

PubMed

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

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

2014-06-01

186

Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase  

PubMed Central

Background Diabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, we aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN. Methods The protective effects of RSV on DN were evaluated in streptozotocin (STZ)-induced diabetic rats. Results The plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine IL-1?. RSV reduced IL-1? but increased TNF-? and IL-6 levels in the diabetic kidneys. Conclusions Our findings suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.

2011-01-01

187

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.

Ramachandran, Subramaniam; Rajasekaran, Aiyalu; Manisenthilkumar, KT

2012-01-01

188

Antidiabetic and antihyperlipidemic potential of Abelmoschus esculentus (L.) Moench. in streptozotocin-induced diabetic rats  

PubMed Central

Objectives: The present investigation was aimed to study the antidiabetic and antihyperlipidemic potential of Abelmoschus esculentus peel and seed powder (AEPP and AESP) in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Acute toxicity of AEPP and AESP was studied in rats at 2000 mg/kg dose and diabetes was induced in rats by administration of STZ (60 mg/kg, i.p.). After 14 days of blood glucose stabilization, diabetic rats received AEPP, AESP, and glibenclamide up to 28 days. The blood samples were collected on day 28 to estimate the hemoglobin (Hb), glycosylated hemoglobin (HbA1c), serum glutamate-pyruvate transferase (SGPT), total protein (TP), and lipid profile levels. Results: In acute toxicity study, AESP and AESP did not show any toxicity or death up to a dose of 2000 mg/kg. Therefore, to assess the antidiabetic action, one by fifth and one by tenth dose of both powders were selected. Administration of AEPP and AESP at 100 and 200 mg/kg dose in diabetic rats showed significant (P < 0.001) reduction in blood glucose level and increase in body weight than diabetic control rats. A significant (P < 0.001) increased level of Hb, TP, and decreased level of HbA1c, SGPT were observed after the treatment of both doses of AEPP and AESP. Also, elevated lipid profile levels returned to near normal in diabetic rats after the administration of AEPP and AESP, 100 and 200 mg/kg dose, compared to diabetic control rats. Conclusion: The present study results, first time, support the antidiabetic and antihyperlipidemic potential of A. esculentus peel and seed powder in diabetic rats.

Sabitha, V.; Ramachandran, S.; Naveen, K. R.; Panneerselvam, K.

2011-01-01

189

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

190

Expression changes of mitogen-activated protein kinase phosphatase-1 (MKP-1) in myocardium of streptozotocin-induced diabetic rats.  

PubMed

MAP Kinase Phosphatase-1 (MKP-1) is a dual specific phosphatase selective for MAP kinases, and was believed to implicate in the development of cardiac hypertrophy. However, whether MKP-1 is involved in the pathogenesis of diabetic cardiomyopathy is still unknown. We employed streptozotocin (STZ)-induced diabetic Sprague-Dawley rats to study the alteration of the MKP-1 expressions in the left ventricular myocardium in diabetic and normal groups by immunohistochemistry and real-time quantitative reverse transcription-polymerase chain reaction. The weight, blood sugar and urine sugar were measured before and after model induction in both control and diabetic groups. Changes of heart ultrastructure were analyzed by using transmission electron microscopy. The data of weight, blood sugar and urine sugar indicated no significant difference between the two groups before animal model induction. Eight weeks after the induction of diabetes, the differences between the control and the diabetic groups in weight, blood sugar and urine sugar were significant ( P<0.01). When compared with control, diabetic myocardium ultrastructural changes included myofibrillar disarrangements, mitochondria disruption, and increase in nuclear membrane invaginations. A significant decrease of MKP-1 expression was observed in the diabetic rats' myocardium ( P<0.01). Our study provides experimental evidences that hyperglycemia could damage myocardial ultrastructure. Moreover, we provided first evidence that down-regulation of cardioprotective peptide MKP-1, the MAPK pathway negative regulator, in myocardium of streptozotocin-induced diabetic rats, which may contribute to the deterioration of cardiac function and lead to diabetic cardiomyopathy. PMID:17647144

Weng, Y; Shen, F; Li, J; Shen, Y; Zhang, X

2007-07-01

191

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

SciTech Connect

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

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

1991-01-01

192

Upregulation of glutamatergic transmission in anterior cingulate cortex in the diabetic rats with neuropathic pain.  

PubMed

Peripheral neuropathic pain is a common complication in the diabetic patients, and the underlying central mechanism remains unclear. Forebrain anterior cingulate cortex (ACC) is critically involved in the supraspinal perception of physical and affective components of noxious stimulus and pain modulation. Excitatory glutamatergic transmission in the ACC extensively contributed to the maintenance of negative affective component of chronic pain. The present study examined the adaptation of glutamatergic transmission in the ACC in rats with diabetic neuropathic pain. Injection with streptozotocin (STZ) induced hyperglycemia, thermal hyperalgesia and mechanical allodynia in the rats. In these rats, significant enhanced basal glutamatergic transmission was observed in the ACC neurons. The increased presynaptic glutamate release and enhanced conductance of postsynaptic glutamate receptors were also observed in the ACC neurons of these modeled rats. Increased phosphorylation of PKM?, but not the expression of total PKM?, was also observed in the ACC. Microinjection of PKM? inhibitor ZIP into ACC attenuated the upregulation of glutamate transmission and painful behaviors in STZ-injected rats. These results revealed a substantial central sensitization in the ACC neurons in the rodents with diabetic neuropathic pain, which may partially underlie the negative affective components of patients with diabetic neuropathic pain. PMID:24686190

Li, Weifang; Wang, Peng; Li, Hua

2014-05-01

193

Growth hormone exacerbates diabetic renal damage in male but not female rats  

PubMed Central

Background Human and animal studies support the idea that there are sex differences in the development of diabetic renal disease. Our lab and others have determined that in addition to Ang II (through the AT1R), growth hormone (GH) contributes to renal damage in models of renal failure; however, the impact of sex and GH on the mechanisms initiating diabetic renal disease is not known. This study examined the effect of sex and GH on parameters of renal damage in early, uncontrolled streptozotocin (STZ)-induced diabetes. Methods Adult male and female Sprague–Dawley rats were injected with vehicle (control), STZ, or STZ?+?GH and euthanized after 8 weeks. Results Mild but significant glomerulosclerosis (GS) and tubulointerstitial fibrosis (TIF) was observed in both kidneys from male and female diabetic rats, with GH significantly increasing GS and TIF by 30% and 25% in male rats, but not in female rats. STZ increased TGF-? expression in both kidneys from male and female rats; however, while GH had no further effect on TGF-? protein in diabetic females, GH increased TGF-? protein in the male rat’s kidneys by an additional 30%. This sex-specific increase in renal injury following GH treatment was marked by increased MCP-1 and CD-68+ cell density. STZ also reduced renal MMP-2 and MMP-9 protein expression in both kidneys from male and female rats, but additional decreases were only observed in GH-treated diabetic male rats. The sex differences were independent of AT1R activity. Conclusions These studies indicate that GH affects renal injury in diabetes in a sex-specific manner and is associated with an increase in pro-inflammatory mediators.

2013-01-01

194

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.

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

2011-01-01

195

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.

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

2013-01-01

196

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.

2014-01-01

197

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

198

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

PubMed

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

199

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

PubMed Central

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

Kamboj, Anil; Kumar, Sunil; Kumar, Vipin

2013-01-01

200

Effects of Endurance Training on Lipid Metabolism and Glycosylated Hemoglobin Levels in Streptozotocin-induced Type 2 Diabetic Rats on a High-fat Diet  

PubMed Central

[Purpose] Exercise has been recognized as a simple and economical therapeutic modality that effectively benefits patients with diabetes, for instance, increasing insulin sensitivity in type 2 diabetes. However, thus far, no studies have examined the effect of endurance training exercises on type 2 diabetes. Therefore, this study examined the effect of endurance training exercise regimens on body weight, glucose and insulin levels, lipid profiles, and HbA1c levels in STZ-induced type 2 diabetic rats on a high-fat diet. HbA1c was considered an indicator of glucose control during endurance training. [Methods] A total of 36 rats were included in this study. Diabetes was induced by administering STZ to 2 groups of 12 rats each, and, the remaining 12 rats were classified as the normal group. Biochemical parameters were measured 28 days later, and included: serum total cholesterol, triglyceride, high-density lipoprotein, glycosylated hemoglobin, glucose, and insulin levels. [Results] A significant decrease in serum TC and TG levels, and an increase in HDL cholesterol level were observed in the endurance training group. Moreover, blood glucose and HbA1c levels after 28 days of exercising were significantly lower in the endurance training group than in the control group (p<0.05). [Conclusion] These results indicate that endurance training affects body weight and, lipid profiles, as well as fasting blood glucose, HbA1c, and insulin levels, in STZ-induced type 2 diabetic rats on a high- fat diet. We suggest that endurance training exercises may exhibit therapeutic, preventative, and protective effects against diabetes mellitus through improving lipid metabolism, glycemic control, and HbA1c levels.

Heo, Myoung; Kim, Eunjung

2013-01-01

201

Early Visual Deficits in Streptozotocin-Induced Diabetic Long Evans Rats  

PubMed Central

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

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

2013-01-01

202

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

PubMed Central

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

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

2013-01-01

203

Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.  

PubMed

Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-?, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain. PMID:24680376

El-Akabawy, Gehan; El-Kholy, Wael

2014-05-01

204

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

PubMed

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

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

2010-10-01

205

Effect ofCoccinia indica (L.) andAbroma augusta (L.) on glycemia, lipid profile and on indicators of end-organ damage in streptozotocin induced diabetic rats.  

PubMed

InAyurvedic system of medicine in India, not only extracts of one plant or the other but also a combination of plant extracts are used for the treatment of diabetes mellitus. The present paper reports the combined effect ofAbroma augusta andCoccinia indica known to be useful for the treatment of diabetes in Ayurveda on the fasting blood sugar, glucose tolerance and lipid profile of Streptozotocin (STZ) induced albino rats. 300mg of water extract of the mixture of dried powdered roots ofA. augusta and leaves ofC. indica in equal proportions was given once daily for 8 weeks. After 8 weeks of treatment of Streptozotocin (STZ) diabetic rats, the fasting blood sugar came down to almost normal value and improvement in glucose tolerance and serum lipid profile were also observed. PMID:23105393

Eshrat, M Halim

2003-07-01

206

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

PubMed Central

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

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

2013-01-01

207

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

Microsoft Academic Search

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

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

2003-01-01

208

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

PubMed Central

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

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

2012-01-01

209

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.

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

2014-01-01

210

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

PubMed Central

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

2012-01-01

211

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

PubMed Central

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

2014-01-01

212

Protection of testicular dysfunctions by MTEC, a formulated herbal drug, in streptozotocin induced diabetic rat.  

PubMed

Single injection of streptozotocin (STZ) resulted diabetes mellitus which was reflected here by the levels of fasting blood glucose and serum insulin. Moreover, this experimental diabetes also resulted testicular dysfunctions evaluated by count, viability and motility of sperm as well as by the activities of key enzymes for androgen synthesis. Diabetes induced testicular oxidative stress has been indicated here by the monitoring of testicular peroxidase and catalase activities as well as by quantification of TBARS and CD of testis. Testicular glucose was increased and leydig cell nuclear area was decreased in STZ induced diabetes. Treatment of herbal formulated drug named as MTEC consist of aqueous-methanol extract of Musa paradisiaca, Tamarindus indica, Eugenia jambolana and Coccinia indica to streptozotocin induced diabetic rat at the ratio of 2:2:1:1 at the dose of 60 mg/d for two times a day for 14 d resulted a significant protection in fasting blood glucose and serum insulin levels (p<0.05) along with correction of testicular above parameters towards the control level (p<0.05). This herbal formulated drug has no general toxic effects on the body weight, as well as on the activities of serum glutamate and pyruvate transaminases in serum. The results support the validity of this herbal drug for the management of testicular disorders noted in diabetic state. PMID:17202665

Mallick, Chhanda; Mandal, Suvra; Barik, Bikashranjan; Bhattacharya, Atanu; Ghosh, Debidas

2007-01-01

213

Berberine regulates the expression of E-prostanoid receptors in diabetic rats with nephropathy.  

