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Sample records for diabetic rats functional

  1. Renal function in streptozotocin-diabetic rats

    DEFF Research Database (Denmark)

    Jensen, P K; Christiansen, J S; Steven, K

    1981-01-01

    Renal function was examined with micropuncture methods in the insulin-treated streptozotocin-diabetic rat. Kidney glomerular filtration rate was significantly higher in the diabetic rats (1.21 ml/min) than in the control group (0.84 ml/min) Nephron glomerular filtration rate increased in proportion...... to the rise in kidney glomerular filtration rate (diabetic rats: 37.0 nl/min; control rats: 27.9 nl/min). Likewise renal plasma flow was significantly higher in the diabetic rats (4.1 ml/min) than in the control group (3.0 ml/min). Glomerular capillary pressure was identical in both groups (56.0 and 56.0 mm......-1mmHg-1). Kidney weight was significantly higher in the diabetic rats (1.15 g; control rats: 0.96 g) while body weight was similar in both groups (diabetic rats: 232 g; control rats: 238 g). Calculations indicate that the increases in transglomerular hydraulic pressure, renal plasma flow...

  2. Diabetic rat testes: morphological and functional alterations.

    Science.gov (United States)

    Ricci, G; Catizone, A; Esposito, R; Pisanti, F A; Vietri, M T; Galdieri, M

    2009-12-01

    Reproductive dysfunction is a consequence of diabetes, but the underlying mechanisms are poorly understood. This study investigated the histological and molecular alterations in the testes of rats injected with streptozotocin at prepuperal (SPI rats) and adult age (SAI rats) to understand whether diabetes affects testicular tissue with different severity depending on the age in which this pathological condition starts. The testes of diabetic animals showed frequent abnormal histology, and seminiferous epithelium cytoarchitecture appeared altered as well as the occludin distribution pattern. The early occurrence of diabetes increased the percentage of animals with high number of damaged tubules. The interstitial compartment of the testes was clearly hypertrophic in several portions of the organs both in SPI and SAI rats. Interestingly, fully developed Leydig cells were present in all the treated animals although abnormally distributed. Besides the above-described damages, we found a similar decrease in plasma testosterone levels both in SPI and SAI rats. Oxidative stress (OS) is involved in the pathogenesis of various diabetic complications, and in our experimental models we found that manganese superoxide dismutase was reduced in diabetic animals. We conclude that in STZ-induced diabetes, the altered spermatogenesis, more severe in SPI animals, is possibly due to the effect of OS on Leydig cell function which could cause the testosterone decrease responsible for the alterations found in the seminiferous epithelium of diabetic animals.

  3. Effects of Duration of Diabetes on Cognitive Functions in Streptozotocin Induced Young Diabetic Rats

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    Rajashree R

    2012-07-01

    Full Text Available Background: Children with early onset Type I diabetes have been reported to show modest deficits on a wide range of neuropsychological tests. However, the contribution of duration of the disease with respect to cognitive dysfunction remains unresolved. The present study aims to determine the effects of different duration of hyperglycemia on cognitive function in young diabetic rats. Objectives: To determine the effect of 10 and 20 days duration of diabetes on cognitive functions. Materials and methods: Diabetes was induced in young rat pups, by streptozotocin injection (i.p at a dose of 50 mg /kg.BW. Diabetic state was confirmed on 30th post natal day. 10 and 20 days after inducing diabetes, the rats were tested in passive avoidance box and Morris water maze, over a period of 10 days. Results: Diabetic rats showed significantly impaired cognitive functions, compared to their age matched controls. The cognitive impairment was greater in rats with 20 days of diabetic state compared to their 10 days counterparts. Conclusion: It is essential to diagnose and treat diabetes as early as possible in case of young children with Type I diabetes of early onset to prevent irreversible cognitive functions

  4. Diaphragmatic function is enhanced in fatty and diabetic fatty rats

    Science.gov (United States)

    Carreira, Serge; Na, Na; Carillion, Aude; Jiang, Cheng; Beuvin, Maud; Lacorte, Jean-Marc; Bonnefont-Rousselot, Dominique; Riou, Bruno; Coirault, Catherine

    2017-01-01

    Background Obesity is associated with a decrease in mortality in the intensive care unit (ICU) (the "obesity paradox"). We hypothesized that obesity may paradoxically improve diaphragmatic function. Methods Diaphragm contractility was prospectively recorded in vitro in adult male Zucker lean (control), fatty, and diabetic fatty rats, at rest, after 12h mechanical ventilation and after fatigue. We analyzed diaphragm morphology, cytokines, and protein expression of the protein kinase signaling pathways. Results Diaphragm active-force (AF) was higher in fatty (96±7mN.mm-2,P = 0.02) but not in diabetic fatty rats (90±17mN.mm-2) when compared with controls (84±8mN.mm-2). Recovery from fatigue was improved in fatty and diabetic fatty groups compared with controls. Ventilator-induced diaphragmatic dysfunction was observed in each group, but AF remained higher in fatty (82±8mN.mm-2,P = 0.03) compared with controls (70±8mN.mm-2). There was neutral lipid droplet accumulation in fatty and diabetic fatty. There were shifts towards a higher cross-sectional-area (CSA) of myosin heavy chain isoforms (MyHC)-2A fibers in fatty and diabetic fatty compared with control rats (P = 0.002 and Pobese rats before and after mechanical ventilation, and is associated with activation of AKT pathway signaling and complex changes in morphology. PMID:28328996

  5. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

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    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R.; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨm), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress. PMID:26180820

  6. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    Science.gov (United States)

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  7. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Omar Ortiz-Avila

    2015-01-01

    Full Text Available Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats. Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential ΔΨm, besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  8. Regulative Function of Low Molecular Chitosan on Blood Sugar in Experimental Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    Hua-Bing YANG; Yong WU

    2005-01-01

    @@ 1 Introduction Chitosan has good action on reducing blood sugar with low poisonous side-effect. Low molecular chitosan(LMC) is the oxide of high molecular chitosan, which has water-solubility and the function of lowering blood sugar of diabetic rats. In this experiment, STZ was adopted to duplicate the model rats of Type Ⅱ diabetes mellitus, the regulative function of LMC on Type Ⅱ diabetic blood sugar was observed for further inquiry into its functionary mechanism.

  9. Acetylsalicylic acid protects erectile function in diabetic rats.

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

    2014-01-01

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

  10. Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocininduced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Lu-lu ZHANG; Guang-ji WANG; Lin XIE; Liang LU; Shi JIN; Xin-yue JING; Dan YAO; Nan HU; Li LIU; Ru DUAN; Xiao-dong LIU

    2011-01-01

    Aim: To investigate the changes of expression and function of P-glycoprotein (P-GP) in cerebral cortex, hippocampus, liver, intestinal mucosa and kidney of streptozocin-induced diabetic rats.Methods: Diabetic rats were prepared via a single dose of streptozocin (65 mg/kg, ip). Abcb1/P-GP mRNA and protein expression levels in tissues were evaluated using quantitative real time polymerase chain reaction (QRT-PCR) analysis and Western blot, respectively.P-GP function was investigated via measuring tissue-to-plasma concentration ratios and body fluid excretion percentages of rhodamine 123.Results: In 5- and 8-week diabetic rats, Abcb1a mRNA levels were significantly decreased in cerebral cortices and intestinal mucosa,but dramatically increased in hippocampus and kidney. In liver, the level was increased in 5-week diabetic rats, and decreased in 8-week diabetic rats. Abcb1b mRNA levels were increased in cerebral cortex, hippocampus and kidney, but reduced in liver and intestinal mucosa in the diabetic rats. Western blot results were in accordance with the alterations of Abcb1a mRNA levels in most tissues examined. P-GP activity was markedly decreased in most tissues of diabetic rats, except kidney tissues.Conclusion: Alterations in the expression and function of Abcb1/P-GP under diabetic conditions are tissue specific, Abcb1 specific and diabetic duration-dependent.

  11. Dietary resistant maltodextrin ameliorates testicular function and spermatogenesis in streptozotocin-nicotinamide-induced diabetic rats.

    Science.gov (United States)

    Liu, C-Y; Hsu, Y-J; Chien, Y-W E; Cha, T-L; Tsao, C-W

    2016-05-01

    This study investigated the effect of resistant maltodextrin (RMD) on reproduction in streptozotocin (STZ)-nicotinamide-induced type 2 diabetic male rats. Forty male rats were induced with diabetes by a single intraperitoneal injection of STZ (50 mg kg(-1)) and nicotinamide (100 mg kg(-1)). Five groups were analysed in total: normal, diabetic rats without RMD, diabetic rats with RMD 1.2 g per 100 g diet (1×), with RMD 2.4 g per 100 g (2×), and with RMD 6.0 g per 100 g (5×). The groups of diabetic rats with the RMD supplement, compared to those without supplement, showed improved plasma glucose control, attenuated insulin resistance and recovery of testosterone level and spermatogenesis stage. The STZ-nicotinamide-induced diabetes mellitus (DM) caused a significant reduction in serum testosterone, testis androgen receptor (AR), steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) protein, but a statistical recovery in each of these was observed in the 5× group. TUNEL-positive cells were observed in the diabetic without RMD group, and RMD treatment reduced apoptotic germ cells. The expression of Bax/Bcl2 was induced in the diabetic group and also significantly reduced in the 5× group. Dietary RMD may improve metabolic control in STZ-nicotinamide-induced diabetic rats and attenuate hyperglycaemia-related impaired male reproduction and testicular function.

  12. Effect of umbelliferone on tail tendon collagen and haemostatic function in streptozotocin-diabetic rats.

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    Ramesh, Balakrishnan; Pugalendi, Kodukkur Viswanathan

    2007-08-01

    Diabetes mellitus is known to affect collagen in various tissues. Umbelliferone (7-hydroxycoumarin), a natural antioxidant and benzopyrone, is found in golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). Plant-derived phenolic coumarins have been shown to act as dietary antioxidants. In this study, we have investigated the influence of umbelliferone on collagen content and its effects on the tail tendon in streptozotocin-diabetic rats. Male albino Wistar rats (180-200 g) were made diabetic by intraperitoneal administration of streptozotocin (40 mg/kg). Normal and diabetic rats were treated with umbelliferone for 45 days. Diabetic rats had increased glucose and decreased insulin levels. Tail tendons of diabetic rats had increased total collagen, glycation and fluorescence, and decreased levels of neutral, acid and pepsin-soluble collagens. We have studied the effect of umbelliferone on haemostatic function because umbelliferone is also a coumarin derivative like the anticoagulant, warfarin. Diabetic rats had a significant decrease in prothrombin, clotting and bleeding time, and treatment with umbelliferone made these parameters almost normal. Our results show that umbelliferone controls glycaemia and has a beneficial effect on collagen content and its properties, i.e. collagen related parameters, in the tail tendon, which indicates recovery from the risk (recovery of animals from the risk of complications) of collagen-mediated diabetic polyneuropathy and diabetic nephropathy.

  13. Influence of fluvastatin on cardiac function and baroreflex sensitivity in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Fang XIE; Chao SUN; Li-hua SUN; Jing-yuan LI; Xin CHEN; Hui CHE; Guan-yi LU; Bao-feng YANG; Jing AI

    2011-01-01

    Aim: To investigate whether fluvastatin is able to ameliorate the impaired cardiac function or baroreflex sensitivity (BRS) in rats with type 1 diabetes.Methods: Type 1 diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and then administered fluvastatin (1.5,cardiac function and BRS were measured in diabetic rats after fluvastatin treatment for 30 d.Results: The polydipsia, polyphagia and abnormal biochemical indexes of blood were significantly ameliorated by the the 3.0- and 6.0-mg doses of fluvastatin in STZ-induced diabetic rats. FBG was decreased in diabetic rats after fluvastatin treatment for 30 d. The left ventricular systolic pressure (LVSP) and the maximum rate of change of left ventricular pressure in the isovolumic contraction and relaxation period (±dp/dtmax) were elevated, and left ventricular diastolic pressure (LVEDP) was decreased by fluvastatin. The attenuated heart rate responses to arterial blood pressure (ABP) increase induced by phenylephrine (PE) and ABP decrease induced by sodium nitroprusside (SNP) were reversed by the 3.0-mg dose of fluvastatin.Conclusion: Fluvastatin regulates blood lipid levels and decreases the FBG level in diabetic rats. These responses can protect the diabetic heart from complications by improving cardiac function and BRS.

  14. FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE SPINAL CORD DURING SENSORY STIMULATION IN DIABETIC RATS

    Science.gov (United States)

    Malisza, Krisztina L.; Jones, Cheryl; Gruwel, Marco L.H.; Foreman, Derek; Fernyhough, Paul; Calcutt, Nigel A.

    2009-01-01

    Purpose To determine if differences exist between control and diabetic rats in functional MRI activity of the spinal cord and if fMRI can provide a means of early detection of diabetic neuropathy. Materials and Methods fMRI of the spinal cord, using noxious electrical stimulation (15 V (~8 mA), 0.3 ms, 3 Hz) of the hind paw, was performed in groups of control and streptozotocin (STZ)-induced type 1 diabetic rats. Results Diabetic rats were lighter, hyperglycemic and had lower blood pH than controls. FMRI activity at the lumbar enlargement of the spinal cord was identified in the dorsal horn ipsilateral to stimulus of all animals. Signal intensity changes across the lumbar spinal cord during periods of activity were not significantly different between control and diabetic rats, with a trend towards greater signal changes in controls. When specific regions of the spinal cord were analyzed, control rats exhibited significantly increased BOLD fMRI activity in both ipsilateral and contralateral dorsal horn compared to diabetic rats. Conclusion The results of this study are consistent with reports that primary afferent input to the spinal cord is diminished by diabetes, and suggest that BOLD fMRI may be useful in early detection of diabetic neuropathy. PMID:19629995

  15. Regulative Function of Low Molecular Chitosan on Blood Sugar in Experimental Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionChitosan has good action on reducing blood sugar with low poisonous side-effect. Low molecular chitosan(LMC) is the oxide of high molecular chitosan, which has water-solubility and the function of lowering blood sugar of diabetic rats.In this experiment, STZ was adopted to duplicate the model rats of Type Ⅱ diabetes mellitus, the regulative function of LMC on Type Ⅱ diabetic blood sugar was observed for further inquiry into its functionary mechanism.2 Materials and Methods2.1 Animals Normal ma...

  16. Protocatechuic acid protects brain mitochondrial function in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Semaming, Yoswaris; Sripetchwandee, Jirapas; Sa-Nguanmoo, Piangkwan; Pintana, Hiranya; Pannangpetch, Patchareewan; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2015-10-01

    Brain mitochondrial dysfunction has been demonstrated in diabetic animals with neurodegeneration. Protocatechuic acid (PCA), a major metabolite of anthocyanin, has been shown to exert glycemic control and oxidative stress reduction in the heart. However, its effects on oxidative stress and mitochondrial function in the brain under diabetic condition have never been investigated. We found that PCA exerted glycemic control, attenuates brain mitochondrial dysfunction, and contributes to the prevention of brain oxidative stress in diabetic rats.

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

    NARCIS (Netherlands)

    Gispen, W.H.; Dam, P.S. van; Bravenboer, B.; Asbeck, B.S. van; Marx, J.J.

    1999-01-01

    Antioxidants can improve nerve dysfunction in hyperglycaemic rats. We evaluated whether the standard supplementation of rat food with vitamin E (normally added for preservation purposes) or high-dose vitamin E treatment improves nerve conduction in maturing streptozotocin-diabetic rats, a model

  18. Vascular filtration function in galactose-fed versus diabetic rats: The role of polyol pathway activity

    Energy Technology Data Exchange (ETDEWEB)

    Pugliese, G.; Tilton, R.G.; Speedy, A.; Chang, K.; Province, M.A.; Kilo, C.; Williamson, J.R. (Washington Univ. School of Medicine, St Louis, MO (USA))

    1990-07-01

    These studies were undertaken to assess the effects of increased galactose (v increased glucose) metabolism via the polyol pathway on vascular filtration function in the kidneys, eyes, nerves, and aorta. Quantitative radiolabeled tracer techniques were used to assess glomerular filtration rate (GFR) and regional tissue vascular clearance of plasma 131I-bovine serum albumin (BSA) in five groups of male Sprague-Dawley rats: nondiabetic controls, streptozotocin-diabetic rats, nondiabetic rats fed a 50% galactose diet, diabetic rats treated with sorbinil (an aldose reductase inhibitor), and galactose-fed rats treated with sorbinil. Sorbinil was added to the diet to provide a daily dose of approximately .2 mmol/kg body weight. After 2 months of diabetes or galactose ingestion, albumin clearance was increased twofold to fourfold in the eye (anterior uvea, choroid, and retina), sciatic nerve, aorta, and kidney; GFR was increased approximately twofold and urinary excretion of endogenous albumin and IgG were increased approximately 10-fold. Sorbinil treatment markedly reduced or completely prevented all of these changes in galactose-fed, as well as in diabetic rats. These observations support the hypothesis that increased metabolism of glucose via the sorbitol pathway is of central importance in mediating virtually all of the early changes in vascular filtration function associated with diabetes in the kidney, as well as in the eyes, nerves, and aorta. On the other hand, renal hypertrophy in diabetic rats and polyuria, hyperphagia, and impaired weight gain in galactose-fed and in diabetic rats were unaffected by sorbinil and therefore are unlikely to be mediated by increased polyol metabolism.

  19. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

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    Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos [Departamento de Fisiologia - Universidade Federal de Sergipe (UFS), São Cristóvão, SE (Brazil); Oliveira, Antônio Cesar Cabral de; Wichi, Rogério Brandão [Departamento de Educação Física - UFS, São Cristóvão, SE (Brazil); Santos, Márcio Roberto Viana, E-mail: marciorvsantos@bol.com.br [Departamento de Fisiologia - Universidade Federal de Sergipe (UFS), São Cristóvão, SE (Brazil)

    2014-07-15

    Resistance exercise effects on cardiovascular parameters are not consistent. The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

  20. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Marcelo Mendonça Mota

    2014-07-01

    Full Text Available Background: Resistance exercise effects on cardiovascular parameters are not consistent. Objectives: The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Methods: Wistar rats were divided into three groups: control group (n = 8; sedentary diabetic (n = 8; and trained diabetic (n = 8. Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. Results: A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2% and an increase in the trained diabetic group (95 ± 3% without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05 in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05 in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg as compared to the sedentary diabetic group. Conclusions: Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

  1. THE EFFECTS OF REGULAR AEROBIC EXERCISE ON RENAL FUNCTIONS IN STREPTOZOTOCIN INDUCED DIABETIC RATS

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    Hatice Kurdak

    2010-06-01

    Full Text Available Diabetic nephropathy is a feared complication of diabetes since it can lead to end-stage renal failure and also it is a risk factor of cardiovascular disease. The important clinical problems caused by diabetic nephropathy are proteinuria and decreased renal function. Exercise is a cornerstone of diabetes management, along with diet and medication. Since acute exercise causes proteinuria and decreases glomerular filtration rate, the effect of exercise on diabetic nephropathy is controversial. The aim of this study was to investigate the effect of regular aerobic exercise on microalbuminuria and glomerular filtration rate in diabetic rats. Moderate diabetes was induced by streptozotocin (45 mg/kg IV in rats and an aerobic exercise- training program on a treadmill was carried out for 8 weeks. Four groups of rats; control sedentary (CS, control exercise (CE, diabetic sedentary (DS and diabetic exercise (DE were included in the study. Blood glucose levels were determined from the plasma samples taken at the end of 4 weeks of stabilization period and 8 weeks of training program. Creatinine clearance (CCr and microalbuminuria (MA levels were determined to evaluate renal functions. The analyzed data revealed that regular aerobic exercise: 1 significantly decreased the plasma glucose level of the DE group compared to the DS group (p < 0.05, 2 significantly decreased the microalbuminuria level of the DE group compared to those of DS group (p < 0.01, 3 significantly decreased the creatinine clearance levels of the DE and CE groups compared to those of CS group (p < 0.05. The results of this study suggest that despite of decreasing creatinine clearance, regular submaximal aerobic exercise has a preventive effect on development of microalbuminuria and thus may retard nephropathy in diabetic rats

  2. Antioxidant and androgenic effects of dietary ginger on reproductive function of male diabetic rats.

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    Ghlissi, Zohra; Atheymen, Rim; Boujbiha, Mouhamed Ali; Sahnoun, Zouheir; Makni Ayedi, Fatma; Zeghal, Khaled; El Feki, Abdelfattah; Hakim, Ahmed

    2013-12-01

    This study evaluated the antioxidant and androgenic properties of ginger roots on the reproductive function of male diabetic rats. Animals were divided into three groups; the control (Control), diabetic (Diab) and diabetic fed with dietary ginger for 30 d (Diab + Z). Thereafter, blood samples were collected and reproductive organs (testis, epididymis, prostate and seminal vesicle) were removed for determination of sperm parameters, malondialdehyde (MDA) level, glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and aspartate and lactate aminotransferase (AST and ALT) activities. Dietary ginger decreased blood glucose and MDA level, increased reproductive organ weights and testosterone level, improved semen quantity and motility, and ameliorated the SOD, CAT and GPx activities as well as testis AST, ALT, LDH and ALP activities. Intake of ginger roots improves the antioxidant and androgenic reproductive function of male diabetic rats in addition to its antidiabetic property.

  3. Administration of sesamol improved blood-brain barrier function in streptozotocin-induced diabetic rats.

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    VanGilder, R L; Kelly, K A; Chua, M D; Ptachcinski, R L; Huber, Jason D

    2009-07-01

    Uncontrolled or poorly controlled blood glucose during diabetes is an important factor in worsened vascular function. While evidence suggests that hyperglycemia-induced oxidative stress plays a prominent role in development of microangiopathy of the retina, kidney, and nerves, the role oxidative stress plays on blood-brain barrier (BBB) function and structure has lagged behind. In this study, a natural antioxidant, sesamol, was administered to streptozotocin (STZ)-induced diabetic rats to examine the role that oxidative stress plays on BBB structure and function. Experiments were conducted at 56 days after STZ injection. Male Sprague-Dawley rats randomly were divided into four treatment groups CON--control; STZ--STZ-induced diabetes; CON + S--control + sesamol; STZ + S--STZ-induced diabetes + sesamol. Functional and structural changes to the BBB were measured by in situ brain perfusion and western blot analysis of changes in tight junction protein expression. Oxidative stress markers were visualized by fluorescent confocal microscopy and assayed by spectrophotometric analysis. Results demonstrated that the increased BBB permeability observed in STZ-induced diabetic rats was attenuated in STZ + S rats to levels observed in CON. Sesamol treatment reduced the negative impact of STZ-induced diabetes on tight junction protein expression in isolated cerebral microvessels. Oxidative stress markers were elevated in STZ as compared to CON. STZ + S displayed an improved antioxidant capacity which led to a reduced expression of superoxide and peroxynitrite and reduced lipid peroxidation. In conclusion, this study showed that sesamol treatment enhanced antioxidant capacity of the diabetic brain and led to decreased perturbation of hyperglycemia-induced changes in BBB structure and function.

  4. Shen Wu capsule affects the cognitive function and apoptosis protein in the ischemic-diabetic compound model rats

    Institute of Scientific and Technical Information of China (English)

    Chenlian-zhen; Lilin; Anwen-lin; Zhangli; Chujin

    2004-01-01

    Aim: To explore the mechanism of diabetes mellitus eneephalopathy and the effect of cognitive function of Chinese patent medicine Shen Wu capsule and intervention to apoptosis in the ischemic diabetic compound model rats. Methods:The compound model of Wistar rats was duplicated with streptozotocin (STZ) (60mg/kg) once intraperitoneally and transient

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

    Science.gov (United States)

    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.

  6. The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

    Science.gov (United States)

    Jahn, Matheus Parmegiani; Gomes, Luana Ferreira; Jacob, Maria Helena Vianna Metello; da Rocha Janner, Daiane; Araújo, Alex Sander da Rosa; Belló-Klein, Adriane; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos

    2011-05-01

    Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β(1) (TGF-β(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Aortic depressor nerve function examined in diabetic rats by means of two different approaches.

    Science.gov (United States)

    do Carmo, Jussara M; Huber, Domitila A; Castania, Jaci A; Fazan, Valéria P S; Fazan, Rubens; Salgado, Helio C

    2007-03-30

    The present study examined in anesthetized rats, 5 or 120 days after the onset of streptozotocin-induced diabetes, the aortic depressor nerve (ADN) function by means of pressure-nerve activity curve (fitted by sigmoidal regression) and cross-spectral analysis between mean arterial pressure (MAP) and ADN activity. From the sigmoidal regression curve it was calculated the upper and lower ADN activity plateau, range, average gain and MAP halfway between the lower and upper plateau (MAP50). By means of spectral analysis it was calculated the transfer function magnitude (ratio of ADN activity/MAP) as an index of ADN sensitivity (gain) during induced (withdrawal and reinfusion of blood) slow (0.35 Hz) oscillations of MAP simulating Mayer's waves and spontaneous oscillations (approximately 1.5 Hz) caused by respiratory movement. Diabetic rats exhibited, at 5 or 120 days, lower MAP and heart rate. The parameters calculated by means of the sigmoidal regression curve, as well as the ADN activity gain during slow or spontaneous oscillations of MAP, were similar in diabetic and control rats. In conclusion, it was demonstrated that ADN activity was not altered after 5 or 120 days of experimental diabetes, even though the literature documents, at this time frame of diabetes, a conspicuous derangement of the baroreflex.

  8. The Effects of Ivabradine on Cardiac Function after Myocardial Infarction are Weaker in Diabetic Rats

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    Xue Cao

    2016-10-01

    Full Text Available Background/Aims: Plasma norepinephrine (NE and brain natriuretic peptide (BNP, termed BNP-45 in rats are considered as essential neurohormones indicating heart failure progression. The purposes of this study were to examine the effects of ivabradine (IBD on cardiac function and plasma NE and BNP-45 after chronic ischemic heart failure (CHF in non-diabetic rats and diabetic rats. We further determined if sympathetic NE uptake-1 (a major pathway to metabolize NE mechanism is responsible for the role played by IBD. Methods: We ligated rat's coronary artery to induce CHF; and injected streptozotocin (STZ to induce diabetic hyperglycemia. Echocardiography was employed to determine cardiac function. We used ELISA to examine plasma NE and BNP-45; and Western Blot analysis to examine the protein levels of NE uptake-1 in sympathetic nerves. Results: CHF increased the levels of NE and BNP-45 in non-STZ rats and STZ rats. Systemic injection of IBD significantly attenuated the augmented NE and BNP-45 and impaired left ventricular function induced by CHF in those rats. This effect appeared to be less in STZ rats. A liner relation was observed between the NE/BNP-45 levels and left ventricular function after administration of IBD. Also, IBD was observed to have a recovery effect on the downregulated NE uptake-1 evoked by CHF, but to a smaller degree in STZ rats. Conclusion: Our data revealed specific signaling mechanisms by which IBD improves the cardiac function as IBD alleviates impaired NE uptake-1and thereby decreases heightened NE and BNP-45 induced by CHF. Our data also demonstrated that the effects of IBD are weakened after diabetic hyperglycemia likely due to worsen NE uptake-1 pathway. Thus, targeting sympathetic NE uptake-1 signaling molecules has clinical implications for treatment and management of CHF in diabetes. Our data were also to shed light on strategies for application of this drug because NE and BNP play an important role in regulation of

  9. Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats.

    Science.gov (United States)

    Jimenéz-Aranda, Aroa; Fernández-Vázquez, Gumersindo; Mohammad A-Serrano, María; Reiter, Russel J; Agil, Ahmad

    2014-08-01

    Mitochondrial dysfunction in adipose tissue may contribute to obesity-related metabolic derangements such as type 2 diabetes mellitus (T2DM). Because mitochondria are a target for melatonin action, the goal of this study was to investigate the effects of melatonin on mitochondrial function in white (WAT) and beige inguinal adipose tissue of Zücker diabetic fatty (ZDF) rats, a model of obesity-related T2DM. In this experimental model, melatonin reduces obesity and improves the metabolic profile. At 6 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control (C-ZDF and C-ZL) and treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk (M-ZDF and M-ZL). After the treatment period, animals were sacrificed, tissues dissected, and mitochondrial function assessed in isolated organelles. Melatonin increased the respiratory control ratio (RCR) in mitochondria from white fat of both lean (by 26.5%, P types of fat, white and beige, in both lean and obese rats. These results demonstrate that chronic oral melatonin improves mitochondrial respiration and reduces the oxidative status and susceptibility to apoptosis in white and beige adipocytes. These melatonin effects help to prevent mitochondrial dysfunction and thereby to improve obesity-related metabolic disorders such as diabetes and dyslipidemia of ZDF rats.

  10. Effects of Short-term Renovascular Hypertension and Type 2 Diabetes on Cardiac Functions in Rats

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    Ali Akbar Nekooeian

    2014-01-01

    Full Text Available Background: The cardiac effects simultaneously occurring during experimental hypertension and diabetes have rarely been investigated. This study aimed at examining the effects of short-term renovascular hypertension and type 2 diabetes on cardiac functions. Methods: Five groups (7 each of male Sprague-Dawley rats, including a control group, a diabetes (induced by Streptozocin and Nicotinamide group, a renovascular hypertensive (induced by placing Plexiglas clips on the left renal arteries group, a sham group, and a simultaneously hypertensive-diabetic group, were used. The animals’ hearts were used for isolated heart studies, and the indices of cardiac functions and coronary effluent creatine kinase MB were measured. The results were analyzed using One-way Analysis of Variance, followed by the Duncan Multiple Range test. Results: The diabetic group had a significantly lower rate of rise (-29.5% and decrease (-36.18% in ventricular pressure, left ventricular developed pressure (-28.8%, and rate pressure product (-35%, and significantly higher creatine kinase MB (+166% and infarct size (+36.2% than those of the control group. The hypertensive group had a significantly higher rate of rise (+12.17% and decrease (+16.2% in ventricular pressure, left ventricular developed pressure (+16%, and rate pressure product (+24%, and significantly lower creatine kinase MB (-30% and infarct size (-27% than those of the sham group. Simultaneously, the diabetic and hypertensive rats had a significantly higher rate of rise (+32% and decrease (+30.2% in ventricular pressure, left ventricular developed pressure (+17.2%, and rate pressure product (+22.2%, and significantly lower creatine kinase MB (-24% and infarct size (-16.2% than those of the diabetic group. Conclusion: The findings indicated that the simultaneity of hypertension with type 2 diabetes attenuated diabetes-induced cardiac impairment.

  11. Galanin-like peptide rescues reproductive function in the diabetic rat.

    Science.gov (United States)

    Stoyanovitch, Angela G; Johnson, Marlie A; Clifton, Donald K; Steiner, Robert A; Fraley, Gregory S

    2005-08-01

    Galanin-like peptide (GALP) is expressed in the hypothalamic arcuate nucleus and is regulated by leptin and insulin. Centrally administered GALP stimulates gonadotropin secretion and sexual behavior in the rat. Type 1 diabetes is associated with reduced expression of GALP, as well as an overall decline in reproductive function. We postulated that tonic activity of GALP in the brain is required to sustain normal reproductive activity. To test this hypothesis, we examined whether central (intracerebroventricular) immunoblockade of GALP would reduce sexual behaviors and serum levels of luteinizing hormone (LH) in normal adult male rats. We found that GALP antibody reversibly reduced serum levels of LH and abolished male sexual behaviors (P < 0.05 and 0.001, respectively). Second, we tested whether intracerebroventricular GALP could restore normal plasma LH levels and sexual behavior in diabetic animals. We compared groups of diabetic rats that received intracerebroventricular GALP or vehicle and found that GALP increased serum levels of LH and sexual behavior. Third, we examined whether intracerebroventricular administration of affinity-purified GALP antibody could block the effect of insulin and leptin in reversing the effects of diabetes on LH and sexual behavior. We found that treatment of diabetic animals with insulin and leptin nearly normalized LH levels and sexual behaviors; however, this effect was attenuated by intracerebroventricular administration of GALP antibody (P < 0.05). These observations demonstrate that endogenous GALP provides trophic support to the neuroendocrine reproductive axis, including sexual behavior.

  12. TYPE 1 DIABETES AND ITS LONG DURATION EFFECT ON COGNITIVE FUNCTIONS: AN ASSESSMENT IN ALLOXAN INDUCED DIABETIC RATS

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    Mahaboob Basha P

    2013-10-01

    Full Text Available Despite the enormous research in the field of Diabetology, its prevalence and complications are raising. Studies made on diabetic subjects showed deficits in cognition and memory in children suffering from long term diabetes. The relationship between cognitive dysfunction and type-1 diabetes of early onset has not been addressed properly. Hence, this study was made to investigate the effect of different duration diabetes onset on cognitive dysfunction. Using alloxan (200 mg/kg bw induced diabetic rats learning and memory assessments were made, in addition oxidative stress indices studied. The results indicate that the duration of diabetes has significant contribution in learning and memory deficits, which were irreversible and the activity levels of CAT (P < 0.05, SOD, GST (P < 0.05, and GPx (P < 0.05 showed greater impact of free radical damage on hippocampal circuitry. The atrophic changes observed in hippocampal region corroborates the difficulties in learning and memory, and the degenerative changes were most striking in the cells of CA-1 and CA-3 hippocampal regions which could be linked to deficits in certain cognitive domains, such as memory, information processing speed, executive function, attention and motor speed. It is evident from data that brain tissue is not spared by diabetes and diabetic encephalopathy occurs due to metabolic perturbations by hyperglycaemia, insulin deficiency. The findings of this study strongly advocate that learning ability and memory have a direct relation to the duration of the diabetes. The clinical implication of the study highlights the importance of early diagnosis and treatment of juvenile diabetes induced cognitive deficits among children.

  13. Liver function of Streptozotocin- Induced Diabetic Rats Orally ...

    African Journals Online (AJOL)

    phytochemicals (especially saponins), carbohydrate and food energy ... The role of the liver in metabolism, including detoxification ... in lipid metabolism and increased gluconeogenesis and ..... Hypoglycemic Activities in Rats and Rabbits.

  14. Cardiac and Renal Function are Progressively Impaired with Aging in Zucker Diabetic Fatty Type II Diabetic Rats

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    John Baynes

    2009-01-01

    Full Text Available This study investigated the temporal relationship between cardiomyopathy and renal pathology in the type II diabetic Zucker diabetic fatty (ZDF rat. We hypothesized that changes in renal function will precede the development of cardiac dysfunction in the ZDF rat. Animals (10 weeks old were divided into four experimental groups: Lean Control (fa/? LC (n = 7, untreated ZDF rats (n = 7 sacrificed at 16 weeks of age, and LC (n = 7 untreated ZDF rats (n = 9 sacrificed at 36 weeks of age. LV structural/functional parameters were assessed via Millar conductance catheter. Renal function was evaluated via markers of proteinuria and evidence of hydronephrosis. LV mass was significantly less in the ZDF groups at both time points compared to age-matched LC. End diastolic volume was increased by 16% at 16 weeks and by 37% at 36 weeks of age (p < 0.05 vs. LC. End diastolic pressure and end systolic volume were significantly increased (42% and 27% respectively at 36 weeks of age in the ZDF compared to LC. Kidney weights were significantly increased at both 16 and 36 week in ZDF animals (p < 0.05 vs. LC. Increased urinary albumin and decreased urinary creatinine were paralleled by a marked progression in the severity of hydronephrosis from 16 to 36 weeks of age in the ZDF group. In summary, there is evidence of progressive structural and functional changes in both the heart and kidney, starting as early as 16 weeks, without evidence that one pathology precedes or causes the other in the ZDF model of type II diabetes.

  15. Cardiac and renal function are progressively impaired with aging in Zucker diabetic fatty type II diabetic rats.

    Science.gov (United States)

    Baynes, John; Murray, David B

    2009-01-01

    This study investigated the temporal relationship between cardiomyopathy and renal pathology in the type II diabetic Zucker diabetic fatty (ZDF) rat. We hypothesized that changes in renal function will precede the development of cardiac dysfunction in the ZDF rat. Animals (10 weeks old) were divided into four experimental groups: Lean Control (fa/?) LC(n = 7), untreated ZDF rats (n = 7) sacrificed at 16 weeks of age, and LC (n = 7) untreated ZDF rats (n = 9) sacrificed at 36 weeks of age. LV structural/functional parameters were assessed via Millar conductance catheter. Renal function was evaluated via markers of proteinuria and evidence of hydronephrosis. LV mass was significantly less in the ZDF groups at both time points compared to age-matched LC. End diastolic volume was increased by 16% at 16 weeks and by 37% at 36 weeks of age (p < 0.05 vs. LC). End diastolic pressure and end systolic volume were significantly increased (42% and 27%respectively) at 36 weeks of age in the ZDF compared to LC. Kidney weights were significantly increased at both 16 and 36 week in ZDF animals (p < 0.05 vs. LC). Increased urinary albumin and decreased urinary creatinine were paralleled by a marked progression in the severity of hydronephrosis from 16 to 36 weeks of age in the ZDF group. In summary, there is evidence of progressive structural and functional changes in both the heart and kidney, starting as early as 16 weeks,without evidence that one pathology precedes or causes the other in the ZDF model of type II diabetes.

  16. Impaired insulin signaling affects renal organic anion transporter 3 (Oat3 function in streptozotocin-induced diabetic rats.

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    Anusorn Lungkaphin

    Full Text Available Organic anion transporter 3 (Oat3 is a major renal Oats expressed in the basolateral membrane of renal proximal tubule cells. We have recently reported decreases in renal Oat3 function and expression in diabetic rats and these changes were recovered after insulin treatment for four weeks. However, the mechanisms by which insulin restored these changes have not been elucidated. In this study, we hypothesized that insulin signaling mediators might play a crucial role in the regulation of renal Oat3 function. Experimental diabetic rats were induced by a single intraperitoneal injection of streptozotocin (65 mg/kg. One week after injection, animals showing blood glucose above 250 mg/dL were considered to be diabetic and used for the experiment in which insulin-treated diabetic rats were subcutaneously injected daily with insulin for four weeks. Estrone sulfate (ES uptake into renal cortical slices was examined to reflect the renal Oat3 function. The results showed that pre-incubation with insulin for 30 min (short term stimulated [3H]ES uptake into the renal cortical slices of normal control rats. In the untreated diabetic rats, pre-incubation with insulin for 30 min failed to stimulate renal Oat3 activity. The unresponsiveness of renal Oat3 activity to insulin in the untreated diabetic rats suggests the impairment of insulin signaling. Indeed, pre-incubation with phosphoinositide 3-kinase (PI3K and protein kinase C zeta (PKCζ inhibitors inhibited insulin-stimulated renal Oat3 activity. In addition, the expressions of PI3K, Akt and PKCζ in the renal cortex of diabetic rats were markedly decreased. Prolonged insulin treatment in diabetic rats restored these alterations toward normal levels. Our data suggest that the decreases in both function and expression of renal Oat3 in diabetes are associated with an impairment of renal insulin-induced Akt/PKB activation through PI3K/PKCζ/Akt/PKB signaling pathway.

  17. Effects of Unilateral Nephrectomy on Renal Function in Male Spontaneously Diabetic Torii Fatty Rats: A Novel Obese Type 2 Diabetic Model

    Science.gov (United States)

    Katsuda, Yoshiaki; Kemmochi, Yusuke; Maki, Mimi; Sano, Ryuhei; Toriniwa, Yasufumi; Ishii, Yukihito; Miyajima, Katsuhiro; Kakimoto, Kochi; Ohta, Takeshi

    2014-01-01

    The Spontaneously Diabetic Torii (SDT) fatty rat is a new model for obese type 2 diabetes. The aim of the present study was to investigate the effect of 1/2 nephrectomy (Nx) on renal function and morphology and on blood pressure in SDT fatty rats. Male SDT fatty rats underwent 1/2 Nx or a sham operation (Sham). Subsequently, animals were studied with respect to renal function and histological alterations. Induction of 1/2 Nx in SDT fatty rats led to functional and morphological damage to the remnant kidney and to hypertension, which are considered main characteristics of chronic kidney disease, at a younger age compared with the sham group. In conclusion, the SDT fatty rat is useful in investigations to elucidate the pathogenesis of human diabetic nephropathy and in new drug discovery. PMID:25177706

  18. Effects of Unilateral Nephrectomy on Renal Function in Male Spontaneously Diabetic Torii Fatty Rats: A Novel Obese Type 2 Diabetic Model

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    Yoshiaki Katsuda

    2014-01-01

    Full Text Available The Spontaneously Diabetic Torii (SDT fatty rat is a new model for obese type 2 diabetes. The aim of the present study was to investigate the effect of 1/2 nephrectomy (Nx on renal function and morphology and on blood pressure in SDT fatty rats. Male SDT fatty rats underwent 1/2 Nx or a sham operation (Sham. Subsequently, animals were studied with respect to renal function and histological alterations. Induction of 1/2 Nx in SDT fatty rats led to functional and morphological damage to the remnant kidney and to hypertension, which are considered main characteristics of chronic kidney disease, at a younger age compared with the sham group. In conclusion, the SDT fatty rat is useful in investigations to elucidate the pathogenesis of human diabetic nephropathy and in new drug discovery.

  19. 3',4'-Dihydroxyflavonol reduces superoxide and improves nitric oxide function in diabetic rat mesenteric arteries.

    Directory of Open Access Journals (Sweden)

    Chen-Huei Leo

    endothelial NO synthase (eNOS. Treatment of the 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. CONCLUSIONS/SIGNIFICANCE: DiOHF improves NO activity in diabetes by reducing Nox2-dependent superoxide production and preventing eNOS uncoupling to improve endothelial function.

  20. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    Science.gov (United States)

    Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

    2017-01-01

    Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes. PMID:28408970

  1. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Christian Luck

    2017-01-01

    Full Text Available Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1. However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL and diabetic obese Zucker (ZO rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.

  2. Aspirin prevents diabetic oxidative changes in rat lacrimal gland structure and function.

    Science.gov (United States)

    Jorge, Angélica Gobbi; Módulo, Carolina Maria; Dias, Ana Carolina; Braz, Alexandre Martins; Filho, Rubens Bertazolli; Jordão, Alceu A; de Paula, Jayter Silva; Rocha, Eduardo Melani

    2009-04-01

    The aim of this study is to evaluate whether aspirin reduces Diabetis Mellitus (DM) oxidative damage in the lacrimal gland (LG), and ocular surface (OS). Ten weeks after streptozotocin induced DM and aspirin treatment, LG and OS of rats were compared for tear secretion, hidtology, peroxidase activity, and expression of uncoupling proteins (UCPs). DM reduction of tear secretion was prevented by aspirin (P aspirin-treated diabetic rats. Peroxidase activity levels were higher and UCP-2 was reduced in DM LG but not in aspirin treated (P = 0.0025 and P aspirin indicate a direct inhibitory effect on oxidative pathways in LG and their inflammatory consequences, preserving the LG structure and function against hyperglycemia and/or insulin deficiency damage.

  3. Beneficial Effect of Metformin on Nerve Regeneration and Functional Recovery After Sciatic Nerve Crush Injury in Diabetic Rats.

    Science.gov (United States)

    Ma, Junxiong; Liu, Jun; Yu, Hailong; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2016-05-01

    Neuroprotective effects of metformin have been increasingly recognized in both diabetic and non-diabetic conditions. Thus far, no information has been available on the potential beneficial effects of metformin on peripheral nerve regeneration in diabetes mellitus. The present study was designed to investigate such a possibility. Diabetes was established by a single injection of streptozotocin at 50 mg/kg in rats. After sciatic nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with metformin (30, 200 and 500 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. It was found that metformin significantly enhanced axonal regeneration and functional recovery compared to saline after sciatic nerve injury in diabetic rats. In addition, metformin at 200 and 500 mg/kg showed better performance than that at 30 mg/kg. Taken together, metformin is capable of promoting nerve regeneration after sciatic nerve injuries in diabetes mellitus, highlighting its therapeutic values for peripheral nerve injury repair in diabetes mellitus.

  4. [The function of the oxytocin-synthesizing system of the hypothalamus in rats with diabetes mellitus undergoing hypoxic training].

    Science.gov (United States)

    Kolesnyk, Iu M; Abramov, A V; Trzhetsyns'kyĭ, S D; Hancheva, O V

    1999-01-01

    The state of hypothalamic oxytocin-synthesizing system in Wistar rats were investigating. The morphometric measurements and immunocytochemical detection of oxytocin-containing cells was used for determining of the functional state of supraoptic nucleus, anterior and posterior-medialis magnocellular subdivisions of paraventricular nucleus. It was established intermittent hypoxic training exert positive influence on rats with experimental diabetes mellitus. This effects depending on increasing synthesis and secretion of hypothalamic oxytocin. Intermittent hypoxic training elevate contents of immunoreactive oxytocin without changing morphometric characteristics in neurons of supraoptic and paraventricular nuclei and median eminence of hypothalamus. In comparison oxytocin contents in these neurons elevade less significance in diabetic rats, but it was observed increasing of nucleolus volume in hypothalamic oxytocin-synthesizing neurons. Intermittent hypoxic training of diabetic rats stimulate more significance elevating oxytocin contents in hypothalamic neurons and median eminence that evidence high level activity of hypothalamic oxytocin-synthesizing system.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Chronic administration of atorvastatin could partially ameliorate erectile function in streptozotocin-induced diabetic rats

    Science.gov (United States)

    Park, Juhyun; Kwon, Oh Seong; Cho, Sung Yong; Paick, Jae-Seung; Kim, Soo Woong

    2017-01-01

    The efficacy of statins is related to the ‘common soil’ hypothesis, which proposes oxidative stress and inflammation as main pathophysiologic processes in the disease group of diabetes and endothelial dysfunction. This study evaluated the recovery of erectile function after administration of chronic statin alone in streptozotocin (STZ)-induced diabetes mellitus (DM) rats, focusing on the anti-oxidative effects and consequentially recuperated endothelial function. A total of 45 male Sprague-Dawley rats (8 weeks old) were divided into three groups (n = 15 each): an age-matched normal control group (Control group), an uncontrolled DM group (DM group), and a statin-treated group (Statin group). The rats in the DM and Statin group received an injection of STZ (60 mg/kg). Beginning 10 weeks after the establishment of DM, the Statin group received daily treatment with atorvastatin (10 mg/kg) via oral gavage for four weeks. After 14 weeks, the results of the experiment were evaluated. The ratios of intracavernosal pressure (ICP) to mean arterial pressure (MAP) were recorded with cavernosometry (20 Hz, 3 V, 0.2 msec for 30 seconds) before and after the intravenous administration of udenafil (1 mg/kg). Expression of alpha-smooth muscle actin (α-SMA) was evaluated using cavernosal tissue. In addition, changes in RhoA translocation ratio and myosin phosphatase target subunit 1 (MYPT1) phosphorylation were evaluated with western blot. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also analyzed as measurements of oxidative stress levels. The ICP/MAP and area under the curve (AUC)/MAP ratios of the Statin group were obviously superior to the DM group, but were not comparable to the Control group (PStatin group than in the DM group (P = 0.015), and was comparable to the Control group. In contrast, MDA levels were not considerably different among the groups (P = 0.217). The RhoA translocation ratio was not significantly different among the groups (P = 0

  7. Nerve function and oxidative stress in diabetic and vitamin E deficient rats

    NARCIS (Netherlands)

    Gispen, W.H.; Dam, P.S. van; Asbeck, B.S. van; Bravenboer, B.; Oirschot, J.F.L.M. van; Marx, J.J.

