Curcumin Alleviates Diabetic Retinopathy in Experimental Diabetic Rats.

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Yang, Fang; Yu, Jinqiang; Ke, Feng; Lan, Mei; Li, Dekun; Tan, Ke; Ling, Jiaojiao; Wang, Ying; Wu, Kaili; Li, Dai

2018-03-29

To investigate the potential protective effects of curcumin on the retina in diabetic rats. An experimental diabetic rat model was induced by a low dose of streptozotocin combined with a high-energy diet. Rats which had blood glucose levels ≥11.6 mmol/L were used as diabetic rats. The diabetic rats were randomly divided into 3 groups: diabetic rats with no treatment (DM), diabetic rats treated with 100 mg/kg curcumin (DM + Cur 100 mg/kg), and diabetic rats treated with 200 mg/kg curcumin (DM + Cur 200 mg/kg). Curcumin was orally administered daily for 16 weeks. After 16 weeks of administration, the rats were euthanized, and eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes of retinal ganglion cells, inner layer cells, retinal capillary, and membranous disks were observed by electron microscopy. Malondialdehyde, superoxide dismutase, and total antioxidant capacity were measured by ELISA. Expression levels of vascular endothelial growth factor (VEGF) in retina tissues were examined by immunohistochemical staining and ELISA. Expression levels of Bax and Bcl-2 in retina tissues were determined by immunohistochemical staining and Western blotting. Curcumin reduced the blood glucose levels of diabetic rats and decreased diabetes-induced body weight loss. Curcumin prevented attenuation of the retina in diabetic rats and ameliorated diabetes-induced ultrastructure changes of the retina, including thinning of the retina, apoptosis of the retinal ganglion cells and inner nuclear layer cells, thickening of retinal capillary basement membrane and disturbance of photoreceptor cell membranous disks. We also found that curcumin has a strong antioxidative ability in the retina of diabetic rats. It was observed that curcumin attenuated the expression of VEGF in the retina of diabetic rats. We also discovered that curcumin had an antiapoptotic effect by upregulating the expression of Bcl-2 and downregulating

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

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Subbuswamy K. Prabu

2011-05-01

Full Text Available 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.

Assessment of diabetic peripheral neuropathy in streptozotocin-induced diabetic rats with magnetic resonance imaging

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Wang, Dongye; Zhang, Xiang; Lu, Liejing; Li, Haojiang; Zhang, Fang; Chen, Yueyao; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong (China)

2014-09-10

To determine the role of magnetic resonance (MR) imaging and quantitative T2 value measurements in the assessment of diabetic peripheral neuropathy (DPN). Sequential MR imaging, T2 measurement, and quantitative sensory testing of sciatic nerves were performed in streptozotocin-induced diabetic rats (n = 6) and normal control rats (n = 6) over a 7-week follow-up period. Histological assessment was obtained from 48 diabetic rats and 48 control rats once weekly for 7 weeks (n = 6 for each group at each time point). Nerve signal abnormalities were observed, and the T2 values, mechanical withdrawal threshold (MWT), and histological changes were measured and compared between diabetic and control animals. Sciatic nerves in the diabetic rats showed a gradual increase in T2 values beginning at 2 weeks after the induction (P = 0.014), while a decrease in MWT started at 3 weeks after the induction (P = 0.001). Nerve T2 values had a similar time course to sensory functional deficit in diabetic rats. Histologically, sciatic nerves of diabetic rats demonstrated obvious endoneural oedema from 2 to 3 weeks after the induction, followed by progressive axonal degeneration, Schwann cell proliferation, and coexistent disarranged nerve regeneration. Nerve T2 measurement is potentially useful in detecting and monitoring diabetic neuropathy. (orig.)

Assessment of diabetic peripheral neuropathy in streptozotocin-induced diabetic rats with magnetic resonance imaging

International Nuclear Information System (INIS)

Wang, Dongye; Zhang, Xiang; Lu, Liejing; Li, Haojiang; Zhang, Fang; Chen, Yueyao; Shen, Jun

2015-01-01

To determine the role of magnetic resonance (MR) imaging and quantitative T2 value measurements in the assessment of diabetic peripheral neuropathy (DPN). Sequential MR imaging, T2 measurement, and quantitative sensory testing of sciatic nerves were performed in streptozotocin-induced diabetic rats (n = 6) and normal control rats (n = 6) over a 7-week follow-up period. Histological assessment was obtained from 48 diabetic rats and 48 control rats once weekly for 7 weeks (n = 6 for each group at each time point). Nerve signal abnormalities were observed, and the T2 values, mechanical withdrawal threshold (MWT), and histological changes were measured and compared between diabetic and control animals. Sciatic nerves in the diabetic rats showed a gradual increase in T2 values beginning at 2 weeks after the induction (P = 0.014), while a decrease in MWT started at 3 weeks after the induction (P = 0.001). Nerve T2 values had a similar time course to sensory functional deficit in diabetic rats. Histologically, sciatic nerves of diabetic rats demonstrated obvious endoneural oedema from 2 to 3 weeks after the induction, followed by progressive axonal degeneration, Schwann cell proliferation, and coexistent disarranged nerve regeneration. Nerve T2 measurement is potentially useful in detecting and monitoring diabetic neuropathy. (orig.)

Functional food supplements to ameliorate the secondary complications in high fructose fed diabetic rats.

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Gite, S S; Yadav, S A; Nilegaonkar, S S; Agte, V V

2017-05-24

Functional foods are the most natural and safest source of health ingredients, providing health benefits beyond basic nutrition, and hence can be used as supplements for the prevention of secondary complications in diabetes. Persistent diabetes may cause glycation of various tissue proteins such as of those in lens, kidney, blood, and brain, which may further lead to the development of pathological conditions such as cataract and cardiovascular diseases. This study on adult rats was designed to assess if the functional food supplements A and B (proprietary blends of antioxidant rich plant materials) can reduce secondary complications such as cataract, dyslipidemia, and oxidative stress under severe diabetic conditions. After nine weeks of intervention of the supplements, it was found that the % HbA1c levels in the formulation group B significantly (p functional foods in the effective management of secondary complications associated with severe diabetic conditions.

Islet graft survival and function: concomitant culture and transplantation with vascular endothelial cells in diabetic rats.

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Pan, Xiaoming; Xue, Wujun; Li, Yang; Feng, Xinshun; Tian, Xiaohui; Ding, Chenguang

2011-12-15

Human islet transplantation is a great potential therapy for type I diabetes. To investigate islet graft survival and function, we recently showed the improved effects after co-culture and co-transplantation with vascular endothelial cells (ECs) in diabetic rats. ECs were isolated, and the viability of isolated islets was assessed in two groups (standard culture group and co-culture group with ECs). Then streptozotocin-induced diabetic rats were divided into four groups before islet transplantation as follows: group A with infusion of islet grafts; group B with combined vascular ECs and islet grafts; groups C and D as controls with single ECs infusion and phosphate-buffered saline injection, respectively. Blood glucose and insulin concentrations were measured daily. Expression of vascular endothelial growth factor was investigated by immunohistochemical staining. The mean microvascular density was also calculated. More than 90% of acridine orange-propidium iodide staining positive islets demonstrated normal morphology while co-cultured with ECs for 7 days. Compared with standard control, insulin release assays showed a significantly higher simulation index in co-culture group except for the first day (Ptransplantation, there was a significant difference in concentrations of blood glucose and insulin among these groups after 3 days (Pislet group (P=0.04). Co-culture with ECs in vitro could improve the survival and function of isolated rat islet, and co-transplantation of islets with ECs could effectively prolong the islet graft survival in diabetic rats.

Protective effects of sodium selenite on lead nitrate-induced hepatotoxicity in diabetic and non-diabetic rats.

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Kalender, Suna; Apaydin, Fatma Gökçe; Baş, Hatice; Kalender, Yusuf

2015-09-01

In the present study, the effect of sodium selenite on lead induced toxicity was studied in Wistar rats. Sodium selenite and lead nitrate were administered orally for 28 days to streptozotocin induced diabetic and non-diabetic rats. Eight groups of rats were used in the study: control, sodium selenite, lead nitrate, lead nitrate+sodium selenite, streptozotocin-induced diabetic-control, diabetic-sodium selenite, diabetic-lead nitrate, diabetic-lead nitrate+sodium selenite groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in liver tissues were investigated in all groups. There were statistically significant changes in liver function tests, antioxidant enzyme activities and lipid peroxidation levels in lead nitrate and sodium selenite+lead nitrate treated groups, also in diabetic and non-diabetic groups. Furthermore, histopathological alterations were demonstrated in same groups. In the present study we found that sodium selenite treatment did not show completely protective effect on diabetes mellitus caused damages, but diabetic rats are more susceptible to lead toxicity than non-diabetic rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of Livingstone Potato ( N.E.Br on Diabetes and Its Complications in Streptozotocin Induced Diabetes in Rats

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Chinedum Ogbonnaya Eleazu

2014-10-01

Full Text Available BackgroundThe effect of livingstone potato (Plectranthus esculenthus N.E.Br on diabetes and its complications in Streptozotocin induced diabetic rats was investigated. The duration of the experiment was 4 weeks.MethodsThe blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The liver and kidney function parameters in the serum of the rats were determined using Biosystem Kits.ResultsThe diabetic rats given livingstonepotato incorporated feeds, had 129.7% decrease in their hyperglycemia with corresponding amelioration of their elevated urinary protein, sugars, specific gravity, renal growth, liver growth as well as 15.64% decrease in body weights compared with the nondiabetic rats that had 5.54% decrease in blood glucose and 20.39% increase in body weight unlike the diabetic control rats that had 18.34% decrease in blood glucose and 52.68% decrease in body weight. There were significant differences (P0.05 in the relative heart weights of all the rats in the three different groups. In terms of liver and kidney function parameters, values obtained for the diabetic rats given livingstone potato incorporated feeds were not significantly different from that of the nondiabetic rats except for total bilurubin, aspartate transaminase, and creatinine (P>0.05 while they were significantly different from the values obtained for the diabetic control rats (P<0.05. In addition, the serum amylase of the diabetic control rats were significantly higher (P<0.05 than that of the nondiabetic and diabetic rats treated with livingstone potato incorporated feeds.ConclusionResults show the antidiabetic actions of livingstone potato and its ability to ameliorate glomerular complication and liver hypertrophy in diabetics.

Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats.

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Stracke, H; Hammes, H P; Werkmann, D; Mavrakis, K; Bitsch, I; Netzel, M; Geyer, J; Köpcke, W; Sauerland, C; Bretzel, R G; Federlin, K F

2001-01-01

In rats with streptozotocin (STZ) induced diabetes the effect of (watersoluble) thiamine nitrate and of (lipidsoluble) benfotiamine on peripheral nerve function (motor nerve conduction velocity) as well as on the formation of advanced glycation end-products in peripheral nerve tissue was studied. In one group of animals drug administration was started immediately after diabetes induction (prevention study) and in another group two months after diabetes induction (treatment study). Motor nerve conduction velocity (NCV) dropped by 10.5% in diabetic animals, carboxymethyl-lysine (CML) rose to a 3.5fold concentration, deoxyglucosone (3DG)-type AGE formation was increased 5.1fold compared with controls. After three months preventive administration of both vitamin B(1) preparations NCV had increased substantially compared with results in diabetic controls. It was nearly normal after six months with benfotiamine, while the administration of thiamine nitrate resulted in no further amelioration. NCV was nearly normalized after six months of benfotiamine application but not with thiamine. Furthermore, benfotiamine induced a major inhibition of neural imidazole-type AGE formation and completely prevented diabetes induced glycoxidation products (CML). Treatment with thiamine did not significantly affect AGE or cmL levels. Unlike treatment with water-soluble thiamine nitrate timely administration of liposoluble prodrug benfotiamine was effective in the prevention of functional damage and of AGE and cmL formation in nerves of diabetic rats.

Hibiscus sabdariffa (Roselle) Polyphenol-rich Extract Averts Cardiac Functional and Structural Abnormalities in Type 1 Diabetic Rats.

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Mohammed Yusof, Nur Liyana; Zainalabidin, Satirah; Mohd Fauzi, Norsyahida; Budin, Siti Balkis

2018-05-04

Diabetes mellitus is often associated with cardiac functional and structural alteration, an initial event leading to cardiovascular complications. Hibiscus sabdariffa or roselle has been widely proven as an antioxidant and recently has incited research interest for its potential in treating cardiovascular disease. Therefore, this study aimed to determine the cardioprotective effects of H. sabdariffa (roselle) polyphenol-rich extract (HPE) in type-1 induced diabetic rats. Twenty-four male Sprague-Dawley rats were randomized into four groups (n=6/group): non-diabetic (NDM), diabetic alone (DM), diabetic supplemented with HPE (DM+HPE) and metformin (DM+MET). Type-1 diabetes was induced with streptozotocin (55 mg/kg/i.p). Rats were forced-fed HPE (100 mg/kg) and metformin (150 mg/kg) daily for eight weeks. Results showed that HPE supplementation improved hyperglycemia and dyslipidemia significantly (p<0.05) in DM+HPE compared to DM group. HPE supplementation attenuated cardiac oxidative damage in DM group, indicated by low malondialdehyde and advanced oxidation protein product. As for the antioxidant status, HPE significantly (p<0.05) increased glutathione level, as well as catalase and superoxide dismutase 1 and 2 activities. These findings correlate with cardiac function, whereby HPE supplementation improved left ventricle developed pressure, coronary flow, cardiac contractility and relaxation rate significantly (p<0.05). Histological analysis showed a marked decrease in cardiomyocyte hypertrophy and fibrosis in DM+HPE compared to DM group. Ultrastructural changes and impairment of mitochondria induced by diabetes were minimized by HPE supplementation. Collectively, these findings suggest that HPE is a potential cardioprotective agent in a diabetic setting through its hypoglycemic, anti-hyperlipidemia and antioxidant properties.

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

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Zhong-Cheng Xin

2013-05-01

Full Text Available 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 α-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.

3',4'-Dihydroxyflavonol reduces superoxide and improves nitric oxide function in diabetic rat mesenteric arteries.

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Chen-Huei Leo

diabetic rats with DiOHF significantly reduced vascular ROS and restored NO-mediated endothelium-dependent relaxation. Treatment of the diabetic rats with DiOHF also increased eNOS expression, both in total and as a dimer.DiOHF improves NO activity in diabetes by reducing Nox2-dependent superoxide production and preventing eNOS uncoupling to improve endothelial function.

L-glutamine supplementation prevents the development of experimental diabetic cardiomyopathy in streptozotocin-nicotinamide induced diabetic rats.

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Sachin L Badole

Full Text Available 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.

Anti-diabetic effect of dietary mango (Mangifera indica L.) peel in streptozotocin-induced diabetic rats.

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Gondi, Mahendranath; Basha, Shaik Akbar; Bhaskar, Jamuna J; Salimath, Paramahans V; Rao, Ummiti J S Prasada

2015-03-30

In the present study, the composition of mango peel powder (MPP) collected from the mango pulp industry was determined and the effect of MPP on ameliorating diabetes and its associated complications was studied. Mango peel was rich in polyphenols, carotenoids and dietary fibre. Peel extract contained various bioactive compounds and was found to be rich in soluble dietary fibre. Peel extract exhibited antioxidant properties and protected against DNA damage. Therefore, the effect of peel on ameliorating diabetes was investigated in a rat model of diabetes. A significant increase in urine sugar, urine volume, fasting blood glucose, total cholesterol, triglycerides and low density lipoprotein, and decrease in high density lipoprotein were observed in the rats; however, these parameters were ameliorated in diabetic rats fed with diet supplemented with mango peel at 5% and 10% levels in basal diet. Treatment of diabetic rats with MPP increased antioxidant enzyme activities and decreased lipid peroxidation in plasma, kidney and liver compared to untreated diabetic rats. Glomerular filtration rate and microalbuminuria levels were ameliorated in MPP treated diabetic group. Mango peel, a by-product, can be used as an ingredient in functional and therapeutic foods. © 2014 Society of Chemical Industry.

Effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats.

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Di Petta, Antonio; Simas, Rafael; Ferreira, Clebson L; Capelozzi, Vera L; Salemi, Vera M C; Moreira, Luiz F P; Sannomiya, Paulina

2015-10-01

Chronic obstructive pulmonary disease is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate the effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats. Wistar rats were divided into control non-diabetic instilled with saline (CS) or elastase (CE), diabetic instilled with saline (DS) or elastase (DE), DE treated with insulin (DEI) groups and echocardiographic measurements, morphometric analyses of the heart and lungs, and survival analysis conducted 50 days after instillation. Diabetes mellitus was induced [alloxan, 42 mg/kg, intravenously (iv)] 10 days before the induction of emphysema (elastase, 0.25 IU/100 g). Rats were treated with NPH insulin (4 IU before elastase plus 2 IU/day, 50 days). Both CE and DE exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in right ventricular (RV) wall thickness (P = 0.0022), cavity area (P = 0.0001) and cardiomyocyte thickness (P = 0.0001). Diabetic saline group demonstrated a reduction in left ventricular (LV) wall, interventricular (IV) septum, cardiomyocyte thickness and an increase in cavity area, associated with a reduction in LV fractional shortening (P emphysema, even in the presence of insulin. Diabetes per se induced left ventricular dysfunction, which was less evident in the presence of RV hypertrophy. Survival rate was substantially reduced as a consequence, at least in part, of the coexistence of RV hypertrophy and diabetic cardiomyopathy. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Anti-Diabetic Effect of Portulaca oleracea L. Polysaccharideandits Mechanism in Diabetic Rats.

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Bai, Yu; Zang, Xueli; Ma, Jinshu; Xu, Guangyu

2016-07-25

Diabetes mellitus (DM) is a metabolic syndrome caused by multiple genetic and environmental factors. Traditional Chinese medicine preparations have shown a comprehensive and function-regulating characteristic. Purslane (Portulaca oleracea L.) is an annual succulent herb. Currently, there have been some related reports on the treatment of diabetes with purslane. The current study was designed to separate and purify the polysaccharide, a systematic study of its physical and chemical properties, antioxidant activity, and anti-diabetic mechanism, in order to provide a theoretical basis for the development of drugs of purslane. A crude water soluble polysaccharide extracted from purslane was named CPOP (crude Portulaca oleracea L. polysaccharide). Effects of CPOP on bodyweight, glucose tolerance test (GTT), fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity index (ISI), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), methane dicarboxylic aldehyde (MDA), and superoxygen dehydrogenises (SOD) were investigated. The results indicate that the oral administration of CPOP could significantly increase the body weight and significantly improve the glucose tolerance in diabetic rats. Meanwhile, CPOP could significantly reduce the FBG level, and elevate the FINS level and ISI value in diabetic rats. In addition, CPOP could significantly reduce TNF-α and IL-6 levels in diabetic rats; CPOP could also reduce MDA and SOD activities in the liver tissue of diabetic rats. These results suggest that the anti-diabetic effect of CPOP may be associated with its antioxidant and anti-inflammatory effects.

Anti-Diabetic Effect of Portulaca oleracea L. Polysaccharideandits Mechanism in Diabetic Rats

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Yu Bai

2016-07-01

Full Text Available Diabetes mellitus (DM is a metabolic syndrome caused by multiple genetic and environmental factors. Traditional Chinese medicine preparations have shown a comprehensive and function-regulating characteristic. Purslane (Portulaca oleracea L. is an annual succulent herb. Currently, there have been some related reports on the treatment of diabetes with purslane. The current study was designed to separate and purify the polysaccharide, a systematic study of its physical and chemical properties, antioxidant activity, and anti-diabetic mechanism, in order to provide a theoretical basis for the development of drugs of purslane. A crude water soluble polysaccharide extracted from purslane was named CPOP (crude Portulaca oleracea L. polysaccharide. Effects of CPOP on bodyweight, glucose tolerance test (GTT, fasting blood glucose (FBG, fasting serum insulin (FINS, insulin sensitivity index (ISI, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, methane dicarboxylic aldehyde (MDA, and superoxygen dehydrogenises (SOD were investigated. The results indicate that the oral administration of CPOP could significantly increase the body weight and significantly improve the glucose tolerance in diabetic rats. Meanwhile, CPOP could significantly reduce the FBG level, and elevate the FINS level and ISI value in diabetic rats. In addition, CPOP could significantly reduce TNF-α and IL-6 levels in diabetic rats; CPOP could also reduce MDA and SOD activities in the liver tissue of diabetic rats. These results suggest that the anti-diabetic effect of CPOP may be associated with its antioxidant and anti-inflammatory effects.

Changes in cardiovascular function and vascular Na-K pump activity in streptozotocin (STZ)-diabetic rats

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Anon.

1986-01-01

Blood pressure, vascular reactivity and Na-K pump function were examined in male Sprague-Dawley rats and rats made diabetic with a single dose of STZ (50 mg/Kg, I.V.). In each group, body weight, systolic blood pressure and heart rate were determined weekly, and serum glucose was measured biweekly for 12 weeks. Contractile responses and Na-K pump activity of vascular smooth muscle were studied in caudal artery strips. At 12 weeks after treatment, STZ rats had elevated serum glucose but decreased body weight and heart rate in comparison to control rats. Systolic blood pressure of STZ rats was not significantly increased at any time during the treatment period. Contractile responses of caudal artery strips to norepinephrine and serotonin did not indicate altered sensitivity (ED50) of vascular smooth muscle in STZ rats. The responsiveness (g tension/g wet wt.), however, was significantly increased in artery strips from STZ rats. Analysis of ouabain-inhibitable 86 Rb-uptake of caudal artery by the double-reciprocal plot showed that neither the rate of 86 Rb-uptake nor the affinity for rubidium were altered by STZ treatment. The data indicate that nonspecific increases in the reactivity of caudal arteries to excitatory agents occur in diabetic rats which may precede the development of hypertension. The enhanced reactivity is not associated with alteration of the vascular Na-K pump activity

X-ray lethality in diabetic rats

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Cember, H.; Thorson, T.M. Jr.

1978-01-01

Rats were made diabetic with streptozotocin and were irradiated with X-rays at various exposure levels in order to determine the LD-50/30 day dose. Non-diabetic control rats were exposed in a similar manner. The LD-50 exposures for the diabetic rats and the control rats were 436 R, and 617 R respectively. In view of the high prevalence of diabetes among the adult population, this finding may have important implications for diabetic workers who may be exposed accidentally to high levels of ionizing radiation

A Polysaccharide from Ganoderma atrum Improves Liver Function in Type 2 Diabetic Rats via Antioxidant Action and Short-Chain Fatty Acids Excretion.

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Zhu, Ke-Xue; Nie, Shao-Ping; Tan, Le-He; Li, Chuan; Gong, De-Ming; Xie, Ming-Yong

2016-03-09

The present study was to evaluate the beneficial effect of polysaccharide isolated from Ganoderma atrum (PSG-1) on liver function in type 2 diabetic rats. Results showed that PSG-1 decreased the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), while increasing hepatic glycogen levels. PSG-1 also exerted strong antioxidant activities, together with upregulated mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), glucose transporter-4 (GLUT4), phosphoinositide 3-kinase (PI3K), and phosphorylated-Akt (p-Akt) in the liver of diabetic rats. Moreover, the concentrations of short-chain fatty acids (SCFA) were significantly higher in the liver, serum, and faeces of diabetic rats after treating with PSG-1 for 4 weeks. These results suggest that the improvement of PSG-1 on liver function in type 2 diabetic rats may be due to its antioxidant effects, SCFA excretion in the colon from PSG-1, and regulation of hepatic glucose uptake by inducing GLUT4 translocation through PI3K/Akt signaling pathways.

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

International Nuclear Information System (INIS)

Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting

2010-01-01

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 17β-estradiol (E 2 ) on hyperglycemia and islet β-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 2 orally at 500 μg/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet β-cell proliferation. E 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 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 2 on islet cells was linked to the functions of the estrogen receptor α. Notably, these protective effects of E 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 2 can promote the regeneration of damaged pancreatic islets by stimulating β-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 2 may be beneficial in diabetic patients with an accelerated loss of islet β-cells.

Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats.

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Sharma, Sameer; Kulkarni, Shrinivas K; Chopra, Kanwaljit

2006-10-01

Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.

Total parenteral nutrition in diabetic rats

International Nuclear Information System (INIS)

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

1986-01-01

Parenteral Nutrition with hypertonic glucose is frequently given to diabetic patients. Large amounts of insulin can be required. The purpose of this investigation was to develop a totally parenterally nourished diabetic rat model. 200 g Female Sprague Dawley rats were made diabetic by i.v. injection of streptozotocin (50 mg/kg). Rats were then allowed to recover for at least 1 week before undergoing surgical insertion of a central venous catheter for parenteral feeding. TPN was begun 3 days after surgery. Prior to this they were allowed unlimited access to food and water. Control (non-streptozotocin treated) rats were run at the same time. Protein turnover was investigated by using 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

Treatment of diabetic rats with encapsulated islets.

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Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

2008-12-01

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We encapsulated 1000 rat islets and implanted them subcutaneously (SQ) into diabetic biobreeding (BB) rats and STZ-induced diabetic rats, defined as two or more consecutive days of blood glucose>350 mg/dl. Rats were monitored for weight and blood glucose. Untreated BB rats rapidly lost weight and were euthanized at >20% weight loss that occurred between 4 and 10 days from implantation. For period of 30-40 days following islet implantation weights of treated rats remained steady or increased. Rapid weight loss occurred after surgical removal of devices that contained insulin positive islets. STZ-treated rats that received encapsulated islets showed steady weight gain for up to 130 days, whereas untreated control rats showed steady weight loss that achieved >20% at around 55 days. Although islet implants did not normalize blood glucose, treated rats were apparently healthy and groomed normally. Autologous or allogeneic islets were equally effective in providing treatment. TheraCyte devices can sustain islets, protect allogeneic cells from immune attack and provide treatment for diabetic-mediated weight loss in both BB rats and STZ-induced diabetic rats.

Functional and molecular characterization of hyposensitive underactive bladder tissue and urine in streptozotocin-induced diabetic rat.

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Jayabalan Nirmal

Full Text Available 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.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 (EP1 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.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.

Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats.

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Shan, Hai-Tao; Zhang, Hai-Bo; Chen, Wen-Tao; Chen, Feng-Zhi; Wang, Tao; Luo, Jin-Tai; Yue, Min; Lin, Ji-Hong; Wei, An-Yang

2017-01-01

Stem cell transplantation and low-energy shock-wave therapy (LESWT) have emerged as potential and effective treatment protocols for diabetic erectile dysfunction. During the tracking of transplanted stem cells in diabetic erectile dysfunction models, the number of visible stem cells was rather low and decreased quickly. LESWT could recruit endogenous stem cells to the cavernous body and improve the microenvironment in diabetic cavernous tissue. Thus, we deduced that LESWT might benefit transplanted stem cell survival and improve the effects of stem cell transplantation. In this research, 42 streptozotocin-induced diabetic rats were randomized into four groups: the diabetic group (n = 6), the LESWT group (n = 6), the bone marrow-derived mesenchymal stem cell (BMSC) transplantation group (n = 15), and the combination of LESWT and BMSC transplantation group (n = 15). One and three days after BMSC transplantation, three rats were randomly chosen to observe the survival numbers of BMSCs in the cavernous body. Four weeks after BMSC transplantation, the following parameters were assessed: the surviving number of transplanted BMSCs in the cavernous tissue, erectile function, real-time polymerase chain reaction, and penile immunohistochemical assessment. Our research found that LESWT favored the survival of transplanted BMSCs in the cavernous body, which might be related to increased stromal cell-derived factor-1 expression and the enhancement of angiogenesis in the diabetic cavernous tissue. The combination of LESWT and BMSC transplantation could improve the erectile function of diabetic erectile function rats more effectively than LESWT or BMSC transplantation performed alone.

Effects of FoxO1 on podocyte injury in diabetic rats

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Guo, Feng; Zhang, Yuanyuan; Wang, Qingzhu; Ren, Lei; Zhou, Yingni [Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Ma, Xiaojun [Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Wu, Lina [Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Qin, Guijun, E-mail: hyqingj@zzu.edu.cn [Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China)

2015-10-16

Objective: This study was designed to investigate the protective effect of forkhead transcription factor O1 (FoxO1) on podocyte injury in rats with diabetic nephropathy. Methods: Streptozotocin-induced diabetic rats were served as DM group, while DM rats transfected with blank lentiviral vectors (LV-pSC-GFP) or lentiviral vectors carrying constitutively active FoxO1 (LV-CA-FoxO1) were served as LV-NC group or LV-CA group, respectively. The control group (NG) consisted of uninduced rats that received an injection of diluent buffer. At 2, 4, and 8 weeks after transfection, the levels of urine albumin, blood glucose, blood urea nitrogen, serum creatinine and urine podocalyxin were measured. Real-time PCR and western blotting were performed to measure mRNA and protein levels of FoxO1, podocalyxin, nephrin, and desmin in renal cortex. In addition, light and electron microscopy were used to detect structural changes in the glomerulus and podocytes. Results: Compared with the rats in LV-NC and DM groups, LV-CA rats showed a significant increase in FoxO1 mRNA and protein levels and a distinct decrease in urine albumin, blood urea nitrogen, and serum creatinine (except at the two-week time point) levels (p < 0.05). Podocalyxin and nephrin mRNA and protein levels increased (p < 0.05), whereas desmin mRNA and protein levels decreased (p < 0.05). Pathological changes in glomerulus were also ameliorated in LV-CA group. Conclusions: Upregulating expression of FoxO1 by transduction with recombinant lentivirus ameliorates podocyte injury in diabetic rats. - Highlights: • The structures and functions of podocytes were impaired in STZ-induced diabetic rats. • Constitutively active FoxO1 ameliorates structure injury and preserves function of podocytes in diabetic rats. • FoxO1 may alleviate the pathological changes associated with diabetic nephropathy.

Effects of FoxO1 on podocyte injury in diabetic rats

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Guo, Feng; Zhang, Yuanyuan; Wang, Qingzhu; Ren, Lei; Zhou, Yingni; Ma, Xiaojun; Wu, Lina; Qin, Guijun

2015-01-01

Objective: This study was designed to investigate the protective effect of forkhead transcription factor O1 (FoxO1) on podocyte injury in rats with diabetic nephropathy. Methods: Streptozotocin-induced diabetic rats were served as DM group, while DM rats transfected with blank lentiviral vectors (LV-pSC-GFP) or lentiviral vectors carrying constitutively active FoxO1 (LV-CA-FoxO1) were served as LV-NC group or LV-CA group, respectively. The control group (NG) consisted of uninduced rats that received an injection of diluent buffer. At 2, 4, and 8 weeks after transfection, the levels of urine albumin, blood glucose, blood urea nitrogen, serum creatinine and urine podocalyxin were measured. Real-time PCR and western blotting were performed to measure mRNA and protein levels of FoxO1, podocalyxin, nephrin, and desmin in renal cortex. In addition, light and electron microscopy were used to detect structural changes in the glomerulus and podocytes. Results: Compared with the rats in LV-NC and DM groups, LV-CA rats showed a significant increase in FoxO1 mRNA and protein levels and a distinct decrease in urine albumin, blood urea nitrogen, and serum creatinine (except at the two-week time point) levels (p < 0.05). Podocalyxin and nephrin mRNA and protein levels increased (p < 0.05), whereas desmin mRNA and protein levels decreased (p < 0.05). Pathological changes in glomerulus were also ameliorated in LV-CA group. Conclusions: Upregulating expression of FoxO1 by transduction with recombinant lentivirus ameliorates podocyte injury in diabetic rats. - Highlights: • The structures and functions of podocytes were impaired in STZ-induced diabetic rats. • Constitutively active FoxO1 ameliorates structure injury and preserves function of podocytes in diabetic rats. • FoxO1 may alleviate the pathological changes associated with diabetic nephropathy.

The Effect of Methanolic Extract of Otostegia persica on Serum Glucose Level and Renal Function Indicators in Streptozotocin Induced Diabetic Rats

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Mahdiye Hedayati

2012-05-01

Full Text Available Background: Regarding the antioxidant property of Otostegia persica extract and the role of antioxidants in Diabetes mellitus treatment, in this study the effect of extract on serum glucose level and renal function indicators was determined in diabetic male rats. Materials and Methods: Diabetes mellitus (type I was inducted in male rats using intraperitoneal injection of streptozotocin (STZ (65 mg/kg. To determine blood glucose, urea, and creatinine serum levels; fasting blood samples were collected twice (before STZ injection and 5 days later. The rats with their serum glucose level exceeding 250 mg/dl were considered diabetic and divided into 10 groups separately received Otostegia persica alcoholic extract (100, 200, and 300 mg/kg/day doses, glibenclamide with 600 µg/kg dose and 0.5 ml distilled water for 3 and 6 days using gavage. After 3 and 6 days, blood samples were collected again and glucose, urea, and creatinine serum levels were assessed using spectrophotometry technique by respective kits.Results: Treating diabetic rats by Otostegia persica extract (100, 200, and 300 mg/kg/day doses for 6 days results in a significant decrease of glucose and creatinine, yet an increase of serum urea with 200 mg/kg dose. Also, administration of the extract for 3 days (300 mg/kg reduced glucose, and (in various doses urea and creatinine serum levels. Conclusion: Otostegia persica extract has hypoglycemic effect and administering it in diabetes mellitus not only had no undesirable renal side effects, but also improved renal function to some extent.

Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

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Qinna NA

2015-05-01

Full Text Available Nidal A Qinna,1 Adnan A Badwan2 1Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, 2Research and Innovation Centre, The Jordanian Pharmaceutical Manufacturing Co. Plc. (JPM, Amman, Jordan Abstract: Streptozotocin (STZ is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL, noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were

Coupling of the Functional Stability of Rat Myocardium and Activity of Lipid Peroxidation in Combined Development of Postinfarction Remodeling and Diabetes Mellitus

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S. A. Afanasiev

2016-01-01

Full Text Available Coupling of the functional stability of rat myocardium and activity of lipid peroxidation processes in combined development of postinfarction remodeling and diabetes mellitus has been studied. The functional stability of myocardium was studied by means of the analysis of inotropic reaction on extrasystolic stimulus, the degree of left ventricular hypertrophy, and the size of scar zone. It was shown that in combined development of postinfarction cardiac remodeling of heart (PICR with diabetes mellitus (DM animal body weight decreased in less degree than in diabetic rats. Animals with combined pathology had no heart hypertrophy. The amplitude of extrasystolic contractions in rats with PICR combined with DM had no differences compared to the control group. In myocardium of rats with PICR combined with DM postextrasystolic potentiation was observed in contrast with the rats with PICR alone. The rats with combined pathology had the decreased value of TBA-active products. Thus, the results of study showed that induction of DM on the stage of the development of postinfarction remodeling increases adaptive ability of myocardium. It is manifested in inhibition of increase of LPO processes activity and maintaining of force-interval reactions of myocardium connected with calcium transport systems of sarcoplasmic reticulum of cardiomyocytes.

The effect of alloxan diabetes on the activity of some mixed function oxidases in male rats.

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Nedjar, A; Stoytchev, T

1990-01-01

The effect of alloxan-induced diabetes on the duration of hexobarbital sleep (HB sleep) the activity of ethylmorphine-N-demethylase (EMND), aniline hydroxylase (AH), the content of microsomal cytochrome P-450 and b5, on the activity of ethoxycumarine-0-deethylase (ECOD) and ethoxyresorufine-0-deethylase (EROD) after induction with beta naphthoflavone (beta-NF), as well as the activity of benzphetamine-N-demethylase and pentoxyresorufine-O-dealkylase (PROD) after induction with phenobarbital (PB), was studied in experiments on male Wistar rats. In rats with alloxan diabetes there was a significant prolongation of HB sleep (by 106%) and inhibition of the liver EMND (by 54%), while the AH activity increased by 131%, with a parallel rise in the content of microsomal cytochromes P-450 (by 67%) and b5 (by 113%). In rats with alloxan diabetes the enzyme-inducing effect of beta-NF with respect to the activities of EROD and ECOD is reduced, although diabetes by itself causes a rise in the ECOD activity in untreated animals. When induced with PB, the PROD and benzphetamine-N-demethylase activity in diabetic rats is lower than in the healthy animals. However, if the enzyme activity after the application of inducers is referred to the respective starting enzyme activities of the two groups of animals, it is found that the enzyme-inducing effect of PB is preserved and even slightly potentiated in the diabetic rats compared with the healthy ones: the increases in the benzphetamine-N-demethylase activity is by 60% in the diabetic rats, compared with a rise of 28% in the healthy animals, of the PROD activity 19 times for the diabetic compared with 16 times increase for the healthy rats.