PubMed

Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease and to improve advanced kidney injury are required. Berberine (BBR) has preventive effects on diabetes and its complications. This study is to investigate the effects of BBR on the expression of E-prostanoid receptors (EPs) in rats with high-fat diet and streptozotocin (STZ)-induced DN and underlying molecular mechanisms of BBR on DN rats. DN model was induced in male Sprague-Dawley rats with high-fat diet and low dose of STZ injection. BBR (50, 100, 200 mg/kg/d) were orally administered to rats after STZ injection and conducted for 8 weeks. The levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) in renal cortex were measured by enzyme-linked immunosorbent assay. Expression of EPs receptors (EP1-EP4) were determined by western blotting. 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 (Wang et al. in Mol Biol Rep 40:2405-2418, 2013). The level of IL-6 and PGE2 were significantly increased in DN model group compared with normal group, BBR could apparently reduced the level of IL-6 and PGE2. Furthermore, the expression of EP1 and EP3 were both increased and EP4 was lessened in the DN model group compared with normal group, BBR could down-regulate total protein expression of EP1 and EP3 of renal cortex in DN rats and up-regulate the expression of EP4, and there is no significant difference on the expression of EP2 among all groups. 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 EPs in EP-G protein-cAMP signaling pathway. PMID:24488262

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

2014-05-01

214

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

215

Gastric subserous space islet transplantation: Techniques and initial results in diabetic inbred Lewis rats.  

PubMed

Background Implantation site is an important factor affecting the effect of islet transplantation. In the literature, the gastric subserous space (GSS) is rarely used as the implantation site of islets. Our present study reports the initial results with a limited numbers of islets transplanted into the GSS in Lewis rats and compares the outcomes between the GSS and the liver. Material and Methods STZ was used to induce diabetes in Lewis rats, using a limited numbers of islets from the donors of the same species transplanted into the GSS and also into the portal vein (PV). Fasting blood glucose levels were measured and the transplanted insulin-positive islets were detected using immunohistochemical method. Results The fasting blood glucose levels were significantly reduced compared with that in the pre-transplantation period in rats of the GSS group. Oral glucose tolerance testing (OGTT) on day 28 after transplantation revealed an excellent functional capacity. Insulin-positive islets were identified in the stomach throughout the study. However, we found no difference in fasting blood glucose between pre- and post-transplantation and no insulin-positive islets were discovered in rats of the PV group. Conclusions Under the treatment of a limited numbers of islets, the gastric subserous space reveals a preferable capacity for glycometabolism of STZ-induced Lewis diabetic rats compared with the portal vein. PMID:25011700

Liu, Xinnong; Zhang, Jinhang; Li, Yang; Hu, Sanyuan; Zhang, Guangyonng; Wang, Lei

2014-01-01

216

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.

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

2013-01-01

217

Antihyperglycemic and antioxidative potential of Psidium guajava fruit in streptozotocin-induced diabetic rats.  

PubMed

Psidium guajava Linn. (family Myrtaceae; PG) is a tropical fruit with a blood-glucose-lowering effect in diabetic rats, but its mechanism of action is still unknown. We investigated the antihyperglycemic efficacy and mechanisms of action of PG in streptozotocin (STZ)-induced diabetic rats. After 4 weeks of PG supplementation (125 and 250 mg/kg), PG significantly restored the loss of body weight caused by STZ and reduced blood glucose levels in a dose-dependent manner compared with that in diabetic control rats. Mechanistically, PG protected pancreatic tissues, including islet ?-cells, against lipid peroxidation and DNA strand breaks induced by STZ, and thus reduced the loss of insulin-positive ?-cells and insulin secretion. Moreover, PG also markedly inhibited pancreatic nuclear factor-kappa B protein expression induced by STZ and restored the activities of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. We conclude that PG has a significant antihyperglycemic effect, and that this effect is associated with its antioxidative activity. PMID:21679740

Huang, Chin-Shiu; Yin, Mei-Chin; Chiu, Lan-Chi

2011-09-01

218

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

PubMed Central

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

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

2011-01-01

219

Treatment with AT(1) receptor blocker restores diabetes-induced alterations in intracellular Ca(2+) transients and contractile function of rat myocardium.  

PubMed

We investigated the effect of treatment with an angiotensin II receptor blocker, candesartan-cilexetil, on the mechanical and electrophysiological properties of cardiomyocytes isolated from streptozotocin-induced diabetic (STZ) rats. Contractile activity and electrophysiological properties were measured in papillary muscle and ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 5mg/kg/day candesartan-cilexetil for 4 weeks. Alterations in the kinetics of contractile activity and intracellular Ca(2+) transients were observed as well as a typical prolongation of action potential duration and significant decrease of potassium currents in diabetic rat heart preparations. Candesartan-cilexetil treatment recovered significantly prolonged action potential and depressed potassium currents in diabetic rats. It was also shown that treatment with AT(1) blocker restored altered kinetics of both the Ca(2+) transients in cardiomyocytes and the contractile activity in papillary muscle strips of diabetic rats. We also showed that incubation of cardiomyocytes from diabetic rats with a protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM) had a similar effect to candesartan treatment on the Ca(2+) transients. Thus, angiotensin II receptor blockade protects the heart from the development of cellular alterations typically related with diabetes, and this action of AT(1) receptors seems to be related with the activity of PKC. PMID:15680918

Ozdemir, Semir; Ugur, Mehmet; Gürdal, Hakan; Turan, Belma

2005-03-01

220

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.

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

2014-01-01

221

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

PubMed Central

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

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

2012-01-01

222

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

PubMed Central

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

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

2012-01-01

223

Analysis of the membrane fluidity of erythrocyte ghosts in diabetic, spontaneously hypertensive rats.  

PubMed

Diabetes and hypertension are closely related diseases associated with changes in membrane fluidity. Here, we measured the membrane fluidity of erythrocyte ghosts from spontaneously hypertensive rats (SHR), with or without streptozotocin (STZ)-induced diabetes, at the ages of 1, 3 and 6 months, by introducing the use of the intramolecular excimer forming dipyrenylpropane (DPyP) in this model. Type 2 diabetes mellitus (T2DM) was induced in 48-h-old, newborn male SHR by intraperitoneal injection of STZ. We found lower excimer to monomer (I (e)/I (m)) DPyP ratios in diabetic SHR than in control SHR at 3 and 6 months old, indicating a decrease in membrane fluidity. Simultaneously, the composition of fatty acids was determined and it was found that the unsaturated to saturated fatty acids ratio (U/S) was compatible with changes in membrane fluidity. These results suggest that the change in fatty acid composition of erythrocyte ghosts contributes significantly to the decreased membrane fluidity detected with DPyP in diabetic SHR. PMID:19404568

Pérez-Hernández, Ismael H; Avendaño-Flores, Yesica S; Mejía-Zepeda, Ricardo

2010-12-01

224

Candesartan Differentially Regulates Epithelial Sodium Channel in Cortex Versus Medulla of Streptozotocin-Induced Diabetic Rats.  

PubMed

Diabetes is associated with an activated renal renin-angiotensin-aldosterone system (RAAS) and it was shown that streptozotocin (STZ)-induced diabetic rats had increased whole kidney protein levels of the epithelial sodium channel subunits (?-, ?- and ?-ENaC). However, the role of the RAAS on the regional, i.e., cortical versus medullary, regulation of ENaC is unclear. Male Sprague-Dawley rats were injected with STZ (intravenous, 65 mg/kg·bw, n=12/group). After 14 days, half of them received drinking water with candesartan (2 mg/kg·bw/day), an angiotensin-II type-1 receptor (AT1R) antagonist, for one week. In the medulla, i.e., inner stripe of the outer medulla (ISOM), base and/or tip of the inner medulla, immunoblotting revealed increased protein abundances of ?1 Na-K-ATPase and ENaC subunits with diabetes (200-600% of controls), which were not reversed by candesartan. In fact, candesartan increased all ENaC subunits and ?1 Na-K-ATPase in the ISOM and/or base in control rats. In contrast, in the cortex, diabetes did not increase these proteins. However, candesartan reduced cortical ?- and ?-ENaC regardless of diabetic state. In summary, diabetes-induced increases in ENaC were seen preferentially in the medulla. These changes appeared to be due to a mechanism clearly distinct from AT1R activation, because they were not abolished by candesartan. In fact, candesartan treatment tended to increase some of these medullary proteins, perhaps in compensation for increased NaCl load. In contrast, cortical ?- and ?-ENaC were reduced by candesartan regardless of diabetic state suggesting their regulation by AT1R at this site; however this did not appear to be a site of diabetes-induced ENaC up-regulation. PMID:20151042

Klein, Janet D; Rash, Arjun; Sands, Jeff M; Ecelbarger, Carolyn M; Tiwari, Swasti

2009-01-01

225

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

PubMed Central

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

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

2010-01-01

226

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

PubMed

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

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

2010-07-01

227

Antidiabetic and antihyperlipidemic activity of asiatic acid in diabetic rats, role of HMG CoA: in vivo and in silico approaches.  

PubMed

Hyperlipidemia is an associated complication of diabetes and also a major risk factor for cardiovascular diseases. The present study was designed to examine the antihyperlipidemic effect of asiatic acid (AA) in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40 mg/kg b.w.). Diabetic rats show increased plasma glucose, total cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density liprotein, atherogenic index and decreased insulin and high density lipoprotein in diabetic rats. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase increased significantly in contrast to the activities of lipoprotein lipase and lecithin cholesterol acyltransferase. In addition, the molecular docking of AA against HMG CoA reductase involved in cholesterol biosynthesis using Argus software. Diabetic rats were treated with AA shifted all these parameters towards normalcy. AA has shown best ligand binding energy 11.8122 kcal/mol. The antihyperlipidemic effect of AA was compared with glibenclamide; a well-known antihyperglycemic drug. In conclusion, this study indicates that AA showed an antihyperlipidemic effect in addition to its antidiabetic effect in experimental diabetes. PMID:24075211

Ramachandran, Vinayagam; Saravanan, Ramalingam; Senthilraja, Poomalai

2014-02-15

228

Insulin therapy modulates mitochondrial dynamics and biogenesis, autophagy and tau protein phosphorylation in the brain of type 1 diabetic rats.  

PubMed

The main purpose of this study was to examine whether streptozotocin (STZ)-induced type 1 diabetes (T1D) and insulin (INS) treatment affect mitochondrial function, fission/fusion and biogenesis, autophagy and tau protein phosphorylation in cerebral cortex from diabetic rats treated or not with INS. No significant alterations were observed in mitochondrial function as well as pyruvate levels, despite the significant increase in glucose levels observed in INS-treated diabetic rats. A significant increase in DRP1 protein phosphorylated at Ser616 residue was observed in the brain cortex of STZ rats. Also an increase in NRF2 protein levels and in the number of copies of mtDNA were observed in STZ diabetic rats, these alterations being normalized by INS. A slight decrease in LC3-II levels was observed in INS-treated rats when compared to STZ diabetic animals. An increase in tau protein phosphorylation at Ser396 residue was observed in STZ diabetic rats while INS treatment partially reversed that effect. Accordingly, a modest reduction in the activation of GSK3? and a significant increase in the activity of phosphatase 2A were found in INS-treated rats when compared to STZ diabetic animals. No significant alterations were observed in caspases 9 and 3 activity and synaptophysin and PSD95 levels. Altogether our results show that mitochondrial alterations induced by T1D seem to involve compensation mechanisms since no significant changes in mitochondrial function and synaptic integrity were observed in diabetic animals. In addition, INS treatment is able to normalize the alterations induced by T1D supporting the importance of INS signaling in the brain. PMID:24747740

Santos, R X; Correia, S C; Alves, M G; Oliveira, P F; Cardoso, S; Carvalho, C; Duarte, A I; Santos, M S; Moreira, P I

2014-07-01

229

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

PubMed Central

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

2014-01-01

230

Alteration of aortic function from streptozotocin-diabetic rats with Kilham's virus is associated with inducible nitric oxide synthase.  