    1997-01-01

    Nerve dysfunction in diabetes is associated with increased oxidative stress. Vitamin E depletion also leads to enhanced presence of reactive oxygen species (ROS). We compared systemic and endoneurial ROS activity and nerve conduction in vitamin E-depleted control and streptozotocin-diabetic rats (CE

  8. Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus

    DEFF Research Database (Denmark)

    Hu, Yaomin; Kaisaki, Pamela J; Argoud, Karène

    2009-01-01

    of spontaneous (genetically determined) mild hyperglycaemia and insulin resistance (Goto-Kakizaki-GK) and experimentally induced severe hyperglycaemia (Wistar-Kyoto-WKY rats injected with streptozotocin [STZ]). RESULTS: Different patterns of transcription regulation in the two rat models of diabetes likely...... number of protein coding sequences of unknown function which can be considered as functional and, when they map to DN loci, positional candidates for DN. Further expression analysis of rat orthologs of human DN positional candidate genes provided functional annotations of known and novel genes...

  9. Insulin Modulates Liver Function in a Type I Diabetes Rat Model

    Directory of Open Access Journals (Sweden)

    Eduardo L. Nolasco

    2015-07-01

    Full Text Available Background/Aims: Several studies have been performed to unravel the association between diabetes and increased susceptibility to infection. This study aimed to investigate the effect of insulin on the local environment after cecal ligation and puncture (CLP in rats. Methods: Diabetic (alloxan, 42 mg/kg i.v., 10 days and non-diabetic (control male Wistar rats were subjected to a two-puncture CLP procedure and 6 h later, the following analyses were performed: (a total and differential cell counts in peritoneal lavage (PeL and bronchoalveolar lavage (BAL fluids; (b quantification of tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC-1 and CINC-2 in the PeL and BAL fluids by enzyme-linked immunosorbent assay (ELISA; (c total leukocyte count using a veterinary hematology analyzer and differential leukocyte counts on stained slides; (d biochemical parameters (urea, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP by colorimetric analyses; and (e lung, kidney, and liver morphological analyses (hematoxylin and eosin staining. Results: Relative to controls, non-diabetic and diabetic CLP rats exhibited an increased in the concentration of IL-1β, IL-6, IL-10, CINC-1, and CINC-2 and total and neutrophil in the PeL fluid. Treatment of these animals with neutral protamine Hagedorn insulin (NPH, 1IU and 4IU, respectively, s.c., 2 hours before CLP procedure, induced an increase on these cells in the PeL fluid but it did not change cytokine levels. The levels of ALT, AST, ALP, and urea were higher in diabetic CLP rats than in non-diabetic CLP rats. ALP levels were higher in diabetic sham rats than in non-diabetic sham rats. Treatment of diabetic rats with insulin completely restored ALT, AST, and ALP levels. Conclusion: These results together suggest that insulin attenuates liver dysfunction during early two-puncture CLP-induced peritoneal

  10. Effect of spermine on lipid profile and HDL functionality in the streptozotocin-induced diabetic rat model.

    Science.gov (United States)

    Jafarnejad, A; Bathaie, S Z; Nakhjavani, M; Hassan, M Z

    2008-01-30

    This study aimed to investigate the effect of spermine (Spm) as a chemical chaperone and glycation inhibitor on the lipid profile and HDL functionality in the short- and long-term treatment of the STZ-induced diabetic rats. Male Wistar rats were divided into 4 groups (control, n=7; diabetic, n=9). Two groups (named 2 and 3) were injected intraperitoneally with streptozotocin. Control rats (named 1 and 4) were injected with vehicle alone. The treatment of diabetic and control animals (groups 3 and 4) with 60 micromol/l of Spm in drinking water was begun. The study continued up to the end of the fifth month. The serum glucose and insulin level, AGE formation, lipid profile, paraoxonase 1 (PON1), and lecithin: cholesterol acyl transferase (LCAT) activities were measured. Significantly lower plasma PON1, and LCAT activities and higher serum AGE, TG, TC and LDL-c, and lower HDL-c were seen in diabetic rats as compared to control groups (Pdiabetic groups decreased gradually after receiving Spm. In addition, due to Spm administration, an increase in the HDL-c level was observed after the first month of the experiment (Pdiabetic group that received Spm was significant after the second and the forth month of the experiment, Pdiabetic rats. Spermine, despite a lack of significant changes on glucose metabolism and insulin secretion, was found to improve diabetes complications.

  11. Pycnogenol® and its fractions influence the function of isolated heart in rats with experimental diabetes mellitus.

    Science.gov (United States)

    Kralova, Eva; Jankyova, Stanislava; Mucaji, Pavel; Gresakova, Eva; Stankovicova, Tatiana

    2015-02-01

    The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractions (buthanolic, water, ethyl acetate) on heart function in rats with experimental diabetes mellitus (DM) and compare their effects to the diabetic group. Their antioxidant activity "in vitro" was also determined. DM rats (streptozotocin over 3 consecutive days at a dose of 25 mg/kg of body weight) had increased systolic blood pressure, thicker left ventriculi wall (LV) and weaker myocardial contraction, prolonged QT interval in comparison to controls rats. In comparison to the diabetic group, PYC (20 mg/kg b.w./day) suppressed the influence of DM on the LV, improved contraction, increased coronary flow and displayed negative effect on electrical activity of hearts. The most effective of PYC's fractions was the water fraction. It improved biometric parameters and hemodynamic function of the DM hearts, enhanced shortening the QT interval, reduced the amount of dysrhythmias of the DM hearts and had the strongest antioxidant activity. In conclusion, DM damaged isolated rat heart function. Only the water fraction improved the function of the diabetic heart. The different results of three fractions and PYC on myocardial function may be caused by a various lipo- and hydro-philic action of the PYC components.

  12. Melatonin intake since weaning ameliorates steroidogenic function and sperm motility of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    da Costa, C F P; Gobbo, M G; Taboga, S R; Pinto-Fochi, M E; Góes, R M

    2016-05-01

    Melatonin may be used as an antioxidant in therapy against systemic sequelae caused by oxidative stress in diabetes. However, as melatonin has a major role in regulating reproductive activity, its consequence on reproductive parameters under diabetes needs to be better clarified. We have studied whether prior and concomitant treatment of juvenile Wistar rats with low doses of melatonin interferes in reproductive damage induced by experimental diabetes after 1 and 8 weeks. The consequences of melatonin administration since weaning on reproductive parameters of healthy rats at adulthood were also evaluated. Melatonin was provided in drinking water (10 μg/kg b.w./day) after weaning (5-week-old). Diabetes was induced by streptozotocin injection (4.5 mg/100 g b.w.) at 13-week-old rats, and rats were euthanized 1 and 8 weeks after disease onset. Diabetes decreased circulating testosterone levels (~35% to 1 week; ~62% to 2 months; p diabetes reduced the sperm reserve and led to atrophy of epididymal cauda. Both 1-week and 2-month diabetes impaired sperm motility, decreased the number of spermatozoa with progressive movement, and increased the number of immotile sperm. Melatonin intake reduced serum testosterone levels ~29% in healthy 14-week-old and ~23% in 21-week-old rats and reduced daily testicular sperm production ~26% in the latter disease stage, but did not interfere in sperm reserves and transit time for both experimental periods. Exogenous melatonin prevented the serum testosterone decrease and damage to sperm motility in diabetic rats and attenuated reduction in sperm counts and transit time induced by 1-week diabetes but did not avoid this decrease at 2-month diabetes. Low doses of melatonin administered prior to and during experimental diabetes attenuated damage to testicular steroidogenic activity and preserved sperm motility, but not sperm reserves in the rat. Our data indicated a differential action of melatonin in normoglycemic and hyperglycemic

  13. Salvianolic acid B improves vascular endothelial function in diabetic rats with blood glucose fluctuations via suppression of endothelial cell apoptosis.

    Science.gov (United States)

    Ren, Younan; Tao, Shanjun; Zheng, Shuguo; Zhao, Mengqiu; Zhu, Yuanmei; Yang, Jieren; Wu, Yuanjie

    2016-11-15

    Vascular endothelial cell injury is an initial event in atherosclerosis. Salvianolic acid B (Sal B), a main bioactive component in the root of Salvia miltiorrhiza, has vascular protective effect in diabetes, but the underlying mechanisms remain unclear. The present study investigated the effect of Sal B on vascular endothelial function in diabetic rats with blood glucose fluctuations and the possible mechanisms implicated. The results showed that diabetic rats developed marked endothelial dysfunction as exhibited by impaired acetylcholine induced vasodilation. Supplementation with Sal B resulted in an evident improvement of endothelial function. Phosphorylation (Ser 1177) of endothelial nitric oxide synthase (eNOS) was significantly restored in Sal B treated diabetic rats, accompanied by an evident recovery of NO metabolites. Sal B effectively reduced vascular endothelial cell apoptosis, with Bcl-2 protein up-regulated and Bax protein down-regulated markedly. Treatment with Sal B led to an evident amelioration of oxidative stress in diabetic rats as manifested by enhanced antioxidant capacity and decreased contents of malondialdehyde in aortas. Protein levels of NOX2 and NOX4, two main isoforms of NADPH oxidase known as the major source of reactive oxygen species in the vasculature, were markedly decreased in Sal B treated groups. In addition, treatment with Sal B led to an evident decrease of serum lipids. Taken together, this study indicates that Sal B is capable of improving endothelial function in diabetic rats with blood glucose fluctuations, of which the underlying mechanisms might be related to suppression of endothelial cell apoptosis and stimulation of eNOS phosphorylation (Ser 1177).

  14. [Effect of tobacco smoke on lipids peroxidation and liver function in streptozotocin diabetic rats--preliminary study].

    Science.gov (United States)

    Florek, Ewa; Jabłecka, Anna; Olszewski, Jan; Piekoszewski, Wojciech; Kulza, Maksymilian; Seńczuk-Przybyłowska, Monika; Chuchracki, Marek

    2010-01-01

    Diabetes is considered a group of diseases with chronic hyperglycemia caused by various organ disorders, failure or damage as a common feature. Hyperglycemia exerts toxic effect on endothelium, promotes oxidative stress, inhibits bioavailability of nitrogen monoxide (NO) and leads to formation of advanced glycation end products. Moreover, hyperglycemia induces production of reactive oxygen specimens (ROS) through several distinct mechanisms, such as: glucose autoxydation activation of polyol (sorbitol-aldose reductase) pathway, non-enzymatic glycation and neutrophil granulocyte's stimulation. These changes lead to uncontrolled oxidation and peroxidation of lipids, nucleic acids, certain enzymes and most of all--oxidative protein damage (OPD) in many tissues. The aim of this study was to evaluate influence of exposure to tobacco smoke on lipid peroxidation and liver function in experimentally induced diabetes. The research showed that the protein level in blood serum did not change neither in case of induced diabetes nor after tobacco smoke exposure. However a statistically significant increase of lipid peroxidation was observed in rats with pharmacologically induced diabetes. In animals exposed to tobacco smoke only lipid peroxidation increasing trend was demonstrated, while in animals with induced diabetes and exposed to tobacco smoke a statistically significant decrease of lipid peroxidation was noticed. In the adopted experimental model basically no alterations of hepatic aminotranspherases were observed, with exception of AIAT in the group of diabetic animals compared to rats in the control group. Results of the study do not explicitly explain the influence of tobacco smoking in experimentally induced diabetes on lipid peroxidation and liver functions.

  15. The beneficial effects of ranolazine on cardiac function after myocardial infarction are greater in diabetic than in nondiabetic rats.

    Science.gov (United States)

    Mourouzis, Iordanis; Mantzouratou, Polixeni; Galanopoulos, Georgios; Kostakou, Erietta; Dhalla, Arvinder K; Belardinelli, Luiz; Pantos, Constantinos

    2014-09-01

    Ranolazine (RAN) is known to exert both anti-ischemic and antidiabetic actions. Thus, this study has explored the hypothesis that RAN would have greater effect on the recovery of cardiac function in diabetic mellitus (DM) rat hearts following myocardial infarction (MI). Myocardial infarction was induced in nondiabetic (MI, n = 14) and diabetic (streptozotocin induced; DM-MI, n = 13) Wistar rats by permanent ligation of the left coronary artery. Cardiac function was evaluated using echocardiography (left ventricular ejection fraction %) and in isolated heart preparations by measuring left ventricular developed pressure (LVDP), and the positive and negative first derivative of LVDP (± dp/dt). Ranolazine (20 mg/kg, ip once a day) was administered 24 hours after surgical procedure for 4 weeks to nondiabetic (MI + RAN, n = 17) and diabetic rats (DM-MI + RAN, n = 15). The RAN improved the recovery of function in both the nondiabetic and the diabetic postinfarcted hearts but this effect was greater and achieved statistical significance only in the diabetic group. The RAN resulted in increased levels of phosphorylated protein kinase B (Akt) and mammalian target of rapamycin (mTOR, a component of Akt signaling) in both nondiabetic and diabetic infarcted hearts without changes in the activation of mitogen-activated protein kinases (MAPKs; p38 MAPK, c-Jun N-terminal kinase, and extracellular signal-regulated kinase). In addition, in diabetic hearts, RAN resulted in a significant increase in the ratio of sarcoplasmic Ca(2+)-ATPase/phospholamban (a target of Akt signaling, 2.0-fold increase) and increased levels of phosphorylated calcium-regulated adenosine monophosphate-activated protein kinase (AMPK; 2.0-fold increase). In diabetic animals, RAN increased insulin and lowered glucose levels in serum. In conclusion, the beneficial effect of RAN on the recovery of cardiac function after MI was greater in DM rats. This response was associated with activation of Akt/mTOR and AMPK

  16. Effect of standardized extract ofCosinium fenestratum stem bark on liver and kidney function parameters in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Patrick Nwabueze Okechukwu; Adolph William Ndyeabura; Chiam Nyet Chiang; Gabriel Akyirem Akowuah

    2013-01-01

    Objective:To investigate the effects of standardized dichloromethane(DCM) extract ofCosinium fenestratum(C. fenestratum) stem bark on liver and kidney function parameters in streptozotocin (STZ)-induced diabetic rats.Methods:Standardization of the extract was performed through high performance liquid chromatography(HPLC) using berberine(BE) as marker compound.The standardizedC. fenestratum stem bark extract(SCFE) was administered orally at a dose of100 mg/kg toSTZ-induced diabetic rats for15 d.Results:The quantity ofBE in the extract was2.09% w/w.Blood glucose levels, blood urea nitrogen(BUN), alkaline phosphatase(ALP) and creatinine were significantly(P<0.05) elevated inSTZ-induced diabetic rats as compared to normal control groups.Treatment of diabetic rats with the extract significantly(P<0.05) reduced,ALP, creatinine, andBUN levels as compared to the diabetic control group.The total white blood cells(WBC) count was reduced in diabetic rats.Treatment of diabetic rats withSCFE significantly(P<0.05) increased the totalWBC count as compared to the values of diabetic control rats.Conclusion:The observations of the present study show that extract of C. fenestratum stem bark has hepato-renal protective effect inSTZ-induced diabetic rats.

  17. Taurine Supplementation Improves Erectile Function in Rats with Streptozotocin-induced Type 1 Diabetes via Amelioration of Penile Fibrosis and Endothelial Dysfunction.

    Science.gov (United States)

    Ruan, Yajun; Li, Mingchao; Wang, Tao; Yang, Jun; Rao, Ke; Wang, Shaogang; Yang, Weiming; Liu, Jihong; Ye, Zhangqun

    2016-05-01

    For patients with diabetes, erectile dysfunction (ED) is common and greatly affects quality of life. However, these patients often exhibit a poor response to first-line oral phosphodiesterase type 5 inhibitors. To investigate whether taurine, a sulfur-containing amino acid, affects diabetic ED (DED). Type 1 diabetes mellitus was induced in male rats by using streptozotocin. After 12 weeks, an apomorphine test was conducted to confirm DED. Only rats with DED were administered taurine or vehicle for 4 weeks. Age-matched nondiabetic rats were administered saline intraperitoneally for 4 weeks. Erectile function was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Erectile function was significantly reduced in the diabetic rats compared with in the nondiabetic rats, and was improved in the diabetic rats treated with taurine. The corpus cavernosum of the rats with DED exhibited severe fibrosis and decreased smooth muscle content. Deposition of extracellular matrix proteins was increased in the diabetic rats, while expression of endothelial nitric oxide synthase/cyclic guanosine monophosphate/nitric oxide pathway-related proteins was reduced. Taurine supplementation ameliorated erectile response as well as histologic and molecular alterations. Taurine supplementation improves erectile function in rats with DED probably by potential antifibrotic activity. This finding provides evidence for a potential new therapy for DED. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  18. Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats.

    Science.gov (United States)

    Allagui, Mohamed Salah; Feriani, Anouer; Bouoni, Zouhour; Alimi, Hichem; Murat, Jean Claud; El Feki, Abdelfattah

    2014-09-01

    The present study aimed to investigate the potential effects of vitamins (C and E)/melatonin co-administration on the hematologic and hepatic functions and oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood glucose levels (hyperglycemia) associated with serious hematologic disorders (P diabetic rats were, however, noted to undergo significant increases by 42% (P diabetic rats when compared to the controls. Interestingly, the treatment with vitamins (C, E) in combination with melatonin was noted to reduce the plasma levels of glucose, lower the MDA levels, and restore the hematologic parameters and biochemical and antioxidant levels of diabetic rats back to normal values, alleviating diabetes metabolic disorders in rats.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2014-09-15

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

  1. Amelioration of altered antioxidant status and membrane linked functions by vanadium and Trigonella in alloxan diabetic rat brains

    Indian Academy of Sciences (India)

    Mohammad Rizwan Siddiqui; Asia Taha; K Moorthy; Mohd Ejaz Hussain; S F Basir; Najma Zaheer Baquer

    2005-09-01

    Trigonella foenum graecum seed powder (TSP) and sodium orthovanadate (SOV) have been reported to have antidiabetic effects. However, SOV exerts hypoglycemic effects at relatively high doses with several toxic effects. We used low doses of vanadate in combination with TSP and evaluated their antidiabetic effects on antioxidant enzymes and membrane-linked functions in diabetic rat brains. In rats, diabetes was induced by alloxan monohydrate (15 mg/100 g body wt.) and they were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP and a combination of 0.2 mg/ml SOV with 5% TSP for 21 days. Blood glucose levels, activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Na+/K+ ATPase, membrane lipid peroxidation and fluidity were determined in different fractions of whole brain after 21 days of treatment. Diabetic rats showed high blood glucose ( < 0.001), decreased activities of SOD, catalase and Na+/K+ ATPase ( < 0.01, < 0.001 and < 0.01), increased levels of GPx and MDA ( < 0.01 and < 0.001) and decreased membrane fluidity ( < 0.01). Treatment with different antidiabetic compounds restored the above-altered parameters. Combined dose of Trigonella and vanadate was found to be the most effective treatment in normalizing these alterations. Lower doses of vanadate could be used in combination with TSP to effectively counter diabetic alterations without any toxic effects.

  2. Biological Function of Acetic Acid-Improvement in Obesity and Glucose Tolerance by Acetic Acid in Type 2 Diabetic Rats.

    Science.gov (United States)

    Yamashita, Hiromi

    2016-07-29

    Fatty acids derived from adipose tissue are oxidized by β-oxidation to form ketone bodies as final products under the starving condition. Previously, we found that free acetic acid was formed concomitantly with the production of ketone bodies in isolated rat liver perfusion, and mitochondrial acetyl CoA hydrolase was appeared to be involved with the acetic acid production. It was revealed that acetic acid was formed as a final product of enhanced β-oxidation of fatty acids and utilized as a fuel in extrahepatic tissues under the starving condition. Under the fed condition, β-oxidation is suppressed and acetic acid production is decreased. When acetic acid was taken daily by obesity-linked type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats under the fed condition, it protected OLETF rats against obesity. Furthermore, acetic acid contributed to protect from the accumulation of lipid in the liver as well as abdominal fat in OLETF rats. Transcripts of lipogenic genes in the liver were decreased, while transcripts of myoglobin and Glut4 genes in abdominal muscles were increased in the acetic acid-administered OLETF rats. It is indicated that exogenously administered acetic acid would have effects on lipid metabolism in both the liver and the skeletal muscles, and have function that works against obesity and obesity-linked type 2 diabetes.

  3. The effectiveness of evening primrose oil and alpha lipoic acid in recovery of nerve function in diabetic rats

    Directory of Open Access Journals (Sweden)

    Abeer Mohamed Rashad

    2011-09-01

    Full Text Available Objectives: Diabetic polyneuropathy is a serious complication of diabetes mellitus and the most frequent neuropathy worldwide. Evening primrose oil (EPO is rich in omega-6 essential fatty acid component and gamma-linolenic acid. Alpha lipoic acid (ALPA has a protective effect against lipid peroxidation and helps in scavenging free radicals. Data regarding the effect of treatment with EPO on diabetic parameters and neuropathic manifestations are conflicting. This study aimed to determine the therapeutic efficacy of EPO and ALPA in correcting diabetic parameters and functional and structural neuropathic manifestations in streptozotocin (STZ induced diabetic rats.Materials and methods: In this study, the effects of two week oral treatment with EPO (1.25 g/kg was compared to that of ALPA (100 mg/kg and insulin (2 IU/day, utilized singly or in combination.Results: Compared with untreated diabetic rats, EPO and ALPA resulted in reduction of serum levels of glucose (p<0.05, total cholesterol (p<0.01, triglycerides (p<0.01, low density lipoprotein cholesterol (p<0.01, thiobarbituric acid reactive substance (a marker of oxidative stress (p<0.05, and increased in levels of high density lipoprotein cholesterol (p<0.05 and total antioxidant capacity (p<0.05. Enhanced positive effect was observed with combination therapy.Conclusion: This work indicates that EPO and ALPA, particularly when used in combination, improve glycemic control, lipid abnormalities and antioxidant capacity, thus restore the impaired functional properties of peripheral nerves to a great extent. J Clin Exp Invest 2011; 2 (3: 245-253.

  4. Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes

    NARCIS (Netherlands)

    Wessels, B.; Ciapaite, J.; van den Broek, N. M. A.; Houten, S. M.; Nicolay, K.; Prompers, J. J.

    2015-01-01

    Aim: To determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function in a rat model of diabetes. Methods: Both the lean, healthy rats and the obese, diabetic rats are Zucker Diabetic Fatty (ZDF) rats. The homozygous fa/fa ZDF rats are obese and diabetic. The he

  5. Upregulation of PPARbeta/delta is associated with structural and functional changes in the type I diabetes rat diaphragm.

    Directory of Open Access Journals (Sweden)

    Nadège Salvi

    Full Text Available BACKGROUND: Diabetes mellitus is associated with alterations in peripheral striated muscles and cardiomyopathy. We examined diaphragmatic function and fiber composition and identified the role of peroxisome proliferator-activated receptors (PPAR alpha and beta/delta as a factor involved in diaphragm muscle plasticity in response to type I diabetes. METHODOLOGY/PRINCIPAL FINDINGS: Streptozotocin-treated rats were studied after 8 weeks and compared with their controls. Diaphragmatic strips were stimulated in vitro and mechanical and energetic variables were measured, cross bridge kinetics assessed, and the effects of fatigue and hypoxia evaluated. Morphometry, myosin heavy chain isoforms, PPAR alpha and beta/delta gene and protein expression were also assessed. Diabetes induced a decrease in maximum velocity of shortening (-14%, P<0.05 associated with a decrease in myosin ATPase activity (-49%, P<0.05, and an increase in force (+20%, P<0.05 associated with an increase in the number of cross bridges (+14%, P<0.05. These modifications were in agreement with a shift towards slow myosin heavy chain fibers and were associated with an upregulation of PPARbeta/delta (+314% increase in gene and +190% increase in protein expression, P<0.05. In addition, greater resistances to fatigue and hypoxia were observed in diabetic rats. CONCLUSIONS/SIGNIFICANCE: Type I diabetes induced complex mechanical and energetic changes in the rat diaphragm and was associated with an up-regulation of PPARbeta/delta that could improve resistance to fatigue and hypoxia and favour the shift towards slow myosin heavy chain isoforms.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Modeling diabetic sensory neuropathy in rats.

    Science.gov (United States)

    Calcutt, Nigel A

    2004-01-01

    The procedures to induce insulin-deficient diabetes in rats using streptozotocin are described along with a number of insulin treatment regimes that can be used to maintain these animals at different degrees of glycemia for periods of weeks to months. Streptozotocin-diabetic rats develop tactile allodynia, hyperalgesia following paw formalin injection and abnormal responses to thermal stimulation and the detailed methods used to evaluate these behavioral indices of abnormal sensory function are provided.

  9. Experimental Gestational Diabetes Mellitus Induces Blunted Vasoconstriction and Functional Changes in the Rat Aorta

    Directory of Open Access Journals (Sweden)

    Cecilia Tufiño

    2014-01-01

    Full Text Available Diabetic conditions increase vascular reactivity to angiotensin II in several studies but there are scarce reports on cardiovascular effects of hypercaloric diet (HD induced gestational diabetes mellitus (GDM, so the objective of this work was to determine the effects of HD induced GDM on vascular responses. Angiotensin II as well as phenylephrine induced vascular contraction was tested in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4 before and 3 weeks during pregnancy with standard (SD or hypercaloric (HD diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired vasoconstrictor response (P<0.05 versus SD in intact (e+ but not in endothelium-free (e− vessels. Losartan reduced GDM but not SD e− vasoconstriction (P<0.01 versus SD. AT1R, AT2R, and COX-1 and COX-2 protein expression were significantly increased in GDM vessels (P<0.05 versus SD. Results suggest an increased participation of endothelium vasodilator mediators, probably prostaglandins, as well as of AT2 vasodilator receptors as a compensatory mechanism for vasoconstrictor changes generated by experimental GDM. Considering the short term of rat pregnancy findings can reflect early stage GDM adaptations.

  10. Functional reentry and circus movement arrhythmias in the small intestine of normal and diabetic rats.

    Science.gov (United States)

    Lammers, Wim J E P; Stephen, B; Karam, S M

    2012-04-01

    In a few recent studies, the presence of arrhythmias based on reentry and circus movement of the slow wave have been shown to occur in normal and diseased stomachs. To date, however, reentry has not been demonstrated before in any other part of the gastrointestinal system. No animals had to be killed for this study. Use was made of materials obtained during the course of another study in which 11 rats were treated with streptozotocin and housed with age-matched controls. After 3 and 7 mo, segments of duodenum, jejunum, and ileum were isolated and positioned in a tissue bath. Slow wave propagation was recorded with 121 extracellular electrodes. After the experiment, the propagation of the slow waves was reconstructed. In 10 of a total of 66 intestinal segments (15%), a circus movement of the slow wave was detected. These reentries were seen in control (n = 2) as well as in 3-mo (n = 2) and 7-mo (n = 6) diabetic rats. Local conduction velocities and beat-to-beat intervals during the reentries were measured (0.42 ± 0.15 and 3.03 ± 0.67 cm/s, respectively) leading to a wavelength of 1.3 ± 0.5 cm and a circuit diameter of 4.1 ± 1.5 mm. This is the first demonstration of a reentrant arrhythmia in the small intestine of control and diabetic rats. Calculations of the size of the circuits indicate that they are small enough to fit inside the intestinal wall. Extrapolation based on measured velocities and rates indicate that reentrant arrhythmias are also possible in the distal small intestine of larger animals including humans.

  11. Effects of curcumin and captopril on the functions of kidney and nerve in streptozotocin-induced diabetic rats: role of angiotensin converting enzyme 1.

    Science.gov (United States)

    Abd Allah, Eman S H; Gomaa, Asmaa M S

    2015-10-01

    Oxidative stress and inflammation are involved in the development and progression of diabetes and its complications. The renin-angiotensin system also plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that curcumin and captopril would restore the kidney and nerve functions of diabetic rats through their angiotensin converting enzyme 1 (ACE1) inhibiting activity as well as their antioxidant and anti-inflammatory effects. Diabetes was induced by a single intraperitoneal injection of streptozotocin (100 mg·kg(-1) body weight). One week after induction of diabetes, rats were treated with 100 mg·kg(-1)·day(-1) curcumin or 50 mg·kg(-1)·day(-1) captopril orally for 6 weeks. Compared with diabetic control rats, curcumin- or captopril-treated diabetic rats had significantly improved blood glucose, lipid profile, kidney/body weight ratio, serum creatinine, blood urea nitrogen (BUN), and pain thresholds assessed by Von Frey filaments, hot plate test, and tail-flick test. Diabetic control rats showed increased levels of total peroxide, renal and neural tumor necrosis factor-α and interleukin-10, and renal ACE1 compared with nondiabetic rats. Although treatment with either curcumin or captopril restored the altered variables, captopril was more effective in reducing these variables. ACE1 was positively correlated with BUN and creatinine and negatively correlated with paw withdrawal threshold, hot plate reaction time, and tail-flick latency, suggesting a possible causal relationship. We conclude that curcumin and captopril protect against diabetic nephropathy and neuropathy by inhibiting ACE1 as well as oxidation and inflammation. These findings suggest that curcumin and captopril may have a role in the treatment of diabetic nephropathy and neuropathy.

  12. Changes of phasic and tonic smooth muscle function of jejunum in type 2 diabetic Goto-Kakizaki rats

    DEFF Research Database (Denmark)

    Zhao, Jing-Bo; Chen, Peng-Min; Gregersen, Hans

    2013-01-01

    AIM: To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions. METHODS: Seven diabetic Goto-Kakizaki (GK) male rats, 32-wk old (GK group), and 9 age-matched normal Wistar rats (Normal group...... group after CA application compared to distensions without CA application (pressure, 1.01 ± 0.07 vs 1.99 ± 0.19 cmH2O, P change the pressure and stress threshold in the Normal group (pressure, 2.13 ± 0.32 vs 2.34 ± 0.32 cm......) were included in the study. Jejunal segments were distended up to a pressure of 10 cm H2O in an organ bath containing 37 °C Krebs solution with addition of carbachol (CA). The pressure and outer diameter changes were synchronously recorded. Passive conditions were obtained using calcium-free Krebs...

  13. Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats.

    Science.gov (United States)

    Gregory, Joshua A; Jolivalt, Corinne G; Goor, Jared; Mizisin, Andrew P; Calcutt, Nigel A

    2012-10-01

    Diabetic neuropathy includes damage to neurons, Schwann cells and blood vessels. Rodent models of diabetes do not adequately replicate all pathological features of diabetic neuropathy, particularly Schwann cell damage. We, therefore, tested the hypothesis that combining hypertension, a risk factor for neuropathy in diabetic patients, with insulin-deficient diabetes produces a more pertinent model of peripheral neuropathy. Behavioral, physiological and structural indices of neuropathy were measured for up to 6 months in spontaneously hypertensive and age-matched normotensive rats with or without concurrent streptozotocin-induced diabetes. Hypertensive rats developed nerve ischemia, thermal hyperalgesia, nerve conduction slowing and axonal atrophy. Thinly myelinated fibers with supernumerary Schwann cells indicative of cycles of demyelination and remyelination were also identified along with reduced nerve levels of myelin basic protein. Similar disorders were noted in streptozotocin-diabetic rats, except that thinly myelinated fibers were not observed and expression of myelin basic protein was normal. Superimposing diabetes on hypertension compounded disorders of nerve blood flow, conduction slowing and axonal atrophy and increased the incidence of thinly myelinated fibers. Rats with combined insulinopenia, hyperglycemia and hypertension provide a model for diabetic neuropathy that offers an opportunity to study mechanisms of Schwann cell pathology and suggests that hypertension may contribute to the etiology of diabetic neuropathy.

  14. Interleukin-1 beta inhibits rat thyroid cell function in vivo and in vitro by an NO-independent mechanism and induces hypothyroidism and accelerated thyroiditis in diabetes-prone BB rats

    DEFF Research Database (Denmark)

    Reimers, J I; Rasmussen, A K; Karlsen, A E;

    1996-01-01

    Interleukin-1 beta has been implicated as a pathogenic factor in the development of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentrations of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were...... to interleukin-1 beta. However, reverse transcription PCR analysis of mRNA isolated from interleukin-1 beta-exposed FRTL-5 cells revealed a transitory expression of the inducible NO synthase, which was markedly lower than inducible NO synthase induction in interleukin-1 beta-exposed isolated rat islets...... hypothyroidism in non-diabetic diabetes-prone BB rats. The data suggest that NO does not mediate interleukin-1 beta-induced inhibition of rat thyroid function in vivo or in vitro in FRTL-5 cells, and the induction of hypothyroidism by interleukin-1 beta in diabetes-prone BB rats is speculated to be due...

  15. MAS-mediated antioxidant effects restore the functionality of angiotensin converting enzyme 2-angiotensin-(1-7)-MAS axis in diabetic rat carotid.

    Science.gov (United States)

    Pernomian, Larissa; Gomes, Mayara Santos; Restini, Carolina Baraldi Araujo; de Oliveira, Ana Maria

    2014-01-01

    We hypothesized that endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species during type I-diabetes impairs carotid ACE2-angiotensin-(1-7)-Mas axis functionality, which accounts for the impaired carotid flow in diabetic rats. We also hypothesized that angiotensin-(1-7) chronic treatment of diabetic rats restores carotid ACE2-angiotensin-(1-7)-Mas axis functionality and carotid flow. Relaxant curves for angiotensin II or angiotensin-(1-7) were obtained in carotid from streptozotocin-induced diabetic rats. Superoxide or hydrogen peroxide levels were measured by flow cytometry in carotid endothelial cells. Carotid flow was also determined. We found that endothelial AT1-activated NAD(P)H oxidase-driven generation of superoxide and hydrogen peroxide in diabetic rat carotid impairs ACE2-angiotensin-(1-7)-Mas axis functionality, which reduces carotid flow. In this mechanism, hydrogen peroxide derived from superoxide dismutation inhibits ACE2 activity in generating angiotensin-(1-7) seemingly by activating I(Cl,SWELL0, while superoxide inhibits the nitrergic Mas-mediated vasorelaxation evoked by angiotensin-(1-7). Angiotensin-(1-7) treatment of diabetic rats restored carotid ACE2-angiotensin-(1-7)-Mas axis functionality by triggering a positive feedback played by endothelial Mas receptors, that blunts endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species. Mas-mediated antioxidant effects also restored diabetic rat carotid flow, pointing to the contribution of ACE2-angiotensin-(1-7)-Mas axis in maintaining carotid flow.

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

    Science.gov (United States)

    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.

  17. Combining sitagliptin/metformin with a functional fiber delays diabetes progression in Zucker rats.

    Science.gov (United States)

    Reimer, Raylene A; Grover, Gary J; Koetzner, Lee; Gahler, Roland J; Lyon, Michael R; Wood, Simon

    2014-03-01

    Our primary objective was to determine whether administering the viscous and fermentable polysaccharide PolyGlycopleX (PGX) with metformin (MET) or sitagliptin/metformin (S/MET) reduces hyperglycemia in Zucker diabetic fatty (ZDF) rats more so than monotherapy of each. Glucose tolerance, adiposity, satiety hormones and mechanisms related to dipeptidyl peptidase 4 activity, gut microbiota and, hepatic and pancreatic histology were examined. Male ZDF rats (9-10 weeks of age) were randomized to: i) cellulose/vehicle (control, C); ii) PGX (5% wt/wt)/vehicle (PGX); iii) cellulose/metformin (200  mg/kg) (MET); iv) cellulose/S/MET (10  mg/kg+200  mg/kg) (S/MET); v) PGX (5%)+MET (200  mg/kg) (PGX+MET); vi) cellulose/sitagliptin/MET (5%)+(10  mg/kg+200  mg/kg) (PGX+S/MET) for 6 weeks. PGX+MET and PGX+S/MET reduced glycemia compared with C and singular treatments (P=0.001). Weekly fasted and fed blood glucose levels were lower in PGX+MET and PGX+S/MET compared with all other groups at weeks 4, 5, and 6 (P=0.001). HbA1c was lower in PGX+S/MET than C, MET, S/MET, and PGX at week 6 (P=0.001). Fat mass was lower and GLP1 was higher in PGX+S/MET compared with all other groups (P=0.001). β-cell mass was highest and islet degeneration lowest in PGX+S/MET. Hepatic lipidosis was significantly lower in PGX+S/MET compared with PGX or S/MET alone. When combined with PGX, both MET and S/MET markedly reduce glycemia; however, PGX+S/MET appears advantageous over PGX+MET in terms of increased β-cell mass and reduced adiposity. Both combination treatments attenuated diabetes in the obese Zucker rat.

  18. Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats

    DEFF Research Database (Denmark)

    Feigh, M; Andreassen, K V; Neutzsky-Wulff, A V

    2012-01-01

    Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male Zucker diabetic fatty...

  19. Protective Effects of Morus alba Leaves Extract on Ocular Functions of Pups from Diabetic and Hypercholesterolemic Mother Rats

    Directory of Open Access Journals (Sweden)

    H.I.H. El-Sayyad, M.A. El-Sherbiny, M.A. Sobh, A.M. Abou-El-Naga, M.A.N. Ibrahim, S.A. Mousa

    2011-01-01

    Full Text Available Phytotherapy is frequently considered to be less toxic and free from side effects than synthetic drugs. Hence, the present study was designed to investigate the protective use of crude water extract of Morus alba leaves on ocular functions including cataractogenesis, biochemical diabetic and hypercholesterolemic markers, retinal neurotransmitters and retinopathy of rat pups maternally subjected to either diabetes and/or hypercholesterolemia. Application of crude water extract of Morus alba resulted in amelioration of the alterations of maternal serum glucose, LDL, HDL, total cholesterol and creatine phosphokinase activity as well as retinal neurotransmitters including acetylcholine (ACE, adrenaline (AD, nor-adrenaline (NAD, serotonin (5-HT, histamine (HS, dopamine (DA and gamma amino butyric acid (GABA. The retina of pups of either diabetic and/or hypercholesterolemia mothers exhibited massive alterations of retinal neurotransmitters. The alterations of retinal neurotransmitters were correlated with the observed pathological alterations of retinal pigmented epithelium, photoreceptor inner segment and ganglion cells and increased incidence of DNA fragmentation and apoptosis cell death. However, protection with Morus alba extract led to amelioration of the pathological alterations of retinal neurons and estimated neurotransmitters. Furthermore, a striking incidence of cataract was detected in pups of either diabetic and/or hypercholesterolemic mothers. Highest cataractogenesis was observed in pups of combined -treated groups. Our data indicate that experimental maternal diabetes alone or in combination with hypercholesterolemia led to alteration in the ocular structures of their pups, with an increasing incidence of cataract and retinopathy, and the effects of the extract might be attributed to the hypoglycaemic, antihypercholesterolemic and anti-oxidative potential of flavonoids, the major components of the plant extract.

  20. Combined insulin treatment and intense exercise training improved basal cardiac function and Ca(2+)-cycling proteins expression in type 1 diabetic rats.

    Science.gov (United States)

    Le Douairon Lahaye, Solène; Gratas-Delamarche, Arlette; Malardé, Ludivine; Zguira, Sami; Vincent, Sophie; Lemoine Morel, Sophie; Carré, François; Rannou Bekono, Françoise

    2012-02-01

    This study investigated the effects of 8 weeks of intense exercise training combined with insulin treatment on the Ca(2+)-cycling protein complex expression and their functional consequences on cardiac function in type 1 diabetic rat hearts. Diabetic Wistar rats were randomly assigned into the following groups: received no treatment, insulin-treated diabetic, trained diabetic, and trained insulin-treated diabetic. A control group was also included. Insulin treatment and (or) treadmill intense exercise training were conducted over 8 weeks. Basal cardiac function was evaluated by Langendorff technique. Cardiac expression of the main Ca(2+)-cycling proteins (RyR2, FKBP 12.6, SERCA2, PLB, NCX1) was assessed by Western blot. Diabetes altered basal cardiac function (±dP/dt) and decrease the expression of the main Ca(2+)-cycling proteins expression: RyR2, SERCA2, and NCX1 (p < 0.05). Whereas combined treatment was not able to normalize -dP/dt, it succeeded to normalize +dP/dt of diabetic rats (p < 0.05). Moreover, both insulin and intense exercise training, applied solely, increased the expression of the Ca(2+)-cycling proteins: RyR2, SERCA2, PLB. and NCX1 (p < 0.05). But this effect was higher when the 2 treatments were combined. These data are the first to show that combined insulin treatment and intense exercise training during diabetes synergistically act on the expression of the main Ca(2+)-cycling proteins, providing insights into mechanisms by which the dual treatment during diabetes improves cardiac function.

  1. 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

    Directory of Open Access Journals (Sweden)

    Viviam de O. Silva

    2017-09-01

    Full Text Available 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.

  2. Carvedilol protected diabetic rat hearts via reducing oxidative stress

    Institute of Scientific and Technical Information of China (English)

    HUANG He; SHAN Jiang; PAN Xiao-hong; WANG Hui-ping; QIAN Ling-bo

    2006-01-01

    Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant properties. To study the effect of carvedilol on the antioxidant status in diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage carvedilol-administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde, activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac tissues were measured. The diabetic rats not only had cardiac disfunction, weaker activities of antioxidant enzymes, but also showed lower expression of Bcl-2. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that earvedilol partly improves cardiac function via its antioxidant properties in diabetic rats.

  3. A combination of nutriments improves mitochondrial biogenesis and function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats.

    Directory of Open Access Journals (Sweden)

    Weili Shen

    Full Text Available BACKGROUND: Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA, and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-alpha (Ppar alpha, peroxisome proliferator-activated receptor-delta (Ppar delta, and carnitine palmitoyl transferase-1 (Mcpt-1 and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain. CONCLUSIONS/SIGNIFICANCE: These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose

    Directory of Open Access Journals (Sweden)

    Joy Shilpa

    2010-09-01

    Full Text Available Abstract Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT2A receptor subtype, gene expression studies on 5-HT2A, 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p p max and Kd showed a significant decrease (p 2A receptor binding parameters Bmax showed a significant decrease (p p d in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p A. marmelose to diabetic rats reversed the 5-HT content, Bmax , Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.

  6. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose.

    Science.gov (United States)

    Abraham, Pretty Mary; Kuruvilla, Korah P; Mathew, Jobin; Malat, Anitha; Joy, Shilpa; Paulose, C S

    2010-09-25

    Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT(2A) receptor subtype, gene expression studies on 5-HT(2A), 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, B(max), Kd of 5-HT, 5-HT(2A) and gene expression of 5-HT(2A), 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT(2A) and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p anxiety-related traits in diabetic rats which were corrected by combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.

  7. Protein kinase C modulation of the regulation of sarcoplasmic reticular function by protein kinase A-mediated phospholamban phosphorylation in diabetic rats.

    Science.gov (United States)

    Watanuki, Satoko; Matsuda, Naoyuki; Sakuraya, Fumika; Jesmin, Subrina; Hattori, Yuichi

    2004-01-01

    1. The goal of this study was to elucidate the possible mechanisms by which protein kinase A (PKA)-mediated regulation of the sarcoplasmic reticulum (SR) via phospholambin protein phosphorylation is functionally impaired in streptozotocin-induced diabetic rats. 2. Phospholamban (PLB) protein and mRNA levels were 1.3-fold higher in diabetic than in control hearts, while protein expression of cardiac SR Ca(2+)-ATPase (SERCA2a) was unchanged. 3. Basal and isoprenaline-stimulated phosphorylation of PLB at Ser(16) or Thr(17) was unchanged in diabetic hearts. However, stronger immunoreactivity was observed at the basal level in diabetic hearts when antiphosphoserine antibody was used. 4. Basal (32)P incorporation into PLB was significantly higher in diabetic than in control SR vesicles, but the extent of the PKA-mediated increase in PLB phosphorylation was the same in the two groups of vesicles. 5. Stimulation of Ca(2+) uptake by PKA-catalyzed PLB phosphorylation was weaker in diabetic than in control SR vesicles. The PKA-induced increase in Ca(2+) uptake was attenuated when control SR vesicles were preincubated with protein kinase C (PKC). 6. PKC activities were increased by more than two-fold in the membranous fractions from diabetic hearts in comparison with control values, regardless of whether Ca(2+) was present. This was associated with increases in the protein content of PKCdelta, PKCeta, PKCiota, and PKClambda in diabetic membranous fractions. 7. The changes observed in diabetic rats were reversed by insulin therapy. 8. These results suggest that PKA-dependent phosphorylation may incompletely counteract the function of PLB as an inhibitor of SERCA2a activity in diabetes in which PKC expression and activity are enhanced.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. Effect of Diabetes Mellitus and Its Control on Myocardial Contractile Function in Rats

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    Bassem M. Alsawy

    2014-09-01

    CONCLUSION: We concluded that the induction of both types of diabetes resulted in decreased myocardial performance parameters. The  treatment of type 1 and type 2 diabetes by insulin and oral rosiglitazone respectively improved to a great extent the altered metabolism and  mechanical myocardial parameters, with more improving effect of  insulin in type 1 than rosiglitazone in type 2 DM.

  11. Effects of benazepril on renal function and kidney expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    SUN Shu-zhen; WANG Yi; LI Qian; TIAN Yong-jie; LIU Ming-hua; YU Yong-hui

    2006-01-01

    Background Excessive deposition of extracellular matrix (ECM) in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting. The renal protective effect of these pathways on matrix accumulation has not been fully elucidated. The present study was understaken to investigate the activity of matrix metalloproteinase-2 (MMP-2), the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in kidney tissues of diabetic rats, and to explore the degradative pathway of type Ⅳ collagen (Ⅳ-C) and the renal protective effects of ACE inhibition-benazepril.Methods Twenty-four healthy male Wistar rats were divided randomly into normal control group (NC group),untreated diabetes mellitus group (DM group), and diabetes mellitus group treated with benazepril (DL group).The rat model of diabetes mellitus was induced by intraperitoneal injection of streptozocin (60 mg/kg). After the volume of water was given to the other two groups. At the end of 12 weeks, renal function was evaluated with 24-hour urinary protein (Upro), clearance of creatinine (Ccr), and blood urea nitrogen (BUN). MMP-2 activity was determined by gelatin zymography. The levels of MMP-2,TIMP-2 and collagen Ⅳ (Ⅳ-C) protein in the kidney tissue were assessed by immunohistochemistry. The gene expression of MMP-2 and TIMP-2 was measured by reverse transcription polymerase chain reaction (RT-PCR).Results The levels of BUN, Upro and Ccr in the DM group were higher than those in the NC group. In the DM group, the mRNA, enzymatic activity and proteins of MMP-2 decreased, but the expressions of Ⅳ-C and TIMP-2 increased. All diabetes-associated changes in renal function and MMP/TIMP were attenuated after benazepril treatment with reduced Ⅳ-C accumulation.Conclusions The changes of MMP-2 and TIMP-2 expressions in kidney tissues of diabetes rats may contribute to the

  12. 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

  13. 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.

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

    Science.gov (United States)

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

    2014-02-01

    Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 10⁷ colony-forming units (cfu)/d) and 3040 mg/l (with 10⁹ cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats.

  15. The effect of dietary Cu and diabetes on indices of Cu nutriture in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Rucker, R.B.; Uriu-Hare, J.Y.; Tinker, D.; Keen, C.L. (Univ. of California, Davis (United States))

    1991-03-11

    The uptake-retention of 67Cu is affected by dietary Cu and diabetes. Consequently, the functional activities of select enzymes and tissue Cu status were assessed. STZ-diabetic and control rats were fed Cu suppl. or def. diets. Rats were gavaged with 28 {mu}Ci 67Cu, and killed 8, 16, 24, 32, 64, or 128 h later. Diabetic rats were hyperphagic, hyperglycemic and hypoinsulinemic; with no effect of diet. Plasma ceruloplasmin activity (Cp) was lower in Cu def. rats; diabetic rats tended to have higher Cp than controls. Cu def. rats had low Cu levels in liver, kidney and plasma. Cu suppl. diabetic rats had higher liver and kidney Cu compared to Cu def. diabetic rats. Gel chromatography of liver showed that with time, there was a transfer of 67Cu from low to higher MW ligands. In nondiabetic rats, more 67Cu was associated with the higher MW ligands. The converse was observed for diabetic rats. There was no effect of diabetes on liver 67Cu localization. Diabetic rats had higher metallothionein (MT) concentrations in liver and kidney compared to controls Cu deficiency lowered MT values in both diabetic and control rats. CuZn SOD Cu activity was lowered with Cu def. and diabetes, while Mn SOD activity was similar among groups. Plasma lipid peroxide levels were lower in diabetic rats than controls. The results show that Cu metabolism is affected in diabetes, and the changes are functionally significant.