A Comparison of Food-grade Folium mori Extract and 1-Deoxynojirimycin for Glycemic Control and Renal Function in Streptozotocin-induced Diabetic Rats

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Shiang-Suo Huang

2014-07-01

Full Text Available Folium mori (桑葉 Sāng Yè, leaf of Morus alba L.; FM is known to possess hypoglycemic effects, and 1-deoxynojirimycin (1-DNJ has been proposed as an important functional compound in FM. However, the hypoglycemic activity of purified 1-DNJ has been rarely studied. It is also not known how FM and 1-DNJ affect the development of DM nephropathy. This study compared the antidiabetic effect of a commercial FM product with that of purified 1-DNJ in streptozotocin-induced diabetic rats. Seven days after induction, the diabetic rats were gavaged with FM (1, 3, 10, and 30 mg/kg/day, 1-DNJ (30 mg/kg/day, or vehicle (distilled deionized water; 2 ml/kg/day for 7 days. All doses of FM ameliorated fasting and post-prandial blood glucose concomitantly with an increase in peripheral and pancreatic levels of insulin and improved homeostasis model assessment (HOMA-IR in diabetic rats in a dose-dependent manner. Increased thiobarbituric acid reactive substances (TBARS and nitrate/nitrite levels in the kidney, liver, and muscle of diabetic rats were reversed by all doses of FM. The renal function of the diabetic rats was normalized by all doses of FM, while blood pressure changes were reversed by FM at doses of 3 mg/kg and above. Moreover, most of the above-mentioned parameters were improved by FM at doses of 3 mg/kg and above to a similar extent as that of 1-DNJ. The results showed superior antidiabetic potential of the commercial FM product for glycemic control and protection against the development of diabetic nephropathy.

Blood-ocular and blood-brain barrier function in streptozocin-induced diabetes in rats

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Maeepea, O.; Karlsson, C.; Alm, A.

1984-01-01

Edetic acid labeled with chromium 51 was injected intravenously in normal rats and in rats with streptozocin-induced diabetes. One hour after the injection the animals were killed and the concentrations of edetic acid 51Cr in vitreous body, retina, and brain were determined. No significant difference was observed between the two groups for either tissue. In a second series, a mixture of tritiated 1-glucose and aminohippuric acid tagged with carbon 14 was injected instead of edetic acid. A substantial accumulation of aminohippuric acid 14C compared with tritiated 1-glucose was observed in the vitreous body and the brain of diabetic rats in comparison with the control group. It is concluded that untreated streptozocin-induced diabetes in rats for one to two weeks will not cause a generalized increase in the permeability of the blood-ocular or the blood-brain barriers, but organic acids may accumulate in the vitreous body as well as in the brain as a consequence of reduced outward transport through these barriers

Histopathological, Ultrastructural and Apoptotic Changes in Diabetic Rat Placenta

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Mehmet Gül

2015-09-01

Full Text Available Background: The exchange of substances between mother and fetus via the placenta plays a vital role during development. A number of developmental disorders in the fetus and placenta are observed during diabetic pregnancies. Diabetes, together with placental apoptosis, can lead to developmental and functional disorders. Aims: Histological, ultrastructural and apoptotic changes were investigated in the placenta of streptozotocin (STZ induced diabetic rats. Study Design: Animal experimentation. Methods: In this study, a total of 12 female Wistar Albino rats (control (n=6 and diabetic (n=6 were used. Rats in the diabetic group, following the administration of a single dose of STZ, showed blood glucose levels higher than 200 mg/dL after 72 hours. When pregnancy was detected after the rats were bred, two pieces of placenta and the fetuses were collected on the 20th day of pregnancy by cesarean incision under ketamine/xylazine anesthesia from in four rats from the control and diabetic groups. Placenta tissues were processed for light microscopy and transmission electron microscopy (TEM. Hematoxylin-eosin (HE and periodic acid Schiff-diastase (PAS-D staining for light microscopic and caspase-3 staining for immunohistochemical investigations were performed for each placenta. Electron microscopy was performed on thin sections contrasted with uranyl acetate and lead nitrate. Results: Weight gain in the placenta and fetuses of diabetic rats and thinning of the decidual layer, thickening of the hemal membrane, apoptotic bodies, congestion in intervillous spaces, increased PAS-D staining in decidual cells and caspase-3 immunoreactivity were observed in the diabetic group. After the ultrastructural examination, the apoptotic appearance of the nuclei of trophoblastic cells, edema and intracytoplasmic vacuolization, glycogen accumulation, dilation of the endoplasmic reticulum and myelin figures were observed. In addition, capillary basement membrane thickening

Red Cabbage (Brassica oleracea Ameliorates Diabetic Nephropathy in Rats

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Hazem A. H. Kataya

2008-01-01

Full Text Available The protective action against oxidative stress of red cabbage (Brassica oleracea extract was investigated. Diabetes was induced in male Wistar rats using streptozotocin (60 mg/kg body weight. Throughout the experimental period (60 days, diabetic rats exhibited many symptoms including loss of body weight, hyperglycemia, polyuria, polydipsia, renal enlargement and renal dysfunction. Significant increase in malondialdehyde, a lipid peroxidation marker, was observed in diabetic kidney. This was accompanied by a significant increase in reduced glutathione and superoxide dismutase activity and a decrease in catalase activity and in the total antioxidant capacity of the kidneys. Daily oral ingestion (1 g/kg body weight of B. oleracea extract for 60 days reversed the adverse effect of diabetes in rats. B. oleracea extract lowered blood glucose levels and restored renal function and body weight loss. In addition, B. oleracea extract attenuated the adverse effect of diabetes on malondialdehyde, glutathione and superoxide dismutase activity as well as catalase activity and total antioxidant capacity of diabetic kidneys. In conclusion, the antioxidant and antihyperglycemic properties of B. oleracea extract may offer a potential therapeutic source for the treatment of diabetes.

Renoprotective effect of lansoprazole in streptozotocin-induced diabetic nephropathy in wistar rats.

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Kaur, Rupinder; Sodhi, Rupinder Kaur; Aggarwal, Neha; Kaur, Jaspreet; Jain, Upendra K

2016-01-01

Proton pump inhibitors (PPIs) have exhibited glucose lowering action in animal models of diabetes; however, their potential in diabetes-related complications has not yet been evaluated. Hence, the present study has been undertaken to investigate the renoprotective potential of lansoprazole in streptozotocin-induced diabetic nephropathy in wistar rats. Diabetic nephropathy was induced with a single injection of streptozotocin (STZ, 45 mg/kg, i.p.). Lansoprazole (40 mg/kg; 80 mg/kg, p.o.; 4 weeks) was administered to diabetic rats after 4 weeks of STZ treatment. A battery of biochemical tests such as serum glucose, glycated hemoglobin, blood urea nitrogen (BUN), serum creatinine, albumin, and kidney weight/body weight (%) ratio were performed to evaluate the renal functions. Oxidative stress was determined by estimating renal thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) levels. Lipid profile was assessed by determining serum cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL). The STZ-treated rats demonstrated deleterious alterations in kidney functions, enhanced oxidative stress, and disturbed lipid profile. Administration of lansoprazole to diabetic rats significantly reduced serum glucose, glycated hemoglobin, BUN, creatinine, albumin levels, and oxidative stress. Serum lipids like TC and TG were decreased, and HDL was enhanced in lansoprazole-treated STZ rats. The findings of our study indicate that renoprotective effects of lansoprazole may be attributed to its glucose-lowering, lipid-lowering, and antioxidative potential.

Penile alterations at early stage of type 1 diabetes in rats

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Mingfang Tao

Full Text Available ABSTRACT Objective Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. Materials and methods Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS in midshaft penile tissues. The cross-sectional areas of the whole midshaft penis and the corpora cavernosa were quantified. The smooth muscle in the corpora cavernosa and nNOS in the dorsal nerves were quantified. Results The weight, but not the length, of the penis was lower in diabetics. The cross-sectional areas of the total midshaft penis and the corpora cavernosa were lower in diabetic rats compared with controls 9 weeks, but not 3 weeks after diabetes induction. The cross-sectional area of smooth muscle in the corpora cavernosa as percentage of the overall area of the corpora cavernosa was lower in diabetic rats than in controls 9 weeks, but not 3 weeks after diabetes induction. Percentage change of nNOS in dorsal nerves was similar at 3 weeks, and has a decreased trend at 9 weeks in diabetic rats compared with controls. Conclusions Diabetes causes temporal alterations in the penis, and the significant changes in STZ rat model begin 3-9 weeks after induction. Further studies on the reversibility of the observed changes are warranted.

Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

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Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

2015-09-01

Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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Jing Wang

2014-05-01

Full Text Available 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 β2-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.

Jiangtang Xiaozhi Recipe () prevents diabetic retinopathy in streptozotocin-induced diabetic rats.

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Li, Lin; Li, Yan-Lin; Zhou, Yun-Feng; Ge, Zheng-Yan; Wang, Li-Li; Li, Zhi-Qiang; Guo, Yu-Jie; Jin, Long; Ren, Ye; Liu, Jian-Xun; Xu, Yang

2017-06-01

To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA). High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (Pdiabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment. JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.

Development of diabetes does not alter behavioral and molecular circadian rhythms in a transgenic rat model of type 2 diabetes mellitus.

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Qian, Jingyi; Thomas, Anthony P; Schroeder, Analyne M; Rakshit, Kuntol; Colwell, Christopher S; Matveyenko, Aleksey V

2017-08-01

Metabolic state and circadian clock function exhibit a complex bidirectional relationship. Circadian disruption increases propensity for metabolic dysfunction, whereas common metabolic disorders such as obesity and type 2 diabetes (T2DM) are associated with impaired circadian rhythms. Specifically, alterations in glucose availability and glucose metabolism have been shown to modulate clock gene expression and function in vitro; however, to date, it is unknown whether development of diabetes imparts deleterious effects on the suprachiasmatic nucleus (SCN) circadian clock and SCN-driven outputs in vivo. To address this question, we undertook studies in aged diabetic rats transgenic for human islet amyloid polypeptide, an established nonobese model of T2DM (HIP rat), which develops metabolic defects closely recapitulating those present in patients with T2DM. HIP rats were also cross-bred with a clock gene reporter rat model (Per1:luciferase transgenic rat) to permit assessment of the SCN and the peripheral molecular clock function ex vivo. Utilizing these animal models, we examined effects of diabetes on 1 ) behavioral circadian rhythms, 2 ) photic entrainment of circadian activity, 3 ) SCN and peripheral tissue molecular clock function, and 4 ) melatonin secretion. We report that circadian activity, light-induced entrainment, molecular clockwork, as well as melatonin secretion are preserved in the HIP rat model of T2DM. These results suggest that despite the well-characterized ability of glucose to modulate circadian clock gene expression acutely in vitro, SCN clock function and key behavioral and physiological outputs appear to be preserved under chronic diabetic conditions characteristic of nonobese T2DM. Copyright © 2017 the American Physiological Society.

Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats

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Juárez-Rojop Isela Esther

2012-11-01

Full Text Available Abstract Background Traditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of C. papaya leaves in diabetic rats. Several studies have reported that some parts of the C. papaya plant exert hypoglycemic effects in both animals and humans. Methods Diabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ. The aqueous extract of C. papaya was administered in three different doses (0.75, 1.5 and 3 g/100 mL as drinking water to both diabetic and non-diabetic animals during 4 weeks. Results The aqueous extract of Carica papaya (0.75 g and 1.5 g/100 mL significantly decreased blood glucose levels (pC. papaya could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, C. papaya prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of C. papaya extract was also detected in diabetic rats. Conclusions This study showed that the aqueous extract of C. papaya exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas.

Effect of hypocholesterolemia on cholesterol synthesis in small intestine of diabetic rats

International Nuclear Information System (INIS)

Feingold, K.R.; Moser, A.H.

1987-01-01

Studies by our and other laboratories have demonstrated that cholesterol synthesis is increased in the small intestine of insulinopenic diabetic animals. In normal animals, many factors have been shown to regulate cholesterol synthesis in the small intestine, including changes in plasma cholesterol levels. The purpose of this study was to determine the effect of lowering plasma cholesterol levels on small intestine cholesterol synthesis in streptozocin-induced diabetic rats. In diabetic rats, 4-aminopyrazolo[3,4-d]pyrimidine (4-APP)-induced hypocholesterolemia (plasma cholesterol levels less than 20 mg/dl) resulted in a 2.5-fold increase in small intestine cholesterol synthesis, which was most marked in the distal small intestine, decreasing proximally. In the distal small intestine the incorporation of 3 H 2 O into cholesterol was 0.28 +/- 0.04 mumol.h-1.g-1 in diabetic rats versus 1.60 +/- 0.38 in diabetic rats administered 4-APP (P less than .01). This stimulation of cholesterol synthesis occurred in the upper villus, middle villus, and crypt cells isolated from the middle intestine of the 4-APP-treated diabetic animals. In agreement with these observations, functional hypocholesterolemia due to Triton WR-1339 administration also stimulated cholesterol synthesis 2.5-fold in the small intestine of normal and diabetic animals. In the distal small intestine, cholesterol synthesis was 0.43 +/- 0.10 mumol.h-1.g-1 in the diabetic rats versus 1.08 +/- 0.21 in diabetic rats treated with Triton WR-1339 (P less than .05). In both the 4-APP and Triton WR-1339 experiments, the response of the diabetic rats was similar to that observed in normal rats

Beneficial effects of exercise training in heart failure are lost in male diabetic rats.

Science.gov (United States)

Boudia, Dalila; Domergue, Valérie; Mateo, Philippe; Fazal, Loubina; Prud'homme, Mathilde; Prigent, Héloïse; Delcayre, Claude; Cohen-Solal, Alain; Garnier, Anne; Ventura-Clapier, Renée; Samuel, Jane-Lise

2017-12-01

Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n = 53) or high-fat, high-sucrose diet ( n = 66) for 6 mo. After 2 mo of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation. Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for an additional 8 wk or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry, and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 wk resulted in a higher working power developed by MI animals with diabetes and improved glycaemia but not ejection fraction or pathological phenotype. In contrast, exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet. NEW & NOTEWORTHY Exercise training is beneficial in patients with heart failure (HF) or diabetes. However, less is known of the possible benefit of exercise training for HF patients with diabetes. Using a rat model where both diabetes and MI had been induced, we showed that 2 mo after MI, 8 wk of exercise training failed to improve

Arginase promotes skeletal muscle arteriolar endothelial dysfunction in diabetic rats.

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Fruzsina K. Johnson

2013-05-01

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

Effect of dietary antioxidant supplementation (Cuminum cyminum) on bacterial susceptibility of diabetes-induced rats.

Science.gov (United States)

Moubarz, Gehan; Embaby, Mohamed A; Doleib, Nada M; Taha, Mona M

2016-01-01

Diabetic patients are at risk of acquiring infections. Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Diabetes causes generation of reactive oxygen species that increases oxidative stress, which may play a role in the development of complications as immune-deficiency and bacterial infection. The study aimed to investigate the role of a natural antioxidant, cumin, in the improvement of immune functions in diabetes. Diabetes was achieved by interperitoneal injection of streptozotocin (STZ). Bacterial infection was induced by application of Staphylococcus aureus suspension to a wound in the back of rats. The antioxidant was administered for 6 weeks. Results revealed a decrease in blood glucose levels in diabetic rats (p cumin may serve as anti-diabetic treatment and may help in attenuating diabetic complications by improving immune functions. Therefore, a medical dietary antioxidant supplementation is important to improve the immune functions in diabetes.

The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes.

Science.gov (United States)

Cheng, Xing; Xia, Zhengyuan; Leo, Joyce M; Pang, Catherine C Y

2005-09-05

We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

Hematological changes in opium addicted diabetic rats.

Science.gov (United States)

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

2013-01-01

Chronic opioid treatment in animal models has shown to alter hematological parameters. 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. Peripheral blood samples were collected from diabetic, opium-addicted, diabetic opium-addicted and normal male and female rats and hematological parameters were measured. 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. 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.

Metallothionein metabolism in the streptozotocin-diabetic rat

International Nuclear Information System (INIS)

Chen, M.L.; Failla, M.L.

1986-01-01

Earlier reports from their laboratory showed the induction of the insulin-deficient diabetic state in adult rats was associated with an accumulation of zinc, copper, and a metallothionein-like zinc and copper binding protein in the soluble fraction of liver and kidney. Based upon chromatographic and electrophoretic properties, -SH to metal ratio and amino acid composition, they now report that elevated concentrations of metallothioneins (MT)-I and -II are indeed present in diabetic rat liver and kidney cytosol. The relative rates of MT synthesis in tissues from diabetic and control rats were measured by comparing incorporation of 35 S-cysteine into MT vs. total cytoplasmic proteins at 5 h after injection of the precursor. The relative rates of MT synthesis in livers from rats diabetic for 10 d and fed either chow or purified diet containing 13 or 35 ppm copper were 1.4, 2.3 and 2.8 times greater, respectively, than control rats fed the same diets. Higher relative rates of MT synthesis were also observed in kidneys from diabetic rats fed purified diets compared to controls. Maximal relative rates of MT synthesis in diabetic liver and kidney were observed at 4 and 10 d, respectively, after onset of diabetes. The half-lives of cytoplasmic MT in liver and kidney from diabetic (10 d) rats were 1.3 and 2.6 days, respectively; half-lives of MT in control liver and kidney were 5.0 and 2.1 days, respectively

Pioglitazone reverses down-regulation of cardiac PPARγ expression in Zucker diabetic fatty rats

International Nuclear Information System (INIS)

Pelzer, Theo; Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Segerer, Stephan; Lichtenwald, Margit; Law, Marilyn P.; Schaefers, Michael; Ertl, Georg; Neyses, Ludwig

2005-01-01

Peroxisome proliferator-activated receptor-γ (PPARγ) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPARγ in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPARγ agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPARγ, glucose transporter-4 and α-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPARγ, glut-4, and α-MHC expression levels in diabetic ZDF rats. Cardiac [ 18 F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARγ agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPARγ expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin

The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats.

Science.gov (United States)

Fernandes, Sheila Marques; Cordeiro, Priscilla Mendes; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Vattimo, Maria de Fatima Fernandes

2016-10-01

The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously - i.v - in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evaluated. Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy.

Adrenergic blockade in diabetic and uninephrectomized rats

DEFF Research Database (Denmark)

Thulesen, J; Poulsen, Steen Seier; Jørgensen, P E

1999-01-01

The present study reports on the effects of adrenergic blocking agents on the renal growth and on the renal content and urinary excretion of epidermal growth factor (EGF) in streptozotocin-induced diabetic or uninephrectomized rats. Diabetic and uninephrectomized rats were allocated to groups...... treated with either saline or adrenergic antagonists and compared to controls and sham-operated controls, respectively. 24-hour urine samples were obtained on days 7, 14, and 21 and renal tissue samples on day 21. The 24-hour urinary excretion of EGF from controls and saline-treated diabetic rats...... was comparable. In adrenergic antagonist treated diabetic rats, it was reduced by at least 40% throughout the study period. Uninephrectomy caused a 50% reduction in the urinary excretion of EGF. This was not influenced by treatment with an adrenergic antagonist. After 3 weeks, saline-treated diabetic rats had...

Treatment of diabetic rats with encapsulated islets

OpenAIRE

Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

2008-01-01

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte? immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We enca...

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

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Yusuke Kemmochi

2013-01-01

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

The Antidiabetic Activity of Nigella sativa and Propolis on Streptozotocin-Induced Diabetes and Diabetic Nephropathy in Male Rats

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Haddad A. El Rabey

2017-01-01

Full Text Available This study was conducted to compare the ameliorative effect of Nigella sativa and propolis methanol extract on streptozotocin-induced diabetic male rats and treating diabetic nephropathy. Forty male Albino rats were divided into four groups; the first group was the negative control fed standard diet. The other 30 rats were injected with streptozotocin to induce diabetes by a single intravenous injection and then divided equally into three groups; the second group was the positive diabetic control; the third and the fourth groups were treated orally with 20% w/w Nigella sativa seeds methanol extract and propolis methanol extract (20% w/w, respectively. The rats of the second group showed increased glucose levels and lipid peroxide accompanied with reduction in superoxide dismutase, catalase, and glutathione-S-transferase enzyme activities compared with the negative control. Carboxymethyl lysine, interleukin-6, and immunoglobulins were also increased as a result of diabetes. Kidney function parameters were also elevated, while potassium and sodium levels were decreased. Moreover, tissues of kidney and pancreas showed severe histopathological changes. Treating the diabetic rats with Nigella sativa and propolis methanol extract in the third and fourth groups, respectively, ameliorated all altered biochemical and pathological examinations approaching the negative control. Propolis was more effective than Nigella sativa.

in Alloxan-induced Diabetic Rats

African Journals Online (AJOL)

HP

Group 4: Diabetic rats that were administered. 500 mg/kg body weight extracts. Group 5: Diabetic rats that were administered. 300 mg/kg body weight of metformin. The drug and extracts treatment was done for a period of 21 days using orogastric tube. Collection of blood samples. Following 21 days of extract administration, ...

Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

International Nuclear Information System (INIS)

Winocour, P.D.; Colwell, J.A.

1985-01-01

Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis

Evaluation of Urinary Tryptophan Metabolite Levels in Non-diabetic Compared to Diabetic Rats

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Loredana Elena OLAR

2017-11-01

Full Text Available Diabetes mellitus is one of the most common metabolic disorders in animals. Thus, currently, it is imperative to introduce non-invasive, economical and rapid methods for the investigation of diabetes in animals. In this study, the urine samples collected from 10 non-diabetic and 10 streptozotocin-induced diabetic rats were investigated by the spectrofluorimetric technique. Emission spectra for the urine samples were obtained following an excitation wavelength of 280 and 400 nm. The investigated fluorophores were mainly tryptophan metabolites, and significant differences resulted between the mean heights of the emission bands attributed to these fluorophore compounds in diabetic compared to non-diabetic rats. The shape of the spectral windings after the utilization of these two excitation wavelengths was almost similar for diabetic and non-diabetic rats; however, there were some discriminatory elements between the two types of investigated samples. In conclusion, the obtained urine fluorescence spectra allow a clear differentiation between diabetic and non-diabetic rats.

Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

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Guberski Dennis

2008-10-01

Full Text Available Abstract We investigated the role of polyol pathway enzymes aldose reductase (AR and sorbitol dehydrogenase (SDH in mediating injury due to ischemia-reperfusion (IR in Type 2 diabetic BBZ rat hearts. Specifically, we investigated, (a changes in glucose flux via cardiac AR and SDH as a function of diabetes duration, (b ischemic injury and function after IR, (c the effect of inhibition of AR or SDH on ischemic injury and function. Hearts isolated from BBZ rats, after 12 weeks or 48 weeks diabetes duration, and their non-diabetic littermates, were subjected to IR protocol. Myocardial function, substrate flux via AR and SDH, and tissue lactate:pyruvate (L/P ratio (a measure of cytosolic NADH/NAD+, and lactate dehydrogenase (LDH release (a marker of IR injury were measured. Zopolrestat, and CP-470,711 were used to inhibit AR and SDH, respectively. Myocardial sorbitol and fructose content, and associated changes in L/P ratios were significantly higher in BBZ rats compared to non-diabetics, and increased with disease duration. Induction of IR resulted in increased ischemic injury, reduced ATP levels, increases in L/P ratio, and poor cardiac function in BBZ rat hearts, while inhibition of AR or SDH attenuated these changes and protected hearts from IR injury. These data indicate that AR and SDH are key modulators of myocardial IR injury in BBZ rat hearts and that inhibition of polyol pathway could in principle be used as a therapeutic adjunct for protection of ischemic myocardium in Type 2 diabetic patients.

Effect of streptozotocin-induced diabetes on myocardial blood flow reserve assessed by myocardial contrast echocardiography in rats

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Weytjens Caroline

2008-09-01

Full Text Available Abstract The role of structural and functional abnormalities of small vessels in diabetes cardiomyopathy remains unclear. Myocardial contrast echocardiography allows the quantification of myocardial blood flow at rest and during dipyridamole infusion. The aim of the study was to determine the myocardial blood flow reserve in normal rats compared with Streptozotocin-induced diabetic rats using contrast echocardiography. Methods We prospectively studied 40 Wistar rats. Diabetes was induced by intravenous streptozotocin in 20 rats. All rats underwent baseline and stress (dipyridamole: 20 mg/kg high power intermittent imaging in short axis view under anaesthesia baseline and after six months. Myocardial blood flow was determined and compared at rest and after dipyridamole in both populations. The myocardial blood flow reserve was calculated and compared in the 2 groups. Parameters of left ventricular function were determined from the M-mode tracings and histological examination was performed in all rats at the end of the study. Results At six months, myocardial blood flow reserve was significantly lower in diabetic rats compared to controls (3.09 ± 0.98 vs. 1.28 ± 0.67 ml min-1 g-1; p Conclusion In this animal study, diabetes induced a functional alteration of the coronary microcirculation, as demonstrated by contrast echocardiography, a decrease in capillary density and of the cardiac systolic function. These findings may offer new insights into the underlying mechanisms of diabetes cardiomyopathy.

Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

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Zaladek-Gil F.

1999-01-01

Full Text Available In previous studies we have shown stimulation of renal acid excretion in the proximal tubules of rats with diabetes of short duration, with no important alterations in glomerular hemodynamics; on the other hand, in thyroparathyroidectomized rats (TPTX model, a significant decrease in renal acid excretion, glomerular filtration rate (GFR and renal plasma flow (RPF was detected. Since important changes in the parathyroid hormone-vitamin D-Ca axis are observed in the diabetic state, the present study was undertaken to investigate the renal repercussions of thyroparathyroidectomy in rats previously made diabetic by streptozotocin (45 mg/kg. Four to 6 days after the induction of diabetes (DM, a group of rats were thyroparathyroidectomized (DM + TPTX. Renal functional parameters were evaluated by measuring the inulin and sodium para-aminohippurate clearance on the tenth day. The decrease in the GFR and RPF observed in TPTX was not reversed by diabetes since the same alterations were observed in DM + TPTX. Net acid (NA excretion was unchanged in DM (6.19 ± 0.54, decreased in TPTX (3.76 ± 0.25 and returned to normal levels in DM + TPTX (5.54 ± 0.72 when compared to the control group (6.34 ± 0.14 µmol min-1 kg-1. The results suggest that PTH plays an important vasodilator role regarding glomerular hemodynamics, since in its absence the impairment in GFR and RPF was not reversed by the diabetic state. However, with respect to acid excretion, the presence of diabetes was able to overcome the negative stimulus represented by TPTX.

Anti-diabetic activity of crude Pistacia lentiscus in alloxan-induced diabetes in rats

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Muhammad Saad Ur Rehman

2015-08-01

Full Text Available The purpose of this study was to investigate the anti-diabetic effect of crude Pistacia lentiscus gum (mastic gum in alloxan-treated diabetic rat model. The crude P. lentiscus (100 mg/kg showed significant (p<0.001 reduction in blood glucose as compared to control. Liver function test also showed significant changes (p<0.001 as compared to alloxan-treated group. The results of this study showed that crude P. lentiscus gum have considerable efficacy in curing diabetes and have hepatoprotective effect.

Thymus transplantation and disease prevention in the diabetes-prone Bio-Breeding rat

International Nuclear Information System (INIS)

Georgiou, H.M.; Bellgrau, D.

1989-01-01

Bio-Breeding rat T lymphocytes proliferate poorly in response to alloantigen. Transplantation of Bio-Breeding rats with fetal thymus tissue from diabetes resistant rats leads to an improvement in the T cell proliferative response, but only if the thymus contains bone marrow-derived, radiation-resistant thymic antigen presenting cells of the diabetes-resistant phenotype. The current study provides evidence that thymus transplantation leading to the restoration of Bio-Breeding T cell proliferative function can also significantly reduce the incidence of insulitis and prevent the development of diabetes. It appears that a defect in the bone marrow-derived thymic APC population contributes to an abnormal maturation of Bio-Breeding T lymphocytes which in turn predisposes animals to insulitis and diabetic disease

Effects of taurine on oxidative-antioxidative status of renal tissue in diabetic rats

International Nuclear Information System (INIS)

Chen Yingjian; Tu Xiaowen; Yin Qiuxia; Hu Chenjing

2004-01-01

Objective: To investigate the effects of taurine on the oxidative-antioxidative status of renal tissue in diabetic rats. Methods: Diabetic models of rat were induced with streptozotocin. Half of the models (n=7) were treated with taurine for 4 weeks. Blood glucose, uric acid and MDA, 24h urinary albumin and renal cortical homogenate MDA, SOD, GSH-Px contents were determined with appropriate laboratory technics in 1) diabetic rats without taurine treatment, n=7 2) diabetic rats treated with taurine, n=7 and 3) control rats, n=7. Results: There were no significant differences between the blood glucose levels in the two groups of diabetic rats. Blood uric acid and 24h urinary albumin contents in the untreated diabetic rats were significantly higher than those in the controls (P<0.01). However, in the taurine treated rats, the blood uric acid levels approximated to those in the controls, with decreased but still higher than normal 24h urinary albumin contents. In the untreated rats, the renal cortical SOD and GSH-Px activities were about the same as those in control rats but there were significantly higher levels of blood and cortical MDA contents (P<0.01). With taurine treatment, the SOD and GSH-Px activities were significantly higher than those in the two other groups (P<0.05); the MDA contents were lower than those in non-treated rats (P<0.05), but still higher than those in controls (P<0.05). Conclusion: Taurine could enhance the anti-oxidative capability and attenuated the oxidative stress in diabetic rats renal tissue with partial protection of renal function. (authors)

Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

International Nuclear Information System (INIS)

Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

2009-01-01

Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I

International Nuclear Information System (INIS)

Binz, K.; Joller, P.; Froesch, P.; Binz, H.; Zapf, J.; Froesch, E.R.

1990-01-01

Atrophy of the thymus is one of the consequences of severe insulin deficiency. The authors describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. They also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less [ 3 H]thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased [ 3 H]thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-1 antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. They conclude that IGF-I has important effects on the thymocyte number and the presence of CD4 + /CD8 + immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state

Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

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Petropoulos, Sophie; Guillemin, Claire; Ergaz, Zivanit; Dimov, Sergiy; Suderman, Matthew; Weinstein-Fudim, Liza; Ornoy, Asher; Szyf, Moshe

2015-06-01

Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

Dual therapy of vildagliptin and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats.

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Sharma, Ashish Kumar; Kanawat, Devendra Singh; Mishra, Akanksha; Dhakad, Prashant Kumar; Sharma, Prashant; Srivastava, Varnika; Joshi, Sneha; Joshi, Megha; Raikwar, Sachin Kumar; Kurmi, Muneem Kumar; Srinivasan, Bharthu Parthsarthi

2014-12-01

The objective of this article is to investigate the combination of telmisartan with vildagliptin therapy versus monotherapy of vildagliptin and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats. In adult rats streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg) were injected intraperitoneally to produce diabetic nephropathy. Rats of either sex allotted to the following groups: (i) triple therapy: metformin (120 mg/kg, o.d.) + pioglitazone (1.25 mg/kg, o.d.) + glimepiride (0.7 mg/kg, o.d.); (ii) dual therapy: vildagliptin (8.76 mg/kg, o.d.) + telmisartan (6.48 mg/kg, o.d.); (iii) vildagliptin (8.76 mg/kg, o.d.); and (iv) telmisartan (6.48 mg/kg, o.d.); therapy was carried out for 35 days orally. Weekly at days 7, 14, 21, 28 and 35, blood pressure, blood glucose level, body weight, blood serum creatinine level, protein albumin level in urine, and blood urea nitrogen (BUN) were estimated. Renal structural changes were observed. Blood pressure, blood glucose level, blood serum creatinine level, protein albumin level in urine, BUN and renal deterioration increased significantly in diabetic rats compared with normal control rats. The vildagliptin + telmisartan treatment group showed no weight gain and controlled blood pressure, renovascular structural and biochemical parameters in diabetic neuropathy rats. The addition of telmisartan to vildagliptin demonstrated the best control over blood pressure, glycemia and diabetic nephropathy markers, renal structural changes and improvement of renal function as opposed to monotherapy with either drug, possibly because of the dual inhibitory effect on the renin-angiotensin system. © The Author(s) 2013.

Hydrogen sulfide accelerates wound healing in diabetic rats.

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Wang, Guoguang; Li, Wei; Chen, Qingying; Jiang, Yuxin; Lu, Xiaohua; Zhao, Xue

2015-01-01

The aim of this study was to explore the role of hydrogen sulfide on wound healing in diabetic rats. Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (STZ) (in 0.1 mol/L citrate buffer, Ph 4.5) at dose of 70 mg/kg. Diabetic and age-matched non-diabetic rats were randomly assigned to three groups: untreated diabetic controls (UDC), treated diabetic administrations (TDA), and non-diabetic controls (NDC). Wound Healing Model was prepared by making a round incision (2.0 cm in diameter) in full thickness. Rats from TDA receive 2% sodium bisulfide ointment on wound, and animals from UDC and NDC receive control cream. After treatment of 21 days with sodium bisulfide, blood samples were collected for determination of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), antioxidant effects. Granulation tissues from the wound were processed for histological examination and analysis of western blot. The study indicated a significant increase in levels of VEGF and ICAM-1 and a decline in activity of coagulation in diabetic rats treated with sodium bisulfide. Sodium bisulfide treatment raised the activity of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein expression, and decreased tumor necrosis factor α (TNF-α) protein expression in diabetic rats. The findings in present study suggested that hydrogen sulfide accelerates the wound healing in rats with diabetes. The beneficial effect of H2S may be associated with formation of granulation, anti-inflammation, antioxidant, and the increased level of vascular endothelial growth factor (VEGF).

Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats.

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Chaturvedi, Padmaja; Kwape, Tebogo Elvis

2015-12-01

This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes.

Tangzhining exhibits a protective effect against cognitive dysfunction in diabetic rats

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Song, Xiaomei; Wang, Wei; Kang, Yaguo; Zhang, Xin; Jiang, Yi; Yue, Zhenggang; Tang, Zhishu

2015-01-01

Previous studies have suggested that diabetes significantly impairs the cognitive function. Tangzhining (TZN), as a kind of Traditional Chinese Medicine (TCM), has been widely used to treat diabetes in China. However, the effect of TZN on treatment of diabetes-induced learning and memory deficits has not been well documented. The present study was to investigate the effect of TZN on diabetes-induced learning and memory deficits and delineate the underlying molecular mechanism. Diabetic rats w...

ANTI-DIABETIC EFFECTS OF TURMERIC IN ALLOXAN INDUCE D DIABETIC RATS

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Jeevangi; Manjunath; Deepak D; Prakash G; Prashant; Chetan

2013-01-01

ABSTRACT: OBJECTIVE AND BACKGROUND: Turmeric (Curcuma longa) is one of the common constituents of our daily food. The present study wa s undertaken to evaluate the anti-diabetic effects of ethanolic extract of Rhizomes of curcuma longa in alloxan induced diabetic rats and compared with of Pioglitazone, which is the standard anti-diabetic agent. METHODS: Alloxan monohydrate is used to induce diabetes mellitus in albino rats in the dose of 120mg/kg i.p. and ...

Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats

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Malone Michael A

2006-01-01

Full Text Available Abstract Background Streptozotocin-induced diabetes (STZ-D in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement. Aim The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats. Methods Wistar rats (48 were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24 were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks. Results The heart rates for the STZ-D rats (290 ± 19 bpm were less than control rats (324 ± 20 bpm (p Conclusion Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.

Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats

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Miklos Szokol

2017-10-01

Full Text Available The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH, in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT. Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF, fractional shortening (FS, isovolumetric relaxation time (IVRT, mitral annular plane systolic excursion (MAPSE, and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status.

Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung

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Faeze Daghigh

2017-12-01

Full Text Available Objective(s: The role of isoflavones in pulmonary structure and function during menopause is not well studied. Moreover, the important role of estrogen in the physiological function of respiratory system has been revealed. Genistein, as an isoflavone, mimics estrogenic in diabetic and ovariectomized rats. Here, we hypothesized that genistein would reverse changes in the protein expression levels related to estrogen deficiency in the lung of ovariectomized diabetic rats. Materials and Methods: Wistar female rats were assigned to four experimental groups (n=10 in each group: sham, rats underwent laparotomy without removing the ovaries; OVX, rats that underwent ovariectomy; OVX.D, rats underwent bilateral ovariectomy and were fed a high-fat diet (HFD; OVX.D.G, ovariectomized diabetic rats with genistein administration (1 mg/kg /day. After ovariectomy, rats continued to feed HFD for a 4-week period. After 4 weeks of HFD feeding, a single dose of 30 mg/kg of streptozotocin was administered in the diabetic group. Genistein was administered for eight weeks. At the end of the experiment, lung tissue was removed and Western blotting technique and hematoxylin-eosin staining were used for evaluation of the lung. Results: Treatment with genistein significantly decreased inflammatory and apoptotic biomarkers in the ovariectomized diabetic rats compared to non-treated animals (P

Telmisartan attenuates diabetes induced depression in rats.

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Aswar, Urmila; Chepurwar, Shilpa; Shintre, Sumit; Aswar, Manoj

2017-04-01

Role of brain renin angiotensin system (RAS) is well understood and various clinical studies have proposed neuroprotective effects of ARB's. It is also assumed that diabetic depression is associated with activation of brain RAS, HPA axis dysregulation and brain inflammatory events. Therefore, the present study was designed to investigate the antidepressant effect of low dose telmisartan (TMS) in diabetes induced depression (DID) in rats. Diabetes was induced by injecting streptozotocin. After 21days of treatment the rats were subjected to forced swim test (FST). The rats, with increased immobility time, were considered depressed and were treated with vehicle or TMS (0.05mg/kg, po) or metformin (200mg/kg, po) or fluoxetine (20mg/kg, po). A separate group was also maintained to study the combination of metformin and TMS. At the end of 21days of treatments, FST, open field test (OFT) and elevated plus maze (EPM) paradigm were performed. Blood was drawn to estimate serum cortisol, nitric oxide (NO), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Persistent hyperglycemia resulted in depression and anxiety in rats as observed by increased immobility, reduced latency for immobility, reduced open arm entries and time spent. The depressed rats showed a significant rise in serum cortisol, NO, IL-6 and IL-1β (pdepression and anxiety. It also significantly attenuated serum cortisol, NO, IL-6 and IL-1β (pdepressive mood, reduces pro-inflammatory mediators and ameliorates the HPA axis function; thereby providing beneficial effects in DID. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis.

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Kutlu, O; Karaguzel, E; Gurgen, S G; Okatan, A E; Kutlu, S; Bayraktar, C; Kazaz, I O; Eren, H

2016-05-01

We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions. © 2015 Blackwell Verlag GmbH.

Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

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Juan P. Hernández-Fonseca

2009-01-01

Full Text Available Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.

Melatonin improves spatial navigation memory in male diabetic rats

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Farrin Babaei-Balderlou

2012-09-01

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

Long-term effects of maternal diabetes on blood pressure and renal function in rat male offspring.

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Jie Yan

Full Text Available AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM is increasing rapidly worldwide. Previous animal models were established to study consequences of offspring after exposure to severe intrauterine hyperglycemia. In this study we are aiming to characterize the blood pressure levels and renal function of male offspring obtained from diabetic mothers with moderate hyperglycemia. METHODS: We established a rat model with moderate hyperglycemia after pregnancy by a single intraperitoneal injection of streptozotocin (STZ. The male offspring were studied and fed with either normal diet or high salt diet after weaning. Arterial pressure and renal function were measured. RESULTS: Arterial pressure of male offspring increased from 12 weeks by exposure to intrauterine moderate hyperglycemia. At 20 weeks, high salt diet accelerated the blood pressure on diabetic offspring compared to diabetic offspring fed with normal diet. We found offspring exposed to intrauterine moderate hyperglycemia had a trend to have a higher creatinine clearance rate and significant increase of urinary N-acetyl-β-D-glucosaminidase (NAG excretion indicating an early stage of nephropathy progression. CONCLUSIONS/INTERPRETATION: We observed the high blood pressure level and early renal dysfunction of male offspring obtained from diabetic mothers with moderate hyperglycemia. Furthermore, we investigated high salt diet after weaning on offspring exposed to intrauterine hyperglycemia could exacerbate the blood pressure and renal function. Renin angiotensin system (RAS plays an important role in hypertension pathogenesis and altered gene expression of RAS components in offspring with in utero hyperglycemia exposure may account for the programmed hypertension. Therefore, our study provides evidence "fetal programming" of maternal diabetes is critical for metabolic disease development.

Salvianolic Acid A Protects the Peripheral Nerve Function in Diabetic Rats through Regulation of the AMPK-PGC1α-Sirt3 Axis

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Guanhua Du

2012-09-01

Full Text Available Salvianolic acid A (SalA is one of the main efficacious, water-soluble constituents of Salvia miltiorrhiza Bunge. This study investigated the protective effects of SalA on peripheral nerve in diabetic rats. Administration of SalA (0.3, 1 and 3 mg/kg, ig was started from the 5th week after strepotozotocin (STZ60 mg/kg intraperitoneal injection and continued for 8 weeks. Paw withdrawal mechanical threshold (PWMT and motor nerve conduction velocity (MNCV were used to assess peripheral nerve function. The western blot methods were employed to test the expression levels of serine-threonine liver kinase B1 (LKB1, AMP-activated protein kinase (AMPK, peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α, silent information regulator protein3 (sirtuin 3/Sirt3 and neuronal nitric oxide synthase (nNOS in sciatic nerve. Results showed that SalA administration could increase PWMT and MNCV in diabetic rats; reduce the deterioration of sciatic nerve pathology; increase AMPK phosphorylation level, up-regulate PGC-1α, Sirt3 and nNOS expression, but had no influence on LKB1. These results suggest that SalA has protective effects against diabetic neuropathy. The beneficial effects of SalA on peripheral nerve function in diabetic rats might be attributed to improvements in glucose metabolism through regulation of the AMPK-PGC1α-Sirt3 axis.

Mesenchymal stem cells ameliorate impaired wound healing through enhancing keratinocyte functions in diabetic foot ulcerations on the plantar skin of rats.

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Kato, Jiro; Kamiya, Hideki; Himeno, Tatsuhito; Shibata, Taiga; Kondo, Masaki; Okawa, Tetsuji; Fujiya, Atsushi; Fukami, Ayako; Uenishi, Eita; Seino, Yusuke; Tsunekawa, Shin; Hamada, Yoji; Naruse, Keiko; Oiso, Yutaka; Nakamura, Jiro

2014-01-01

Although the initial healing stage involves a re-epithelialization in humans, diabetic foot ulceration (DFU) has been investigated using rodent models with wounds on the thigh skin, in which a wound contraction is initiated. In this study, we established a rodent model of DFU on the plantar skin and evaluated the therapeutic efficacy of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in this model. The wounds made on the hind paws or thighs of streptozotocin induced diabetic or control rats were treated with BM-MSCs. Expression levels of phosphorylated focal adhesion kinase (pFAK), matrix metaroprotease (MMP)-2, EGF, and IGF-1, were evaluated in human keratinocytes, which were cultured in conditioned media of BM-MSCs (MSC-CM) with high glucose levels. Re-epithelialization initiated the healing process on the plantar, but not on the thigh, skin. The therapy utilizing BM-MSCs ameliorated the delayed healing in diabetic rats. In the keratinocytes cultured with MSC-CM, the decreased pFAK levels in the high glucose condition were restored, and the MMP2, EGF, and IGF-1 levels increased. Our study established a novel rat DFU model. The impaired healing process in diabetic rats was ameliorated by transplantation of BM-MSCs. This amelioration might be accounted for by the modification of keratinocyte functions. Copyright © 2014 Elsevier Inc. All rights reserved.

Skin changes in streptozotocin-induced diabetic rats.

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Andrade, Thiago Antônio Moretti; Masson-Meyers, Daniela Santos; Caetano, Guilherme Ferreira; Terra, Vânia Aparecida; Ovidio, Paula Payão; Jordão-Júnior, Alceu Afonso; Frade, Marco Andrey Cipriani

2017-09-02

Diabetes can cause serious health complications, which can affect every organ of the body, including the skin. The molecular etiology has not yet been clarified for all diabetic skin conditions. Thus, this study aimed to investigate the changes of diabetes in skin compared to non-diabetic skin in rats. Fifteen days after establishing the diabetic status, skin samples from the dorsum-cervical region were harvested for subsequent analysis of alterations caused by diabetes. Our results demonstrate that diabetes stimulated higher inflammation and oxidative stress in skin, but antioxidant defense levels were lower compared to the non-diabetic group (p skin changes compared to non-diabetic skin in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Genomic and metabolic disposition of non-obese type 2 diabetic rats to increased myocardial fatty acid metabolism.

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Sriram Devanathan

Full Text Available Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM. While numerous reports have demonstrated increased myocardial fatty acid (FA utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET to estimate myocardial blood flow (MBF and myocardial FA metabolism. Echocardiograms (ECHOs were performed to assess cardiac function. Levels of triglycerides (TG and non-esterified fatty acids (NEFA were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI and decrease in peak early diastolic mitral annular velocity (E' compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats' exhibit increased genomic disposition to FA and TG metabolism independent of obesity.

Anti-Diabetic Potential of Ocimum gratissimum Leaf Fractions in Fortified Diet-Fed Streptozotocin Treated Rat Model of Type-2 Diabetes

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Stanley I. R. Okoduwa

2017-10-01

Full Text Available Background: Ocimum gratissimum (OG is used in the traditional management of diabetes in Nigeria. This study investigated the anti-diabetic potential of OG leaf fractions (OGLF in a rat model of Type-2 diabetes (T2D. Method: Methanol crude extract of OG leaf was fractionated with solvents of increasing order of polarity (n-hexane, chloroform, ethyl-acetate, n-butanol and water. The anti-diabetic potential of the fractions was evaluated in vivo. T2D was induced in Albino Wistar rats and treated with OGLF. Result: The T2D rats showed significant elevation in serum levels of fasting blood glucose (FBG, liver and kidney function biomarkers. At 4-weeks of intervention with OGLF, the untreated diabetic control group maintained severe hyperglycaemia in the presence of 61.7% serum insulin, 17.3% pancreatic β-cell function (HOMA-β and 51.5% Insulin sensitivity. The glucose tolerance ability was enhanced in the n-butanol-fraction (OGb treated group. With 74.8% available serum insulin and 38.6% improvement in insulin sensitivity, the OGb treated group had a 63.5% reduction in FBG and it was found to be most effective as it ameliorates a majority of the changes caused in the studied parameters in diabetic rats. Conclusions: The data from this study suggest that OGb fraction is a potential candidate for the development of an effective drug for the management of T2D.

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

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Tadashi Okamura

2013-01-01

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

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

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Eric P. Davidson

2014-01-01

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

Beneficial effects of Hibiscus rosa-sinensis L. flower aqueous extract in pregnant rats with diabetes

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Afiune, Luana Alves Freitas; Leal-Silva, Thaís; Sinzato, Yuri Karen; Moraes-Souza, Rafaianne Queiroz; Soares, Thaigra Sousa; Campos, Kleber Eduardo; Fujiwara, Ricardo Toshio; Herrera, Emilio; Damasceno, Débora Cristina

2017-01-01

Purpose The Hibiscus rosa-sinensis flower is widely used in Brazilian traditional medicine for the treatment of diabetes and has shown antifertility activity in female Wistar rats. However, there is no scientific confirmation of its effect on diabetes and pregnancy. The aim of this study was evaluate the effect of aqueous extract of H. rosa-sinensis flowers on maternal-fetal outcome in pregnant rats with diabetes. Methods Diabetes was induced by streptozotocin (STZ, 40 mg/kg) in virgin, adult, female Wistar rats. After diabetes induction, the rats were mated. The pregnant rats were distributed into four groups (n minimum = 11 animals/group): non-diabetic, non-diabetic treated, diabetic, and diabetic treated. Oral aqueous extract of Hibiscus rosa-sinensis was administered to rats in the treatment groups during pregnancy. At term pregnancy, maternal reproductive outcomes, fetal parameters, and biochemical parameters were analyzed. Results The non-diabetic treated group showed decreased high density lipoprotein cholesterol, increased atherogenic index (AI) and coronary artery risk index (CRI), and increased preimplantation loss rate compared to the non-diabetic group. Although treatment with H. rosa-sinensis led to no toxicity, it showed deleterious effects on cardiac and reproductive functions. However, the diabetic treated group showed increased maternal and fetal weights, reduced AI and CRI, and reduced preimplantation loss rate compared to the untreated diabetic group. Conclusion Our results demonstrate beneficial effects of this flower only in pregnant rats with diabetes and their offspring. Although these findings cannot be extrapolated to human clinical use, they show that the indiscriminate intake of H. rosa-sinensis may be harmful to healthy individuals and its use should be completely avoided in pregnancy. PMID:28644857

Beneficial effects of Hibiscus rosa-sinensis L. flower aqueous extract in pregnant rats with diabetes.

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Afiune, Luana Alves Freitas; Leal-Silva, Thaís; Sinzato, Yuri Karen; Moraes-Souza, Rafaianne Queiroz; Soares, Thaigra Sousa; Campos, Kleber Eduardo; Fujiwara, Ricardo Toshio; Herrera, Emilio; Damasceno, Débora Cristina; Volpato, Gustavo Tadeu

2017-01-01

The Hibiscus rosa-sinensis flower is widely used in Brazilian traditional medicine for the treatment of diabetes and has shown antifertility activity in female Wistar rats. However, there is no scientific confirmation of its effect on diabetes and pregnancy. The aim of this study was evaluate the effect of aqueous extract of H. rosa-sinensis flowers on maternal-fetal outcome in pregnant rats with diabetes. Diabetes was induced by streptozotocin (STZ, 40 mg/kg) in virgin, adult, female Wistar rats. After diabetes induction, the rats were mated. The pregnant rats were distributed into four groups (n minimum = 11 animals/group): non-diabetic, non-diabetic treated, diabetic, and diabetic treated. Oral aqueous extract of Hibiscus rosa-sinensis was administered to rats in the treatment groups during pregnancy. At term pregnancy, maternal reproductive outcomes, fetal parameters, and biochemical parameters were analyzed. The non-diabetic treated group showed decreased high density lipoprotein cholesterol, increased atherogenic index (AI) and coronary artery risk index (CRI), and increased preimplantation loss rate compared to the non-diabetic group. Although treatment with H. rosa-sinensis led to no toxicity, it showed deleterious effects on cardiac and reproductive functions. However, the diabetic treated group showed increased maternal and fetal weights, reduced AI and CRI, and reduced preimplantation loss rate compared to the untreated diabetic group. Our results demonstrate beneficial effects of this flower only in pregnant rats with diabetes and their offspring. Although these findings cannot be extrapolated to human clinical use, they show that the indiscriminate intake of H. rosa-sinensis may be harmful to healthy individuals and its use should be completely avoided in pregnancy.

Beneficial effects of Hibiscus rosa-sinensis L. flower aqueous extract in pregnant rats with diabetes.

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Luana Alves Freitas Afiune

Full Text Available The Hibiscus rosa-sinensis flower is widely used in Brazilian traditional medicine for the treatment of diabetes and has shown antifertility activity in female Wistar rats. However, there is no scientific confirmation of its effect on diabetes and pregnancy. The aim of this study was evaluate the effect of aqueous extract of H. rosa-sinensis flowers on maternal-fetal outcome in pregnant rats with diabetes.Diabetes was induced by streptozotocin (STZ, 40 mg/kg in virgin, adult, female Wistar rats. After diabetes induction, the rats were mated. The pregnant rats were distributed into four groups (n minimum = 11 animals/group: non-diabetic, non-diabetic treated, diabetic, and diabetic treated. Oral aqueous extract of Hibiscus rosa-sinensis was administered to rats in the treatment groups during pregnancy. At term pregnancy, maternal reproductive outcomes, fetal parameters, and biochemical parameters were analyzed.The non-diabetic treated group showed decreased high density lipoprotein cholesterol, increased atherogenic index (AI and coronary artery risk index (CRI, and increased preimplantation loss rate compared to the non-diabetic group. Although treatment with H. rosa-sinensis led to no toxicity, it showed deleterious effects on cardiac and reproductive functions. However, the diabetic treated group showed increased maternal and fetal weights, reduced AI and CRI, and reduced preimplantation loss rate compared to the untreated diabetic group.Our results demonstrate beneficial effects of this flower only in pregnant rats with diabetes and their offspring. Although these findings cannot be extrapolated to human clinical use, they show that the indiscriminate intake of H. rosa-sinensis may be harmful to healthy individuals and its use should be completely avoided in pregnancy.

Increase of ATP-sensitive potassium (KATP channels in the heart of type-1 diabetic rats

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Chen Zhih-Cherng

2012-01-01

Full Text Available Abstract Background An impairment of cardiovascular function in streptozotocin (STZ-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (KATP channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac KATP channels in diabetic disorders. Methods Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr were used to examine the effect of hyperglycemia on cardiac function and the expression of KATP channels. KATP channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of KATP channels by Western blot and Northern blot analysis. Results The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of KATP channel. Two subunits of cardiac KATP channel (SUR2A and kir 6.2 were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac KATP in these diabetic rats. Conclusions Both mRNA and protein expression of cardiac KATP channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some KATP channel drugs.

Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats.

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Jiang, Hua; Feng, Jueping; Du, Zhongxia; Zhen, Hui; Lin, Mei; Jia, Shaohui; Li, Tao; Huang, Xinyuan; Ostenson, Claes-Goran; Chen, Zhengwang

2014-09-01

Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin-eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired β-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced diabetic rats.

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Aloulou, Ahmed; Hamden, Khaled; Elloumi, Dhouha; Ali, Madiha Bou; Hargafi, Khaoula; Jaouadi, Bassem; Ayadi, Fatma; Elfeki, Abdelfattah; Ammar, Emna

2012-05-16

Diabetes has become a serious health problem and a major risk factor associated with troublesome health complications, such as metabolism disorders and liver-kidney dysfunctions. The inadequacies associated with conventional medicines have led to a determined search for alternative natural therapeutic agents. The present study aimed to investigate and compare the hypoglycemic and antilipidemic effects of kombucha and black tea, two natural drinks commonly consumed around the world, in surviving diabetic rats. Alloxan diabetic rats were orally supplied with kombucha and black tea at a dose of 5 mL/kg body weight per day for 30 days, fasted overnight, and sacrificed on the 31st day of the experiment. Their bloods were collected and submitted to various biochemical measurements, including blood glucose, cholesterol, triglcerides, urea, creatinine, transaminases, transpeptidase, lipase, and amylase activities. Their pancreases were isolated and processed to measure lipase and α-amylase activities and to perform histological analysis. The findings revealed that, compared to black tea, kombucha tea was a better inhibitor of α-amylase and lipase activities in the plasma and pancreas and a better suppressor of increased blood glucose levels. Interestingly, kombucha was noted to induce a marked delay in the absorption of LDL-cholesterol and triglycerides and a significant increase in HDL-cholesterol. Histological analyses also showed that it exerted an ameliorative action on the pancreases and efficiently protected the liver-kidney functions of diabetic rats, evidenced by significant decreases in aspartate transaminase, alanine transaminase, and gamma-glytamyl transpeptidase activities in the plasma, as well as in the creatinine and urea contents. The findings revealed that kombucha tea administration induced attractive curative effects on diabetic rats, particularly in terms of liver-kidney functions. Kombucha tea can, therefore, be considered as a potential strong

Experimental treatment of diabetic mice with microencapsulated rat islet cells transplantation

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Luo Yun; Xue Yilong; Li Yanling; Li Xinjian

2006-01-01

To observe treatment effects of diabetic mice with microcapsulated and non-microcapsulated rat islet cell transplantation, pancreas of SD rat was perfused with collagenase through cloledchus, and then the pancreatic tissues were isolated and digested. Histopaque-1077 was used to purify the digested pancreas. Islet cells were collected and implanted into the peritoneal cavity of diabetic mice. The isolated islets had a response upon glucose stimulation. When the microcapsulated islets and non- microcapsulated islets were transplanted into diabetic mices the high blood glucose level could be decreased to normal. The normal blood glucose level in the diabetic mice transpanted with microcapsulated islets could be maintained for over 30 days,but it could be mainlained only for 2-3 days in the diabetic mice transplanted with non-microcapsulated islets. Thus it is believed that microcapsulated islet cell transplantation exerts good effect on diabetic mice and the microcapsules possessed good immunoisolating function. (authors)

Glucose metabolic alterations in hippocampus of diabetes mellitus rats and the regulation of aerobic exercise.

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Li, Jingjing; Liu, Beibei; Cai, Ming; Lin, Xiaojing; Lou, Shujie

2017-11-04

Diabetes could negatively affect the structures and functions of the brain, especially could cause the hippocampal dysfunction, however, the potential metabolic mechanism is unclear. The aim of this study was to investigate the changes of glucose metabolism in hippocampus of diabetes mellitus rats and the regulation of aerobic exercise, and to analyze the possible mechanisms. A rat model of type 2 diabetes mellitus was established by high-fat diet feeding in combination with STZ intraperitoneal injection, then 4 weeks of aerobic exercise was conducted. The glucose metabolites and key enzymes involved in glucose metabolism in hippocampus were respectively detected by GC/MS based metabolomics and western blot. Metabolomics results showed that compared with control rats, the level of citric acid was significantly decreased, while the levels of lactic acid, ribose 5-phosphate, xylulose 5-phosphate and glucitol were significantly increased in the diabetic rat. Compared with diabetic rats, the level of citric acid was significantly increased, while the lactic acid, ribose 5-phosphate and xylulose 5-phosphate were significantly decreased in the diabetic exercise rats. Western blot results showed that lower level of citrate synthase and oxoglutarate dehydrogenase, higher level of aldose reductase and glucose 6-phosphatedehydrogenase were found in the diabetic rats when compared to control rats. After 4 weeks of aerobic exercise, citrate synthase was upregulated and glucose 6-phosphatedehydrogenase was downregulated in the diabetic rats. These results suggest that diabetes could cause abnormal glucose metabolism, and aerobic exercise plays an important role in regulating diabetes-induced disorder of glucose metabolism in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats.

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Raish, Mohammad; Ahmad, Ajaz; Jan, Basit L; Alkharfy, Khalid M; Ansari, Mushtaq Ahmad; Mohsin, Kazi; Jenoobi, Fahad Al; Al-Mohizea, Abdullah

2016-10-01

Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats.

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Shen, Szu-Chuan; Cheng, Fang-Chi; Wu, Ning-Jung

2008-11-01

This study investigated the effect of aqueous and ethanol soluble solid extracts of guava (Psidium guajava Linn.) leaves on hypoglycemia and glucose metabolism in type 2 diabetic rats. Low-dose streptozotocin (STZ) and nicotinamide were injected into Sprague-Dawley (SD) rats to induce type 2 diabetes. Acute and long-term feeding tests were carried out, and an oral glucose tolerance test (OGTT) to follow the changes in plasma glucose and insulin levels was performed to evaluate the antihyperglycemic effect of guava leaf extracts in diabetic rats.The results of acute and long-term feeding tests showed a significant reduction in the blood sugar level in diabetic rats fed with either the aqueous or ethanol extract of guava leaves (p guava leaf extracts increased the plasma insulin level and glucose utilization in diabetic rats. The results also indicated that the activities of hepatic hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase in diabetic rats fed with aqueous extracts were higher than in the normal diabetic group (p guava leaf extract and the health function of guava leaves against type 2 diabetes.

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

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Nabi Shaik Abdul

2013-02-01

Full Text Available Abstract 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

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

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Liu, Zhong-wei; Wang, Jun-kui; Qiu, Chuan; Guan, Gong-chang; Liu, Xin-hong; Li, Shang-jian; Deng, Zheng-rong

2015-03-01

Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

Protective effect of melatonin in the diabetic rat retina.

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Mehrzadi, Saeed; Motevalian, Manijeh; Rezaei Kanavi, Mozhgan; Fatemi, Iman; Ghaznavi, Habib; Shahriari, Mansoor

2018-03-01

Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes. The aim of this study was to evaluate the effects of melatonin (MEL) on retinal injury in diabetic rats. In this study, 21 rats were randomly divided into three groups: control, diabetic, and diabetic + MEL. Streptozotocin was used to induce diabetes at a dose of 50 mg/kg, i.p., and blood glucose was measured to choose the diabetic rats for the study. MEL (20 mg/kg) was given orally for 7 weeks in diabetic rats starting 1 week after induction of diabetes. After 8 weeks, the groups were compared in terms of mean scores of fluorescein leakage, using fluorescein angiography. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were estimated in retina using commercially available assays. Structural changes in retinas were evaluated by light microscopy. Results showed that diabetes significantly increased the mean scores of fluorescein leakage, and MDA and ROS levels compared to control group. Treatment of the diabetic rats with MEL for 7 weeks prevented the alterations induced by diabetes in comparison with the diabetic control group.Based on these findings, it can be concluded that MEL might have beneficial effects in prevention of DR. © 2018 Société Française de Pharmacologie et de Thérapeutique.

Lupine Alleviate Hyperglycemia in Streptozotocin Diabetic gamma- Irradiated Rats

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El-Sayed, S.M.

2010-01-01

This study was to examine the regulatory effect of lupine on the diabetic profile developed in Streptozotocin (STZ) induced diabetic albino rats. The effectiveness of lupine against diabetes in gamma irradiated rats was purposed in the present study. Rats were received lupine seeds powder suspension (1 g/kg body weight for 14 consecutive days) before whole body exposure to 8 Gy of gamma radiation and /or STZ (55 mg/kg body weight, single dose) injection. The results pointed out that radiation exposure sustained the diabetic profile in rats received STZ comparing with STZ diabetic not irradiated rats. The prolonged administration of lupine suspension before STZ induction of diabetic and/or irradiated rats reduced the changes in the level of blood glucose, insulin concentration, liver glycogen, and the activity of glucose-6-phosphatase associated with significant amelioration in blood antioxidant status (superoxide dismutase, SOD; catalase, CAT; glucose-6-phosphate dehydrogenase, G-6-PD activities and reduced glutathione concentration GSH). Also, the level of blood lipid peroxides (TBARS) were reduced greatly when compared with its matched value in diabetic and /or gamma irradiated rats. It could be postulated that lupine powder suspension might be attenuate the diabetic profile development throughout reducing oxidative damages and modulating the antioxidant status. In addition, lupine could be considered as one of a remarkable radio protective agent owing to its antioxidants property

Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats.

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Watts, Tammara; Berti, Irene; Sapone, Anna; Gerarduzzi, Tania; Not, Tarcisio; Zielke, Ronald; Fasano, Alessio

2005-02-22

Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased intestinal permeability plays a role in the pathogenesis of T1D. In the BB diabetic-prone rat model of T1D, intestinal intraluminal zonulin levels were elevated 35-fold compared to control BB diabetic-resistant rats. Zonulin up-regulation was coincident with decreased small intestinal transepithelial electrical resistance, and was followed by the production of autoantibodies against pancreatic beta cells, which preceded the onset of clinically evident T1D by approximately 25 days. In those diabetic prone rats that did not progress to diabetes, both intraluminal zonulin and transepithelial electrical resistance were similar to those detected in diabetic-resistant animal controls. Blockade of the zonulin receptor reduced the cumulative incidence of T1D by 70%, despite the persistence of intraluminal zonulin up-regulation. Moreover, treatment responders did not seroconvert to islet cell antibodies. Combined together, these findings suggest that the zonulin-induced loss in small intestinal barrier function is involved in the pathogenesis of T1D in the BB diabetic-prone animal model.

Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression

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Casper G. Schalkwijk

2013-07-01

Full Text Available Diabetes significantly increases the risk of heart failure. The increase in advanced glycation endproducts (AGEs and oxidative stress have been associated with diabetic cardiomyopathy. We recently demonstrated that there is a direct link between AGEs and oxidative stress. Therefore, the aim of the current study was to investigate if a reduction of AGEs by overexpression of the glycation precursor detoxifying enzyme glyoxalase-I (GLO-I can prevent diabetes-induced oxidative damage, inflammation and fibrosis in the heart. Diabetes was induced in wild-type and GLO-I transgenic rats by streptozotocin. After 24-weeks of diabetes, cardiac function was monitored with ultrasound under isoflurane anesthesia. Blood was drawn and heart tissue was collected for further analysis. Analysis with UPLC-MSMS showed that the AGE Nε-(1-carboxymethyllysine and its precursor 3-deoxyglucosone were significantly elevated in the diabetic hearts. Markers of oxidative damage, inflammation, and fibrosis were mildly up-regulated in the heart of the diabetic rats and were attenuated by GLO-I overexpression. In this model of diabetes, these processes were not accompanied by significant changes in systolic heart function, i.e., stroke volume, fractional shortening and ejection fraction. This study shows that 24-weeks of diabetes in rats induce early signs of mild cardiac alterations as indicated by an increase of oxidative stress, inflammation and fibrosis which are mediated, at least partially, by glycation.

Protective effect of thymoquinone improves cardiovascular function, and attenuates oxidative stress, inflammation and apoptosis by mediating the PI3K/Akt pathway in diabetic rats.

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Liu, Hui; Liu, Hong-Yang; Jiang, Yi-Nong; Li, Nan

2016-03-01

Thymoquinone is the main active monomer extracted from black cumin and has anti‑inflammatory, antioxidant and anti‑apoptotic functions. However, the protective effects of thymoquinone on cardiovascular function in diabetes remain to be fully elucidated. The present study aimed to investigate the molecular mechanisms underling the beneficial effects of thymoquinone on the cardiovascular function in streptozotocin‑induced diabetes mellitus (DM) rats. Supplement thymoquinone may recover the insulin levels and body weight, inhibit blood glucose levels and reduce the heart rate in DM‑induced rats. The results indicated that the heart, liver and lung to body weight ratios, in addition to the blood pressure levels, were similar for each experimental group. Treatment with thymoquinone significantly reduced oxidative stress damage, inhibited the increased endothelial nitric oxide synthase protein expression and suppressed the elevation of cyclooxygenase‑2 levels in DM‑induced rats. In addition, thymoquinone significantly suppressed the promotion of tumor necrosis factor‑α and interleukin‑6 levels in the DM‑induced rats. Furthermore, administration of thymoquinone significantly reduced caspase‑3 activity and the promotion of phosphorylated‑protein kinase B (Akt) protein expression levels in DM‑induced rats. These results suggest that the protective effect of thymoquinone improves cardiovascular function and attenuates oxidative stress, inflammation and apoptosis by mediating the phosphatidylinositol 3‑kinase/Akt pathway in DM‑induced rats.

Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

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Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

2013-12-01

Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine.

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Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

2017-01-01

Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. We aimed to characterize the stimulus-response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress-strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity ( P <0.05). The stress relaxed less in the diabetic intestinal segment ( P <0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients.

Impaired insulin secretion in the spontaneous diabetes rats.

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Kimura, K; Toyota, T; Kakizaki, M; Kudo, M; Takebe, K; Goto, Y

1982-08-01

Dynamics of insulin and glucagon secretion were investigated by using a new model of spontaneous diabetes rats produced by the repetition of selective breeding in our laboratories. The perfusion experiments of the pancreas showed that the early phase of insulin secretion to continuous stimulation with glucose was specifically impaired, although the response of the early phase to arginine was preserved. The glucose-induced insulin secretion in the nineth generation (F8) which had a more remarkably impaired glucose tolerance was more reduced than in the sixth generation (F5). No significant difference of glucagon secretion in response to arginine or norepinephrine was noted between the diabetes rats and control ones. The present data indicate that the defective insulin secretion is a primary derangement in a diabetic state of the spontaneous diabetes rat. This defect in the early phase of glucose-induced insulin secretion suggests the specific impairment of the recognition of glucose by the pancreatic beta-cells. The spontaneous diabetes rats are very useful as a model of disease for investigating pathophysiology of non-insulin dependent diabetes mellitus.

The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats

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Feng, Qianjin; Niu, Xin; Liu, Xinshe; Xu, Kaixia; Yang, Xiangzhu; Wang, Huifeng

2014-01-01

In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the control group (group II, n = 11), and (3) rats of normal pregnancy group (group III, n = 11). Compared with gestational diabetes mellitus rats as the control group, Zuogui Wan can change the indexes of fasting blood glucose, body weight, total cholesterol, insulin, and metabolism cage index significantly in Zuogui Wan gestational diabetes mellitus group. We can conclude that Zuogui Wan has the therapeutic effect on gestational diabetes mellitus. PMID:25136475

Anti-diabetic effects of shubat in type 2 diabetic rats induced by combination of high-glucose-fat diet and low-dose streptozotocin.

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Manaer, Tabusi; Yu, Lan; Zhang, Yi; Xiao, Xue-Jun; Nabi, Xin-Hua

2015-07-01

Shubat, probiotic fermented camel milk, has been used both as a drink with ethnic flavor and a medicine among Kazakh population for diabetic patients. Kazakh people have lower diabetic prevalence and impaired fasting glucose (IFG) than do other ethnic groups living in Xinjiang China, which might be related to the beneficial properties of shubat. We therefore prepared shubat in laboratory and tested anti-diabetic activity and evaluated its possible hypolipidemic and renoprotective effects in type 2 diabetic rats. Type 2 diabetic rats were induced by an administration of high-glucose-fat diet for 6 weeks and an intraperitoneal injection of streptozotocin (STZ, 30mg/kg). Diabetic rats were divided randomly into four groups and treated for 28 days with sitagliptin (30mg/kg) or shubat (6.97×10(6) lactic acid bacteria+2.20×10(4) yeasts) CFU/mL, (6.97×10(7) lactic acid bacteria+2.20×10(5) yeasts) CFU/mL and (6.97×10(8) lactic acid bacteria+2.20×10(6) yeasts) CFU/mL. In addition, a normal control group and a diabetic control group were used for comparison. All drugs were given orally once daily 10mL/kg for 4 weeks. Fasting blood glucose (FBG) and body weight (BW) were measured before treatment and every week thereafter. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), serum creatinine (SCr), blood urea nitrogen (BUN), C-peptide, glycated hemoglobin (HbAlc), glucagon-like peptide-1 (GLP-1) levels and pancreas tissue sections were tested after 4 weeks. Shubat demonstrated positive hypoglycemic activity on FBG, HbAlc, C-peptide and GLP-1 levels, high dose shubat decreased FBG (Pdiabetic controls. Histological analysis showed shubat protected the function of islets of type 2 diabetic rats. The results of this study indicate that shubat has significant hypoglycemic potential in T2D rats and may modulate lipid metabolism and protect renal function in the type 2 diabetic condition, which

Enhanced Glucose Tolerance and Pancreatic Beta Cell Function by Low Dose Aspirin in Hyperglycemic Insulin-Resistant Type 2 Diabetic Goto-Kakizaki (GK Rats

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Layla Amiri

2015-07-01

Full Text Available Background/Aim: Type 2 diabetes is the most common metabolic disorder, characterized by insulin resistance and pancreatic islet beta-cell failure. The most common complications associated with type 2 diabetes are hyperinsulinemia, hyperglycemia, hyperlipidemia, increased inflammatory and reduced insulin response. Aspirin (ASA and other non-steroidal anti-inflammatory drugs (NSAIDs have been associated with the prevention of diabetes, obesity and related cardiovascular disorders. Aspirin has been used in many clinical and experimental trials for the prevention of diabetes and associated complications. Methods: In this study, five month old Goto-Kakizaki (GK rats, which showed signs of mild hyperglycemia (fasting blood glucose 80-95 mg/dl vs 55-60 mg/dl Wistar control rats were used. Two subgroups of GK and Wistar control rats were injected intraperitoneally with 100 mg aspirin/kg body weight/ day for 5 weeks. Animals were sacrificed and blood and tissues were collected after performing glucose tolerance (2 h post 2g IP glucose ingestion tests in experimental and control groups. Results: Aspirin caused a moderate decrease in hyperglycemia. However, we observed a significant improvement in glucose tolerance after ASA treatment in GK rats compared to the nondiabetic Wistar rats. Also, the ASA treated GK rats exhibited a significant decrease in insulinemia. ASA treatment also caused a marked reduction in the pro-inflammatory prostaglandin, PGE2, which was significantly higher in GK rats. On the other hand, no significant organ toxicity was observed after ASA treatment at this dose and time period. However, the total cholesterol and lipoprotein levels were significantly increased in GK rats, which decreased after ASA treatment. Immunofluorescence staining for insulin/glucagon secreting pancreatic cells showed improved beta-cell structural and functional integrity in ASA-treated rats which was also confirmed by SDS-PAGE and Western blot analysis

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats

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Gomez R.