PubMed

Kilham's rat virus (KRV) is a parvovirus commonly known to affect laboratory rats. Qualitative immunohistochemical analysis revealed that aorta isolated from KRV-infected streptozotocin (STZ)-induced diabetic adult rats expressed markedly greater levels of inducible nitric oxide synthase (iNOS) than aorta from KRV-infected controls. In contrast with the prevailing literature, nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was not blunted by STZ-diabetes, but was comparable to relaxations of aorta from controls. However, with increasing ex vivo duration, a decreased response to acetylcholine was observed in the STZ-diabetic aorta. In addition, whereas contraction responses to phenylephrine were not significantly altered over time in control tissue, aorta from STZ-diabetic rats developed increased tensions. The data suggest that increased iNOS-derived nitric oxide masks expected acetylcholine-mediated relaxation deficits as a result of KRV-infection, and that the deficit is unmasked by iNOS turnover ex vivo. PMID:16249104

Nangle, Matthew R; Cotter, Mary A; Cameron, Norman E

2006-11-01

231

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

PubMed Central

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

Lee, Soo Jung; Zhang, Gui Fang

2011-01-01

232

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.

Shin, Jae Hoon; Seong, Je Kyung

2014-01-01

233

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.

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

2014-01-01

234

In Vivo Assessment of Antihyperglycemic and Antioxidant Activity from Oil of Seeds of Brassica Nigra in Streptozotocin Induced Diabetic Rats  

PubMed Central

Purpose: This study was made to investigate the antihyperglycemic and antioxidant potential of oil of seeds of Brassica nigra (BNO) in streptozotocin -nicotinamide (STZ) induced type 2 diabetic rats. Methods: BNO was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic study. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. Results: Administration of BNO at a dose 500 mg/kg and 1000 mg/kg body weight p.o. to STZ diabetic rats showed reduction in blood glucose level from 335 mg/dl to 280 mg/dl at 4th h and from 330 mg/dl to 265 mg/dl respectively which was found significant (p<0.01) as compared with diabetic control. BNO (500 mg/kg and 1000 mg/kg) and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin-nicotinamide induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in glycosylated hemoglobin in test groups as compared to control group. In vivo antioxidant studies on STZ-nicotinamide induced diabetic rat’s revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH). Conclusion: Thus the results showed that the oil of seeds of Brassica nigra has significant antihyperglycemic and antioxidant activity.

Kumar, Manoj; Sharma, Sunil; Vasudeva, Neeru

2013-01-01

235

Effects of Momordica charantia on pancreatic histopathological changes associated with streptozotocin-induced diabetes in neonatal rats.  

PubMed

The aim of this research was to determine the effects of Momordica charantia (MC) fruit aqueous extract on pancreatic histopathological changes in neonatal STZ-induced type-II diabetic rats. Diabetes mellitus was induced in one day Sprague-Dawley neonatal rats using a single intrapretoneal injection of streptozotocin (STZ) (85 mg/kg body weight) and monitored for 12 weeks thereafter. The diabetic rats were separated into three groups, as follows: the diabetic control group (i.e. nSTZ), the diabetic group (i.e. nSTZ/M) - which was orally given 20 mg/kg of MC fruit extract, and the diabetic group (i.e. nSTZ/G) - that was treated with glibenclamide, 0.1 mg/kg for a period of four weeks. At the end of treatment, the animals were sacrificed and blood samples were collected from the saphenous vein to measure the blood glucose and serum insulin level. The pancreatic specimens were removed and processed for light microscopy, electron microscopy examination and immunohistochemical study. The results of this study showed that MC fruit aqueous extract reduced the blood glucose level as well as glibenclamide and increased the serum insulin level in the treated diabetic rats (P<0.05). The fruit extract of MC alleviated pancreatic damage and increased the number of ?-cells in the diabetic treated rats (P<0.05). Our results suggest that oral feeding of MC fruit extract may have a significant role in the renewal of pancreatic ?-cells in the nSTZ rats. PMID:21117023

Abdollahi, M; Zuki, A B Z; Goh, Y M; Rezaeizadeh, A; Noordin, M M

2011-01-01

236

Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.  

PubMed

Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug. PMID:24237189

Khan, Haseena Banu Hedayathullah; Shanmugavalli, R; Rajendran, Deepa; Bai, Mookambikai Ramya; Sorimuthu, Subramanian

2013-12-01

237

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

238

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

PubMed

The purpose of this study was to investigate the possible antioxidant effect of an aqueous extract of Ajuga iva (Ai) in streptozotocin (STZ)-induced diabetic rats. Twelve diabetic rats were divided into two groups fed a casein diet supplemented or not with Ai (0.5%), for 4 weeks. In vitro, the Ai extract possessed a very high antioxidant effect (1 mg/ml was similar to those of trolox 300 mmol/l). The results indicated that plasma thiobarbituric acid reactive substances (TBARS) values were reduced by 41% in Ai-treated compared with untreated diabetic rats. TBARS concentrations were lower 1.5-fold in liver, 1.8-fold in heart, 1.9-fold in muscle and 2.1-fold in brain in Ai-treated than untreated group. In erythrocytes, Ai treatment increased significantly the activities of glutathione peroxidase (GSH-Px) (+25%) and glutathione reductase (GSSH-Red) (+22%). Superoxide dismutase activity was increased in muscle (+22%), while GSH-Px activity was significantly higher in liver (+28%), heart (+40%) and kidney (+45%) in Ai-treated compared with untreated group. Liver and muscle GSSH-Red activity was, respectively, 1.6- and 1.5-fold higher in Ai-treated than untreated diabetic group. Catalase activity was significantly increased in heart (+36%) and brain (+32%) in Ai-treated than untreated group. Ai treatment decreased plasma nitric oxide (-33%), carbonyls (-44%) and carotenoids (-68%) concentrations. In conclusion, this study indicates that Ajuga iva aqueous extract improves the antioxidant status by reducing lipid peroxidation and enhancing the antioxidant enzymes activities in plasma, erythrocytes and tissues of diabetic rats. PMID:19196501

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

2009-06-01

239

Effect of the administration of Solanum nigrum fruit on blood glucose, lipid profiles, and sensitivity of the vascular mesenteric bed to phenylephrine in streptozotocin-induced diabetic rats  

PubMed Central

Background Solanum nigrum fruit is traditionally used in Asia to manage, control, and treat diabetes but there is no scientific evidence of the efficacy of Solanum nigrum fruit in treatment of diabetes. We designed this study to investigate the effect of the administration of oral doses of aqueous extract from Solanum nigrum fruit on plasma glucose, lipid profiles, and the sensitivity of the vascular mesenteric bed to Phenylephrine in diabetic and non-diabetic rats. Material/Methods Animals were divided into 5 groups (n=10): 2 groups served as non-diabetic controls (NDC), and the other groups had diabetes induced with a single injection of streptozotocin (STZ). Solanum nigrum-treated chronic diabetic (CD-SNE) and Solanum nigrum-treated controls (ND-SNE) received 1g/l of Solanum nigrum added to drinking water for 8 weeks. The mesenteric vascular beds were prepared using the McGregor method. Results Administration of Solanum nigrum caused Ca/Mg ratio, plasma glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), total cholesterol, and triglyceride concentrations to return to normal levels, and was shown to decrease alteration in vascular reactivity to vasoconstrictor agents. Conclusions Our results support the hypothesis that Solanum nigrum could play a role in the management of diabetes and the prevention of vascular complications in STZ-induced diabetic rats.

Sohrabipour, Shahla; Kharazmi, Fatemah; Soltani, Nepton; Kamalinejad, Mohammad

2013-01-01

240

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

241

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

242

The spontaneously diabetic Torii rat with gastroenteropathy  

Microsoft Academic Search

The spontaneously diabetic Torii (SDT) rat was recently recognized as a new animal model of non-obese type 2 diabetes. As the severe diabetic ocular complications seen in SDT rats already have been investigated, we examined another common diabetic complication, gastroenteropathy. Male SDT rats developed diabetes at 20 weeks and diarrhea at 28 weeks of age. Gastrointestinal motility was evaluated at

Kotaro Yamada; Masaya Hosokawa; Shimpei Fujimoto; Kazuaki Nagashima; Kazuhito Fukuda; Hideya Fujiwara; Eiichi Ogawa; Yoshihito Fujita; Naoya Ueda; Futoshi Matsuyama; Yuichiro Yamada; Yutaka Seino; Nobuya Inagaki

2007-01-01

243

Characterization of Upper Thoracic Spinal Neurons Receiving Noxious Cardiac and/or Somatic Inputs in Diabetic Rats  

PubMed Central

The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes. Type 1 diabetes was induced with streptozotocin (50 mg/kg) in 14 male Sprague-Dawley rats and citrate buffer was injected in 14 control rats. After 4–11 weeks, the rats were anesthetized with pentobarbital, ventilated and paralyzed. A laminectomy enabled extracellular recording of T3 spinal cord neuronal activity. Intrapericardial administration of a mixture of algogenic chemicals (bradykinin, serotonin, prostaglandin E2 (all at 10?5 M), and adenosine (10?3 M)) was applied to activate nociceptors of cardiac afferent nerve endings. Furthermore, somatic receptive properties were examined by applying innocuous (brush and light pressure) and noxious (pinch) cutaneous mechanical stimuli. Diabetes-induced increases in spontaneous activity were observed in subsets of neurons exhibiting long-lasting excitatory responses to administration of the algogenic mixture. Algogenic chemicals altered activity of a larger proportion of neurons from diabetic animals (73/111) than control animals (55/115, P < 0.05). Some subtypes of neurons exhibiting long-lasting excitatory responses, elicited prolonged duration and others, had a shortened latency. Some neurons exhibiting short-lasting excitatory responses in diabetic animals elicited a shorter latency and some a decreased excitatory change. The size of the somatic receptive field was increased for cardiosomatic neurons from diabetic animals. Cutaneous somatic mechanical stimulation caused spinal neurons to respond with a mixture of hyper- and hypoexcitability. In conclusion, diabetes induced changes in the spinal processing of cardiac input and these might contribute to cardiovascular autonomic neuropathy in patients with diabetes.

Ghorbani, Marie Louise M.; Qin, Chao; Wu, Mingyuan; Farber, Jay P.; Sheykhzade, Majid; Fjalland, Bjarne; Nyborg, Niels C.B.; Foreman, Robert D.

2011-01-01

244

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

PubMed Central

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

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

2014-01-01

245

Magnesium attenuates chronic hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat model of diabetic neuropathic pain  

PubMed Central

Neuropathic pain is a common diabetic complication affecting 8–16% of diabetic patients. It is characterized by aberrant symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. Magnesium (Mg) deficiency has been proposed as a factor in the pathogenesis of diabetes-related complications, including neuropathy. In the central nervous system, Mg is also a voltage-dependant blocker of the N-methyl-d-aspartate receptor channels involved in abnormal processing of sensory information. We hypothesized that Mg deficiency might contribute to the development of neuropathic pain and the worsening of clinical and biological signs of diabetes and consequently, that Mg administration could prevent or improve its complications. We examined the effects of oral Mg supplementation (296 mg l?1 in drinking water for 3 weeks) on the development of neuropathic pain and on biological and clinical parameters of diabetes in streptozocin (STZ)-induced diabetic rats. STZ administration induced typical symptoms of type 1 diabetes. The diabetic rats also displayed mechanical hypersensitivity and tactile and thermal allodynia. The level of phosphorylated NMDA receptor NR1 subunit (pNR1) was higher in the spinal dorsal horn of diabetic hyperalgesic/allodynic rats. Magnesium supplementation failed to reduce hyperglycaemia, polyphagia and hypermagnesiuria, or to restore intracellular Mg levels and body growth, but increased insulinaemia and reduced polydipsia. Moreover, it abolished thermal and tactile allodynia, delayed the development of mechanical hypersensitivity, and prevented the increase in spinal cord dorsal horn pNR1. Thus, neuropathic pain symptoms can be attenuated by targeting the Mg-mediated blockade of NMDA receptors, offering new therapeutic opportunities for the management of chronic neuropathic pain.