  16. Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats.

    Science.gov (United States)

    Ortiz-Avila, Omar; Gallegos-Corona, Marco Alonso; Sánchez-Briones, Luis Alberto; Calderón-Cortés, Elizabeth; Montoya-Pérez, Rocío; Rodriguez-Orozco, Alain R; Campos-García, Jesús; Saavedra-Molina, Alfredo; Mejía-Zepeda, Ricardo; Cortés-Rojo, Christian

    2015-08-01

    Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation. Streptozocin-induced diabetes elicited a noticeable increase in the content of C22:6, leading to augmented mitochondrial peroxidizability index and higher levels of lipid peroxidation. Mitochondrial respiration and complex I activity were impaired in diabetic rats with a concomitant increase in ROS generation using a complex I substrate. This was associated to a more oxidized state of glutathione, All these alterations were prevented by avocado oil except by the changes in mitochondrial fatty acid composition. Avocado oil did not prevented hyperglycemia and polyphagia although did normalized hyperlipidemia. Neither diabetes nor avocado oil induced steatosis. These results suggest that avocado oil improves mitochondrial ETC function by attenuating the deleterious effects of oxidative stress in the liver of diabetic rats independently of a hypoglycemic effect or by modifying the fatty acid composition of mitochondrial membranes. These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis.

  17. Cocoa-rich diet attenuates beta cell mass loss and function in young Zucker diabetic fatty rats by preventing oxidative stress and beta cell apoptosis.

    Science.gov (United States)

    Fernández-Millán, Elisa; Cordero-Herrera, Isabel; Ramos, Sonia; Escrivá, Fernando; Alvarez, Carmen; Goya, Luis; Martín, María Angeles

    2015-04-01

    We have recently shown that cocoa flavanols may have anti-diabetic potential by promoting survival and function of pancreatic beta-cells in vitro. In this work, we investigated if a cocoa-rich diet is able to preserve beta-cell mass and function in an animal model of type 2 diabetes and the mechanisms involved. Our results showed that cocoa feeding during the prediabetic state attenuates hyperglycaemia, reduces insulin resistant, and increases beta cell mass and function in obese Zucker diabetic rats. At the molecular level, cocoa-rich diet prevented beta-cell apoptosis by increasing the levels of Bcl-xL and decreasing Bax levels and caspase-3 activity. Cocoa diet enhanced the activity of endogenous antioxidant defenses, mainly glutathione peroxidase, preventing thus oxidative injury induced by the pre-diabetic condition and leading to apoptosis prevention. These findings provide the first in vivo evidence that a cocoa-rich diet may delay the loss of functional beta-cell mass and delay the progression of diabetes by preventing oxidative stress and beta-cell apoptosis.

  18. Effects of Micronutrients on Oxidative Stress and Islet Function in Type 1 Diabetes Mellitus Rats: Relationships to Th2 Type Cytokines, Interleukin-4, and Interluekin-10

    Institute of Scientific and Technical Information of China (English)

    ZHANG Gui-zhen; LI Mei-hua; SONG Yang; LIU Ting; GAO Shen; SUN Ying

    2007-01-01

    To observe the effects of the micronutrients on oxidative and autoimmune destruction of islets so as to prevent a person from the onset and development of type 1 Diabetes Mellitus(T1DM), the interleukin-4 and interleukin-10 expressions of lymphocytes in peripheral blood and spleen of T1 DM rats were determined by flow cytometry. GSH-Px activity and MDA level in the rats' pancreas were measured using biochemical methods. The insulin contents in serum and β cell insulin secret storage were tested by RIA and IHC, respectively. There was an increase in the percentages of 1L-4 and IL-10 positive lymphocytes in the peripheral blood and spleen of the groups of rats supplemented with various combinations of micronutrients(p <0. 01 and p <0. 05, respectively); the blood glucose concentration decreased (p<0.05); both the functional β cell in islets and the insulin content in pancreatic tissue increased(p<0.05 and p<0.01); the GSH-Px activity and MDA level of pancreas in the rats enhanced and decreased respectively(p<0.01 and p<0.05). The results suggest that micronutrients may alleviate the islet lesions by upregulating the expressions of IL-4 and IL-10 and lowering oxidative stress in diabetic rats.

  19. Morphological and functional aspects of acute kidney injury after fetal programing in the offspring of diabetic rats.

    Science.gov (United States)

    Pucci, Karla Roberta Martins; Pereira Júnior, Carlos Donizete; Idaló, Priscila Barbosa; Moreira, Ana Carolina Santana Pinheiro; Rocha, Laura Penna; Rodrigues, Aldo Rogélis Aquiles; Reis, Luiz Carlos Dos; Gomes, Roseli A da Silva; Rocha, Lenaldo Branco; Guimarães, Camila Souza de Oliveira; Reis, Marlene Antônia Dos; Câmara, Niels Olsen Saraiva; Corrêa, Rosana Rosa Miranda

    2015-03-01

    To evaluate the effects of folic acid (FA)-induced renal failure in young offspring of diabetic mothers. The offspring of streptozotocin-induced diabetic dams were divided into four groups: CC (controls receiving vehicle); DC (diabetics receiving vehicle); CA (controls receiving FA solution, 250 mg/kg) and DA (diabetics receiving FA solution, 250 mg/kg). Renal function tests and morphometry results were analyzed. An increase in creatinine and urea levels was observed in CA and DA groups at two and five months. FA administration caused a significant reduction in the number of glomeruli in the offspring of diabetic dams. The diabetes group treated with FA had fewer glomeruli compared to controls at two and five months. FA caused an increase in the area of the urinary space both in controls and offspring of diabetic dams at two and five months. The number of glomeruli and area of the urinary space at two months were negatively correlated. Fetal programing promotes remarkable changes in kidney morphology and function in offspring. We suggest that the morphological changes in the kidneys are more pronounced when fetal programing is associated with newly acquired diseases, e.g. renal failure induced by FA.

  20. Ursolic Acid provides kidney protection in diabetic rats.

    Science.gov (United States)

    Ling, Chen; Jinping, Lu; Xia, Li; Renyong, Yang

    2013-12-01

    Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and the leading cause of end-stage renal failure. However, the treatment of DN is still a problem in the world. Inflammatory process plays a critical role in the development of DN. Therefore, anti-inflammatory treatment of DN is worth exploring now and in the future. The study aimed to evaluate the impact of ursolic acid (UA) on renal function in streptozotocin-induced diabetes. Rats with streptozotocin-induced diabetes were treated with UA for 16 weeks. After 16 weeks, urine albumin excretion, serum creatinine, and blood urea nitrogen were measured. In addition, renal oxidative stress level, nuclear factor kappa-B (NF-κB) activity, P-selectin expression, and kidney histopathologic changes were evaluated. Sixteen weeks following streptozotocin injection, the rats produced significant alteration in renal function and increased oxidative stress, NF-κB activity, and P-selectin expression in the kidneys. Interestingly, UA significantly prevented biochemical and histopathologic changes in the kidneys associated with diabetes. Compared with untreated diabetic rats, UA treatment lowered urine albumin excretion, renal oxidative stress level, NF-κB activity, and P-selectin expression. Moreover, UA treatment also improved renal histopathologic changes in rats with diabetes. UA treatment exhibited a protective effect on kidneys in diabetic rats, implying that UA could be a potential treatment for diabetic nephropathy.

  1. Effects of mycophenolate mofetil vs cyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Constantin Fotiadis; Paraskevi Xekouki; Apostolos E Papalois; Pantelis T Antonakis; Ioannis Sfiniadakis; Dimitrios Flogeras; Eleutheria Karampela; George Zografos

    2005-01-01

    AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. METHODS: Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C receivedmycophenolate mofetil (MMF) (20 mg/kg). The animalswere killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. RESULTS: Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P<0.01). No difference in allograft survival between the CsA and MMF groups was found. However,MMF had less renal and hepatic toxicity and allowed weight gain.CONCLUSION: Monotherapy with MMF for immunosu ppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

    Science.gov (United States)

    Yu, Liming; Gong, Bing; Duan, Weixun; Fan, Chongxi; Zhang, Jian; Li, Zhi; Xue, Xiaodong; Xu, Yinli; Meng, Dandan; Li, Buying; Zhang, Meng; Bin Zhang; Jin, Zhenxiao; Yu, Shiqiang; Yang, Yang; Wang, Huishan

    2017-01-01

    Enhancing mitochondrial biogenesis and reducing mitochondrial oxidative stress have emerged as crucial therapeutic strategies to ameliorate diabetic myocardial ischemia/reperfusion (MI/R) injury. Melatonin has been reported to be a safe and potent cardioprotective agent. However, its role on mitochondrial biogenesis or reactive oxygen species (ROS) production in type 1 diabetic myocardium and the underlying mechanisms remain unknown. We hypothesize that melatonin ameliorates MI/R injury in type 1 diabetic rats by preserving mitochondrial function via AMPK-PGC-1α-SIRT3 signaling pathway. Both our in vivo and in vitro data showed that melatonin reduced MI/R injury by improving cardiac function, enhancing mitochondrial SOD activity, ATP production and oxidative phosphorylation complex (II, III and IV), reducing myocardial apoptosis and mitochondrial MDA, H2O2 generation. Importantly, melatonin also activated AMPK-PGC-1α-SIRT3 signaling and increased SOD2, NRF1 and TFAM expressions. However, these effects were abolished by Compound C (a specific AMPK signaling blocker) administration. Additionally, our cellular experiment showed that SIRT3 siRNA inhibited the cytoprotective effect of melatonin without affecting p-AMPK/AMPK ratio and PGC-1α expression. Taken together, we concluded that melatonin preserves mitochondrial function by reducing mitochondrial oxidative stress and enhancing its biogenesis, thus ameliorating MI/R injury in type 1 diabetic state. AMPK-PGC1α-SIRT3 axis plays an essential role in this process. PMID:28120943

  4. Evaluation of White Sesame Seed Oil on Glucose Control and Biomarkers of Hepatic, Cardiac, and Renal Functions in Male Sprague-Dawley Rats with Chemically Induced Diabetes.

    Science.gov (United States)

    Aslam, Farhan; Iqbal, Sanaullah; Nasir, Muhammad; Anjum, Aftab Ahmad; Swan, Pamela; Sweazea, Karen

    2017-05-01

    White sesame seed oil (WSSO) has been used in cooking and food preparations for centuries. It has many purported health benefits and may be a promising nutraceutical. The primary purpose of this study was to examine the effects of WSSO on fasting blood glucose (GLU) and insulin (INS) in male Sprague-Dawley rats with chemically induced diabetes. A secondary aim was to explore other hematological biomarkers of hepatic, cardiac, and renal function. Sixty-three male Sprague-Dawley rats were randomized into standard diet groups, normal control (NCON) (n = 21) and diabetic control (DCON) (n = 21), and a diabetic sesame oil (DSO) (n = 21) group, which were fed a diet containing 12% WSSO. Blood samples were analyzed at 0, 30, and 60 days. Differences between groups and across days were assessed with two-way repeated measures analysis of variance. At baseline, GLU and INS were similar in both diabetic groups, mean 248.4 ± 2.8 mg/dL and mean 23.4 ± 0.4 μU/mL, respectively. At 60 days, GLU was significantly (P < .05) higher in DCON (298.0 ± 2.3 mg/dL) compared with DSO (202.1 ± 1.0 mg/dL). INS showed similar favorable trends after WSSO supplementation. Consumption of WSSO significantly improved glucose control and other biomarkers of hepatic stress, as well as cardiac and renal health. WSSO may be a viable functional food to help reduce the detrimental effects of diabetes.

  5. Metformin Improves Endothelial Function and Reduces Blood Pressure in Diabetic Spontaneously Hypertensive Rats Independent from Glycemia Control : Comparison to Vildagliptin

    NARCIS (Netherlands)

    Hamidi Shishavan, Mahdi; Henning, Robert H; van Buiten, Azuwerus; Goris, Maaike; Deelman, Leo E; Buikema, Hendrik

    2017-01-01

    Metformin confers vascular benefits beyond glycemia control, possibly via pleiotropic effects on endothelial function. In type-1-diabetes-mellitus (T1DM-)patients metformin improved flow-mediated dilation but also increased prostaglandin(PG)-F2α, a known endothelial-contracting factor. To explain

  6. Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat

    NARCIS (Netherlands)

    Visser, J. T. J.; Lammers, K.; Hoogendijk, A.; Boer, M. W.; Brugman, S.; Beijer-Liefers, S.; Zandvoort, A.; Harmsen, H.; Welling, G.; Stellaard, F.; Bos, N. A.; Fasano, A.; Rozing, J.

    2010-01-01

    Aims/hypothesis Impaired intestinal barrier function is observed in type I diabetes patients and animal models of the disease. Exposure to diabetogenic antigens from the intestinal milieu due to a compromised intestinal barrier is considered essential for induction of the autoimmune process leading

  7. Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells.

    Science.gov (United States)

    Ahad, Amjid; Ahsan, Haseeb; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2015-10-05

    Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality in diabetic patients that accounts for about 40% of deaths in type 2 diabetes. p38 mitogen activated protein kinase (p38 MAPK), a serine-threonine kinase, plays an important role in tissue inflammation and is known to be activated under conditions of oxidative stress and hyperglycemia. The role of p38 MAPK has been demonstrated in DN, and its inhibition has been suggested as an alternative approach in the treatment of DN. In the present study, we investigated the nephroprotective effects of an anti-inflammatory phenolic compound, gallic acid (GA, 3,4,5-trihydroxybenzoic acid), in high fat diet/streptozotocin (HFD/STZ) induce type 2 diabetic wistar albino rats. GA (25 mg/kgbw and 50 mg/kgbw, p.o.) treatment for 16 weeks post induction of diabetes led to a significant reduction in the levels of blood glucose, HbA1c, serum creatinine, blood urea nitrogen and proteinuria as well as a significant reduction in the levels of creatinine clearance. GA significantly inhibited the renal p38 MAPK and nuclear factor kappa B (N-κB) activation as well as significantly reduced the levels of renal transforming growth factor beta (TGF-β) and fibronectin. Treatment with GA resulted in a significant reduction in the serum levels of proinflammatory cytokines viz. interleukin 1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α). Moreover, GA significantly lowered renal pathology and attenuated renal oxidative stress. In cultured rat NRK 52E proximal tubular epithelial cells, GA treatment inhibited high glucose induced activation of p38 MAPK and NF-κB as well as suppressed proinflammatory cytokine synthesis. The results of the present study provide in vivo and in vitro evidences that the p38 MAPK pathway plays an important role in the pathogenesis of DN, and GA attenuates the p38 MAPK-mediated renal dysfunction in HFD/STZ induced type 2 diabetic rats.

  8. 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...

  9. Diabetic cardiomyopathy in Zucker diabetic fatty rats: the forgotten right ventricle

    Directory of Open Access Journals (Sweden)

    Lubberink Mark

    2010-06-01

    Full Text Available Abstract Background In patients with myocardial infarction or heart failure, right ventricular (RV dysfunction is associated with death, shock and arrhythmias. In patients with type 2 diabetes mellitus, structural and functional alterations of the left ventricle (LV are highly prevalent, however, little is known about the impact of diabetes on RV characteristics. The purpose of the present study was to investigate whether LV changes are paralleled by RV alterations in a rat model of diabetes. Methods Zucker diabetic fatty (ZDF and control (ZL rats underwent echocardiography and positron emission tomography (PET scanning using [18F]-2-fluoro-2-deoxy-D-glucose under hyperinsulinaemic euglycaemic clamp conditions. Glucose, insulin, triglycerides and fatty acids were assessed from trunk blood. Another group of rats received an insulin or saline injection to study RV insulin signaling. Results ZDF rats developed hyperglycaemia, hyperinsulinaemia and dyslipidaemia (all p M-value (r = 0.91, p M-value (r = 0.77, p Conclusions LV changes were paralleled by RV alterations in insulin-stimulated glucose utilisation and RV systolic function in a rat model of diabetes, which may be attributed to ventricular interdependence as well as to the uniform effect of diabetes. Since diabetic patients are prone to develop diabetic cardiomyopathy and myocardial ischaemia, it might be suggested that RV dysfunction plays a central role in cardiac abnormalities in this population.

  10. Neuroprotective effects of octreotide on diabetic neuropathy in rats.

    Science.gov (United States)

    Solmaz, Volkan; Çınar, Bilge Piri; Yiğittürk, Gürkan; Özlece, Hatice Köse; Avni Eroglu, Hüseyin; Tekatas, Aslan; Erbaş, Oytun; Taşkıran, Dilek

    2017-02-26

    The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (pdiabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (pdiabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

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

    Directory of Open Access Journals (Sweden)

    Norihide Yokoi

    2013-01-01

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

  12. Developed beverage from roselle calyx and selected fruits modulates β-cell function, improves insulin sensitivity, and attenuates hyperlipidaemia in diabetic rats

    Directory of Open Access Journals (Sweden)

    Ochuko L. Erukainure

    2015-12-01

    Full Text Available The aim of this study is to report the antidiabetic properties of a beverage developed from roselle calyx and selected fruits in male albino rats. The beverage was designed to contain 30% pawpaw (Carica papaya L., 10% grapefruit (Citrus paradisi, 20% guava leaves (Psidium guajava L. and 40% roselle calyx aqueous extracts. Four groups of five rats each were acclimatized on pelletized mouse chow for seven days, after which diabetes was induced by a single ip injection of alloxan in all groups except group 1, which served as control. Group 2 served as negative control while groups 3 and 4 were treated with the beverage at 2.5 and 5 ml/kg bw respectively. Food intake, body weight, and blood glucose levels were monitored. They were sacrificed by cervical dislocation after a 2 week treatment. Blood serum was analysed to evaluate insulin levels, β cell function, insulin resistance and lipid profile. Histological studies were carried out on pancreatic tissues. Treatment with both doses of the beverage led to a significant reduction (p < 0.05 in blood glucose, total cholesterol triglyceride, LDL and increased HDL levels. It also improved serum insulin levels, β cell function, reduced insulin resistance and restored pancreatic beta cells compared to the diabetic group. These antidiabetic properties may be as a consequence of modulation of the β-cell function, reduction of insulin resistance and preservation/restoration of β-cell integrity. However, treatment with the single dose showed signs of hyperinsulinaemia.

  13. Effects of valsartan on diabetic cardiomyopathy in rats with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    YANG Zhong-hua; PENG Xiao-dong

    2010-01-01

    Background The development of diabetic cardiomyopathy is multifactorial. Insulin resistance (IR) and excessive activity of the renin-angiotensin system are confirmed reasons for diabetic cardiomyopathy. Renin-angiotensin system (RAS) inhibitors can reduce tissue Ang Ⅱ levels, with beneficial effects on cardiovascular function. Therefore, in type-2diabetes mellitus (T2DM), blockade of the RAS may have the function of protecting against diabetic cardiomyopathy through increasing insulin sensitivity and inhibiting excessive activity of RAS. However, this has not been confirmed.Methods The effect of valsartan, an angiotensin receptor blocker (ARB), on diabetic cardiomyopathy in the presence of T2DM was studied. Wistar rats with T2DM and T2DM treated with valsartan were studied. Glucose infusion rates (GIR),index of IR, heart weight, the heart weight-to-body weight ratio (HW/BW), myocardial apoptotic index, cardiac hydroxyprolin content, and cardiac tissue collagen type Ⅰ and collagen type Ⅲ content were measured.Results GIR in T2DM rats and T2DM rats treated with valsartan decreased (P <0.01). In T2DM rats treated with valsartan, heart weight, myocardial apoptotic index, cardiac hydroxyprolin content, and cardiac tissue collagen type Ⅰ and collagen type Ⅲ content were higher than in control rats, but lower than in T2DM rats. In rats with T2DM, GIR was negatively and significantly correlated with all the variables. However, in T2DM rats treated with valsartan or normal control rats, none of the correlations was significant.Conclusions In the presence of T2DM, diabetic cardiomyopathy is related with IR. Valsartan can not alleviate IR, but can protect against diabetic cardiomyopathy and remove the correlation between IR and diabetic cardiomyopathy.

  14. Boldine Prevents Renal Alterations in Diabetic Rats

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    Romina Hernández-Salinas

    2013-01-01

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

  15. (99m)Tc sulfur colloid and (99m)Tc mebrofenin hepatobiliary functional liver imaging in normal and diabetic rats.

    Science.gov (United States)

    Al-Saeedi, Fatma; Loutfi, Issa

    2011-01-01

    To use (99m)Tc sulfur colloid ((99m)Tc-SC) and (99m)Tc mebrofenin ((99m)Tc-BrIDA) to study liver function in normal and diabetic rats. Radionuclide imaging was performed on 2 groups of rats, using (99m)Tc-SC for one group and (99m)Tc-BrIDA for the other (20 rats per group) before and after induction of diabetes mellitus (DM) using streptozotocin administration (55 mg/kg i.p.). Dynamic acquisition was obtained for 1 h after the injection of 37 MBq of radiotracer. For the (99m)Tc-SC group, organ/tissue uptake was determined by drawing regions of interest (ROI) over the heart, liver, spleen and also the whole body (WB). The ratio of the ROI of each organ to the WB ROI was calculated. For (99m)Tc-BrIDA, ratios of cumulative count rates in liver, liver parenchyma, biliary tree and abdomen ROI to a WB ROI were also calculated. Statistical analysis was performed to compare the ratios of organ/tissue uptake to WB uptake before and after DM induction using the paired t test. (99m)Tc-SC uptake ratios (means ±SD) showed a lower liver-to-WB uptake ratio (0.75 ± 0.05) in the rats after DM induction compared to baseline (0.81 ± 0.06), while the cardiac blood pool showed higher uptake ratios in the rats after DM induction (p = 0.026). For (99m)Tc-BrIDA, there was no significant difference in radiotracer uptake ratios obtained from the rats before and after DM induction (p = 0.41). Using functional liver imaging, there was a statistically significant decrease in the liver phagocytic/reticuloendothelial system function after DM induction, as evidenced by decreased (99m)Tc-SC liver uptake and increased blood pool compared to prediabetes, while the hepatobiliary function remained unchanged after DM induction using (99m)Tc-BrIDA imaging. Copyright © 2011 S. Karger AG, Basel.

  16. [INFLUENCE OF MEDICINAL PLANT EXTRACTS ON THE FUNCTIONS AND ANTIOXIDANT PROTECTION OF ERYTHROCYTES IN RATS WITH EXPERIMENTAL DIABETES MELLITUS].

    Science.gov (United States)

    Vengerovskii, A I; Yakimova, T V; Nasanova, O N

    2016-01-01

    Experiments on rats with diabetes mellitus model induced by streptosotocin and high (30%) fat diet showed that the daily treatment with aqueous extracts of great nettle leaves (100 mg/kg) and common burdock roots (25 mg/kg) for a period of 10 days led to a decrease in the glycemic index and triglyceride level and produced protective action on erythrocytes both in animals kept on a fat-rich diet and on the background of a low-caloric ration. Both medicinal plant extracts were comparable with reference drug metformin in reducing the concentration of glycosylated hemoglobin (by 12-31%) and ectoglobular hemoglobin (1.7-1.8 times, p diet with usual (8%) fat content improved the metabolic indices to a lower degree (on the average by 13-21%, p < 0.05) than did the proposed phytotherapy.

  17. Renal Function and Hemodynamic Study in Obese Zucker Rats

    OpenAIRE

    Park, Sung Kwang; Kang, Sung Kyew

    1995-01-01

    Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies w...

  18. Monocyte functions in diabetes mellitus

    DEFF Research Database (Denmark)

    Geisler, C; Almdal, T; Bennedsen, J

    1982-01-01

    The aim of this study was to investigate the functions of monocytes obtained from 14 patients with diabetes mellitus (DM) compared with those of monocytes from healthy individuals. It was found that the total number of circulating monocytes in the 14 diabetic patients was lower than that from...... for the elucidation of concomitant infections in diabetic patients are discussed....

  19. Neuromedin B Restores Erectile Function by Protecting the Cavernous Body and the Nitrergic Nerves from Injury in a Diabetic Rat Model.

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    Hiroaki Nishimatsu

    Full Text Available Erectile dysfunction (ED is a major health problem worldwide and affects approximately 75% of diabetic patients, likely due to severely damaged cavernous body. While screening for cytokines produced by adipose tissue-derived stem cells, we detected neuromedin B (NMB. To explore a potential treatment option for ED, we examined whether NMB was capable of restoring erectile function. We also examined the potential mechanism by which NMB could restore erectile function. Male Wistar rats were injected with streptozotocin (STZ to induce diabetes. An adenovirus expressing NMB (AdNMB was injected into the penis 6 weeks after STZ administration. Four weeks after the injection of AdNMB, erectile function, penile histology, and protein expression were analyzed. As assessed by the measurement of intracavernous pressure, AdNMB injection significantly restored erectile function compared with the injection of an adenovirus expressing green fluorescent protein. This restoration was associated with conservation of the cavernous body structure and neural nitric oxide synthase (nNOS-expressing nerves, together with recovery of α-smooth muscle actin, vascular endothelial-cadherin, and nNOS expression. Furthermore, NMB significantly stimulated the survival of SH-SY5Y cells derived from human neuroblastoma tissue with characteristics similar to neurons. Collectively, these results suggested that NMB restored erectile function via protection of the cavernous body from injury and stimulation of the survival of the associated nerves. NMB may be useful to treat ED patients with a severely damaged cavernous body.

  20. DIFFERENTIAL RENAL GENE EXPRESSION IN EXPERIMENTAL DIABETIC RATS AFTER ASTRAGALUS MEMBRANACEUS TREATMENT

    Institute of Scientific and Technical Information of China (English)

    WU Yi; HUANG Sheng-lin; YING Lei; ZHAO Han-fang; YANG Rong; NI Zhao-hui

    2006-01-01

    Objective To find the genes involved in pathogenesis of diabetic nephropathy using gene chip technology. Methods We established a type 1 diabetic rat model by streptozotocin injection and divided these diabetic rats into two groups: diabetic rats group( D group) and diabetic rats group treated with Astragalus Membranaceus (DA group). The renal tissue was collected and total RNA was extracted for gene chips. With the help of gene chip, we tried to discover the differential-displayed genes between these two groups. Results Totally 201 differential-displayed genes were found between the two groups, among which 126 genes were up-regulated and 75 genes were down-regulated in the rat renal tissue. Conclusion With gene chip results, we find several genes which are associated with diabetes in the rat renal tissue. The further research on the function of these genes will be helpful to understand the mechanism of diabetic nephropathy.

  1. The Effect of Hydroalcoholic Extracts of Prangos Ferulacea on Blood Factors of Kidney and Liver Functions in Diabetic Male Wistar Rats

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    Tahereh zare

    2012-12-01

    Full Text Available Background and Objective: Diabetes mellitus is a chronic disease recognized by a reduction in insulin secretion due to the malfunction of β cells in the pancreas or an increase in the cell's resistance to insulin. Prangos Ferulacea has been known as an analgesic and anti-inflammatory herb in the general population. The aim of the present study was to evaluate the effect of the hydroalcoholic extracts of Prangos Ferulacea on the blood factors of kidney and liver functions in diabetes induced by streptozotocin in Wistar rats. Materials and Methods: In this experimental study, six groups of animals were selected. Three groups out of six were administered with intra peritoneal injection of streptozotocin to induce diabetes. Group I was fed a normal diet. Group II and III of the animals received 300 and 500 mg/kg/day Prangos Ferulacea extract. Group IV received distilled water (diabetic control, and the animals of groups V and VI were treated with Prangos Ferulacea extract 300 and 500 mg/kg body weight, respectively, for three weeks. Blood glucose, ALT, AST, ALP, creatinine, albumin, urea and BUN were measured in all the animals. The collected data were analyzed using SPSS software via the one-way ANOVA. Results: Treatment with the Prangos Ferulacea extract resulted in a significant decrease in blood glucose, ALT, AST and creatinine but no significant decrease in ALP, albumin, urea, and BUN levels. Conclusion: The results of this study showed that hydroalcoholic extracts of Prangos Ferulacea had antidiabetic effects and consequently might alleviate the liver and kidney damage caused by streptozotocin-induced diabetes mellitus.

  2. Targeting heme oxygenase-1 in early diabetic nephropathy in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Abo El Gheit, R; Emam, M N

    2016-12-01

    Diabetic nephropathy (DN) is one of the most common microvascular diabetic complications. This study was designed to evaluate the possible protective effect and underlying mechanisms of HO-1 induction in streptozotocin (STZ)-induced early DN in rats. The diabetic rats were divided into three groups: STZ-diabetic, cobalt protoporphyrin (CoPP)-treated diabetic, and zinc protoporphyrin IX (ZnPP)-treated diabetic groups. Compared to the STZ-diabetic group, CoPP-induced HO-1 upregulation improved the diabetic state and renal functional parameters, suppressed the renal proinflammatory marker, NF-κB, abrogated the elevated renal hydroxyprolin, and decreased the enhanced renal nicotinamide adenine dinucleotide phosphate oxidase activity with parallel reduction of urinary oxidative stress markers. On the contrary, treatment with ZnPP abrogated HO-1 levels, aggravated the diabetic condition with further increases in renal oxidative stress, fibrotic and inflammatory markers, and exacerbated renal dysfunction in diabetic animals. These findings suggest that the reduced diabetic renal injury upon HO-1 induction implicates the role of HO-1 induction as a potential treatment for DN.

  3. EFFECT OF CAMEL MILK ON ALLOXAN-INDUCED DIABETIC RATS

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    Eman G. E. Helal*, Samia M. Abd-Elwahab**, and Anwaar Alkamel Mohammad

    2012-10-01

    Full Text Available Back ground: Diabetes is a chronic metabolic disease which affects large number of population all over the world. Such disease is associated with many complications which may leads finally to patient's mortality. Camel milk supplementation reduces the insulin requirement in Type I diabetic patients. So this study was planned to evaluate the effect of camel milk as hypoglycemic agent.Material and method: Thirty male adult albino rats were used to investigate the effect of camel milk (CM treating diabetic rats. Rats were divided into three equal groups, control, diabetic non treated and diabetic CM treated groups. After thirty days of treatment all rats of each group were sacrificed. The body weight of each rat was determined at the beginning and the end of each period. Blood glucose, serum insulin, lipid and protein profiles, liver and kidney functions, blood picture and liver glycogen were determined for each rat at the end of each period. Pancreatic samples were obtained and processed for microscopic and quantitative evaluation after staining the prepared sections with both Heamatoxylin and eosin as well as special stain for demonstration of the different pancreatic cells in the Islet of Langerhans. Results: The obtained results showed that the induced diabetes was diagnosed by laboratory assessment to body weight loss, hyperglycemia, and hypoinsulinemia, significant increase in liver and kidney functions, lipid and protein profiles and decreased liver glycogen content. While, CM treatment led to a significant improvement in all these parameter except liver function. Microscopically there was definite vaculation, degeneration, karyolysis and pyknosis of beta pancreatic cells in diabetic group while the other pancreatic cells were not affected (alpha and delta cells. The use of CM treatment of this study greatly improves such cellular changes.Conclusion: it was recommended that the use of the CM as a hypoglycemic agent may be of good results

  4. The effects of crocin, insulin and their co-administration on the heart function and pathology in streptozotocin-induced diabetic rats

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    Amir Farshid

    2016-11-01

    Full Text Available Objective: Crocinisa saffron constituent with a potent anti-oxidant activity. The present study investigated the effects of crocin and insulin treatments (alone or in combination on cardiac function and pathology in diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (i.p. injection of streptozotocin (STZ, 50 mg/kg. Thereafter, crocin (5, 10 and 20 mg/kg, i.p., subcutaneous (s.c. injection of insulin (4 IU/kg and their combination were administeredfor eight weeks. Blood glucose level andwhole heart and body weights were measured. Electrocardiography (ECG was carried out using the lead II. Serum concentrations of lactate dehydrogenase (LDH, creatine kinase-MB isoenzyme (CK-MB, and the heart tissue malodialdehyde (MDA and superoxide dismutase (SOD contents were determined. The heart lesions were evaluated by light microscopy. Results: STZ decreased body weight and increased whole heart weight/body weight ratio. It also decreased heart rate, and increased RR and QT intervals and T wave amplitude. STZ increased blood glucose, serum LDH andCK-MB levels, augmentedheart tissue MDA content, decreased SOD content of heart tissue, and produced hemorrhages, degeneration, interstitial edema, and fibroblastic proliferation in the heart tissue. Crocin (10 and 20 mg/kg, i.p., insulin (4 IU/kg, s.c. and their combination (5 mg/kg of crocin with 4 IU/kg of insulin treatments recovered the ECG, biochemical and histopathological changes induced by STZ. Conclusion: The results showed cardioprotective  effects of crocin and insulin in STZ-induced diabetic rats. The antioxidant and anti-hyperglycemic properties of crocin and insulin may be involved in their cardioprotective actions.

  5. 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.

  6. Streptozotocin induced diabetes in lyon hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    LeaEMONNOT; JeanSASSARD; MingLO

    2004-01-01

    AIM: Lyon hypertensive (LH) rats, compared to their normotensive controls (LL) exhibit an increased blood pressure (BP)associated with a marked proteinuria and a metabolic syndrom including elevated plasma lipids and insulin/glucose ratio. The aim of the present work was to determine wether a type 2 diabetes could be induced in LH rats so as to obtain a model suitable for study of the relationships between diabetes and hypertension.

  7. Effect of maternal diabetes on gliogensis in neonatal rat hippocampus

    Science.gov (United States)

    Sadeghi, Akram; Esfandiary, Ebrahim; Hami, Javad; Khanahmad, Hossein; Hejazi, Zahra; Razavi, Shahnaz

    2016-01-01

    Background: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14). Materials and Methods: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14. Results: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P 0.05). Conclusion: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus. PMID:27656611

  8. Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.

    Science.gov (United States)

    Agil, Ahmad; El-Hammadi, Mazen; Jiménez-Aranda, Aroa; Tassi, Mohamed; Abdo, Walied; Fernández-Vázquez, Gumersindo; Reiter, Russel J

    2015-08-01

    Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P diabetic-induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial citrate synthase (P melatonin augments ATP production (P melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity.

  9. High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia

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    Kenneth N. Grisé

    2016-01-01

    Full Text Available Indices of cardiovascular autonomic neuropathy (CAN in experimental models of Type 1 diabetes mellitus (T1DM are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C, sedentary T1DM (D, control exercise (CX, or T1DM exercise (DX. Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9–17 mM through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY, and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY, including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM.

  10. B vitamins alleviate indices of neuropathic pain in diabetic rats.

    Science.gov (United States)

    Jolivalt, Corinne G; Mizisin, Leah M; Nelson, Austin; Cunha, Joice M; Ramos, Khara M; Bonke, Dieter; Calcutt, Nigel A

    2009-06-10

    There are sporadic reports that assorted combinations of B vitamins can alleviate pain in diabetic patients, but there is neither agreement on the relative efficacy of individual B vitamins nor understanding of the mechanisms involved. We therefore investigated the efficacy of a cocktail of the vitamins B1, B6 and B12 in alleviating behavioral indices of sensory dysfunction such as allodynia and hyperalgesia in diabetic rats and also the relative contribution of individual components of the cocktail. Repeated daily treatment with the cocktail of B vitamins for 7-9 days ameliorated tactile allodynia and formalin-evoked hyperalgesia in a dose-dependent manner and also improved sensory nerve conduction velocity in diabetic rats. Investigation of the contribution of individual B vitamins suggested that all three participated with variable efficacy in the alleviation of allodynia after protracted, but not single dose treatment. Only vitamin B6 improved sensory nerve conduction velocity slowing in diabetic rats when given alone. To address potential mechanisms of action, we measured markers of oxidative stress (lipid and protein oxidation) and inflammation (cyclooxygenase-2 (COX-2) and TNFalpha protein) in the nerve but treatment with the vitamin B cocktail did not significantly affect any of these parameters. The positive effects of B vitamins on functional and behavioral disorders of diabetic rats suggest a potential for use in treating painful diabetic neuropathy.

  11. Estrogen and exercise may enhance beta-cell function and mass via insulin receptor substrate 2 induction in ovariectomized diabetic rats.

    Science.gov (United States)

    Choi, Soo Bong; Jang, Jin Sun; Park, Sunmin

    2005-11-01

    The prevalence and progression of type 2 diabetes have increased remarkably in postmenopausal women. Although estrogen replacement and exercise have been studied for their effect in modulating insulin sensitivity in the case of insufficient estrogen states, their effects on beta-cell function and mass have not been studied. Ovariectomized (OVX) female rats with 90% pancreatectomy were given a 30% fat diet for 8 wk with a corresponding administration of 17beta-estradiol (30 microg/kg body weight) and/or regular exercise. Amelioration of insulin resistance by estrogen replacement or exercise was closely related to body weight reduction. Insulin secretion in first and second phases was lower in OVX during hyperglycemic clamp, which was improved by estrogen replacement and exercise but not by weight reduction induced by restricted diets. Both estrogen replacement and exercise overcame reduced pancreatic beta-cell mass in OVX rats via increased proliferation and decreased apoptosis of beta-cells, but they did not exhibit an additive effect. However, restricted diets did not stimulate beta-cell proliferation. Increased beta-cell proliferation was associated with the induction of insulin receptor substrate-2 and pancreatic homeodomain protein-1 via the activation of the cAMP response element binding protein. Estrogen replacement and exercise shared a common pathway, which led to the improvement of beta-cell function and mass, via cAMP response element binding protein activation, explaining the lack of an additive effect with combined treatments. In conclusion, decreased beta-cell mass leading to impaired insulin secretion triggers glucose dysregulation in estrogen insufficiency, regardless of body fat. Regular moderate exercise eliminates the risk factors of contracting diabetes in the postmenopausal state.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-05-01

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

  13. Long-term function of islets encapsulated in a re-designed alginate microcapsule construct in omentum pouches of immune-competent diabetic rats

    Science.gov (United States)

    Pareta, Rajesh; McQuilling, John P; Sittadjody, Sivanandane; Jenkins, Randy; Bowden, Stephen; Orlando, Giuseppe; Farney, Alan C; Brey, Eric M; Opara, Emmanuel C

    2014-01-01

    Objectives Our study aim was to determine encapsulated islet graft viability in an omentum pouch and the effect of FGF-1 released from our redesigned alginate microcapsules on the function of the graft. Methods Isolated rat islets were encapsulated in an inner core made with 1.5% low-viscosity high-mannuronic acid (LVM) alginate followed by an external layer made with 1.25% low-viscosity high-guluronic acid (LVG) alginate with or without FGF-1, in microcapsules measuring 300 – 400 μm in diameter. The two alginate layers were separated by a perm-selective membrane made with 0.1 % Poly-L-Ornithine (PLO), and the inner LVM core was partially chelated using 55 mM sodium citrate for 2 min. Results A marginal mass of encapsulated islet allografts (~2000 islets/kg) in Streptozotocin-diabetic Lewis rats caused significant reduction in blood glucose levels similar to the effect observed with encapsulated islet isografts. Transplantation of allo-islets co-encapsulated with FGF-1 did not result in better glycemic control, but induced greater body weight maintenance in transplant recipients compared to those that received only allo-islets. Histological examination of the retrieved tissue demonstrated morphologically and functionally intact islets in the microcapsules, with no signs of fibrosis. Conclusion We conclude that the omentum is a viable site for encapsulated islet transplantation. PMID:24681880

  14. Testicular lesions of streptozotocin diabetic rats.

    Science.gov (United States)

    Oksanen, A

    1975-01-01

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

  15. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2008-01-01

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

  18. Hesperidin ameliorates streptozotocin and high fat diet induced diabetic nephropathy in rats

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    Dilpesh P. Jain

    2014-12-01

    Full Text Available Objective: The present study investigates protective effect of hesperidin on streptozotocin and high fat diet induced diabetic nephropathy in experimental type 2 diabetic rats. Methods: Sprague Dawley rats were fed with high fat emulsion and high fat diet for 2 weeks to induce glucose intolerance and then injected with streptozotocin (35 mg/kg, i.p.. Following 48 h of streptozotocin injection blood glucose level was estimated to confirm hyperglycemia. After 4 weeks of diabetes induction diabetic rats were orally treated with hesperidin (50, 100 and 200 mg/kg body weight for 4 weeks. At the end of the treatment kidney functions, oxidative stress indices, biochemical estimations and histopathological examination were carried out to assess the efficacy of the treatment. Results: Diabetic rats exhibited significant rise in blood glucose level, altered kidney functions, oxidative stress and histological abnormalities compared to control rats. Hesperidin treatment significantly reduced the elevated levels of blood glucose, creatinine, urea nitrogen, total cholesterol and triglyceride when compared with diabetic control rats. Significant rise in renal hypertrophy, hyperfiltration, microalbuminuria as well as oxidative stress in the diabetic rats were effectively attenuated with hesperidin treatment, dose dependently. Moreover, basement membrane thickening and mesangial expansion observed in the kidney of diabetic rats restored near to normal structure. Conclusion: Results of the present study suggest that hesperidin ameliorate early diabetic nephropathy. [J Exp Integr Med 2014; 4(4.000: 261-267

  19. Pulpal and periodontal diseases increase triglyceride levels in diabetic rats.

    Science.gov (United States)

    Cintra, Luciano Tavares Angelo; da Silva Facundo, Aguinaldo Cândido; Azuma, Mariane Maffei; Sumida, Dóris Hissako; Astolphi, Rafael Dias; Bomfim, Suely Regina Mogami; Narciso, Luís Gustavo; Gomes-Filho, João Eduardo

    2013-07-01

    The aim of this study was to evaluate triglyceride and cholesterol levels in diabetic rats and their relationship with pulpal and periodontal diseases. Eighty male rats (Rattus norvegicus albinus, Wistar) were divided into the following eight groups comprising ten animals each: normal rats (G1), rats with pulpal diseases (G2), rats with periodontal diseases (G3), rats with both pulpal and periodontal diseases (G4), diabetic rats (G5), diabetic rats with pulpal diseases (G6), diabetic rats with periodontal diseases (G7), and diabetic rats with both periodontal and pulpal diseases (G8). Diabetes was induced by injecting streptozotocin, periapical lesions were induced by exposing pulpal tissue to the oral environment, and periodontal diseases were induced by periodontal ligature. The animals were killed after 30 days, and lipid profile was enzymatically measured using Trinder's method. The total assessed values were statistically analyzed by analysis of variance and Tukey test (p triglyceride levels of diabetic rats with periodontal disease and of diabetic rats with both periodontal and pulpal diseases were significantly higher than those of normal rats and nondiabetic group rats, respectively. The differences in the cholesterol levels among the groups were not significant. We found that the association of pulpal and periodontal diseases with diabetes increased triglyceride levels in rats. Changes in lipid profile may be related to the presence of oral infections and diabetes.

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

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    Nelli Giribabu

    2014-01-01

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

  1. Cardiac dysfunction in the diabetic rat: quantitative evaluation using high resolution magnetic resonance imaging

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    Alenezy Mohammed D

    2006-04-01

    Full Text Available Abstract Background Diabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy. Methods In this study, we used high field magnetic resonance imaging (MRI to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration in comparison with age/sex matched controls. Results Our analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats. Conclusion Thus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes.

  2. 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.

  3. [Berberine inhibits cardiac fibrosis of diabetic rats].

    Science.gov (United States)

    Lu, Kun; Shen, Yongjie; He, Jinfeng; Liu, Guoling; Song, Wei

    2016-10-01

    Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) , collagen type 1 (Col1) and collagen type 3 (Col3) in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci (STZ). Forty-three diabetic rats were randomly divided into diabetic model group (n=9), berberine treated groups of different doses [50, 100, 150 mg/(kg.d), gavage administration for 12 weeks; n=9, 9, 8 respectively], and metformin group as positive control (n=8); other 8 normal rats served as a negative control group. After the last administration, fasting blood glucose, left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured; rats' heart were taken to calculate the heart mass index (HMI); ELISA was used to detect the serum levels of TGF-β1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining; collagen volume fraction (CVF) was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group, the fasting blood glucose, LVSP, LVEDP absolute value, HMI, the degree of cardiac fibrosis, the expressions of TGF-β1, CTGF, Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg/(kg.d). Conclusion Berberine improves cardiac fibrosis in diabetic rats through down-regulating the expressions of TGF-β1 and CTGF and reducing the synthesis and deposition of Col1 and Col3.

  4. Monocyte functions in diabetes mellitus.

    Science.gov (United States)

    Geisler, C; Almdal, T; Bennedsen, J; Rhodes, J M; Kølendorf, K

    1982-02-01

    The aim of this study was to investigate the functions of monocytes obtained from 14 patients with diabetes mellitus (DM) compared with those of monocytes from healthy individuals. It was found that the total number of circulating monocytes in the 14 diabetic patients was lower than that from the healthy individuals. Phagocytosis of Candida albicans was decreased in the monocytes from the patients, whereas pinocytosis of acridine and phagocytosis of latex and sheep red blood cells were normal. The chemotactic response towards casein was enhanced. The possible consequences of these findings for the elucidation of concomitant infections in diabetic patients are discussed.

  5. Evaluation of Effect of Nishamalaki on STZ and HFHF Diet Induced Diabetic Neuropathy in Wistar Rats.

    Science.gov (United States)

    Dawane, Jayshree Shriram; Pandit, Vijaya Anil; Bhosale, Madhura Shirish Kumar; Khatavkar, Pallawi Shashank

    2016-10-01

    Diabetic neuropathy is one of the most common complications affecting 50% of diabetic patients. Neuropathic pain is the most difficult types of pain to treat. There is no specific treatment for neuropathy. Nishamalaki (NA), combination of Curcuma longa and Emblica officinalis used to treat Diabetes Mellitus (DM). So, efforts were made to test whether NA is useful in prevention of diabetic neuropathy. To evaluate the effect of NA on diabetic neuropathy in type 2 diabetic wistar rats. Group I (Control) vehicle treated consists of 6 rats. Diabetes induced in 36 wistar rats with Streptozotocin (STZ) (35mg/kg) intra-peritoneally followed by High Fat High Fructose diet. After confirmation of development of diabetes; rats divided into six groups (n=6). Group II - VII Diabetic Control, NA low dose, NA High dose, Glibenclamide, Pioglitazone and Epalrestat. Animals received drug treatment for next 12 weeks. Monitoring of Blood Sugar Level (BSL) done every 15 days and lipid profile at the end. Eddy's hot plate and tail immersion test performed to assess thermal hyperalgesia and cold allodynia. Walking function test performed to assess motor function. Diabetic rats exhibited significant (pNishamalaki improved lipid profile. Apart from controlling hyperglycaemia and reducing lipid levels, NA effectively prevented the development of diabetic neuropathy.

  6. Relationship between Immunological Abnormalities in Rat Models of Diabetes Mellitus and the Amplification Circuits for Diabetes

    Science.gov (United States)

    Shimomura, Tomoko; Asao, Hironobu; Wakabayashi, Ichiro

    2017-01-01

    A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models. In this review, we introduce rat models of diabetes and summarize the immune reactions in diabetic rat models. Finally, we speculate on the relationship between immune reactions and diabetic episodes. For example, diabetes-prone Biobreeding rats, type 1 diabetes model rats, exhibit increased autoreactive cellular and inflammatory immune reactions, while Goto-Kakizaki rats, type 2 diabetes model rats, exhibit increased Th2 reactions and attenuation of phagocytic activity. Investigation of immunological abnormalities in various diabetic rat models is useful for elucidating complicated mechanisms in the pathophysiology of diabetes. Studying immunological alterations, such as predominance of Th1/17 or Th2 cells, humoral immunity, and innate immune reactions, may improve understanding the structure of amplification circuits for diabetes in future studies.

  7. 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.