2001-01-01

Full Text Available Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg, moclobemide (30 mg/kg, clonazepam (0.25 mg/kg, fluoxetine (20 mg/kg sertraline (30 mg/kg or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.

The potential of pigeon pea (Cajanus cajan) beverage as an anti-diabetic functional drink

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Ariviani, S.; Affandi, D. R.; Listyaningsih, E.; Handajani, S.

2018-01-01

The number of patients with diabetes continues to increase. Diabetes complications might induce serious diseases such as kidney, nervous, cardiovascular diseases and stroke. Diabetic complications can be prevented by keeping blood glucose and cholesterol at normal levels. This study aims to determine the potential of pigeon pea beverage for lowering glucose and total cholesterol plasma levels and increasing the antioxidant status of diabetic-hypercholesterolemia rats. The research was conducted using 18 Sprague Dawley male rats aged 3 months old with an average body weight of 154 g. The rats were divided into three groups: normal group, D-H group (diabetic-hypercholesterolemia group), and pigeon pea beverage group. The results showed that pigeon pea beverage diet showed hypoglycemic and hypocholesterolemic activities, and could improve the antioxidant status of diabetic-hypercholesterolemia rats. Plasma glucose and total cholesterol levels of diabetic-hypercholesterolemia rats decreased 33.86% and 19.78% respectively. The improvement of the plasma antioxidant status was indicated by the decrease of plasma MDA (malondialdehyde) level, reaching 37.16%. The research result provides an alternative to diabetes management by using the local bean as an anti-diabetic functional drink.

EVALUATION OF THE POSSIBLE ANTIOXIDANT EFFECTS OF NIGELLA SATIVA AND CURCUMA LONGA IN AMELIORATING DIABETIC NEPHROPATHY IN RATS

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OSMAN, N.N.; FARAG, M.F.S.; DARWISH, M.M

2009-01-01

Chronic hyperglycemia in diabetes leads to the overproduction of free radicals and the evidence is increasing because these radicals are responsible for the development of diabetic nephropathy. Diabetic nephropathy is an important microvascular complication and one of the main causes of end stage renal disease. The aim of the present study was to test the hypothesis that combined treatment with Nigella sativa (NS) and Curcuma longa (CL) is more effective than each of them alone in improving renal function and oxidative stress in alloxan-induced diabetic rats.Diabetes was induced in male albino rats with a single intravenous injection of alloxan (150 mg/kg). Two weeks after alloxan injection, rats were divided into five groups; control, diabetic and diabetic rats received either NS (10ml/kg/day), or CL (80mg/kg/day) and their combination by gastric intubation for 4 weeks.Diabetic rats exhibited many symptoms including loss of body weight, hyperglycemia, polyuria, renal enlargement and renal dysfunction. Significant increase in TBARS (lipid peroxidation marker) was observed in diabetic kidney. This was accompanied by a significant decrease in GSH content, SOD and CAT activities in the kidneys. Daily oral ingestion of NS and/or CL extract for 4 weeks has attenuated the oxidative stress in the kidney and reversed the adverse effect of diabetes in rats by lowering blood glucose levels, increased plasma insulin and restored body weight loss and renal function.These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible anti-oxidative mechanism being responsible for the nephroprotective action of NS and CL.

Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced diabetic rats

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Aloulou Ahmed

2012-05-01

Full Text Available Abstract Background Diabetes has become a serious health problem and a major risk factor associated with troublesome health complications, such as metabolism disorders and liver-kidney dysfunctions. The inadequacies associated with conventional medicines have led to a determined search for alternative natural therapeutic agents. The present study aimed to investigate and compare the hypoglycemic and antilipidemic effects of kombucha and black tea, two natural drinks commonly consumed around the world, in surviving diabetic rats. Methods Alloxan diabetic rats were orally supplied with kombucha and black tea at a dose of 5 mL/kg body weight per day for 30 days, fasted overnight, and sacrificed on the 31st day of the experiment. Their bloods were collected and submitted to various biochemical measurements, including blood glucose, cholesterol, triglcerides, urea, creatinine, transaminases, transpeptidase, lipase, and amylase activities. Their pancreases were isolated and processed to measure lipase and α-amylase activities and to perform histological analysis. Results The findings revealed that, compared to black tea, kombucha tea was a better inhibitor of α-amylase and lipase activities in the plasma and pancreas and a better suppressor of increased blood glucose levels. Interestingly, kombucha was noted to induce a marked delay in the absorption of LDL-cholesterol and triglycerides and a significant increase in HDL-cholesterol. Histological analyses also showed that it exerted an ameliorative action on the pancreases and efficiently protected the liver-kidney functions of diabetic rats, evidenced by significant decreases in aspartate transaminase, alanine transaminase, and gamma-glytamyl transpeptidase activities in the plasma, as well as in the creatinine and urea contents. Conclusions The findings revealed that kombucha tea administration induced attractive curative effects on diabetic rats, particularly in terms of liver-kidney functions

Effects of β-Glucans Ingestion on Alveolar Bone Loss, Intestinal Morphology, Systemic Inflammatory Profile, and Pancreatic β-Cell Function in Rats with Periodontitis and Diabetes

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Silva, Viviam de O.; Lobato, Raquel V.; Orlando, Débora R.; Borges, Bruno D.B.; de Sousa, Raimundo V.

2017-01-01

This study aimed to evaluate the effects of β-glucan ingestion (Saccharomyces cerevisiae) on the plasmatic levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10), alveolar bone loss, and pancreatic β-cell function (HOMA-BF) in diabetic rats with periodontal disease (PD). Besides, intestinal morphology was determined by the villus/crypt ratio. A total of 48 Wistar rats weighing 203 ± 18 g were used. Diabetes was induced by the intraperitoneal injection of streptozotocin (80 mg/kg) and periodontal inflammation, by ligature. The design was completely randomized in a factorial scheme 2 × 2 × 2 (diabetic or not, with or without periodontitis, and ingesting β-glucan or not). The animals received β-glucan by gavage for 28 days. Alveolar bone loss was determined by scanning electron microscopy (distance between the cementoenamel junction and alveolar bone crest) and histometric analysis (bone area between tooth roots). β-glucan reduced plasmatic levels of TNF-α in diabetic animals with PD and of IL-10 in animals with PD (p < 0.05). β-glucan reduced bone loss in animals with PD (p < 0.05). In diabetic animals, β-glucan improved β-cell function (p < 0.05). Diabetic animals had a higher villus/crypt ratio (p < 0.05). In conclusion, β-glucan ingestion reduced the systemic inflammatory profile, prevented alveolar bone loss, and improved β-cell function in diabetic animals with PD. PMID:28906456

INTERVAL TRAINING IS INSUFFICIENT TO ATTENUATE METABOLIC DISTURBANCES IN DIABETIC RATS

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Ricelli Endrigo Ruppel da Rocha

Full Text Available ABSTRACT Introduction: Type 1 diabetes is a metabolic disease associated to blood disturbances and disorder of the innate immune system functionality. Objective: This study investigated the effect of two weeks interval training on blood biochemistry and immunological parameters in rats with type 1 diabetes. Methods: Male Wistar rats were divided into three groups: sedentary (SE, n = 10, diabetic sedentary (DI, n = 10, diabetic interval training (DIT, n = 10. IV injection of streptozotocin (45 mg/kg induced diabetes. Interval training consisted of swimming exercise for 30 seconds with 30 seconds of rest for 30 minutes three times a week during two weeks, with an overload of 15% of the total body mass. The evaluations performed were fasting blood glucose, triglycerides, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol concentrations, phagocytic capacity, cationic vesicles content, superoxide anion, and production of hydrogen peroxide of blood neutrophils and peritoneal macrophages. Results: The results showed that two weeks interval training did not attenuate the hyperglycemic state at rest and did not decrease blood lipids in the DIT group. Diabetes increased the functionality of blood neutrophils and peritoneal macrophages in the DI group. Interval training increased the content of cationic vesicles and the phagocytic capacity of blood neutrophils and peritoneal macrophages in the DIT group. Conclusion: It was found that two weeks of interval training increased the functionality parameters of innate immune cells, although this has been insufficient to attenuate the biochemical disorders caused by diabetes.

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

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Annida, B; Stanely Mainzen Prince, P

2004-01-01

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

Low Intensity Physical Exercise Attenuates Cardiac Remodeling and Myocardial Oxidative Stress and Dysfunction in Diabetic Rats

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C. Gimenes

2015-01-01

Full Text Available We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed, exercised control (C-Ex, sedentary diabetes (DM-Sed, and exercised diabetes (DM-Ex. Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73±0.49; C-Ex: 5.67±0.53; DM-Sed: 6.41±0.54; DM-Ex: 5.81±0.50 mm; P<0.05 DM-Sed vs C-Sed and DM-Ex. Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. Conclusion. Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.

Interval training attenuates the metabolic disturbances in type 1 diabetes rat model.

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Rocha, Ricelli Endrigo Ruppel; Coelho, Isabela; Pequito, Daniela Cristina T; Yamagushi, Adriana; Borghetti, Gina; Yamazaki, Ricardo Key; Brito, Gleisson Alisson Pereira de; Machado, Juliano; Kryczyk, Marcelo; Nunes, Everson Araújo; Venera, Graciela; Fernandes, Luiz Claudio

2013-11-01

This study investigated the effect of interval training on blood biochemistry and immune parameters in type 1 diabetic rats. Male Wistar rats were divided into four groups: sedentary (SE, n = 15), interval training (IT, n = 17), diabetic sedentary (DSE, n = 17), diabetic interval training (DIT, n = 17). Diabetes was induced by i.v. injection of streptozotocin (60 mg/kg). Swimming Interval Training consisted of 30-s exercise with 30-s rest, for 30 minutes, during 6 weeks, four times a week, with an overload of 15% of body mass. Plasma glucose, lactate, triacylglycerol and total cholesterol concentrations, phagocytic capacity, cationic vesicle content, and superoxide anion and hydrogen peroxide production by blood neutrophils and peritoneal macrophages were evaluated. Proliferation of mesenteric lymphocytes was also estimated. Interval training resulted in attenuation of the resting hyperglycemic state and decreased blood lipids in the DIT group. Diabetes increased the functionality of blood neutrophils and peritoneal macrophages in the DSE group. Interval training increased all functionality parameters of peritoneal macrophages in the IT group. Interval training also led to a twofold increase in the proliferation of mesenteric lymphocytes after 6 weeks of exercise in the DIT group. Low-volume high-intensity physical exercise attenuates hyperglycemia and dislipidemia induced by type 1 diabetes, and induces changes in the functionality of innate and acquired immunity.

Periodontitis promotes the diabetic development of obese rat via miR-147 induced classical macrophage activation.

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Xu, Ran; Zeng, Guang; Wang, Shuyong; Tao, Hong; Ren, Le; Zhang, Zhe; Zhang, Qingna; Zhao, Jinxiu; Gao, Jing; Li, Daxu

2016-10-01

Emerging evidence has indicated the bad effect of periodontal inflammation on diabetes control. However, the exact regulatory mechanisms within the association between periodontitis and diabetic development remain unclear. This study aims to investigate the function of microRNAs in regulating periodontitis-induced inflammation in an obese rat model. Experimental periodontitis was introduced into OLETF and LETO rat. Intraperitoneal glucose tolerance test was performed to detect diabetic development. Serum cytokines levels and microRNAs expression were detected by ELISA and RT-PCR analysis respectively. And, macrophages were isolated for gain- and loss-of-function studies, to investigate the regulatory mechanism of miR-147 in periodontitis-induced inflammation. Periodontitis induced proinflammatory response with classical activated macrophages in both rats, but distinctively aggravated the impaired glucose tolerance of OLETF rat with spontaneous type 2 diabetes. Analysis for serum microRNAs expression showed the distinctive and synergistic upregulation of miR-147 with periodontitis-induced effects in rats, while further experiments demonstrated the positive regulatory mechanism of miR-147 on classical activated macrophages with overexpressed proinflammatory markers, showing M1 phenotype. This study provided new evidence for the positive effect of periodontal inflammation on diabetic development, while the regulatory mechanism of miR-147 on classical macrophage activation, was verified, and presumed to contribute to the impaired glucose tolerance aggravated by periodontitis in obese rats. Besides, this study indicated the application of miR-147 for therapeutic approach in the treatment of diabetes with periodontitis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Stem Cell Therapy for Diabetic Erectile Dysfunction in Rats: A Meta-Analysis.

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Mingchao Li

Full Text Available Stem cell therapy is a novel method for the treatment of diabetic erectile dysfunction (ED. Many relative animal studies have been done to evaluate the efficacy of this therapy in rats.This meta-analysis was performed to compare the efficacy of different stem cell therapies, to evaluate the influential factors and to determine the optimal stem cell therapeutic strategy for diabetic ED.We searched the studies analyzing the efficacy of stem cell therapy for diabetic ED in rats published before September 30, 2015 in PubMed, Web of Science and EBSCO. A random effects meta-analysis was conducted to assess the outcomes of stem cell therapy. Subgroup analysis was also performed by separating these studies based on their different characteristics. Changes in the ratio of intracavernous pressure (ICP to mean arterial pressure (MAP and in the structure of the cavernous body were compared.10 studies with 302 rats were enrolled in this meta-analysis. Pooled analysis of these studies showed a beneficial effect of stem cell therapy in improving erectile function of diabetic rats (SMD 4.03, 95% CI = 3.22 to 4.84, P< 0.001. In the stem cell therapy group, both the smooth muscle and endothelium content were much more than those in control group. There was also significant increase in the expression of endothelial nitric oxide synthase (eNOS and neuronal nitric oxide synthase (nNOS, the ratio of smooth muscle to collagen, as well as the secretion of vascular endothelial growth factor (VEGF. Besides, apoptotic cells were reduced by stem cell treatment. The subgroup analysis indicated that modified stem cells were more effective than those without modification.Our results confirmed that stem cell therapy could apparently improve the erectile function of diabetic rats. Some specific modification, especially the gene modification with growth factors, could improve the efficacy of stem cell therapy. Stem cell therapy has potential to be an effective therapeutic

Effect of Bauhinia holophylla treatment in Streptozotocin-induced diabetic rats.

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Pinheiro, Marcelo S; Rodrigues, Luhara S; S, Leila; Moraes-Souza, Rafaianne Q; Soares, Thaigra S; Américo, Madileine F; Campos, Kleber E; Damasceno, Débora C; Volpato, Gustavo T

2017-01-01

Bauhinia holophylla, commonly known as "cow's hoof", is widely used in Brazilian folk medicine for the diabetes treatment. Therefore, the aim of this study was at evaluating the aqueous extract effect of Bauhinia holophylla leaves treatment on the streptozotocin-induced diabetic rats. Diabetes was induced by Streptozotocin (40 mg/Kg) in female Wistar rats. Oral administration of aqueous extract of Bauhinia holophylla leaves was given to non-diabetic and diabetic rats at a dose of 400 mg/kg during 21 days. On day 17 of treatment, the Oral Glucose Tolerance Test was performed to determine the area under the curve. At the end of the treatment, the animals were anesthetized and blood was collected for serum biochemical parameters analysis. After treatment with Bauhinia holophylla extract, non-diabetic and diabetic rats presented no glycemic changes. On the other hand, the plant treatment decreased body weight and increased ALT and AST activities. In conclusion, the treatment with aqueous extract of B. holophylla leaves given to diabetic rats presented no hypoglycemic effect in nondiabetic animals and no antidiabetic effect in diabetic animals with the doses studied. In addition, the diabetic animals treated with the B. holophylla extract showed inconvenient effects and its indiscriminate consumption requires particular carefulness.

Aloe vera gel improves behavioral deficits and oxidative status in streptozotocin-induced diabetic rats.

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Tabatabaei, Seyed Reza Fatemi; Ghaderi, Shahab; Bahrami-Tapehebur, Mohammad; Farbood, Yaghoob; Rashno, Masome

2017-12-01

Oxidative stress has a major role in progression of diabetes-related behavioral deficits. It has been suggested that Aloe vera has anti-diabetic, antioxidative, and neuroprotective effects. The present study was designed to determine the effects of Aloe vera gel on behavioral functions, oxidative status, and neuronal viability in the hippocampus of streptozotocin (STZ)-induced diabetic rats. Fifty five adult male Wistar rats were randomly divided into five groups, including: control (normal saline 8ml/kg/day; P.O.), diabetic (normal saline 8ml/kg/day; P.O.), Aloe vera gel (100mg/kg/day; P.O.), diabetic+Aloe vera gel (100mg/kg/day; P.O.) and diabetic+NPH insulin (10 IU/kg/day; S.C.). All treatments were started immediately following confirmation of diabetes in diabetic groups and were continued for eight weeks. Behavioral functions were evaluated by employing standard behavioral paradigms. Additionally, oxidative status and neuronal viability were assessed in the hippocampus. The results of behavioral tests showed that diabetes enhanced anxiety/depression-like behaviors, reduced exploratory and locomotor activities, decreased memory performance, and increased stress related behaviors. These changes in diabetic rats were accompanied by increasing oxidative stress and neuronal loss in the hippocampus. Interestingly, eight weeks of treatment with Aloe vera gel not only alleviated all the mentioned deficits related to diabetes, but in some aspects, it was even more effective than insulin. In conclusion, the results suggest that both interrelated hypoglycemic and antioxidative properties of Aloe vera gel are possible mechanisms that improve behavioral deficits and protect hippocampal neurons in diabetic animals. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats: a pathophysiological model for the combined effects of hypertension and diabetes

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Pijl, A. J.; van der Wal, A. C.; Mathy, M. J.; Kam, K. L.; Hendriks, M. G.; Pfaffendorf, M.; van Zwieten, P. A.

1994-01-01

The present study was undertaken to investigate the combined effects of hypertension and streptozotocin-induced diabetes mellitus in the rat. Accordingly, four groups of rats were studied: Wistar Kyoto rats (WKY), diabetic WKY, spontaneously hypertensive rats (SHR) and diabetic SHR, respectively.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

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Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

2016-08-09

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Butanol fraction of Parkia biglobosa (Jacq.) G. Don leaves enhance pancreatic β-cell functions, stimulates insulin secretion and ameliorates other type 2 diabetes-associated complications in rats.

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Ibrahim, Mohammed Auwal; Habila, James Dama; Koorbanally, Neil Anthony; Islam, Md Shahidul

2016-05-13

Ethnopharmacological surveys have reported that Parkia biglobosa (Jacq.) G. Don (Leguminosae) is among the plants commonly used in the traditional management of diabetes mellitus in Nigeria and Togo. This study investigated the anti-diabetic activity of the butanol fraction of P. biglobosa leaves (PBBF) in a type 2 diabetes (T2D) model of rats and a possible bioactive compound in the fraction. T2D was induced by feeding rats with a 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of 40mg/kg body weight streptozotocin and the animals were orally treated with 150 and 300mg/kg BW of the PBBF for five days in a week. Another group of rats was non-diabetic but similarly administered with 300mg/kg BW of the PBBF. Food and fluid intakes, body weight changes and blood glucose levels were monitored during the experiment while other relevant diabetes-associated parameters were measured at the end of the experiment. The PBBF treatments significantly (P<0.05) decreased the blood glucose levels and improved the glucose tolerance ability compared to untreated diabetic rats. Furthermore, the treatments were found to improve pancreatic β cell function (HOMA-β), stimulate insulin secretions, decrease insulin resistance (HOMA-IR), restore liver glycogen, ameliorate serum dyslipidaemia and prevent hepatic and renal damages compared to untreated diabetic rats. Phytochemical analysis of the fraction led to the isolation of lupeol which inhibited α-glucosidase and α-amylase in non-competitive and uncompetitive inhibition patterns respectively. It was concluded that PBBF possessed remarkable anti-T2D activity which is mediated through modulation of β-cell function and stimulation of insulin secretion and the lower dose (150mg/kg BW) was found optimum for anti-T2D activity compared to the high dose (300mg/kg BW) in this study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.

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Kurtz, Melisa; Capobianco, Evangelina; Martinez, Nora; Roberti, Sabrina Lorena; Arany, Edith; Jawerbaum, Alicia

2014-10-01

In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands. © 2014 Society for Endocrinology.

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

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Jang Hyun Koh

2014-01-01

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

Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy

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Victoria L. Newton

2017-01-01

Full Text Available Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ- induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ. At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy.

Antidiabetic effects of Artemisia sphaerocephala Krasch. gum, a novel food additive in China, on streptozotocin-induced type 2 diabetic rats.

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Xing, Xiao-Hui; Zhang, Zheng-Mao; Hu, Xin-Zhong; Wu, Rui-Qin; Xu, Chao

2009-09-25

Since ancient times, practicians of traditional Chinese medicine have discovered that Artemisia sphaerocephala Krasch. (Asteraceae) seed powder was useful for the treatment of diabetes. Artemisia sphaerocephala Krasch. gum (ASK gum), which is extracted from seed powder of the plant, is a novel food additive favored by the food industry in China. The objective of this study was to determine the antidiabetic function of ASK gum on type 2 diabetes. Type 2 diabetic rat model was induced with high fat diet and low dose of streptozotocin (STZ). The effects of ASK gum on hyperglycemia, hyperlipemia, insulin resistance, and liver fat accumulation in type 2 diabetic rats were evaluated. The results were compared to those of normal rats and diabetic rats treated with metformin. The addition of ASK gum to the rats' food supply significantly lowered fasting blood glucose, glycated serum protein, serum cholesterol, and serum triglyceride in type 2 diabetic rats, and significantly elevated liver glucokinase, liver glycogen, and serum high density protein cholesterol in the diabetic rats. ASK gum significantly reduced insulin resistance and liver fat accumulation of type 2 diabetes. Artemisia sphaerocephala Krasch. gum can alleviate hyperglycemia, hyperlipemia and insulin resistance of type 2 diabetes.

High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats.

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Toyoda, Kaoru; Suzuki, Yusuke; Muta, Kyotaka; Masuyama, Taku; Kakimoto, Kochi; Kobayashi, Akio; Shoda, Toshiyuki; Sugai, Shoichiro

2018-01-01

Diabetic nephropathy (DN) is one of the complications of diabetes and is now the most common cause of end-stage renal disease. Fructose is a simple carbohydrate that is present in fruits and honey and is used as a sweetener because of its sweet taste. Fructose has been reported to have the potential to progress diabetes and DN in humans even though fructose itself does not increase postprandial plasma glucose levels. In this study, we investigated the effects of high fructose intake on the kidney of the Spontaneously Diabetic Torii (SDT) rats which have renal lesions similar to those in DN patients and compared these with the effects in normal SD rats. This study revealed that a 4-week feeding of the high fructose diet increased urinary excretion of kidney injury makers for tubular injury and accelerated mainly renal tubular and interstitial lesions in the SDT rats but not in normal rats. The progression of the nephropathy in the SDT rats was considered to be related to increased internal uric acid and blood glucose levels due to the high fructose intake. In conclusion, high fructose intake exaggerated the renal lesions in the SDT rats probably due to effects on the tubules and interstitium through metabolic implications for uric acid and glucose.

Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.

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Peilang Yang

Full Text Available Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8 weeks high fat diet (HFD feeding regimen followed by multiple injections of streptozotocin (STZ at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds.

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

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

2014-10-01

The present study aims to investigate anti-hyperglycaemic, anti-hyperlipidaemic and toxic effects of long-term consumption of selected green leafy porridges in a streptozotocin-induced diabetic Wistar rat model. Porridges made with Asparagus racemosus Willd. (AR), Hemidesmus indicus (L) R. Br. W. T. Aiton (HI), Scoparia dulcis L. (SD) and coconut milk porridge (CM) were incorporated into diets of diabetic Wistar rats. Diabetic control (DM) and normal control groups (NC) were provided with standard rat diet. Fasting blood glucose (FBG), HbA1c , C reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), liver enzymes and creatinine were measured. Feed and water intake among diabetic groups were significantly high when compared with those of NC (p  0.05). Among the diabetic groups, lowest TC (119 ± 20.6 mg/dL) and highest HDL-C (33 ± 6.3 mg/dL) were also detected in SD group. Alanine transaminase and creatinine were not significantly different (p > 0.05) among diabetic groups but significant when compared with those of NC. When compared with those of NC, aspartate transaminase levels were significantly (p < 0.05) high in SD, CM and DM groups. Body weight : liver weight and body weight : pancreas weight ratios and CRP were not significantly different among all groups. The study proved that SD porridge reduced weight loss, elicited hypoglycaemic and hypolipidaemic properties, and caused no toxicity in diabetes-induced Wistar rats. Copyright © 2014 John Wiley & Sons, Ltd.

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine

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Zhao J

2017-12-01

Full Text Available Jingbo Zhao,1 Jian Yang,1 Donghua Liao,1 Hans Gregersen2 1Giome Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 2Giome Center, Department of Surgery, Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, Hong Kong Background: Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective: We aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Design: Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR, and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Results: Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05. The stress relaxed less in the diabetic intestinal segment (P<0.05. Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Conclusion: Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients. Keywords: afferents, spike rate, stress–strain, creep

A histological and functional study on hippocampal formation of normal and diabetic rats [v1; ref status: indexed, http://f1000r.es/y9

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Shaimaa N Amin

2013-07-01

Full Text Available Background: The hippocampus is a key brain area for many forms of learning and memory and is particularly sensitive to changes in glucose homeostasis. Aim of the work: To investigate in experimentally induced type 1 and 2 diabetes mellitus in rat model the effect of  diabetes mellitus on cognitive functions and related markers of hippocampal synaptic plasticity, and the possible impact of blocking N-methyl-D-aspartic acid (NMDA receptors by memantine. Materials and methods: Seven rat groups were included: non-diabetic control and non-diabetic receiving memantine; type-1 diabetic groups - untreated, treated with insulin alone and treated with insulin and memantine; and type 2 diabetic groups - untreated and memantine treated. Cognitive functions were assessed by the Morris Water Maze and passive avoidance test. Biochemical analysis was done for serum glucose, serum insulin and insulin resistance. Routine histological examination was done, together with immunohistochemistry for detection of the hippocampal learning and memory plasticity marker, namely activity regulated cytoskeletal-associated protein (Arc, and the astrocytes reactivity marker, namely glial fibrillary acidic protein (GFAP.  Results: Both type 1 and 2 untreated diabetic groups showed significantly impaired cognitive performance compared to the non-diabetic group. Treating the type 1 diabetic group with insulin alone significantly improved cognitive performance, but significantly decreased GFAP and Arc compared to the untreated type 1 group. In addition, the type 2 diabetic groups showed a significant decrease in hippocampus GFAP and Arc compared to the non-diabetic groups. Blocking NMDA receptors by memantine significantly increased cognitive performance, GFAP and Arc in the type 1 insulin-memantine group compared to the type 1-insulin group and significantly increased Arc in the type 2-memantine group compared to the untreated type 2 diabetic group. The non-diabetic group

[Effect of compound Puerarin on the collage IV in streptozotocin-induced diabetic nephropathy rats].

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Li, Qiang-xiang; Zhong, Hui-ju; Gong, Han-ren; Zhu, Fei-yue; Wang, Lin-na; Shen, Dao-jun; Li, Guo; Wang, Cai-yun; Qin, Cheng-sheng

2008-04-01

To observe the effect of compound Puerarin on collagen IV of streptozotocin-induced diabetic rats. Diabetic nephropathy rats were induced by intraperitoneal injection of streptozotocin (STZ). Rats were allocated randomly to control group (10), diabetes model group (10), Vitamin C group (10), Puerarin group (10), vitamin C plus Puerarin group (10). The study period lasted for 12 weeks. During and after the treatment, the general state, blood glucose levels, glycosylated hemoglobin, blood urea nitrogen, serum collagen IV, blood urea nitrogen, serum creatinine, urinary albumin excretion rate of the 24-hour, and clearance rate of creatinine collagen IV protein were determined by immunohistochemistoche analysis as well as type the gene expression of collagen IV alpha 1 mRNA were determined by in situ hybridization analysis in the kidney tissue of different groups. (1) Diabetes mellitus and renal function lesion occurred in the four groups. (2) Vitamin C and Puerarin could improve the general conditions of diabetic Rats, decrease blood urea nitrogen [(8.68 +/- 0.43), (7.98 +/- 0.47) and (5.76 +/- 0.82) micromol/L, serum creatinine [(74.68 +/- 8.20), (75.52 +/- 7.98) and (58.66 +/- 6.65) mmol/L], and urinary albumin excretion rate of the 24-hour [(18.40 +/- 0.37), (17.24 +/- 0.30) and (9.97 +/- 1.27) mg/24 h x 10(-3)]; increase clearance rate of creatinine [(0.59 +/- 0.21), (0.61 +/- 0.14) and (0.69 +/- 0.32) ml/min], the expression of collage IV absorbance [(111.56 +/- 14.61), (110.78 +/- 9.69) and (95.44 +/- 9.97) ] in the diabetic Rats were significantly inhibited at the same time. The compound Puerarin might have some functions on preventing ren by inhibiting expression of type IV collagen.

Structure of the vitreoretinal border region in spontaneously diabetic BB rats

DEFF Research Database (Denmark)

Heegaard, S

1993-01-01

The morphology of the vitreoretinal border region, also termed the inner limiting membrane, was examined in spontaneously diabetic rats (BB rats), in non-diabetes-prone rats (WB rats) and in Buffalo rats (BUF rats) by scanning electron microscopy (SEM) and transmission electron microscopy (TEM......). This was performed in order to visualize a possible increase in thickness of the lamina densa or in the whole vitreoretinal border region complex with duration of diabetes. The median thickness of the lamina densa in the three groups varied between 34 and 68 nm. In BB rats the thickness decreased with age...... and duration of diabetes. In WB rats the lamina densa thickened up to the 9th month and then decreased to the level of the young rats. In BUF rats the lamina densa decreased in thickness with age. The median thickness of the whole vitreoretinal border region varied between: BB rats: 84 and 126 nm (SEM) and 68...

Oxidative stress in normal and diabetic rats.

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Torres, M D; Canal, J R; Pérez, C

1999-01-01

Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (pC18:2) ratios. Greater vitaminE/triglyceride (TG) ratio, however, appeared in the control group. The corresponding vitamin A ratios (vitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected.

Suramin-restricted blood volume in the placenta of normal and diabetic rats is normalized by vitamin E treatment.

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Nash, P; Eriksson, U J

2007-01-01

Previously maternal and fetal alterations resembling human pre-eclampsia were induced in pregnant rats by injections of the angiogenesis inhibitor Suramin. These alterations were aggravated by maternal diabetes and partly rectified by vitamin E supplementation. In the present study we evaluated the morphology of placentae and kidneys in this model. Non-diabetic and streptozotocin-induced diabetic pregnant rats of two rat strains (U and H) were treated with Suramin or saline, and given standard or vitamin E-enriched food. On gestational day 20 one placenta and the left kidney of the mother were collected for morphological and stereological analysis. In the placental trophospongium Suramin treatment caused cysts, which were further enhanced by maternal diabetes. Vitamin E treatment had no effect on the vacuolization. In the placental labyrinth of the non-diabetic rats Suramin treatment restricted maternal placental blood volume and increased the interface between maternal and fetal circulation. These changes were reversed by vitamin E treatment. Diabetes increased slightly the interface between the circulations in both rat strains. Suramin treatment decreased the interface, and vitamin E further decreased the interface in the diabetic U rats, whereas neither treatment affected the maternal-fetal interface in the diabetic H rats. The kidneys of Suramin-treated and diabetic rats were heavier compared to controls. Suramin treatment and maternal diabetes damaged renal glomeruli to a similar extent. Vitamin E treatment diminished the Suramin- and diabetes-induced glomerular damage in U rats, but not in H rats. The average cell count per glomerulus was decreased by Suramin in the U rats. Vitamin E treatment did not affect cell number per glomerulus in any group. We conclude that Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction and pre-eclampsia, also from the histological perspective. The present work supports the notion that one

Comparative effects of mature coconut water (Cocos nucifera and glibenclamide on some biochemical parameters in alloxan induced diabetic rats

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P. P. Preetha

2013-03-01

Full Text Available In the present study, comparative effects of mature coconut water (Cocos nucifera L., Arecaceae and glibenclamide in alloxan induced diabetic rats were evaluated. Diabetes mellitus was induced in Sprague-Dawly rats using alloxan monohydrate (150 mg kg-1 body weight. Treatment with lyophilized form of mature coconut water and glibenclamide in diabetic rats reduced the blood glucose and glycated hemoglobin along with improvement in plasma insulin level. Elevated levels of liver function enzymes markers like alkaline phosphatase, serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase in diabetic rats were significantly reduced on treatment with mature coconut water. In addition to this, diabetic rats showed altered levels of blood urea, serum creatinine, albumin, albumin/globulin ratio which were significantly improved by treatment with mature coconut water and glibenclamide. Activities of nitric oxide synthase in liver and plasma L-arginine were reduced significantly in alloxan induced diabetic rats while treatment with mature coconut water reversed these changes. The overall results show that mature coconut water has significant beneficial effects in diabetic rats and its effects were comparable to that of glibenclamide, a well known antidiabetic drug.

Topical erythropoietin promotes wound repair in diabetic rats.

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Hamed, Saher; Ullmann, Yehuda; Masoud, Muhannad; Hellou, Elias; Khamaysi, Ziad; Teot, Luc

2010-01-01

Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

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

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

2015-01-01

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

Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

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Valladares, Ricardo; Sankar, Dhyana; Li, Nan; Williams, Emily; Lai, Kin-Kwan; Abdelgeliel, Asmaa Sayed; Gonzalez, Claudio F; Wasserfall, Clive H; Larkin, Joseph; Schatz, Desmond; Atkinson, Mark A; Triplett, Eric W; Neu, Josef; Lorca, Graciela L

2010-05-06

The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats

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Muhammad Tayyab Akhtar

2016-08-01

Full Text Available Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM. Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM. Proton Nuclear Magnetic Resonance (1H-NMR spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese–diabetic (obdb rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

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Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

2011-12-01

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

Altered glucose kinetics in diabetic rats during Gram-negative infection

International Nuclear Information System (INIS)

Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J.

1987-01-01

The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge

Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol

International Nuclear Information System (INIS)

Pugliese, G.; Tilton, R.G.; Speedy, A.; Santarelli, E.; Eades, D.M.; Province, M.A.; Kilo, C.; Sherman, W.R.; Williamson, J.R.

1990-01-01

To assess the potential of myo-inositol-supplemented diets to prevent diabetes-induced vascular functional changes, we examined the effects of diets supplemented with 0.5, 1, or 2% myo-inositol on blood flow and vascular filtration function in nondiabetic control rats and rats with streptozocin-induced diabetes (STZ-D). After 1 mo of diabetes and dietary myo-inositol supplementation, (1) 131I-labeled bovine serum albumin (BSA) permeation of vessels was assessed in multiple tissues, (2) glomerular filtration rate (GFR) was estimated as renal plasma clearance of 57Co-labeled EDTA, (3) regional blood flows were measured with 15-microns 85Sr-labeled microspheres, and (4) endogenous albumin and IgG urinary excretion rates were quantified by radial immunodiffusion assay. In STZ-D rats, 131I-BSA tissue clearance increased significantly (2- to 4-fold) in the anterior uvea, choroid-sclera, retina, sciatic nerve, aorta, new granulation tissue, diaphragm, and kidney but was unchanged in skin, forelimb muscle, and heart. myo-Inositol-supplemented diets reduced diabetes-induced increases in 131I-BSA clearance (in a dose-dependent manner) in all tissues; however, only in new granulation tissue and diaphragm did the 2% myo-inositol diet completely normalize vascular albumin permeation. Diabetes-induced increases in GFR and in urinary albumin and IgG excretion were also substantially reduced or normalized by dietary myo-inositol supplements. Increased blood flow in anterior uvea, choroid-sclera, kidney, new granulation tissue, and skeletal muscle in STZ-D rats also was substantially reduced or normalized by the 2% myo-inositol diet. myo-Inositol had minimal if any effects on the above parameters in control rats

Insulin Resistance Is Not Associated with an Impaired Mitochondrial Function in Contracting Gastrocnemius Muscle of Goto-Kakizaki Diabetic Rats In Vivo.