Rondon, L J; Privat, A M; Daulhac, L; Davin, N; Mazur, A; Fialip, J; Eschalier, A; Courteix, C

2010-01-01

246

Investigation of in vivo antioxidant property of Abelmoschus esculentus (L) moench. fruit seed and peel powders in streptozotocin-induced diabetic rats  

PubMed Central

Background: Abelmoschus esculentus (L.) Moench. fruit is a commonly consumed vegetable in many countries due to its rich medicinal value. However, till date, in vivo antioxidant property of A. esculentus has not been scientifically documented in animal models. Objective: The present investigation was aimed to evaluate the in vivo antioxidant property of A. esculentus (L.) Moench. peel and seed powder (AEPP and AESP) in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: In rats, acute toxicity assessment of AEPP and AESP at 2 g/kg did not show any toxicity. Diabetes was induced by STZ (60 mg/kg, i.p.) injection and diabetic rats received AEPP (100 and 200 mg/kg) as well as AESP (100 and 200 mg/ kg) orally up to 28 days. At the end of the 28 day, diabetic rats were killed and liver, kidney and pancreas were collected to determine superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation level. Results: In diabetic rats, significant (P < 0.001) reduction of liver, kidney and pancreas SOD, CAT, GPx, GSH levels and increase in thiobarbituric acid reactive substances (TBARS) were observed as compared to normal control rats. Administration of both doses of AEPP and AESP significantly (P < 0.001 and P < 0.01) increased liver, kidney and pancreas SOD, CAT, GPx, GSH levels and decreased TBARS (P < 0.001) levels in diabetic rats compared to diabetic control rats. Conclusion: Our findings confirmed that A. esculentus peel and seed powder has significant in vivo antioxidant property in diabetic rats.

Sabitha, Vijayakumar; Ramachandran, Subramaniam; Naveen, Koikaramparambil Robert; Panneerselvam, Kaliyamoorthy

2012-01-01

247

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

PubMed

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

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

2012-05-15

248

Effect of Granulocyte Colony-Stimulating Factor on the Peripheral Nerves in Streptozotocin-Induced Diabetic Rat  

PubMed Central

There are controversial reports about the effect of granulocyte colony-stimulating factor (G-CSF) in peripheral nerve protection. Therefore, the present study aimed to investigate the effect of G-CSF on peripheral nerves in streptozotocin (STZ) induced diabetic rats. After STZ or vehicle injection, rats were divided into five groups (n=6) as follows: normal+vehicle, normal+G-CSF (50 µg/kg for 5 days), diabetes mellitus (DM)+vehicle, DM+G-CSF (50 µg/kg for 5 days), and DM+G-CSF extension (50 µg/kg for 5 days and followed by two injections per week up to 24 weeks). Our results showed that the current perception threshold was not significantly different among experimental groups. G-CSF treatment inhibited the loss of cutaneous nerves and gastric mucosal small nerve fibers in morphometric comparison, but statistical significance was not observed. The present results demonstrated that G-CSF has no harmful but minimal beneficial effects with respect to peripheral nerve preservation in diabetic rats.

Lee, Kyung Ae; Park, Kyung Taek; Yu, Hea Min; Jin, Heung Yong; Baek, Hong Sun

2013-01-01

249

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

SciTech Connect

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

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

1991-03-15

250

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.

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

251

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

252

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.

Saravanan, Ganapathy; Ponmurugan, Ponnusamy

2013-01-01

253

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.

2013-01-01

254

[Protective effect of calcium dobesilate against early diabetic nephropathy of rat kidney].  

PubMed

The aim of this study is to study the effect of calcium dobesilate on streptozotocin (STZ)-induced early diabetic nephrophathy (DN) in rats. All male Wistar rats were randomly divided into six groups: normal group; DN blank group; calcium dobesilate 75, 150, and 300 mg x kg(-1) groups and perindopril 0.4 mg x kg(-1) group. Blood glucose and the 24 h urinary albumin were measured dynamically during the experiment, after 8 weeks administration, the level of glycosylated hemoglobin (HbA1c) was determined, the expressions of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloprotein-9 (MMP-9) in cortex of kidney were examined with immunohistochemical staining. The endothelin (ET) in plasma and kidney cortex was measured with radioimmunoassay, renal pathomorphism was observed with light and electron microscopes. Calcium dobesilate could decrease the 24 h urinary albumin and ET in plasma and kidney cortex, down-regulate the expression of PAI-1, and up-regulate MMP-9 in kidney. These findings suggested that calcium dobesilate could protect blood vessel endothelium, inhibit kidney fibrous degeneration, ameliorate renal pathological damage, and protect kidney function in many ways. PMID:19408680

Gao, Mei-Juan; Liu, Ming; Li, Bo; Li, Ming-Long; Bian, Li-Xiang; Yu, Gui-Na

2009-02-01

255

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

SciTech Connect

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

Pleta, M.; Chan, T.

1987-05-01

256

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

PubMed Central

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

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

2013-01-01

257

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

258

Kolaviron improved resistance to oxidative stress and inflammation in the blood (erythrocyte, serum, and plasma) of streptozotocin-induced diabetic rats.  

PubMed

Aims. Bitter kola seed (Garcinia kola, family: Guttiferae) has been used as a social masticatory agent in Africa for several years and is believed to possess many useful medicinal properties. The present study evaluates the antioxidative, anti-inflammatory, and antilipidemic effects of kolaviron (an extract from the Garcinia kola seeds) in the blood of streptozotocin- (STZ) induced diabetic rats. Methods. Diabetic rats were treated with kolaviron (100?mg/kg b·wt) orally, five times a week for a period of six weeks. Serum glucose and HBA1C concentrations were estimated in experimental groups. The activities of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) (in erythrocytes) as well as plasma concentration of malondialdehyde (MDA), a product of lipid peroxidation, oxygen radical absorbing capacity (ORAC) and ferric-reducing antioxidant power (FRAP) were investigated. Serum levels of proinflammatory cytokines and growth factor: interleukin- (IL-) 1, monocyte chemotactic protein-1 (MCP-1), and vascular endothelial growth factor (VEGF), respectively, were also analyzed. Results. Kolaviron treatment markedly improved antioxidant status and abated inflammatory response evidenced by reduction in the levels of proinflammatory cytokines and growth factor, lipid peroxidation product, and the restoration of activities of erythrocyte antioxidant enzymes in the blood of diabetic rats. Conclusion. Kolaviron improved antioxidant status, reduced inflammation, and protected against hyperglycemic-induced oxidative damage in the blood of diabetic rats. PMID:24795542

Ayepola, Omolola R; Brooks, Nicole L; Oguntibeju, Oluwafemi O

2014-01-01

259

Kolaviron Improved Resistance to Oxidative Stress and Inflammation in the Blood (Erythrocyte, Serum, and Plasma) of Streptozotocin-Induced Diabetic Rats  

PubMed Central

Aims. Bitter kola seed (Garcinia kola, family: Guttiferae) has been used as a social masticatory agent in Africa for several years and is believed to possess many useful medicinal properties. The present study evaluates the antioxidative, anti-inflammatory, and antilipidemic effects of kolaviron (an extract from the Garcinia kola seeds) in the blood of streptozotocin- (STZ) induced diabetic rats. Methods. Diabetic rats were treated with kolaviron (100?mg/kg b·wt) orally, five times a week for a period of six weeks. Serum glucose and HBA1C concentrations were estimated in experimental groups. The activities of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) (in erythrocytes) as well as plasma concentration of malondialdehyde (MDA), a product of lipid peroxidation, oxygen radical absorbing capacity (ORAC) and ferric-reducing antioxidant power (FRAP) were investigated. Serum levels of proinflammatory cytokines and growth factor: interleukin- (IL-) 1, monocyte chemotactic protein-1 (MCP-1), and vascular endothelial growth factor (VEGF), respectively, were also analyzed. Results. Kolaviron treatment markedly improved antioxidant status and abated inflammatory response evidenced by reduction in the levels of proinflammatory cytokines and growth factor, lipid peroxidation product, and the restoration of activities of erythrocyte antioxidant enzymes in the blood of diabetic rats. Conclusion. Kolaviron improved antioxidant status, reduced inflammation, and protected against hyperglycemic-induced oxidative damage in the blood of diabetic rats.

Ayepola, Omolola R.; Brooks, Nicole L.; Oguntibeju, Oluwafemi O.

2014-01-01

260

Preventive effect of danhong huayu koufuye on diabetic retinopathy in rats  

PubMed Central

AIM To study the effects of danhong huayu koufuye (DHK) on fasting blood glucose (FBG) and diabetic retinopathy (DR) in streptozotocin (STZ)-induced type 1 diabetic rats to facilitate the rational usage of this drug. METHODS Diabetic rats were induced by injection of a single dose of STZ intraperitoneally at 50mg/kg. Flash electroretinogram (FERG) and oscillatory potentials (OPs) were used to measure retinal function. The microvascular perfusion of ears was performed to study the microcirculation in rats. FBG, body-weight, and 24-h urine volume, water intake and diet intake were also assessed. RESULTS DHK had no effect on FBG in normal rats. However, STZ + DHK group were significantly different from those of Model and moved toward those of normal control. It reversed the increase in diet intake (P?0.05 vs model control) and the loss in body-weight (P?0.05 vs model control) in diabetic rats. DHK decreased the FBG of diabetic rats by 25.6% (P?0.05) and 37.9% (P?0.01) after 14 and 21 days administration as compared with the model control, respectively. Moreover, DHK significantly increased the FERG b-wave amplitude by 80% (P?0.05 vs model control) and decreased the FERG b-wave latency by 15.3% (P?0.01 vs model control) after 24 days administration. The OP1 and OP2 amplitudes in DHK group were 2.6 (P?0.01) and 2.0 (P?0.01) times of model group after 24 days of DHK treatment, respectively. At the same time, OP1 and OP2 latencies in DHK group reduced by 16.0% (P?0.001) and 14.7% (P?0.001) as compared with the model control, respectively. Furthermore, the microvascular perfusion of DHK group was 2.4 times of model group (P?0.001) after 21 days administration. CONCLUSION DHK had no effect on normal FBG. But it had antihyperglycemic activity, and had a preventive and therapeutic effect on DR in diabetic rats.

Lin, Bao-Qin; Zhou, Jiu-Yao; Ma, Yan; Deng, Ying-Jun; Zheng, Chuan-Jie; Lin, Jun-Li

2011-01-01

261

Microglia are Selectively Activated in Endocrine and Cardiovascular Control Centres in Streptozotocin-Induced Diabetic Rats.  

PubMed

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

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

2014-07-01

262

Antihyperglycemic and antioxidant activities of alcoholic extract of Commiphora mukul gum resin in streptozotocin induced diabetic rats.  

PubMed

Background and objectives: The present study investigated the effect of Commiphora mukul ethanol extract gum resin (CMEEt) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, plasma insulin, plasma lipid profile, atherogenic index, hepatic lipid peroxidation (LPO), protein oxidation (PO) and activities of enzymatic antioxidants. Methods: Wistar albino rats were divided into 4 groups, normal control group, CM-treated control group, diabetic control group and CM-treated diabetic group. For induction of diabetes, STZ was administered at a dose of 55mg/kg body weight, meanwhile CM-treated groups were administered CMEEt at a dose of 200mg/kg body weight for 60 days. Body weight, plasma glucose and insulin levels were determined in different experimental days, after end of the experimental period the plasma lipid profile and antioxidant enzymes were determined in hepatic tissue. Results: Increase in plasma glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), hepatic LPO and PO levels with decrease in plasma high density lipoprotein cholesterol (HDL-C), insulin, hepatic reduced glutathione (GSH) content and activities of antioxidant enzymes namely, glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were the salient features observed in diabetic rats. On the other hand, oral administration of CMEEt at a dose of 200mg/kg for 60 days resulted in the prevention of above mentioned abnormalities. Conclusion: The results suggest that CMEEt could be beneficial in the treatment of diabetes, characterized by atherogenous lipoprotein profile, aggravated antioxidant status and impaired glucose metabolism and in their prevention. PMID:21767936

Bellamkonda, Ramesh; Rasineni, Karuna; Singareddy, Sreenivasa Reddy; Kasetti, Ramesh Babu; Pasurla, Ramatholisamma; Chippada, Appa Rao; Desireddy, Saralakumari

2011-09-01

263

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

PubMed

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

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

2014-01-15

264

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

265

Omega-3 polyunsaturated fatty acids inhibit the accumulation of PAS-positive material in the myocardium of STZ-diabetic wistar rats.  