  8. Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

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    Wen Ji Li

    2017-05-01

    Full Text Available Background/Aims: Transforming growth factor-β1 (TGF-β1 plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD. Angiotensin II (Ang II is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-β in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. Methods: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist alone or in combination. Intracavernosal pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were examined. Results: Diabetic rats exhibited decreases in erectile response, severe CVOD, apoptosis, fibrosis, and activation of the TGF-β1 pathway. Treatment with sildenafil had a modest effect on erectile response and an insignificant suppressive effect on CVOD, apoptosis, fibrosis, and the TGF-β1 pathway. Although losartan greatly improved the histological and molecular changes and CVOD as compared with sildenafil, its effect on erectile response was low. The combination of sildenafil and losartan had superior effects on these parameters than did either compound alone. Conclusion: Ang II activation may be involved in apoptosis and fibrosis of the corpus cavernosum through Smad and non-Smad pathways, resulting in CVOD and ED. The low efficacy of sildenafil in a diabetic ED rat model was at least partly due to its inadequate effects on apoptosis, fibrosis, and CVOD.

  9. Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats.

    Science.gov (United States)

    Chen, Qing-Ying; Wang, Guo-Guang; Li, Wei; Jiang, Yu-Xin; Lu, Xiao-Hua; Zhou, Ping-Ping

    2016-01-01

    Diabetic ulcers are one of the most serious and costly chronic complications for diabetic patients. Hyperglycemia-induced oxidative stress may play an important role in diabetes and its complications. The aim of the study was to explore the effect of heme oxygenase-1 on wound closure in diabetic rats. Diabetic wound model was prepared by making an incision with full thickness in STZ-induced diabetic rats. Wounds from diabetic rats were treated with 10% hemin ointment for 21 days. Increase of HO-1 protein expression enhanced anti-inflammation and antioxidant in diabetic rats. Furthermore, HO-1 increased the levels of VEGF and ICAM-1 and expressions of CBS and CSE protein. In summary, HO-1 promoted the wound closure by augmenting anti-inflammation, antioxidant, and angiogenesis in diabetic rats.

  10. Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats

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    Qing-Ying Chen

    2016-01-01

    Full Text Available Diabetic ulcers are one of the most serious and costly chronic complications for diabetic patients. Hyperglycemia-induced oxidative stress may play an important role in diabetes and its complications. The aim of the study was to explore the effect of heme oxygenase-1 on wound closure in diabetic rats. Diabetic wound model was prepared by making an incision with full thickness in STZ-induced diabetic rats. Wounds from diabetic rats were treated with 10% hemin ointment for 21 days. Increase of HO-1 protein expression enhanced anti-inflammation and antioxidant in diabetic rats. Furthermore, HO-1 increased the levels of VEGF and ICAM-1 and expressions of CBS and CSE protein. In summary, HO-1 promoted the wound closure by augmenting anti-inflammation, antioxidant, and angiogenesis in diabetic rats.

  11. Sympathoadrenal activity during exercise in partial diabetic and diabetic rats

    NARCIS (Netherlands)

    Houwing, H; Strubbe, J.H.; Bruggink, J.E; Steffens, A.B

    1997-01-01

    Insulin-dependent diabetes mellitus is associated with altered fat and carbohydrate metabolism and disturbed sympathoadrenal functioning. The aim of this study was to investigate whether the short-term diabetic state alters the activity of the sympathoadrenal system and of the adrenal cortex during

  12. 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.

  13. Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner

    NARCIS (Netherlands)

    Wessels, Bart; Ciapaite, Jolita; van den Broek, Nicole M. A.; Nicolay, Klaas; Prompers, Jeanine J.

    2014-01-01

    Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I of the mitochondrial respiratory chain. This seems contraindicative since muscle mitochondrial dysfunction has been linked to the pat

  14. Hypoglycemic and antioxidant activities of Caesalpinia ferrea Martius leaf extract in streptozotocininduced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Sherien; Kamal; Hassan; Nermin; Mohammed; El-Sammad; Amria; Mamdouh; Mousa; Maha; Hashim; Mohammed; Abd; el; Razik; Hussein; Farrag; Amani; Nassir; Eldin; Hashim; Victoria; Werner; Ulrike; Lindequist; Mahmoud; Abd; El-Moein; Nawwar

    2015-01-01

    Objective: To evaluate the antidiabetic and antioxidant ef ects of aqueous ethanolic extract of Caesalpinia ferrea(C. ferrea) leaf in normal and streptozotocin(STZ) induced diabetic rats.Methods: Male Sprague-Dawley rats divided into 6 groups of 6 rats each were assigned into diabetic and non-diabetic groups. Diabetes was induced in rats by single intraperitoneal administration of STZ(65 mg/kg body weight). C. ferrea extract at the doses of 250 and 500 mg/kg body weight was orally administered to both diabetic and non-diabetic animals for a period of 30 days. After completion of experimental duration serum, liver and pancreas were used for evaluating biochemical and histopathological changes.Results: Oral administration of C. ferrea leaf extract significantly reduced elevated serum glucose, α-amylase, liver function levels and signii cantly increased serum insulin, total protein and body weight as well as improved lipid proi le due to diabetes. Furthermore, the treatment resulted in a marked increase in glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione, and diminished levels of lipid peroxidation in liver and pancreas of diabetic rats. Histopathological studies demonstrated the reduction in the pancreas and liver damage and coni rmed the biochemical i ndings.Conclusions: From the present study, it can be concluded that the C. ferrea leaf extract ef ectively improved hyperglycaemia while inhibiting the progression of oxidative stress in STZ-induced diabetic rats. Hence, it can be used in the management of diabetes mellitus.

  15. Control of glomerular hypertension by insulin administration in diabetic rats.

    OpenAIRE

    Scholey, J.W.; Meyer, T W

    1989-01-01

    Micropuncture studies were performed in Munich Wistar rats made diabetic with streptozotocin and in normal control rats. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (approximately 300 mg/dl). Group 1 diabetic rats studied after routine micropuncture preparation exhibited elevation of the single nephron glomerular filtration rate (SNGFR) due to increases in the glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In gro...

  16. Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats.

    Science.gov (United States)

    Agil, Ahmad; Rosado, Isaac; Ruiz, Rosario; Figueroa, Adriana; Zen, Nourahouda; Fernández-Vázquez, Gumersindo

    2012-03-01

    The aim of this study was to investigate the effects of melatonin on glucose homeostasis in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups, each composed of ten rats: naive (N), vehicle treated (V), and melatonin treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. ZDF rats developed DM (fasting hyperglycemia, 460±39.8mg/dL; HbA(1) c 8.3±0.5%) with both insulin resistance (HOMA-IR 9.28±0.9 versus 1.2±0.1 in ZL) and decreased β-cell function (HOMA1-%B) by 75%, compared with ZL rats. Melatonin reduced fasting hyperglycemia by 18.6% (Pmelatonin lowered insulinemia by 15.9% (Pmelatonin decreased hyperleptinemia by 34% (Pmelatonin reduced serum free fatty acid levels by 13.5% (Pmelatonin administration ameliorates glucose homeostasis in young ZDF rats by improving both insulin action and β-cell function. These observations have implications on melatonin's possible use as a new pharmacologic therapy for improving glucose homeostasis and of obesity-related T2DM, in young subjects.

  17. 消渴康对糖尿病肾病大鼠的治疗作用%Influence of Xiaokekang on Renal Function in Diabetic Nephropathy Rats

    Institute of Scientific and Technical Information of China (English)

    贾德贤; 任丽薇; 季小梅; 王谦; 郝钰; 张秋霞; 柴新楼; 刘颍姝; 田鹏飞; 苏玮莲

    2009-01-01

    Objective:To observe the changes of glyeemia, urine protein, serum creatinine, blood urea nitrogen and glycosylated hemoglobin in diabetic nephropathy rats and treating effects of Xiaokekang. Methods: Streptozotocin (STZ) was abdominally administered and was feeded by high lipid diet to establish diabetic nephropathy model in rats. Animals were divided into three groups: model group, Xiaokekang treatment group and normal group. Changes in glycemia, serum lipids, serum creatinine, blood urea nitrogen were measured at the 8th, 12th and 16th week after STZ injection. Glycosylated hemoglobin was measured at the 16th weeks after STZ injection. Results: Glycemia, serum lipids, serum creatinine were higher at the 8th, 12th and 16th week compared with normal group. Serum creatinine was higher at the 12th and 16th week, and glycosylated hemoglobin was also highter than that of the normal group. Xiaokekang reduced these changes. Conclusion: Xiaokekang can reduce glycemia, serum lipids and protect renal function.%目的:观察糖尿病肾病大鼠血糖、血脂、血清尿素氮、肌酐和糖化血红蛋白的变化以及消渴康的治疗作用.方法:采用腹腔一次性注射链尿佐菌素(STZ)、同时饲喂高脂饲料复制大鼠糖尿病肾病模型.将动物分为模型组、消渴康组和正常对照组,注射STZ4周后治疗组给予消渴康治疗.于注射STZ后8、12、16周取血测定空腹血糖、血脂、血清尿素氮和肌酐,第16周测定糖化血红蛋白.结果:注射STZ后8、12、16周模型组空腹血糖、血脂和尿素氮明显升高,12、16周血清肌酐和16周血液糖化血红蛋白明显高于正常组.消渴康治疗组与模型组同期比较以上指标有不同程度的减轻.结论:消渴康有良好的改善糖尿病高血糖、高血脂和肾功能损害的作用.

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

    Science.gov (United States)

    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.

  19. Effect of Verapamil on Serum Level of Salinomycin in Diabetic Rats

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    Hossein Najafzadeh

    2011-01-01

    Full Text Available Problem statement: The aim of present study was evaluation function of P-glycoprotein with or without verapamil in normal and diabetic rats; which the function of P-glycoprotein was indirectly evaluated by detection of serum slainomycin concentration with HPLC method. Approach: This study was carried in 4 groups of rats including normal rats which received salinomycin and verapamil together salinomycin; and diabetic rats which received salinomycin and verapamil together salinomycin. Serum concentration of salinomycin was measured by HPLC after 3 h from its administration. Results: Results show the serum concentration of salinomycin significantly elevated in diabetic rats which received verapamil together salinomycin; while this concentration did not significantly change in other groups. Conclusion: Since the p-glycoprotein activity decreases in diabetic conditions and verapamil inhibits it; probably transport of salinomycin from blood to tissues or its elimination was decreased that caused its elevated serum concentration.

  20. Hydrogen sulfide alleviates diabetic nephropathy in a streptozotocin-induced diabetic rat model.

    Science.gov (United States)

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

    2014-10-17

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

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

    OpenAIRE

    Weytjens Caroline; Garbar Christian; Degaillier Céline; Hernot Sophie; Droogmans Steven; Cosyns Bernard; Roosens Bram; Schoors Danny; Lahoutte Tony; Franken Philippe R; Van Camp Guy

    2008-01-01

    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 ...

  2. Selenium Nanoparticles Attenuate Oxidative Stress and Testicular Damage in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Dkhil, Mohamed A; Zrieq, Rafat; Al-Quraishy, Saleh; Abdel Moneim, Ahmed E

    2016-11-19

    We investigated the protective and antioxidative effects of selenium nanoparticles (SeNPs) in streptozotocin STZ-induced diabetic rats. STZ-diabetic rats were exposed daily to treatments with SeNPs and/or insulin and then the effect of these treatments on the parameters correlated to oxidative damage of the rat testes were assessed. Biochemical analysis revealed that SeNPs are able to ameliorate the reduction in the serum testosterone caused by STZ-induced diabetes. Furthermore, SeNPs could significantly decrease testicular tissue oxidative stress markers, namely lipid peroxidation and nitric oxide. In contrast, treatment of the STZ-diabetic rats with SeNPs increased the glutathione content and antioxidant enzyme activities in testicular tissues. Moreover, microscopic analysis proved that SeNPs are able to prevent histological damage in the testes of STZ-diabetic rats. Molecular analysis revealed that the mRNA level of Bcl-2 (B-cell lymphoma 2) is significantly upregulated. On the contrary, the mRNA level of Bax (Bcl-2 Associated X Protein) was significantly downregulated. Furthermore, treatment of STZ-diabetic rats with SeNPs led to an elevation in the expression of PCNA (Proliferating Cell Nuclear Antigen Gene). Interestingly, the insulin treatment also exhibited a significant improvement in the testicular function in STZ-diabetic rats. Collectively, our results demonstrated the possible effects of SeNPs in attenuating diabetes-induced oxidative damage, in particular in testicular tissue.

  3. Selenium Nanoparticles Attenuate Oxidative Stress and Testicular Damage in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Mohamed A. Dkhil

    2016-11-01

    Full Text Available We investigated the protective and antioxidative effects of selenium nanoparticles (SeNPs in streptozotocin STZ-induced diabetic rats. STZ-diabetic rats were exposed daily to treatments with SeNPs and/or insulin and then the effect of these treatments on the parameters correlated to oxidative damage of the rat testes were assessed. Biochemical analysis revealed that SeNPs are able to ameliorate the reduction in the serum testosterone caused by STZ-induced diabetes. Furthermore, SeNPs could significantly decrease testicular tissue oxidative stress markers, namely lipid peroxidation and nitric oxide. In contrast, treatment of the STZ-diabetic rats with SeNPs increased the glutathione content and antioxidant enzyme activities in testicular tissues. Moreover, microscopic analysis proved that SeNPs are able to prevent histological damage in the testes of STZ-diabetic rats. Molecular analysis revealed that the mRNA level of Bcl-2 (B-cell lymphoma 2 is significantly upregulated. On the contrary, the mRNA level of Bax (Bcl-2 Associated X Protein was significantly downregulated. Furthermore, treatment of STZ-diabetic rats with SeNPs led to an elevation in the expression of PCNA (Proliferating Cell Nuclear Antigen Gene. Interestingly, the insulin treatment also exhibited a significant improvement in the testicular function in STZ-diabetic rats. Collectively, our results demonstrated the possible effects of SeNPs in attenuating diabetes-induced oxidative damage, in particular in testicular tissue.

  4. Effect of Kaempferia parviflora on sexual performance in streptozotocin-induced diabetic male rats.

    Science.gov (United States)

    Lert-Amornpat, T; Maketon, C; Fungfuang, W

    2017-03-10

    Kaempferia parviflora Wall. Ex.Baker or Krachidum (KP) has been used locally in medicine and food. It has been claimed that KP has aphrodisia properties; however, no scientific data in support of this function in diabetic model have been reported. This study aimed to investigate the efficacy of KP on sexual behaviour and sperm parameter in streptozotocin (STZ)-induced diabetic male rats. Diabetes was induced in twenty male rats by STZ and divided into four groups: diabetic control group, and 3 treatment groups where KP was dose at 140, 280 and 420 mg/kg orally once a day for 6 weeks. Five normal control rats were treated with vehicle. The body weight, blood glucose, food intake, epididymal sperm parameter, sexual behaviour and serum testosterone level were evaluated. The results showed that KP treatment has no effect on the body weight, blood glucose and food intake in diabetic rats. A significant increase in sperm density in diabetic rats was observed (p < .05) at highest dose of KP. Furthermore, KP treatment demonstrated a significant recovery of sexual behaviour and serum testosterone levels in diabetic rats. These results confirm that KP exhibits aphrodisiac properties that improve the sperm density, testosterone level and sexual performance of STZ-induced diabetic rats. © 2017 The Authors. Andrologia Published by Blackwell Verlag GmbH.

  5. Effects of sesame oil on the reproductive parameters of diabetes mellitus-induced male rats.

    Science.gov (United States)

    Abbasi, Zahra; Tabatabaei, Seyed Reza Fatemi; Mazaheri, Yazdan; Barati, Farid; Morovvati, Hasan

    2013-08-01

    The purpose of the present study was to investigate the effect of sesame oil on the reproductive parameters of diabetic male Wistar rats. The adult male rats in a split plot design were divided into normal (n=10), normal 5% (n=5; 5% sesame oil enriched diet), diabetic (Streptozocin induced diabetes; n=9), diabetic 5% (n=9; 5% sesame oil enriched diet), and diabetic 10% (n=9; 10% sesame oil enriched diet) groups. Diet supplementation continued for 56 days. Sesame oil supplementation did not reduce the plasma glucose concentration of rats in the diabetic groups (p>0.05). The total spermatogonia, spermatocytes, Leydig cells/tubule, and the germ cell to Sertoli cell ratio were lower in the diabetic rats than the normal ones (psesame oil to the diet (psesame oil supplementation did not improve them. Incorporation of sesame oil into the diet improved the plasma testosterone concentration of the diabetic rats in a dose-dependent manner (psesame oil supplementation improved the reproductive parameters of diabetic rats at the levels of the testicular microstructure and function, but was not effective in protecting the epididymal sperm.

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

    OpenAIRE

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

    2014-01-01

    Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers,...

  7. Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats.

    Science.gov (United States)

    Körner, A; Celsi, G; Eklöf, A C; Linné, T; Persson, B; Aperia, A

    1992-05-01

    The effects of aldose reductase inhibition on kidney function were studied in rats with streptozotocin-induced diabetes mellitus. Diabetic rats were fed sorbinil (20 and 50 mg/kg) by daily gastric gavage and were compared with untreated diabetic rats and normal rats. The rats were under daily supervision with regard to blood glucose control, insulin administration and body weight. The aim was to promote continuous body growth and to maintain the blood glucose concentration at around 22 mmol/l without large day-to-day fluctuations. The renal functional changes observed in this well-established diabetic model closely resembled those reported in human Type 1 (insulin-dependent) diabetes mellitus. Sorbinil treatment completely prevented renal cortical sorbital accumulation, but did not abolish kidney enlargement or the increase in ultrafiltration pressure and glomerular filtration rate. Albumin excretion was increased to the same extent in the sorbinil-treated and in the untreated diabetic rats. We conclude that increased metabolism of glucose to sorbitol does not cause the hyperfiltration in rats with streptozotocin-induced diabetes.

  8. Arginine-supplemented enteral nutrition in critically ill diabetic and obese rats: a dose-ranging study evaluating nutritional status and macrophage function.

    Science.gov (United States)

    Bonhomme, Sandra; Belabed, Linda; Blanc, Marie-Céline; Neveux, Nathalie; Cynober, Luc; Darquy, Sylviane

    2013-01-01

    Critically ill diabetic and obese patients are at high risk of complications. Arginine availability is lowered in diabetes and in stress situations, yet arginine is necessary for immune response, mainly by its action through nitric oxide (NO). These facts argue for arginine-supplemented diets in critically ill patients. However, studies have raised concerns about possible adverse effects of such diets in intensive-care patients. We therefore analyzed the metabolic and immunologic effects of an arginine-enriched diet in stressed diabetic-obese rats. Zucker Diabetic Fatty rats (fa/fa) were made endotoxemic by an intraperitoneal injection of lipopolysaccharide and then fed 4-d enteral nutrition enriched with arginine (ARG group) or a non-essential amino acid mix (NEAA group). The two groups each were subdivided into three subgroups: the ARG subgroups received 0.5 g (ARG0.5), 2 g (ARG2), and 5 g (ARG5) of arginine per kilogram daily, and the NEAA groups were made isonitrogenous with the corresponding ARG subgroups (NEAA0.5, NEAA2, and NEAA5). Plasma and urinary biomarkers were measured. Cytokine and NO production levels and inducible NO synthase and arginase protein levels were determined from peritoneal macrophages. The survival rate was lower in the ARG5 and NEAA5 subgroups than in all the other subgroups. The nitrogen balance was higher in the ARG5 group than in the NEAA5 group. Plasma triacylglycerol levels were lower in the ARG2 group than in the NEAA2 group. Interleukin-6, tumor necrosis factor-α, and NO production in the macrophages decreased and arginase-1 was upregulated in the ARG-treated rats. In this model, mortality was increased by the nitrogen burden rather than by arginine per se. Arginine improved nitrogen balance and had an anti-inflammatory action on macrophages by regulating NO production, probably through arginase-1 expression. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. An early diagnostic tool for diabetic peripheral neuropathy in rats

    NARCIS (Netherlands)

    S. Kambiz (Shoista); J.W. van Neck (Han); S.G. Cosgun (Saniye G.); M.H.N. van Velzen (M. H N); J.A.M.J.L. Janssen (Joseph); Avazverdi, N. (Naim); S.E.R. Hovius (Steven); E.T. Walbeehm (Erik)

    2015-01-01

    textabstractThe skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study w

  10. An early diagnostic tool for diabetic peripheral neuropathy in rats

    NARCIS (Netherlands)

    Kambiz, S.; Neck, J.W. van; Cosgun, S.G.; Velzen, M.H. van; Janssen, J.A.M.; Avazverdi, N.; Hovius, S.E.; Walbeehm, E.T.

    2015-01-01

    The skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to invest

  11. Anti-diabetic effect of methanolic leaf extract of Pongamia pinnata on streptozotocin induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Selvaraju Kavipriya; Narayanaswamy Tamilselvan; Thirunavukkarasu Thirumalai; Gangaipillai Arumugam

    2013-01-01

    Objective: To study the anti-diabetic effect of methanolic leaf extract of Pongamia pinnata (P. pinnata) on streptozotocin induced diabetic rats.Methods:Anti-diabetic activity of P. pinnata leaf extract at dosage of 500 mg/kg and 1 g/kg body weight was evaluated.Results:The levels of glucose, triglycerides, total cholesterol and serum glutamic pyruvic transaminase were significantly increased in streptozotocin induced diabetic rats when compared to that of the normal rats. After supplemented with plant extract, significant lower blood glucose level was recorded.Conclusions:The methanolic leaf extract of P. pinnata has been potent anti-diabetic effect in male albino rats.

  12. Control of glomerular hypertension by insulin administration in diabetic rats.

    Science.gov (United States)

    Scholey, J W; Meyer, T W

    1989-01-01

    Micropuncture studies were performed in Munich Wistar rats made diabetic with streptozotocin and in normal control rats. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (approximately 300 mg/dl). Group 1 diabetic rats studied after routine micropuncture preparation exhibited elevation of the single nephron glomerular filtration rate (SNGFR) due to increases in the glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 diabetic rats infusion of insulin to achieve acute blood glucose control normalized the glomerular transcapillary pressure gradient while increasing the glomerular ultrafiltration coefficient, so that SNGFR remained elevated. Persistent elevation of SNGFR despite normalization of the transcapillary pressure gradient was also observed in group 3 diabetic rats infused with insulin plus sufficient dextrose to maintain hyperglycemia. These studies indicate that glomerular capillary hypertension in diabetes is an acutely reversible consequence of insulin deficiency and not the result of renal hypertrophy. PMID:2649514

  13. The effects of Tremella aurantia on testosterone and corticosterone productions in normal and diabetic rats.

    Science.gov (United States)

    Lo, Hui-Chen; Yang, Jyuer-Ger; Liu, Bi-Ching; Chen, Yen-Wen; Huang, Yuan-Li; Poon, Song Ling; Liu, Ming-Yie; Huang, Bu-Miin

    2004-01-01

    Tremella aurantia (TA) has been traditionally used as food and crude medicine in Chinese society. The polysaccharide isolated from the fruiting bodies of TA exhibits significant hypoglycemic activity in diabetic mouse models of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Diabetes will cause sexual dysfunction in patients. In the present study, we examined if the treatment of TA on IDDM and NIDDM rats will restore steroidogenesis and then the reproductive function. The fruiting bodies (FB), mycelium (TM) and polysaccharide (GX) of TA were fed to the IDDM and NIDDM rats, and testosterone and corticosterone levels in plasma, the weight of steroidogenic organs, and the expression of steroidogenic acute regulatory (StAR) protein and P450scc enzyme were determined. Plasma testosterone productions were significantly suppressed with the feeding of FB or TM in normal rat (p diabetes rats (p 0.05). There was no significant difference of the testosterone production between normal and NIDDM rats (p > 0.05). In plasma corticosterone production, there were no differences among control, FB- or TM-fed normal rats (p > 0.05). Corticosterone levels were reduced in IDDM rats compared to control, and FB or TM could restore its level. Corticosterone levels were induced in NIDDM rats compared to control (p feeding in NIDDM rat had lesser testis weight compared to NIDDM rats. The expression of StAR protein and P450scc enzyme were not different among groups in IDDM and NIDDM rats. Plasma testosterone productions were suppressed in normal rats with the feeding of TA (FB and TM). IDDM rats did have lower testosterone, but not in NIDDM, and FB or TM could not restore the inhibitory effects. The induction of IDDM or NIDDM rats did affect steroidogenesis and steroidogenic organ weights, and the feeding of TA had different effects on steroidogenesis in different types of diabetic rats.

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

    Science.gov (United States)

    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.

  15. Melatonin and succinate reduce rat liver mitochondrial dysfunction in diabetes.

    Science.gov (United States)

    Zavodnik, I B; Lapshina, E A; Cheshchevik, V T; Dremza, I K; Kujawa, J; Zabrodskaya, S V; Reiter, R J

    2011-08-01

    Mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species in response to hyperglycemia during diabetes lead to pathological consequences of hyperglycemia. The aim of the present work was to investigate the role of a specific functional damage in rat liver mitochondria during diabetes as well as to evaluate the possibility of metabolic and antioxidative correction of mitochondrial disorders by pharmacological doses of succinate and melatonin. In rat liver mitochondria, streptozotocin-induced diabetes was accompanied by marked impairments of metabolism: we observed a significant activation of α-ketoglutarate dehydrogenase (by 60%, pdiabetic animals, melatonin (10 mg/kg b.w., 30 days) or succinate (50 mg/kg b.w., 30 days) reversed the oxygen consumption rate V(3) and the acceptor control ratio to those in nondiabetic animals. Melatonin enhanced the inhibited activity of catalase in the cytoplasm of liver cells and prevented mitochondrial glutathione-S-transferase inhibition while succinate administration prevented α-ketoglutarate dehydrogenase activation. The mitochondria dysfunction associated with diabetes was partially remedied by succinate or melatonin administration. Thus, these molecules may have benefits for the treatment of diabetes. The protective mechanism may be related to improvements in mitochondrial physiology and the antioxidative status of cells.

  16. Effect of Scrophularia ningpoensis extract on diabetes in rats | Lu ...

    African Journals Online (AJOL)

    Effect of Scrophularia ningpoensis extract on diabetes in rats. ... glucose and plasma insulin levels were evaluated in order to determine antihyperglycemic effect. ... free radicals and is thus capable of reducing the risk of diabetic complications.

  17. Chronic treatment with qiliqiangxin ameliorates aortic endothelial cell dysfunction in diabetic rats.

    Science.gov (United States)

    Chen, Fei; Wu, Jia-Le; Fu, Guo-Sheng; Mou, Yun; Hu, Shen-Jiang

    2015-03-01

    Qiliqiangxin (QL), a traditional Chinese medicine, has been shown to be beneficial for chronic heart failure. However, whether QL can also improve endothelial cell function in diabetic rats remains unknown. Here, we investigated the effect of QL treatment on endothelial dysfunction by comparing the effect of QL to that of benazepril (Ben) in diabetic Sprague-Dawley rats for 8 weeks. Cardiac function was evaluated by echocardiography and catheterization. Assays for acetylcholine-induced, endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation, serum nitric oxide (NO), and nitric oxide synthase (NOS) as well as histological analyses were performed to assess endothelial function. Diabetic rats showed significantly inhibited cardiac function and EDR, decreased expression of serum NO and phosphorylation at Ser(1177) on endothelial NOS (eNOS), and impaired endothelial integrity after 8 weeks. Chronic treatment for 8 weeks with either QL or Ben prevented the inhibition of cardiac function and EDR and the decrease in serum NO and eNOS phosphorylation caused by diabetes. Moreover, either QL or Ben suppressed inducible NOS (iNOS) protein levels as well as endothelial necrosis compared with the diabetic rats. Additionally, QL prevented the increase in angiotensin-converting enzyme 1 and angiotensin II receptor type 1 in diabetes. Thus, chronic administration of QL improved serum NO production, EDR, and endothelial integrity in diabetic rat aortas, possibly through balancing eNOS and iNOS activity and decreasing renin-angiotensin system expression.

  18. 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 < 0.001), in addition to improving immune functions by decreasing total IgE approaching to the normal control level. Also, inflammatory cytokine (IL-6, IL-1β and TNF) levels, as well as total blood count decreased in diabetic rats as compared to the control group. Thus, 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.

  19. Neuroprotective effect of RYGB in Zucker fatty diabetic rats

    OpenAIRE

    2014-01-01

    The aim of this study is to explore the therapeutic potential of RYGB, a common used bariatric surgery, on diabetic polyneuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats. In animal model experiments, rats were made diabetic by STZ administration, and after 12 weeks of diabetes, two groups were studied: RYGB and sham surgery control (PF). Change in oral glucose tolerance, insulin sensitivity, and the plasma concentrations of insulin, glucagon, glucagon-like peptide-1 (GLP-1) were ...

  20. Melatonin improves spatial navigation memory in male diabetic rats

    Directory of Open Access Journals (Sweden)

    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.

  1. Sargassum polycystum extract attenuates oxidative stress on diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Muhamad Firdaus; Setyawati Soeharto

    2016-01-01

    ABSTRACT Objective:To evaluate hypoglycemic, free radical scavenging and improving antioxidant enzymes activities on diabetic-induced streptozotocin rats bySargassum polycystum (S. polycystum) extract. Methods: The seaweed extract was obtained by maceration, concentration and freeze drying, respectively. Acute toxicity was investigated on 25 rats. Forty eight of rats were used to study anti-stress oxidative of extract and divided into eight groups, where the first and fifth group were normal and diabetic control. The normal and diabetic treated groups were administered orally with extracts ofS. polycystum for 28 days. The blood glucose and body weight of rats were observed each week. The blood was obtained for determination of malondialdehide, superoxide dismutase, catalase and glutathione peroxidase, respectively. Results:Extract ofS. polycystum revealed no mortality and it was grouped as relatively non-toxic substance. The normal rats revealed difference statistically to the diabetic rats. The diabetic rats treated extract showed decreasing of blood glucose level and increasing of body weight. The diabetic rats were treated with 450 mg/kg of extract showed the higher oxidative stress augmentation than other diabetic treatments. It was caused free radical scavenging and induction of antioxidant enzymes activity by brown seaweed extract. Conclusions: The extract ofS. echinocarpum reduce oxidative stress on diabetic-induced streptozotocin rats and demonstrate as candidate of antioxidant diabetic substances.

  2. Chronopharmacokinetics of puerarin in diabetic rats

    Directory of Open Access Journals (Sweden)

    C T Zhang

    2013-01-01

    Full Text Available Puerarin injection has been widely used for clinic treatment of diabetes recently. To assess the relationship between the administration time of puerarin and the blood concentration of puerarin as well as its pharmacokinetic parameters, the diabetic rat model was used in current study. The rats were randomly divided into morning and evening groups according to the administration time. After the puerarin injection, blood glucose was tested in order to know whether the efficiency of puerarin was influenced by its concentration and pharmacokinetic parameters. Our results show that the average concentration of puerarin in the evening group is significantly higher than that in the morning group. The numbers of t 1/2α, t 1/2β, CL and AUC (0-∞ are significantly different between the morning and evening groups. The blood glucose level in the evening group was lower than that in the morning group. The speed of its onset is higher and the blood glucose level declines much more significantly in the evening group. These findings suggest that the concentration and pharmacokinetic parameters of puerarin affect its efficiency in diabetic rats. Therefore, it might be better to give puerarin in evening than in the morning for the mellitus treatment.

  3. Mitochondrial proteome analysis reveals depression of the Ndufs3 subunit and activity of complex I in diabetic rat brain.

    Science.gov (United States)

    Taurino, Federica; Stanca, Eleonora; Siculella, Luisa; Trentadue, Raffaella; Papa, Sergio; Zanotti, Franco; Gnoni, Antonio

    2012-04-18

    Type-1 diabetes resulting from defective insulin secretion and consequent hyperglycemia, is associated with "diabetic encephalopathy." This is characterized by brain neurophysiological and structural changes resulting in impairment of cognitive function. The present proteomic analysis of brain mitochondrial proteins from streptozotocin-induced type-1 diabetic rats, shows a large decrement of the Ndufs3 protein subunit of complex I, decreased level of the mRNA and impaired catalytic activity of the complex in the diabetic rats as compared to controls. The severe depression of the expression and enzymatic activity of complex I can represent a critical contributing factor to the onset of the diabetic encephalopathy in type-1 diabetes.

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

    OpenAIRE

    Muhammad Saad Ur Rehman; Sairah Hafeez Kamran; Mobasher Ahmad; Usman Akhtar

    2015-01-01

    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

  5. Gabapentin prevents hyperalgesia during the formalin test in diabetic rats.

    Science.gov (United States)

    Ceseña, R M; Calcutt, N A

    1999-03-05

    The anticonvulsant agent gabapentin exhibits antihyperalgesic properties in animal models of neuropathic pain. Diabetic rats display increased nocifensive behavior during the formalin test of persistent chemical irritation to the paw, suggesting the presence of abnormal pain processing mechanisms. We therefore, investigated the efficacy of gabapentin on formalin-evoked behavior in diabetic rats. Diabetic rats showed increased (P < 0.05) flinching during the normally quiescent phase of the 5.0% formalin test. Gabapentin (50 mg/kg i.p. 30 min pre-test) suppressed flinching during phases 1 and 2 of the formalin test in both control and diabetic rats but not the increased flinching of diabetic rats during the quiescent phase. When 0.5% formalin was used, diabetic rats exhibited increased flinching during both the quiescent phase and phase 2. Gabapentin was without effect in controls but suppressed (P < 0.01) the increased flinching in diabetic rats. Gabapentin displays efficacy against abnormal sensory processing in diabetic rats and may be of benefit for treating painful diabetic neuropathy.

  6. Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations.

    Directory of Open Access Journals (Sweden)

    Gerd Luippold

    Full Text Available The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose-lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ-rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1

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

    Science.gov (United States)

    Hernández-Fonseca, Juan P.; Rincón, Jaimar; Pedreañez, Adriana; Viera, Ninoska; Arcaya, José L.; Carrizo, Edgardo; Mosquera, Jesús

    2009-01-01

    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. PMID:19812703

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Al-Seeni, Madeha N.; Bakhashwain, Amal S.

    2017-01-01

    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. PMID:28298934

  10. The efficacy of Aesculus hippocastanum seeds on diabetic nephropathy in a streptozotocin-induced diabetic rat model.

    Science.gov (United States)

    Elmas, Onur; Erbas, Oytun; Yigitturk, Gurkan

    2016-10-01

    Cytokines, such as transforming growth factor (TGF)-ß1, and increased oxidative stress are considered to be responsible for the development of diabetic nephropathy. We hypothesized that Aesculus hippocastanum (AH) seeds may have preventive effects on oxidative stress and TGF-β-related diabetic nephropathy in streptozotocin (STZ)-induced diabetic nephropathy in rats. Twenty-one male Sprague-Dawley albino rats were divided into three groups (n=7). Except for the control group, they all had diabetic nephropathy induced by an intraperitoneal injection of STZ. While the diabetes group did not receive any medication, the diabetes+AH group was given the medication for 4 weeks. After the experiment, analyses were performed to evaluate the glomerular area, severity of sclerosis, and fibronectin immunoexpression, as well as levels of malondialdehyde (MDA), TGF-β, blood urea nitrogen (BUN), blood glucose, creatinine, and proteinuria. It was found that glomerular area, severity of sclerosis, fibronectin immunoexpression, and levels of MDA, TGF-β, BUN, creatinine, and proteinuria were decreased in the diabetes+AH group. It is known that diabetic nephropathy is induced, to a large extent, by hyperglycemia. In the present study, AH extract ameliorated diabetic nephropathy without decrease in blood glucose levels. In the study, AH seeds showed beneficial effects on the functional properties of the kidney and microscopic improvements in diabetic nephropathy.

  11. Choline treatment affects the liver reticuloendothelial system and plasma fatty acid composition in diabetic rats.

    Science.gov (United States)

    Al-Saeedi, Fatma J; Cheng, Behling

    2013-07-01

    This study investigated effects of choline treatment on hepatic reticuloendothelial and biliary functions and plasma fatty acid composition in diabetic rats. Diabetes was induced by streptozotocin (STZ). Choline was administered to untreated rats and a portion of STZ-treated rats for two sequences of five consecutive days, separated by a 2-day interval. Hepatic functions were studied using (99m) Tc Tin (II) colloid (TIN) and 99 mTc mebrofenin [bromo-iminodiacetic acid (BrIDA)] imaging. The TIN-uptake ratios (organ/whole body) of heart, liver and spleen, and the BrIDA-uptake ratios (organ or tissue/whole body) of liver, biliary tree and abdomen were obtained following imaging studies. Fatty acids were analysed by GC/MS. Choline treatment did not attenuate hyperglycaemic development. Diabetic rats showed (i) a decreased TIN-uptake ratio in liver with co-increased ratios in heart and spleen; choline treatment diminished these changes, (ii) elevated BrIDA-uptake ratios in biliary tree and abdomen but not in liver; choline treatment did not attenuate the elevations and (iii) decreases in plasma palmitoleic acid and oleic acid, reflecting an impaired stearoyl-CoA desaturase function; choline treatment did not affect the diminutions, but caused a decrease in arachidonic acid with a co-increase in linoleic acid. Some rats developed hypoproteinemia (HPO). HPO rats also exhibited decreases in plasma palmitoleic acid and oleic acid. Diabetes caused almost absence of palmitoleic acid in HPO rats. Choline treatment exerted no effect on the plasma fatty acid composition of diabetic HPO rats. Choline treatment affected hepatic reticuloendothelial function and plasma fatty acid composition, but not hepatobiliary function, in diabetic rats. Whether choline treatment is beneficial requires further studies. © 2013 The Authors Clinical Physiology and Functional Imaging © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  12. Bone marrow stromal cells inhibits HMGB1-mediated inflammation after stroke in type 2 diabetic rats.

    Science.gov (United States)

    Hu, J; Liu, B; Zhao, Q; Jin, P; Hua, F; Zhang, Z; Liu, Y; Zan, K; Cui, G; Ye, X

    2016-06-02

    High-mobility group box 1 (HMGB1), a ligand of receptor for advanced glycation endproducts (RAGE), functions as a proinflammatory factor. It is mainly involved in inflammatory activation and contributes to the initiation and progression of stroke. By using a model of transient middle cerebral artery occlusion (MCAo) in type 2 diabetic rats, we investigated the changes of pro-inflammation mediators, blood-brain barrier (BBB) leakage and functional outcome after stroke. Type 2 diabetic rats did not show an increased lesion volume, but exhibited significantly increased expression of HMGB1 and RAGE, BBB leakage, as well as decreased functional outcome after stroke compared with control rats. Injection of bone marrow stromal cells (BMSCs) into type 2 diabetic rats significantly reduced the expression of HMGB1 and RAGE, attenuated BBB leakage, and improved functional outcome after stroke. BMSCs-treated type 2 diabetic rats inhibited inflammation and improved functional outcome after stroke. Furthermore, in vitro data support the hypothesis that BMSCs-induced reduction of HMGB1 and RAGE in T2DM-MCAo rats contributed to attenuated inflammatory response in the ischemic brain, which may lead to the beneficial effects of BMSCs treatment. Further investigation of BMSCs treatment in type 2 diabetic stroke is warranted.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Topal, Gökçe; Koç, Ebru; Karaca, Cetin; Altuğ, Tuncay; Ergin, Bülent; Demirci, Cihan; Melikoğlu, Gülay; Meriçli, Ali H; Kucur, Mine; Ozdemir, Osman; Uydeş Doğan, B Sönmez

    2013-03-01

    Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5)  M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-α and IL-6 and by preventing lipid peroxidation. Copyright © 2012 John Wiley & Sons, Ltd.

  15. 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.

  16. Increased RhoA translocation in aorta of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Jiping TANG; Ikuyo KUSAKA; Amber R MASSEY; Shadon ROLLINS; John H ZHANG

    2006-01-01

    Aim: To analyze RhoA expression and activation in the aorta of diabetic rats. Methods: Male SD rats (n=70) were divided into 2 groups: the diabetic group and the control group. Diabetes was induced by intravenous injection of streptozotocin (55 mg/kg). The Rats were studied 3 weeks after the induction of diabetes. Western blotting was used to measure the expression and activation of Rho. Results: Heart rate was measured 24 h/d; it decreased by 58±13 beats/min in the diabetic rats. Isometric tension showed that the contraction of diabetic aorta was significantly reduced compared with that of control aorta when stimulated by KCl and serotonin. The relaxation of the diabetic aorta was reduced when stimulated by acetylcholine. An enhanced RhoA translocation in the aortic tissues of diabetic rats was determined by a 90% increase in membrane-bound RhoA, indicating that the activation of RhoA is markedly increased in the diabetic aorta. Conclusion: Our data suggest that upregulated RhoA could be involved in the vascular dysfunction of diabetic rats.

  17. Cerebral blood flow response to propranolol in streptozotocin diabetic rats

    DEFF Research Database (Denmark)

    Lass, Preben; Knudsen, G M

    1990-01-01

    The influence of propranolol on cerebral blood flow (CBF) was tested in streptozotocin diabetic rats and in control animals. Resting CBF values were 40% lower in the diabetic rats compared with controls. Intravenous injection of propranolol (2 mg kg-1) decreased CBF significantly in the control...

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

    Science.gov (United States)

    Hasanein, Parisa

    2011-06-01

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

  19. Skin changes in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    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.

  20. Antihyperglycemic and antihyperlipidemic activity of plectranthus amboinicus on normal and alloxan-induced diabetic rats.

    Science.gov (United States)

    Viswanathaswamy, A H M; Koti, B C; Gore, Aparna; Thippeswamy, A H M; Kulkarni, R V

    2011-03-01

    The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg). Normal as well as diabetic rats were divided into groups (n=6) receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg) of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 μg/kg) was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect.

  1. Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats.

    Science.gov (United States)

    Tuzcu, Mehmet; Baydas, Giyasettin

    2006-05-10

    Previous studies indicate that diabetes mellitus might be accompanied by a certain erosion of brain function such as cognitive impairment. The aim of this study was to examine and compare the effects of melatonin and vitamin E on cognitive functions in diabetic rats. Diabetes was induced in male albino rats via intraperitoneal streptozotocin injection. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. The levels of lipid peroxidation and glutathione were detected in hippocampus and frontal cortex. The diabetic rats developed significant impairment in learning and memory behaviors as indicated by the deficits in water maze tests as compared to control rats. Furthermore, lipid peroxidation levels increased and glutathione concentration decreased in diabetic rats. Treatment with melatonin and vitamin E significantly ameliorated learning and memory performance. Furthermore, both antioxidants reversed lipid peroxidation and glutathione levels toward their control values. These results suggest that oxidative stress may contribute to learning and memory deficits in diabetes and further suggest that antioxidant melatonin and vitamin E can improve cognitive impairment in streptozotocin-induced diabetes.

  2. Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats.

    Science.gov (United States)

    Kubota, Masatoshi; Watanabe, Reiko; Yamaguchi, Miki; Hosojima, Michihiro; Saito, Akihiko; Fujii, Mikio; Fujimura, Shinobu; Kadowaki, Motoni

    2016-10-01

    We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (Pdiabetes, fatty liver and diabetic nephropathy.

  3. Pathophysiological Characteristics of Diabetic Ocular Complications in Spontaneously Diabetic Torii Rat

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    Tomohiko Sasase

    2010-01-01

    Full Text Available The Spontaneously Diabetic Torii (SDT rat, a nonobese type 2 diabetes model, develops severe diabetic retinopathy as result of chronic severe hyperglycemia. Although existing diabetes animal models also develop ocular complications, severe retinal lesions frequently observed in human diabetes patients such as preretinal neovascularization or retinal detachment are not found. Distinctive features in SDT rat are hypermature cataract, tractional retinal detachment with fibrous proliferation, and massive hemorrhaging in the anterior chamber. These pathophysiological changes are caused by sustained hyperglycemic condition and subsequent increased expression of vascular endothelial growth factor (VEGF in retina, iris, and ciliary body. Although some differences in diabetic retinopathy exist between SDT rats and humans (e.g., a low incidence of neovascular formation and poor development of nonperfused area are found in this animal, SDT rat will be a useful model in studies of the pathogenesis and treatment of diabetic retinopathy.

  4. Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Al-Amin, Zainab M; Thomson, Martha; Al-Qattan, Khaled K; Peltonen-Shalaby, Riitta; Ali, Muslim

    2006-10-01

    In the present study, the hypoglycaemic potentials of ginger (Zingiber officinale) were studied in rats. An aqueous extract of raw ginger was administered daily (500 mg/kg, intraperitoneally) for a period of 7 weeks to streptozotocin (STZ)-induced diabetic rats. Fasting blood serum was analysed for blood glucose, cholesterol and triacylglycerol levels. The STZ-injected rats exhibited hyperglycaemia accompanied with weight loss, indicating their diabetic condition. At a dose of 500 mg/kg, raw ginger was significantly effective in lowering serum glucose, cholesterol and triacylglycerol levels in the ginger-treated diabetic rats compared with the control diabetic rats. The ginger treatment also resulted in a significant reduction in urine protein levels. In addition, the ginger-treated diabetic rats sustained their initial weights during the treatment period. Moreover, ginger decreased both water intake and urine output in the STZ-induced diabetic rats. The present results indicate that raw ginger possesses hypoglycaemic, hypocholesterolaemic and hypolipidaemic potential. Additionally, raw ginger is effective in reversing the diabetic proteinuria observed in the diabetic rats. Thus, ginger may be of great value in managing the effects of diabetic complications in human subjects.

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

    Energy Technology Data Exchange (ETDEWEB)

    Binz, K.; Joller, P.; Froesch, P.; Binz, H.; Zapf, J.; Froesch, E.R. (University Hospital, Zurich (Switzerland))

    1990-05-01

    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 ({sup 3}H)thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased ({sup 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{sup +}/CD8{sup +} 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.

  6. Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides.

    Science.gov (United States)

    Calenda, Giulia; Tong, Yuehong; Kanika, Nirmala D; Tar, Moses T; Suadicani, Sylvia O; Zhang, Xinhua; Melman, Arnold; Rougeot, Catherine; Davies, Kelvin P

    2011-10-01

    Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man.

  7. Metallothionein metabolism in the streptozotocin-diabetic rat

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-03-05

    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 /sup 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Renal Function and Hemodynamic Study in Obese Zucker Rats

    Science.gov (United States)

    Park, Sung Kwang; Kang, Sung Kyew

    1995-01-01

    Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies were performed in these rats. Results Functional studies showed that obese Zucker rats exhibited increases in kidney weight and GFR(obese Zucker, 1.23±.07)ml/min; lean Zucker, 0.93±.03ml/min). Micropuncture studies revealed that the increase in GFR in obese Zucker rats was attributable to the increases in the single nephron plasma flow rate and glomerular transcapillary hydraulic pressure. The glomerular ultrafiltration coefficient was the same in both groups. Morphologic studies revealed that the increase in GFR in obese Zucker rats was associated with an increase in glomerular volume. Conclusions These results suggest that obesity and hyperinsulinemia, which are the characteristics of type II diabetes, can be associated with glomerular hyperfiltration and glomerular capillary hypertension. PMID:7626557

  10. 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

  11. BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats

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    Laura A. Maile

    2014-01-01

    Full Text Available This study determined if blocking ligand occupancy of the αVβ3 integrin could inhibit the pathophysiologic changes that occur in the early stages of diabetic nephropathy (DN. Diabetic rats were treated with either vehicle or a monoclonal antibody that binds the β3 subunit of the αVβ3 integrin. After 4 weeks of diabetes the urinary albumin to creatinine ratio (UACR increased in both diabetic animals that subsequently received vehicle and in the animals that subsequently received the anti-β3 antibody compared with control nondiabetic rats. After 8 weeks of treatment the UACR continued to rise in the vehicle-treated rats; however it returned to levels comparable to control nondiabetic rats in rats treated with the anti-β3 antibody. Treatment with the antibody prevented the increase of several profibrotic proteins that have been implicated in the development of DN. Diabetes was associated with an increase in phosphorylation of the β3 subunit in kidney homogenates from diabetic animals, but this was prevented by the antibody treatment. This study demonstrates that, when administered after establishment of early pathophysiologic changes in renal function, the anti-β3 antibody reversed the effects of diabetes normalizing albuminuria and profibrotic proteins in the kidney to the levels observed in nondiabetic control animals.