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Michael Macia

Full Text Available Insulin resistance, altered lipid metabolism and mitochondrial dysfunction in skeletal muscle would play a major role in type 2 diabetes mellitus (T2DM development, but the causal relationships between these events remain conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in Goto-Kakizaki (GK rats, a non-obese T2DM model developing peripheral insulin resistant without abnormal level of plasma non-esterified fatty acids (NEFA. Wistar rats were used as controls. Mechanical performance and energy metabolism were assessed strictly non-invasively using magnetic resonance (MR imaging and 31-phosphorus MR spectroscopy (31P-MRS. Compared with control group, plasma insulin and glucose were respectively lower and higher in GK rats, but plasma NEFA level was normal. In resting GK muscle, phosphocreatine content was reduced whereas glucose content and intracellular pH were both higher. However, there were not differences between both groups for basal oxidative ATP synthesis rate, citrate synthase activity, and intramyocellular contents for lipids, glycogen, ATP and ADP (an important in vivo mitochondrial regulator. During a standardized fatiguing protocol (6 min of maximal repeated isometric contractions electrically induced at a frequency of 1.7 Hz, mechanical performance and glycolytic ATP production rate were reduced in diabetic animals whereas oxidative ATP production rate, maximal mitochondrial capacity and ATP cost of contraction were not changed. These findings provide in vivo evidence that insulin resistance is not caused by an impairment of mitochondrial function in this diabetic model.

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

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Zhen-Zhen eKou

2014-01-01

Full Text Available 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.

Attenuation of Diabetic Nephropathy by Carvacrol through Anti-oxidative Effects in Alloxan-Induced Diabetic Rats

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Hamid Reza Jamshidi

2018-03-01

Full Text Available Background and Objectives: Diabetes, a common metabolic disorder, is prevalent in many countries. Nephropathy is a main debate’s side effect. Role of oxidative stress is well known in induction of diabetic nephropathy while carvacrol is a potent anti-oxidant that might attenuate oxidative stress. The aim of this study was to explore the effect of carvacrol in decreasing nephropathy-induced oxidative damage in diabetic rats. Methods: Thirty five Wistar rats (200-250 g were divided to 7 groups. The rats received alloxan (i.p., 200 mg/kg for induction of diabetes. After one week, fasting blood sugar (FBS was assessed and the rats with FBS>250 mg/dL were considered as diabetic. Three weeks after alloxan injection, the blood urea (BUN and creatinine (Cr were determined for confirmation of inducing nephropathy. Then, the animals were treated with carvacrol for one week. Finally, they were anesthetized and blood was collected from animal’s heart for calculation of BUN and Cr. Furthermore, the kidneys were for oxidative stress markers such as glutathione capacity, protein carbonyl, lipid peroxidation and catalase activity. Results: Our results showed that glutathione level and catalase activity significantly increased after treatment with carvacrol. Same results were found in rats that received vitamin E. Also, lipid peroxidation, protein carbonyl content, BUN and Cr levels significantly decreased after treatment with carvacrol in comparison with diabetic rats. Conclusion: Our results showed that carvacrol improved nephropathy-induced oxidative damage similar to vitamin E. Therefore, it may be suggested that carvacrol can be suggested as a useful supplement in decreasing diabetic complaints along with anti-diabetic drugs.

Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

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Siddiqui, Shabeena [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India); Ahsan, Haseeb [Department of Biochemistry, Faculty of Dentistry, Jamia Millia Islamia, New Delhi 110025 (India); Khan, Mohammad Rashid [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India); Siddiqui, Waseem A., E-mail: wasiddiqui01@gmail.com [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India)

2013-12-01

Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. - Highlights: • The nephroprotective effect of TRF in type-2 diabetic rats was investigated. • Treatment with TRF improved glycemic status, lipid profile and renal functions in rats

Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

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Siddiqui, Shabeena; Ahsan, Haseeb; Khan, Mohammad Rashid; Siddiqui, Waseem A.

2013-01-01

Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. - Highlights: • The nephroprotective effect of TRF in type-2 diabetic rats was investigated. • Treatment with TRF improved glycemic status, lipid profile and renal functions in rats

Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

Energy Technology Data Exchange (ETDEWEB)

Siddiqui, Shabeena [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India); Ahsan, Haseeb [Department of Biochemistry, Faculty of Dentistry, Jamia Millia Islamia, New Delhi 110025 (India); Khan, Mohammad Rashid [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India); Siddiqui, Waseem A., E-mail: wasiddiqui01@gmail.com [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India)

2013-12-01

Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. - Highlights: • The nephroprotective effect of TRF in type-2 diabetic rats was investigated. • Treatment with TRF improved glycemic status, lipid profile and renal functions in rats

Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

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Brouwers, Olaf; Niessen, Petra M G; Miyata, Toshio

2014-01-01

AIMS/HYPOTHESIS: In diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed...... the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes. METHODS: Wild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection...... podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation...

Effects of multiple low dose radiation on spleen T lymphocyte subgroups in eight-week diabetic rats

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Guan Feng; Li Yanbo; Zhao Hongguang; Guo Wei; Wang Zhicheng; Gong Shouliang; Guo Caixia

2008-01-01

Objective: To explore the changes of spleen lymphocyte subgroups in diabetic rats after multiple low dose radiation (LDR). Methods: The experiment was divided into normal control group, pure diabetes mellitus (DM) group, and DM plus different doses of irradiation groups (the irradiation doses were 0.025, 0.050 and 0.075 Gy, respectively). The diabetic rat model was induced by intraperitoneal injection of streptozotocin. After the diabetic rats were irradiated 15 times, the percentages of spleen CD4 + and CD8 + T cells and ratio of CD4 + /CD8 + T cells were detected with flow cytometry on the fourth weekend. Results: The diabetic rats manifested obvious polydipsia, polyphagia, polyuria and weight loss. On the fourth weekend after irradiation, as compared with normal control group, the percentage of spleen CD4 + T cells increased significantly (P + T cells decreased significantly (P + /CD8 + T cells was increased significantly (P + T cells were declined markedly in both 0.050 and 0.075 Gy plus DM groups (P + T cells increased significantly in LDR plus DM groups (P + /CD8 + T cells was declined obviously (P<0.01). Conclusion: The multiple LDR could regulate the immune function in diabetic rats, and rectificate the immunological imbalance in order to protect body. (authors)

RES hyperphagocytosis by rats with streptozotocin-induced diabetes mellitus.

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Cornell, R P

1981-03-01

In contrast to previous studies of neutrophils from diabetic animals and humans in vitro and of macrophages from diabetic humans in vivo, which reported phagocytic depression, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon was observed in rats at 14 and 28 days after diabetes induction with streptozotocin (STZ). Carbon clearance half times were significantly enhanced to 6.3 +/- 0.79 and 8.1 +/- 1.04 min at 14 and 28 days post-STZ, respectively, compared with the nondiabetic value (12.7 +/- 0.98 min). The severity of uncontrolled STZ-induced diabetes in rats was confirmed by significant hypoinsulinemia, hyperglucagonemia, hyperglycemia, and hyperlipidemia. Although body weights of STZ-diabetic animals declined progressively, liver weights as a percent of body weight increased above the control value at 14 and 28 days post-STZ. In fact, expression of carbon phagocytosis as the corrected phagocytic index, which accounts for changes in liver and spleen weights relative to body weight, eliminated the significant difference between STZ-diabetic and nondiabetic animals. Antibiotic treatment of diabetic rats failed to alter the hyperphagocytosis, implying that a chronic bacterial infection was not the cause of phagocytic stimulation. Daily insulin replacements, but not a single large insulin dose to 14-day post-STZ rats, reversed the enhanced phagocytosis of colloidal carbon.

Previous exercise training has a beneficial effect on renal and cardiovascular function in a model of diabetes.

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Kleiton Augusto dos Santos Silva

Full Text Available 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.

Resistant starch but not enzymatic treated waxy maize delays development of diabetes in Zucker Diabetic Fatty rats

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Hedemann, Mette Skou; Hermansen, Kjeld; Pedersen, Sven

2017-01-01

excretion during week 8 in rats fed the GLU and EMS diets than that of rats fed S and RS showed that they were diabetic. Urinary nontargeted metabolomics revealed that the diabetic state of rats fed S, GLU, and EMS diets influenced microbial metabolism, as well as amino acid, lipid, and vitamin metabolism......Background: The incidence of type 2 diabetes (T2D) is increasing worldwide, and nutritional management of circulating glucose may be a strategic tool in the prevention of T2D. Objective: We studied whether enzymatically modified waxy maize with an increased degree of branching delayed the onset...... glucose concentrations in feed-deprived rats, none of the groups developed diabetes. However, in week 9, plasma glucose after feed deprivation was significantly lower in rats fed the S and RS diets (13.5 mmol/L) than in rats fed the GLU and EMS diets (17.0–18.9 mmol/L), and rats fed RS had lower HbA1c (4...

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

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Prasad, K

2000-06-01

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant activity and has been shown to prevent hypercholesterolemic atherosclerosis. An investigation was made of the effects of SDG on the development of diabetes in diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes [insulin dependent diabetes mellitus (IDDM)] to determine if this type of diabetes is due to oxidative stress and if SDG can prevent the incidence of diabetes. The rats were divided into three groups: Group I, BioBreeding normal rats (BBn rats) (n = 10); group II, BBdp untreated (n = 11); and group III, BBdp treated with SDG 22 mg/kg body wt, orally) (n = 14). Oxidative stress was determined by measuring lipid peroxidation product malondialdehyde (MDA) an index of level of reactive oxygen species in blood and pancreas; and pancreatic chemiluminescence (Pancreatic-CL), a measure of antioxidant reserve. Incidence of diabetes was 72.7% in untreated and 21.4% in SDG-treated group as determined by glycosuria and hyperglycemia. SDG prevented the development of diabetes by approximately 71%. Development of diabetes was associated with an increase in serum and pancreatic MDA and a decrease in antioxidant reserve. Prevention in development of diabetes by SDG was associated with a decrease in serum and pancreatic-MDA and an increase in antioxidant reserve. These results suggest that IDDM is mediated through oxidative stress and that SDG prevents the development of diabetes.

Protective effects of a coumarin derivative in diabetic rats.

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Bucolo, Claudio; Ward, Keith W; Mazzon, Emanuela; Cuzzocrea, Salvatore; Drago, Filippo

2009-08-01

Retinal microvascular cells play a crucial role in the pathogenesis of diabetic retinopathy. The endothelial effects of cloricromene, a novel coumarin derivative, on diabetic retinopathy induced by streptozotocin (STZ) in the rat were investigated. Cloricromene (10 mg/kg intraperitoneally) was administered daily in diabetic rats, and 60 days later eyes were enucleated for localization of nitrotyrosine, ICAM-1, VEGF, ZO-1, occludin, claudin-5, and VE-cadherin by immunohistochemical analysis. The effect of treatment was also evaluated by TNFalpha, ICAM-1, VEGF, and eNOS protein levels measurement in the retina with the respective ELISA kits. Blood-retinal barrier (BRB) integrity was also evaluated by Evans blue. Increased amounts of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina. Cloricromene treatment significantly lowered retinal TNFalpha, ICAM-1, VEGF, and eNOS. Furthermore, immunohistochemical analysis for VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions revealed positive staining in the retina from STZ-treated rats. The degree of staining for VEGF, ICAM-1, nitrotyrosine, and tight junctions was markedly reduced in tissue sections obtained from diabetic rats treated with cloricromene. Treatment with cloricromene suppressed diabetes-related BRB breakdown by 45%. This study provides the first evidence that the new coumarin derivative cloricromene attenuates the degree of inflammation preserving the BRB in diabetic rats.

Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation

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Yderstræde, Knud Bonnet; Starklint, Henrik; Steinbrüchel, Daniel Andreas

1993-01-01

Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets...... to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes...... that recurrent diabetes is not inevitable following syngeneic fetal pancreas transplantation to spontaneously diabetic BB rats. Recurrent diabetes was only occasionally associated with mononuclear cell infiltration. Transplanted tissue was well-preserved and vascularized; mega-islets were a constant finding....

Decreased autophosphorylation of EGF receptor in insulin-deficient diabetic rats

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Okamoto, M.; Kahn, C.R.; Maron, R.; White, M.F.

1988-01-01

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 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

Effect of dietary fish oil and corn oil on blood biochemical factors in diabetic Rat

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Mehdi Shariati

2005-09-01

Full Text Available Background: The potential role of omega – 3 (ω-3 and omega-6 (ω-6 fatty acids on blood biochemical factors are in interest and controversy. Some experiences showed that omega – 3 (ω-3 and omega-6 (ω-6 fatty acids have a potential effect on triglyceride, LDL-cholesterol, HDL-cholesterol and total cholesterol levels in diabetes mellitus. Methods: Male rats were divided into four groups (one normal group and three diabetic groups. Induction of diabetes was done by streptozotocin [50mg/kg, s.c. (STZ]. In diabetic groups, one group was Control, received STZ alone, and the other diabetic groups were fed with fish oil or corn oil for 8 weeks after 4 weeks of induction of diabetes. Plasma glucose, total cholesterol, triglyceride, LDL- choleserol and HDL-cholesterol were measured at 4 and 8 weeks after intervention. Results: Fish oil and corn oil diets had an inhibitory effect on increased plasma glucose in diabetic rat by 46.8% and 40.7%, respectively. Diabetic rats in the control group demonstrated increased plasma total cholesterol, triglyceride and LDL-cholesterol levels, but plasma total cholesterol, triglyceride and LDL-cholesterol levels were significantly decreased and HDL-cholesterol level was increased by both diets in interventional groups. Conclusion: Corn oil and fish oil supplementation have a role on plasma glucose and lipid profile in diabetic rats. To understand the functional mechanisms of these diets, further studies remain to be accomplished.

Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization

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Jiayin Sun

2016-01-01

Full Text Available Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI through improving bone marrow endothelial progenitor cell (EPC mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1, amlodipine (2.5 mgkg−1 day−1, or vehicle by gavage (n=20 per group. Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5. Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.

The TetO rat as a new translational model for type 2 diabetic retinopathy by inducible insulin receptor knockdown.

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Reichhart, Nadine; Crespo-Garcia, Sergio; Haase, Nadine; Golic, Michaela; Skosyrski, Sergej; Rübsam, Anne; Herrspiegel, Christina; Kociok, Norbert; Alenina, Natalia; Bader, Michael; Dechend, Ralf; Strauss, Olaf; Joussen, Antonia M

2017-01-01

Although the renin-angiotensin system plays an important role in the progression of diabetic retinopathy, its influence therein has not been systematically evaluated. Here we test the suitability of a new translational model of diabetic retinopathy, the TetO rat, for addressing the role of angiotensin-II receptor 1 (AT1) blockade in experimental diabetic retinopathy. Diabetes was induced by tetracycline-inducible small hairpin RNA (shRNA) knockdown of the insulin receptor in rats, generating TetO rats. Systemic treatment consisted of an AT1 blocker (ARB) at the onset of diabetes, following which, 4-5 weeks later the retina was analysed in vivo and ex vivo. Retinal function was assessed by Ganzfeld electroretinography (ERG). Retinal vessels in TetO rats showed differences in vessel calibre, together with gliosis. The total number and the proportion of activated mononuclear phagocytes was increased. TetO rats presented with loss of retinal ganglion cells (RGC) and ERG indicated photoreceptor malfunction. Both the inner and outer blood-retina barriers were affected. The ARB treated group showed reduced gliosis and an overall amelioration of retinal function, alongside RGC recovery, whilst no statistically significant differences in vascular and inflammatory features were detected. The TetO rat represents a promising translational model for the early neurovascular changes associated with type 2 diabetic retinopathy. ARB treatment had an effect on the neuronal component of the retina but not on the vasculature.

Antioxidant Effects of Biochanin A in Streptozotocin Induced Diabetic Rats

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Hamideh Sadri

2017-08-01

Full Text Available ABSTRACT Bioflavonoid-containing diets have been reported to be beneficial in diabetes. In the current study, the effect of Biochanin A (BCA on blood glucose, antioxidant enzyme activities and oxidative stress markers in diabetic rats were investigated. 30 male Wistar rats were divided into five groups. Two of them were selected as control; group1: control (receiving 0.5%DMSO, and group2: Control+BCA (receiving 10 mg/kg.bw BCA. Diabetes was induced in other rats with injection of (55 mg/kg.bw streptozotocin; group3: diabetic control (receiving 0.5%DMSO, groups 4 and 5 were treated with 10 and 15 mg/kg.bw BCA respectively. After 6 weeks the following results were obtained. Fasting blood glucose (FBG, Triglyceride (TG, total cholesterol (TC, low density lipoprotein cholesterol (LDL-C, very low density lipoprotein cholesterol (VLDL-C and malondialdehyde (MDA levels significantly increased and body weight, high density lipoprotein cholesterol (HDL-C, superoxide dismutase (SOD and catalase (CAT activity and total antioxidant status (TAS significantly decreased in diabetic rats as compared to control rats. Oral administration of BCA in 10 and 15 mg/kg.bw, FBG, TG, TC, LDL-C, VLDL-C were decreased significantly in all treated rats. MDA was decreased in all treated rats but it was significant just in 15 mg/kg.bw BCA. HDL, CAT, SOD, and TAS were significantly increased in treated group with 15 mg/kg.bw. The obtained results indicated hypoglycemic and hypolipidemic effect of BCA. Also BCA reduced oxidative stress in diabetic rats.

Gallic acid improves the memory and pain in diabetic rats

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maryam Rafieirad

2013-08-01

Full Text Available Background: Complications of diabetes can be caused by the production of free radicals, which lead to memory problems and increase the risk of dementia. Diabetics are at risk of nervous pains. Gallic acid has antioxidant properties and activity against free radicals. In this study the effect of oral administration of Gallic acid, were examined on passive‌ avoidance ‌memory and pain in diabetic rats. Materials and Methods: Rats were divided into control, diabetes with STZ (60mg/kg, 3-groups of control and 3‌groups of diabetic rats and received Gallic ‌‌acid (10, 50&100 mg/kg oral, for two weeks. Blood glucose levels were measured from tail. Results: Results showed a significant reduction in memory (delayed coming down from the podium in the diabetic group all days except day of learning (P≤0.01. Dose of 50 mg/kg Gallic‌ acid caused a significant increase in non-diabetic rats on the first day of memory (P≤0.01, third and seventh (P≤0.05 and dose of 10 mg/kg on the first day (P≤0.05. Compared with diabetic group a significant increase was observed in the first day (P≤0.01, third and seventh (P≤0.05 in diabetics receiving doses of 50 and 10mg/kg Gallic‌ acid. The reflex for tail pulling away from the center of pain was significantly lower (P≤0.01 in the diabetic group. And only the dose of 50 caused a significant increase in the diabetic group (P≤0.01. Conclusion: Probably Gallic‌ acid with strong antioxidant effect led to scavenge free radicals and reduced the complications of diabetes, including pain and may have effects on neural pathways in specific brain regions and has led to improved memory in normal rats and diabetic.

Partial recovery of erythrocyte glycogen in diabetic rats treated with phenobarbital

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da-Silva C.A.

1997-01-01

Full Text Available Erythrocytes may play a role in glucose homeostasis during the postprandial period. Erythrocytes from diabetic patients are defective in glucose transport and metabolism, functions that may affect glycogen storage. Phenobarbital, a hepatic enzyme inducer, has been used in the treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM, increasing the insulin-mediated glucose disposal. We studied the effects of phenobarbital treatment in vivo on glycemia and erythrocyte glycogen content in control and alloxan-diabetic rats during the postprandial period. In control rats (blood glucose, 73 to 111 mg/dl in femoral and suprahepatic veins the erythrocyte glycogen content was 45.4 ± 1.1 and 39.1 ± 0.8 µg/g Hb (mean ± SEM, N = 4-6 in the femoral artery and vein, respectively, and 37.9 ± 1.1 in the portal vein and 47.5 ± 0.9 in the suprahepatic vein. Diabetic rats (blood glucose, 300-350 mg/dl presented low (P<0.05 erythrocyte glycogen content, i.e., 9.6 ± 0.1 and 7.1 ± 0.7 µg/g Hb in the femoral artery and vein, respectively, and 10.0 ± 0.7 and 10.7 ± 0.5 in the portal and suprahepatic veins, respectively. After 10 days of treatment, phenobarbital (0.5 mg/ml in the drinking water did not change blood glucose or erythrocyte glycogen content in control rats. In diabetic rats, however, it lowered (P<0.05 blood glucose in the femoral artery (from 305 ± 18 to 204 ± 45 mg/dl and femoral vein (from 300 ± 11 to 174 ± 48 mg/dl and suprahepatic vein (from 350 ± 10 to 174 ± 42 mg/dl, but the reduction was not sufficient for complete recovery. Phenobarbital also stimulated the glycogen synthesis, leading to a partial recovery of glycogen stores in erythrocytes. In treated rats, erythrocyte glycogen content increased to 20.7 ± 3.8 µg/g Hb in the femoral artery and 30.9 ± 0.9 µg/g Hb in the suprahepatic vein (P<0.05. These data indicate that phenobarbital activated some of the insulin-stimulated glucose metabolism steps which were

Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity

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

2006-01-01

Previously, we reported high hepatotoxic sensitivity of type 2 diabetic (DB) rats to three dissimilar hepatotoxicants. Additional work revealed that a normally nonlethal dose of CCl 4 was lethal in DB rats due to inhibited compensatory tissue repair. The present study was conducted to investigate the importance of compensatory tissue repair in determining the final outcome of hepatotoxicity in diabetes, using another structurally and mechanistically dissimilar hepatotoxicant, thioacetamide (TA), to initiate liver injury. A normally nonlethal dose of TA (300 mg/kg, ip), caused 100% mortality in DB rats. Time course studies (0 to 96 h) showed that in the non-DB rats, liver injury initiated by TA as assessed by plasma alanine or aspartate aminotransferase and hepatic necrosis progressed up to 48 h and regressed to normal at 96 h resulting in 100% survival. In the DB rats, liver injury rapidly progressed resulting in progressively deteriorating liver due to rapidly expanding injury, hepatic failure, and 100% mortality between 24 and 48 h post-TA treatment. Covalent binding of 14 C-TA-derived radiolabel to liver tissue did not differ from that observed in the non-DB rats, indicating similar bioactivation-based initiation of hepatotoxicity. S-phase DNA synthesis measured by [ 3 H]-thymidine incorporation, and advancement of cells through the cell division cycle measured by PCNA immunohistochemistry, were substantially inhibited in the DB rats compared to the non-DB rats challenged with TA. Thus, inhibited cell division and compromised tissue repair in the DB rats resulted in progressive expansion of liver injury culminating in mortality. In conclusion, it appears that similar to type 1 diabetes, type 2 diabetes also increases sensitivity to dissimilar hepatotoxicants due to inhibited compensatory tissue repair, suggesting that sensitivity to hepatotoxicity in diabetes occurs in the absence as well as presence of insulin

Furan-induced hepatotoxic and hematologic changes in diabetic rats: the protective role of lycopene.

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Baş, Hatice; Pandır, Dilek; Kalender, Suna

2016-09-01

Furan forms as a result of thermal treatment of food and induces harmful effects on organisms. In our work, lycopene, furan, and a combination of the two were given to diabetic male rats for 28 days. Hematological changes, total protein and cholesterol, triglyceride, and albumin levels, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase activities of the serum, malondialdehyde levels, glutathione peroxidase, catalase, glutathione-S-transferase, superoxide dismutase activities, DNA damage in liver tissues and hepatic histopathological alterations were compared to a control group. There were significant changes in the liver function tests, DNA damage, activities of antioxidant enzymes, and malondialdehyde levels between diabetic control and non-diabetic control groups, between diabetic control and diabetic lycopene groups, and also between diabetic furan and diabetic control groups. In diabetic lycopene and diabetic furan + lycopene treated groups we designated the preventive effects of lycopene against diabetes and furan, however, on the analysed parameters only. In spite of some pathological alterations designated in diabetic furan treated group's liver, fewer pathological alterations were observed in furan+lycopene treated groups at the end of week 4. Consequently, lycopene significantly reduced furan- and diabetes-induced toxicity in rat liver.

Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

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Aires, M.B. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Santos, J.R.A. [Departamento de Enfermagem, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Souza, K.S.; Farias, P.S. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Santos, A.C.V. [Departamento de Enfermagem, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Fioretto, E.T. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Maria, D.A. [Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP (Brazil)

2015-07-10

The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

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Aires, M.B.; Santos, J.R.A.; Souza, K.S.; Farias, P.S.; Santos, A.C.V.; Fioretto, E.T.; Maria, D.A.

2015-01-01

The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers

Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markers

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Munarriz Ricardo

2006-05-01

Full Text Available Abstract Background Diabetes is associated with declining sexual function in women. However, the effects of diabetes on genital tissue structure, innervation and function remains poorly characterized. In control and streptozotocin-treated female rats, we investigated the effects of diabetes on vaginal blood flow, tissue morphology, and expression of arginase I, endothelial nitric oxide synthase (eNOS and cGMP-dependent protein kinase (PKG, key enzymes that regulate smooth muscle relaxation. We further related these changes with estrogen receptor alpha (ERα and androgen receptor (AR expression. Results In addition to significantly elevated blood glucose levels, diabetic rats had decreased mean body weight, lower levels of plasma estradiol, and higher plasma testosterone concentration, compared to age-matched controls. Eight weeks after administration of buffer (control or 65 mg/kg of streptozotocin (diabetic, the vaginal blood flow response to pelvic nerve stimulation was significantly reduced in diabetic rats. Histological examination of vaginal tissue from diabetic animals showed reduced epithelial thickness and atrophy of the muscularis layer. Diabetic animals also had reduced vaginal levels of eNOS and arginase I, but elevated levels of PKG, as assessed by Western blot analyses. These alterations were accompanied by a reduction in both ERα and AR in nuclear extracts of vaginal tissue from diabetic animals. Conclusion In ovariectomized (estrogen deficient animals, previous reports from our lab and others have documented changes in blood flow, tissue structure, ERα, arginase I and eNOS that parallel those observed in diabetic rats. We hypothesize that diabetes may lead to multiple disruptions in sex steroid hormone synthesis, metabolism and action. These pathological events may cause dramatic changes in tissue structure and key enzymes that regulate cell growth and smooth muscle contractility, ultimately affecting the genital response during

Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

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Ricardo Valladares

Full Text Available BACKGROUND: The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. METHODOLOGY/PRINCIPAL: Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat. In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. CONCLUSIONS: It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in Bio

Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Punica granatum Linn. leaves extract

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Snehal Nitin Mestry

2017-07-01

Full Text Available With an objective to develop Complementary and Alternative Medicine for the treatment of diabetic nephropathy, the present study investigated the protective effects of methanolic extract of Punica granatum leaves (MPGL in streptozotocin-induced diabetic nephropathy. Diabetic nephropathy has become a leading cause of end stage renal failure worldwide. P. granatum, due to its anti-diabetic, anti-inflammatory and antioxidant activities may retard the progression of diabetic nephropathy. In this study, diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p. in rats. STZ-diabetic rats were treated with oral doses of MPGL (100, 200 and 400 mg/kg for 8 weeks. At the end of the experimental period, body and kidney weight and blood glucose levels were determined. Serum and urine parameters were investigated. Antioxidant enzymes and lipid peroxide levels were determined in the kidney along with histopathological examination of the same. MPGL significantly increased body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in the STZ-diabetic rats. The extract also decreased the levels of creatinine, blood urea nitrogen, total cholesterol, triglycerides, advanced glycation end products and albumin in serum and urine, respectively. MPGL significantly increased the antioxidant parameters in the kidney. Histological evaluation revealed that MPGL treated STZ-diabetic rats demonstrated reduced vacuolar degeneration of tubules; periodic acid Schiff base (PAS positivity staining intensity in glomeruli and basement membrane thickening. Present findings provide experimental evidence that MPGL has potential antioxidant, antihyperglycemic and anti-glycation activities which might be helpful in slowing the progression of diabetic nephropathy.

Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Punica granatum Linn. leaves extract.

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Mestry, Snehal Nitin; Dhodi, Jayesh Bachu; Kumbhar, Sangita Balbhim; Juvekar, Archana Ramesh

2017-07-01

With an objective to develop Complementary and Alternative Medicine for the treatment of diabetic nephropathy, the present study investigated the protective effects of methanolic extract of Punica granatum leaves (MPGL) in streptozotocin-induced diabetic nephropathy. Diabetic nephropathy has become a leading cause of end stage renal failure worldwide. P. granatum , due to its anti-diabetic, anti-inflammatory and antioxidant activities may retard the progression of diabetic nephropathy. In this study, diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.) in rats. STZ-diabetic rats were treated with oral doses of MPGL (100, 200 and 400 mg/kg) for 8 weeks. At the end of the experimental period, body and kidney weight and blood glucose levels were determined. Serum and urine parameters were investigated. Antioxidant enzymes and lipid peroxide levels were determined in the kidney along with histopathological examination of the same. MPGL significantly increased body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in the STZ-diabetic rats. The extract also decreased the levels of creatinine, blood urea nitrogen, total cholesterol, triglycerides, advanced glycation end products and albumin in serum and urine, respectively. MPGL significantly increased the antioxidant parameters in the kidney. Histological evaluation revealed that MPGL treated STZ-diabetic rats demonstrated reduced vacuolar degeneration of tubules; periodic acid Schiff base (PAS) positivity staining intensity in glomeruli and basement membrane thickening. Present findings provide experimental evidence that MPGL has potential antioxidant, antihyperglycemic and anti-glycation activities which might be helpful in slowing the progression of diabetic nephropathy.

Urtica Dioica Distillate Regenerates Pancreatic Beta Cells in Streptozotocin-Induced Diabetic Rats

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Gohari, Ali; Noorafshan, Ali; Akmali, Masoumeh; Zamani-Garmsiri, Fahimeh; Seghatoleslam, Atefeh

2018-01-01

Background Urtica dioica is known as an anti-hyperglycemic plant. Urtica dioica distillate (UD) is a traditional Iranian drink, locally known as “aragh gazaneh”. In spite of its widespread consumption in Iran, according to traditional Iranian medicine, there is no scientific report on the usefulness of UD for diabetic patients. This survey was designed to evaluate its protective effects for the recovery from diabetes by determining the serum insulin, blood glucose, volume of pancreatic islets, and the number and volume of β-cells in diabetic rats. Methods A total of 48 Sprague-Dawley male rats (200-250 g) were randomly distributed into 6 groups (n=8), including non-diabetic plus distilled water (DW), non-diabetic plus UD, diabetic plus DW, diabetic plus UD, diabetic plus insulin, and diabetic plus glibenclamide. DW, UD, and glibenclamide were administered via intragastric gavage and insulin was injected subcutaneously. After four weeks of experiments, blood samples were collected for serum insulin and blood glucose assay. Pancreas was also evaluated using stereological method. The SPSS software was used for statistical analysis. Kruskal-Wallis, repeated measurements, and Mann-Whitney U test were applied for comparisons between the groups. Results The treatment of diabetic rats with UD reduced the blood glucose dramatically (P<0.001) and increased serum insulin levels significantly (P=0.03) in comparison to the diabetic plus DW rats. Treatment with UD did not affect the mean β-cell volumes in the diabetic rats when compared to the diabetic plus DW rats, but the islet volumes and β-cell numbers were significantly recovered. Conclusion UD treatment in diabetic rats improves hyperglycemia by partially restoring plasma insulin levels. The data suggest that UD prevents islet atrophy and/or regenerate pancreatic β-cells. PMID:29749986

Effect of Acute Administration of loganin on Spatial Memory in Diabetic Male Rats

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Gisou Mohaddes

2013-02-01

Full Text Available Purpose: Diabetes is associated with memory and learning disorder. The purpose of this study is to determine the effect of acute oral administration of loganin on memory in diabetic male rats. Methods: 42 male Wistar rats (250-300 g were divided into six groups: Control, Diabetic (1 week, Diabetic (12 weeks, Loganin, Diabetic (1 week + Loganin, Diabetic (12 weeks + Loganin. Diabetes was induced by IP injection of Streptozotocin (60 mg/kg. Loganin (40 mg/kg, po was administrated 1 hour before test. Then, spatial memory was compared between groups with Morris Water Maze tests. Results: Administration of loganin during acquisition, significantly (p<0.05 decreased both escape latency and traveled distance to find hidden platform in 1 and 12 weeks diabetic rats. In evaluation of recall phase of memory, loganin significantly (p<0.05 increased time and distance spent in the target quadrant in 1 and 12 weeks diabetic rats. Conclusion: Acute administration of loganin could improve spatial memory in diabetic rats.

Effects of sleeve gastrectomy in neonatally streptozotocin-induced diabetic rats.

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Yan Wang

Full Text Available BACKGROUND: Sleeve gastrectomy (SG has emerged recently as a stand-alone bariatric procedure to treat morbid obesity and enhance glucose homeostasis. The aim of the study was to evaluate its effects in neonatally streptozotocin (STZ-induced diabetic rats (n-STZ diabetic rats. METHODOLOGY AND PRINCIPAL FINDINGS: To induce diabetes, STZ (90 mg/kg was administered intraperitoneally to 2-day-old male pups. When 12 weeks old, diabetic rats were randomized into sleeve operation group (SLG, n = 6 and sham operation group (SOG, n = 6. Body weights were monitored weekly, and daily consumption of water and food were followed for eight consecutive weeks postoperatively. Serum glucose levels were measured periodically at the 4th and 8th week after surgery. Insulin, ghrelin, glucose-dependent insulinotropic polypeptide (GIP and Glucagon-like peptide-1 (GLP-1 levels were assayed at the end of the study. Our data showed that SLG rats exhibited significantly lower body weight gain in addition to reduced food and water intakes postoperatively compared to their sham-operation counterparts. However, resolution of diabetes was not observed in our study. Correspondingly, there were no significant differences between SOG rats and SLG rats in glucose metabolism-associated hormones, including insulin, GIP and GLP-1. In contrast, ghrelin level significantly decreased (P<0.01 in SLG group (58.01 ± 3.75 pg/ml after SG surgery compared to SOG group (76.36 ± 3.51 pg/ml. CONCLUSIONS: These observations strongly suggest that SG is effective in controlling body weight. However, SG did not achieve resolution or improvement of diabetes in n-STZ diabetic rats.

Effect of irradiation on the healing of extraction sockets in diabetic rats

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Kim, Il Joong; Hwang, Eui Hwan; Lee, Sang Rae [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

2003-03-15

To observe the histologic pattern of healing in molar tooth extraction sockets of streptozotocin-induced diabetic rats following irradiation. Mature Sprague-Dawley rats were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced by injecting streptozotocin. Control rats were injected with a citrate buffer only. After 5 days, the right maxillary first molar was extracted under general anesthesia from each of the rats. After the extraction, rats in the diabetic-irradiated group were irradiated with a single absorbed dose of 10 Gy to the head and neck region. The rats were killed at 1, 3, 7, 14, 21, and 28 days after treatment. Tissue sections were stained with hematoxylin-eosin and Masson's trichrome. In the diabetic and diabetic-irradiated groups, the early healing process of the socket extraction was similar to the control group, but bone formation was delayed at 7 days after the treatment. In the diabetic-irradiated group, alveolar bone surrounding the extraction socket showed sighs of necrosis at 3 days after treatment, and hemorrhage was observed in connective tissue within the extraction socket at 14 days after treatment. The experiment revealed that the healing process of the extraction socket was severely delayed and retarded by irradiation in the diabetic state.