PubMed

This study was conducted to investigate the effect of Omega-3 PUFA on streptozotocin (STZ)-induced diabetic cardiomyopathy in wistar rats. After 4 weeks of STZ (60 mg/kg, i.v.) administration, the diabetic animals were randomly divided into two groups: Diabetic control and Omega-3 PUFA treated diabetic rats. Omega-3 PUFA (0.5 ml/kg) was administered to the latter group for 10 weeks. Age matched normal rats served as Normal controls. During the study, plasma glucose, glycosylated hemoglobin, plasma cholesterol, LDL and HDL cholesterol, triglyerides were evaluated in all the groups. Omega-3 PUFA treatment did not normalise but instead blunted the effect of diabetes with regards to the above parameters significantly (P<0.01). At the end of the experiment, morphometric and histochemical studies were performed on heart and myocardial enzyme markers were studied. In the diabetic control group, diabetic cardiomyopathy was characerised by elevated CPK (DC 110+/-8.85 vs. NC 39+/-5.83) and morphological changes in heart. Gravimetric ratios showed increased heart-to-body weight ratio in diabetic control over normal control group. (DC 3.38+/-0.05 vs. NC 2.48+/-0.03). Histochemical evidence showed increased accumulation of PAS-positive material in myocardial interstitium (++++). The Omega-3 PUFA treatment blunted all these adverse effects of diabetes on heart significantly (P<0.001). However, further studies are warranted to elucidate the mechanism by which Omega-3 PUFA decreases the accumulation of PAS-positive material in diabetic myocardium. PMID:12714197

Christopher, C Lawrance; Mathuram, L N; Genitta, G; Cyrus, I; Jaya Sundar, S

2003-04-01

266

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

PubMed Central

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

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

2013-01-01

267

The effects of rosiglitazone on oxidative stress and lipid profile in left ventricular muscles of diabetic rats.  

PubMed

We investigated the effect of rosiglitazone (RSG), a high-affinity ligand for the peroxisome proliferator-activated receptor gamma which mediates insulin-sensitizing actions, on the lipid profile and oxidative status in streptozotocin (STZ)-induced Type 2 diabetes mellitus (DM) rats. Wistar albino male rats were randomly divided into an untreated control group (C), a C + RSG group which was treated with RSG (4 mg kg(-1)) two times a day by gavage, a diabetic group (D) that was treated with a single intraperitoneal injection of STZ (45 mgkg(-1)), D + RSG group which were treated with RSG two times a day by gavage, respectively. Lipid profiles, HbA(1c) and blood glucose levels in the circulation and malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in left ventricular muscle were measured. Treatment of D rats with RSG resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA(1c) levels in D + RSG group reached the C rat values at the end of the treatment period. There was a statistically significant difference between the C + RSG and C groups in 3-NT levels. In group D, 3-NT and MDA levels were found to be increased when compared with C, C + RSG and D + RSG groups. In the D + RSG group, MDA levels were found to be decreased when compared with C and C + RSG. Our study suggests that the treatment of D rats with RSG for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus in diabetes-related vascular diseases, RSG treatment may be cardioprotective. PMID:18348180

Kavak, Servet; Ayaz, Lokman; Emre, Mustafa; Inal, Tamer; Tamer, Lülüfer; Günay, Ismail

2008-06-01

268

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

PubMed Central

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

Pari, Leelavinothan; Latha, Muniappan

2004-01-01

269

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.

2013-01-01

270

Complex modulation of the expression of PKC isoforms in the rat brain during chronic type 1 diabetes mellitus.  

PubMed

We previously demonstrated that chronic hyperglycemia has a detrimental influence on neurovascular coupling in the brain-an effect linked to an alteration in the protein kinase C (PKC)-mediated phosphorylation pattern. Moreover, the activity of PKC was increased, in diabetic rat brain, in a tissue fraction composed primarily of the superficial glia limitans and pial vessels, but trended toward a decrease in cerebral cortical gray matter. However, that study did not examine the expression patterns of PKC isoforms in the rat brain. Thus, in a rat model of streptozotocin (STZ)-induced chronic type 1 diabetes mellitus (T1DM), and in non-diabetic (ND) controls, two hypotheses were addressed. First, chronic T1DM is accompanied by changes in the expression of PKC-?, ?II, ?, ?, and ? Second, those changes differ when comparing cerebral cortex and glio-pial tissue. In addition, we analyzed the expression of a form of PKC-?, phosphorylated on threonine 514 (pT514-PKC-?), as well as the receptor for activated C kinase 1 (RACK1). The expression pattern of different PKC isoforms was altered in a complex and tissue-specific manner during chronic hyperglycemia. Notably, in the gray matter, PKC-? expression significantly decreased, while pT514-PKC-? expression increased. However, PKC-?II, -?, -?, -?, and RACK1 expressions did not change. Conversely, in glio-pial tissue, PKC-? and RACK1 were upregulated, whereas PKC-?, pT514-PKC-?, and PKC-? were downregulated. PKC-?II, and PKC-?, were unchanged. These findings suggest that the PKC activity increase previously seen in the glio-pial tissue of diabetic rats may be due to the selective upregulation of PKC-?, and ultimately lead to the impairment of neurovascular coupling. PMID:23103504

Vetri, Francesco; Chavez, Rafael; Xu, Hao-Liang; Paisansathan, Chanannait; Pelligrino, Dale A

2013-01-15

271

Neuromodulatory effects of hesperidin in mitigating oxidative stress in streptozotocin induced diabetes.  

PubMed

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

Ashafaq, Mohammad; Varshney, Laxmi; Khan, Mohammad Haaris Ajmal; Salman, Mohd; Naseem, Mehar; Wajid, Saima; Parvez, Suhel

2014-01-01

272

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

PubMed Central

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

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

2014-01-01

273

Streptozotocin-Induced Early Thermal Hyperalgesia is independent of Glycemic State of Rats: Role of Transient Receptor Potential Vanilloid 1(TRPV1) and Inflammatory mediators  

PubMed Central

Background Streptozotocin (STZ) is used as a common tool to induce diabetes and to study diabetes-induced complications including diabetic peripheral neuropathy (DPN). Previously, we have reported that STZ induces a direct effect on neurons through expression and function of the Transient receptor potential vanilloid 1 (TRPV1) channel in sensory neurons resulting in thermal hyperalgesia, even in non-diabetic STZ-treated mice. In the present study, we investigated the role of expression and function of TRPV1 in the central sensory nerve terminals in the spinal cord in STZ-induced hyperalgesia in rats. Results We found that a proportion of STZ-treated rats were normoglycemic but still exhibited thermal hyperalgesia and mechanical allodynia. Immunohistochemical data show that STZ treatment, irrespective of glycemic state of the animal, caused microglial activation and increased expression of TRPV1 in spinal dorsal horn. Further, there was a significant increase in the levels of pro-inflammatory mediators (IL-1?, IL-6 and TNF-?) in spinal cord tissue, irrespective of the glycemic state. Capsaicin-stimulated release of calcitonin gene related peptide (CGRP) was significantly higher in the spinal cord of STZ-treated animals. Intrathecal administration of resiniferatoxin (RTX), a potent TRPV1 agonist, significantly attenuated STZ-induced thermal hyperalgesia, but not mechanical allodynia. RTX treatment also prevented the increase in TRPV1-mediated neuropeptide release in the spinal cord tissue. Conclusions From these results, it is concluded that TRPV1 is an integral component of initiating and maintaining inflammatory thermal hyperalgesia, which can be alleviated by intrathecal administration of RTX. Further, the results suggest that enhanced expression and inflammation-induced sensitization of TRPV1 at the spinal cord may play a role in central sensitization in STZ-induced neuropathy.

2011-01-01

274

Administration of pigment epithelium-derived factor delivered by adeno-associated virus inhibits blood-retinal barrier breakdown in diabetic rats  

PubMed Central

Purpose To evaluate the effect of the recombinant adeno-associated virus (rAAV) vector that expresses human pigment epithelium-derived factor (hPEDF) on reducing blood–retinal barrier (BRB) breakdown in the experimental diabetic rat model. Methods Diabetes was induced by an intraperitoneal (i.p.) injection of streptozotocin (STZ) into 10-week-old male Wister rats. rAAV2-cytomegalovirus (CMV)-hPEDF was delivered into the right eyes by intravitreal injection on the first day after diabetes induction. The contralateral eyes received intravitreal injection of rAAV2-CMV-green fluorescent protein as the paired control. Gene delivery and expression of vascular endothelial growth factor (VEGF), occludin, and intercellular adhesion molecule-1 (ICAM-1) were determined with reverse transciptase PCR or western blotting. BRB breakdown changes were quantified by measuring albumin leakage from retinal blood vessels after an intravenous (i.v.) injection of Evans blue albumin. Results Retinal transfection with the hPEDF gene construct led to sustained hPEDF gene expression for 6 months, significantly suppressing VEGF mRNA expression in the retina after 1, 3, and 6 months of diabetes induced by STZ compared with paired controls. Moreover, hPEDF dramatically reduced the levels of retinal ICAM-1 but increased the expression of occludin. Furthermore, BRB breakdown was much lower in hPEDF-injected diabetic animals in comparison with controls after 6 months. Conclusions A single intravitreal injection of rAAV2-CMV-hPEDF can relieve BRB breakdown in STZ-induced diabetic rats for 6 months. The effect is associated with downregulation of retinal VEGF mRNA and ICAM-1 expression and a reduction in the loss of retinal occludin induced by diabetes. The approach of gene transfer may reduce diabetic macular edema, providing long-term protection for diabetic patients at risk of macular edema.

Yu, Hai; Jiang, Jing

2010-01-01

275

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

276

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.

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

2014-01-01

277

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

PubMed Central

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

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

2012-01-01

278

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

PubMed Central

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

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

2013-01-01

279

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

PubMed Central

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

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

2010-01-01

280

Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons  

PubMed Central

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (INaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of INaT and a decrease of potassium currents, especially slowly inactivating potassium currents (IAS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of INaT and total potassium current as well as IAS currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral analgesic action of gastrodin for the treatment of chronic pain, including PDN.

Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

2012-01-01

281

Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons.  

PubMed

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients' quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I(NaT)) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I(NaT) and a decrease of potassium currents, especially slowly inactivating potassium currents (I(AS)); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I(NaT) and total potassium current as well as I(AS) currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral analgesic action of gastrodin for the treatment of chronic pain, including PDN. PMID:22761855

Sun, Wei; Miao, Bei; Wang, Xiu-Chao; Duan, Jian-Hong; Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

2012-01-01

282

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.

2013-01-01

283

Fenugreek attenuation of diabetic nephropathy in alloxan-diabetic rats: attenuation of diabetic nephropathy in rats.  