  12. Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats

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    Haiyan Xu

    2017-01-01

    Full Text Available This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway.

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

    Science.gov (United States)

    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.

  14. Determinants of glomerular filtration and plasma flow in experimental diabetic rats.

    Science.gov (United States)

    Michels, L D; Davidman, M; Keane, W F

    1981-12-01

    GFR and, to a lesser extent, RPF are elevated soon after the onset of human diabetes mellitus. The mechanisms involved in these functional changes are unknown. Since the experimental diabetic rat has renal morphological changes similar to those observed in man, we investigated whole-kidney and superficial-nephron glomerular function in this animal model early during the course of the disease. Alloxan-induced diabetes (50 mg/kg BW) is frequently characterized by severe hyperglycemia and retarded body growth. Supplemental insulin administration (6 U of NPH insulin daily) results in normal body growth, although hyperglycemia persists. As a result, we studied four groups of diabetic rats (1) after 1 month of untreated diabetes, (2) after 3 months of untreated diabetes, (3) after 3 months of untreated diabetes followed by 1 month of insulin supplementation, and (4) after 3 months of insulin-supplemented diabetes. After 1 month of untreated diabetes, GFR and SNGFR each declined by 20% compared to age-matched control rats. RPF and SNGFR were both reduced by 33% as a consequence of a 41% increase in RT. Reduced SNGPF together with a 7 mm Hg reduction in PGC caused the fall in GFR and SNGFR. KWs were not significantly different from those of control rats. The functional changes that occurred after 1 month of untreated diabetes did not significantly deteriorate after 3 months of the disease. Insulin supplementation, when instituted for 1 month after 3 months of untreated diabetes, produced no significant improvement in either whole-kidney or superficial-nephron hemodynamics even though body and kidney growth were stimulated. In contrast, insulin supplementation initiated at the onset of diabetes increased both SNGFR and SNGFR to 23% above control values. GFR and RPF each increased in proportion to the 18% increment in kidney size. RT was reduced in these rats, and the pressures that govern glomerular ultrafiltration were not altered from control values. We conclude that in

  15. 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.

    Science.gov (United States)

    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.

  16. 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.

  17. [Simvastatin's effect on insulin resistance in rats with diabetes mellitus].

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    Iskakova, S; Zharmakhanova, G; Bekmukhambetov, Y; Dworacka, M; Dworacki, G

    2015-05-01

    The aim of this experimental study was to estimate the effect of Simvastatin on glycemic variability-related insulin resistance in the course of diabetes mellitus (DM) in rats. Fifty seven male Wistar rats were divided into four groups: I - rats with diabetes mellitus and glycemic variability treated with Simvastatin (20 mg/kg body weight, intragastral during 8 weeks); II - placebo-treated rats with DM and glycemic variability; III - placebo treated rats with DM and IV - nondiabetic control rats. DM was induced by feeding rats with high-fat diet (61%) during five weeks and low-dose of Streptozotocin (30 mg/kg, intraperitoneally). Daily glucose excursions were stimulated by feeding animals twice a day. We measured fasting blood glucose, glycated hemoglobin (HbA1c), insulin and HOMAIR was calculated. Higher insulin resistance in diabetic rats is related to greater daily glycemic variability. In our study was installed significant increasing HOMAIR in diabetics rats with glycemic excursions comparison with the control. Our results showed that the simvastatin-treatment decreases the indices glycemic variability and HOMA in diabetic rats with glycemic excursions.

  18. Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats.

    Science.gov (United States)

    Mahfoz, Amal M; El-Latif, Hekma A Abd; Ahmed, Lamiaa A; Hassanein, Nahed M; Shoka, Afaf A

    2016-12-01

    Since chronic kidney disease due to diabetic nephropathy (DN) is becoming an ever larger health burden worldwide, more effective therapies are desperately needed. In the present study, the anti-diabetic and renoprotective effects of aliskiren have been evaluated in streptozotocin (STZ)-induced DN in rats. DN was induced by a single intraperitoneal injection of STZ (65 mg/kg). Three weeks after STZ, rats were divided into four groups; normal, diabetic, diabetic treated with gliclazide (10 mg/kg/day) for 1 month, and diabetic treated with aliskiren (50 mg/kg/day) for 1 month. At the end of the experiment, mean arterial blood pressure and heart rate were recorded. Rats were then euthanized and serum was separated for determination of glucose, insulin, kidney function tests, superoxide dismutase activity (SOD), adiponectin, and tumor necrosis factor-alpha (TNF-α). One kidney was used for estimation of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) contents. Other kidney was used for histopathological study and immunohistochemical measurement of caspase-3 and transforming growth factor beta (TGF-β). In addition, islets of Langerhans were isolated from normal rats by collagenase digestion technique for in vitro study. Aliskiren normalized STZ-induced hyperglycemia, increased insulin level both in vivo and in vitro, normalized kidney function tests and blood pressure, and alleviated STZ-induced kidney histopathological changes. This could be related to the ability of aliskiren toward preserving hemodynamic changes and alleviating oxidative stress and inflammatory and apoptotic markers induced by STZ in rats. However, aliskiren was more effective than gliclazide in relieving STZ-induced DN. These findings support the beneficial effect of aliskiren treatment in DN which could be attributed to its anti-diabetic, renoprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects. Moreover, clinical studies are required to establish the

  19. The Spontaneously Diabetic Torii Rat: An Animal Model of Nonobese Type 2 Diabetes with Severe Diabetic Complications

    OpenAIRE

    Tomohiko Sasase; Takeshi Ohta; Taku Masuyama; Norihide Yokoi; Akihiro Kakehashi; Masami Shinohara

    2013-01-01

    The Spontaneously Diabetic Torii (SDT) rat is an inbred strain of Sprague-Dawley rat and recently is established as a nonobese model of type 2 diabetes (T2D). Male SDT rats show high plasma glucose levels (over 700 mg/dL) by 20 weeks. Male SDT rats show pancreatic islet histopathology, including hemorrhage in pancreatic islets and inflammatory cell infiltration with fibroblasts. Prior to the onset of diabetes, glucose intolerance with hypoinsulinemia is also observed. As a result of chronic s...

  20. 氨基胍对糖尿病大鼠心功能和心肌间质纤维化的影响%Effect of aminoguanidine on myocardial interstitial fibrosis and cardiac function in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    戴启明; 刘乃丰

    2012-01-01

    目的 探讨氨基胍抑制DM大鼠心肌间质纤维化的机制及其对心功能的影响. 方法 雄性SD大鼠30只,随机分成正常对照组(NC)、DM组和氨基胍干预(A)组,每组各10只.采用STZ-次性腹腔注射建立DM动物模型.12周后检测大鼠血清AGEs、左室心肌胶原含量、结缔组织生长因子(CTGF) mRNA和蛋白质表达及血流动力学. 结果 与NC组相比,DM大鼠血清AGEs的荧光值(7.21±2.2 vs 2.63±0.62,P<0.01)、左室心肌组织胶原含量(16±3% vs 12±2%,P<0.01)及CTG-FmRNA和蛋白质表达水平(0.077±0.0037 vs 0.0102±0.0034,0.51±0.01 vs 0.34±0.02,P<0.01)均明显升高,心功能明显减低;应用氨基胍干预后上述异常明显减轻.结论 氨基胍通过抑制AGEs的形成及心肌组织的CTGF的表达来逆转DM大鼠心肌间质纤维化并改善心脏功能.%Objective To investigate the effect of aminoguanidine on myocardial interstitial fibrosis and cardiac function in diabetic rats, and explore the mechanism of the actions. Methods Thirty male SD rats were randomly divided into 3 groups: normal control, STZ-induced diabetic rats, and diabetic rats treated with aminoguanidine. After 12 weeks, hemodynamics, advanced glycation end products (AGEs) in serum and values of collagen content , the expression of connective tissue growth factor (CTGF) mRNA and protein in the left ventricular tissue were measured. Results Compared with the control, AGEs fluorescence of serum(7. 21 ±2. 2 vs 2. 63+0. 62,P<0. 01),collagen content (16 + 3% vs 12±2%, P< 0. 01), the expression of CTGF mRNA(0. 077±0. 0037 vs 0. 0102±0. 0034,P< 0. 01) and protein (0. 51 ±0. 01 vs 0. 34±0. 02,P< 0. 01) of myocardium were significantly increased in the diabetic group. The cardiac function was significantly lower in the diabetic group than in the control group. However, the above-mentioned abnormalities were obviously attenuated by administration of aminoguanidine. Conclusions AGEs play an important role in

  1. Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Chen, Xiaofei; Zhao, Tong; Huang, Xin; Wu, Liying; Wu, Kuiwu; Fan, Ming; Zhu, Lingling

    2016-05-01

    Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88 ± 5.69 mmol/L vs. 14.79 ± 5.84 mmol/L, p  0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, pintermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28 ± 0.11 vs. 1.39 ± 0.11, p intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular glycogenesis may play a role in the underlying mechanism.

  2. Study of the Pharmacokinetic Changes of Tramadol in Diabetic Rats

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    Lida Hakemi

    2013-03-01

    Full Text Available Background:Besides the pathological states, diabetes mellitus may also alter the hepatic biotransformation of pharmaceutical agents. It is advantageous to understand the effect of diabetes on the pharmacokinetic of drugs. The objective of this study was to define the pharmacokinetic changes of tramadol and its main metabolites after in vivo intraperitoneal administration and ex vivo perfused liver study in diabetic rat model.Tramadol (10 mg/kg was administered to rats (diabetic and control groups of six intraperitoneally and blood samples were collected at different time points up to 300 min. In a parallel study, isolated liver perfusion was done (in diabetic and control rats by Krebs-Henseleit buffer (containing 500 ng/ml tramadol. Perfusate samples were collected at 10 min intervals up to 180 min. Concentration of tramadol and its metabolites were determined by HPLC.Results:Tramadol reached higher concentrations after i.p. injection in diabetics (Cmax of 1607.5 ± 335.9 ng/ml compared with control group (Cmax of 561.6 ± 111.4. M1 plasma concentrations were also higher in diabetic rats compared with control group. M2 showed also higher concentrations in diabetic rats. Comparing the concentration levels of M1 in diabetic and control perfused livers, showed that in contrast to intact animals, the metabolic ratios of M1 and M5 (M/T were significantly higher in diabetic perfused liver compared to those of control group.Conclusions:The pharmacokinetic of tramadol and its three metabolites are influenced by diabetes. As far as M1 is produced by Cyp2D6, its higher concentration in diabetic rats could be a result of induction in Cyp2D6 activity, while higher concentrations of tramadol can be explained by lower volume of distribution.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yusuke Kemmochi

    2014-01-01

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

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

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    Ramdas Pandhare

    2012-09-01

    Conclusion: These results suggested that APSAE has reduced development of diabetic nephropathy in streptozotocin-induced diabetic rats and could have beneficial effect in reducing the progression of diabetic nephropathy.

  6. Development of diabetes-induced acidosis in the rat retina.

    Science.gov (United States)

    Dmitriev, Andrey V; Henderson, Desmond; Linsenmeier, Robert A

    2016-08-01

    We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  8. The effect of fenugreek on nociceptive response in diabetic rats

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    Mehrdad Roghani

    2009-01-01

    Full Text Available   Abstract  Introduction: Diabetic rats display exaggerated hyperalgesic behavior in response to noxious stimuli that may resemble and model aspects of painful diabetic neuropathy in humans. This study was designed to investigate the effect of Trigonella foenum-graecum (TFG on formalin-induced nociceptive responses (standard formalin test in streptozotocin (STZ-induced diabetic rats.  Methods: For this purpose, STZ-diabetic rats received intraperitoneal injection of aqueous leaf extract of TFG (200 mg/kg every other day for a period of one month.  Results: It was found out that TFG treatment did cause a significant reduction in blood glucose in diabetic rats and TFG-treated diabetic rats exhibited a lower nociceptive score as compared to untreated-diabetic ones. Meanwhile, TFG treatment reduced the nociceptive score in both phases of the formalin test. In contrast, sodium salicylate as positive control only reduced this score in the second phase of the test.  Discussion: The results suggest therapeutic potential of aqueous extract of fenugreek for treating painful diabetic neuropathy. 

  9. Activation of the intrinsic cell death pathway, increased apoptosis and modulation of astrocytes in the cerebellum of diabetic rats.

    Science.gov (United States)

    Lechuga-Sancho, Alfonso M; Arroba, Ana I; Frago, Laura M; Pañeda, Covadonga; García-Cáceres, Cristina; Delgado Rubín de Célix, Arancha; Argente, Jesús; Chowen, Julie A

    2006-08-01

    Poorly controlled diabetes mellitus results in structural and functional changes in many brain regions. We demonstrate that in streptozotocin-induced diabetic rats cell death is increased and proliferation decreased in the cerebellum, indicating overall cell loss. Levels of both the proform and cleaved forms of caspases 3, 6 and 9 are increased, with no change in caspases 7, 8 or 12. Colocalization of glial fibrillary acidic protein (GFAP) and cleaved caspase 3 and GFAP in TUNEL-positive cells increased in diabetic rats. Changes in GFAP levels paralleled modifications in proliferating cell nuclear antigen (PCNA), increasing at 1 week of diabetes and decreasing thereafter, and proliferating GFAP-positive cells were decreased in the cerebellum of diabetic rats. These results suggest that astrocytes are dramatically affected in the cerebellum, including an increase in cell death and a decrease in proliferation, and this could play a role in the structural and functional changes in this brain area in diabetes.

  10. Hypolipidimic effect of some medicinal plants on diabetic rats

    Directory of Open Access Journals (Sweden)

    Eman G.E.Helal * and Mohamed M. A. Shahat

    2006-06-01

    Full Text Available Our aim was to evaluate the hypolipidimic effect of aqueous extract of a famous mixture used in Saudi Arabia folk medicine that consists of Nigella sativa, Commiphora myrrha, Boswellia carterii Birdw, Ferule assa-foetida and Aloe vera and also the extract of each plant alone on alloxan induced diabetic rats. Material and Methods :-The present study was carried out on 80 adult male albino rats (120 ± 20 g.b.wt. , the rats were divided randomly into 8 groups, the first group served as control group, the second group as alloxan induced diabetic rats, the third group was diabetic rats treated with mixture of folk medicinal plant ( 0.01g /100 g b. wt. ,the fourth group: diabetic rats treated with Nigella sativa ( 0.01g /100 g b. wt. , the fifth group: diabetic rats treated with Aloe vera ( 0.005g /100 g b. wt. , the sixth group: diabetic rats treated with Ferule assa-foetida ( 0.01 g /100 g b. wt., the seventh: diabetic rats treated with Boswellia carterii Birdw ( 1ml/100 g b. wt. and the eighth group: diabetic rats treated with Commiphora myrrha ( 0.01 g ml/100 g b. wt. Results :- Serum total lipid, serum total cholesterol, LDL­cholesterol, and triglyceride recorded significant increases in diabetic, Nigella sativa, Commiphora myrrha, Boswellia carterii birdw and Aloe vera treated group. While the mixture and Ferule assa-foetida treated group, showed insignificant changes in serum total lipid, triglyceride, serum total cholesterol and LDL­cholesterol. On other hand, the mixture treated group and Ferule assa-foetida treated group showed significant decreased in the previous parameters. The serum HDL­cholesterol was significantly reduced in diabetic group throughout the experimental periods, otherwise, all treated group revealed insignificant changes till the end of experiment when compare with undiabetic rats. Conclusion: The aqueous extract of a mixture consists of Nigella sativa, Commiphora myrrha, Boswellia carterii Birdw, Ferule assa

  11. Activation of retinoid receptor-mediated signaling ameliorates diabetes-induced cardiac dysfunction in Zucker diabetic rats.

    Science.gov (United States)

    Guleria, Rakeshwar S; Singh, Amar B; Nizamutdinova, Irina T; Souslova, Tatiana; Mohammad, Amin A; Kendall, Jonathan A; Baker, Kenneth M; Pan, Jing

    2013-04-01

    Diabetic cardiomyopathy (DCM) is a significant contributor to the morbidity and mortality associated with diabetes and metabolic syndrome. Retinoids, through activation of retinoic acid receptor (RAR) and retinoid x receptor (RXR), have been linked to control glucose and lipid homeostasis, with effects on obesity and diabetes. However, the functional role of RAR and RXR in the development of DCM remains unclear. Zucker diabetic fatty (ZDF) and lean rats were treated with Am580 (RARα agonist) or LGD1069 (RXR agonist) for 16 weeks, and cardiac function and metabolic alterations were determined. Hyperglycemia, hyperlipidemia and insulin resistance were observed in ZDF rats. Diabetic cardiomyopathy was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NF-κB signaling and diminished Akt phosphorylation, along with decreased glucose transport and increased cardiac lipid accumulation, and ultimately diastolic dysfunction. Am580 and LGD1069 attenuated diabetes-induced cardiac dysfunction and the pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signaling pathways. Am580 inhibited body weight gain, attenuated the increased cardiac fatty acid uptake, β-oxidation and lipid accumulation in the hearts of ZDF rats. However, LGD1069 promoted body weight gain, hyperlipidemia and cardiac lipid accumulation. In conclusion, our data suggest that activation of RAR and RXR may have therapeutic potential in the treatment of diabetic cardiomyopathy. However, further studies are necessary to clarify the role of RAR and RXR in the regulation of lipid metabolism and homeostasis.

  12. Gallbladder function in diabetic patients

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    Shreiner, D.P.; Sarva, R.P.; Van Thiel, D.; Yingvorapant, N.

    1986-03-01

    Gallbladder emptying and filling was studied in eight diabetic and six normal control patients. None of the patients had gallstones. Cholescintigraphy was performed using (/sup 99m/Tc)disofenin, and gallbladder emptying was studied using a 45-min i.v. infusion of the octapeptide of cholecystokinin (OP-CCK) 20 ng/kg X hr. The peak filling rate was greater in diabetic than in normal subjects; however, emptying of the gallbladder in response to OP-CCK was significantly less in the diabetic subjects (51.6 +/- 10.4% compared with 77.2 +/- 4.9%). When the diabetic group was subdivided into obese and nonobese diabetics, the obese diabetics had a much lower percentage of emptying than the nonobese diabetics (30.0 +/- 10.4% compared with 73.1 +/- 9.3%). These findings suggest that obese diabetics may have impaired emptying of the gallbladder even in the absence of gallstones. The more rapid rate of gallbladder filling in obesity may indicate hypotonicity of the gallbladder. The combination of these abnormalities may predispose the obese diabetic to the development of gallstones.

  13. Effect of α-lipoic acid on cognitive function after cardiopulmonary bypass in diabetic rats%α-硫辛酸对糖尿病大鼠体外循环后认知功能的影响

    Institute of Scientific and Technical Information of China (English)

    尹光明; 姚尚龙; 舒化青

    2012-01-01

    Objective To evaluate the effect of α-lipoic acid on the cognitive function after cardiopulmonary bypass (CPB) in diabetic rats.Methods Health adult male Sprague-Dawley rats,weighing 400-500 g,aged 16-22 weeks,were used in this study.Diabetes mellitus was induced by intraperitoneal streptozocin 60 mg/kg and confirmed by blood glucose≥ 16.7 mmol/L.Thirty-two diabetic rats were randomly divided into 2 groups (n =16 each):diabetes mellitus group (group D) and α-lipoi cacid group (group L).In group L,α-lipoic acid 30 mg/kg was intraperitoneally injected once a day for 7 consecutive days starting from 6th week after induction of diabetes mellitus.While the equal volume of normal saline was given instead in group D.The two groups underwent CPB after the last administration.Before induction of diabetes mellitus,on 5th week after induction of diabetes mellitus,before CPB,at the end of CPB,and on 3 and 5 days after termination of CPB,10 rats were chosen from each group and venous blood samples were collected for determination of plasma TNF-α and IL-10 concentrations.Ten rats in each group were chosen for detection of cognitive function before induction of diabetes mellitus,before CPB and 5 days after termination of CPB.The rats were then sacrificed and hippocampi were isolated for measurement of NF-κB activity.Results Compare with group D,the plasma TNF-α concentration,times of electric shock and activity of NF-κB in hippocampal tissues were significantly decreased and the plasma IL-10 concentration was increased in group L (P < 0.05 or 0.01).Conclusion α-lipoic acid can improve the cognitive function after CPB in diabetic rats and inhibition of activation of NF-κB in hippocampal neurons is involved in the mechanism.%目的 评价α-硫辛酸对糖尿病大鼠体外循环(CPB)后认知功能的影响.方法 成年雄性SD大鼠,体重400~ 450 g,16 ~ 22周龄,腹腔注射1%链脲佐菌素60 mg/kg建立糖尿病模型.取糖尿

  14. Effect of Scrophularia ningpoensis extract on diabetes in rats

    African Journals Online (AJOL)

    Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, ... determined in both diabetic control and treated rats. ..... Eds, Drug, Diet and Disease: Mechanistic Approach to.

  15. Root Extract and Fractions in Streptozotocin-Induced Diabetic Rats

    African Journals Online (AJOL)

    cholesterol, triglycerides and high density lipoprotein (HDL) levels in hyperlipidemic untreated rats ... Analysis of oxidative stress markers ... Keywords: Diabetes, Hyperlipidermia, Plumeria alba, Fructose-enriched fat diet, Oxidative stress.

  16. The Spontaneously Diabetic Torii Rat: An Animal Model of Nonobese Type 2 Diabetes with Severe Diabetic Complications

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    Tomohiko Sasase

    2013-01-01

    Full Text Available The Spontaneously Diabetic Torii (SDT rat is an inbred strain of Sprague-Dawley rat and recently is established as a nonobese model of type 2 diabetes (T2D. Male SDT rats show high plasma glucose levels (over 700 mg/dL by 20 weeks. Male SDT rats show pancreatic islet histopathology, including hemorrhage in pancreatic islets and inflammatory cell infiltration with fibroblasts. Prior to the onset of diabetes, glucose intolerance with hypoinsulinemia is also observed. As a result of chronic severe hyperglycemia, the SDT rats develop profound complications. In eyes, retinopathy, cataract, and neovascular glaucoma are observed. Proliferative retinopathy, especially, resulting from retinal neovascular vessels is a unique characteristic of this model. In kidney, mesangial proliferation and nodular lesion are observed. Both peripheral neuropathy such as decreased nerve conduction velocity and thermal hypoalgesia and autonomic neuropathy such as diabetic diarrhea and voiding dysfunction have been reported. Osteoporosis is another complication characterized in SDT rat. Decreased bone density and low-turnover bone lesions are observed. Taking advantage of these features, SDT rat has been used for evaluating antidiabetic drugs and drugs/gene therapy for diabetic complications. In conclusion, the SDT rat is potentially a useful T2D model for studies on pathogenesis and treatment of diabetic complications in humans.

  17. Neutrophil function and metabolism in individuals with diabetes mellitus

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    T.C. Alba-Loureiro

    2007-08-01

    Full Text Available Neutrophils act as first-line-of-defense cells and the reduction of their functional activity contributes to the high susceptibilityto and severity of infections in diabetes mellitus. Clinical investigations in diabetic patients and experimental studies in diabetic rats and mice clearly demonstrated consistent defects of neutrophil chemotactic, phagocytic and microbicidal activities. Other alterations that have been reported to occur during inflammation in diabetes mellitus include: decreased microvascular responses to inflammatory mediators such as histamine and bradykinin, reduced protein leakage and edema formation, reduced mast cell degranulation, impairment of neutrophil adhesionto the endothelium and migration to the site of inflammation, production of reactive oxygen species and reduced release of cytokines and prostaglandin by neutrophils, increased leukocyte apoptosis, and reduction in lymph node retention capacity. Since neutrophil function requires energy, metabolic changes (i.e., glycolytic and glutaminolytic pathways may be involved in the reduction of neutrophil function observed in diabetic states. Metabolic routes by which hyperglycemia is linked to neutrophil dysfunction include the advanced protein glycosylation reaction, the polyol pathway, oxygen-free radical formation, the nitric oxide-cyclic guanosine-3'-5'monophosphate pathway, and the glycolytic and glutaminolytic pathways. Lowering of blood glucose levels by insulin treatment of diabetic patients or experimental animals has been reported to have significant correlation with improvement of neutrophil functional activity. Therefore, changes might be primarily linked to a continuing insulin deficiency or to secondary hyperglycemia occurring in the diabetic individual. Accordingly, effective control with insulin treatment is likely to be relevant during infection in diabetic patients.

  18. Ameliorative effect of ethanolic Gymnema sylvestre extract on diabetic cardiomyopathy against streptozotocin-induced diabetes in Wistar rats

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    Vinay Kumar

    2013-01-01

    Full Text Available Background: Diabetes leads to a cardiomyopathy characterized by myocyte loss. Streptozotocin (STZ-induced diabetic cardiomyopathy is characterized by decreased left ventricular contractility and diminished ventricular compliance with marked abnormal systolic and diastolic function. Aim: The ameliorative effect of ethanolic Gymnema sylvestre extract (GSE was evaluated in diabetic cardiomyopathy against STZ-induced diabetes. Materials and Methods: Diabetes was induced by a single intravenous injection of (STZ, 45 mg/kg in male Wistar rats. Blood pressure, serum lactate dehydrogenase (LDH, glucose apolipoprotein B and lipids as well as heart weight, caspase-3, sodium potassium adenosine triphosphatase Na + K + ATPase, and DNA laddering were determined. Results and Conclusions: Administration of GSE (120 mg/kg/p.o. treatment significantly ( P < 0.01 reduced myocyte loss by suppressing the levels of cardiac caspase-3, DNA laddering; mean arterial blood pressure and heart rate as well as serum LDH, glucose, apolipoprotein B, and lipids levels. Further, it increased the heart weight and cardiac Na + K + ATPase activity in diabetic rats. The cardiomyopathy suppression is accompanied by decrease in cardiac caspase-3 levels, DNA laddering, blood pressures, serum LDH, apolipoprotein-B and glucose. Thus, this present study reports the anti-apoptotic potential of GSE in STZ-induced diabetic cardiomyopathy.

  19. Spinal pharmacology of tactile allodynia in diabetic rats

    OpenAIRE

    1997-01-01

    Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown.Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by ass...

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

    Science.gov (United States)

    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.

  1. 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.

  2. Chronic bilateral renal denervation attenuates renal injury in a transgenic rat model of diabetic nephropathy.

    Science.gov (United States)

    Yao, Yimin; Fomison-Nurse, Ingrid C; Harrison, Joanne C; Walker, Robert J; Davis, Gerard; Sammut, Ivan A

    2014-08-01

    Bilateral renal denervation (BRD) has been shown to reduce hypertension and improve renal function in both human and experimental studies. We hypothesized that chronic intervention with BRD may also attenuate renal injury and fibrosis in diabetic nephropathy. This hypothesis was examined in a female streptozotocin-induced diabetic (mRen-2)27 rat (TGR) shown to capture the cardinal features of human diabetic nephropathy. Following diabetic induction, BRD/sham surgeries were conducted repeatedly (at the week 3, 6, and 9 following induction) in both diabetic and normoglycemic animals. Renal denervation resulted in a progressive decrease in systolic blood pressure from first denervation to termination (at 12 wk post-diabetic induction) in both normoglycemic and diabetic rats. Renal norepinephrine content was significantly raised following diabetic induction and ablated in denervated normoglycemic and diabetic groups. A significant increase in glomerular basement membrane thickening and mesangial expansion was seen in the diabetic kidneys; this morphological appearance was markedly reduced by BRD. Immunohistochemistry and protein densitometric analysis of diabetic innervated kidneys confirmed the presence of significantly increased levels of collagens I and IV, α-smooth muscle actin, the ANG II type 1 receptor, and transforming growth factor-β. Renal denervation significantly reduced protein expression of these fibrotic markers. Furthermore, BRD attenuated albuminuria and prevented the loss of glomerular podocin expression in these diabetic animals. In conclusion, BRD decreases systolic blood pressure and reduces the development of renal fibrosis, glomerulosclerosis, and albuminuria in this model of diabetic nephropathy. The evidence presented strongly suggests that renal denervation may serve as a therapeutic intervention to attenuate the progression of renal injury in diabetic nephropathy.

  3. Cerebral antioxidant enzyme increase associated with learning deficit in type 2 diabetes rats.

    Science.gov (United States)

    Suge, Rie; Shimazu, Tomokazu; Hasegawa, Hajime; Inoue, Ikuo; Hayashibe, Hidemasa; Nagasaka, Hironori; Araki, Nobuo; Katayama, Shigehiro; Nomura, Masahiko; Watanabe, Shu-Ichi

    2012-10-24

    In this study, we examined alterations in the enzymatic antioxidant defenses associated with learning deficits induced by type 2 diabetes, and studied the effects of the peroxisome proliferator-activated receptor γ agonist pioglitazone on these learning deficits. Learning ability was assessed by visual discrimination tasks in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as a model of spontaneous type 2 diabetes. Levels of the antioxidant enzymes glutathione peroxidase (GPx), Cu(2+)-Zn(2+) superoxide dismutase (CuZn-SOD) and manganese SOD were measured in the cortex, hippocampus and striatum. Half the rats received oral pioglitazone (20mg/kg/day) from the early stage of diabetes (22 weeks old) to 27 weeks old. OLETF rats showed learning deficits compared with control, Long-Evans Tokushima Otsuka (LETO) rats. GPx levels in the cortex and hippocampus were increased in OLETF rats compared with LETO rats, with an inverse correlation between GPx in the hippocampus and learning score. CuZn-SOD levels were also increased in the hippocampus in OLETF rats. Pioglitazone reduced blood glucose and increased serum adiponectin levels, but had no effect on learning tasks or antioxidant enzymes, except for CuZn-SOD. These results suggest that an oxidative imbalance reflected by increased brain antioxidant enzymes plays an important role in the development of learning deficits in type 2 diabetes. Early pioglitazone administration partly ameliorated diabetic symptoms, but was unable to completely recover cerebral oxidative imbalance and functions. These results suggest that diabetes-induced brain impairment, which results in learning deficits, may have occurred before the appearance of the symptoms of overt diabetes.

  4. Effects of Kaempferia parviflora Wall. Ex Baker on endothelial dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Malakul, Wachirawadee; Thirawarapan, Suwan; Ingkaninan, Kornkanok; Sawasdee, Pattara

    2011-01-27

    The aim of the present study was to investigate an ethanolic extract of Kaempferia parviflora (KPE) reduces oxidative stress and preserves endothelial function in aortae from diabetic rats. Diabetes was induced in Sprague-Dawley rats by streptozotocin (STZ) treatment (55 mg/kg i.v.). Vascular reactivity and superoxide generation were assessed in aortic rings using standard organ bath techniques and lucigenin-enhanced chemiluminescence, respectively. Eight weeks after STZ treatment blood glucose was elevated compared to citrate treated control rats and there was an increased aortic generation of superoxide anion. In aortic rings acetylcholine-induced relaxation was impaired whereas endothelium-independent relaxation to sodium nitroprusside was unaffected. When aortic rings were acutely exposed to KPE (1, 10 and 100 μg/ml) there was a significant reduction in the detection of superoxide anion and enhanced relaxation to acetylcholine. Two separate groups of rats (control and diabetic) were orally administered daily with KPE (100 mg/kg body weight) for 4 weeks. KPE treatment reduced superoxide generation and increased the nitrite levels in diabetic aortae, and enhanced acetylcholine-induced relaxation. In the presence of N(G)-nitro-L-arginine (L-NNA), the relaxation to acetylcholine in aortic rings of diabetic rats was only partially inhibited, but was totally abolished in aortic rings from the KPE-treated diabetic rats. Indomethacin did not affect relaxation to acetylcholine in aortic rings of any group. These results suggest that KPE, acutely in vitro or after 4 weeks administration in vivo, reduces oxidant stress, increases NO bioavailability and preserves endothelium-dependent relaxation in aortae from diabetic rats. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. 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.

  6. Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes.

    Science.gov (United States)

    Olver, T Dylan; McDonald, Matthew W; Grisé, Kenneth N; Dey, Adwitia; Allen, Matti D; Medeiros, Philip J; Lacefield, James C; Jackson, Dwayne N; Rice, Charles L; Melling, C W James; Noble, Earl G; Shoemaker, J Kevin

    2014-06-15

    Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.

  7. Increased caspase-3 immunoreactivity of erythrocytes in STZ diabetic rats.

    Science.gov (United States)

    Fırat, Uğur; Kaya, Savaş; Cim, Abdullah; Büyükbayram, Hüseyin; Gökalp, Osman; Dal, Mehmet Sinan; Tamer, Mehmet Numan

    2012-01-01

    Eryptosis is a term to define apoptosis of erythrocytes. Oxidative stress and hyperglycemia, both of which exist in the diabetic intravascular environment, can trigger eryptosis of erythrocytes. In this experimental study, it is presented that the majority of erythrocytes shows caspase-3 immunoreactivity in streptozocin- (STZ)-induced diabetic rats. Besides that, caspase-3 positive erythrocytes are aggregated and attached to vascular endothelium. In conclusion, these results may start a debate that eryptosis could have a role in the diabetic complications.

  8. The Relationship Between Inflammation and Impaired Wound Healing in a Diabetic Rat Burn Model.

    Science.gov (United States)

    Tian, Ming; Qing, Chun; Niu, Yiwen; Dong, Jiaoyun; Cao, Xiaozan; Song, Fei; Ji, Xiaoyun; Lu, Shuliang

    2016-01-01

    Inflammation, initiated by polymorphonuclear neutrophil (PMNs) infiltration, is the first step in wound healing. The aim of this study is to investigate the function of neutrophils in a diabetes-impaired wound healing model and to explore the underlying mechanisms leading to neutrophil dysfunction. Superficial second-degree burns were created in the streptozotocin (STZ)-induced diabetic rat model, and the changes in the levels of advanced glycation end products (AGE), receptor of AGE (RAGE), inflammatory cytokines and oxidative markers, as well as cell apoptosis were determined. The effects of AGE on isolated PMNs were also determined in vitro. We found that deposition of AGE in diabetic rat skin activated the neutrophils before injury. However, the dense inflammatory band failed to form in the diabetic rats after injury. Compared with the controls, enhanced expression of RAGE and accelerated cell apoptosis were observed in the burned skin of diabetic rats. The altered expression pattern of inflammatory cytokines (tumor necrosis factor-alpha and interleukin-8) and oxidative markers (glutathione peroxidase, myeloperoxidase, hydrogen peroxide, and malondialdehyde) between burned skin of diabetic and control rats revealed delayed neutrophil chemotaxis and respiratory burst. Furthermore, the results in vitro showed that exposure to AGE inhibited the viability of PMNs, promoted RAGE production and cell apoptosis, and prevented the migration of PMNs, consistent with the findings in vivo. Besides, AGE-treated neutrophils showed increased secretion of inflammatory cytokines and increased oxidative stress. Combined, our results suggest that an interaction between AGE and its receptors inhibits neutrophil viability and function in the diabetic rat burn model.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  11. [Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes].

    Science.gov (United States)

    Mathison Natera, Y; Finol, H J; Quero, Z; González, R; González, J

    2010-01-01

    Decreased levels of glycosaminoglycans (GAGs) have been observed in the kidney and other organs, in human and animal models of diabetes. Long-term administration of heparins and other glycosaminoglycans has demonstrated a beneficial effect on morphological and functional kidney abnormalities in diabetic rats. We assessed the effect of pentosan polysulfate sodium (PPS), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on kidney involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague-Dawley rats by i.v. administration of streptozotocin (STZ). Animals were randomly allocated to three groups: C = control, STZ and STZ + PPS = pretreated with PPS (15 mg/kg, s.c.). After three months of follow-up, blood and 24 h-urine samples were obtained, the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinary albumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs STZ = 7.75 ± 1.8 mg/24 h) and PPS treatment partially prevented the albumin rise (3.7 ± 0.7 mg/24 h), without affecting the metabolic control HbA1c (C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + PPS = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). PPS administration prevents the tubular basement membrane thickening and the loss of cytoarchitecture induced by experimental diabetes. Our data demonstrate that long-term administration of PPS has a favourable effect on morphological and functional abnormalities in kidneys of diabetic rats and suggests a potential therapeutic use for this compound.

  12. Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats

    Science.gov (United States)

    Tucker, B. J.; Anderson, C. M.; Thies, R. S.; Collins, R. C.; Blantz, R. C.

    1992-01-01

    Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS).

  13. 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.

  14. 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.

  15. Hypoxic neuropathy versus diabetic neuropathy : an electrophysiological study in rats

    NARCIS (Netherlands)

    Gispen, W.H.; Hendriksen, P.H.; Oey, P.L.; Wieneke, G.H.; Huffelen, A.C. van

    1992-01-01

    In the experimental rat model of diabetes a slowing of nerve conduction velocity and a resistance to ischemic conduction failure have been found as an indication of polyneuropathy. The same electrophysiological abnormalities have been demonstrated in a model in which healthy rats are kept under hypo

  16. Anti-hyperglycemic activity of selenium nanoparticles in streptozotocin-induced diabetic rats

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    Al-Quraishy S

    2015-10-01

    Full Text Available Saleh Al-Quraishy,1 Mohamed A Dkhil,1,2 Ahmed Esmat Abdel Moneim2 1Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt Abstract: The study was designed to investigate the anti-hyperglycemic activity of selenium nanoparticles (SeNPs in streptozotocin-induced diabetic rats. Fifty-five mg/kg of streptozotocin was injected in rats to induce diabetes. Animals either treated with SeNPs alone or with insulin (6 U/kg showed significantly decreased fasting blood glucose levels after 28 days of treatment. The serum insulin concentration in untreated diabetic animals was also enhanced by SeNPs. The results demonstrated that SeNPs could significantly decrease hepatic and renal function markers, total lipid, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels, and glucose-6-phosphatase activity. At the same time, SeNPs increased malic enzyme, hexokinase and glucose-6-phosphate dehydrogenase activity, liver and kidney glycogen contents, and high-density lipoprotein cholesterol levels. In addition, SeNPs were able to prevent the histological injury in the hepatic and renal tissues of rats. However, insulin injection also exhibited a significant improvement in diabetic animals after 28 days of treatment. This study suggests that SeNPs can alleviate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats, possibly by eliciting insulin-mimetic activity. Keywords: diabetes, selenium, liver, kidney, toxicity

  17. Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats

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    Schaan B.D.

    2004-01-01

    Full Text Available Streptozotocin (STZ-induced diabetes in rats is characterized by cardiovascular dysfunction beginning 5 days after STZ injection, which may reflect functional or structural autonomic nervous system damage. We investigated cardiovascular and autonomic function, in rats weighing 166 ± 4 g, 5-7, 14, 30, 45, and 90 days after STZ injection (N = 24, 33, 27, 14, and 13, respectively. Arterial pressure (AP, mean AP (MAP variability (standard deviation of the mean of MAP, SDMMAP, heart rate (HR, HR variability (standard deviation of the normal pulse intervals, SDNN, and root mean square of successive difference of pulse intervals (RMSSD were measured. STZ induced increased glycemia in diabetic rats vs control rats. Diabetes reduced resting HR from 363 ± 12 to 332 ± 5 bpm (P < 0.05 5 to 7 days after STZ and reduced MAP from 121 ± 2 to 104 ± 5 mmHg (P = 0.007 14 days after STZ. HR and MAP variability were lower in diabetic vs control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 ± 0.9 to 3.4 ± 0.4 ms, P = 0.04 and SDMMAP from 6.6 ± 0.6 to 4.2 ± 0.6 mmHg, P = 0.005. Glycemia was negatively correlated with resting AP and HR (r = -0.41 and -0.40, P < 0.001 and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P < 0.01. Even though STZ-diabetic rats presented bradycardia and hypotension early in the course of diabetes, their autonomic function was reduced only 30-45 days after STZ injection and these changes were negatively correlated with plasma glucose, suggesting a metabolic origin.

  18. 转染VEGF165的内皮祖细胞移植恢复糖尿病ED大鼠的勃起功能%Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xin Gou; Yong Chen; Wei-Yang He; Ming-Zhao Xiao; Ming Qiu; Ming Wang; Yuan-Zhong Deng; Chao-Dong Liu; Zao-Sing Tang; Re Li

    2011-01-01

    The present study investigated the effect of transplanting endothelial progenitor cells (EPCs) transfected with the vascular endothelial growth factor gene (VEGF165) into the corpora cavernosa of rats with diabetic erectile dysfunction (ED). A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure (ICP) monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation (P<0.01 for both comparisons). Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.

  19. 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.

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

    OpenAIRE

    Gisou Mohaddes; Saeideh Hasani Azami; Shirin Babri

    2013-01-01

    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 administrate...

  1. Effect of diabetes on glycogen metabolism in rat retina.

    Science.gov (United States)

    Sánchez-Chávez, Gustavo; Hernández-Berrones, Jethro; Luna-Ulloa, Luis Bernardo; Coffe, Víctor; Salceda, Rocío

    2008-07-01

    Glucose is the main fuel for energy metabolism in retina. The regulatory mechanisms that maintain glucose homeostasis in retina could include hormonal action. Retinopathy is one of the chemical manifestations of long-standing diabetes mellitus. In order to better understand the effect of hyperglycemia in retina, we studied glycogen content as well as glycogen synthase and phosphorylase activities in both normal and streptozotocin-induced diabetic rat retina and compared them with other tissues. Glycogen levels in normal rat retina are low (46 +/- 4.0 nmol glucosyl residues/mg protein). However, high specific activity of glycogen synthase was found in retina, indicating a substantial capacity for glycogen synthesis. In diabetic rats, glycogen synthase activity increased between 50% and 100% in retina, brain cortex and liver of diabetic rats, but only retina exhibited an increase in glycogen content. Although, total and phosphorylated glycogen synthase levels were similar in normal and diabetic retina, activation of glycogen synthase by glucose-6-P was remarkable increased. Glycogen phosphorylase activity decreased 50% in the liver of diabetic animals; it was not modified in the other tissues examined. We conclude that the increase in glycogen levels in diabetic retina was due to alterations in glycogen synthase regulation.

  2. Anti-diabetic effects of hydroalcohlic juglans regia male flower extract on blood glucose level and on liver enzymes activity in intact and diabetogenized adult male rat

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    Seyyed Ebrahim Hosseini

    2012-08-01

    Full Text Available Background and Aim: Diabetes is a metabolic disorder resulting from defects in insulin secretion or function. Walnut is a nutrient used in traditional medicine to treat diabetes. In the current study, anti-diabetic effects of the Hydroalcoholic extract of walnut male flowers on diabetogenized rats by using Streptozocin were evaluated.   Materials and Methods: Seventy two adult male Wistar rats weighing 200-225 g each were randomly selected and divided into three main groups, i.e. control, diabetic, and non-diabetic(intact The control group included 8 rats (n=8. The diabetic and non-diabetic groups covered 32 rats each. Each of these groups were divided into four 8 rats including the control, diabetic, experimental 1, 2, and 3 which received 2, 4, or 6 g/kg of the extract per day for 15 days ,respectively. The three diabetic groups were each treated with the above doses of the extract, and the fourth group received no treatment. Diabetes was induced in diabetic rats through intraperitoneal injection of 60 mg/kg of Streptozotocin. At the end, blood samples were taken from the experimental and control groups and the serum levels of insulin and glucose were measured.   Results: A significant reduction in blood sugar and increase of insulin in diabetics receiving Hydroalcoholic extract of male flowers walnut was observed compared with non-diabetic ones.   Conclusion: Hydroalcoholic extract of male Walnut flowers, due to increasing insulin, causes reduction of blood sugar.

  3. Xanthohumol modulates inflammation, oxidative stress, and angiogenesis in type 1 diabetic rat skin wound healing.

    Science.gov (United States)

    Costa, Raquel; Negrão, Rita; Valente, Inês; Castela, Ângela; Duarte, Delfim; Guardão, Luísa; Magalhães, Paulo J; Rodrigues, José A; Guimarães, João T; Gomes, Pedro; Soares, Raquel

    2013-11-22

    Type 1 diabetes mellitus is responsible for metabolic dysfunction, accompanied by chronic inflammation, oxidative stress, and endothelium dysfunction, and is often associated with impaired wound healing. Phenol-rich food improves vascular function, contributing to diabetes prevention. This study has evaluated the effect of phenol-rich beverage consumption in diabetic rats on wound healing, through angiogenesis, inflammation, and oxidative stress modulation. A wound-healing assay was performed in streptozotocin-induced diabetic Wistar rats drinking water, 5% ethanol, and stout beer with and without 10 mg/L xanthohumol (1), for a five-week period. Wounded skin microvessel density was reduced to normal values upon consumption of 1 in diabetic rats, being accompanied by decreased serum VEGF-A and inflammatory markers (IL-1β, NO, N-acetylglucosaminidase). Systemic glutathione and kidney and liver H2O2, 3-nitrotyrosine, and protein carbonylation also decreased to healthy levels after treatment with 1, implying an improvement in oxidative stress status. These findings suggest that consumption of xanthohumol (1) by diabetic animals consistently decreases inflammation and oxidative stress, allowing neovascularization control and improving diabetic wound healing.

  4. Regulation of elongation factor-1 expression by vitamin E in diabetic rat kidneys.

    Science.gov (United States)

    Al-Maghrebi, May; Cojocel, Constantin; Thompson, Mary S

    2005-05-01

    Translation elongation factor-1 (EF-1) forms a primary site of regulation of protein synthesis and has been implicated amongst others in tumorigenesis, diabetes and cell death. To investigate whether diabetes-induced oxidative stress affects EF-1 gene expression, we used a free radical scavenger, vitamin E. The following groups of rats (5/group) were studied: control, vitamin E control, diabetic and diabetic treated with vitamin E. Markers of hyperglycemia, kidney function, oxidative stress, and kidney hypertrophy were elevated in diabetic rats. Increased urinary protein excretion indicated early signs of glomerular and tubular dysfunction. The mRNA and protein levels of the three EF-1 subunits (A, Balpha, and Bgamma) were determined in renal cortex extracts using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), northern blot analysis and western blotting. EF-1A mRNA expression in renal cortex extracts was significantly increased by at least 2-fold (p glycemic and oxidative stresses in renal cortex and kidney hypertrophy. EF-1A mRNA and protein levels were also reduced to control levels. In conclusion, EF-1A but not EF-1Balpha and EF-1Bgamma gene expression is significantly enhanced in the renal cortex of diabetic rats. Normalization of enhanced EF-1A expression by vitamin E treatment suggests a role for EF-1A during diabetes-induced oxidative stress.

  5. 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.

  6. Cytoprotective Effect of Silymarin against Diabetes-Induced Cardiomyocyte Apoptosis in Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    Muobarak J Tuorkey; Nabila I El-Desouki; Rabab A Kamel

    2015-01-01

    Objective The beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis. Methods Rats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg·d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated. Results Unlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreaticβ-cells activity. Conclusion The findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreaticβ-cells.

  7. Cardioprotective Activity of Pongamia pinnata in Streptozotocin-Nicotinamide Induced Diabetic Rats

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    Sachin L. Badole

    2015-01-01

    Full Text Available Pongamia pinnata (L. Pierre has been used in traditional medicine for the treatment for diabetes and metabolic disorder. The aim of this study was to investigate the effect of petroleum ether extract of the stem bark of P. pinnata (known as PPSB-PEE on cardiomyopathy in diabetic rats. Diabetes was induced in overnight fasted Sprague-Dawley rats by using injection of streptozotocin (55 mg/kg, i.p.. Nicotinamide (100 mg/kg, i.p. was administered 20 min before administration of streptozotocin. Rats were divided into group I: nondiabetic, group II: diabetic control (tween 80, 2%; 10 mL/kg, p.o. as vehicle, and group III: PPSB-PEE (100 mg/kg, p.o.. The blood glucose level, ECG, hemodynamic parameters, cardiotoxic and antioxidant biomarkers, and histology of heart were carried out after 4 months after STZ with nicotinamide injection. PPSB-PEE treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters; and histological changes in STZ induced diabetic rats. PPSB-PEE (100 mg/kg, p.o. decreased blood glucose level, improved electrocardiographic parameters (QRS, QT, and QTc intervals and hemodynamic parameters (SBP, DBP, EDP, max dP/dt, contractility index, and heart rate, controlled levels of cardiac biomarkers (CK-MB, LDH, and AST, and improved oxidative stress (SOD, MDA, and GSH in diabetic rats. PPSB-PEE is a promising remedy against cardiomyopathy in diabetic rats.