Effect of irradiation on the healing of extraction sockets in diabetic rats

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Kim, Il Joong; Hwang, Eui Hwan; Lee, Sang Rae

2003-01-01

To observe the histologic pattern of healing in molar tooth extraction sockets of streptozotocin-induced diabetic rats following irradiation. Mature Sprague-Dawley rats were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced by injecting streptozotocin. Control rats were injected with a citrate buffer only. After 5 days, the right maxillary first molar was extracted under general anesthesia from each of the rats. After the extraction, rats in the diabetic-irradiated group were irradiated with a single absorbed dose of 10 Gy to the head and neck region. The rats were killed at 1, 3, 7, 14, 21, and 28 days after treatment. Tissue sections were stained with hematoxylin-eosin and Masson's trichrome. In the diabetic and diabetic-irradiated groups, the early healing process of the socket extraction was similar to the control group, but bone formation was delayed at 7 days after the treatment. In the diabetic-irradiated group, alveolar bone surrounding the extraction socket showed sighs of necrosis at 3 days after treatment, and hemorrhage was observed in connective tissue within the extraction socket at 14 days after treatment. The experiment revealed that the healing process of the extraction socket was severely delayed and retarded by irradiation in the diabetic state.

Reticuloendothelial hyperphagocytosis occurs in streptozotocin-diabetic rats. Studies with colloidal carbon, albumin microaggregates, and soluble fibrin monomers

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Cornell, R.P.

1982-01-01

In contrast to previous studies of diabetic humans and animals, which reported unchanged or depressed function, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon, 125 I-albumin microaggregates, and 125 I-fibrin monomers were observed in rats as early as 14 days after the induction of diabetes with streptozotocin (STZ). The fact that enhanced phagocytosis by RE macrophages was prevented by chronic insulin replacement therapy indicates that the diabetic internal environment of hyperglycemia and hypoinsulinemia was perhaps responsible for the observed changes. Experiments involving organ localization of intravenously administered particles, perfusion of isolated livers, and microscopic examination of the liver all suggested that increased Kupffer cell activity was the primary event in RES hyperphagocytosis by STZ-diabetic rats. Both hypertrophy and hyperplasia of Kupffer cells were apparent in livers of STZ-diabetic animals as evidenced by photomicrographs and hepatic cell quantification. Plasma fibronectin, which binds fibrin monomers to RE macrophages before phagocytosis, was significantly decreased in the circulation of STZ-diabetic rats, but the level of cell-associated fibronectin was not measured. Renal localization of urea-soluble 125 I-fibrin monomers exceeded splenic and pulmonary uptake in normal control rats and was enhanced in animals with STZ-diabetes. Changes in fibronectin levels, fibrin monomer localization, and Kupffer cell size and numbers in experimental diabetes in rats may have implications for the pathogenesis of vascular disease involving phagocytic mesangial and foam cells in diabetic humans

Reticuloendothelial hyperphagocytosis occurs in streptozotocin-diabetic rats. Studies with colloidal carbon, albumin microaggregates, and soluble fibrin monomers.

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Cornell, R P

1982-02-01

In contrast to previous studies of diabetic humans and animals, which reported unchanged or depressed function, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon, 125I-albumin microaggregates, and 125I-fibrin monomers were observed in rats as early as 14 days after the induction of diabetes with streptozotocin (STZ). The fact that enhanced phagocytosis by RE macrophages was prevented by chronic insulin replacement therapy indicates that the diabetic internal environment of hyperglycemia and hypoinsulinemia was perhaps responsible for the observed changes. Experiments involving organ localization of intravenously administered particles, perfusion of isolated livers, and microscopic examination of the liver all suggested that increased Kupffer cell activity was the primary event in RES hyperphagocytosis by STZ-diabetic rats. Both hypertrophy and hyperplasia of Kupffer cells were apparent in livers of STZ-diabetic animals as evidenced by photomicrographs and hepatic cell quantification. Plasma fibronectin, which binds fibrin monomers to RE macrophages before phagocytosis, was significantly decreased in the circulation of STZ-diabetic rats, but the level of cell-associated fibronectin was not measured. Renal localization of urea-soluble 125I-fibrin monomers exceeded splenic and pulmonary uptake in normal control rats and was enhanced in animals with STZ-diabetes. Changes in fibronectin levels, fibrin monomer localization, and Kupffer cell size and numbers in experimental diabetes in rats may have implications for the pathogenesis of vascular disease involving phagocytic mesangial and foam cells in diabetic humans.

Study on cognitive impairment in diabetic rats by different behavioral experiments

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Yu-bin, Ji; Zeng-yi, Li; Guo-song, Xin; Chi, Wei; Hong-jian, Zhu

2017-12-01

Object recognition test and Y maze test are widely used in learning and memory behavior evaluation techniques and methods. It was found that in the new object recognition experiment, the diabetic rats did more slowly than the normal rats in the discrimination of the old and new objects, and the learning and memory of the rats in the diabetic rats were injured. And the ratio of retention time and the number of errors in the Y maze test was much higher than that in the blank control group. These two methods can reflect the cognitive impairment in diabetic rats.

Changes in the pharmacokinetics of glibenclamide in rats with streptozotocin-induced diabetes mellitus

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Yuqing Li

2012-04-01

Full Text Available The aim of this study was to investigate the pharmacokinetics of glibenclamide (Gli administrated orally and intravenously to normal and diabetic rats. The AUC(0–720 min of orally administered Gli in diabetic rats (321.24 mg min/L was greater than that (57.752 mg min/L in normal rats. CL (0.019 L/min/kg was significantly slower than that (0.092 L/min/kg of normal rats. The AUC(0–480min of intravenous Gli in diabetic rats (1528.280 mg min/L also was significantly greater than that (509.523 mg min/L in normal rats, and CL was decreased approximately 3-fold. No significant difference in intestinal absorption of Gli was observed between normal and diabetic rats as determined by in situ single-pass intestinal perfusion. The clearance of Diclofenac (a substrate of CYP2C9 was determined to evaluate changes in hepatic drug-metabolizing enzyme activity in rats. The CL in diabetic rats was significantly lower (42.43% decrease than that in normal rats. Hepatic protein expression of CYP2C9 was measured using Western blot analysis; compared with normal rats, the hepatic protein expression of CYP2A9 was decreased in diabetic rats. Therefore, the slower clearance of Gli in diabetic rats can be attributed primarily to the lower expression of hepatic CYP2C9.

Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia

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Lu Guan-Yi

2010-12-01

Full Text Available Abstract Background The Daming capsule (DMC is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM. This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ-induced diabetic rats with hyperlipoidemia. Methods Wistar rats were randomly divided into three groups: untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM rats, and DM rats treated with DMC. The baroreflex sensitivity was examined during intravenous injection of phenylephrine (PE or sodium nitroprusside (SNP and quantified by the change in heart rate over the change in mean arterial blood pressure (ΔHR/ΔMABP. Morphological remodeling of baroreceptors was analyzed by transmission electron microscopy (TEM. The mRNA levels and expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT-PCR and Western blotting. Results Compared to untreated DM rats, DMC significantly elevated the ratio of ΔHR/ΔMABP by enhancing the compensatory reduction in HR (-ΔHR in response to PE-induced hypertension (+ΔMABP (P P P A receptor expression. Conclusion The Daming capsule partially reversed the parasympathetic baroreflex impairment observed in STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented the degeneration of neurons and myelinated axons in the brain stem NAm and reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute to the medicinal properties of DMC in diabetic rats.

The effects of diabetes on the rat parotid gland

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Park, Chull Jea; Hwang, Eui Hwan; Lee, Sang Rae

1996-01-01

The purpose of the study was to observe microscopic change of salivary gland tissue, which is a cause of xerostomia in diabetic condition; for this target, the author injected streptozotocin 0.1 ml/100 gm b.w. on the rat, Sprague Dawley, to induce diabetes, and then observed microscopic changes in parotid gland tissue using light microscopy and electron microscopy. The results were as follows: 1. Parotid gland tissue of the diabetic rat was atrophied or degenerated in lapse of experimental time, but began to re pair from 14 days alter diabetic induction. 2. In the basal lamina of the vessel of parotid gland tissue in the diabetic rat, lamina lucida was discontinued and la mina densa was increased in thickness, but the number of capillary was gradually increased and dilated. 3. In acinic and intercalated ductal cells of parotid gland in the diabetic rat, changes of mitochondria, RER, secretor y granule, free ribosome were prominent. In conclusion, the present study demonstrated that degenerative changes of the parotid gland tissue were due to not completely thickening of the basal lamina of vessels, but many other causal factors, because thickness of the basal lamina of vessels was not related with degenerative changes.

Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats.

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Bădescu, S V; Tătaru, C P; Kobylinska, L; Georgescu, E L; Zahiu, D M; Zăgrean, A M; Zăgrean, L

2016-01-01

Diabetes mellitus modifies the expression of adenosine receptors in the brain. Caffeine acts as an antagonist of A1 and A2A adenosine receptors and was shown to have a dose-dependent biphasic effect on locomotion in mice. The present study investigated the link between diabetes and locomotor activity in an animal model of streptozotocin-induced diabetes, and the effects of a low-medium dose of caffeine in this relation. The locomotor activity was investigated by using Open Field Test at 6 weeks after diabetes induction and after 2 more weeks of chronic caffeine administration. Diabetes decreased locomotor activity (total distance moved and mobility time). Chronic caffeine exposure impaired the locomotor activity in control rats, but not in diabetic rats. Our data suggested that the medium doses of caffeine might block the A2A receptors, shown to have an increased density in the brain of diabetic rats, and improve or at least maintain the locomotor activity, offering a neuroprotective support in diabetic rats. Abbreviations : STZ = streptozotocin, OFT = Open Field Test.

Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum of diabetic rats

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Anju TR

2010-02-01

Full Text Available Abstract Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D and hypoglycemic group (D + IIH and C + IIH. α7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and α7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar

Cell apoptosis of taste buds in circumvallate papillae in diabetic rats.

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Cheng, B; Pan, S; Liu, X; Zhang, S; Sun, X

2011-09-01

Diabetes mellitus may result in taste disturbance. The present study has revealed that cell apoptosis of taste buds in circumvallate papillae may contribute to the taste disturbance in a rat model of type2 diabetes. Type2 diabetes was induced in Wistar rats by feeding them with a high-fat diet (30% fat), and a single intraperitoneal injection of streptozotocin (30 mg/kg). The increased cell apoptosis of taste buds in circumvallate papilla sections was detected by TUNEL staining in diabetic rats, and the ultrastructure was further examined by transmission electronic microscopy. Immunohistochemical and Western blot analyses revealed the downregulation of Bcl-2, upregulation of Bax, and increased activation of caspase-9 and -3, in diabetic rats, indicating that the apoptosis of taste bud cells may be mediated via the intrinsic mitochondrial pathway in diabetics. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Inulin-type fructan improves diabetic phenotype and gut microbiota profiles in rats.

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Zhang, Qian; Yu, Hongyue; Xiao, Xinhua; Hu, Ling; Xin, Fengjiao; Yu, Xiaobing

2018-01-01

Accumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats. A diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed. We found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck , G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3-V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae , Phascolarctobacterium , and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio , which produce lipopolysaccharide (LPS). The

Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

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Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

2014-10-01

This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

Increased intraretinal PO2 in short-term diabetic rats.

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Lau, Jennifer C M; Linsenmeier, Robert A

2014-12-01

In diabetic retinopathy, neovascularization is hypothesized to develop due to hypoxia in the retina. However, evidence for retinal hypoxia is limited, and the progressive changes in oxygenation are unknown. The objective of this study was to determine if retinal hypoxia occurs early in the development of diabetes. Intraretinal oxygen (PO2) profiles were recorded with oxygen-sensitive microelectrodes in control and diabetic Long-Evans rats at 4 and 12 weeks after induction of diabetes. Diabetes did not affect oxygen consumption in the photoreceptors in either dark or light adaptation. Oxygenation of the inner retina was not affected after 4 weeks of diabetes, although vascular endothelial growth factor levels increased. At 12 weeks, average inner retinal PO2, normalized to choriocapillaris PO2, was higher in diabetic rats than in age-matched controls, which was opposite to what was expected. Thus retinal hypoxia is not a condition of early diabetes in rat retina. Increased inner retinal PO2 may occur because oxygen consumption decreases in the inner retina. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

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Xiao-Yuan Mao

2014-05-01

Full Text Available The present study was designed to probe the effects of Huperzine A (HupA on diabetes-associated cognitive decline (DACD using a streptozotocin (STZ-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT, Acetylcholinesterase (AChE, malondialdehyde (MDA, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.

Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

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Mao, Xiao-Yuan; Cao, Dan-Feng; Li, Xi; Yin, Ji-Ye; Wang, Zhi-Bin; Zhang, Ying; Mao, Chen-Xue; Zhou, Hong-Hao; Liu, Zhao-Qian

2014-01-01

The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis. PMID:24857910

Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats

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Serizawa Ken-ichi

2011-11-01

Full Text Available Abstract Background Nicorandil, an anti-angina agent, reportedly improves outcomes even in angina patients with diabetes. However, the precise mechanism underlying the beneficial effect of nicorandil on diabetic patients has not been examined. We investigated the protective effect of nicorandil on endothelial function in diabetic rats because endothelial dysfunction is a major risk factor for cardiovascular disease in diabetes. Methods Male Sprague-Dawley rats (6 weeks old were intraperitoneally injected with streptozotocin (STZ, 40 mg/kg, once a day for 3 days to induce diabetes. Nicorandil (15 mg/kg/day and tempol (20 mg/kg/day, superoxide dismutase mimetic were administered in drinking water for one week, starting 3 weeks after STZ injection. Endothelial function was evaluated by measuring flow-mediated dilation (FMD in the femoral arteries of anaesthetised rats. Cultured human coronary artery endothelial cells (HCAECs were treated with high glucose (35.6 mM, 24 h and reactive oxygen species (ROS production with or without L-NAME (300 μM, apocynin (100 μM or nicorandil (100 μM was measured using fluorescent probes. Results Endothelial function as evaluated by FMD was significantly reduced in diabetic as compared with normal rats (diabetes, 9.7 ± 1.4%; normal, 19.5 ± 1.7%; n = 6-7. There was a 2.4-fold increase in p47phox expression, a subunit of NADPH oxidase, and a 1.8-fold increase in total eNOS expression in diabetic rat femoral arteries. Nicorandil and tempol significantly improved FMD in diabetic rats (nicorandil, 17.7 ± 2.6%; tempol, 13.3 ± 1.4%; n = 6. Nicorandil significantly inhibited the increased expressions of p47phox and total eNOS in diabetic rat femoral arteries. Furthermore, nicorandil significantly inhibited the decreased expression of GTP cyclohydrolase I and the decreased dimer/monomer ratio of eNOS. ROS production in HCAECs was increased by high-glucose treatment, which was prevented by L-NAME and nicorandil

Antidiabetic activities of aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves in streptozotocin-induced diabetic rats.

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Toma, Alemayehu; Makonnen, Eyasu; Mekonnen, Yelamtsehay; Debella, Asfaw; Adisakwattana, Sirichai

2015-07-18

Moringa stenopetala has been used in traditional health systems to treat diabetes mellitus. The aim of this study was to investigate the antidiabetic activity of aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves in streptozotocin (STZ) induced diabetic rats. The aqueous ethanol extract and n-butanol fraction of Moringa stenopetala leaves hydroalcoholic (500 mg/kg body weight) and metformin (150 mg/kg body weight) were administered to diabetic rats. Blood glucose, lipid profiles, liver and kidney function were examined after 14 days of experiment. Histopathological profile of the pancreas was also observed in diabetic rats at the end of study. An oral sucrose challenge test was also carried out to assess the post prandial effect of the extract. Oral administration of the aqueous ethanol and n-butanol extracts of Moringa stenopetala leaves (500 mg/kg body weight) and metformin (150 mg/kg) significantly reduced blood glucose level (PMoringa stenopetala leaves possess antihyperglycemic and antihyperlipidemic properties, and alleviate STZ-induced pancreatic damage in diabetic rats. The beneficial effects of plant material in inhibition of diabetes-induced complications are being investigated.

Functional K(ATP) channels in the rat retinal microvasculature: topographical distribution, redox regulation, spermine modulation and diabetic alteration.

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Ishizaki, Eisuke; Fukumoto, Masanori; Puro, Donald G

2009-05-15

The essential task of the circulatory system is to match blood flow to local metabolic demand. However, much remains to be learned about this process. To better understand how local perfusion is regulated, we focused on the functional organization of the retinal microvasculature, which is particularly well adapted for the local control of perfusion. Here, we assessed the distribution and regulation of functional K(ATP) channels whose activation mediates the hyperpolarization induced by adenosine. Using microvascular complexes freshly isolated from the rat retina, we found a topographical heterogeneity in the distribution of functional K(ATP) channels; capillaries generate most of the K(ATP) current. The initiation of K(ATP)-induced responses in the capillaries supports the concept that the regulation of retinal perfusion is highly decentralized. Additional study revealed that microvascular K(ATP) channels are redox sensitive, with oxidants increasing their activity. Furthermore, the oxidant-mediated activation of these channels is driven by the polyamine spermine, whose catabolism produces oxidants. In addition, our observation that spermine-dependent oxidation occurs predominately in the capillaries accounts for why they generate most of the K(ATP) current detected in retinal microvascular complexes. Here, we also analysed retinal microvessels of streptozotocin-injected rats. We found that soon after the onset of diabetes, an increase in spermine-dependent oxidation at proximal microvascular sites boosts their K(ATP) current and thereby virtually eliminates the topographical heterogeneity of functional K(ATP) channels. We conclude that spermine-dependent oxidation is a previously unrecognized mechanism by which this polyamine modulates ion channels; in addition to a physiological role, spermine-dependent oxidation may also contribute to microvascular dysfunction in the diabetic retina.

Effect of irradiation on the temporomandibular joint in streptozotocin-induced diabetic rat

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Ahn, Ki Dong; Hwang, Eui Hwan; Lee, Sang Rae [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

2004-06-15

To investigate the histopathological changes in the temporomandibular joint in streptozotocin-induced diabetic rat following irradiation. Sprague-Dawley rats weighing about 250 gm were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control group were injected with citrate buffer only. After 5 days, the head and neck region of the rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the temporomandibular joint were sectioned and observed using a histopathological method. In the diabetic group, severe bone resorption in the mandibular condyle was observed throughout the period of experiment. Necrosis of bone marrow and trabeculae was observed at 28 days after diabetic state. Atrophy and fibrosis in the retrodiscal tissue was gradually progressed during the time of the experiment. In the diabetic-irradiated group, severe bone resorption in the mandibular condyle was observed during the early experimental phases, but regeneration of bone marrow was initiated at 14 days after diabetic state and irradiation. Also, calcification of abnormal trabeculae was observed at 28 days after diabetic state and irradiation. The retrodiscal tissue was degenerated in the early experimental phases, but it had been gradually regenerated during the experimental time. This experiment suggests that bone resorption and degeneration in the mandibular condyle are caused by the induction of diabetes, and abnormal bone formation is induced after irradiation in diabetic state.

Effect of irradiation on the temporomandibular joint in streptozotocin-induced diabetic rat

International Nuclear Information System (INIS)

Ahn, Ki Dong; Hwang, Eui Hwan; Lee, Sang Rae

2004-01-01

To investigate the histopathological changes in the temporomandibular joint in streptozotocin-induced diabetic rat following irradiation. Sprague-Dawley rats weighing about 250 gm were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control group were injected with citrate buffer only. After 5 days, the head and neck region of the rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the temporomandibular joint were sectioned and observed using a histopathological method. In the diabetic group, severe bone resorption in the mandibular condyle was observed throughout the period of experiment. Necrosis of bone marrow and trabeculae was observed at 28 days after diabetic state. Atrophy and fibrosis in the retrodiscal tissue was gradually progressed during the time of the experiment. In the diabetic-irradiated group, severe bone resorption in the mandibular condyle was observed during the early experimental phases, but regeneration of bone marrow was initiated at 14 days after diabetic state and irradiation. Also, calcification of abnormal trabeculae was observed at 28 days after diabetic state and irradiation. The retrodiscal tissue was degenerated in the early experimental phases, but it had been gradually regenerated during the experimental time. This experiment suggests that bone resorption and degeneration in the mandibular condyle are caused by the induction of diabetes, and abnormal bone formation is induced after irradiation in diabetic state.

Fructose-fed streptozotocin-injected rat: an alternative model for type 2 diabetes.

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Wilson, Rachel D; Islam, Md Shahidul

2012-01-01

The main objective of the study was to develop an alternative non-genetic rat model for type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats (190.56 ± 23.60 g) were randomly divided into six groups, namely: Normal Control (NC), Diabetic Control (DBC), Fructose-10 (FR10), Fructose-20 (FR20), Fructose-30 (FR30) and Fructose-40 (FR40) and were fed a normal rat pellet diet ad libitum for 2 weeks. During this period, the two control groups received normal drinking water whilst the fructose groups received 10, 20, 30 and 40% fructose in drinking water ad libitum, respectively. After two weeks of dietary manipulation, all groups except the NC group received a single injection (i.p.) of streptozotocin (STZ) (40 mg/kg b.w.) dissolved in citrate buffer (pH 4.4). The NC group received only a vehicle buffer injection (i.p.). One week after the STZ injection, animals with non-fasting blood glucose levels > 300 mg/dl were considered as diabetic. Three weeks after the STZ injection, the animals in FR20, FR30 and FR40 groups were eliminated from the study due to the severity of diabetes and the FR10 group was selected for the remainder of the 11 weeks experimental period. The significantly (p < 0.05) higher fluid intake, blood glucose, serum lipids, liver glycogen, liver function enzymes and insulin resistance (HOMA-IR) and significantly (p < 0.05) lower body weight, oral glucose tolerance, number of pancreatic β-cells and pancreatic β-cell functions (HOMA-β) of FR10 group demonstrate that the 10% fructose-fed followed by 40 mg/kg of BWSTZ injected rat can be a new and alternative model for T2D.

Morphine hyposensitivity in streptozotocin-diabetic rats: Reversal by dietary l-arginine treatment.

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Lotfipour, Shahrdad; Smith, Maree T

2018-01-01

Painful diabetic neuropathy (PDN) is a long-term complication of diabetes. Defining symptoms include mechanical allodynia (pain due to light pressure or touch) and morphine hyposensitivity. In our previous work using the streptozotocin (STZ)-diabetic rat model of PDN, morphine hyposensitivity developed in a temporal manner with efficacy abolished at 3 months post-STZ and maintained for 6 months post-STZ. As this time course mimicked that for the temporal development of hyposensitivity to the pain-relieving effects of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde) in STZ-diabetic rats, we hypothesized that progressive depletion of endogenous NO bioactivity may underpin the temporal loss of morphine sensitivity in STZ-diabetic rats. Furthermore, we hypothesized that replenishment of NO bioactivity may restore morphine sensitivity in these animals. Diabetes was induced in male Dark Agouti rats by intravenous injection of STZ (85 mg/kg). Diabetes was confirmed on day 7 if blood glucose concentrations were ≥15 mmol/L. Mechanical allodynia was fully developed in the bilateral hindpaws by 3 weeks of STZ-diabetes in rats and this was maintained for the study duration. Morphine hyposensitivity developed in a temporal manner with efficacy abolished by 3 months post-STZ. Administration of dietary l-arginine (NO precursor) at 1 g/d to STZ-diabetic rats according to a 15-week prevention protocol initiated at 9 weeks post-STZ prevented abolition of morphine efficacy. When given as an 8-week intervention protocol in rats where morphine efficacy was abolished, dietary l-arginine at 1 g/d progressively rescued morphine efficacy and potency. Our findings implicate NO depletion in the development of morphine hyposensitivity in STZ-diabetic rats. © 2017 John Wiley & Sons Australia, Ltd.

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

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Esmaeal Tamaddonfard

2013-01-01

Full Text Available 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.

Antidiabetic effects of Cuscuta reflexa Roxb. in streptozotocin induced diabetic rats.

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Rath, Diptirani; Kar, Durga Madhab; Panigrahi, Sandeep Kumar; Maharana, Laxmidhar

2016-11-04

Cuscuta reflexa Roxb. (Convolvulaceae) is traditionally used to treat diabetes mellitus by tribal people of north-east India and Bangladesh. To evaluate the anti-diabetic effects of methanol and aqueous extracts of the aerial parts of Cuscuta reflexa Roxb. in normal, glucose loaded and Streptozotocin (STZ) induced diabetic rats. The methanol (MECR) and aqueous (AECR) extracts (200 and 400mg/kg body weight) were administered orally to normal and diabetic rats with Metformin and solvent control as comparison groups. Long term effects like FBG, OGTT, lipid profile, HbA1c, body weight, histopathology of major organs, etc. were investigated. MECR and AECR did not have hypoglycemic effects in normal rats. Both AECR and MECR (400mg/kg) treatments showed significant reduction in blood glucose during OGTT in diabetic rats at 3h. Single oral administration of methanol and aqueous extracts (400mg/kg) to diabetic rats significantly reduced (p<0.05) blood glucose level to 61.90% and 55.39% respectively as compared to the Metformin group i.e. 68.32% at the end of 8h. MECR (400mg/kg body weight for 30 days to diabetic rats) showed a significant decrease (p<0.01) of blood glucose level to 60.00% as compared to other groups. The treatment also resulted an improvement in body weights, decreased HbA1c and restored lipid profile. Histopathological injury was not observed, rather repair of beta cells was seen in extract treated diabetic rats. Methanolic extract of C. reflexa has significant antidiabetic effects and improves metabolic alterations thereby justifying its traditional folkloric claims. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

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Zehra Eren

2014-12-01

Full Text Available Background/Aims: The aim of the present study was to investigate the effect of combination of aliskiren with paricalcitol on experimental diabetic nephropathy (DN model in rats. Methods: Forty male Sprague Dawley rats were divided into 5 groups of 8 rats each, namely the control (Group C, diabetes (Group D, aliskiren (Group A, paricalcitol (Group P, and aliskiren plus paricalcitol (Group A+P groups. Aliskiren was given by oral-gavage at a dose of 50 mg/kg/day once daily for 12 weeks. Paricalcitol was given by intraperitoneally at a dose of 0,4 µg/kg/three day of week for 12 weeks. Renal function parameters, oxidative stress biomarkers, mRNA expression of renin-angiotensin system parameters and kidney histology were determined. Results: Group A+P had lower mean albümin-to-creatinine ratio (ACR (p=0.004 as well as higher creatinine clearance (CCr (pConclusion: Our data seem to suggest a potential role of aliskiren plus paricalcitol acting synergystically for reducing the progression of diabetic nephropathy in an experimental rat model.

Anti-prediabetic effect of rose hip (Rosa canina) extract in spontaneously diabetic Torii rats.

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Chen, Si Jing; Aikawa, Chiwa; Yoshida, Risa; Kawaguchi, Tomoaki; Matsui, Toshiro

2017-09-01

Prediabetes, a high-risk state for developing diabetes showing impaired glucose tolerance but a normal fasting blood glucose level, has an increasing prevalence worldwide. However, no study investigating the prevention of impaired glucose tolerance at the prediabetic stage by anti-diabetic functional foods has been reported. Thus, the present study aimed to evaluate the anti-prediabetic effect of rose hip in a prediabetic rat model. Spontaneously diabetic Torii (SDT) rats were supplemented with hot-water extract of rose hip at a dose of 100 mg kg -1 body weight day -1 for 12 weeks. The results obtained showed that the supplementation of rose hip extract improved impaired glucose tolerance, promoted insulin secretion, preserved pancreatic beta-cell function and suppressed plasma advanced glycation end-products formation of methylglyoxal-derived hydroimidazolone (MG-H1) residue and N ϵ -carboxymethyl-lysine residues (e.g. MG-H1, control: 465.5 ± 43.8 versus rose hip: 59.1 ± 13.0 pmol mg protein -1 , P rose hip could exert an anti-prediabetic effect in a rat model. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Leptin reverses hyperglycemia and hyperphagia in insulin deficient diabetic rats by pituitary-independent central nervous system actions.

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Alexandre A da Silva

Full Text Available The hypothalamic-pituitary-adrenal (HPA axis has been postulated to play a major role in mediating the antidiabetic effects of leptin. We tested if the pituitary is essential for the chronic central nervous system mediated actions of leptin on metabolic and cardiovascular function in insulin-dependent diabetic and non-diabetic rats. Male 12-week-old hypophysectomized Sprague-Dawley rats (Hypo, n = 5 were instrumented with telemetry probes for determination of mean arterial pressure (MAP and heart rate (HR 24-hrs/day and an intracerebroventricular (ICV cannula was placed into the brain lateral ventricle for continuous leptin infusion. In additional groups of Hypo and control rats (n = 5/group, diabetes was induced by single injection of streptozotocin (50 mg/kg, IP. Hypo rats were lighter, had lower MAP and HR (83±4 and 317±2 vs 105±4 mmHg and 339±4 bpm, with similar caloric intake per kilogram of body weight and fasting plasma glucose levels (84±4 vs 80±4 mg/dl compared to controls. Chronic ICV leptin infusion (7 days, 0.62 μg/hr in non-diabetic rats reduced caloric intake and body weight (-10% in Hypo and control rats and markedly increased HR in control rats (~25 bpm while causing only modest HR increases in Hypo rats (8 bpm. In diabetic Hypo and control rats, leptin infusion reduced caloric intake, body weight and glucose levels (323±74 to 99±20 and 374±27 to 108±10 mg/dl, respectively; however, the effects of leptin on HR were abolished in Hypo rats. These results indicate that hypophysectomy attenuates leptin's effect on HR regulation without altering leptin's ability to suppress appetite or normalize glucose levels in diabetes.

Impaired mitochondrial metabolism and protein synthesis in streptozotocin diabetic rat hepatocytes

International Nuclear Information System (INIS)

Memon, R.A.; Bessman, S.P.; Mohan, C.

1990-01-01

Isolated hepatocytes prepared from control, streptozotocin diabetic rats were incubated at 30 degrees C in Krebs-Henseleit bicarbonate buffer, pH 7.4, containing 0.5 mM concentration of each of the 20 natural amino acids. Effect of insulin on the oxidation of 2,3- 14 C and 1,4- 14 C succinate (suc) carbons and their incorporation into hepatocyte protein, lipid and various metabolic intermediates was studied. Mitochondrial oxidation of suc carbons and their incorporation into protein and lipid was significantly lower in diabetic and insulin treated diabetic rats. Diabetic rats failed to exhibit any significant insulin effect on the oxidation of either 2,3 or 1,4- 14 C suc carbons. Amphibolic channeling of 2,3- 14 C suc carbons into amino acids was significantly reduced in hepatocytes of diabetic rats, however, more of these carbons were diverted into the gluconeogenesis pathway. Diabetes caused a far greater decrease in the oxidation of 2,3- 14 C suc carbons as compared to 1,4- 14 C suc. Based on an earlier report that insulin stimulates only the intramitochondrial Krebs cycle reactions, the authors conclude that the diminished level of anabolic activities in the diabetic rat hepatocytes is due to the subsequent reduction in amphibolic channeling of metabolic intermediates

Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

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Mathew Jobin

2009-04-01

Full Text Available Abstract Acetylcholine (ACh, the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. Previous reports from our laboratory on streptozotocin (STZ induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax and affinity (Kd of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

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

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Jian-Qin Wang

2014-01-01

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

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

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

2014-01-01

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

Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

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Gengyin Wang

2016-08-01

Full Text Available Background/Aims: To explore the effects of sulforaphane (SFN on neuronal apoptosis in hippocampus and memory impairment in diabetic rats. Methods: Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group. Streptozotocin (STZ was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1 were detected by western blotting. Neurotrophic factor levels and AKT/GSK3β pathway were also detected. Results: Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3β, NGF and BDNF expressions. Conclusion: SFN could prevent the memory impairment and apoptosis of hippocampal neurons in diabetic rat. The possible mechanism was related to the regulation of neurotropic factors and Akt/GSK3β pathway.

Salicylate prevents virus-induced type 1 diabetes in the BBDR rat.

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Chaoxing Yang

Full Text Available Epidemiologic and clinical evidence suggests that virus infection plays an important role in human type 1 diabetes pathogenesis. We used the virus-inducible BioBreeding Diabetes Resistant (BBDR rat to investigate the ability of sodium salicylate, a non-steroidal anti-inflammatory drug (NSAID, to modulate development of type 1 diabetes. BBDR rats treated with Kilham rat virus (KRV and polyinosinic:polycytidylic acid (pIC, a TLR3 agonist develop diabetes at nearly 100% incidence by ~2 weeks. We found distinct temporal profiles of the proinflammatory serum cytokines, IL-1β, IL-6, IFN-γ, IL-12, and haptoglobin (an acute phase protein in KRV+pIC treated rats. Significant elevations of IL-1β and IL-12, coupled with sustained elevations of haptoglobin, were specific to KRV+pIC and not found in rats co-treated with pIC and H1, a non-diabetogenic virus. Salicylate administered concurrently with KRV+pIC inhibited the elevations in IL-1β, IL-6, IFN-γ and haptoglobin almost completely, and reduced IL-12 levels significantly. Salicylate prevented diabetes in a dose-dependent manner, and diabetes-free animals had no evidence of insulitis. Our data support an important role for innate immunity in virus-induced type 1 diabetes pathogenesis. The ability of salicylate to prevent diabetes in this robust animal model demonstrates its potential use to prevent or attenuate human autoimmune diabetes.

Antihyperglycemic and antidyslipidemic activity of Musa paradisiaca-based diet in alloxan-induced diabetic rats.

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Ajiboye, Basiru O; Oloyede, Hussein O B; Salawu, Musa O

2018-01-01

This study was aimed at investigating the antihyperglycemic and antidyslipidemic activity of Musa paradisiaca -based diets in alloxan-induced diabetic mellitus rats. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg b.w) in 48 randomly selected rats. The rats were randomly grouped into four as follows: normal rats fed Dioscorea rotundata -based diet, diabetic control rats fed D. rotundata -based diet, diabetic rats fed D. rotundata -based diet and administered metformin (14.2 mg/kg body weight) orally per day, and diabetic rats fed M. paradisiaca -based diet. Body weight and fasting blood glucose level were monitored, on 28th days the rats were sacrificed, liver was excised. Thereafter, the hyperglycemic and dyslipidemic statii of the induced diabetic animals were determined. The M. paradisiaca -based diet significantly ( p  paradisiaca -based diet demonstrated significant reduction ( p  paradisiaca -based diet significantly ( p  <   .05) reversed the activities of aspartate aminotransferase and alanine aminotransferase when compared with diabetic control animals. The consumption of this diet may be useful in ameliorating hyperglycemia and dyslipidemia in diabetes mellitus patients.

Effects of diabetes and gender on mechanical properties of the arterial system in rats: aortic impedance analysis.

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Chang, Kuo-Chu; Hsu, Kwan-Lih; Tseng, Yung-Zu

2003-01-01

We determined the effects of diabetes and gender on the physical properties of the vasculature in streptozotocin (STZ)-treated rats based on the aortic input impedance analysis. Rats given STZ 65 mg/kg i.v. were compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured and were then subjected to Fourier transformation for the analysis of aortic input impedance. Wave transit time was determined using the impulse response function of the filtered aortic input impedance spectra. Male but not female diabetic rats exhibited an increase in cardiac output in the absence of any significant changes in arterial blood pressure, resulting in a decline in total peripheral resistance. However, in each gender group, diabetes contributed to an increase in wave reflection factor, from 0.47 +/- 0.04 to 0.84 +/- 0.03 in males and from 0.46 +/- 0.03 to 0.81 +/- 0.03 in females. Diabetic rats had reduced wave transit time, at 18.82 +/- 0.60 vs 21.34 +/- 0.51 msec in males and at 19.63 +/- 0.37 vs 22.74 +/- 0.57 msec in females. Changes in wave transit time and reflection factor indicate that diabetes can modify the timing and magnitude of the wave reflection in the rat arterial system. Meanwhile, diabetes produced a fall in aortic characteristic impedance from 0.023 +/- 0.002 to 0.009 +/- 0.001 mmHg/min/kg/ml in males and from 0.028 +/- 0.002 to 0.014 +/- 0.001 mmHg/min/kg/ml in females. With unaltered aortic pressure, both the diminished aortic characteristic impedance and wave transit time suggest that the muscle inactivation in diabetes may occur in aortas and large arteries and may cause a detriment to the aortic distensibility in rats with either sex. We conclude that only rats with male gender diabetes produce a detriment to the physical properties of the resistance arterioles. In spite of male or female gender, diabetes decreases the aortic distensibility and impairs the wave reflection phenomenon in the rat arterial system.