PubMed

Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. To prevent the development of this disease and to improve advanced kidney injury, effective therapies directed toward the key molecular target are required. In this paper, the efficacy of fenugreek to restore the kidney function of diabetic rats via its antioxidant and anti-inflammatory activities has been studied. Novel data showing the efficacy of fenugreek to attenuate progression of diabetic nephropathy and production of interleukin-6 (IL-6) in rats compared with a diabetic untreated group were obtained. Rats were classified into five groups; control, diabetic untreated, and three diabetic groups treated with fenugreek, rosiglitazone, and metformin. Treatment with fenugreek has been continued for 12 weeks. Fenugreek was found to significantly reduce the high levels of glucose, urea, creatinine, sodium, potassium, and IL-6 in serum compared with the diabetic untreated group. In addition, levels of malondialdehyde and IL-6 in the kidney homogenate were significantly reduced as a result of the fenugreek treatment compared with the diabetic untreated group. Moreover, concentration of GSH and the activity of both superoxide dismutase and catalase were considerably increased in the diabetic treated groups compared with the diabetic untreated group. Furthermore, glomerular mesangial expansion was reduced in the treated animal groups. These findings suggest a therapeutic potential of fenugreek against diabetic nephropathy, explain its antioxidative/anti-inflammatory properties and provide a direction for future research. PMID:22237966

Sayed, Ahmed Amir Radwan; Khalifa, Mahmoud; Abd el-Latif, Fathy Fahim

2012-06-01

284

Effect of kaikasaponin III obtained from Pueraria thunbergiana flowers on serum and hepatic lipid peroxides and tissue factor activity in the streptozotocin-induced diabetic rat.  

PubMed

We investigated the effect of kaikasaponin III (KS-III) on Phase I and II enzymes and tissue factor (TF) activity to elucidate the pharmacological actions of this immunosuppressive saponin in the diabetic rat. This compound was obtained from the flower of Pueraria thunbergiana (Leguminosae) by chromatographic isolation. This crude drug (Puerariae Flos) has been used as a therapeutic agent for diabetes mellitus in traditional Korean medicine. KS-III prolonged the bleeding time and plasma clotting time in streptozotocin (STZ)-treated rats and increased the TF activity, suggesting that this compound has anti-thrombosis activity in STZ-induced rats. It also inhibited the formation of malondialdehyde (MDA) and hydroxy radicals in serum and liver, but promoted superoxide dismutase (SOD) activity. Low MDA concentrations and low xanthine oxidase and aldehyde oxidase activities were observed in the KS-III-treated rats, suggesting that such Phase I enzyme activities are the major source of lipid peroxidation. However, KS-III increased Phase II enzyme activities such as SOD, glutathione peroxidase, and catalase, suggesting the activation of free radical-scavenging enzymes. These results suggest that KS-III may exhibit its hypoglycemic and hypolipidemic effects by up-regulating or down-regulating antioxidant mechanisms via the changes in Phase I and II enzyme activities. PMID:15117550

Choi, Jongwon; Shin, Myung-Hee; Park, Kun-Young; Lee, Kyung-Tae; Jung, Hyun-Ju; Lee, Myung-Sun; Park, Hee-Juhn

2004-01-01

285

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

PubMed

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

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

2014-08-01

286

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

287

Curcumin ameliorates macrophage infiltration by inhibiting NF-?B activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy  

PubMed Central

Background Chronic inflammation plays an important role in the progression of diabetic nephropathy (DN) and that the infiltration of macrophages in glomerulus has been implicated in the development of glomerular injury. We hypothesized that the plant polyphenolic compound curcumin, which is known to exert potent anti-inflammatory effect, would ameliorate macrophage infiltration in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes was induced with STZ (55 mg/kg) by intraperitoneal injection in rats. Three weeks after STZ injection, rats were divided into three groups, namely, control, diabetic, and diabetic treated with curcumin at 100 mg/kg/day, p.o., for 8 weeks. The rats were sacrificed 11 weeks after induction of diabetes. The excised kidney was used to assess macrophage infiltration and expression of various inflammatory markers. Results At 11 weeks after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, blood urea nitrogen and proteinuria, along with marked reduction in the body weight. All of these abnormalities were significantly reversed by curcumin. Hyperglycemia induced the degradation of I?B? and NF-?B activation and as a result increased infiltration of macrophages (52%) as well as increased proinflammatory cytokines: TNF-? and IL-1?. Curcumin treatment significantly reduced macrophage infiltration in the kidneys of diabetic rats, suppressed the expression of above proinflammatory cytokines and degradation of I?B?. In addition, curcumin treatment also markedly decreased ICAM-1, MCP-1 and TGF-?1 protein expression. Moreover, at nuclear level curcumin inhibited the NF-?B activity. Conclusion Our results suggested that curcumin treatment protect against the development of DN in rats by reducing macrophage infiltration through the inhibition of NF-?B activation in STZ-induced diabetic rats.

2011-01-01

288

Nitrergic relaxations and phenylephrine contractions are not compromised in isolated urethra in a rat model of diabetes.  

PubMed

In vivo experiments in a diabetic rat model revealed compromised nitrergic urethral relaxations and increased sensitivity to adrenergic agonists. This study evaluated contractile and relaxation properties of urethral smooth muscle after streptozotocin (STZ)-induced diabetes, in vitro, with the aim of determining whether in vivo deficiencies are related to smooth muscle dysfunction. Urethral tissue was collected from adult female Sprague-Dawley rats naive, STZ-treated, vehicle-treated and sucrose-fed at 9-12week post treatment. Strips from proximal, mid, and distal urethra were placed in tissue baths and stimulated using electric field stimulation (EFS) and pharmacological agents. nNOS staining was evaluated using immunohistochemistry. Phenylephrine (PE, 10?M) contracted all urethral strips with the highest amplitude in mid urethra, in all treatment groups. Likewise, EFS-induced relaxation amplitudes were larger and were observed more frequently in mid urethra. Relaxations were inhibited by the NOS inhibitor, L-NAME (1-100?M). Sodium nitroprusside (0.01-1?M), an NO donor, reversed PE-induced contractions. No statistical differences were observed between treatment groups with respect to any parameters. Qualitative immunohistochemistry showed no differences in the urethral nNOS innervation patterns across the treatment groups. In summary, nitrergic relaxations and adrenergic-induced contractions in the isolated diabetic rat urethra display similar properties to controls, suggesting no dysfunction on the nitrergic or alpha1 adrenergic receptor function in the smooth muscle. This further implies that compromised urethral relaxation and increased adrenergic agonist sensitivity observed in vivo in this model may be due to the disruption of neural signaling between the urethra and the spinal cord, or within the CNS. PMID:24656892

Al-Noah, Z; McKenna, D; Langdale, C; Thor, K B; Marson, L; Burgard, E; Kullmann, F Aura

2014-07-01

289

Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats.  

PubMed

The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats. PMID:18797156

Nakano, Masako; Onodera, Aya; Saito, Emi; Tanabe, Miyako; Yajima, Kazue; Takahashi, Jiro; Nguyen, Van Chuyen

2008-08-01

290

Streptozotocin, Type I Diabetes Severity and Bone  

PubMed Central

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

2009-01-01

291

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

PubMed Central

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

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

2012-01-01

292

Effect of Telmisartan in Experimentally Induced Diabetetes Mellitus in Rats  

PubMed Central

Background: Increased oxidative stress is involved in the pathogenesis of diabetic nephropathy and neuropathy. Angiotensin II is a know factor in the pathogenesis of diabetic complications. The protective effects of ACEIs is known in diabetic nephropathy. Thus, Angiotensin receptor antagonists may have the same role. In this study, possible antidiabetic effect of Telmisartan and its tissues antioxidant effect in (STZ) induced diabetic rats, were studied Methods : The present study was done on 40 rats. They were divided into 2 main groups. Group I: 10 rats as control group, received distilled water. Group II: 30 rats subdivided into 3 equal subgroups as follow: Subgroup IIA: control diabetic group, received 55 mg/kg STZ intraperitoneally. Sub group IIB: diabetic rats, received 10 mg/kg telmisartan daily intragastrically. Sub group IIC: diabetic rats received 10mg/kg gliclazide daily intragastrically. Diabetes was induced by intraperitoneal injection of 55 mg/kg STZ for 8 weeks evidenced by significant increase in serum glucose, HBA1c and decreased Hb levels. Results : Diabetic rats showed a significant increase in tissue TBARs and a significant decrease in tissue (GSH) and (SOD) enzymes. Telmisartan or Gliclazide in diabetic rats produced a beneficial effect on serum glucose, Hb, HBA1c and restored tissue GSH and SOD with a fall in tissues TBARS. Conclusion : Telmisartan might be proved useful in the treatment of diabetes and its complications, as Gliclazide is restricted by its secondary failure rate and side effects.

Hamed, Amal A.; Malek, Hala A

2007-01-01

293

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.

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

294

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

295

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

PubMed Central

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

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

2013-01-01

296

RENAL TRANSPLANTATION IN DIABETES MELLITUS IN RATS  

PubMed Central

Immunoglobulins and complement are deposited in the glomerular mesangium of rats with progressive glomerulosclerosis secondary to chemically induced diabetes mellitus. Isotransplantation of a kidney from a rat diabetic for 6 mo into a normal recipient results within 2 mo in the disappearance of IgG, IgM, and ?1C from the mesangium and arrest or reversal of the light microscopic glomerular lesions. Kidneys isotransplanted from normal donors into diabetic rats developed mesangial matrix thickening and deposition of IgG, IgM) and ?1C in the mesangium. No glomerular changes occur upon transplantation of a normal kidney into a normal rat. These findings indicate that diabetic glomerular changes in the rat are reversible and are secondary to the diabetic state rather than to the inducing agent.

Lee, Chue Shue; Mauer, S. Michael; Brown, David M.; Sutherland, David E. R.; Michael, Alfred F.; Najarian, John S.

1974-01-01

297

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

298

Antihyperglycaemic effect of Mangifera indica in rat.  

PubMed

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

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

1999-09-01

299

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

PubMed

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

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

2013-05-01

300

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.

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

2014-01-01

301

Hematological Changes in Opium Addicted Diabetic Rats  

PubMed Central

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

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

2013-01-01

302

Total parenteral nutrition in diabetic rats  

SciTech Connect

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

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

1986-03-01

303

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

304

Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells.  

PubMed

Pancreatic injury induces replacement of exocrine acinar cells with ductal cells. These ductal cells have the potential to regenerate the pancreas, but their origin still remains unknown. It has been reported that adult pancreatic acinar cells have the potential to transdifferentiate to ductal progenitor cells. In this regards, we established novel adult pancreatic duct-like progenitor cell lines YGIC4 and YGIC5 and assessed the usefulness of these ductal progenitors in the cell therapy of diabetic rats. Acinar cells were cultured from pancreata of male Sprague Dawley rats and gradually attained ductal cell characteristics, such as expression of CK19 and CFTR with a concomitant down-regulation of amylase expression over time, suggesting transdifferentiation from acinar to ductal cells. During cell culture, the expression of Pdx-1, c-Kit, and vimentin peaked and then decreased, suggesting that transdifferentiation recapitulated embryogenesis. Overexpression of pancreas development regulatory genes and CK19, as well as the ability to differentiate into insulin-producing cells, suggests that the YGIC5 cells had characteristics of pancreatic progenitor cells. Finally, YGIC5 cells coexpressing Green fluorescent protein (GFP) and glucagon-like peptide (GLP)-1 under the activation of a zinc-inducible metallothionein promoter were intravenously infused to STZ-induced diabetic rats. Hyperglycemia was ameliorated with elevation of plasma insulin, and GFP-positive donor cells were colocalized in the acinar and islet areas of recipient pancreata following zinc treatment. In conclusion, after establishing pancreatic progenitor cell lines YGIC4 and YGIC5 under the concept of acinar to ductal transdifferentiation in vitro, we demonstrate how these adult pancreatic stem/progenitor cells can be used to regulate adult pancreatic differentiation toward developing therapy for pancreatic disease such as diabetes mellitus. PMID:19125629

Lee, Jieun; Wen, Jing; Park, Jeong Youp; Kim, Sun-A; Lee, Eun Jig; Song, Si Young

2009-09-01

305

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

PubMed Central

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

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

2014-01-01

306

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

PubMed

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

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

2014-01-01

307

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.

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

2008-01-01

308

Ciliary neurotrophic factor reverses aberrant mitochondrial bioenergetics through the Jak/STAT pathway in cultured sensory neurons derived from streptozotocin-induced diabetic rodents.  