  8. Hypoglycemic activity of Ailanthus excelsa leaves in normal and streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Cabrera, W; Genta, S; Said, A; Farag, A; Rashed, K; Sánchez, S

    2008-03-01

    The hypoglycemic activity of a 70% methanol extract from the leaves of Ailanthus excelsa Roxb. (Simaroubaceae) was studied in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Oral administration of the extract at doses of 14, 70 and 350 mg/kg body weight caused no significant changes in fasting blood glucose levels of normal rats. In an oral glucose tolerance test, the extract produced a significant decrease in glycemia 90 min after the glucose pulse. Daily administration of A. excelsa extract for 60 days produced a significant hypoglycemic effect in diabetic animals. In addition, this treatment improved the altered renal function observed in diabetic control rats. This study suggests that Ailanthus leaf extract could be potentially useful for post-prandial hyperglycemia treatment.

  9. Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats.

    Science.gov (United States)

    Akhani, Sanjay P; Vishwakarma, Santosh L; Goyal, Ramesh K

    2004-01-01

    The fresh and dried rhizome of Zingiber officinale Roscoe (commonly known as ginger) is widely used in traditional medicine. We have studied the effect of the juice of Z. officinale (4 mL kg(-1), p.o. daily) for 6 weeks on streptozotocin (STZ)-induced type I diabetic rats with particular reference to the involvement of serotonin (5-hydroxytryptamine; 5-HT) receptors in glycaemic control. In normoglycaemic rats, 5-HT (1mg kg(-1), i.p.) produced hyperglycaemia and hypoinsulinaemia, which was significantly prevented by the juice of Z. officinale. STZ-diabetes produced a significant increase in fasting glucose levels that was associated with a significant decrease in serum insulin levels. Treatment with Z. officinale produced a significant increase in insulin levels and a decrease in fasting glucose levels in diabetic rats. In an oral glucose tolerance test, treatment with Z. officinale was found to decrease significantly the area under the curve of glucose and to increase the area under the curve of insulin in STZ-diabetic rats. Treatment with Z. officinale also caused a decrease in serum cholesterol, serum triglyceride and blood pressure in diabetic rats. Our data suggest a potential antidiabetic activity of the juice of Z. officinale in type I diabetic rats, possibly involving 5-HT receptors.

  10. Cardiovascular effects of endomorphins in alloxan-induced diabetic rats.

    Science.gov (United States)

    Liu, Jing; Yu, Ye; Fan, Ying-zhe; Chang, Hui; Liu, Hong-mei; Cui, Yun; Chen, Qiang; Wang, Rui

    2005-04-01

    Endomorphins, the endogenous, potent and selective mu-opioid receptor agonists, have been shown to decrease systemic arterial pressure (SAP) in rats. In the present study, responses to endomorphins were investigated in systemic vascular bed of alloxan-induced diabetic rats and in non-diabetic rats. Diabetes was induced by alloxan (220 mg/kg, i.p.) in male Wistar rats. At 4-5 weeks after the onset of diabetes, intravenous injections of endomorphins (1-30 nmol/kg) led to an increase of SAP and heart rate (HR) consistently and dosed-dependently. SAP increased 7.68+/-3.73, 11.19+/-4.55, 21.19+/-2.94 and 27.48+/-6.21% from the baseline at the 1, 3, 10 and 30 nmol/kg dose, respectively, of endomorphin 1 (n=4; pendomorphin 2. The hypertension could be antagonized markedly by i.p. 2 mg/kg of naloxone. On the other hand, bilateral vagotomy would attenuate the effects of hypertension and diminished the changes of HR in response to endomorphins. With diabetic rats, 6-10 weeks after the induction of diabetes, intravenous injections of endomorphins produced non-dose-related various changes in SAP, such as a single decrease, or a single increase, or biphasic changes characterized by an initial decrease followed by a secondary increase, or no change at all. These results suggest that diabetes may lead to the dysfunction of the cardiovascular system in response to endomorphins. Furthermore, the diabetic rats of 4-5 weeks after alloxan-treatment, the increase in SAP and HR caused by i.v. endomorphins might be explained by a changed effect of vagus and by a naloxone-sensitive mechanism.

  11. 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.

  12. Cardioprotective Effect of Sodium Ferulate in Diabetic Rats

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    Xiaohong Xu, Haijuan Xiao, Jiangpei Zhao, Tongfeng Zhao

    2012-01-01

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

  13. Increased spike broadening and slow afterhyperpolarization in CA1 pyrimidal cells of streptozoyocin-induced-diabetic rats

    NARCIS (Netherlands)

    Gispen, W.H.; Kamal, A.; Artola, A.; Biessels, G.J.; Ramakers, G.M.J.

    2003-01-01

    Diabetes mellitus is associated with impairments of cognitive function both in humans and animal models. In diabetic rats cognitive deficits are related to alterations in activity-dependent synaptic plasticity in the hippocampus. Many similarities with the pathophysiology of normal brain aging have

  14. Long-term AICAR administration and exercise prevents diabetes in ZDF rats.

    Science.gov (United States)

    Pold, Rasmus; Jensen, Lasse S; Jessen, Niels; Buhl, Esben S; Schmitz, Ole; Flyvbjerg, Allan; Fujii, Nobuharu; Goodyear, Laurie J; Gotfredsen, Carsten F; Brand, Christian L; Lund, Sten

    2005-04-01

    Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.

  15. Antihyperglycemic and antihyperlipidemic activity of Plectranthus amboinicus on normal and alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    A. H. M. Viswanathaswamy

    2011-01-01

    Full Text Available The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg. Normal as well as diabetic rats were divided into groups (n=6 receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 μg/kg was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect.

  16. Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Kamal, A; Artola, A; Biessels, G J; Gispen, W H; Ramakers, G M J

    2003-01-01

    Diabetes mellitus is associated with impairments of cognitive function both in humans and animal models. In diabetic rats cognitive deficits are related to alterations in activity-dependent synaptic plasticity in the hippocampus. Many similarities with the pathophysiology of normal brain aging have been noted, and the view emerges that the effects of diabetes on the brain are best described as "accelerated brain aging."In the present study we examined whether CA1 pyramidal neurons from streptozotocin-induced diabetic rats display an increased slow afterhyperpolarization, often considered as a hallmark of neuronal aging. We found no differences in resting membrane potential, input resistance, membrane time-constant, and action potential amplitude and duration between CA1 pyramidal neurons from streptozotocin-induced diabetic and age-matched control rats. During a train of action potentials, however, there is an increased broadening of the action potentials in diabetic animals, so-called "spike broadening." The amplitude of the slow afterhyperpolarization elicited by a train of action potentials is indeed increased in diabetic animals. Interestingly, when the slow afterhyperpolarization is elicited by a Ca(2+) spike, there is no difference between control and diabetic rats. This indicates that the increased slow afterhyperpolarization in diabetes is likely to be due to an increased Ca(2+) influx resulting from the increased spike broadening. These data underscore the notion that the diabetic brain at the neuronal level shares properties with brain aging.

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

    Science.gov (United States)

    Ghanbari, Elham; Nejati, Vahid; Khazaei, Mozafar

    2016-01-01

    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. PMID:27679827

  18. The diabetic rat kidney mediates inosituria and selective urinary partitioning of D-chiro-inositol.

    Science.gov (United States)

    Chang, Hao-Han; Choong, Bernard; Phillips, Anthony R J; Loomes, Kerry M

    2015-01-01

    Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 µM) and DCI (5 µM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease.

  19. Corrections by melatonin of liver mitochondrial disorders under diabetes and acute intoxication in rats.

    Science.gov (United States)

    Cheshchevik, Vitali T; Dremza, Iosif K; Lapshina, Elena A; Zabrodskaya, Svetlana V; Kujawa, Jolanta; Zavodnik, Ilya B

    2011-08-01

    The aim of the present work was to investigate the mechanisms of oxidative damage of the liver mitochondria under diabetes and intoxication in rats as well as to evaluate the possibility of corrections of mitochondrial disorders by pharmacological doses of melatonin. The experimental (30 days) streptozotocin-induced diabetes mellitus caused a significant damage of the respiratory activity in rat liver mitochondria. In the case of succinate as a respiratory substrate, the ADP-stimulated respiration rate V₃ considerably decreased (by 25%, p diabetic liver damage. Acute rat carbon tetrachloride-induced intoxication resulted in considerable decrease of the phosphorylation coefficient because of uncoupling of the oxidation and phosphorylation processes in the liver mitochondria. The melatonin administration during diabetes (10 mg·kg⁻¹ body weight, 30 days, daily) showed a considerable protective effect on the liver mitochondrial function, reversing the decreased respiration rate V₃ and the diminished ACR to the control values both for succinate-dependent respiration and for glutamate-dependent respiration. The melatonin administration to intoxicated animals (10 mg·kg⁻¹ body weight, three times) partially increased the rate of succinate-dependent respiration coupled with phosphorylation. The impairment of mitochondrial respiratory plays a key role in the development of liver injury under diabetes and intoxication. Melatonin might be considered as an effector that regulates the mitochondrial function under diabetes.

  20. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: Study in vasopressin-deficient Brattleboro rats

    OpenAIRE

    Bardoux, Pascale; Martin, Hélène; Ahloulay, Mina; Schmitt, François; Bouby, Nadine; Trinh-Trang-Tan, Marie-Marcelle; Bankir, Lise

    1999-01-01

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattlebor...

  1. The Effect of Blood Glucose Fluctuation on Cognitive Function in type 2 Diabetic Rats%血糖波动对2型糖尿病大鼠认知功能的影响

    Institute of Scientific and Technical Information of China (English)

    韩慧慧; 刘国荣; 梁芙茹

    2016-01-01

    Objective:To explore the effect of blood glucose fluctuation on the cognitive function in diabetic rats .Meth‐ods:24 Wistar rats were randomly divided into three groups:normal group(N group ,n=8) ,high glucose sustain diabe‐tes model group(MS group ,n=8);and glucose fluctuate diabetes model group(MF group ,n=8) ,in which model was intervened by diet .After twelve weeks of establishing MF ,Morris Water maze was used to perform training trial and probe trial in order to detect spatial learning and memory abilities .Results:Compared with N group ,MS group and MF group ,the escape latency and latency distance were significantly increased (P<0 .05) ,the number of rats passing hid‐den platform in the quadrant of hidden platform in 120s significantly decreased(P<0 .05) .Compared with MF group and MS group ,the escape latency increased significantly (P<0 .05) ,the latency was significantly longer distance (P<0 .05) ,120s within the stipulated time of crossing the platform location number also decreased significantly(P<0.05) . Conclusion:Type 2 diabetic rats learning and memory ability decreased ,blood glucose fluctuation can aggravate the cog‐nitive dysfunction in diabetic rats .%目的:探讨血糖波动对糖尿病大鼠认知功能的影响。方法:Wistar雄性大鼠24只,随机分成正常对照组(N组,n=8),持续性高血糖组(MS组,n=8)和血糖波动组(MF组,n=8),MF组通过饮食干预造成血糖波动大鼠模型。血糖波动12周后,进行MORRIS水迷宫实验。结果:与N组相比,MS组及MF组逃避潜伏期及潜伏期距离均升高(P<0.05),空间探索实验显示120s内穿越平台所在位置的次数均下降(P<0.05)。MF组和MS组相比,逃避潜伏期及潜伏期距离明显延长(P<0.05),120s规定时间内穿越平台所在位置次数也明显下降(P<0.05)。结论:2型糖尿病大鼠学习记忆能力下降,血糖波动可加重糖尿病大鼠的认知功能障碍。

  2. Astaxanthin Inhibits Expression of Retinal Oxidative Stress and Inflammatory Mediators in Streptozotocin-Induced Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Po-Ting Yeh

    Full Text Available We evaluated whether orally administered astaxanthin (AST protects against oxidative damage in the ocular tissues of streptozotocin (STZ-induced diabetic rats.Fifty 6-week-old female Wistar rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 40 or to remain uninduced (n = 10. The diabetic rats were randomly selected into four groups and they were separately administered normal saline, 0.6 mg/kg AST, 3 mg/kg AST, or 0.5 mg/kg lutein daily for eight weeks. Retinal functions of each group were evaluated by electroretinography. The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by immunohistochemistry, western blot analysis, ELISA, RT-PCR, and electrophoretic mobility shift assay (EMSA. Retinal functions were preserved by AST and lutein in different levels. Ocular tissues from AST- and lutein-treated rats had significantly reduced levels of oxidative stress mediators (8-hydroxy-2'-deoxyguanosine, nitrotyrosine, and acrolein and inflammatory mediators (intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fractalkine, increased levels of antioxidant enzymes (heme oxygenase-1 and peroxiredoxin, and reduced activity of the transcription factor nuclear factor-kappaB (NF-κB.The xanthophyll carotenoids AST and lutein have neuroprotective effects and reduce ocular oxidative stress, and inflammation in the STZ diabetic rat model, which may be mediated by downregulation of NF-κB activity.

  3. The effect of reduced glutathione on glomerular endothelial function in diabetic rats%还原型谷胱甘肽对糖尿病大鼠肾小球内皮功能的影响

    Institute of Scientific and Technical Information of China (English)

    刘滇军; 刘辉辉; 沈建明; 田少江; 王黎萍; 李骏峰

    2014-01-01

    Objective:To observe the feature of glomerular endothelial function in rats with early diabetic nephropathy(DN),and evaluate the effect of reduced glutathione on glomerular endothelial function in diabetic rats. Methods:Streptozotocin(60mg/ kg) was injected into peritoneal cavity in the rats to establish animal DN model. The diabetic rats were randomly divided into DN model group and reduced glutathione treated group. Coherent kits were used to detect glomerular nitrogen monoxide( NO) ,the activity of glomerular endothelial nitric oxide synthase ( eNOS ) , von Willebrand factor ( vWF ) , urinary albumin ( UA ) , superoxide dismutase ( SOD ) , malondialdehyde( MDA ) and glutathione peroxidase. Results:Compared with normal control group, glomerular NO, activities of glomerular eNOS were significantly decreased in early DN rats,while the level of vWF and UA significantly increased(P<0. 01),and the level of UA was correlated with the level of glomerular vWF(P <0. 05). Glomerular SOD,glutathione peroxidase significantly decreased in early DN rats,while MDA was significantly increased(P <0. 01). Compared with DN model group,glomerular NO, activities of glomerular eNOS were significantly increased in early DN rats treated with reduced glutathione,while the level of vWF and UA were significantly decreased,and glomerular MDA was significantly increased in early DN rats treated with reduced glutathione( P<0. 01). Conclusions:Glomerular endothelial function is indiscriminate in early DN rats,while the level of oxidative stress significantly increases. Reduced glutathione improves glomerular endothelial dysfunction in early DN rats,maybe through reducing oxidative stress.%目的:观察早期糖尿病肾病( diabetic nephropathy,DN)大鼠肾小球内皮功能的特点,探讨还原型谷胱甘肽对早期DN大鼠内皮功能的影响。方法:将大鼠分为对照组、模型组和治疗组,应用链脲佐菌素腹腔注射建立DN模型,治疗组每天腹腔注射还原型

  4. Impact of alogliptin and pioglitazone on lipid metabolism in islets of prediabetic and diabetic Zucker Diabetic Fatty rats.

    Science.gov (United States)

    Cai, Ying; Lydic, Todd A; Turkette, Thomas; Reid, Gavin E; Olson, L Karl

    2015-05-01

    Prolonged exposure of pancreatic beta (β) cells to elevated glucose and free fatty acids (FFA) as occurs in type 2 diabetes results in loss of β cell function and survival. In Zucker Diabetic Fatty (ZDF) rats, β cell failure is associated with increased triacylglyceride (TAG) synthesis and disruption of the glycerolipid/FFA (GL/FFA) cycle, a critical arm of glucose-stimulated insulin secretion (GSIS). The aim of this study was to determine the impact of activation of PPARγ and increased incretin action via dipeptidyl-peptidase inhibition using pioglitazone and/or alogliptin, respectively, on islet lipid metabolism in prediabetic and diabetic ZDF rats. Transition of control prediabetic ZDF rats to diabetes was associated with reduced plasma insulin levels, reduced islet insulin content and GSIS, reduced stearoyl-CoA desaturase 2 (SCD 2) expression, and increased islet TAG, diacylglyceride (DAG) and ceramides species containing saturated FA. Treatment of prediabetic ZDF rats with a combination of pioglitazone and alogliptin, but not individually, prevented the transition to diabetes and was associated with marked lowering of islet TAG and DAG levels. Pioglitazone and alogliptin, however, did not restore SCD2 expression, the degree of FA saturation in TAG, DAG or ceramides, islet insulin content, or lower ceramide levels. These findings are consistent with activation of PPARγ and increased incretin action working in concert to restore GL/FFA cycle in β cells of ZDF rats. Restoration of the GL/FFA cycle without correcting islet FA desaturation, production of islet ceramides, and/or insulin sensitivity, however, may place these islets at risk for β cell failure.

  5. Intravitreal injection of IGFBP-3 restores normal insulin signaling in diabetic rat retina.

    Directory of Open Access Journals (Sweden)

    Youde Jiang

    Full Text Available Diabetes-induced changes in growth factor binding protein 3 (IGFBP-3 and tumor necrosis factor alpha (TNFα have been linked to decreased insulin receptor signaling in diabetic retinopathy. Our previous studies in retinas of diabetic rats have shown that Compound 49b, a novel β-adrenergic receptor agonist, prevented diabetic changes by increasing IGFBP-3 and decreasing TNFα, thus restoring insulin signaling and protection against diabetic retinopathy. The current study was designed to determine whether boosted expression of IGFBP-3 NB (a non-IGF-1 binding form of IGFBP-3 alone is sufficient to mimic the full actions of Compound 49b in protecting against diabetic retinopathy, as well as testing whether IGFBP-3 NB is linked to a restoration of normal insulin signal transduction. Two months after initiation of streptozotocin-induced diabetes, rats received a single intravitreal injection of IGFBP-3 NB plasmid in the right eye. Four days after injection, electroretinogram (ERG analyses were performed prior to sacrifice. Whole retinal lysates from control, diabetic, diabetic + control plasmid, and diabetic+ IGFBP-3 NB were analyzed for IGFBP-3, TNFα, suppressor of cytokine signaling 3 (SOCS3, and insulin receptor signaling partners using Western blotting or ELISA. Data show that a single intraocular injection of IGFBP-3 NB in diabetic animals significantly reduced TNFα levels, concomitant with reductions in IRS-1Ser307, SOCS3, and pro-apoptotic markers, while restoring insulin receptor phosphorylation and increasing anti-apoptotic marker levels. These cellular changes were linked to restoration of retinal function. Our findings establish IGFBP-3 as a pivotal regulator of the insulin receptor/TNFα pathway and a potential therapeutic target for diabetic retinopathy.

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

    Directory of Open Access Journals (Sweden)

    Yingli Jin

    2014-01-01

    evidently reduced by fenugreek treatment. Furthermore, the upregulation of TGF-β1 and CTGF at a transcriptional and translational level in DN rats was distinctly inhibited by fenugreek. Consequently, fenugreek prevents DN development in a STZ-induced diabetic rat model.

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

    Science.gov (United States)

    Grigorov, Ilijana; Bogojević, Desanka; Jovanović, Sofija; Petrović, Anja; Ivanović-Matić, Svetlana; Zolotarevski, Lidija; Poznanović, Goran; Martinović, Vesna

    2014-06-01

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

  8. Luteolin improves the impaired nerve functions in diabetic neuropathy: behavioral and biochemical evidences.

    Science.gov (United States)

    Li, Ming; Li, Qiang; Zhao, Qingsong; Zhang, Jinchao; Lin, Jiang

    2015-01-01

    Peripheral neuropathies are a major cause of morbidity in patients with diabetes mellitus. Up to now, drugs for improving the impaired nerve functions has been lacking for diabetic neuropathy. The antioxidant and neuroprotective effects of luteolin make it an attractive candidate for diabetic neuropathy. The present study was designed to investigate the putative beneficial effect of luteolin on diabetic neuropathy. Diabetic rats were intraperitoneally treated with daily luteolin (50 mg/kg, 100 mg/kg and 200 mg/kg) or vehicle for 3 weeks from the 28(th) day after streptozotocin injection. Behavioral, electrophysiological and biochemical studies were performed to evaluate the effect of luteolin on the impaired nerve functions in diabetic neuropathy. It was found that luteolin dose dependently alleviated abnormal sensation, improved nerve conduction velocities and nerve blood flow in diabetic rats. Biochanical analysis showed that luteolin significantly lowered the reactive oxygen species production and malondialdehyde level, as well as increased antioxidants activities in a dose dependent manner. In addition, luteolin significantly up-regulated the protein levels of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in diabetic nerves. Taken together, luteolin is capable of improving diabetes-induced deficit in motor and sensory functions, which could be attributable, at least in part, to its Nrf2-dependent antioxidant capacity. The findings in the present study highlight the therapeutic value of luteolin for diabetic neuropathy.

  9. Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats.

    Science.gov (United States)

    Delic, Denis; Eisele, Claudia; Schmid, Ramona; Luippold, Gerd; Mayoux, Eric; Grempler, Rolf

    2016-05-03

    The aim of the present pilot study was the identification of micro-RNA changes over time during the development and progression of type 2 diabetes (T2D) in Zucker diabetic fatty rats (ZDF rats). T2D is a complex metabolic disorder that is characterized, inter alia, by progressive failure of pancreatic β cells to produce insulin, but also by functional or morphological modifications of others organ, such as liver, adipose tissue and the cardiovascular system. Micro-RNAs are a novel class of biomarkers that have the potential to represent biomarkers of disease progression. In this study, the onset and progression of diabetes was followed in ZDF rats from six weeks until 17 weeks of age. After an initial phase of hyperinsulinemia, the animals developed T2D and lost the capacity to produce sufficient insulin. Circulating miRNAs were measured from plasma samples at four time points: pre-diabetes (six weeks of age), hyperinsulinemia (eight weeks), β cell failure (11 weeks) and late-stage diabetes (17 weeks) using TaqMan miRNA arrays. Bioinformatic analysis revealed distinct changes of circulating miRNAs over time. Several miRNAs were found to be increased over the course of the disease progression, such as miR-122, miR-133, miR-210 and miR-375. The most significantly decreased miRNAs were miR-140, miR-151-3p, miR-185, miR-203, miR-434-3p and miR-450a. Some of the miRNAs have also been identified in type 2 diabetic patients recently and, therefore, may have the potential to be useful biomarkers for the disease progression of T2D and/or the treatment response for anti-diabetic medications.

  10. Cryptotanshinone Inhibits STAT3 Signaling to Alleviate Cardiac Fibrosis in Type 1-like Diabetic Rats.

    Science.gov (United States)

    Lo, Shih-Hsiang; Hsu, Chao-Tien; Niu, Ho-Shan; Niu, Chiang-Shan; Cheng, Juei-Tang; Chen, Zhih-Cherng

    2017-04-01

    Cryptotanshinone is an active principal ingredient isolated from Salvia miltiorrhiza (Danshen), a medicinal plant used in China to treat cardiac disorders. The objective of this study was to investigate the effect of cryptotanshinone on myocardial fibrosis in diabetic rats. In streptozotocin-induced type 1 diabetic model hyperglycemic rats (STZ-treated rats), fasting blood glucose levels and heart weight/body weight ratio were markedly increased but both were not modified by cryptotanshinone. Additionally, cardiac performance in catheterized STZ-treated rats was improved. The histological results from Masson staining showed that cryptotanshinone attenuated cardiac fibrosis in STZ-treated rats. Moreover, both the mRNA and protein levels of the signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9, and connective tissue growth factor were reduced by cryptotanshinone in high glucose-cultured cardiomyocytes, similar to the reductions observed in the hearts of STZ-treated rats. In conclusion, while STAT3 regulates matrix metalloproteinase-9 and connective tissue growth factor expression in diabetic rats with cardiac fibrosis, cryptotanshinone inhibited fibrosis to improve cardiac function by suppressing the STAT3 pathway. Cryptotanshinone is suitable as an alternative remedy for therapy of cardiac fibrosis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Elevated levels of the serum endogenous inhibitor of nitric oxide synthase and metabolic control in rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Xiong, Yan; Fu, Yun-feng; Fu, Si-hai; Zhou, Hong-hao

    2003-08-01

    This study was designed to determine the relationship between elevated levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and metabolic control in rats with streptozotocin-induced diabetes. Serum levels of ADMA were measured by high-performance liquid chromatography at 8 weeks after diabetes was induced. Endothelium-dependent relaxation to acetylcholine was tested in aortic rings from nondiabetic age-matched control, untreated diabetic, and insulin-treated diabetic rats to evaluate endothelial function. Serum concentrations of glucose, glycosylated serum protein, and malondialdehyde were examined to estimate metabolic control. Serum levels of ADMA increased dramatically in untreated diabetic rats compared with control rats. This elevation in ADMA levels was accompanied by impairment of the endothelium-dependent relaxation response to acetylcholine in aortic rings. Long-term insulin treatment not only prevented the elevation of serum ADMA levels, but also improved the impairment of endothelium-dependent relaxation in diabetic rats. Serum levels of glucose, glycosylated serum protein, and malondialdehyde were significantly increased in parallel with the elevation of ADMA in untreated diabetic rats compared with control rats. These parameters were normalized after diabetic rats received insulin treatment for 8 weeks. These results provide the first evidence that an elevation in the concentration of ADMA in rats with streptozotocin-induced diabetes is closely related to metabolic control of the disease.

  12. Effect of Food Restriction on Adipose Tissue in Spontaneously Diabetic Torii Fatty Rats

    Directory of Open Access Journals (Sweden)

    Hisayo Morinaga

    2009-01-01

    Full Text Available Spontaneously Diabetic Torii-fa/fa (SDT fatty rat is a new model of obese type 2 diabetes. SDT fatty rat exhibits obesity associated with hyperphagia. In this study, SDT fatty rats were subjected to pair-feeding with SDT-+/+ (SDT rats from 6 to 22 weeks of age. The ratio of visceral fat weight to subcutaneous fat weight (V/S decreased at 12 weeks of age in the pair-feeding rats. The intraperitoneal fat weight such as epididymal and retroperitoneal fat weight decreased, whereas mesenteric fat weight had no change. Cell size of the epididymal fat in the pair-feeding rats tended to decrease. Glucose oxidation level in epididymal fat in the pair-feeding rats at 12 weeks of age was recovered to a similar level with that in SDT rats. These results indicated that SDT fatty rat is a useful model to evaluate the functional or the morphological features in adipose tissue and develop a novel drug for antiobesity.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Axonal and dendritic changes are associated with diabetic encephalopathy in rats: an important risk factor for Alzheimer's disease.

    Science.gov (United States)

    Zhou, Yanping; Luo, Yi; Dai, Jiapei

    2013-01-01

    Axonopathy is closely linked to and promotes diabetic peripheral neuropathy and a subset of neurological diseases including Alzheimer's disease (AD), but its involvement in the development of diabetic encephalopathy remains unknown. In the present study, we aimed to ascertain the role of axonopathy in the development of diabetic encephalopathy and the possible relationship between diabetic encephalopathy and AD. The streptozotocin (STZ)-induced diabetic rat model was used. A Y-maze task, in vivo neuronal tracing, immunohistochemistry, and western blot analysis were performed to evaluate the cognitive functions, axonal and dendritic changes, and the expressions of amyloid-β (Aβ) and hyperphosphorylated tau in relation to the development of diabetic encephalopathy in this diabetic model. Coincident with significant memory impairment, the diabetic rats showed obvious axonal and dendritic changes, termed axonopathy and dendropathy, respectively, which mainly manifested as the swelling of axons, varicosities, and dendrites in the cognitive-associated brain regions compared to the non-diabetic animals. The site-specific hyperphosphorylated tau, but not deposits of Aβ, was detected in the diabetic rat brains. These data reveal a key role of axonopathy and dendropathy accompanied with the site-specific hyperphosphorylated tau in the course of diabetic encephalopathy, which may be the early link to the neuropathological processes of AD.

  15. Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Eren Çerman

    Full Text Available Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP labelled bone marrow derived stem cells (BMSC and left eyes with balanced salt solution (Sham. Animals were grouped as Baseline (n = 51, Diabetic (n = 45, Diabetic+BMSC (n = 45 eyes, Diabetic+Sham (n = 45 eyes, Healthy+BMSC (n = 6 eyes, Healthy+Sham (n = 6 eyes. Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function.

  16. Ability of alpha-lipoic acid to reverse the diabetic cystopathy in a rat model

    Institute of Scientific and Technical Information of China (English)

    Yuan-jun JIANG; Da-xin GONG; Hai-bo LIU; Chun-ming YANG; Zhi-xi SUN; Chui-ze KONG

    2008-01-01

    Aim: The present study was conducted to investigate whether alpha-lipoic acid (α-LA) is able to reverse impaired bladder function induced by diabetes in a rat model and to explore the possible mechanism mediating the effect. Methods: Male Sprague-Dawley rats were divided randomly into 3 age-matched groups: control, diabetes mellitus (DM) treated with vehicle, and DM with α-LA treatment. The diabetic rats were induced by a single intraperitoneal (ip) injection of streptozotocin (60 mg/kg). Six weeks after the induction of DM, the two groups received another 6 weeks of treatment with vehicle or α-LA (100 mg/kg, ip). Body weight and blood glucose levels were measured weekly. The bladder function was evaluated by in vitro cystometry. The oxidative stress status was determined by biochemical methods, and the level of nerve growth factor was investigated by enzyme-linked immunosorbent assay. Results: The streptozotocin-induced diabetic rats showed impaired bladder function characterized by increased bladder capacity, decreased bladder contractility (voiding efficiency), and an increase in residual urine. Treat-ment with α-LA significantly normalized the increased bladder capacity for induc-ing voiding, single-voided volume, and post-void residual volume, α-LA treat-ment significantly reversed the increased level of malondialdehyde and reduced the activities of both superoxide dismutase and catalase. DM caused a decrease in the bladder nerve growth factor (NGF) level, and α-LA upregulated the level of NGF in the diabetic rat bladder. Conclusion: These results indicate that α-LA has a beneficial effect on diabetes-induced cystopathy by ameliorating oxidative stress and normalizing the NGF level in the bladder.

  17. Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xin-ting WANG; Jia LI; Li LIU; Nan HU; Shi JIN; Can LIU; Dan MEI; Xiao-dong LIU

    2012-01-01

    Aim:Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions.The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications.Methods:Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats.On d 35 after the injection,liver,heart,intestine,kidney,pancreas,cerebral cortex and hippocampus were isolated from the rats.The content of total and free cholesterol in the tissues was determined using HPLC.The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses,respectively.Results:In diabetic rats,the level of free cholesterol was significantly decreased in the peripheral tissues,but significantly elevated in hippocampus,as compared with those in the control rats.Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues,but significant change was only found in kidney and liver.In diabetic rats,the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex,but the change had no statistical significance.Conclusion:Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus.The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.

  18. Ameliorative effect of combination of benfotiamine and fenofibrate in diabetes-induced vascular endothelial dysfunction and nephropathy in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Chakkarwar, Vishal Arvind; Singh, Manjeet

    2009-01-01

    The study has been designed to investigate the effect of benfotiamine and fenofibrate in diabetes-induced experimental vascular endothelial dysfunction (VED) and nephropathy. The single administration of streptozotocin (STZ) (50 mg/kg, i.p.) produced diabetes, which was noted to develop VED and nephropathy in 8 weeks. The diabetes produced VED by attenuating acetylcholine-induced endothelium dependent relaxation, impairing the integrity of vascular endothelium, decreasing serum nitrite/nitrate concentration and increasing serum TBARS and aortic superoxide anion generation. Further, diabetes altered the lipid profile by increasing the serum cholesterol, triglycerides and decreasing the high density lipoprotein. The nephropathy was noted to be developed in the diabetic rat that was assessed in terms of increase in serum creatinine, blood urea, proteinuria, and glomerular damage. The benfotiamine (70 mg/kg, p.o.) and fenofibrate (32 mg/kg, p.o.) or lisinopril (1 mg/kg, p.o., a standard agent) treatments were started in diabetic rats after 1 week of STZ administration and continued for 7 weeks. The treatment with benfotiamine and fenofibrate either alone or in combination attenuated diabetes-induced VED and nephropathy. In addition, the combination of benfotiamine and fenofibrate was noted to be more effective in attenuating the diabetes-induced VED and nephropathy when compared to treatment with either drug alone or lisinopril. Treatment with fenofibrate normalizes the altered lipid profile in diabetic rats, whereas benfotiamine treatment has no effect on lipid alteration in diabetic rats. It may be concluded that diabetes-induced oxidative stress, lipids alteration, and consequent development of VED may be responsible for the induction of nephropathy in diabetic rats. Concurrent administration of benfotiamine and fenofibrate may provide synergistic benefits in preventing the development of diabetes-induced nephropathy by reducing the oxidative stress and lipid

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 星状神经节阻滞对糖尿病大鼠细胞免疫功能的影响%Effect of stellate ganglion block on cellular immune function in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    郎海丽; 胡小兰; 陈勇; 周志东; 蔡俊赢; 余树春; 徐国海

    2016-01-01

    目的 评价星状神经节阻滞对糖尿病大鼠细胞免疫功能的影响.方法 健康雄性SD大鼠,3月龄,体重240~ 280 g,采用腹腔注射1%链脲佐菌素60 mg/kg制备糖尿病模型.取糖尿病模型制备成功的大鼠48只,采用随机数字表法分为2组(n=24):糖尿病组(DM组)和星状神经节阻滞组(SGB组);另取健康同龄大鼠24只作为对照组(C组).SGB组于糖尿病模型制备成功1周后行右颈交感干离断术,C组和DM组仅分离右颈交感干.分别于颈交感干离断术前(T0)、术后1、3、7d(T13)时,随机取6只大鼠,采集下腔静脉血样,测定血糖浓度,采用ELISA法检测血浆去甲肾上腺素(NE)浓度,采用FACSCalibur流式细胞仪检测全血T淋巴细胞亚群CD3+、CD4+和CD8+的水平,计算CD4+/CD8+比值;处死前称重,解剖分离胸腺组织称重,计算胸腺指数(胸腺重量÷大鼠体重).结果 与C组比较,DM组和SGB组T0-3时血糖升高,全血CD3+和CD4+的水平、CD4+/CD8+比值和胸腺指数降低(P<0.05),CD8+水平差异无统计学意义(P>0.05),SGB组T1-3时血浆NE浓度降低(P<0.05),DM组血浆NE浓度差异无统计学意义(P>0.05);与DM组比较,SGB组T1-3时血糖及血浆NE浓度降低,全血CD3+和CD4+的水平、CD4+/CD8+比值和胸腺指数升高(P<0.05),CD8+水平差异无统计学意义(P>0.05).结论 星状神经节阻滞可改善糖尿病大鼠细胞免疫功能.%Objective To evaluate the effect of stellate ganglion block (SGB) on cellular immune function in diabetic rats.Methods Healthy male Sprague-Dawley rats,aged 3 months,weighing 240-280 g,were used in this study.Diabetes mellitus was induced by intraperitoneal 1% streptozotocin 60 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L 3 days later.Forty-eight rats with diabetes mellitus were randomly divided into 2 groups (n=24 each) using a random number table:diabetes mellitus group (group DM) and group SGB.Another 24 healthy rats,aged 3 months,were selected and served as

  1. Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI.

    Directory of Open Access Journals (Sweden)

    Guangliang Ding

    Full Text Available Treatment of stroke with bone marrow stromal cells (BMSC significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM. T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo. T2DM rats received BMSC (5x106, n = 8 or an equal volume of phosphate-buffered saline (PBS (n = 8 via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05 decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T1-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T2 maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI.

  2. Protective effect of total flavonoids extracted from the leaves of Murraya paniculata (L.) Jack on diabetic nephropathy in rats.

    Science.gov (United States)

    Zou, Jingtao; Yu, Xiaofeng; Qu, Shaochun; Li, Xuwen; Jin, Yongri; Sui, Dayuan

    2014-02-01

    This study was designed to evaluate the effects of total flavonoids extracted from the leaves of Murraya paniculata (L.) Jack (TFMP) on diabetic nephropathy. High fat diet and streptozotocin-induced diabetic rats were treated with the TFMP (35 or 70 mg/kg) for 13 weeks. Changes of renal function parameters were examined at the end of administration. Some kidneys were collected for histological and immunohistochemistry studies, the other ones for biochemical parameters analysis. TFMP significantly decreased the levels of serum blood urea nitrogen, serum creatinine, creatinine clearance, interleukin-6, urinary albumin, 24h-urinary albumin excretion rate, kidney weight to body weight ratio and fasting blood glucose in diabetic rats. Meanwhile, the levels of triglycerides, total and LDL cholesterols in the TFMP treated diabetic rats were lower and the high-density lipoprotein cholesterol level was higher than that in the diabetic rats. TFMP treatment significantly blocked the decrease of superoxide dismutase and glutathione peroxidase and increase of malondialdehyde levels in diabetic rats. Furthermore, the TFMP not only decreased the expression of TGF-β1 and CTGF protein, but also reduced diabetes-induced morphological alterations of the kidney. These results suggest that TFMP is a protective agent against renal damage in diabetic nephropathy.

  3. Combined MMF and insulin therapy prevents renal injury in experimental diabetic rats.

    Science.gov (United States)

    Wu, Xiaoyan; Zha, Dongqing; Xiang, Guangsheng; Zhang, Bo; Xiao, Shu-Yuan; Jia, Ruhan

    2006-12-01

    Conventional therapies for diabetic mellitus are not effective in preventing the progression from early diabetic nephropathy (DN) to end-stage renal disease. The role of inflammation in the pathogenesis of DN has been implicated both clinically and experimentally, which provides an alternative therapeutic target for DN. Anti-inflammatory impact of mycophenolate mofetil (MMF) alone and in combination with insulin had been observed in a rat model of experimental DN. In this study, the diabetic rats were subjected to different treatments. Compared to control, the expression levels of CD68, NGF, and NF-kappaB p65, as determined immunohistochemically, were elevated in diabetic rats. Treatment with combined MMF/insulin is associated with a significant reduction in renal tissue of NGF and NF-kappaB p65 expression, macrophage infiltration. It also partially improved the renal function and attenuated renal hypertrophy at early stage of DN. CD68 was found to positively correlate with urinary albumin excretion and NGF. The combined use of MMF/insulin seemed to offer more protections in rats with experimental diabetic renal injury, and the protective effects of MMF might be due to its anti-inflammatory actions through inhibition of NF-kappaB activation and reduction of T cells and macrophage infiltration and/or other kidney chemokine productions.

  4. Progressive histopathological changes in pancreatic islets of Zucker Diabetic Fatty rats.

    NARCIS (Netherlands)

    Janssen, S.W.J.; Hermus, A.R.M.M.; Lange, W.; Knijnenburg, Q.; Laak, J.A.W.M. van der; Sweep, C.G.J.; Martens, G.J.M.; Verhofstad, A.A.J.

    2001-01-01

    Thus far, histopathological changes in the pancreatic islets of Zucker Diabetic Fatty (ZDF) rats, an animal model of type 2 diabetes mellitus (or non-insulin-dependent diabetes mellitus), have only been studied in male rats and in 18-weeks old rats or younger. In this study, we have examined in both

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Eicosanoids, β-cell function, and diabetes.

    Science.gov (United States)

    Luo, Pengcheng; Wang, Mong-Heng

    2011-08-01

    Arachidonic acid (AA) is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes into eicosanoids, which are involved in diverse diseases, including type 1 and type 2 diabetes. During the last 30 years, evidence has been accumulated that suggests important functions for eicosanoids in the control of pancreatic β-cell function and destruction. AA metabolites of the COX pathway, especially prostaglandin E(2) (PGE(2)), appear to be significant factors to β-cell dysfunction and destruction, participating in the pathogenesis of diabetes and its complications. Several elegant studies have contributed to the sorting out of the importance of 12-LOX eicosanoids in cytokine-mediated inflammation in pancreatic β cells. The role of CYP eicosanoids in diabetes is yet to be explored. A recent publication has demonstrated that stabilizing the levels of epoxyeicosatrienoic acids (EETs), CYP eicosanoids, by inhibiting or deleting soluble epoxide hydrolase (sEH) improves β-cell function and reduces β-cell apoptosis in diabetes. In this review we summarize recent findings implicating these eicosanoid pathways in diabetes and its complications. We also discuss the development of animal models with targeted gene deletion and specific enzymatic inhibitors in each pathway to identify potential targets for the treatment of diabetes and its complications.

  8. Effects of Hypericum perforatum extract on diabetes-induced learning and memory impairment in rats.

    Science.gov (United States)

    Hasanein, Parisa; Shahidi, Siamak

    2011-04-01

    Cognitive impairment occurs in diabetes mellitus. Hypericum perforatum has been used in folk medicine to improve mental performance. Here it is hypothesized that chronic treatment with an extract of Hypericum perforatum (6, 12 and 25 mg/kg, p.o.) would have effects on passive avoidance learning (PAL) and memory in control and streptozotocin-induced diabetic rats. Treatments were begun at the onset of hyperglycaemia. PAL was assessed 30 days later. A retention test was done 24 h after training. At the end, the animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. Hypericum treatment (12 and 25 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. A dose of 6 mg/kg did not affect cognitive function. Hypericum administration did not alter the body weight and plasma glucose levels. Antioxidant properties and cholinergic facilitatory effects of Hypericum may be involved in its nootropic effects. These results show that Hypericum perforatum prevented the deleterious effects of diabetes on PAL and memory. As Hypericum would be free of major side effects compared with other nootropic medications, it may provide a new potential alternative for demented diabetic patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan.

    Science.gov (United States)

    Kakimoto, Tetsuhiro; Okada, Kinya; Hirohashi, Yoshihiro; Relator, Raissa; Kawai, Mizue; Iguchi, Taku; Fujitaka, Keisuke; Nishio, Masashi; Kato, Tsuyoshi; Fukunari, Atsushi; Utsumi, Hiroyuki

    2014-07-01

    Diabetic nephropathy is a major complication in diabetes and a leading cause of end-stage renal failure. Glomerular podocytes are functionally and structurally injured early in diabetic nephropathy. A non-obese type 2 diabetes model, the spontaneously diabetic Torii (SDT) rat, is of increasing preclinical interest because of its pathophysiological similarities to human type 2 diabetic complications including diabetic nephropathy. However, podocyte injury in SDT rat glomeruli and the effect of angiotensin II receptor blocker treatment in the early stage have not been reported in detail. Therefore, we have evaluated early stages of glomerular podocyte damage and the beneficial effect of early treatment with losartan in SDT rats using desmin as a sensitive podocyte injury marker. Moreover, we have developed an automated, computational glomerulus recognition method and illustrated its specific application for quantitatively studying glomerular desmin immunoreactivity. This state-of-the-art method enabled automatic recognition and quantification of glomerular desmin-positive areas, eliminating the need to laboriously trace glomerulus borders by hand. The image analysis method not only enabled assessment of a large number of glomeruli, but also clearly demonstrated that glomerular injury was more severe in the juxtamedullary region than in the superficial cortex region. This applied not only in SDT rat diabetic nephropathy but also in puromycin aminonucleoside-induced nephropathy, which was also studied. The proposed glomerulus image analysis method combined with desmin immunohistochemistry should facilitate evaluations in preclinical drug efficacy studies as well as elucidation of the pathophysiology of diabetic nephropathy. © 2014 Society for Endocrinology.

  11. Influence of streptozotocin-induced diabetes and insulin treatment on the pituitary-testicular axis during sexual maturation in rats.

    Science.gov (United States)

    Sudha, S; Valli, G; Julie, P M; Arunakaran, J; Govindarajulu, P; Balasubramanian, K

    2000-01-01

    Effects of streptozotocin (STZ)-diabetes and insulin treatment on the functioning of pituitary-testicular axis during sexual maturation was studied. Prepubertal (30 days old) and pubertal (50 days old) male Wistar rats were made diabetic by a single injection of STZ. A group of diabetic rats was given insulin (3U/100 g b.wt./day in 2 equally divided doses), 3 days after STZ treatment. Prepubertal and pubertal rats of all groups were killed on postnatal days 51 and 71, respectively. STZ-diabetes caused marked reduction in serum LH, FSH, prolactin, testosterone and testicular interstitial fluid testosterone as well as the activities of Leydig cellular steroidogenic enzymes (3beta-and 17beta-hydroxysteroid dehydrogenases). Insulin treatment to diabetic rats maintained these changes at control range except FSH and prolactin in prepubertal rats. The results indicate that (i) diabetes-induced steroidogenic lesions in Leydig cells represent a direct consequence of dysfunctioning of pituitary-testicular axis, (ii) the adverse effects of diabetes on pituitary-testicular functions are influenced by age of its induction and (iii) optimum insulin level is essential for the acquisition of Leydig cellular steroidogenic efficacy during sexual development.

  12. 链霉素诱导的2型糖尿病大鼠模型的肾脏功能变化%Changes of Renal Function in Type 2 Diabetic Rats Model Induced by Streptozotocin

    Institute of Scientific and Technical Information of China (English)

    冯犁; 李广阔; 钟森

    2014-01-01

    Objective Observe the changes of renal function in the type 2 diabetic rats model induced by streptozotocin,and explore whether this model is suitable for the study of diabetes renal damage.Methods Diabetes mellitus animal models were induced by intraperitoneal injection of streptozotocin (STZ)and a high-fat diet.The diabetic rats are categorized as the diabetes group(DG,n =10),the normal SD rats are categorized as the normal control group(NCG,n =8).The blood glu-cose,blood urea nitrogen,serum creatinine,serum AGE,urine microalbumin and kidney weight index were measured 8 weeks after STZ injection in two groups.The expressions of RAGE,PKC and PKA in renal tissue were measured by Real Time PCR(RT -PCR)and Western blot.Results The blood glucose,blood urea nitrogen,serum creatinine,serum AGE,u-rine microalbumin and Kidney weight index level of DG group were significantly higher than NCG group(P <0.05).The mRNA and protein expression of RAGE and PKC of DG group were higher than NCG group(P <0.05).The mRNA and protein expression of PKA of DG group were significantly lower than NCG group.(P <0.05).Conclusion The type 2 dia-betic rat model induced by STZ has significant damage of renal function in 8 weeks after STZ injection;The important up-stream factors of kidney damage-RAGE,PKC and PKA were significantly changed,Therefore this animal model could be used for the study of diabetic renal damage and it's suitable for observation of early diabetic nephropathy.%目的:通过观察链霉素诱导的2型糖尿病大鼠模型肾脏功能的变化,以探讨此种模型是否适用于糖尿病肾损害的研究。方法采用链脲佐菌素(streptozotocin ,STZ)辅以高脂饮食建立2型糖尿病大鼠模型,筛选造模成功的大鼠为糖尿病组,并与正常大鼠比较,造模后8周观察两组大鼠血糖、血尿素氮(blood urea nitrogen,BUN)、血肌酐(creatinine,CR)、血糖基化终末产物(Advanced glycation end products ,AGE)

  13. Protein turnover in adipose tissue from fasted or diabetic rats

    Science.gov (United States)

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

    1986-01-01

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

  14. Protein turnover in adipose tissue from fasted or diabetic rats

    Science.gov (United States)

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

    1986-01-01

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

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

    Science.gov (United States)

    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.