Decrease of Plasma Glucose by Hibiscus taiwanensis in Type-1-Like Diabetic Rats

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Wang, Lin-Yu; Chung, Hsien-Hui

2013-01-01

Hibiscus taiwanensis (Malvaceae) is widely used as an alternative herb to treat disorders in Taiwan. In the present study, it is used to screen the effect on diabetic hyperglycemia in streptozotocin-induced diabetic rats (STZ-diabetic rats). The extract of Hibiscus taiwanensis showed a significant plasma glucose-lowering action in STZ-diabetic rats. Stems of Hibiscus taiwanensis are more effective than other parts to decrease the plasma glucose in a dose-dependent manner. Oral administration of Hibiscus taiwanensis three times daily for 3 days into STZ-diabetic rats increased the sensitivity to exogenous insulin showing an increase in insulin sensitivity. Moreover, similar repeated administration of Hibiscus taiwanensis for 3 days in STZ-diabetic rats produced a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. Taken together, our results suggest that Hibiscus taiwanensis has the ability to lower plasma glucose through an increase in glucose utilization via elevation of skeletal GLUT 4 and decrease of hepatic PEPCK in STZ-diabetic rats. PMID:23690841

Intermittent fasting modulation of the diabetic syndrome in sand rats. II. In vivo investigations.

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Belkacemi, Louiza; Selselet-Attou, Ghalem; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J

2010-11-01

This study deals with the effects of daily intermittent fasting for 15 h upon the development of diabetes in sand rats exposed to a hypercaloric diet. The same pattern of daily intermittent fasting was imposed on sand rats maintained on a purely vegetal diet (control animals). Over the last 30 days of the present experiments, non-fasting animals gained weight, whilst intermittently fasting sand rats lost weight. In this respect, there was no significant difference between control animals and either diabetic or non-diabetic sand rats exposed to the hypercaloric diet. The postprandial glycemia remained fairly stable in the control animals. During a 3-week transition period from a purely vegetal to a hypercaloric diet, the post-prandial glycemia increased by 5.95 ± 1.26 mM (n=6) in diabetic sand rats, as distinct from an increase of only 0.45 ± 0.56 mM (n=6) in the non-diabetic animals. During the intermittent fasting period, the postprandial glycemia decreased significantly in the diabetic animals, but not so in the non-diabetic sand rats. Before the switch in food intake, the peak glycemia at the 30th min of an intraperitoneal glucose tolerance test was already higher in the diabetic than non-diabetic rats. In both the non-diabetic and diabetic sand rats, intermittent fasting prevented the progressive deterioration of glucose tolerance otherwise observed in non-fasting animals. These findings reveal that, at least in sand rats, intermittent daily fasting prevents the progressive deterioration of glucose tolerance otherwise taking place when these animals are exposed to a hypercaloric diet.

Ginsenoside Rh2 Improves Cardiac Fibrosis via PPARδ–STAT3 Signaling in Type 1-Like Diabetic Rats

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Shih-Hsiang Lo

2017-06-01

Full Text Available Ginsenoside Rh2 (Rh2 is an active principal ingredient contained in ginseng (Panax ginseng Meyer, a medicinal herb used to enhance health worldwide. The present study is designed to investigate the effect of Rh2 on myocardial fibrosis in diabetic rats. In a streptozotocin-induced model of type-1 diabetic rats (STZ-diabetic rats, the increased fasting blood glucose levels and heart weight/body weight (HW/BW ratio were substantially alleviated by Rh2. Moreover, Rh2 improved cardiac performance in STZ-diabetic rats. Histological results from Masson staining showed that Rh2 attenuated cardiac fibrosis in STZ-diabetic rats. The effects of Rh2 were reversed by GSK0660 at a dose sufficient to inhibit peroxisome proliferator-activated receptor δ (PPARδ in STZ-diabetic rats. The role of PPARδ was subsequently investigated in vitro. Rh2 restored the decreased PPARδ expression level in high glucose-cultured cardiomyocytes. Moreover, increased protein levels of fibrotic signals, including signal transducer and activator of transcription 3 (STAT3, connective tissue growth factor (CCN2 and fibronectin, were reduced by Rh2 in high glucose-cultured cardiomyocytes. These effects of Rh2 were reversed by GSK0660 or siRNA specific for PPARδ Taken together, PPARδ activation may inhibit STAT3 activation to reduce CCN2 and fibronectin expression in diabetic rats with cardiac fibrosis. Moreover, Rh2 improves cardiac function and fibrosis by increasing PPARδ signaling. Therefore, Rh2 is suitable to develop as an alternative remedy for cardiac fibrosis.

In vivo postprandial lipid partitioning in liver and muscle of diabetic rats is disturbed

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Prompers, J.J.; Jonkers, R.A.M.; Loon, van L.J.C.; Nicolay, K.

2012-01-01

Objective: To study in vivo lipid partitioning in insulin-resistant liver and muscle of diabetic rats using magnetic resonance spectroscopy (MRS). Methods: Four groups of n=6 male Zucker diabetic fatty rats were used for this study: obese, pre-diabetic fa/fa rats and lean, non-diabetic fa/+

EFFECT OF FERMENTED CHUB MACKEREL EXTRACT ON LIPID METABOLISM OF DIABETIC RATS

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U. Santoso

2014-10-01

Full Text Available The present study was conducted to evaluate the effect of fermented chub mackerel extract(FCME on lipid metabolism in diabetic rats. Four week-old male Wistar rats were divided into threegroups based on weight. All rats were induced with diabetes mellitus by single intraperitoneal injectionof streptozotocin at 45 mg/kg body weight. Thereafter, they were randomly distributed to threetreatments with 7 rats assigned to each treatment. One group was the control with no additive, and twotreatmentgroups were given the purified diets supplemented with 1% or 2% FCME. Experimentalresults showed that in comparison to the control, diabetic rats fed FCME increased feed intake (P<0.01and body weight gain (P<0.05. FCME inclusion significantly reduced the activities of acetyl-CoAcarboxylase (P<0.01 and fatty acid synthetase (P<0.05 in diabetic rats. FCME significantly increasedcholesterol 7 -hydroxylase with no effect on HMG-CoA reductase activity. FCME had no effect onhepatic triglyceride, free cholesterol and phospholipid. FCME inclusion at 1% level significantlyreduced serum triglyceride. FCME significantly increased HDL-cholesterol (P<0.05 with no effect onLDL + VLDL-cholesterol, and significantly reduced atherogenic index. FCME did not significantlyaffect serum insulin and glucose concentration. In conclusion, FCME supplementation altered lipidmetabolism in diabetic rats. FCME supplementation reduced the risk of atherosclerosis in diabetic rats.

Effects of Icariside II on Corpus Cavernosum and Major Pelvic Ganglion Neuropathy in Streptozotocin-Induced Diabetic Rats

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Guang-Yi Bai

2014-12-01

Full Text Available Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg. Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily. Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro was greatly attenuated in the ICA II-treated group (p < 0.01. ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes.

Hypoglycemic of Cajanus scarabaeoides in glucose overloaded and streptozotocin-induced diabetic rats

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Suman Pattanayak, Siva Shankar Nayak, Durgaprasad Panda and Vikas Shende

2009-12-01

Full Text Available In light of traditional claim of Cajanus scarabaeoides (L in the treatment of diabetes, we studied the effects of different solvent extracts in normal, glucose over loaded normal rats and streptozotocin-induced diabetic rats. The methanolic extract (500 mg/kg orally was produce significantly reduce blood glucose level at normal, glucose over loaded normal rats, and streptozotocin-induced diabetic rats after 15 days treatment; whereas petroleum ether and chloroform extract (500 mg/kg orally did not exhibit any significant effect on three groups of rats. Histopathology studies on pancreas of streptozotocin-induced diabetic rats shows inflammatory changes in pancreatic islets, results from selective destroy of insulin producing β-cells. These changes are inhibited by C. scarabaeoides methanolic extract and gliclazide. The antidiabetic activity of methanolic extract may be due to the presence of flavonoids.

Impact of opium on the serum levels of TGF-β in diabetic, addicted and addicted-diabetic rats.

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Asadikaram, Gholamreza; Asiabanha, Majid; Sayadi, Ahmadreza; Jafarzadeh, Abdollah; Hassanshahi, Gholamhossein

2010-09-01

Several cells of immune system such as regulatory T cells and macrophages secrete transforming growth factor-β (TGF-β) in response to different stimuli. This cytokine has inhibitory effect on immune system and diminished production of this cytokine is associated with autoimmune disorders. The aim of this study was to evaluate the influence of opium addiction on serum level of TGF-β in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium addicted, diabetic and addicted-diabetic male and female rats. Serum level of TGF-β was measured by ELISA. The results of our study indicated that the mean serum level of TGF-β in female addicted rats was significantly increased compared to control group (popium and its derivatives have differential inductive effects on the cytokine expression in male and female rats.

Study on Association of Pentraxin 3 and Diabetic Nephropathy in a Rat Model

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Xuehai Chen

2018-01-01

Full Text Available Diabetic nephropathy (DN is a serious microvascular complication of diabetes. Compared with other therapies for diabetic patients, islet transplantation can effectively prevent and reverse diabetes-induced microvascular disease, such as diabetic retinopathy and nephropathy. PTX3 is the only long pentraxin that can be detected in renal tissue. In this study, we investigated the expression of PTX3 when early DN was reversed after islet transplantation. Methods. Diabetes was induced in rats by injecting streptozotocin (STZ. Twelve weeks later, the diabetic rats were divided into 2 groups: the islet transplantation group (IT and the diabetic nephropathy group (DN. Renal injury, renal function, and the expression of PTX3 in the plasma and the kidneys were assessed with urinalysis, immunohistochemical staining, and Western blot, respectively. Results. The expression of PTX3 in the kidney was significantly decreased in the DN group but increased in the IT group because of the reversal of DN. Conclusions. Our data showed that the level of PTX3 in renal tissue is closely related to renal injury in DN. This may be used to quantify the extent of renal injury in DN, provide a potential early indicator of renal tubular injury in early DN patients, and assess DN clinical progression.

Aberrant Pregnancy Adaptations in the Peripheral Immune Response in Type 1 Diabetes: A Rat Model.

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Bart Groen

Full Text Available Despite tight glycemic control, pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy. Other etiological factors may be responsible for the development of adverse pregnancy outcome. Acceptance of the semi-allogeneic fetus is accompanied by adaptations in the maternal immune-response. Maladaptations of the immune-response has been shown to contribute to pregnancy complications. We hypothesized that type 1 diabetes, as an autoimmune disease, may be associated with maladaptations of the immune-response to pregnancy, possibly resulting in pregnancy complications.We studied pregnancy outcome and pregnancy-induced immunological adaptations in a normoglycemic rat-model of type 1 diabetes, i.e. biobreeding diabetes-prone rats (BBDP; 5 non-pregnant rats, 7 pregnant day 10 rats and 6 pregnant day 18 rats , versus non-diabetic control rats (i.e. congenic non-diabetic biobreeding diabetes-resistant (BBDR; 6 non-pregnant rats, 6 pregnant day 10 rats and 6 pregnant day 18 rats and Wistar-rats (6 non-pregnant, 6 pregnant day 10 rats and 5 pregnant day 18 rats.We observed reduced litter size, lower fetal weight of viable fetuses and increased numbers of resorptions versus control rats. These complications are accompanied by various differences in the immune-response between BBDP and control rats in both pregnant and non-pregnant animals. The immune-response in non-pregnant BBDP-rats was characterized by decreased percentages of lymphocytes, increased percentages of effector T-cells, regulatory T-cells and natural killer cells, an increased Th1/Th2-ratio and activated monocytes versus Wistar and BBDR-rats. Furthermore, pregnancy-induced adaptations in BBDP-rats coincided with an increased Th1/Th2-ratio, a decreased mean fluorescence intensity CD161a/NKR-P1b ratio and no further activation of monocytes versus non-diabetic control rats.This study suggests that even in the face of strict normoglycemia, pregnancy complications

Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

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Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

2015-09-01

Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of exposure to cigarette smoke prior to pregnancy in diabetic rats

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Damasceno Débora C

2011-08-01

Full Text Available Abstract Background The purpose of this study was to evaluate the effects of cigarette smoke exposure before pregnancy on diabetic rats and their offspring development. Methods Diabetes was induced by streptozotocin and cigarette smoke exposure was conducted by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Diabetic female Wistar rats were randomly distributed in four experimental groups (n minimum = 13/group: nondiabetic (ND and diabetic rats exposed to filtered air (D, diabetic rats exposed to cigarette smoke prior to and into the pregnancy period (DS and diabetic rats exposed to cigarette smoke prior to pregnancy period (DSPP. At day 21 of pregnancy, rats were killed for maternal biochemical determination and reproductive outcomes. Results The association of diabetes and cigarette smoke in DSPP group caused altered glycemia at term, reduced number of implantation and live fetuses, decreased litter and maternal weight, increased pre and postimplantation loss rates, reduced triglyceride and VLDL-c concentrations, increased levels of thiol groups and MDA. Besides, these dams presented increased SOD and GSH-Px activities. However, the increased antioxidant status was not sufficient to prevent the lipid peroxidation observed in these animals. Conclusion Despite the benefits stemming from smoking interruption during the pregnancy of diabetic rats, such improvement was insufficient to avoid metabolic alterations and provide an adequate intrauterine environment for embryofetal development. Therefore, these results suggest that it is necessary to cease smoking extensive time before planning pregnancy, since stopping smoking only when pregnancy is detected may not contribute effectively to fully adequate embryofetal development.

Effect of intrahippocampal CA1 injection of insulin on spatial learning and memory deficits in diabetic rats

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Golbarg Ghiasi

2011-03-01

Full Text Available Background: Diabetes mellitus is one of the most important diseases in all over the world. Insulin and its receptor are found in specific area of CNS with a variety of regions-specific functions different from its role in direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin and insulin receptor has been shown to be involved in brain cognitive functions. Previous studies about the effect of insulin on memory in diabetes are controversial and further investigation is necessary.Methods: Seventy male NMRI rats (250-300 g were randomly divided into control, diabetic, saline-saline, saline-insulin (12, 18 or 24 mU, diabetic-saline, diabetic-insulin (12, 18 or 24 mU groups. Diabetes was induced by streptozotocin (65 mg/kg, ip. Saline or insulin were injected bilaterally (1 µl/rat into CA1 region of hippocampus during 1 min. Thirty minutes later, water maze training was performed.Results: Insulin had a dose dependent effect. The spatial learning and memory were impaired with diabetes, and improved by insulin. Escape latency and swimming distance in a water maze in insulin treated animals were significantly lower (P<0.05 than control and diabetic groups. Percentage of time spent by animals in a target quarter in probe trial session showed a significant difference among groups. This difference was significant between insulin treated and the other groups (P<0.05.Conclusions: Our findings suggest that injection of insulin into hippocampal CA1 area may have a dose-dependent effect on spatial learning and memory in diabetic rats.

Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats.

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Kim, Dae-Young; Jung, Sun-Young; Kim, Kijeong; Kim, Chang-Ju

2016-08-01

Diabetes mellitus is considered as a risk factor for Alzheimer disease. The aim of the present study was to evaluate the possibility whether treadmill exercise ameliorates Alzheimer disease-associated memory loss in the diabetes mellitus. For this study, the effects of treadmill exercise on short-term memory and spatial learning ability in relation with Wnt signaling pathway were evaluated using the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ. Step-down avoidance task and 8-arm radial maze test were performed for the memory function. Immunohistochemistry for 5-bro-mo-2'-deoxyridine (BrdU) and doublecortin (DCX) and Western blot for Wnt3 and glycogen synthase kinase-3β (GSK-3β) were conducted. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. In the present results, short-term memory and spatial learning ability were deteriorated by induction of diabetes. Treadmill exercise improved short-term memory and spatial learning ability in the diabetic rats. The numbers of BrdU-positive and DCX-positive cells in the hippocampal dentate gyrus were decreased by induction of diabetes. Treadmill exercise increased these numbers in the diabetic rats. Wnt3 expression in the hippocampus was decreased and GSK-3β expression in the hippocampus was increased by induction of diabetes. Treadmill exercise increased Wnt3 expression and suppressed GSK-3β expression in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats.

Anti-diabetic effects of Sargassum oligocystum on Streptozotocin- induced diabetic rat

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Samad Akbarzadeh

2018-03-01

Full Text Available Objective(s: Diabetes is a metabolic syndrome which is associated with the worldwide major public health problems. There are many natural compounds from the sea-market, as a valuable aquatic source, along with the variety of health and therapeutic benefits. In the present research, with respect to the traditional and ethnic uses of Sargassum oligocystum algae for healing of some diseases which have similar metabolic mechanism to the diabetes, its anti-diabetic effects in animal model was proposed. Materials and Methods: The animals (rat were divided into the normal control, diabetic control, positive control and, the test groups. The test groups were gavaged with oral doses of 150 and 300 mg/kg of algae hydroalcoholic extracts. After 30 days of intervention the serum glucose, cholesterol, triglyceride, HDLC, LDLC, insulin, insulin resistance, β-cells function and, the histopathology of pancreatic tissue were evaluated. Results: In animals that were fed with algae extracts a significant decrease in the fasting blood glucose, triglyceride and HOMA-IR and an increase in the HOMA-B with no significant impacts on the insulin, cholesterol and HDL were observed. Also, the histopathology evaluations in the groups which were treated with algae extract revealed the regeneration and reconstitution of damaged pancreatic β-cells. Conclusion: The results give evidence that, the S. oligocystum algae extract has a healing effect on diabetes which can be considered as a new research prospect for the natural therapy of diabetes.

Protective effect of turnip root ethanolic extract on early diabetic nephropathy in the rats

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Bahram Amouoghli-Tabrizi

2011-11-01

Full Text Available Background: Diabetes mellitus is a metabolic disorder and one of its most important consequences is renal insufficiency. A multitude of herbs has been described for the treatment of diabetes mellitus. The aim of present study was to assess the protective effect of turnip root ethanolic extract (TREE on early nephropathy in alloxan-induced diabetic rats.Materials and Method: Eighty male Wistar rats were randomly allocated into 4 equal groups including: healthy rats, normal healthy rats receiving TREE, diabetic rats and diabetic rats receiving TREE. Diabetes was induced by a single injection of alloxan (120 mg/kg; i.p. The extract (200 mg/kg was gavaged to TREE treatment groups daily for 8 weeks. At the end of experiment; serum levels of urea, uric acid and creatinine were assessed. The lipid peroxidation product, thiobarbituric acid-reacting substances (TBARS, and activities of superoxide dismutase, catalase and glutathione peroxidase were measured in the renal tissue. Finally, the biochemical findings were matched with histopathological verification. Statistically, the quantitative data obtained, compared among the groups by one-way analysis of variance followed by Tukey post-test. Statistical significance was considered at p<0.05.Results: In the diabetic rats, TREE significantly decreased the levels of serum biomarkers of renal injury. Furthermore, TREE significantly decreased the lipid peroxidation and elevated the decreased levels of antioxidant enzymes in diabetic rats. Histopathological findings were in agreement with the biochemical findings.Conclusion: TREE has protective effect on early diabetic nephropathy in the rats with experimentally induced diabetes

Long-Term Type 1 Diabetes Enhances In-Stent Restenosis after Aortic Stenting in Diabetes-Prone BB Rats

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Geanina Onuta

2011-01-01

Full Text Available Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s of long-term autoimmune diabetes on development of in-stent restenosis. We here describe the development of in-stent restenosis in long-term (~7 months spontaneously diabetic and age-matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP rats (n=6-7 in each group. Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA1c levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long-term diabetic rats compared with nondiabetic controls. In conclusion, long-term autoimmune diabetes in BBDP rats enhances in-stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes-enhanced in-stent restenosis as well as to test new therapeutic modalities.

Gender-Dimorphic Regulation of Skeletal Muscle Proteins in Streptozotocin-Induced Diabetic Rats

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Minji Choi

2013-03-01

Full Text Available Background: Despite the fact that sexual differences increase diabetic risk and contribute to the need for gender-specific care, there remain contradictory results as to whether or not sexual dimorphism increases susceptibility to the development of type 1 diabetes mellitus. Methods: To examine gender-dimorphic regulation of skeletal muscle proteins between healthy control and STZ-induced diabetic rats of both genders, we performed differential proteome analysis using two-dimensional electrophoresis combined with mass spectrometry. Results: Animal experiments revealed that STZ treatment rendered female rats more susceptible to induction of diabetes than their male littermates with significantly lower plasma insulin levels due to hormonal regulation. Proteomic analysis of skeletal muscle identified a total of 21 proteins showing gender-dimorphic differential expression patterns between healthy controls and diabetic rats. Most interestingly, gender-specific proteome comparison showed that male and female rats displayed differential regulation of proteins involved in muscle contraction, carbohydrate, and lipid metabolism, as well as oxidative phosphorylation and cellular stress. Conclusion: The current proteomic study revealed that impaired protein regulation was more prominent in the muscle tissue of female diabetic rats, which were more susceptible to STZ-induced diabetes. We expect that the present proteomic data can provide valuable information for evidence-based gender-specific treatment of diabetes.

Antihyperlipidemic Effect of a Polyherbal Mixture in Streptozotocin-Induced Diabetic Rats

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Ahmad Ghorbani

2013-01-01

Full Text Available The effects of a polyherbal mixture containing Allium sativum, Cinnamomum zeylanicum, Citrullus colocynthis, Juglans regia, Nigella sativa, Olea europaea, Punica granatum, Salvia officinalis, Teucrium polium, Trigonella foenum, Urtica dioica, and Vaccinium arctostaphylos were tested on biochemical parameters in diabetic rats. The animals were randomized into three groups: (1 normal control, (2 diabetic control, and (3 diabetic rats which received diet containing 15% (w/w of this mixture for 4 weeks. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg. At the end of experiment, the mixture had no significant effect on serum hepatic enzymes, aspartate aminotransferase, and alanine aminotransferase activities. However, the level of fasting blood glucose, water intake, and urine output in treated group was lower than that in diabetic control rats (P<0.01. Also, the levels of triglyceride and total cholesterol in polyherbal mixture treated rats were significantly lower than those in diabetic control group (P<0.05. Our results demonstrated that this polyherbal mixture has beneficial effects on blood glucose and lipid profile and it has the potential to be used as a dietary supplement for the management of diabetes.

Antioxidant activity of citrullus colocynthis pulp extract in the RBC's of alloxan-induced diabetic rats

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Dallak, M.; Jaliah, B.I.

2010-01-01

Previous studies in our laboratory showed that Citrullus colocynthis pulp seedless extract have antihyperglycemic and insulinotropic effects in alloxan induced diabetes. Reactive oxygen species have been implicated in the mechanism of damage of red blood cells and anaemia in diabetic patients. So the current study was carried out to investigate the protective role of citrullus colocynthis against oxidative stress in the RBC's of alloxan induced diabetic rats. Methods: Rats were divided into four groups each of ten rats, the first group was normal non diabetic rats given normal saline orally and was named control group, the second group was diabetic rats given normal saline orally and were named normal saline treated-diabetic rats, the third and fourth group were diabetic rats treated with the pulp extract or glibenclamide (a positive control) orally. Evaluations were made for haematological parameters in the blood and for lipid peroxidation and oxidative stress enzymes activities in the RBC's of all experimental rats. Results: The diabetic rats had a significant decrease (p<0.05) in total erythrocytes count and Packed Cell Volume (PCV) and a normal Haemoglobin (Hb) value in the blood. They also showed decreased levels of Thiobarbituric Acid Reactive Substances (TBARS) and decreased activities of Superoxide Dismutase (SOD) and Catalase (CAT) in the RBC's hemolysate. On other hand, oral administration of citrullus colocynthis or glibenclamide alleviated these altered parameters in the treated rats, they resulted in a significant increase (p<0.05) in the in total erythrocytes count and PCV (Haematocrit) values in the blood and caused a significant decreased levels of TBARS and increased activities of SOD and CAT in the RBC's of those diabetic treated rats when compared to diabetic rats given normal saline. The effect was more profound in citrullus colocynthis treated diabetic rats. Conclusion: Citrullus colocynthis pulp extract possesses a potent antioxidant property

Hypoglycemic and Hypolipidemic Effects of the Cracked-Cap Medicinal Mushroom Phellinus rimosus (Higher Basidiomycetes) in Streptozotocin-Induced Diabetic Rats.

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Rony, Kuttikkadan A; Ajith, Thekkuttuparambil A; Janardhanan, Kainoor K

2015-01-01

Phellinus rimosus is a parasitic host specific polypore mushroom with profound antioxidant, antihepatotoxic, anti-inflammatory, antitumor, and antimutagenic activities. This study investigated the hypoglycemic and hypolipidemic activities of the wood-inhabiting polypore mushroom Ph. Rimosus in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by single intraperitoneal injection of STZ (45 mg/kg) to Wistar rats. The effects of 30 days treatment with Ph. Rimosus (50 and 250 mg/ kg) and glibenclamide (0.65 mg/kg) on blood glucose level, serum insulin, serum lipid profile, liver glycogen, liver function enzymes, and non-enzymic and enzymic antioxidants activities in pancreas, liver, and kidney were evaluated in STZ-induced diabetic rats. Oral administration of Ph. Rimosus extract exhibited a significant reduction in blood glucose, triacylglycerol, total cholesterol, LDL-cholesterol, and liver function enzymes, and increased serum insulin, liver glycogen, and HDL-cholesterol levels in STZ-induced diabetic rats. Furthermore, Ph. Rimosus treatment increased antioxidant status in pancreas, liver, and kidney tissues with concomitant decreases in levels of thiobarbituric acid- reactive substances. Results of this study indicated that Ph. Rimosus possessed significant hypoglycemic and hypolipidemic activities and this effect may be related to its insulinogenic and antioxidant effect.

Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress.

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Punaro, Giovana R; Maciel, Fabiane R; Rodrigues, Adelson M; Rogero, Marcelo M; Bogsan, Cristina S B; Oliveira, Marice N; Ihara, Silvia S M; Araujo, Sergio R R; Sanches, Talita R C; Andrade, Lucia C; Higa, Elisa M S

2014-02-15

This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8 mL/day for 8 weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications. Copyright © 2014 Elsevier Inc. All rights reserved.

A novel approach of proteomics to study the mechanism of action of grape seed proanthocyanidin extracts on diabetic retinopathy in rats

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无

2008-01-01

Background Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness among the people of occupational age. To prevent the progress of retina injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating diabetic complications, while little is discussed about the functional protein changes. Methods We used streptozotocin (STZ) to induce diabetes in rats. GSPE (250 mg/kg body weight per day) were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin and advanced glycation end products (AGEs) were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate retina protein profiles among control, STZ-induced diabetic rats, and GSPE treated diabetic rats. Results GSPE significantly reduced the AGEs of diabetic rats (P <0.05). Moreover, GSPE significantly suppressed the vascular lesions of central regions, decreased capillary enlargements and neovascularization, similar to those of the control rats under light microscope. Eighteen proteins were found either up-regulated or down-regulated in the retina of STZ-induced diabetic rats. And seven proteins in the retina of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in many important biological processes such as heat shock, ubiquitin-proteasome system, cell proliferation, cell growth and glucose metabolism. Conclusions These findings might promote a better understanding for the mechanism of DR, and provide novel targets for evaluating the effects of GSPE therapy.

Effects of diabetes on tooth movement and root resorption after orthodontic force application in rats.

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Arita, K; Hotokezaka, H; Hashimoto, M; Nakano-Tajima, T; Kurohama, T; Kondo, T; Darendeliler, M A; Yoshida, N

2016-05-01

To investigate the effects of diabetes on orthodontic tooth movement and orthodontically induced root resorption in rats. Twenty-three 10-week-old male Sprague-Dawley rats divided into control (n = 7), diabetes (n = 9), and diabetes + insulin (n = 7) groups. Diabetes was induced by administering a single intraperitoneal injection of streptozotocin. Rats with a blood glucose level exceeding 250 mg/dl were assigned to the diabetes group. Insulin was administered daily to the diabetes + insulin group. A nickel-titanium closed-coil spring of 10 g was applied for 2 weeks to the maxillary left first molar in all rats to induce mesial tooth movement. Tooth movement was measured using microcomputed tomography images. To determine the quantity of root resorption, the mesial surfaces of the mesial and distal roots of the first molar were analyzed using both scanning electron microscopy and scanning laser microscopy. After 2 weeks, the amount of tooth movement in the diabetic rats was lower than that in the control rats. Root resorption was also significantly lower in the diabetic rats. These responses of the rats caused by diabetes were mostly diminished by insulin administration. Diabetes significantly reduced orthodontic tooth movement and orthodontically induced root resorption in rats. The regulation of blood glucose level through insulin administration largely reduced these abnormal responses to orthodontic force application. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

d-limonene ameliorates diabetes and its complications in streptozotocin-induced diabetic rats.

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Bacanlı, Merve; Anlar, Hatice Gül; Aydın, Sevtap; Çal, Tuğbagül; Arı, Nuray; Ündeğer Bucurgat, Ülkü; Başaran, A Ahmet; Başaran, Nurşen

2017-12-01

It is known that diabetes causes some complications including alterations in lipid profile, hepatic enzyme levels but also it causes oxidative stress. Limonene, a major component of Citrus oils, has important health beneficial effects in lowering the level of oxidative stress due to its antioxidant activity. The aim of this study was to investigate the effects of D-limonene on streptozotocin (STZ)-induced diabetes in Wistar albino rats. For this purpose, DNA damage was evaluated by alkaline comet assay. Changes in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSHPx) and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), total glutathione (GSH), malondialdehyde (MDA), insulin, total bilirubin and BCA protein, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol and triglyceride were also evaluated. D-limonene treatment was found to significantly decrease DNA damage, GR enzyme activities and MDA levels and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities and altered lipid and liver enzyme parameters in diabetic rats. According to our results, it seems that D-limonene might have a role in the prevention of the complication of diabetes in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of dietary Cu and diabetes on tissue 67Cu retention kinetics in rats

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Uriu-Hare, J.Y.; Rucker, R.B.; Keen, C.L.

1991-01-01

Compared to controls, diabetes results in higher plasma, liver and kidney Cu concentrations. Since alterations in Cu metabolism may be associated with diabetic pathology, the authors investigated how Cu metabolism is affected by diabetes and dietary Cu intake. Nondiabetic and STZ diabetic rats were fed Cu suppl. or Cu def. diets for 5 wks. Rats were intubated with 28 μCi 67 Cu and killed after 8, 16, 24, 32, 64, or 128 h. There were marked effects of both diet and diabetes on 67 Cu metabolism. Independent of diabetes, deficient rats had a higher % of retained 67 Cu, in liver, plasma, RBC, muscle, spleen, brain, lung, uterus, and intestine than adequate Cu rats. Independent of dietary Cu, diabetic rats had a lower % of retained 67 Cu in liver, plasma, RBC, muscle, spleen, lung, bone, pancreas, skin, uterus and heart than controls. Differential effects were noted for kidney; adequate Cu diabetic rats had a higher % of retained 67 Cu than all other groups. Marked effects of both diet and diabetes were evident when tissue Cu turnover was examined. Compared to Cu suppl. rats, Cu def. rats had a slower turnover of 67 Cu, in liver, plasma, intestine, pancreas, eye, brain, muscle, spleen, lung and heart. Diabetic rats had a slower turnover of 67 Cu than nondiabetic rats in liver, plasma, intestine, pancreas, eye, kidney, RBC and uterus. The data imply that a focus on Cu metabolism with regard to cellular Cu trafficking and pathology may be warranted

Delayed progression of diabetic cataractogenesis and retinopathy by Litchi chinensis in STZ-induced diabetic rats.

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Kilari, Eswar Kumar; Putta, Swathi

2017-03-01

The study was carried out to evaluate the effect of the aqueous fruit pericarp extract of Litchi chinensis (APLC) on parameters which leads to diabetic cataractogenesis and retinopathy in the streptozotocin-induced diabetic rats. The objective of the study is to evaluate the APLC for in vivo antioxidant activity and its role in inhibiting the polyol pathway and formation of advanced glycation end products (AGEs). The diabetic animals were treated with L. chinensis for a period of 12 weeks. At the end of 12 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract such as oxidative stress by protein content, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and polyolpathway by aldose reductase (AR) in lens homogenates, alterations in protein carbonyl content (PCO) and AGEs in both serum and lens the APLC-treated diabetic rats were compared against diabetic control rats. Cataract progression due to hyperglycemia was monitored by slit lamp bio microscope and classified into four stages. Fundoscope test and retinal histopathology were done for assessing retinopathy. Statistically significant reduction in glucose, and elevation of protein content, SOD, CAT, and GSH levels and decreased levels of AR and PCO in lens homogenate and significant reduction in AGEs serum and lens homogenate were observed. Slit lamp examination, fundoscope, and histopathology showed improvement in retinal changes in APLC-treated rats compared to diabetic control animals. The treatment with APLC found to delay the progression of diabetic cataractogenesis and retinopathy, which might be due to its antioxidant activity, because of the presence of active phytochemicals in APLC.

Lectins binding during alloxan-induced diabetes in rat soleus muscle

African Journals Online (AJOL)

Membrane structural changes of soleus muscle of alloxan-diabetic rats were detected with a panel of six biotinylated lectins. Samples of muscles were obtained from normal and diabetic rats. The biotinylated lectins in staining were detected by avidin-peroxidase complex. Lectin stainning of soleus muscle cryostat sections ...

Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats.

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Radhika, P; Annapurna, A; Rao, S Nageswara

2012-05-01

A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. A significant (Ppaniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats.

Protective role of marine macroalgae extracts against STZ induced diabetic rats

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Marine macroalgae

2017-12-01

Full Text Available Objective: To study the anti-diabetic activity of marine macroalgae extracts (n = 31, purification and characterization of sulphated galactopyran (SGP from Gracilaria opuntia (FM4 in diabetic rats. Methods: The animals were separated into groups and STZ (55 mg/kg body weight was used to induce diabetics. Glucose, HbA1c, insulin, C-peptide levels and in vivo antioxidant levels were estimated and histopathological studies were done in STZ-induced diabetic and marine macroalgae treated rats. Results: Based on glucose and HbA1c levels and in vivo antioxidant levels, among the 31 marine macroalgae extracts, FM4 has showed high anti-diabetic activity. Hence, FM4 was purified and characterized by 1H-NMR spectra and FT-IR as sulphated galactopyran. During the survival analysis, SGP at dose of 100 mg/kg showed significant (P < 0.05 survival rate and elevations in C-peptide and insulin levels. The histopathological modulations of SGP were observed in diabetic rat tissues such as liver, kidney and brain. Hence obtained results reveal that SGP treated diabetic rats has significant changes in C-peptide and insulin levels which regulates the blood glucose levels and recovered the histopathological changes. Conclusions: Marine macroalgae have significant anti-diabetic activity. Hence, they could be used as nutraceutical supplement or natural green remedy against diabetes mellitus.

Free radical activity during development of insulin-dependent diabetes mellitus in the rat

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Pitkaenen, O.M.; Akerblom, H.K.; Sariola, H.; Andersson, S.M. (Univ. of Helsinki (Finland)); Martin, J.M. (Hospital for Sick Children, Toronto, Ontario (Canada)); Hallman, M. (Univ. of California, Irvine (United States))

1991-01-01

Free radical-induced lipid peroxidation was quantified by measuring expired pentane from diabetic prone BB Wistar rats of 45-90 d of age. Insulin-dependent diabetes mellitus was manifest at the age of 71 {plus minus} 8 d. Expired pentane increased from 2.1 {plus minus} 0.7 to 5.0 {plus minus}3.0 pmol/100g/min (p <0.01) at manifestation of the disease and remained high throughout the test period. In healthy age-matched control rats it persisted low. In rats made diabetic with streptozotocin, expired pentane remained low. The changes in expired pentane suggest that the development of endogenous insulin-dependent diabetes mellitus in BB rats is associated with increased free radical activity. This is not due to hyperglycemia or ketosis per se, and reflects a fundamental difference in the free radical activity between the spontaneously diabetic BB rats and the disease produced by streptozotocin. Development of spontaneous insulin-dependent diabetes in BB rats is associated with increased free radical activity that persists after the manifestation of the disease.