PubMed

Mitochondrial dysfunction occurs in sensory neurons and contributes to diabetic neuropathy. Ciliary neurotrophic factor (CNTF) stimulates axon regeneration in type 1 diabetic rodents and prevents deficits in axonal caliber, nerve conduction, and thermal sensation. We tested the hypothesis that CNTF enhances sensory neuron function in diabetes through JAK/STAT (Janus kinase/signal transducers and activators of transcription) signaling to normalize impaired mitochondrial bioenergetics. The effect of CNTF on gene expression and neurite outgrowth of cultured adult dorsal root ganglia (DRG) sensory neurons derived from control and streptozotocin (STZ)-induced diabetic rodents was quantified. Polarization status and bioenergetics profile of mitochondria from cultured sensory neurons were determined. CNTF treatment prevented reduced STAT3 phosphorylation (Tyr 705) in DRG of STZ-diabetic mice and also enhanced STAT3 phosphorylation in rat DRG cultures. CNTF normalized polarization status of the mitochondrial inner membrane and corrected the aberrant oligomycin-induced mitochondrial hyperpolarization in axons of diabetic neurons. The mitochondrial bioenergetics profile demonstrated that spare respiratory capacity and respiratory control ratio were significantly depressed in sensory neurons cultured from STZ-diabetic rats and were corrected by acute CNTF treatment. The positive effects of CNTF on neuronal mitochondrial function were significantly inhibited by the specific JAK inhibitor, AG490. Neurite outgrowth of sensory neurons from age-matched control and STZ-induced diabetic rats was elevated by CNTF and blocked by AG490. We propose that CNTF's ability to enhance axon regeneration and protect from fiber degeneration in diabetes is associated with its targeting of mitochondrial function and improvement of cellular bioenergetics, in part, through JAK/STAT signaling. PMID:24682898

Chowdhury, Subir Roy; Saleh, Ali; Akude, Eli; Smith, Darrell R; Morrow, Dwane; Tessler, Lori; Calcutt, Nigel A; Fernyhough, Paul

2014-07-01

309

Pharmacokinetics and pharmacodynamics of gliclazide from immediate and modified release formulation tablets in rats.  

PubMed

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

310

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.

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

2014-01-01

311

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.

2014-01-01

312

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

313

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

Microsoft Academic Search

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

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

2011-01-01

314

Thujone corrects cholesterol and triglyceride profiles in diabetic rat model.  

PubMed

Thujone, which is the major constituent in Salvia sp. (Lamiaceae), was found to correct the lipid profile (cholesterol and triglycerides) in diabetic rats. Oral treatment with thujone (5 mg kg?¹ body weight dose) significantly adjusted cholesterol and triglyceride levels in diabetic rats (p ? 0.05) to normal levels compared to diabetic untreated rats. This provides a premise in the field of finding new agents to treat diabetic complications. PMID:21740283

Baddar, Nour W Al-Haj; Aburjai, Talal A; Taha, Mutasem O; Disi, Ahmad M

2011-07-01

315

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

316

Curcumin Alleviates Diabetic Cardiomyopathy in Experimental Diabetic Rats  

PubMed Central

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

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

2012-01-01

317

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

PubMed Central

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

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

2013-01-01

318

Oxidative stress status accompanying diabetic bladder cystopathy results in the activation of protein degradation pathways  

PubMed Central

Objectives To investigate the role that oxidative stress plays in the development of diabetic cystopathy. Materials and methods Comparative gene expression in the bladder of non-diabetic and streptozotocin (STZ)-induced 2-month-old diabetic rats was carried out using microarray analysis. Evidence of oxidative stress was investigated in the bladder by analyzing glutathione S-transferase activity, lipid peroxidation, and carbonylation and nitrosylation of proteins. The activity of protein degradation pathways was assessed using western blot analysis. Results Analysis of global gene expression showed that detrusor smooth muscle tissue of STZ-induced diabetes undergoes significant enrichment in targets involved in the production or regulation of reactive oxygen species (P = 1.27 × 10?10). The microarray analysis was confirmed by showing that markers of oxidative stress were all significantly increased in the diabetic bladder. It was hypothesized that the sequelae to oxidative stress would be increased protein damage and apoptosis. This was confirmed by showing that two key proteins involved in protein degradation (Nedd4 and LC3B) were greatly up-regulated in diabetic bladders compared to controls by 12.2 ± 0.76 and 4.4 ± 1.0-fold, respectively, and the apoptosis inducing protein, BAX, was up-regulated by 6.76 ± 0.76-fold. Conclusions Overall, the findings obtained in the present study add to the growing body of evidence showing that diabetic cystopathy is associated with oxidative damage of smooth muscle cells, and results in protein damage and activation of apoptotic pathways that may contribute to a deterioration in bladder function.

Kanika, Nirmala; Chang, Jinsook; Tong, Yuehong; Tiplitsky, Scott; Lin, Juan; Yohannes, Elizabeth; Tar, Moses; Chance, Mark; Christ, George J.; Melman, Arnold; Davies, Kelvin

2010-01-01

319

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

PubMed

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

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

2014-05-01

320

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

321

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.

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

2013-01-01

322

Protective effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats.  

PubMed

Extracts from various morphological parts of Annona muricata Linn. (Annonaceae) are widely used medicinally in many parts of the world for the management, control and/or treatment of a plethora of human ailments, including diabetes mellitus (DM). The present study was undertaken to investigate the possible protective effects of A. muricata leaf aqueous extract (AME) in rat experimental paradigms of DM. The animals used were broadly divided into four (A, B, C and D) experimental groups. Group A rats served as 'control' animals and received distilled water in quantities equivalent to the administered volumes of AME and reference drugs' solutions intraperitoneally. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of streptozotocin (STZ, 70 mg kg(-1)). Group C rats were additionally treated with AME (100 mg kg(-1) day(-1), p.o.) as from day 3 post STZ injection, for four consecutive weeks. Group D rats received AME (100 mg kg(-1) day(-1) p.o.) only for four weeks. Post-euthanization, hepatic tissues were excised and processed biochemically for antioxidant enzymes and lipid profiles, such as catalase (CAT), reactive oxygen species (ROS), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), respectively. Treatment of Groups B and C rats with STZ (70 mg kg(-1) i. p.) resulted in hyperglycaemia, hypoinsulinaemia, and increased TBARS, ROS, TC, TG and LDL levels. STZ treatment also significantly decreased (p<0.05) CAT, GSH, SOD, GSH-Px activities, and HDL levels. AME-treated Groups C and D rats showed significant decrease (p<0.05) in elevated blood glucose, ROS, TBARS, TC, TG and LDL. Furthermore, AME treatment significantly increased (p<0.05) antioxidant enzymes' activities, as well as serum insulin levels. The findings of this laboratory animal study suggest that A. muricata extract has a protective, beneficial effect on hepatic tissues subjected to STZ-induced oxidative stress, possibly by decreasing lipid peroxidation and indirectly enhancing production of insulin and endogenous antioxidants. PMID:20162039

Adewole, Stephen O; Ojewole, John A O

2008-01-01

323

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

PubMed

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

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

2013-03-01

324

Chronopharmacokinetics of Puerarin in Diabetic Rats  

PubMed Central

Puerarin injection has been widely used for clinic treatment of diabetes recently. To assess the relationship between the administration time of puerarin and the blood concentration of puerarin as well as its pharmacokinetic parameters, the diabetic rat model was used in current study. The rats were randomly divided into morning and evening groups according to the administration time. After the puerarin injection, blood glucose was tested in order to know whether the efficiency of puerarin was influenced by its concentration and pharmacokinetic parameters. Our results show that the average concentration of puerarin in the evening group is significantly higher than that in the morning group. The numbers of t1/2?, t1/2?, CL and AUC(0-?) are significantly different between the morning and evening groups. The blood glucose level in the evening group was lower than that in the morning group. The speed of its onset is higher and the blood glucose level declines much more significantly in the evening group. These findings suggest that the concentration and pharmacokinetic parameters of puerarin affect its efficiency in diabetic rats. Therefore, it might be better to give puerarin in evening than in the morning for the mellitus treatment.

Zhang, C. T.; Shi, D.; Zheng, Y.; Zheng, C. Y.; Li, Q. H.

2013-01-01

325

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

Microsoft Academic Search

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

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

1998-01-01

326

Relationship between MRI and morphometric kidney measurements in diabetic and non-diabetic rats  

Microsoft Academic Search

Relationship between MRI and morphometric kidney measurements in diabetic and non-diabetic rats. The aim of the present study was to determine the applicability of magnetic resonance imaging (MRI) as a non-invasive measure of kidney volume in vivo in diabetic and non-diabetic rats. Magnetic resonance, T1 weighted Spin Echo, images were obtained after injection of contrast in anesthetized control (N =

Thora Christiansen; R Rasch; H Stødkilde-Jørgensen; A Flyvbjerg

1997-01-01

327

Boldine Prevents Renal Alterations in Diabetic Rats  

PubMed Central

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50?mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100?µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects.

Hernandez-Salinas, Romina; Vielma, Alejandra Z.; Arismendi, Marlene N.; Boric, Mauricio P.; Saez, Juan C.; Velarde, Victoria

2013-01-01

328

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

PubMed

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

Umamaheswari, Selvaraj; Mainzen Prince, Ponnaian Stanely

2007-01-01

329

Adipocyte dysfunction in rats with streptozotocin-nicotinamide-induced diabetes.  

PubMed

Administration of streptozotocin (STZ) and nicotinamide (NA) to adult rats allows for the induction of mild diabetes. However, this experimental model has not been fully characterized. This study was undertaken to determine the metabolic and secretory activity of adipose tissue in rats with STZ-NA-induced diabetes. Experiments were performed using epididymal adipocytes isolated from control and mildly diabetic rats. Lipogenesis, glucose transport as well as glucose and alanine oxidation, lipolysis, anti-lipolysis, cAMP levels and adipokine secretion were compared in cells isolated from the control and diabetic rats. Lipogenesis, glucose transport and oxidation were diminished in the adipocytes of diabetic rats compared with the fat cells of control animals. However, alanine oxidation appeared to be similar in the cells of non-diabetic and diabetic animals. Lipolytic response to low epinephrine concentrations was slightly increased in the adipocytes of diabetic rats; however, at higher concentrations of the hormone, lipolysis was similar in both groups of cells. The epinephrine-induced rise in cAMP levels was higher in the adipocytes of STZ-NA-induced diabetic rats, even in the presence of insulin. Lipolysis stimulated by dibutyryl-cAMP did not significantly differ, whereas anti-lipolytic effects of insulin were mildly decreased in the cells of diabetic rats. Secretion of adiponectin and leptin was substantially diminished in the adipocytes of diabetic rats compared with the cells of control animals. Our studies demonstrated that the balance between lipogenesis and lipolysis in the adipose tissue of rats with mild diabetes induced by STZ and NA is slightly shifted towards reduced lipid accumulation. Simultaneously, adiponectin and leptin secretion is significantly impaired. PMID:24628786

Szkudelska, Katarzyna; Nogowski, Leszek; Szkudelski, Tomasz

2014-04-01

330

Engineered Zinc Finger Protein-Mediated VEGF-A Activation Restores Deficient VEGF-A in Sensory Neurons in Experimental Diabetes  

PubMed Central

OBJECTIVE The objectives of the study were to evaluate retrograde axonal transport of vascular endothelial growth factor A (VEGF-A) protein to sensory neurons after intramuscular administration of an engineered zinc finger protein activator of endogenous VEGF-A (VZ+434) in an experimental model of diabetes, and to characterize the VEGF-A target neurons. RESEARCH DESIGN AND METHODS We compared the expression of VEGF-A in lumbar (L)4/5 dorsal root ganglia (DRG) of control rats and VZ+434-treated and untreated streptozotocin (STZ)-induced diabetic rats. In addition, axonal transport of VEGF-A, activation of signal transduction pathways in the DRG, and mechanical sensitivity were assessed. RESULTS VEGF-A immunoreactivity (IR) was detected in small- to medium-diameter neurons in DRG of control rats. Fewer VEGF-A-IR neurons were observed in DRG from STZ-induced diabetic rats; this decrease was confirmed and quantified by Western blotting. VZ+434 administration resulted in a significant increase in VEGF-A protein expression in ipsilateral DRG, 24 h after injection. VEGF-A was axonally transported to the DRG via the sciatic nerve. VZ+434 administration resulted in significant activation of AKT in the ipsilateral DRG by 48 h that was sustained for 1 week after injection. VZ+434 protected against mechanical allodynia 8 weeks after STZ injection. CONCLUSIONS Intramuscular administration of VZ+434 increases VEGF-A protein levels in L4/5 DRG, correcting the deficit observed after induction of diabetes, and protects against mechanical allodynia. Elevated VEGF-A levels result from retrograde axonal transport and are associated with altered signal transduction, via the phosphatidylinositol 3?-kinase pathway. These data support a neuroprotective role for VEGF-A in the therapeutic actions of VZ+434 and suggest a mechanism by which VEGF-A exerts this activity.