  16. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats

    Science.gov (United States)

    Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara EF; Dutra, Bárbara A; Oliveira, Márcio V; de Magalhães, Amélia CM; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M

    2016-01-01

    This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. PMID:26490345

  17. Effects of red mold dioscorea with pioglitazone, a potentially functional food, in the treatment of diabetes

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    Chien-Li Chen

    2015-12-01

    Full Text Available The prevalence of type 2 diabetes mellitus is increasing rapidly, and its treatment with pioglitazone is likely to induce rhabdomyolysis. We aimed to determine the effect of cotreatment with pioglitazone and red mold dioscorea (RMD produced by Monascus purpureus NTU 568 on pancreas function in streptozotocin (STZ-induced diabetic rats. In diabetic rats fed RMD, RMD with pioglitazone, and pioglitazone alone, insulin concentrations increased significantly by 18.6–40.4%, 64.0–100.0%, and 52.8%, respectively, compared with that in the diabetic group (p < 0.05. Oral glucose tolerance was impaired in the STZ-induced diabetic group within 4 weeks, however, oral glucose tolerance in rats treated with RMD or RMD with pioglitazone improved after 4 weeks, 6 weeks, and 8 weeks. Findings from this study might lend support to the use of RMD as a novel functional food for the prevention of diabetes.

  18. Propolis effect on streptozotocin-induced diabetic rats

    OpenAIRE

    DRS Sartori; CL Kawakami; CL Orsatti; JM Sforcin

    2009-01-01

    Propolis is one of the hive products that has been used extensively in folk medicine, due to its several biological and pharmacological properties. Besides, propolis-containing products have been intensely marketed by the pharmaceutical industry and health-food stores. This work was carried out in order to investigate whether propolis treatment could revert the metabolic alterations of streptozotocin-induced diabetic rats. Animals were kept in metabolic cages and diabetes was induced by a sin...

  19. Simvastatin,atorvastatin,and pravastatin equally improve the hemodynamic status of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    María; J; Crespo; José; Quidgley

    2015-01-01

    AIM: To investigate if the effect of statins improving cardiovascular(CV) status of diabetics is drug-specific or class-dependent, and the underlying mechanisms involved.MET HOD S : We compared the results of daily administration over a four-week period of a low dose(10 mg/kg per day) of atorvastatin(AV), simvastatin(SV), and pravastatin(PV) on cardiac performance in diabetic rats. Echocardiographic variables were tested, as well as systolic blood pressure(SBP), acetylcholine(ACh)-induced relaxation, plasma cholesterol levels, and perivascular fibrosis. Malondialdehyde(MDA) and 4-hydroxyalkenal(4-HAE), and endothelial nitric oxide synthase(e NOS) and inducible nitric oxide synthase(i NOS) protein levels were also measured in cardiac and aortic homogenates. RESULTS: In untreated diabetic rats, cholesterol levels were higher than in control rats(CT; n = 8, P < 0.05), and the low dose of statins used did not modify these levels. In diabetic rats, SBP was higher than in CT, and was significantly reduced by all three statins(n = 10, P < 0.05). Echocardiographic parameters(EF, SV, and COI) were all lower in untreated diabetic rats than in CT(n = 10, P < 0.05). These CV parameters were equallyimproved by all three statins. The maximal relaxation(EMax) induced by ACh in aortic ring from diabetic rats was also improved. Moreover, this relaxation was abolished by 1 mmol/L NG-nitro-L-arginine methyl ester, suggesting the involvement of a NO-dependent mechanism. CONCLUSION: AV, SV, and PV are equally effective in improving CV performance in diabetic rats. All tree statins decreased media thickness, perivascular fibrosis, and both MDA and 4-HAE in the aortas of diabetic rats, without affecting e NOS and i NOS protein levels. The observed hemodynamic benefits are cholesterolindependent. These benefits appear to be secondary to the improved endothelial function, and to the reduced vascular tone and remodeling that result from decreased oxidative stress.

  20. Pulmonary functions in patients with diabetes mellitus

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    Muhammad Irfan

    2011-01-01

    Full Text Available Background: A reduction in lung capacity has been reported previously among diabetics. According to WHO estimates, Pakistan is currently eighth in the prevalence of diabetes mellitus (DM and will become fourth by the year 2025 with over 15 million individuals. This study was designed to see the impairment of lung functions on spirometry in DM patients. Objective: Our aim was to investigate the pulmonary functions tests of Pakistani patients with DM. Materials and Methods: Between January to July 2004, 128 subjects who were never-smokers and had no acute or chronic pulmonary disease were recruited. Sixty-four of these subjects had DM and 64 were healthy matched controls. All underwent screening with detailed history, anthropometry, lipid profile, and spirometric measurements at the Aga Khan University Hospital, Karachi, Pakistan. Results: The mean age of diabetics and matched control were 54.3±9 and 54.0±8 (P<0.87 years, respectively. Diabetes patients showed a significant reduction in the forced vital capacity (FVC [mean difference (95% CI - 0.36 (-0.64, -0.07 P<0.01], forced expiratory volume in one second (FEV 1 [- 0.25(-0.50, -0.003 P<0.04], and slow vital capacity (SVC [- 0.28(-0.54, -0.01 P<0.04], relative to nondiabetic controls. There was no significant difference noted in the forced expiratory ratio and maximum mid-expiratory flow between the groups. There was also a significant higher level of triglycerides noted among diabetics (P<0.001. Conclusion: Diabetic patients showed impaired lung function independent of smoking. This reduced lung function is likely to be a chronic complication of diabetes mellitus.

  1. 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.

  2. Acute exercise adjustments of cardiovascular autonomic control in diabetic rats.

    Science.gov (United States)

    Da Pureza, Demilto Yamagushi; Jorge, Luciana; Sanches, Iris Callado; Irigoyen, Maria-Cláudia; De Souza, Romeu Rodrigues; De Angelis, Kátia

    2012-07-01

    We evaluated the role of cardiovascular autonomic changes in hemodynamics at rest and in response to exercise in streptozotocin-induced diabetic rats. Male Wistar rats were divided into nondiabetic (ND, n = 8) and diabetic (D, n = 8) groups. Arterial pressure signals were recorded in the basal state and after atropine or propranolol injections at rest, during exercise and during recovery. At rest, vagal tonus was reduced in D (37 ± 3 bpm) in comparison with the ND group (61 ± 9 bpm). Heart rate during exercise was lower in D in relation to ND rats associated with reduced vagal withdrawal in the D group. The D rats had an increase in vagal tonus in the recovery period (49 ± 6 bpm). Exercise-induced hemodynamic adjustment impairment in diabetic rats was associated with reduced cardiac vagal control. The vagal dysfunction was attenuated after aerobic exercise, reinforcing the positive role of this approach in the management of cardiovascular risk in diabetics. Copyright © 2012 Wiley Periodicals, Inc.

  3. Effects of grape seed proanthocyanidin extract on renal injury in type 2 diabetic rats.

    Science.gov (United States)

    Bao, Lei; Zhang, Zhaofeng; Dai, Xiaoqian; Ding, Ye; Jiang, Yanfei; Li, Yujie; Li, Yong

    2015-01-01

    Grape seed proanthocyanidin extract (GSPE) is known to be an effective natural polyphenol capable of removing free radicals in vivo. It has been reported that GSPE has biological functions including antioxidant, anti-cancer, anti-hyperglycemic, anti-radiation, and prevention and treatment of cardiovascular diseases. This study aims to investigate the effects of GSPE on renal injury in type 2 diabetic rats induced with low-dose streptozotocin and a high-carbohydrate/high-fat diet. Rats (n=12 per group) were administered GSPE at either a low (125 mg/kg · bw), medium (250 mg/kg · bw) or high (500 mg/kg · bw) dose, while control rats and diabetes mellitus group rats received no specific treatment. After 16 weeks, GSPE slightly increased body weight and decreased food consumption, water intake and urine volume in rats. Diabetic rats treated with GSPE demonstrated decreased fasting blood glucose, serum insulin, HbA1c and systolic blood pressure (P<0.05). GSPE significantly improved renal function parameters, reduced the expression of tissue inhibitor of metalloproteinase-1 and also increased the activity of matrix metalloproteinase-9. Moreover, GSPE (particularly at a dose of 500 mg/kg · bw) increased the activity of antioxidant enzymes and reduced the levels of c-reactive proteins (P<0.01) in serum and the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 (P<0.05) in the kidney. These findings suggest that GSPE ameliorates renal injury in type 2 diabetic rats through its antioxidative activity and anti-inflammatory effects.

  4. Anti-diabetic effect of Capparis spinosa L. root extract in diabetic rats

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    Mostafa Kazemian Mansur Abad

    2015-06-01

    Full Text Available Objective: Diabetes mellitus is the most common metabolic disorders with severe impact on quality of life. Reducing serum glucose levels and normalization of serum lipid is of great clinical importance for treating diabetes. To our knowledge, there are not any evidences about the anti-diabetic action of capparis spinosa root. In the present study the effects of the C. spinosa root extract on diabetic metabolic disorders have been studied in experimental diabetes. Materials and Methods: Rats were divided into six groups: normal control (NC, diabetic control (DC, diabetic rats receiving 0.2, 0.4 g/kg of plant extract or 0.6 mg/kg glibenclamide (groups D0.2, D0.4 or DG respectively. A normal group of rats was also designed to receive 0.2 g/kg of plant extract (N0.2. Rats were rendered diabetic (streptozotocin 60 mg/kg, i.p. and treated with 0.2, 0.4 g/ kg of plant extract or glibenclamide for four weeks. At the end of the experiment, blood was drawn through heart puncture under deep anesthesia. Weight was measured weekly, glucose levels were measured at the first and fourth week and lipid profiles, insulin and liver enzymes at the end of the study. Results: Glucose levels significantly decreased after treating with plant extract (p=0.003. However, insulin levels did not increase in any treating groups. Plant extract could significantly raise HDL and reduce levels of LDL and liver enzymes (ALT and ALP. Conclusion: These results showed that C. spinosa rootextract could improve diabetic related metabolic derangement such as hyperglycemia, dyslipidemia, and elevated liver markers in an insulin-independent manner.

  5. Ischemic conditioning protects from axoglial alterations of the optic pathway induced by experimental diabetes in rats.

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    Diego C Fernandez

    Full Text Available Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.

  6. Therapeutic insight into molsidomine, a nitric oxide donor in streptozotocin-induced diabetic nephropathy in rats

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    Nathani Minaz

    2016-01-01

    Full Text Available Background: Diabetes-induced oxidative stress and hypertension play a major role in the development of nephropathy. Hence, the present study was undertaken to evaluate the protective effects of molsidomine, a nitric oxide donor in streptozotocin (STZ-induced diabetic nephropathy (DN in rats. Materials and Methods: Type 1 diabetes was induced through a single dose of STZ (52 mg/kg, i.p. in male Wistar rats and then treated with molsidomine (5 and 10 mg/kg; p.o. for 8 weeks. Physical parameters, vital and renal function test including blood glucose, albuminuria, blood urine nitrogen, serum creatinine, and kidney index were determined. Oxidative stress and lipid peroxidation were assessed in the kidney homogenate by means of antioxidant enzymes and malondialdehyde levels. Results: DN rats exhibited a significant renal dysfunction with a reduction in body weight, excessive oxidative stress, and pathological changes. Molsidomine treatment significantly improved vital sign, renal functions, and oxidative stress in DN rats in a dose-dependent manner. The protective effect of molsidomine was also substantiated by pathological changes in the architect of the kidney. Conclusion: Molsidomine shows a significant beneficial effect in Type 1 DN in rats.

  7. Diabetic cardiomyopathy: effects of fenofibrate and metformin in an experimental model – the Zucker diabetic rat

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    Gadot Nicolas

    2009-03-01

    Full Text Available Abstract Background Diabetic cardiomyopathy (DCM contributes to cardiac failure in diabetic patients. It is characterized by excessive lipids accumulation, with increased triacylglycerol (TAG stores, and fibrosis in left ventricle (LV. The mechanisms responsible are incompletely known and no specific treatment is presently defined. We evaluated the possible usefulness of two molecules promoting lipid oxidation, fenofibrate and metformin, in an experimental model of DCM, the Zucker diabetic rat (ZDF. Methods ZDF and controls (C rats were studied at 7, 14 and 21 weeks. After an initial study at 7 weeks, ZDF rats received no treatment, metformin or fenofibrate until final studies (at 14 or 21 weeks. C rats received no treatment. Each study comprised measurements of metabolic parameters (plasma glucose, TAG, insulin levels and sampling of heart for histology and measurements of TAG content and relevant mRNA concentration. Results ZDF rats were insulin-resistant at 7 weeks, type 2 diabetic at 14 weeks and diabetic with insulin deficiency at 21 weeks. Their plasma TAG levels were increased. ZDF rats had at 7 weeks an increased LV TAG content with some fibrosis. LV TAG content increased in untreated ZDF rats at 14 and 21 weeks and was always higher than in C. Fibrosis increased also moderately in untreated ZDF rats. Metformin and fenofibrate decreased plasma TAG concentrations. LV TAG content was decreased by metformin (14 and 21 weeks and by fenofibrate (14 weeks. Fibrosis was reduced by fenofibrate only and was increased by metformin. Among the mRNA measured, fenofibrate increased Acyl-CoA Oxidase mRNA level, metformin decreased Acyl-CoA Synthase and increased AdipoR1 and pro-inflammatory mRNA levels. Conclusion Fenofibrate had favourable actions on DCM. Metformin had beneficial effect on TAG content but not on fibrosis. PPARα agonists could be useful for the prevention and treatment of DCM.

  8. Morphological Changes of Gingiva in Streptozotocin Diabetic Rats

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    C. Tesseromatis

    2009-01-01

    Full Text Available Gingivitis and periodontitis are chronic bacterial diseases of the underlying and surrounding tooth tissues. Diabetes mellitus is responsible for tooth deprivation both by decay and periodontal disease. The streptozotocin-induced diabetes results in a diabetic status in experimental animals similar to that observed in diabetes patients. The aim of the study was to investigate the relationship between the gingival lesions and the microangiopathy changes in streptozotocin-induced diabetes mellitus. Forty male Wistar rats were divided into two groups (control and experimental. Diabetes mellitus was induced by 45 mg/kg IV streptozotocin. The histological investigation of the marginal gingival and the relevant gingival papilla showed inflammation of the lamina propria and the squamous epithelium as well as marked thickness of the arteriole in the diabetic group, but no changes were observed in the control group. The results suggested a probable application of a routine gingival histological investigation in diabetic patients in order to control the progress of disease complications. It may be concluded that histological gingival investigation can be used as a routine assay for the control of the diabetic disease and prevention of its complications.

  9. Spinal orexin-1 receptors mediate anti-hyperalgesic effects of intrathecally-administered orexins in diabetic neuropathic pain model rats.

    Science.gov (United States)

    Kajiyama, Seiji; Kawamoto, Masashi; Shiraishi, Seiji; Gaus, Syafruddin; Matsunaga, Aki; Suyama, Hidemichi; Yuge, Osafumi

    2005-05-17

    Orexin-A and orexin-B are endogenous ligands of orexin receptors that contain orexin-1 and orexin-2. Activation of the orexinergic system can produce antinociceptive effects in acute inflammatory, mono-neuropathic, and postoperative pain animal models, though the effects of orexins on diabetic neuropathic pain have not been previously investigated. In this study, we studied the anti-hyperalgesic effects of intrathecally administered orexins in a streptozotocin-induced diabetic rat. First, dose-dependent effects were investigated by measuring hind paw withdrawal thresholds in response to noxious-heat and punctate stimuli, after which orexin levels in the cerebrospinal fluid of diabetic rats were measured and compared with those of normal rats using a radioimmunoassay method. The functional role of spinal orexin-1 receptors with the anti-hyperalgesic effects of orexins was also investigated using intrathecal pretreatment with SB-334867, a selective orexin-1 receptor antagonist. Intrathecally administered orexins produced an antinociceptive effect in diabetic rats, however, not in normal rats, though the orexin levels in the cerebrospinal fluid of diabetic rats were similar to those in normal rats. In addition, the anti-hyperalgesic effects of orexins were significantly inhibited by pretreatment with SB-334867. These findings demonstrate that the anti-hyperalgesic effects of orexins in diabetic rats are unlikely due to any direct effect by the supplement on decreased endogenous orexins in the cerebrospinal fluid and that orexin-1 receptors in the spinal cord may be involved in the modulation of nociceptive transmission in diabetic neuropathy. We conclude that the spinal orexinergic system may be a possible target for elucidating the mechanisms of diabetes-induced hyperalgesia.

  10. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

    Science.gov (United States)

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

    2013-01-01

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

  11. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

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    Gehan S Georgy

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

  12. Pulmonary function test in type 1 diabetics

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    R.N. Gajbhiye

    2013-07-01

    Full Text Available Objective: Present study was undertaken to find out the effect of diabetes on the respiratory system. Background: Diabetes is a disease with multiple organ involvement. Glycosylation of tissue proteins occur when blood glucose level remain elevated for a prolonged duration. Due to this, there occur irreversible changes in the chemical structure of tissue proteins. Basement membrane and connective tissues in skin, muscles, respiratory system, vascular bed, kidney, peripheral nervous system, etc. are the targets for glycosylation. Pulmonary function testing (P.F.T. is a valuable tool for evaluating the respiratory system, representing an important adjunct to the patient history, various lung imaging studies, and invasive testing such as bronchoscopy and open-lung biopsy. Material and Method: 64 type 1 diabetic subjects and 60 controls were selected for the study. Anthropometric parameters, blood investigations and P.F.T. were performed on all subjects. Result and Discussion: Fasting and Post Meal blood glucose levels as well as HbA1c% were significantly higher in type 1 diabetics as compared to controls. All P.F.T. parameters excepting FEV1 % were also significantly reduced in type 1 diabetics. Decreased values of P.F.T parameters in type 1 diabetics can be attributed to biochemical alteration of connective tissue constituents particularly collagen and elastin as well as by microangiopathy due to nonenzymatic protein glycosylation induced by chronic hyperglycemia.

  13. Antihyperlipidemic and Biochemical Activities of Mcy Protein in Streptozotocin Induced Diabetic Rats

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    Saritha Marella

    2015-02-01

    Full Text Available Background: This study was aimed to evaluate the protective effects of a novel anti-hyperglycemic “Mcy protein” isolated from the fruits of Momordica cymbalaria in streptozotocin induced- diabetes rat model. Materials and Methods: Wild type and Streptozotocin induced diabetic male wistar albino rats were either treated with single intraperitoneal injection of 2.5 mg Mcy protein/kg body weight or acetate buffer daily for 30 days. Fasting blood glucose and, serum and tissue lipid levels were measured along with biochemical analysis for hepatic and renal function tests. Results: Mcy protein significantly reduced the fasting blood glucose and, serum as well as tissue lipid levels (pConclusion: Mcy protein can alleviate hyperlipidemia and help manage diabetes by stimulating insulin secretion without evident toxic effects on liver and kidney.

  14. The variation of macro- and micro-minerals of tissues in diabetic and non-diabetic rats.

    Science.gov (United States)

    Presley, Tennille D; Duncan, A'ja V; Jeffers, Anne B; Fakayode, Sayo O

    2017-01-01

    This study determined the levels of Ca, Mg, Fe, Zn, Cu, and Na in various tissues samples (liver, brain, kidney, intestines, muscle and hair) of diabetic and non-diabetic rats by flame atomic absorption spectroscopy, in order to assess the role of element levels during T2DM. The ratios of Ca/Mg, Zn/Cu, Ca/Zn, and Mg/Zn in diabetic and non-diabetic rat tissues were also calculated. The determined element levels were further subjected to a student-t test statistical analysis and multiple-linear-regression in order to evaluate similarities, differences, and an inter-element association in tissues of diabetic and non-diabetic rats. The results of the study showed high variability in element levels and Ca/Mg Zn/Cu Mg/Zn Ca/Zn ratios in the tissues of diabetic and non-diabetic rats, but are tissue- and element-dependent, suggesting differences in the accumulation of the elements in tissues of diabetics and non-diabetics. The obtained significant differences in the levels of elements and Ca/Mg Zn/Cu Mg/Zn Ca/Zn ratios in several tissues of diabetic and non-diabetic rats in this study suggest that the investigated elements play considerable roles in the T2DM disease process. Strong inter-element associations (R(2)≥0.9) were observed for some elements in tissues of diabetic and non-diabetics rats. However, poor inter-elemental associations were obtained for some elements in the tissues of diabetic and non-diabetic rats. Published by Elsevier GmbH.

  15. Cardiac β-Adrenoceptor Expression Is Reduced in Zucker Diabetic Fatty Rats as Type-2 Diabetes Progresses.

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    James M Haley

    Full Text Available Reduced cardiac β-adrenoceptor (β-AR expression and cardiovascular dysfunction occur in models of hyperglycemia and hypoinsulinemia. Cardiac β-AR expression in type-2 diabetes models of hyperglycemia and hyperinsulinemia, remain less clear. This study investigates cardiac β-AR expression in type-2 diabetic Zucker diabetic fatty (ZDF rats.Ex vivo biodistribution experiments with [3H]CGP12177 were performed in Zucker lean (ZL and ZDF rats at 10 and 16 weeks of age as diabetes develops. Blood glucose, body mass, and diet consumption were measured. Western blotting of β-AR subtypes was completed in parallel. Echocardiography was performed at 10 and 16 weeks to assess systolic and diastolic function. Fasted plasma insulin, free fatty acids (FFA, leptin and fed-state insulin were also measured.At 10 weeks, myocardial [3H]CGP12177 was normal in hyperglycemic ZDF (17±4.1mM compared to ZL, but reduced 16-25% at 16 weeks of age as diabetes and hyperglycemia (22±2.4mM progressed. Reduced β-AR expression not apparent at 10 weeks also developed by 16 weeks of age in ZDF brown adipose tissue. In the heart, Western blotting at 10 weeks indicated normal β1-AR (98±9%, reduced β2-AR (76±10%, and elevated β3-AR (108±6. At 16 weeks, β1-AR expression became reduced (69±16%, β2-AR expression decreased further (68±14%, and β3-AR remained elevated, similar to 10 weeks (112±9%. While HR was reduced at 10 and 16 weeks in ZDF rats, no significant changes were observed in diastolic or systolic function.Cardiac β-AR are reduced over 6 weeks of sustained hyperglycemia in type-2 diabetic ZDF rats. This indicates cardiac [3H]CGP12177 retention and β1- and β2-AR expression are inversely correlated with the progression of type-2 diabetes.

  16. Hypoglycemic and hypocholesterolemic activities of the aqueous preparation of Kalanchoe pinnata leaves in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Nikhil; Menon; Jean; Sparks; Felix; Omoruyi

    2015-01-01

    Objective:To evaluate the hypoglycemic and hypocholesterolemic activities of the aqueous preparation of Kalanchoe pinnata(K.pinnata) leaves in streplozotocin-induced diabetic rats.Methods:Diabetes mellitus was induced in rats by a single administration of streptozotocin(60 mg/Kg).Diabetic rats were then treated with aqueous K.pinnata for 30 d.Serum glucose,proteins.lipid composition,liver and kidney function indices,inflammatory markers,and key enzymes of hepatic carbohydrate and lipid metabolism were determined.Results:The untreated and treated diabetic groups lost weight and consumed less food compared to the normal group.We noted 37.9%decrease in fasting blood glucose in the treated diabetic group compared to 13.2%and 17.0%increases in normal and untreated diabetic groups respectively.Serum cholesterol and triglyceride levels were significantly(P<0.05) reduced in the treated diabetic group compared to the untreated diabetic group.Blood urea nitrogen was significantly(P<0.05) elevated in the untreated and treated diabetic groups compared lo the normal group.Serum alkaline phosphatase and hepatic pyruvate kinase activities were significantly(P<0.05) elevated in the treated diabetic group.Scrum albumin level was signilieantiy(P<0.05) reduced in the untreated diabetic group.Serum IL-6 was significantly(P<0.05) depressed in the treated diabetic group.Conclusions:The observed decrease in body weight,blood glucose and cholesterol level suggests that the aqueous K.pinnata preparation consumption may be beneficial in the management of diabetes mellitus.The observed adverse effect on alkaline phosphatase activity may be due to the combined effect of streptozotocin-induced diabetes and K.pinnata preparation administration.

  17. Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin.

    Science.gov (United States)

    Katsuda, Yoshiaki; Sasase, Tomohiko; Tadaki, Hironobu; Mera, Yasuko; Motohashi, Yu; Kemmochi, Yusuke; Toyoda, Kaoru; Kakimoto, Kochi; Kume, Shinichi; Ohta, Takeshi

    2015-01-01

    The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with Sprague-Dawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats.

  18. Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin

    Science.gov (United States)

    KATSUDA, Yoshiaki; SASASE, Tomohiko; TADAKI, Hironobu; MERA, Yasuko; MOTOHASHI, Yu; KEMMOCHI, Yusuke; TOYODA, Kaoru; KAKIMOTO, Kochi; KUME, Shinichi; OHTA, Takeshi

    2015-01-01

    The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with Sprague-Dawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats. PMID:25736710

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

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    Pasupuleti Visweswara Rao

    2013-01-01

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

  20. Hypolipidimic effect of some medicinal plants on diabetic rats

    OpenAIRE

    Eman G.E.Helal * and Mohamed M. A. Shahat

    2006-01-01

    Our aim was to evaluate the hypolipidimic effect of aqueous extract of a famous mixture used in Saudi Arabia folk medicine that consists of Nigella sativa, Commiphora myrrha, Boswellia carterii Birdw, Ferule assa-foetida and Aloe vera and also the extract of each plant alone on alloxan induced diabetic rats. Material and Methods :-The present study was carried out on 80 adult male albino rats (120 ± 20 g.b.wt. ), the rats were divided randomly into 8 groups, the first group served as control ...

  1. Antioxidant potential of bilirubin-accelerated wound healing in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Ram, Mahendra; Singh, Vishakha; Kumar, Dhirendra; Kumawat, Sanjay; Gopalakrishnan, Anu; Lingaraju, Madhu C; Gupta, Priyanka; Tandan, Surendra Kumar; Kumar, Dinesh

    2014-10-01

    Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats.

  2. Nitrosative Stress in the Rat Retina at the Onset of Streptozotocin-Induced Diabetes.

    Science.gov (United States)

    Hernández-Ramírez, Ernesto; Sánchez-Chávez, Gustavo; Estrella-Salazar, Luis A; Salceda, Rocío

    2017-08-18

    diabetes induction; these levels were reduced by the administration of L-NAME. In addition, stress in Müller cells was determined by immunoreactivity to the glial fibrillary acidic protein. Our findings indicated the occurrence of nitrosative stress at the onset of diabetes in the rat retina and emphasized the role of NO in retinal function and the pathogenesis of retinopathy. © 2017 The Author(s). Published by S. Karger AG, Basel.

  3. Fenofibrate Treatment Enhances Antioxidant Status and Attenuates Endothelial Dysfunction in Streptozotocin-Induced Diabetic Rats

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    Murat Olukman

    2010-01-01

    Full Text Available Diabetic endothelial dysfunction is accompanied by increased oxidative stress and upregulated proinflammatory and inflammatory mediators in the vasculature. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-α results in antioxidant and anti-inflammatory effects. This study was designed to investigate the effect of fenofibrate, a PPAR-α activator, on the endothelial dysfunction, oxidative stress, and inflammation in streptozotocin diabetic rats. Diabetic rats received fenofibrate (150 mg kg−1 day−1 for 4 weeks. Fenofibrate treatment restored the impaired endothelium-dependent relaxation and increased basal nitric oxide availability in diabetic aorta, enhanced erythrocyte/liver superoxide dismutase and catalase levels, ameliorated the abnormal serum/aortic thiobarbituric acid reactive substances, and prevented the increased aortic myeloperoxidase without a significant change in serum total cholesterol and triglyceride levels. It did not affect the decreased total homocysteine level and the increased tumor necrosis factor-α level in the serum of diabetic rats. Fenofibrate-induced prevention of the endothelial function seems to be related to its potential antioxidant and antiinflammatory activity.

  4. Increased sensitivity of the renal vasculature to adenosine in streptozotocin-induced diabetes mellitus rats.

    Science.gov (United States)

    Pflueger, A C; Schenk, F; Osswald, H

    1995-10-01

    Adenosine (ADO) has been implicated as a pathophysiological factor in contrast media (CM)-induced acute renal failure, which has been encountered more often in patients with diabetes and impaired renal function. Therefore, we studied the renal vascular response to exogenous and endogenous ADO in streptozotocin-induced diabetic rats. We found that exogenous ADO (0.01-100 nmol), injected into the abdominal aorta, decreased renal blood flow (RBF) in a dose-dependent manner. The dose-response curve was shifted to the left by factor 30 in diabetic, compared with nondiabetic rats rats. Renal vascular response to endogenous ADO, assessed by postocclusive reduction of RBF after a 30-s renal artery occlusion, was significantly enhanced (P exogenous and endogenous ADO-induced renal vasoconstriction in both groups. We conclude that the ADO A1-receptor signal-transduction chain is altered in diabetic animals and that the enhanced vasoconstrictive action of ADO could be involved in the kidney pathophysiology of diabetes mellitus.

  5. A Novel Role for the Calcium Sensing Receptor in Rat Diabetic Encephalopathy

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    Shiyun Dong

    2015-01-01

    Full Text Available Background: Diabetic encephalopathy is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations ([Ca2+]i at its onset. The calcium sensing receptor (CaSR is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic encephalopathy remains unclear. Methods: In this study, diabetic rats were modeled by STZ (50 mg/kg. At the end of 4, 8 and 12 weeks, the CaSR expression in hippocampus was analyzed by Western blot. In neonatal rat hippocampal neurons, the [Ca2+]i was detected by laser scanning confocal microscopy, the production of reactive oxygen species (ROS in mitochondria, the level of NO and the mitochondrial transmembrane potential were measured by MitoSOX, DAF-FM and JC-1, respectively. Results: Our results showed in hippocampal neurons treated with high glucose, CaSR regulated [Ca2+]i through the PLC-IP3 pathway. CaSR expression was decreased and was involved in the changes in [Ca2+]i. Mitochondrial membrane potential, NO release and expression of p-eNOS decreased, while the production of ROS in mitochondria increased. Conclusion: Down-regulation of CaSR expression was accompanied by neuronal injury, calcium disturbance, increased ROS production and decreased release of NO. Up-regulation of CaSR expression attenuated these changes through a positive compensatory protective mechanism to inhibit and delay diabetic encephalopathy in rats.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pugliese, G.; Tilton, R.G.; Speedy, A.; Santarelli, E.; Eades, D.M.; Province, M.A.; Kilo, C.; Sherman, W.R.; Williamson, J.R. (Washington Univ. School of Medicine, St. Louis, MO (USA))

    1990-03-01

    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.

  7. Lactobacillus plantarum TN627 significantly reduces complications of alloxan-induced diabetes in rats.

    Science.gov (United States)

    Bejar, Wacim; Hamden, Khaled; Ben Salah, Riadh; Chouayekh, Hichem

    2013-12-01

    This study aimed to assess the potential of the probiotic strain Lactobacillus plantarum TN627 for preventing alloxan-induced diabetes in rats. The oral administration of this probiotic was noted to significantly improve the immunological parameters, protect the pancreatic tissues, and reduce the pancreatic and plasmatic α-amylase activities and level of plasma glucose in the treated as compared to the control group of rats. Furthermore, this probiotic treatment was observed to markedly reduce pancreatic and plasmatic lipase activities and serum triglyceride and LDL-cholesterol rates and to increase the level of HDL-Cholesterol. It also exerted efficient protective effects on the liver and kidney functions evidenced by significant decreases in serum aspartate transaminase, alanine transaminase, lactate dehydrogenase, and gamma-glutamyl transpeptidase activities, as well as creatinine and urea contents. Taken together, the findings indicate that L. plantarum TN627 exhibits attractive in vivo antidiabetic effects that may be helpful in preventing diabetic complications in adult rats.

  8. Trx1 Gene Therapy Enhances Angiogenic Signaling and Reduces Ventricular Remodeling in the Infarcted Myocardium of Diabetic Rats

    Science.gov (United States)

    Samuel, Samson Mathews; Thirunavukkarasu, Mahesh; Penumathsa, Suresh Varma; Koneru, Srikanth; Zhan, Lijun; Maulik, Gautam; Sudhakaran, Perumana R.; Maulik, Nilanjana

    2010-01-01

    Background The present study evaluates the reversal of diabetes mediated impairment of angiogenesis in myocardial infarction (MI) model of Type I diabetic rats by intramyocardial administration of adenoviral vector encoding Thioredoxin-1 (Ad.Trx1). Various studies have linked diabetes mediated impairment of angiogenesis to dysfunctional antioxidant systems in which Trx1 plays a central role. Methods and Results Ad.Trx1 was intramyocardially administered immediately after MI to non-diabetic and diabetic rats. Ad.LacZ was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. The myocardial function was measured by echocardiography 30 days after the intervention. The Ad.Trx1 administered group exhibited reduced fibrosis, oxidative stress and cardiomyocyte and endothelial cell apoptosis as compared to diabetic MI group along with increased capillary and arteriolar density. Western blot and immunohistochemical analysis demonstrated myocardial overexpression of Trx1, HO-1, VEGF, p38MAPKβ and decreased p-JNK and p38MAPKα in the Ad.Trx1 treated diabetic group. Alternatively, we have observed significant reduction in the expression of VEGF in SnPP (HO-1 enzyme inhibitor) treated non-diabetic and diabetic animals even after Ad.Trx1 therapy. Echocardiographic analysis after 4 weeks of MI revealed significant improvement in the myocardial functional parameters such as the ejection fraction, fractional shortening and E/A ratio in the Ad.Trx1 administered group as compared to the diabetic MI group. Conclusion We demonstrate that the infarcted myocardium can be rescued from diabetes related impairment of angiogenesis and reduce myocardial functional disorder by Trx1 gene therapy in streptozotocin induced diabetic rats. PMID:20194885

  9. Combating Combination of Hypertension and Diabetes in Different Rat Models

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    Talma Rosenthal

    2010-03-01

    Full Text Available Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD, and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH rats. The use of various drugs, such as angiotensin-converting enzyme (ACE inhibitors (ACEIs, various angiotensin receptor blockers (ARBs, and calcium channel blockers (CCBs, to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment.

  10. Mallotus roxburghianus modulates antioxidant responses in pancreas of diabetic rats.

    Science.gov (United States)

    Roy, V K; Chenkual, L; Gurusubramanian, G

    2016-03-01

    Mallotus roxburghianus has long been used by Mizo tribal people for the treatment of diabetes. Scientific validation at known doses may provide information about its safety and efficacy. Methanolic leaf extract of M. roxburghianus (MRME 100 and 400mg/kg) was tested in comparison with normal and alloxan diabetic rats for 28 days p.o. in terms of body and pancreatic weight, blood glucose level, antioxidant enzymes, expression of visfatin and PCNA, histopathology and histomorphometric measurements of pancreas. The results were evaluated statistically using ANOVA, correlation and regression and Principal component analysis (PCO). MRME (100 and 400mg/kg) treatment significantly (proxburghianus from the alloxan induced diabetic rats. MRME has significant role in protecting animals from alloxan-induced diabetic oxidative stress in pancreas and exhibited promising antihyperglycaemic and antioxidant activities along with significant reversal of disturbed antioxidant status and lipid peroxidative damage. Pancreatic architecture and physiology under diabetic oxidative stress have been significantly modulated by MRME and validated as a drug candidate for antidiabetic treatment. M. roxburghianus treatment restores the antioxidant enzyme system and rejuvenates the islets mass in alloxanized rat by accelerating visfatin and PCNA expression in pancreatic tissue.

  11. Spinal pharmacology of tactile allodynia in diabetic rats

    Science.gov (United States)

    Calcutt, Nigel A; Chaplan, Sandra R

    1997-01-01

    Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown.Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by assessing the efficacy of agents that inhibit specific components of spinal nociceptive processing.Dose-dependent inhibition of tactile allodynia in diabetic rats was noted with the N-type calcium channel antagonist SNX 239, the α2-adrenoceptor agonist dexmedetomidine, the μ-opioid receptor agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 and the non-NMDA receptor antagonist NBQX.No effect on tactile allodynia was noted after intrathecal administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the cyclo-oxygenase inhibitor ketorolac, the L-type calcium channel inhibitor diltiazem or any vehicle.These data suggest that the tactile allodynia of diabetic rats involves spinal glutamatergic pathways but is not associated with spinal release of nitric oxide or prostaglandins. PMID:9421298

  12. Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Tian W

    2015-09-01

    Full Text Available Wenjie Tian,1,2,* Hongen Lei,1,* Ruili Guan,1 Yongde Xu,1 Huixi Li,1 Lin Wang,1 Bicheng Yang,1 Zhezhu Gao,1 Zhongcheng Xin1 1Andrology Center, Peking University First Hospital, Peking University, Beijing, 2Department of Urology, The Second Hospital of Jilin University, Jilin University, Changchun, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate the therapeutic effects and potential mechanisms of icariside II (ICA II on reversing diabetic nephropathy in streptozotocin (STZ-induced type I diabetic rats.Methods: Newborn male Sprague Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU for tracking endogenous label retaining progenitor cells (LRCs. At age of 8 weeks, 48 rats were randomly divided into three groups: normal control group (n=16, diabetes mellitus group (DM; n=16, and diabetes mellitus plus ICA II therapy group (DM+ICA II, n=16. Eight weeks induced for diabetes with STZ, rats in DM group and DM+ICA II group were treated with vehicle or ICA II (5 mg/kg/day for another 8 weeks, respectively. Then, blood creatinine, 24-hour urine protein, blood urea nitrogen, and glycosylated hemoglobin were measured, as well as the expression of von Willebrand factor, malondialdehyde, transforming growth factor-β/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-β/Smad/CTGF signaling, marker of proliferation Ki-67, and EdU+ LRCs in renal tissues.Results: Increased levels of creatinine, 24-hour urine protein, and blood urea nitrogen and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly downregulate the levels of malondialdehyde and TGF-β/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney.Conclusion: ICA

  13. Vascular function in health, hypertension, and diabetes

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva

    2015-01-01

    to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

  14. Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model.

    Science.gov (United States)

    Keller, Amy C; Knaub, Leslie A; McClatchey, P Mason; Connon, Chelsea A; Bouchard, Ron; Miller, Matthew W; Geary, Kate E; Walker, Lori A; Klemm, Dwight J; Reusch, Jane E B

    2016-01-01

    Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p < 0.05). Mitochondrial superoxide increased with high glucose in Wistar SMCs (p < 0.05) with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets.

  15. 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

  16. 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

  17. Long term evaluation of functional and morphological bladder alterations on alloxan-induced diabetes and aging: experimental study in rats Avaliação funcional e morfológica tardia de alterações na bexiga secundárias ao diabetes induzido por aloxano e no envelhecimento: estudo experimental em ratos

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    Antonio Antunes Rodrigues Jr

    2008-01-01

    Full Text Available PURPOSE: to evaluate structural and functional effects of Alloxan- induced diabetes and aging on bladder of rats. METHODS: evaluations were performed in three groups: A - 8 weeks of age, B - 44 weeks of age, C - 44 weeks of age with alloxan-induced diabetes. Muscle layer thickness, extracellular matrix fibrosis and collagen were quantified on digital images of bladder samples. Cystometric evaluations before surgical vesical denervation (SVD, included maximum cystometric capacity (MCC, maximum bladder pressure (MBP, bladder contraction frequency (VCF, duration of bladder contraction (DC, threshold pressure (TP and bladder compliance (BC. After SVD, maximum cystometric capacity (MCC, BC and maximum urethral closing pressure (MUCP were also measured. RESULTS: Reduced extracellular matrix fibrosis concentration and contraction strength were found in the bladders of group C. Before SVD, bladder compliance was not different between groups. Alterations were observed in MCC after SVD. CONCLUSIONS: We did not notice smooth muscle hypertrophy in Alloxan-induced diabetic rats after 44 weeks. There was alteration in the total and relative amount of fibrosis and collagen. The cystometric studies support the idea that this morphological alterations are important to determine the different bladder functional patterns found in the aging and the Alloxan-induced diabetic animals.OBJETIVOS: avaliar alterações estruturais e funcionais da bexiga de ratos machos, associadas ao diabetes induzido por aloxano e ao envelhecimento. MÉTODOS: três grupos de animais: A - 8 semanas de idade; B- 44 semanas de idade; C - 44 semanas de idade com diabetes induzido por aloxano, foram avaliados. Realizadas medidas de espessura da camada muscular, fibrose de matriz extracelular e quantidade de colágeno, através de análise de imagem digital dos tecidos. Realizados também testes cistométricos, antes da desnervação vesical cirúrgica (DVC, para avaliar capacidade vesical (CV

  18. Time course of lithium-induced alterations in renal and endocrine function in normal and Brattleboro rats with hypothalamic diabetes insipidus.

    Science.gov (United States)

    Balment, R J; Jones, I C; Henderson, I W

    1977-04-01

    1. A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2. During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3. The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually re-established, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4. Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5. Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6. Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals were increased. 7. It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.

  19. Co-administration of caffeine and hydromethanolic fraction of Citrullus lanatus seeds improved testicular functions in alloxan-induced diabetic male Wistar rats

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    G.I. Onyeso

    2016-04-01

    Conclusions: The present study showed that co-administration of caffeine and hydromethanolic fraction of C. lanatus seed extract have hypoglycemic effect and may consequently ameliorate the impaired testicular general architecture and inhibits sperm death or testicular damage caused by alloxan-induced diabetes.

  20. Vildagliptin restores renal myogenic function and attenuates renal sclerosis independently of effects on blood glucose or proteinuria in Zucker Diabetic Fatty rat

    NARCIS (Netherlands)

    Vavrinec, Peter; Henning, Robert H.; Landheer, Sjoerd W.; Wang, Yumei; Deelman, Leo E.; van Dokkum, Richard P. E.; Buikema, Hendrik

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is associated with risk for chronic kidney disease (CKD), which is associated with a decrease in renal myogenic tone - part of renal autoregulatory mechanisms. Novel class of drugs used for the treatment of T2DM, dipeptidyl peptidase-4 (DPP-4) inhibitors, have protect

  1. Neonatally induced diabetes: liver glycogen storage in pregnant rats

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    Isabela Lovizutto Iessi

    2012-04-01

    Full Text Available The aim of this sstudy was to evaluate the liver glycogen storage in pregnant rats presenting neonatal streptozotocin-induced diabetes and to establish a relation with glycemia and insulin levels. Wistar rats were divided in to two groups: 1 Mild Diabetes (STZ - received streptozotocin (glycemia from 120 to 300 mg/dL, 2 Control - received vehicle (glycemia below 120 mg/dL. At days 0, 7, 14 and 21 of the pregnancy, body weight and glycemia were evaluated. At day 21 of the pregnancy, the rats were anesthetized for blood and liver collection so as to determine insulin and liver glycogen, which showed no changes in the STZ group as compared to the controls. In the STZ group, maternal weight gain were lower as compared to those in the control group. Significantly increased glycemia was observed at days 0 and 14 of the pregnancy in the STZ group. Therefore, neonatally induced diabetes in the rats did not cause metabolic changes that impaired insulin and liver glycogen relation in these rats.

  2. Clock genes, pancreatic function, and diabetes.

    Science.gov (United States)

    Vieira, Elaine; Burris, Thomas P; Quesada, Ivan

    2014-12-01

    Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic β cells, glucose homeostasis, and diabetes.

  3. Evaluation of wound healing activity of ferulic acid in diabetic rats.

    Science.gov (United States)

    Ghaisas, Mahesh M; Kshirsagar, Shashank B; Sahane, Rajkumari S

    2014-10-01

    In diabetic patients, there is impairment in angiogenesis, neovascularisation and failure in matrix metalloproteineases (MMPs), keratinocyte and fibroblast functions, which affects wound healing mechanism. Hence, diabetic patients are more prone to infections and ulcers, which finally result in gangrene. Ferulic acid (FA) is a natural antioxidant found in fruits and vegetables, such as tomatoes, rice bran and sweet corn. In this study, wound healing activity of FA was evaluated in streptozotocin-induced diabetic rats using excision wound model. FA-treated wounds were found to epithelise faster as compared with diabetic wound control group. The hydroxyproline and hexosamine content increased significantly when compared with diabetic wound control. FA effectively inhibited the lipid peroxidation and elevated the catalase, superoxide dismutase, glutathione and nitric oxide levels along with the increase in the serum zinc and copper levels probably aiding the wound healing process. Hence, the results indicate that FA significantly promotes wound healing in diabetic rats. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  4. Improvement of erectile dysfunction by the active pepide from Urechis unicinctus by high temperature/pressure and ultra - wave assisted lysis in Streptozotocin Induced Diabetic Rats

    Science.gov (United States)

    Kim, Kang Sup; Bae, Woong Jin; Kim, Su Jin; Kang, Kyong-Hwa; Kim, Se-Kwon; Cho, Hyuk Jin; Hong, Sung-Hoo; Lee, Ji Youl; Kim, Sae Woong

    2016-01-01

    ABSTRACT Introduction: We investigate the effect of active peptide from Urechis unicinctus (UU) by high temperature/pressure and ultra-wave assisted lysis on erectile dysfunction in streptozotocin-induced diabetic rats. Materials and Methods: Forty 12-week-old Sprague-Dawley rats were used in this study. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (50mg/kg). One week later, the diabetic rats were randomly divided into four groups: normal control, untreated diabetes control, and groups treated with 100 or 500mg/kg/d UU peptide. Rats were fed with UU peptide by intragastric administration for 8 weeks. After 8 weeks, penile hemodynamic function was evaluated in all groups by measuring the intracavernosal pressure after electrostimulating the cavernous nerve. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) activities were measured and endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) protein expression was determined by Western blot. Results: Maximum intracavernosal pressure in diabetic control rats decreased significantly compared to normal control rats, and was increased significantly compared to untreated diabetic rats after UU peptide supplementation. Treatment with the higher dose of UU peptide significantly increased the NO and cGMP levels compared with the diabetic control group. Decreased activity and expression eNOS and nNOS were found in the diabetic rats compared with the normal control group. Decreased eNOS and nNOS in diabetic rats were improved by UU peptide administration. Conclusions: Active peptide from UU ameliorates erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction. PMID:27564297

  5. Improvement of erectile dysfunction by the active pepide from Urechis unicinctus by high temperature/pressure and ultra - wave assisted lysis in Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Kang Sup Kim

    Full Text Available ABSTRACT Introduction: We investigate the effect of active peptide from Urechis unicinctus (UU by high temperature/pressure and ultra-wave assisted lysis on erectile dysfunction in streptozotocin-induced diabetic rats. Materials and Methods: Forty 12-week-old Sprague-Dawley rats were used in this study. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (50mg/kg. One week later, the diabetic rats were randomly divided into four groups: normal control, untreated diabetes control, and groups treated with 100 or 500mg/kg/d UU peptide. Rats were fed with UU peptide by intragastric administration for 8 weeks. After 8 weeks, penile hemodynamic function was evaluated in all groups by measuring the intracavernosal pressure after electrostimulating the cavernous nerve. Nitric oxide (NO and cyclic guanosine monophosphate (cGMP activities were measured and endothelial nitric oxide synthase (eNOS and neuronal NOS (nNOS protein expression was determined by Western blot. Results: Maximum intracavernosal pressure in diabetic control rats decreased significantly compared to normal control rats, and was increased significantly compared to untreated diabetic rats after UU peptide supplementation. Treatment with the higher dose of UU peptide significantly increased the NO and cGMP levels compared with the diabetic control group. Decreased activity and expression eNOS and nNOS were found in the diabetic rats compared with the normal control group. Decreased eNOS and nNOS in diabetic rats were improved by UU peptide administration. Conclusions: Active peptide from UU ameliorates erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Abdulrahman L. Al-Malki

    2015-01-01

    Full Text Available 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.