Effect of irradiation on the dental pulp tissues in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Kang, Ho Duk; Hwang, Eui Hwan; Lee, Sang Rae

2005-01-01

To observe the histological changes in the pulp tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups : control, diabetes, irradiation, and diabetes-irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes-irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, capillary dilatation was observed. However, there was no obvious morphologic alteration of the odontoblasts. In the irradiation group, generalized necrosis of the dental pulp tissues was observed. Vacuolation of the odontoblasts and dilatation of the capillaries were noted in the early experimental phases. In the diabetes-irradiation group, generalized degeneration of the dental pulp tissues was observed. Vacuolation of the dental pulp cells and the odontoblasts was noted in the late experimental phases. This experiment suggest that dilatation of the capillaries in the dental pulp tissue is induced by diabetic state, and generalized degeneration of the dental pulp tissues is induced by irradiation of the diabetic group.

Hu-Lu-Ba-Wan Attenuates Diabetic Nephropathy in Type 2 Diabetic Rats through PKC-α/NADPH Oxidase Signaling Pathway

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Lishan Zhou

2013-01-01

Full Text Available Hu-Lu-Ba-Wan (HLBW is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH and protein kinase C-alpha (PKC-α related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47phox, and the protein expression of phosphorylated PKC-α in renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-α/NADPH oxidase signaling pathway.

Gender Differences in Metabolic Disorders and Related Diseases in Spontaneously Diabetic Torii-Leprfa Rats

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Takeshi Ohta

2014-01-01

Full Text Available The Spontaneously Diabetic Torii Leprfa (SDT fatty rat is a novel type 2 diabetic model wherein both male and female rats develop glucose and lipid abnormalities from a young age. In this study, we investigated gender differences in abnormalities and related complications in SDT fatty rats. Food intake was higher in males compared to female rats; however, body weight was not different between genders. Progression of diabetes, including increases in blood glucose and declines in blood insulin, was observed earlier in male rats than in females, and diabetic grade was more critical in male rats. Blood lipids tended to increase in female rats. Gonadal dysfunction was observed in both male and female rats with aging. Microangiopathies, such as nephropathy, retinopathy, neuropathy, and osteoporosis, were seen in both genders, and pathological grade and progression were more significant in males. Qualitative and quantitative changes were observed for metabolic disease gender differences in SDT fatty rats. The SDT fatty rat is a useful model for researching gender differences in metabolic disorders and related diseases in diabetes with obesity.

Study of Okra Powder (Abelmoscus Esculentus Effects on Histology of Liver Tissue and Sero-Biochemical Parameters in Diabetic Rats (HFD/STZ

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N erfani majd

2016-12-01

Full Text Available Introduction: Type 2 diabete is a kind of metabolic disease that it is associated with hyperglycemia, hyperlipidemia and disturbed liver function.  The aim of the present study was to evaluate the protective effects of Okra Powder on liver damage in high fat diet fed / streptozotocin (HFD-STZ-induced type 2 diabetic rats. Methods: In this experimental study, 25 Wistar Albino female rats with an average weight of (200–220 g were randomly divided  into 5 groups: Group I: (control group rats were fed the standard diet, Group II: healthy rats that received Okra Powder (200 mg/kg for 4 weeks; Group III (HFD/STZ group: Rats were fed with high-fat diet (HFD (60% fat for 4 weeks  and then injected low dose of STZ (35 mg/kg, Group IV:  Diabetic rats that received Okra Powder (200 mg/kg for 4 weeks. GroupV: Diabetic rats that received metformin (200 mg/kg for 4 weeks. At the end of experiment, biochemical parameters were measured. Liver samples were removed and 5-6 µ sections were made and stained by H&E and Sudan black staining. Results: The results showed that all the biochemical parameters, except HDL-C and serum insulin were increased in diabetic rats, while they were decreased in Okra supplementation group compared  to diabetic rats (p<0.05. The liver structure alterations were improved in treated diabetic rats with Okra Powder and metformin.  Conclusion: Our findings confirmed the potential anti-hyperglycemic and hypolipidemic effects of Okra Powder. Thus, it seems it has an important role in the management of type 2 diabete.

Spirulina platensis Extract Supplementation Attenuates Diabetic Complication in Gamma Irradiated Rats

International Nuclear Information System (INIS)

Ibrahim, R.M.; Sherif, N.H

2014-01-01

Diabetes mellitus, a metabolic disorder, is becoming a major health problem. Although there are a number of drugs available on the market, long time use may cause a number of side effects. Spirulina is a microscopic and filamentous cyanobacterium that contains essential amino acids, essential fatty acids, vitamins, minerals and anti-oxidative components. The objective of this study was to analyze the possible hypo glycemic and hypolipidaemic effects of Spirulina intake against streptozotocin and/or radiation induced diabetes in male albino rats. In the experiment, a total of 60 rats were used and the rats were divided into six groups of ten rats each: group I, normal untreated rats (control) ; group II, animals of this group received only Spirulina (15 mg/kg) for 30 consecutive days; group III, animals were injected intraperitoneally with a freshly prepared solution of streptozotocin(STZ) (45 mg/kg i.p.) in 0.1 M citrate buffer, ph 4.5 for 30 consecutive days ; group IV, as group II then given Spirulina for 30 days , group V, same as group III then exposed to 6 Gy gamma radiation as a single dose shot ; and group VI, Spirulina + diabetic irradiated group, rats were given orally Spirulina (15 mg/kg) then injected in - traperitoneally with (STZ) followed by irradiation at a dose level of 6 Gy as a single dose shot. The results revealed that animal treated with STZ or/and exposed to gamma radiation showed an increase in fasting blood sugar (FBS), glycosylated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (Tg), low density lipoprotein (LDL), plasma insulin and C- peptide in compared to control. Also, a marked increase in the liver tissue of thiobarbituric acid reactive substance (TBARS) and a decrease in glutathione (GSH) and catalase (CAT) was observed. Oral pretreatment of rats with aqueous extract of Spirulina (SPE) counteracted STZ or/and radiation induced lipid peroxidation and encouraging hypoglycemic and hypolipidaemic properties of the treated

Antidiabetic and Renoprotective Effects of Cladophora glomerata Kützing Extract in Experimental Type 2 Diabetic Rats: A Potential Nutraceutical Product for Diabetic Nephropathy

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Chutima Srimaroeng

2015-01-01

Full Text Available Cladophora glomerata extract (CGE has been shown to exhibit antigastric ulcer, anti-inflammatory, analgesic, hypotensive, and antioxidant activities. The present study investigated antidiabetic and renoprotective effects of CGE in type 2 diabetes mellitus (T2DM rats. The rats were induced by high-fat diet and streptozotocin and supplemented daily with 1 g/kg BW of CGE for 12 weeks. The renal transport function was assessed by the uptake of para-aminohippurate mediated organic anion transporters 1 (Oat1 and 3 (Oat3, using renal cortical slices. These two transporters were known to be upregulated by insulin and PKCζ while they were downregulated by PKCα activation. Compared to T2DM, CGE supplemented rats had significantly improved hyperglycaemia, hypertriglyceridemia, insulin resistance, and renal morphology. The baseline uptake of para-aminohippurate was not different among experimental groups and was correlated with Oat1 and 3 mRNA expressions. Nevertheless, while insulin-stimulated Oat1 and 3 functions in renal slices were blunted in T2DM rats, they were improved by CGE supplementation. The mechanism of CGE-restored insulin-stimulated Oat1 and 3 functions was clearly shown to be associated with upregulated PKCζ and downregulated PKCα expressions and activations. These findings indicate that CGE has antidiabetic effect and suggest it may prevent diabetic nephropathy through PKCs in a T2DM rat model.

Antidiabetic and renoprotective effects of Cladophora glomerata Kützing extract in experimental type 2 diabetic rats: a potential nutraceutical product for diabetic nephropathy.

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Srimaroeng, Chutima; Ontawong, Atcharaporn; Saowakon, Naruwan; Vivithanaporn, Pornpun; Pongchaidecha, Anchalee; Amornlerdpison, Doungporn; Soodvilai, Sunhapas; Chatsudthipong, Varanuj

2015-01-01

Cladophora glomerata extract (CGE) has been shown to exhibit antigastric ulcer, anti-inflammatory, analgesic, hypotensive, and antioxidant activities. The present study investigated antidiabetic and renoprotective effects of CGE in type 2 diabetes mellitus (T2DM) rats. The rats were induced by high-fat diet and streptozotocin and supplemented daily with 1 g/kg BW of CGE for 12 weeks. The renal transport function was assessed by the uptake of para-aminohippurate mediated organic anion transporters 1 (Oat1) and 3 (Oat3), using renal cortical slices. These two transporters were known to be upregulated by insulin and PKCζ while they were downregulated by PKCα activation. Compared to T2DM, CGE supplemented rats had significantly improved hyperglycaemia, hypertriglyceridemia, insulin resistance, and renal morphology. The baseline uptake of para-aminohippurate was not different among experimental groups and was correlated with Oat1 and 3 mRNA expressions. Nevertheless, while insulin-stimulated Oat1 and 3 functions in renal slices were blunted in T2DM rats, they were improved by CGE supplementation. The mechanism of CGE-restored insulin-stimulated Oat1 and 3 functions was clearly shown to be associated with upregulated PKCζ and downregulated PKCα expressions and activations. These findings indicate that CGE has antidiabetic effect and suggest it may prevent diabetic nephropathy through PKCs in a T2DM rat model.

Molecular Pathways Involved in the Amelioration of Myocardial Injury in Diabetic Rats by Kaempferol.

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Suchal, Kapil; Malik, Salma; Khan, Sana Irfan; Malhotra, Rajiv Kumar; Goyal, Sameer N; Bhatia, Jagriti; Ojha, Shreesh; Arya, Dharamvir Singh

2017-05-15

There is growing evidence that chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs) which exerts its effect via interaction with the receptor for advanced glycation end products (RAGE). AGE-RAGE activation results in oxidative stress and inflammation. It is well known that this mechanism is involved in the pathogenesis of cardiovascular disease in diabetes. Kaempferol, a dietary flavonoid, is known to possess antioxidant, anti-apoptotic, and anti-inflammatory activities. However, little is known about the effect of kaempferol on myocardial ischemia-reperfusion (IR) injury in diabetic rats. Diabetes was induced in male albino Wistar rats using streptozotocin (70 mg/kg; i.p.), and rats with glucose level >250 mg/dL were considered as diabetic. Diabetic rats were treated with vehicle (2 mL/kg; i.p.) and kaempferol (20 mg/kg; i.p.) daily for a period of 28 days and on the 28th day, ischemia was produced by one-stage ligation of the left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed and the heart tissue was processed for biochemical, morphological, and molecular studies. Kaempferol pretreatment significantly reduced hyperglycemia, maintained hemodynamic function, suppressed AGE-RAGE axis activation, normalized oxidative stress, and preserved morphological alterations. In addition, there was decreased level of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and NF-κB), inhibition of active c-Jun N-terminal kinase (JNK) and p38 proteins, and activation of Extracellular signal regulated kinase 1/2 (ERK1/2) a prosurvival kinase. Furthermore, it also attenuated apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase-3), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells, and increasing the level of anti-apoptotic protein (Bcl-2). In conclusion, kaempferol attenuated

Effect of irradiation on the acinar cells of submandibular gland in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Lee, Seung Hyun; Hwang, Eui Hwan; Lee, Sang Rae

2003-01-01

To observe the histologic changes and clusterin expression in the acinar cells of the submandibular gland in streptozotocin-induced diabetic rat following irradiation. Mature Sprague-Dawley rats were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the Sprague-Dawley rats by injecting streptozotocin, while the control rats were injected with citrate buffer only. After 5 days, rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy to the head and neck region. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the submandibular gland were sectioned and observed using histologic and immunohistochemical methods. Morphologic change of acinar cells was remarkable in the diabetic group, but was not observed in the diabetic-irradiated group. Necrotic tissues were observed in the diabetic-irradiated group. Coloring of toluidine blue stain was most increased at 14 days in the diabetic group, however there were no significant change throughout the period of the experiment in the diabetic-irradiated group. Expression of clusterin was most significant at 14 days in the diabetic group, but gradually decreased with time after 7 days in the diabetic-irradiated group. Degeneration of clusterin was observed in the diabetic-irradiated group. This experiment suggests that the acinar cells of submandibular gland in rats are physiologically apoptosis by the induction of diabetes, but that the apoptosis is inhibited and the acinar cells necrotized after irradiation.

Antioxidant and protective effects of Royal jelly on histopathological changes in testis of diabetic rats

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Elham Ghanbari

2016-08-01

Full Text Available Background: Diabetes is the most common endocrine disease. It has adverse effects on male reproductive function. Royal Jelly (RJ has antioxidant and anti-diabetic effects and show protective effects against diabetes. Objective: This study was conducted to evaluate the effect of RJ on histopathological alterations of the testicular tissue in streptozotocin (STZ-induced diabetic rats. Materials and Methods: In this experimental study, 28 adult Wistar rats were randomly divided into control (C, royal jelly (R, diabetic (D and RJ-treated diabetic (D+R groups. Diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg body weight (BW. The rats from the R and D+R groups received daily RJ (100 mg/kg BW for 6 wks orally. Hematoxylin-Eosin staining was used to analyze histopathological changes including: tunica albuginea thickness (TAT, seminiferous tubules diameter (STsD, Johnsen’s score, tubular differentiation index (TDI, spermiogenesis index (SPI, Sertoli cell index (SCI, meiotic index (MI, and mononuclear immune cells (MICs in testes. The antioxidant status was examined by evaluating testicular levels of ferric reducing antioxidant power (FRAP and catalase (CAT activity. Results: Histological results of the testis from diabetic rats showed significant decrease in STsD, Johnsen’s score, TDI, SPI, SCI and MI, and significant increase in TAT and MICs, while administration of RJ significantly reverted these changes (p<0.05. RJ treatment markedly increased activity of CAT and FRAP. There were significant differences in FRAP levels among C (13.0±0.5, RJ (13.4±0.3, D (7.8±0.6 and D+R (12.4±0.7 groups (p<0.05. Conclusion: RJ improved diabetes-induced impairment in testis, probably through its antioxidant property.

The Effect of Treadmill Exercise on Antioxidant Status in the Hearts of the Diabetic Rats

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I. Salehi

2009-07-01

Full Text Available Introduction & Objective: Diabetes is a metabolic disorder caused by low secretion or resistance to the insulin action. Oxidative stress, as a result of imbalance between the free radical production and antioxidant defense systems is strongly related to diabetes and its complications. The aim of the present study is to evaluate the effect of experimental diabetes and forced treadmill exercise on oxidative stress indexes in heart tissue.Materials & Methods: 40 male wistar rats (20020g were divided into four groups(n=10: control, control with exercise, diabetic, diabetic with exercise. Diabetes was induced by a single dose injection of streptozotocin (50 mg/Kg-1, i.p. Treadmill was performed for 1 hour, 5 days in 8 weeks. At the end of the experiments, the rats were anesthetized by sodium pentobarbital (50 mg/Kg-1, i.p and left ventricle dissociate from heart and maintenance in -80 ºC. Supernatant from homogenization were used to determine the superoxide dismutase (SOD, gluthatione peroxidase (GPX, gluthatione reductase (GR and catalase (CAT activities as enzymatic antioxidant status. Also Maolnyldealdehyde (MDA level as index of lipid peroxidation and total glutathione (T.GSH of the heart tissue were measured.Results: Diabetes significantly reduced CAT and GR activities in diabetic rats compared with control rats. SOD and GPX activities weren't changed in the hearts of the diabetic rats. MDA level, as a lipid peroxidation index, increased in non exercised diabetic rats. In response to exercise, MDA level, CAT, GR and SOD activities showed a significant increase in exercise diabetic rats compared with non exercise diabetic rats.Conclusion: Forced treadmill with moderate severity has harmful effects on cardiovascular system in diabetes because it increases MDA level of heart tissue in exercised diabetic rats.

Interleukin-1 beta (IL-1) does not reduce the diabetes incidence in diabetes-prone BB rats

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Reimers, J I; Mørch, L; Markholst, H

1994-01-01

The cytokine interleukin 1 beta (IL-1) has been implicated as a pathogenetic factor in the initial events leading to insulin-dependent diabetes mellitus. Previous studies investigating the impact of IL-1 on diabetes incidence in spontaneously diabetic rodent models have been conflicting. IL-1...... concentrations at diagnosis, but did not change the diabetes incidence in DP BB rats. The results are not in conflict with the hypothesis that IL-1 is a pathogenetic factor in IDDM, caused by high local concentrations of rat IL-1 in the islets during early insulitis. The results also show the necessity of pair...

Treadmill exercise alleviates diabetic cardiomyopathy by suppressing plasminogen activator inhibitor expression and enhancing eNOS in streptozotocin-induced male diabetic rats.

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Chengji, Wang; Xianjin, Fan

2018-04-01

To investigate the biological mechanism of the effect of different intensity exercises on diabetic cardiomyopathy. 87 raise specific pathogen SPF healthy 6-week-old male Sprague-Dawley rats, fed 6 weeks with high-fat diet for rats were used, and a diabetic model was established by intraperitoneal injection of streptozotocin - randomly selected 43 rats were divided into Diabetic control group (DCG, n  = 10), Diabetic exercise group 1 (DEG1, n  = 11), Diabetic exercise group 2 (DEG2, n  = 11) and Diabetic exercise group 3 (DEG3, n  = 11). The rats in DEG1 were forced to run on a motorized treadmill, the exercise load consisted of running at a speed of 10 m/min, the exercise load of the rats in DEG2 were running at a speed of 15 m/min, the exercise load of the rats in DEG3 were running at a speed of 20 m/min, for one hour once a day for 6 weeks. After 6 weeks of exercise intervention, glucose metabolism-related indexes in rats such as blood glucose (FBG), glycosylated serum protein (GSP) and insulin (FINS); cardiac fibrinolytic system parameters such as PAI-1 (plasminogen activator inhibitor 1), Von Willebrand factor (vWF), protein kinase C (PKC) and diacylglycerol (DAG); and serum level of NO, eNOS and T-NOS were measured. Compared with DCG, fasting blood glucose and GSP were decreased, while insulin sensitivity index and insulin level were increased in all rats of the three exercise groups. FBG decrease was statistically significant ( P  diabetic rats; myocardial PAI-1 in DEG1, DEG2 and DEG3 rats decreased significantly ( P  diabetic cardiomyopathy by affecting the levels of PAI-1 and eNOS, and there is a dependence on intensity. © 2018 The authors.

Antidiabetic And Antioxidant Effects Of Parsley Extract (Petroselinum Crispum) On Diabetic Rats

International Nuclear Information System (INIS)

Mahmoud, K.A.

2011-01-01

Parsley (Petroselinum crispum) is one of the medicinal herbs in Egypt. The aim of the present study is to investigate the effects of parsley (10 mg/kg/day) on diabetic rats. Diabetes was induced in male albino rats with a single intraperitoneal injection of alloxan (150 mg/kg). The volatile compounds were separated by gas chromatographic-mass spectrometric (GC-MS) for analysis of essential oils. The results showed that 18 compounds could be identified (natural antioxidants). Experimental rats were divided into four groups: control, diabetic, diabetic received parsley, and diabetic received irradiated parsley through gastric intubation for 4 weeks. A single administrative dose of alloxan (150 mg/kg) resulted in hyperglycemia, increase in AST, ALT, urea, creatinine, triglycerides, total cholesterol and low density lipoprotein-cholesterol levels and decrease in body weight, serum insulin, total protein and high density lipoprotein-cholesterol levels. Concurrent with those changes, an increased TBARS level was observed. This oxidative stress was related to a decrease in superoxide dismutase (SOD) and glutathione (GSH) levels of alloxan diabetic rats. Intake of parsley extract after diabetes ameliorated hyperglycemia, AST, ALT, body weight, total protein insulin and lipid profiles, and blunted the increase in TBARS and modulated the levels of SOD, CAT and GSH of alloxan treated rats. It could be concluded that parsley extract has a protective effect against hepatotoxicity caused by diabetes

Effect of irradiation on the periodontal tissues in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Park, Dong Sin; Hwang, Eui Hwan; Lee, Sang Rae

2005-01-01

To observe the histopathological changes in the periodontal tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups; control, diabetes, irradiation, and diabetes - irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes - irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, osteoclastic activity was observed in the alveolar bone and the root throughout the period of experiment. Also, osteoblastic and fibroblastic activities were markedly decreased. In the irradiation group, the osteoclasts were observed in the alveolar bone and the dilated capillaries were increased in the early experimental phases. However, vigorous osteoblastic activity was noted in the late experimental phases. In the diabetes- irradiation group, osteoblastic activity in the alveolar bone and the root was observed in the early experimental phases. However, there were no resorption and osteoblastic activity in the alveolar bone and the root in the late experimental phases, and obvious atrophic change of fibrous tissues was noted. This experiment suggests that osteoblastic activity was caused by irradiation in the late experimental phases, but atrophic change of the periodontal ligament tissues was induced after irradiation in diabetic state.

Ultrastructural evaluation of the effects of cinnamon on the nervus ischiadicus in diabetic rats

International Nuclear Information System (INIS)

Bahceci, Selen; Akkus, Murat; Aluclu, Mehmet U; Canoruc, Naime; Bahceci, Mithat; Gokalp, Deniz; Baran, Sedat; Akbalik, Mehmet E

2009-01-01

To investigate the effects of oral cinnamon supplementation on the nervus ischiadicus at the electron microscopical level in rats. This study was performed between 2004-2006 in Dicle University School of Medicine, Diyarbakir, Turkey in 15 adult Sprague-Dawley rats. Rats were divided into 3 groups; control (C) (n=5), diabetic without cinnamon (D) (n=5), and diabetic with cinnamon (D-C) (n=5). Diabetes was induced with intraperitoneal alloxan administration. All diabetic rats were treated with human insulin. All rats were fed with standard pellet chow. The D-C group rats were fed with standard pellet chow plus Cinnamomum cassia at the dose of 400mg/kg. All rats were sacrificed after 3 months and we obtained the nervus ischiadicus of all rats. Contrast stained thin sections evaluated by Jeol-TEM-1010 electron microscope, were not statistically different in both groups and photo samples were obtained. Mean blood glucose, hemoglobin A1C, and lipid profile were not statistically different in both groups. Marked detachment of myelin lamellae at Schmidt-Lanterman clefts, lysis in cristae mitochondrialis and degenerative changes, severe dispersion of organelles in neurolemma, mesoaxon region, and remarkable edema at the endoneurium were found in diabetic rats. On the contrary, mesoaxon, nucleus, nucleolus and myelin sheet were almost of normal appearance at the ultra-structural level in the D-C group. Cinnamon extracts may have beneficial effects on the development of diabetic neuropathy in alloxan induced diabetic rats. (author)

Glucose production and storage in hepatocytes isolated from normal versus diabetic rats

International Nuclear Information System (INIS)

Olivieri, M.C.; Dragland-Meserve, C.J.; Parker Botelho, L.H.

1987-01-01

The rates of glucose production and storage were compared in hepatocytes isolated from normal versus insulin-resistant diabetic rats. A single low-dose (40 mg/kg) IV injection of streptozotocin to 250 g rats resulted in a Type II diabetic animal model which was hyperglycemic with normal insulin levels. Addition of 8 mM 14 C-lactate and 2 mM pyruvate to hepatocytes resulted in a linear increase in total glucose production ( 14 C-glucose and unlabeled glucose) and incorporation into glycogen measured over 120 min. The rate of gluconeogenesis was estimated from the production of 14 C-glucose and the rate of glycogenolysis was estimated from the production of unlabeled glucose in cells incubated in the presence or absence of 14 C-labelled substrate. There was not significant difference in total glucose production in hepatocytes isolated from normal versus diabetic rats, however, the contribution from gluconeogenesis versus glycogenolysis was significantly different. Following a 1 h incubation of cells from normal rats, 42% of the total glucose production was due to gluconeogenesis and 58% was due to glycogenolysis. In cells from diabetic rats, 83% of total glucose production was from gluconeogenesis and 17% from glycogenolysis. Also, incubation with 14 C-lactate/pyruvate resulted in a 3.3-fold increase in 14 C-glucose incorporation into glycogen in hepatocytes isolated from normal rats compared to diabetic rats. These data suggest that alterations occur in the rate-limiting enzymes responsible for glucose production and storage in hepatocytes isolated from a rat model of insulin-resistant Type II diabetes

Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

DEFF Research Database (Denmark)

Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

2009-01-01

(Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative...... was downregulated in hearts from ZDF rats at both the mRNA and protein levels (P diabetic hearts (P obese diabetic rats have......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...

"Healing Effect of Topical Nifedipine on Skin Wounds of Diabetic Rats "

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Abbas Ebadi

2003-07-01

Full Text Available Non-healing foot ulcers in patients with diabetes are the leading causes of complications such as infection and amputation. Ulceration is the most common single precursor to amputation and has been identified as a causative factor in 85% of lower extremity amputations. It seems that poor outcomes are generally associated with infection, peripheral vascular disease and wounds of increasing depth. Nifedipine, a calcium channel blocker that is mainly used for the treatment of cardiovascular disorders has recently been used to treat wounds caused by peripheral vascular disorders. In present study topical Nifedipine 3% has been used to treat skin wounds in normal and diabetic rats. Effects of Nifedipine were evaluated in three different phases of wound healing process. In both experiments (normal and diabetic rats topical Nifedipine significantly improved inflammatory phase. However, maturation phase was only significantly improved in diabetic rats. Nifedipine did not affect proliferation phase in either group significantly. Overall results of this study showed topical Nifedipine improved skin wound healing process in normal and diabetic rats.

Detrended fluctuation analysis of compound action potentials re-corded in the cutaneous nerves of diabetic rats

International Nuclear Information System (INIS)

Quiroz-González, Salvador; Rodríguez-Torres, Erika Elizabeth; Segura-Alegría, Bertha; Pereira-Venegas, Javier; Lopez-Gomez, Rosa Estela; Jiménez-Estrada, Ismael

2016-01-01

Highlights: • Fractal analysis of compound action potentials (CAP) evoked in diabetic nerves. • Diabetic rats showed an increment in the chaotic behavior of CAP responses. • Diabetes provokes impaired transmission of sensory information in rats. - Abstract: The electrophysiological alterations in nerves due to diabetes are classically studied in relation to their instantaneous frequency, conduction velocity and amplitude. However, analysis of amplitude variability may reflect the occurrence of feedback loop mechanisms that adjust the output as a function of its previous activity could indicate fractal dynamics. We assume that a peripheral neuropathy, such as that evoked by diabetes, the inability to maintain a steady flow of sensory information is reflected as a breakdown of the long range power-law correlation of CAP area fluctuation from cutaneous nerves. To test this, we first explored in normal rats whether fluctuations in the trial-to-trial CAP area showed a self-similar behavior or fractal structure by means of detrended fluctuations analysis (DFA), and Poincare plots. In addition, we determine whether such CAP fluctuations varied by diabetes induction. Results showed that CAP area fluctuation of SU nerves evoked in normal rats present a long term correlation and self-similar organization (fractal behavior) from trial to trial stimulation as evidenced by DFA of CAP areas. However, CAPs recorded in diabetic nerves exhibited significant reductions in area, larger duration and increased area variability and different Poincare plots than control nerves. The Hurst exponent value determined with the DFA method from a series of 2000 CAPs evoked in diabetic SU nerves was smaller than in control nerves. It is proposed that in cutaneous nerves of normal rats variability of the CAP area present a long term correlation and self-similar organization (fractal behavior), and reflect the ability to maintain a steady flow of sensory information through cutaneous nerves

DNA protective effects of melatonin on oxidative stress in streptozotocin - induced diabetic rats.

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Selim Sekkin

2015-05-01

the antioxidant system, MEL regulates the expression of several genes such as those of superoxide dismutase (SOD and glutathione peroxidase (2-4. The aim of this study was to research the effects of MEL on oxidative stress and DNA protective effects in streptozotocin-induced diabetic rats. A total of 32 rats were equally divided into 4 experimental groups as Control, Melatonin, Diabetic, and Diabetic + Melatonin. A pancreatic beta-cell cytotoxic agent, single dose streptozotocin (60 mg/kg was given by intraperitoneal route to induce experimental diabetes in rats. Rats with ≥200mg/dL blood glucose level were established as Diabetic and Diabetic + Melatonin groups. MEL (10 mg/kg per day and sodium citrate solution were administrated to rats by intraperitoneal route for 6 weeks. With the termination of the experiment, tissue and blood samples were obtained for further analysis. SOD, catalase (CAT, reduced glutathione (GSH and malondialdehyde (MDA were evaluated in rat liver, renal, brain and pancreas tissues. Body weight, plasma glucose, and %HbA1c levels were studied. DNA damage was analyzed with the comet assay in rat lymphocytes; %Tail DNA and Mean Tail Moment parameters were evaluated (5. Antioxidant and oxidant enzyme levels were similar in the Control and Melatonin groups, although there were significant differences between the Diabetic and Diabetic + Melatonin groups. SOD levels in brain and liver tissues were higher (P<0,001, and CAT activities in renal tissue (P<0,001, GSH levels in pancreas tissue (P<0,01 as well as MDA levels in liver (P<0,001, renal (P<0,001 and brain (P<0,01 tissues were higher in the Diabetic + Melatonin group compared with the Diabetic group. Body weight changes and blood glucose levels of the rats were evaluated during the 6 weeks. The effect of MEL on the body weights of Control and Melatonin as well as Diabetic and Diabetic + Melatonin group rats were similar. MEL had no effect on body weight and the diabetic rats were lighter (P<0

Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study.

Science.gov (United States)

Bolkent, S; Yanardag, R; Ozsoy-Sacan, O; Karabulut-Bulan, O

2004-12-01

Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats. 2004 John Wiley & Sons, Ltd.

The Beneficial Effect of Fesoterodine, a Competitive Muscarinic Receptor Antagonist on Erectile Dysfunction in Streptozotocin-induced Diabetic Rats.

Science.gov (United States)

Yilmaz-Oral, Didem; Bayatli, Nur; Gur, Serap

2017-09-01

To investigate the possible role of fesoterodine (a competitive muscarinic receptor antagonist) on erectile dysfunction in streptozotocin-induced diabetic rats. A total of 16 adult male Sprague-Dawley rats were equally divided into control and diabetic groups. Diabetes was induced by a single intravenous injection of streptozotocin (25-35 mg/kg). In vivo erectile responses were evaluated by the stimulation of cavernosal nerves, and measurements were repeated after the intracavernosal injection of fesoterodine (1 µM) in rats. The relaxation responses to fesoterodine were examined via incubation with various inhibitors. The relaxant responses of corpus cavernosum (CC) strips were observed in the presence or the absence of fesoterodine (10 µM). Intracavernous administration of fesoterodine restored in vivo erectile response at 5.0- and 7.5-V levels, except for 2.5 V in diabetic rats. Basal intracavernosal pressure (5.4 ± 0.9 mm Hg) in diabetic rats was markedly increased after injection of fesoterodine (33.9 ± 7.9 mm Hg, P <.001). In bath studies, fesoterodine resulted in a relaxation of CC in a concentration-dependent manner, which was reduced in diabetic rats. Nifedipine (l-type Ca 2+ channel blocker) inhibited maximum fesoterodine-induced relaxation by 58%. The nonselective K + channel blocker tetraethylammonium and glibenclamide incubation did not change the relaxant response to fesoterodine. The relaxant responses to acetylcholine (10 µM), electrical field stimulation (10 Hz), and sodium nitroprusside (0.01 µM) in diabetic rats were increased after incubation with fesoterodine (10 µM). Fesoterodine improved erectile function and relaxation of isolated strips of rat CC. The underlying mechanism of fesoterodine is likely due to the blocking of l-type calcium channels independent of the nitric oxide-cyclic guanosine monophosphate pathway. Further investigations are warranted to fully elucidate the restorative effects of

Genetic control of differential acetylation in diabetic rats.

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Pamela J Kaisaki

Full Text Available Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rats compared to normoglycemic Brown Norway (BN rats. We show first that a promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then use mass-spectrometry to identify proteome-wide differential lysine acetylation of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include many proteins in pathways connected to diabetes and metabolic syndrome. We finally sequence GK and BN liver transcriptomes and find that mRNA expression of these targets does not differ significantly between GK and BN rats, in contrast to other components of the same pathways. We conclude that physiological differences between GK and BN rats are mediated by a combination of differential protein acetylation and gene transcription and that genetic variation can modulate acetylation independently of expression.

Anti-hyperlipidemic action of Zingiber officinale (Ginger juice in alloxan induced diabetic rats

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Selima Sultana

2012-07-01

Full Text Available Abstract Hyperlipidemia is an important modifiable risk factor contributing to atterosclerosis in diabetes mellitus. Zingiber officinale (ginger widely consumed as spice is known for its hypoglycemic and hypochlosteremic actions. The present study was undertaken to investigate anti-hyperlipidemic action of ginger juice in alloxan-induced diabetic rats. Male Wister rats, 130-150 g wt, fed on standard diet and water ad libitum were divided into 4 groups (n=6 in each group: group I non-diabetic control, group II non-diabetic treated; group III diabetic control and group IV diabetic treated. Diabetes was induced by Inj. alloxan 150 mg Kg–1 b.w., i.p. (group III & IV on Day 2. Rats having blood glucose level of >7 mmol/l on day 5 (72 hrs after alloxan Inj. were considered diabetic and selected for experimentation. Both non-diabetic and diabetic treated groups (Gr II & IV received Zingiber officinale (ginger juice (4 ml Kg–1 b.w., p.o. for 10 days (day 2-day 11 through Ryles tube. On Day 12, animals were sacrificed under light ether anaesthesia, blood was collected by cardiac puncture and serum separated for estimation of lipids. Zingiber officinale (ginger juice significantly (p<0.01 decreased alloxan induced hyperglycemia (group IV, but had no effect on blood glucose level in normal rats (group II; significantly (p<0.001 reduced alloxan induced hyperlipidemia, but produced no significant lipid lowering effects in normal rats (group II. The results suggest a significant anti-hyperlipidemic action of Zingiber officinale (ginger juice in alloxan induced diabetic rats. The findings may be clinically significant and exploited. Ibrahim Med. Coll. J. 2012; 6(2: 55-58

Protective and Therapeutic Role of Low Dose Gamma Radiation on Streptozotocin Induced Diabetes in Rats

International Nuclear Information System (INIS)

Mansour, H.H.; Hafez, H.F.; Shouman, S.A.

2011-01-01

Diabetes mellitus is a multi-factorial disease which is characterized by vascular and renal complication. This study was initiated to investigate the protective and the therapeutic effect of low dose of gamma radiation (LDR) on diabetic complications. A total of 30 adult male rats were divided into 5 groups: Group I: served as control and injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group II: rats became diabetic via intraperitoneal injection with 60 mg/kg streptozotocin (STZ) dissolved in 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group III irradiated rats (IRR): submitted to fractionated dose of whole body gamma rays; 0.25 Gy for 2 consecutive days (whole dose 0.5 Gy), group IV diabetic irradiated rats (STZ + IRR): rats became diabetic as group II then four weeks after diabetes induction (day 28), rats were submitted to 2 fractions of whole body gamma rays as in group III, and group V irradiated diabetic rats (IRR + STZ): rats were injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer then submitted to whole body gamma rays; 0.25 Gy for 2 consecutive days then one hour after the last IRR dose, rats were made diabetic as group II. In pre and post-irradiation of STZ rats, significant changes were observed in serum lipid profiles, hepatic and cardiac serum enzymes. Significant decrease in hepatic and cardiac malondialdehyde (MDA) and total nitrate/nitrite (NO(x)) levels, and significant increase in superoxide dismutase (SOD) and glutathione (GSH) levels were observed as compared to diabetic group. The study suggests that LDR may provide useful protective and therapeutic option in the reversal of oxidative stress induced in diabetic rats