Pawson, Elizabeth J.; Duran-Jimenez, Beatriz; Surosky, Richard; Brooke, Heather E.; Spratt, S. Kaye; Tomlinson, David R.; Gardiner, Natalie J.

2010-01-01

331

Previous Exercise Training Has a Beneficial Effect on Renal and Cardiovascular Function in a Model of Diabetes  

PubMed Central

Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p<0.05). Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p<0.05). The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p<0.05), and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p<0.05). In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p<0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.

Silva, Kleiton Augusto dos Santos; Luiz, Rafael da Silva; Rampaso, Rodolfo Rosseto; de Abreu, Nayda Parisio; Moreira, Edson Dias; Mostarda, Cristiano Teixeira; De Angelis, Katia; de Paulo Castro Teixeira, Vicente; Irigoyen, Maria Claudia; Schor, Nestor

2012-01-01

332

Cardiovascular responses and central catecholamines in streptozocin-diabetic rats.  

PubMed

Brain catecholamine levels, spinal cord levels of the norepinephrine metabolite methoxy-hydroxy-phenylglycol (MHPG), and heart rate were measured in nondiabetic and streptozocin-diabetic rats after sham surgery or bilateral carotid ligation. Although carotid ligation increased heart rate in both diabetic and nondiabetic rats, in diabetic animals the response did not differ from the response to sham surgery. Carotid ligation increased epinephrine concentrations in the medulla/pons of diabetic animals but was not associated with alterations in other central catecholamines. In all diabetic rats spinal ratios of MHPG/norepinephrine (an index of noradrenergic activity) were higher than in nondiabetics, and the change in heart rate (post-surgical-pre-surgical rate) correlated inversely with hypothalamic dopamine (R = -0.60). In sham-operated diabetic rats there were high inverse correlations of the change in heart rate with medullary epinephrine and of pre- and post-surgical heart rate with spinal MHPG/NE (R = -0.87 to -0.95). Central catecholamines and heart rate were not correlated in nondiabetic animals and correlated only weakly when nondiabetic and diabetic animals were pooled. Correlations in diabetic animals were usually abolished or reduced by carotid ligation. These findings suggest a link between central catecholamines and heart rate in diabetic rats subjected to surgical stress. Whether catecholaminergic neurons contribute to abnormal chronotropic responses in diabetic rats or respond to stimuli that affect both heart rate and neural function remains to be determined. PMID:8161945

Stewart, J K; Campbell, T G; Gbadebo, T D; Narasimhachari, N; Manning, J W

1994-02-01

333

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

PubMed

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

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

1997-03-01

334

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

335

Protective effects of bendazac lysine on diabetic peripheral neuropathy in streptozotocin-induced diabetic rats.  

PubMed

1. Diabetic neuropathy is a many faceted complication of both type I and II diabetes. The aim of the present study was to investigate the effects of bendazac lysine (BDL), an anticataract drug, on experimental diabetic peripheral neuropathy (DPN) in rats. 2. Diabetes was induced in rats by intraperitoneal injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200 mg/kg twice a day for 12 weeks. 3. Diabetic rats without treatment showed hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail-flick threshold temperature, decreased motor nerve conduction velocity (nd induced pathological morphological changes of myelinated nerve fibres. All these symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine ameliorated the blood glucose concentration, glycosylated haemoglobin levels and insulin levels in the plasma of diabetic rats, reduced aldose reductase activity in erythrocytes and advanced glycation end-products in both nerves and serum and increase the activity of glutathione peroxidase in the nerves and Na(+)/K(+)-ATPase in the nerves and erythrocytes. 4. Bendazac lysine exerts its protective effects against the progression of diabetic peripheral neuropathy in STZ-diabetic rats through multiple mechanisms and is a potential drug for the prevention of deterioration in DPN. PMID:17184506

Yu, Jun-Xian; Yin, Xiao-Xing; Shen, Jian-Ping; Qiu, Jun; Yin, Hong-Lin; Jiang, Shao-Jun

2006-12-01

336

Synergetic effect of Andrographis paniculata polysaccharide on diabetic nephropathy with andrographolide.  

PubMed

A water-soluble polysaccharide (APP), with a molecular weight of 4.6×10(4) Da, was isolated from Andrographis paniculata and gas chromatography (GC) analysis showed APP was composed of galactose, mannose, fucose, arabinose and rhamnose with molar ratios of 15.4:2.5:4.3:1.5:1.6. The synergetic effect of APP in combination with andrographolide on renal complication in streptozotocin (STZ) induced diabetic mice was investigated. Wistar rats were made diabetic by injection of STZ, and APP and/or andrographolide was administered to diabetic mice for continuous two weeks. APP plus andrographolide not only increased the body weight and creatinine clearance rate (Ccr), but also decreased the levels of serum creatinine, serum urea nitrogen, urinary albumin excretion (UAE), serum urea and blood glucose in diabetic rats, as well as the relative kidney weight. In summary, APP plus andrographolide can improve the metabolic abnormalities of diabetic mice and prevent or delay the progression of diabetic renal complications, which may be useful as a therapeutic agent for inhibiting the progression of diabetic nephropathy. PMID:22766034

Xu, Jie; Li, Zhanting; Cao, Min; Zhang, Han; Sun, Jifeng; Zhao, Jie; Zhou, Qiang; Wu, Zhifen; Yang, Lianjia

2012-12-01

337

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

Microsoft Academic Search

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

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

1998-01-01

338

Kilham rat triggers T-cell-dependent autoimmune diabetes in multiple strains of rat.  

PubMed

Kilham rat virus (KRV) infection of BB/Wor diabetes-resistant (DR) RT1(u) rats induces autoimmune diabetes without direct cytolytic infection of pancreatic beta-cells and is a new model of virus-induced IDDM. To investigate genetic susceptibility to KRV-induced diabetes, major histocompatibility complex congenic and other inbred rats were infected with the virus and studied for the appearance of diabetes and insulitis. KRV infection alone induced insulitis, selective beta-cell necrosis, and diabetes in BB/Wor DR and LEW1.WR1 (RT1 A(u) B/D(u) C(a)) but not other rats. Thus, KRV, an environmentally ubiquitous rat parvovirus, can precipitate autoimmune diabetes in rats that are not susceptible to spontaneous diabetes. If rats are injected with poly(I.C) immediately before KRV infection, diabetes frequency increases to >90% in BB/Wor DR and LEW1.WR1 rats, and PVG.RT1(u) rats are converted from KRV-resistant to KRV-susceptible status. Susceptibility to KRV-induced diabetes thus requires the presence of class I A(u) and class II B/D(u) gene products, which are shared by DR, LEW1.WR1, and PVG.RT1(u) rats. The RT1(u) haplotype is not sufficient for susceptibility, however, because while WF rats are RT1(u), they resist KRV-induced diabetes. If rats are depleted of RT6.1+ regulatory T-cells before KRV infection, the frequency of diabetes is dramatically increased in DR and LEW1.WR1, but not PVG.RT1(u) or other rats. These data confirm a regulatory role of RT6.1+ T-cells in diabetes induction, but indicate that they may not operate as such in all rat strains. KRV-induced diabetes is T-cell-mediated: DR and LEW1.WR1 rats are protected from diabetes by treatment with monoclonal antibodies directed against alpha beta T-cell receptor (TCR)+, CD5+, and CD8+ T-cells. Concanavalin A-activated spleen cells from KRV-infected DR rats adoptively transfer diabetes and insulitis into class II(u) compatible rats, suggesting that KRV infection of susceptible rats leads to the activation of diabetogenic class II(u) restricted T-cells. The ability of a common rat virus to initiate IDDM in multiple strains of rats strengthens the possibility that viruses may also initiate IDDM in human populations. PMID:8621003

Ellerman, K E; Richards, C A; Guberski, D L; Shek, W R; Like, A A

1996-05-01

339

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

340

Decrease of hyperglycemia by syringaldehyde in diabetic rats.  

PubMed

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

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

2014-01-01

341

[Treatment of diabetes in experimental animals by metallocomplexes].  

PubMed

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

Sakurai, Hiromu

2008-03-01

342

Somatostatin and diabetic retinopathy: current concepts and new therapeutic perspectives.  

PubMed

Somatostatin (SST) is abundantly produced by the human retina, and the main source is the retinal pigment epithelium (RPE). SST exerts relevant functions in the retina (neuromodulation, angiostatic, and anti-permeability actions) by interacting with SST receptors (SSTR) that are also expressed in the retina. In the diabetic retina, a downregulation of SST production does exist. In this article, we give an overview of the mechanisms by which this deficit of SST participates in the main pathogenic mechanisms involved in diabetic retinopathy (DR): neurodegeneration, neovascularization, and vascular leakage. In view of the relevant SST functions in the retina and the reduction of SST production in the diabetic eye, SST replacement has been proposed as a new target for treatment of DR. This could be implemented by intravitreous injections of SST analogs or gene therapy, but this is an aggressive route for the early stages of DR. Since topical administration of SST has been effective in preventing retinal neurodegeneration in STZ-induced diabetic rats, it seems reasonable to test this new approach in humans. In this regard, the results of the ongoing clinical trial EUROCONDOR will provide useful information. In conclusion, SST is a natural neuroprotective and antiangiogenic factor synthesized by the retina which is downregulated in the diabetic eye and, therefore, its replacement seems a rational approach for treating DR. However, clinical trials will be needed to establish the exact position of targeting SST in the treatment of this disabling complication of diabetes. PMID:24627166

Hernández, Cristina; Simó-Servat, Olga; Simó, Rafael

2014-06-01

343

Telmisartan treatment ameliorates memory deficits in streptozotocin-induced diabetic mice via attenuating cerebral amyloidosis.  

PubMed

Telmisartan, an angiotensin II type 1-receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM) task exhibited a significant decline of spatial learning and memory. Oral administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg) significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan treatment markedly reduced A???, APP, BACE1, RAGE, and NF-?B p65 of the hippocampus and cortex, but did not beneficially affect hyperglycemia and hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic mice. Taken together, our findings suggest that telmisartan ameliorates memory deficits in type 1 diabetic mice, at least partly because of attenuation of amyloidosis in the brain. PMID:24671053

Du, Guan Tao; Hu, Meng; Mei, Zhen Lin; Wang, Chao; Liu, Guang Jun; Hu, Mei; Long, Yan; Miao, Ming Xing; Chang Li, Jia; Hong, Hao

2014-01-01

344

Testosterone and chronic sildenafil\\/tadalafil anti-apoptotic role in aged diabetic rats  

Microsoft Academic Search

This work aimed to assess the cavernous anti-apoptotic role of using chronic low-dose sildenafil\\/tadalafil with and without testosterone (T) in aged diabetic rats. In all, 140 Sprague-Dawley aged rats were divided into the following groups: controls; induced diabetic rats; diabetic rats that received intramuscular depot T once every 4 weeks; diabetic rats on sildenafil 2 mg kg–1 orally daily; diabetic