  9. Mitochondrial oxidative function and type 2 diabetes

    DEFF Research Database (Denmark)

    Rabøl, Rasmus; Boushel, Robert; Dela, Flemming

    2006-01-01

    oxidative phosphorylation. This review will cover the present knowledge and literature on the topics of the activity of oxidative enzymes and the electron transport chain (ETC) in skeletal muscle of patients with type 2 diabetes. Different methods of studying mitochondrial function are described, including......The cause of insulin resistance and type 2 diabetes is unknown. The major part of insulin-mediated glucose disposal takes place in the skeletal muscle, and increased amounts of intramyocellular lipid has been associated with insulin resistance and linked to decreased activity of mitochondrial...... discussed. Several studies show reduced activity of oxidative enzymes in skeletal muscle of type 2 diabetics. The reductions are independent of muscle fiber type, and are accompanied by visual evidence of damaged mitochondria. In most studies, the reduced oxidative enzyme activity is explained by decreases...

  10. Activated platelets from diabetic rats cause endothelial dysfunction by decreasing Akt/endothelial NO synthase signaling pathway.

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    Keiko Ishida

    Full Text Available Diabetes is associated with endothelial dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. The purpose of this study was to characterize circulating platelets in diabetes and clarify their effects on endothelial function. Male Wistar rats were injected with streptozotocin (STZ to induce diabetes. Each experiment was performed by incubating carotid arterial rings with platelets (1.65×10(7 cells/mL; 30 min isolated from STZ or control rats. Thereafter, the vascular function was characterized in isolated carotid arterial rings in organ bath chambers, and each expression and activation of enzymes involved in nitric oxide and oxidative stress levels were analyzed. Endothelium-dependent relaxation induced by acetylcholine was significantly attenuated in carotid arteries treated with platelets isolated from STZ rats. Similarly, treatment with platelets isolated from STZ rats significantly reduced ACh-induced Akt/endothelial NO synthase signaling/NO production and enhanced TXB2 (metabolite of TXA2, while CD61 (platelet marker and CD62P (activated platelet marker were increased in carotid arteries treated with platelets isolated from STZ rats. Furthermore, the platelets isolated from STZ rats decreased total eNOS protein and eNOS dimerization, and increased oxidative stress. These data provide direct evidence that circulating platelets isolated from diabetic rats cause dysfunction of the endothelium by decreasing NO production (via Akt/endothelial NO synthase signaling pathway and increasing TXA2. Moreover, activated platelets disrupt the carotid artery by increasing oxidative stress.

  11. 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

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

    OpenAIRE

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

    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 transpor...

  13. Effect of Biophytum sensitivum on streptozotocin and nicotinamide-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    Objective: To investigate the effect of aqueous solution of Biophytum sensitivum leaf extract (BSEt) on normal and streptozotocin (STZ)-nicotinamide-induced diabetic rats. Methods: Diabetes was induced in adult male Wistar rats by the administration of STZ-nicotinamide (40, 110 mg/kg b.w., respectively) intraperitoneally. BSEt (200 mg/kg) was administered to diabetic rats for 28 days. The effect of extract on blood glucose, plasma insulin, total haemoglobin, glycosylated haemoglobin, liver glycogen and carbohydrate metabolism regulating enzymes of liver was studied in diabetic rats. Results: BSEt significantly reduced the blood glucose and glycosylated haemoglobin levels and significantly increased the total haemoglobin, plasma insulin and liver glycogen levels in diabetic rats. It also increased the hexokinase activity and decreased glucose-6-phosphatase, fructose-1, 6-bisphosphatase activities in diabetic rats. Conclusions: The results of our study suggest that BSEt possesses a promising effect on STZ-nicotinamide-induced diabetes.

  14. 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.

  15. Effects of vitamin D on renal fibrosis in diabetic nephropathy model rats.

    Science.gov (United States)

    Tian, Yanyan; Lv, Guodong; Yang, Ye; Zhang, Yuanyuan; Yu, Rui; Zhu, Jia; Xiao, Lati; Zhu, Jun

    2014-01-01

    This study is to investigate the effects of vitamin D on renal fibrosis in rat diabetic nephropathy models, as well as the changes and interactions in the expressions of renal fibrogenesis- and inflammation-related genes. Rat diabetic nephropathy models were established by high-fat diets, which were subjected to TGF-β1 manipulation, as well as vitamin D treatment. H&E staining, Masson staining, and TEM detection were performed to assess the effects of vitamin D treatment and/or TGF-β1 manipulation on pathological changes in the renal tissues in these rat diabetic nephropathy models. Immunohistology and real-time PCR were used to evaluate the expressions of TGF-β1, MCP-1, CTGF, and VDR. Histological staining and TEM detection showed that, in both TGF-β1 over-expressed and interfered groups, vitamin D administration alleviated the renal fibrosis, compared with the vehicle treatment. Similar results were observed with the immunohistological staining. Real-time PCR analysis indicated that, when TGF-β1 was over-expressed in diabetic nephropathy, the expressions of MCP-1 and CTGF were also up-regulated, which would be decreased by the treatment of vitamin D. On the other hand, when TGF-β1 was interfered in DN, the expressions of MCP-1 and CTGF were relatively down-regulated, which would be further lowered by vitamin D administration. The mRNA expression of VDR was elevated by vitamin D treatment in these diabetic nephropathy models. Active vitamin D3 and lentivirus-mediated TGF-β1 interference could effectively reduce the renal fibrosis and protect the renal function in diabetic nephropathy rat models, which makes a promising therapeutic strategy for the disease.

  16. Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase.

    Science.gov (United States)

    Winiarska, Katarzyna; Dzik, Jolanta M; Labudda, Mateusz; Focht, Dorota; Sierakowski, Bartosz; Owczarek, Aleksandra; Komorowski, Lukasz; Bielecki, Wojciech

    2016-01-01

    Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47(phox) subunits, elevated level of p47(phox) phosphorylation, and enlarged phospho-p47(phox) and p67(phox) content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho-p47(phox) and p67(phox) . Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.

  17. Effect of repeated stress in early childhood on the onset of diabetes mellitus in male Spontaneously Diabetic Torii rats.

    Science.gov (United States)

    Ookawa, Katumasa; Mochizuki, Kazuo; Yokogoshi, Hidehiko

    2008-02-01

    Spontaneously Diabetic Torii (SDT) rats were discovered from SD rats and represent a confirmed spontaneous type 2 diabetes mellitus model. We investigated the effect of repeated stress in early childhood on SDT rats fed a high-fat diet, on locomotor activity and on the onset of diabetes mellitus. Regarding stress, a water immersion-restraint stress (WIRS) burden was applied 10 times every other day from 4 weeks of age. The results of the study showed, that the locomotor activity of the young SDT rats was clearly lower than that of the SD rats, and their locomotor activity was inferred to be congenitally low. In addition, the stress-burdened SDT rats showed delayed onset of diabetes mellitus and impaired glucose tolerance compared with the rats not receiving stress burden. The locomotor activity of SDT rats is less than that of SD rats, and they SDT rats are thought to have poor at spontaneous energy expenditure. On the other hand, the feeding efficiency of the WIRS-burdened SDT rats was reduced, and in comparison with the SDT rats with no WIRS burden, energy expenditure was increased; this is suggested to influence the onset of diabetes mellitus.

  18. Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats

    Directory of Open Access Journals (Sweden)

    Onyia Jude E

    2010-05-01

    Full Text Available Abstract Objectives Endothelial dysfunction precedes atherogenesis and clinical complications in type 2 diabetes. The vascular dysfunction in Zucker diabetic fatty (ZDF rats was evaluated at different ages along with the effect of treatment with rosiglitazone (Rosi on endothelial function and mechanical remodeling. Methods The Rosi treatment was given to ZDF rats for 3 weeks. The endothelium-dependent vasodilation and α-adrenoceptor-dependent vasoconstriction of femoral arteries were studied using an ex-vivo isovolumic myograph. The biomechanical passive property of the arteries was studied in Ca2+-free condition. The expressions of endothelial nitric oxide synthase (eNOS, α-adrenoceptor, matrix metalloproteinase 9 (MMP9, and elastase were evaluated. Results Endothelium-dependent vasorelaxation of the femoral artery was blunted at low doses in ZDF rats at 11 weeks of age and attenuated at all doses in ZDF rats at 19 weeks of age. The expression of eNOS was consistent with the endothelium-dependent vasorelaxation. The α-adrenoceptor was activated and the mechanical elastic modulus was increased in ZDF rats at 19 weeks of age. The expressions of α-adrenoceptor, MMP9, and elastase were up regulated in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks restored endothelium-dependent vasorelaxation and the expression of eNOS and the adrenoceptor activation at the doses below 10-6 mole/L in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks did not, however, improve the mechanical properties of blood vessel, the expressions of α-adrenoceptor, MMP9, and elastase in ZDF rats. Conclusion The endothelial dysfunction and mechanical remodeling are observed as early as 19 weeks of age in ZDF rat. Rosi treatment for 3 weeks improves endothelial function but not mechanical properties.

  19. Impairment of synaptic development in the hippocampus of diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Matsunaga, Yuki; Negishi, Takayuki; Hatakeyama, Akinori; Kawagoe, Yuta; Sawano, Erika; Tashiro, Tomoko

    2016-10-01

    Insulin receptor signaling has been shown to regulate essential aspects of CNS function such as synaptic plasticity and neuronal survival. To elucidate its roles during CNS development in vivo, we examined the synaptic and cognitive development of the spontaneously diabetic Goto-Kakizaki (GK) rats in the present study. GK rats are non-obese models of type 2 diabetes established by selective inbreeding of Wistar rats based on impaired glucose tolerance. Though they start exhibiting only moderate hyperglycemia without changes in plasma insulin levels from 3 weeks postnatally, behavioral alterations in the open-field as well as significant impairments in memory retention compared with Wistar rats were observed at 10 weeks and were worsened at 20 weeks. Alterations in insulin receptor signaling and signs of insulin resistance were detected in the GK rat hippocampus at 3 weeks, as early as in other insulin-responsive peripheral tissues. Significant reduction of an excitatory postsynaptic scaffold protein, PSD95, was found at 5w and later in the hippocampus of GK rats due to the absence of a two-fold developmental increase of this protein observed in Wistar control rats between 3 and 20w. In the GK rat hippocampus, NR2A which is a NMDA receptor subunit selectively anchored to PSD95 was also reduced. In contrast, both NR2B and its anchoring protein, SAP102, showed similar developmental profiles in Wistar and GK rats with expression peaks at 2 and 3w. The results suggest that early alterations in insulin receptor signaling in the GK rat hippocampus may affect cognitive performance by suppressing synaptic maturation.

  20. Decreased level of epidermal growth factor in milk from diabetic rats

    DEFF Research Database (Denmark)

    Thulesen, J; Nexø, Ebba; Raaberg, Lasse

    1994-01-01

    and in the concentration of EGF in milk from untreated diabetic rats compared with an insulin-treated diabetic group and a control group. Thus, the total output of EGF in milk from diabetic rats was considerably decreased. The concentrations of total protein and haptocorrin, a cobalamin (vitamin B12)-binding protein...

  1. Impaired formalin-evoked changes of spinal amino acid levels in diabetic rats.

    Science.gov (United States)

    Malmberg, Annika B; O'Connor, William T; Glennon, Jeffery C; Ceseña, Rose; Calcutt, Nigel A

    2006-10-18

    To investigate mechanisms by which diabetes alters sensory processing, we measured levels of amino acid neurotransmitters in spinal dialysates from awake, unrestrained control and diabetic rats under resting conditions and following hind paw formalin injection. Under resting conditions, glutamate concentrations in spinal dialysates were significantly (Phyperalgesia in diabetic rats does not appear to be secondary to enhanced glutamatergic input to the spinal cord.

  2. Investigation on the effects of the atmospheric pressure plasma on wound healing in diabetic rats

    Science.gov (United States)

    Fathollah, Sara; Mirpour, Shahriar; Mansouri, Parvin; Dehpour, Ahmad Reza; Ghoranneviss, Mahmood; Rahimi, Nastaran; Safaie Naraghi, Zahra; Chalangari, Reza; Chalangari, Katalin Martits

    2016-02-01

    It is estimated that 15 percent of individuals with diabetes mellitus suffer from diabetic ulcers worldwide. The aim of this study is to present a non-thermal atmospheric plasma treatment as a novel therapy for diabetic wounds. The plasma consists of ionized helium gas that is produced by a high-voltage (8 kV) and high-frequency (6 kHz) power supply. Diabetes was induced in rats via an intravascular injection of streptozotocin. The plasma was then introduced to artificial xerograph wounds in the rats for 10 minutes. Immunohistochemistry assays was performed to determine the level of transforming growth factor (TGF-β1) cytokine. The results showed a low healing rate in the diabetic wounds compared with the wound-healing rate in non-diabetic animals (P diabetic rats (P diabetic wounds (P diabetic rats.

  3. Effect of Toxoplasma gondii infection on kidney function in diabetic OLETF rats%弓形虫感染对糖尿病鼠肾功能的影响

    Institute of Scientific and Technical Information of China (English)

    苑文英; 李云鹏; 李景德; 吴丹; 安海音

    2013-01-01

    protein was measured using the biuret method to determine the effects of toxoplasmosis on the kidneys of diabetic OLETF rats.Results Compared to diabetic OLETF rats in the control group,the infection group had greatly elevated sCr(t34 =3.375,P=0.0034;t36 =4.6512,P=0.0002; t38 =6.2637,P=0.0000;t40 =6.6747,P=0.0000) and BUN (t34 =6.8198,P=0.0000;t'36=4.0757,P<0.05;t'38=4.2556,P<0.05;t'40=4.5844,P<0.05)starting in week 34.Fibrinogenincreased starting in week 36 (t36 =3.071,P =0.0066 ; t38 =4.2111,P =0.0005 ; t40 =3.8726,P =0.0048) and urine protein increased starting in week 38 (t38 =2.2483,P =0.0296 ; t40 =5.1645,P =0.0001).There were statistically significant differences in sCr,BUN,fibrinogen,and urine protein by week 40 (P<0.05 or P<0.01).There were no statistically significant differences (P>0.05) in UA,CK,CH,or TG.Conclusion Toxoplasmosis increased kidney damage in dia betic OLETF rats.Kidney function can be protected by reducing infection with effective treatment.

  4. Protective effect of Sesamin on endothelial function of type-2 diabetic rats%芝麻素对2型糖尿病大鼠主动脉内皮功能的保护作用

    Institute of Scientific and Technical Information of China (English)

    郭莉群; 杨解人; 孔祥

    2012-01-01

    目的 探讨芝麻素改善2型糖尿病大鼠主动脉内皮功能损伤的作用及可能机制.方法 采用长期高脂饮食加小剂量链脲佐菌素(streptozotocin,STZ)建立2型糖尿病大鼠模型.灌服不同剂量芝麻素(120、60 mg·kg-1·d-1)8周后处死动物.离体血管灌流法测大鼠主动脉内皮依赖性舒张反应及NO生物活性,测血清丙二醛(malondialdehyde,MDA)含量和总抗氧化能力(total antioxidative capacity,T-AOC),Western blot测主动脉内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、硝基酪氨酸(nitrotyrosine,NT)和还原型辅酶Ⅱ(NADPH)氧化酶亚基P47phox蛋白表达.结果与模型组相比,芝麻素(120 mg·kg-1·d-1)组内皮依赖性血管舒张功能增强,NO活性升高;血清MDA含量降低,T-AOC水平升高;主动脉eNOS蛋白表达增高,NT和P47phox蛋白表达降低.结论 芝麻素可改善糖尿病大鼠血管内皮功能,其机制与上调血管eNOS表达和减轻NO氧化失活有关.%Aim To study the ameliorative effect of sesamin ( Ses ) on endothelial dysfunction in diabetic rats and related mechanism. Methods Diabetic rats were induced by low dose streptozotocin( STZ ) and fed with high-fat diet. Then, rats were randomly divided into model group and Ses( 120, 60 mg · kg-1 ·d-1, respectively ig, for 8 weeks. ) groups. In addition, control group was set up. Eight weeks later, rats were sacrificed, the malondialdehyde ( MDA ) content, total antioxidative capacity( T-AOC ) in serum were tested, and the protein expression of endothelial nitric oxide synthase ( eNOS ), nitrotyrosine ( NT ) and nicotinam-ide adenine dinucleotide phosphate( NADPH ) oxidase subunit P47phox in aortas were deteced by Western blotting. In addition, vasorelaxation response to acetylcho-line( Ach ), and functional assessment of nitric oxide ( NO ) bioactivity were also determined in aortic rings. Results Compared with model group, vasodilation response of Ses (120 mg · kg-1 ) group was

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

    Energy Technology Data Exchange (ETDEWEB)

    Uriu-Hare, J.Y.; Rucker, R.B.; Keen, C.L. (Univ. of California, Davis (United States))

    1991-03-11

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

  6. MOMORDICA CHARANTIA PROTECTS AGAINST CARDIAC DAMAGE IN STREPTOZOTOCIN-INDUCED DIABETIC WISTAR RATS

    Directory of Open Access Journals (Sweden)

    O. A Komolafe

    2012-06-01

    Full Text Available Diabetes mellitus is one of the most important world health problems, especially in developing countries where prevalence and incidence rates are highest. Diabetic patients are particularly prone to cardiovascular diseases including hypertension, atherosclerosis, diabetic cardiomyopathy, congestive heart failure and cardiac autonomic neuropathy. The present study investigated the effects of Momordica charantia (M. charantia on histological changes of the left ventricle of the heart in streptozotocin-induced diabetic Wistar rats. Forty healthy adult Wistar rats of both sexes were randomly assigned into five groups A, B, C, D and E of eight rats each. Group A were the control (normal rats; B were the experimentally-induced diabetic rats; C were diabetic rats treated with methanolic extracts of M. charantia for two weeks (withdrawal group; D were diabetic rats treated with methanolic extracts of M. charantia for four weeks. E was diabetic rats treated with glimepiride for four weeks. Tissues were harvested, processed routinely in paraffin wax and stained with routine and special stains. Histological studies revealed disorganization of myofibril in the left ventricle of diabetic rats. Histochemical analysis also revealed abnormal deposition of glycogen in left ventricle of diabetic rats. M. charantia and glimperide attenuated the morphological alterations and reduced the glycogen deposits.

  7. Virgin Coconut Oil: Remedial Effects on Renal Dysfunction in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    A. M. Akinnuga

    2014-01-01

    Full Text Available Renal dysfunction is now a prevalent complication of diabetes mellitus. Therefore, this study was carried out to evaluate the remedial effects of virgin coconut oil (VCO on renal dysfunction in diabetic rats. Fifteen albino Wistar rats were divided into 3 groups that comprise normal control group (Group I and diabetic control group (Group II fed with normal rat chows and a diabetic test group (Group III fed with 10% VCO diet. Group II and Group III were made diabetic by single intraperitoneal injection of 150 mg/kg of freshly prepared alloxan monohydrate. After 72 hours of alloxan injection, fasting blood glucose was tested to confirm diabetes mellitus. After 3 weeks, the animals were anaesthetized and sacrificed to collect blood samples for renal function analysis. The creatinine, urea, and blood urea nitrogen values of Group II were significantly different from those of Group I and Group III at P<0.001. Also, there was significant difference (P<0.05 in total protein value between Group II (4.42  ±  0.47 mg/dL and Group I (5.78  ±  0.12 mg/dL as well as Group III (5.86  ±  0.19 mg/dL, but there was no significant difference between that of Group I and Group III (5.78  ±  0.12 mg/dL and 5.86  ±  0.19 mg/dL, resp.. Thus, VCO is effective in preventing renal damage in diabetic patients.

  8. Autonomic innervation of the pancreas in diabetic and non-diabetic rats. A new view on intramural sympathetic structural organization

    NARCIS (Netherlands)

    Luiten, P.G.M.; Horst, G.J. ter; Steffens, A.B.

    1986-01-01

    Using histochemical and immunocytochemical methods the intramural neural tissue of the pancreas was investigated in non-diabetic and in alloxan-diabetic rats. It was demonstrated that the non-diabetic pancreas contains an average of 2.71 cells/mm3 tissue that react positive for activity of acetylcho

  9. Angiotensin Converting Enzyme Activity in the Serum, Lung, Liver and Kidney in Streptozotocin -Induced Diabetic Rats and Diabetic Nephropathy

    OpenAIRE

    Üstündağ, Bilal

    2014-01-01

    To clarify the relationship between the alterations of the levels of angiotensin converting enzyme (ACE) and diabetic nephropathy, ACE activity in the lung, liver, kid-ney and serum were investigated in streptozotocin (STZ)-induced diabetic rats. The levels of serum ACE activity unchanged 3 days post STZ treatment but it was significantly an increase 12 and 30 days post STZ treatment in diabetic rats (p

  10. NLRP3 gene silencing ameliorates diabetic cardiomyopathy in a type 2 diabetes rat model.

    Directory of Open Access Journals (Sweden)

    Beibei Luo

    Full Text Available Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3 inflammasome is associated with metabolic disorder and cell death, which are important triggers in diabetic cardiomyopathy (DCM. We aimed to explore whether NLRP3 inflammasome activation contributes to DCM and the mechanism involved.Type 2 diabetic rat model was induced by high fat diet and low dose streptozotocin. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. Gene silencing therapy was used to investigate the role of NLRP3 in the pathogenesis of DCM. High glucose treated H9c2 cardiomyocytes were used to determine the mechanism by which NLRP3 modulated the DCM. The cell death in vitro was detected by TUNEL and EthD-III staining. TXNIP-siRNA and pharmacological inhibitors of ROS and NF-kB were used to explore the mechanism of NLRP3 inflammasome activation.Diabetic rats showed severe metabolic disorder, cardiac inflammation, cell death, disorganized ultrastructure, fibrosis and excessive activation of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC, pro-caspase-1, activated caspase-1 and mature interleukin-1β (IL-1β. Evidence for pyroptosis was found in vivo, and the caspase-1 dependent pyroptosis was found in vitro. Silencing of NLRP3 in vivo did not attenuate systemic metabolic disturbances. However, NLRP3 gene silencing therapy ameliorated cardiac inflammation, pyroptosis, fibrosis and cardiac function. Silencing of NLRP3 in H9c2 cardiomyocytes suppressed pyroptosis under high glucose. ROS inhibition markedly decreased nuclear factor-kB (NF-kB phosphorylation, thioredoxin interacting/inhibiting protein (TXNIP, NLRP3 inflammasome, and mature IL-1β in high glucose treated H9c2 cells. Inhibition of NF-kB reduced the activation of NLRP3 inflammasome. TXNIP-siRNA decreased the activation of caspase-1 and IL-1β.NLRP3 inflammasome contributed to the development of DCM. NF

  11. Anti-diabetic potentials of Momordica charantia and Andrographis paniculata and their effects on estrous cyclicity of alloxan-induced diabetic rats.

    Science.gov (United States)

    Reyes, B A S; Bautista, N D; Tanquilut, N C; Anunciado, R V; Leung, A B; Sanchez, G C; Magtoto, R L; Castronuevo, P; Tsukamura, H; Maeda, K-I

    2006-04-21

    Momordica charantia and Andrographis paniculata are the commonly used herbs by the diabetic patients in Pampanga, Philippines. While the anti-diabetic potential of Momordica charantia is well established in streptozocin- or alloxan-induced diabetic animals, the anti-diabetic potential of Andrographis paniculata in alloxan-induced diabetic rat is not known. Neither the effects of these herbs on estrous cyclicity of alloxan-induced diabetic rats are elucidated. Thus, in these experiments, Momordica charantia fruit juice or Andrographis paniculata decoction was orally administered to alloxan-induced diabetic rats. Rats that were treated with Momordica charantia and Andrographis paniculata had higher body weight (BW) compared with diabetic positive control (P Momordica charantia and Andrographis paniculata-treated diabetic rats (5 days; P Momordica charantia and Andrographis paniculata could restore impaired estrous cycle in alloxan-induced diabetic rats.

  12. Characterization of upper thoracic spinal neurons responding to esophageal distension in diabetic rats

    DEFF Research Database (Denmark)

    Qin, Chao; Ghorbani, Marie L M; Wu, Mingyuan

    2008-01-01

    The aim of this study was to examine spinal neuronal processing of innocuous and noxious mechanical inputs from the esophagus in diabetic rats. Streptozotocin (50 mg/kg, ip) was used to induce diabetes in 15 male Sprague-Dawley rats, and vehicle (10 mM citrate buffer) was injected into 15 rats...

  13. Dynamic aerobic exercise induces baroreflex improvement in diabetic rats.

    Science.gov (United States)

    Jorge, Luciana; da Pureza, Demilto Y; da Silva Dias, Danielle; Conti, Filipe Fernandes; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2012-01-01

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

  14. Renal and hepatic transporter expression in type 2 diabetic rats.

    Science.gov (United States)

    Nowicki, Michael T; Aleksunes, Lauren M; Sawant, Sharmilee P; Dnyanmote, Ankur V; Mehendale, Harihara M; Manautou, José E

    2008-01-01

    Membrane transporters are critical for the uptake as well as elimination of chemicals and by-products of metabolism from the liver and kidneys. Since these proteins are important determinants of chemical disposition, changes in their expression in different disease states can modulate drug pharmacokinetics. The present study investigated alterations in the renal and hepatic expression of organic anion and cation transporters (Oats/Octs), multidrug resistance-associated proteins (Mrps), breast cancer resistance protein (Bcrp), P-glycoprotein (Pgp), and hepatic Na(+)-taurocholate cotransporting polypeptide (Ntcp) in type 2 diabetic rats. For this purpose, type 2 diabetes was induced by feeding male Sprague-Dawley rats a high fat diet followed by a single dose of streptozotocin (45 mg/kg, i.p., in 0.01 M citrate buffer pH 4.3) on day 14. Controls received normal diet and vehicle. Kidney and liver samples were collected on day 24 for generation of crude plasma membrane fractions and Western blot analysis of Oat, Oct, Mrp, Bcrp, Pgp, and Ntcp proteins. With regards to renal uptake transporters, type 2 diabetes increased levels of Oat2 (2.3-fold) and decreased levels of Oct2 to 50% of control kidneys. Conversely, efflux transporters Mrp2, Mrp4, and Bcrp were increased 5.4-fold, 2-fold, and 1.6-fold, respectively in type 2 diabetic kidneys with no change in levels of Mrp1, Mrp5, or Pgp. Studies of hepatic transporters in type 2 diabetic rats reveal that the protein level of Mrp5 was reduced to 4% of control livers with no change in levels of Bcrp, Mrp1, Mrp2, Mrp4, Ntcp, or Pgp. The changes reported in this study may have implications in type 2 diabetic patients.

  15. Anti-diabetic activity of Ferula assafoetida extract in normal and alloxan-induced diabetic rats.

    Science.gov (United States)

    Abu-Zaiton, Ahmed Saber

    2010-01-15

    The aim of the present study was to evaluate the possible anti-diabetic potential of Asafetida extract against the pancreatic beta-cells damage from alloxan-induced diabetes in rats and some hormones related to diabetes mellitus. Asafetida induced significant reduction in blood glucose and increasing of serum insulin, our data indicate that the level of glucose in the animals that subjected with alloxan was 10.28 +/- 0.85 mmol L(-1) p < 0.05 comparing with control group 3.27 +/- 0.25 p < 0.05, the level of blood glucose in diabetic group when subjected with Asafetida extract decreasing to 6.75 +/- 0.31 p < 0.05. There was significant amount of insulin secretion in diabetic animals when subjected with Asafetida extract 0.48 +/- 0.05 p < 0.05 in comparison with diabetic animal's 0.33 +/- 0.06 p < 0.05. These findings suggested that Asafetida extract treatment exerts therapeutic protective effect in diabetes by preserving pancreatic beta-cells integrity and significant activity extract, which supports traditional usage to prevent diabetic complications.

  16. Effect of D-alpha-tocopherol on tubular nephron acidification by rats with induced diabetes mellitus

    Directory of Open Access Journals (Sweden)

    G. Nascimento Gomes

    2005-07-01

    Full Text Available The objective of the present study was to determine if treatment of diabetic rats with D-alpha-tocopherol could prevent the changes in glomerular and tubular function commonly observed in this disease. Sixty male Wistar rats divided into four groups were studied: control (C, control treated with D-alpha-tocopherol (C + T, diabetic (D, and diabetic treated with D-alpha-tocopherol (D + T. Treatment with D-alpha-tocopherol (40 mg/kg every other day, ip was started three days after diabetes induction with streptozotocin (60 mg/kg, ip. Renal function studies and microperfusion measurements were performed 30 days after diabetes induction and the kidneys were removed for morphometric analyses. Data are reported as means ± SEM. Glomerular filtration rate increased in D rats but decreased in D + T rats (C: 6.43 ± 0.21; D: 7.74 ± 0.45; D + T: 3.86 ± 0.18 ml min-1 kg-1. Alterations of tubular acidification observed in bicarbonate absorption flux (JHCO3 and in acidification half-time (t/2 in group D were reversed in group D + T (JHCO3, C: 2.30 ± 0.10; D: 3.28 ± 0.22; D + T: 1.87 ± 0.08 nmol cm-2 s-1; t/2, C: 4.75 ± 0.20; D: 3.52 ± 0.15; D + T: 5.92 ± 0.19 s. Glomerular area was significantly increased in D, while D + T rats exhibited values similar to C, suggesting that the vitamin prevented the hypertrophic effect of hyperglycemia (C: 8334.21 ± 112.05; D: 10,217.55 ± 100.66; D + T: 8478.21 ± 119.81µm². These results suggest that D-alpha-tocopherol is able to protect rats, at least in part, from the harmful effects of diabetes on renal function.

  17. Ranking candidate genes in rat models of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ståhl Fredrik

    2009-07-01

    Full Text Available Abstract Background Rat models are frequently used to find genomic regions that contribute to complex diseases, so called quantitative trait loci (QTLs. In general, the genomic regions found to be associated with a quantitative trait are rather large, covering hundreds of genes. To help selecting appropriate candidate genes from QTLs associated with type 2 diabetes models in rat, we have developed a web tool called Candidate Gene Capture (CGC, specifically adopted for this disorder. Methods CGC combines diabetes-related genomic regions in rat with rat/human homology data, textual descriptions of gene effects and an array of 789 keywords. Each keyword is assigned values that reflect its co-occurrence with 24 different reference terms describing sub-phenotypes of type 2 diabetes (for example "insulin resistance". The genes are then ranked based on the occurrences of keywords in the describing texts. Results CGC includes QTLs from type 2 diabetes models in rat. When comparing gene rankings from CGC based on one sub-phenotype, with manual gene ratings for four QTLs, very similar results were obtained. In total, 24 different sub-phenotypes are available as reference terms in the application and based on differences in gene ranking, they fall into separate clusters. Conclusion The very good agreement between the CGC gene ranking and the manual rating confirms that CGC is as a reliable tool for interpreting textual information. This, together with the possibility to select many different sub-phenotypes, makes CGC a versatile tool for finding candidate genes. CGC is publicly available at http://ratmap.org/CGC.

  18. Comparison of effect of resveratrol and vanadium on diabetes related dyslipidemia and hyperglycemia in streptozotocin induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Mohamad Reza shiri

    2011-12-01

    Full Text Available Purpose: Resveratrol a natural polyphenolic stilbene derivative has wide variety of biological activities. There is also a large body of evidence demonstrating positive effect of resveratrol in treatment of various metabolic complications including metabolic syndrome, obesity, diabetes and dyslipidemia in adults. The purpose of this study was to investigate anti-hyperglycemic and anti-dyslipidemic effects of resveratrol. Methods: We used 40 diabetic streptozotocin Wistar rats. Rats were randomly divided into 5 treatment groups (n=8 in each including normal control, normal treated with resveratrol, diabetic control , diabetic treated with vanadium , diabetic treated with resveratrol . Resveratrol (25 mg/kgbw and vanadate (0.2 mg/kgbw was orally gavaged for 40 days and blood samples were directly collected from heart. Results: Diabetic rats treated with resveratrol in comparison to control diabetic rats demonstrated a significant (p = 0.001 decline in serum glucose concentration, and high plasma concentrations of total cholesterol and LDL-c were reduced (p = 0.031, p = 0.004 respectively. Furthermore, body weight loss trend that observed in diabetic rats alleviated by resveratrol and vanadate. However triglyceride, VLDL-c and HDL-c levels did not changed significantly. Conclusion: In conclusion Resveratrol ameliorated dyslipidemia and hyperglycemia in diabetic rats. However further investigations in peculiar human studies are required.

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

    Science.gov (United States)

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

    2013-06-01

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

  20. Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist

    Science.gov (United States)

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

    1982-02-01

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

  1. Antihyperglycemic and antihyperlipidemic effects of guar gum on streptozotocin-induced diabetes in male rats

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    Samarghandian Saeed

    2012-01-01

    Full Text Available Background: Herbal medicine is widely used in the treatment of diseases like diabetes mellitus. We investigated the effects of guar gum in diabetic rats for the reduction of the risk of diabetes and cardiovascular disease. Dietary pattern emphasizing foods high in complex carbohydrates and fiber are associated with low blood glucose and cholesterol levels. Materials and Methods: Diet containing 0%, 5%, 10% and 20% (w/w guar gum was fed to diabetic rats for 28 days. Blood serum glucose, triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol levels, atherogenic index levels, body weights and food intake were monitored at 0, 7.14 and 28 days after induction of diabetes. Results: In spite of the fact that diabetes elevated blood lipids in all rats after 14 days, the guar gum diet significantly decreased the serum concentration of cholesterol, triacylglicerols and LDL-C and atherogenic index. The most significant result in this study was the reduction of blood glucose in diabetic rats treated with the guar gum diet after 28 days versus non- and glibenclamide-treated rats. The gum promoted a general improvement in the condition of the diabetic rats in body weight and food intake in comparison with nontreated rats. Conclusion: The results of this research suggest that guar gum was significantly effective in comparison with glibenclamide in the treatment of hyperlipidemia and hyperglycemia in diabetes rats. Therefore, it may be suggested as a reliable fiber in diabetic regimes in diabetic patients.

  2. 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.

  3. 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.

  4. 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.

  5. Effect of diabetes and insulin treatment on nitric oxide synthase content in rat corpus cavemosum

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    Zhi-Shun XU; Qiang FU; Sheng-Tian ZHAO; Hai-Nan LIU

    2001-01-01

    Aim: To study the effect of diabetes mellitus and insulin treatment on rat penile nitric oxide synthase content.Methods: Male Wistar rats were divided at random into two groups: the Control ( n = 8) and the Diabetic ( n =17). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The diabetic animals were then ran domly divided into two subgroups: diabetic rats without insulin treatment ( n = 7) and diabetic rats with insulin treat ment ( n = 10). The neuronal nitric oxide synthase (nNOS) in the penile corpus cavemosum were assayed by immrmo histochemical staining with specific antibody to nNOS and the nNOS-positive nerve fibers were counted semiquantita tively under a high power microscope. Results: The nNOS- positive nerve fibres in diabetic rats with treatment was higher than that in diabetic rats without treatment ( P < 0.05) and lower than that in the controls ( P < 0.01 ). The nNOS-positive nerve fibres in diabetic rat without treatment were also lower than that in the controls ( P < 0.01). Con clusion: In streptozotocin-induced diabetic rats, the nNOS content in the penile corpus cavernosum was significantly decre~ed. Insulin treatment at the dose level employed partially restores the penile nNOS content in these rats.

  6. Catechin Treatment Ameliorates Diabetes and Its Complications in Streptozotocin-Induced Diabetic Rats

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    Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh

    2017-01-01

    Context: Diabetes mellitus causes atherosclerosis and lipid abnormalities. Hypolipidemic and antioxidative properties of catechin (CTN) have been reported in several studies. Objective: This study assesses the possible protective effects of CTN against oxidative damage in the diabetic rats. Materials and Methods: The rats were divided into the control, untreated diabetic, and 3 CTN-treated diabetic groups (20, 40, and 80 mg/kg/d, intraperitoneal). The diabetic rats were induced by streptozotocin. Catechin was injected for 4 weeks. At the end of the experimental period, glucose, lipid profile, apoprotein A-I (apo A-I), apoprotein B (apo B), malondialdehyde (MDA) levels, and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in serum. Statistical analyses were performed using the InStat 3.0 program. Results: Streptozotocin caused an elevation of glucose, MDA, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apo B with reduction in high-density lipoprotein cholesterol (HDL-C), apo A-I, SOD, CAT, and GST in the serum (P < .05). The findings showed that the significant elevation in the body weight, glucose, MDA, TG, TC, LDL-C, and apo B and reduction in HDL-C, apo A-I, SOD, CAT, and GST were ameliorated in the CTN-treated diabetic groups versus the untreated group, in a dose-dependent manner (P < .05). Conclusion: The present investigation proposes that CTN may ameliorate diabetes and its complications by modification of oxidative stress. PMID:28228702

  7. The Effect of the Flavonoid Quercetin on Pain Sensation in Diabetic Rats

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    Jamshid Narenjkar

    2011-04-01

    Full Text Available Introduction: Hyperalgesia is considered as one of the marked signs of subchronic diabetes mellitus in patients that could affect their lifestyle. This study was designed to investigate the anti-nociceptive effect of chronic administration of quercetin in streptozotocin (STZ-diabetic rats using formalin and hot tail immersion tests. Methods: Rats were divided into control, control or diabetic groups receiving sodium salicylate, untreated diabetic, and quercetin-treated control and diabetic groups. The treatment groups received i.p. administration of quercetin at a dose of 10 mg/kg for 6 weeks. Finally, hyperalgesia were assessed using standard formalin and hot tail immersion tests. Meanwhile, some markers of oxidative stress were also measured in brain tissue.Results: Quercetin or SS treatment of diabetic rats significantly reduced pain score in chronic phase of formalin test (p<0.05. Regarding hot tail immersion test, diabetic rats showed a significant reduction in tail flick latency as compared to control ones (p<0.05 and quercetin treatment of diabetic rats did significantly increase this latency relative to untreated diabetics (p<0.05. Quercetin treatment of diabetic rats also significantly decreased brain level of malondialdehyde (MDA (p<0.05 and nitrite (p<0.05 and slightly increased activity of superoxide dismutase (SOD relative to diabetics. Discussion: Taken together, chronic administration of quercetin could attenuate nociceptive score in chronic phase of formalin test in streptozotocin-diabetic rats and could also increase threshold of thermal nociception.  

  8. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats

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    Silva Gláucio A

    2011-05-01

    Full Text Available Abstract Background Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD. Aim of the study The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Methods Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE - diabetic rats fed with a control diet and that exercised. Results The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Conclusion Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats.

  9. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats

    Science.gov (United States)

    2011-01-01

    Background Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD). Aim of the study The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Methods Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised. Results The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Conclusion Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats. PMID:21569626

  10. 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.

  11. Effects of pioglitazone on cognition function and expression of TNF-α and Aβ in hippocampal tissues of diabetic rats%吡格列酮对糖尿病大鼠认知功能及海马组织TNF-α、Aβ的影响

    Institute of Scientific and Technical Information of China (English)

    向慧; 徐寒松; 赵胜

    2011-01-01

    OBJECTIVE To observe the effects of pioglitazone on cognition function and expression of tumor necrosis factorα(TNF-α) and β-amyloid peptide (Aβ) in hippocampal tissues of diabetic rats. METHODS Forty-five Wistar rats were randomly divided into normal control group, diabetic model group, and pioglitazone treatment group. Streptozotocin-induced diabetic rat model was established. In the pioglitazone treatment group, the rats were treated with pioglitazone for 12 weeks. The cognition ability of rats was assayed with the Morris water maze test. The expression of TNF-α and Aβ was detected by ELISA. RFSULTS The Morris water maze test showed that escape latency was longer in the pioglitazone treatment group and the diabetic model group than that in the normal control group (P<0. 05), Compared with the diabetic model group, the pioglitazone treatment group showed a significant decrease in the mean time of escape latencies (P<0. 05), and an increased percentage of time spent in the central area and the more times navigating the original platform position(P<0. 05). The expression of TNF-α and Aβ in the pioglitazone treatment and the diabetic model groups was significantly higher than that in normal group (P<0. 01 ). Compared with diabetic model group, the expression of TNF-α and Aβ in pioglitazone treatment group was decreased(P<0. 05). CONCLUSION There exists impairment of cognitive function in diabetic rats, pioglitazone therapy can improve cognition function in diabetic rat. This may be related to it s effect of decreasing the expression of TNF-α and Aβ.%目的:观察吡格列酮对糖尿病大鼠认知功能及海马组织TNF-α、β-淀粉样蛋白(Aβ)的影响.方法:随机将45只Wistar大鼠分为正常对照组、糖尿病组、吡格列酮组,STZ25mg·kg-1腹腔注射建立糖尿病大鼠模型,给予吡格列酮10mg·kg-1·d-1灌胃干预12周后,采用Morris水迷宫试验测试其认知能力,ELISA法检测各组大鼠海马组织TNF-α

  12. ISOLATION OF HEPATIC OVAL CELLS FROM DIFFERENT MODEL RATS INCLUDING DIABETIC RATS

    Institute of Scientific and Technical Information of China (English)

    LU Ying-li; YE Ting-ting; XIA Fang-zhen; WANG Ning-jian; YANG Hua; CHEN Yi

    2009-01-01

    Objective To acquire oval cells (progenitor stem cells) from adult rat liver of different models including diabetic rats. Methods Thirty Sprague-Dawley (SD) rats were divided into 5 groups randomly: control, 2-acetylaminofluorene (2-AAF), 2-AAF+partial hepatectomy (PH), 2-AAF+carbon tetrachloride (CCl4), and diabetic groups. As two-step collagenase perfusion protocol of Seglen, oval cells were isolated by Percoll density gradient centrifugation. Thy1.1 positive cells were sorted by flow cytometry, and then cultured in Dulbeccos minimum Eagles medium (DMEM). Immunofluorescence staining was applied to labelling Thy1.1. Results Different rates of Thy1.1 positive oval cells were found in different rat model groups: 0.5% in 2-AAF, 0.3% in 2-hAAF+PH, 0.2% in 2-AAF+CCl4 , 0.1% in diabetic, and 0.0% in control. Isolated cells adhered to plate with fusiform or polygon as epithelial cells. Conclusion Progenitor stem cells exist in injured liver tissue including those from diabetic rats.

  13. Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Shanmugam, Kondeti Ramudu; Mallikarjuna, Korivi; Kesireddy, Nishanth; Sathyavelu Reddy, Kesireddy

    2011-04-01

    The aim of the present study was to investigate the effect of ginger on oxidative stress markers in the mitochondrial fractions of cerebral cortex (CC), cerebellum (CB), hippocampus (HC) and hypothalamus (HT) of diabetic rats. Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage. A marked decrease in anti-oxidant marker enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH) and increase in malondialdehyde (MDA) was observed in the diabetic rats. Decreased activities of anti-oxidant enzymes in diabetic rats were augmented on oral administration of ginger. Moreover, ginger administration depleted the MDA level, which was earlier increased in the diabetic rats. These results suggest that ginger exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating the MDA levels to the normal levels in the diabetic rats. Thus, ginger may be used as therapeutic agent in preventing complications in diabetic patients.

  14. Altered magnesium transport in slices of kidney cortex from chemically-induced diabetic rats

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    Hoskins, B.

    1981-10-01

    The uptake of magnesium-28 was measured in slices of kidney cortex from rats with alloxan-diabetes and from rats with streptozotocin-diabetes of increasing durations. In both forms of chemically-induced diabetes, magnesium-28 uptake by kidney cortex slices was significantly increased over uptake measured in kidney cortex slices from control rats. Immediate institution of daily insulin therapy to the diabetic rats prevented the diabetes-induced elevated uptake of magnesium without controlling blood glucose levels. Late institution of daily insulin therapy was ineffective in restoring the magnesium uptake to control values. These alterations in magnesium uptake occurred prior to any evidence of nephropathy (via the classic indices of proteinuria and increased BUN levels). The implications of these findings, together with our earlier demonstrations of altered calcium transport by kidney cortex slices from chemically-induced diabetic rats, are discussed in terms of disordered divalent cation transport being at least part of the basic pathogenesis underlying diabetic nephropathy.

  15. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

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    Yali Liu

    2016-01-01

    Full Text Available A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle.

  16. 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.

  17. Assessment of pharmacokinetic interaction of spirulina with glitazone in a type 2 diabetes rat model.

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    Gupta, Annu; Nair, Anroop; Kumria, Rachna; Al-Dhubiab, Bandar-E; Chattopadhyaya, Ipshita; Gupta, Sumeet

    2013-12-01

    The objective of the current study was to assess the possible pharmacokinetic interactions of spirulina with glitazones in an insulin resistance rat model. Wistar male albino rats were equally divided into five groups: insulin resistant rats+spirulina (500 mg/kg)+pioglitazone (10 mg/kg), insulin resistant rats+pioglitazone (10 mg/kg), insulin resistant rats+spirulina (500 mg/kg)+rosiglitazone (10 mg/kg), insulin resistant rats+rosiglitazone (10 mg/kg), and insulin resistant rats+spirulina (500 mg/kg). Described doses of pioglitazone, rosiglitazone, or spirulina were per orally administered and the plasma drug concentrations were determined. The pharmacokinetic parameters such as Tmax, Cmax, AUC(0-α), t1/2, and Kel were determined by plotting the drug concentration as a function of time. The data observed in this acute study indicated that there was no statistically significant difference in any of the pharmacokinetic parameters (Tmax, Cmax, AUC(0-α), t1/2, and Kel) of glitazones (pioglitazone, rosiglitazone) or spirulina, when they were coadministered. Given the promising results, this study concludes that the coadministration of spirulina does not influence the pharmacokinetics of glitazones in a type 2 diabetes rat model. Further chronic in vivo studies are recommended to assess the real time effect.

  18. Blockage of Peripheral NPY Y1 and Y2 Receptors Modulates Barorefex Sensitivity of Diabetic Rats

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    Jing Liu

    2013-03-01

    Full Text Available Background/Aims: Abnormal baroreceptor reflex sensitivity (BRS and elevated plasma neuropeptide Y (NPY are prevalent in diabetic patients. The present study was conducted to determine whether NPY Y1 receptor (Y1R and NPY Y2 receptor (Y2R contribute to the regulatin of BRS in diabetic rats. Methods: Diabetes mellitus (DM rats with hyperlipidemia were developed by an emulsion diet enriched with fat, sucrose and fructose followed by streptozocin (STZ. Y1R and Y2R specific antagonists (BIBP 3226 and BIIE 0246 were administered by a mini-osmotic pump. Systolic blood pressure (SBP, heart rate (HR, BRS and heart functions, as well as the plasma NPY and lipid level were measured after treatment for 4 weeks. Results: Both BIBP 3226 and BIIE 0246 treatment reversed the elevated total cholesterol (TC and low density lipoprotein (LDL-C level, and reduced high density lipoprotein (HDL-C level in DM rats. BIIE 0246 may attenuate the increased triglyceride (TG level in DM rats. In addition, neither BIBP 3226 nor BIIE 0246 treatment produced significant effects on BRS, SBP or HR (P>0.05 in DM rats, even after PE and SNP challenge. However, BIBP 3226 and BIIE 0246 further impaired LVSP, LVEDP, +dp/dtmax and -dp/dtmax. Conclusion: This study provided us with the evidence that the inhibition of peripheral Y1R and Y2R did not affect impaired BRS but amplified the deterioration of the compromised cardiac function in STZ-induced DM rats with hyperlipidemia.

  19. Effects of artificial cordyceps sinensis on epithelial-mesenchymal transition in the podocytes of diabetic rats

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    蔡芸莹

    2013-01-01

    Objective To assess the effects of artificial cordyceps sinensis(Jin shuibao) on the numbers of podocytes and epithelial-mesenchymal transition in diabetic rats. Methods Diabetes was induced by intraperitoneal injection of low dose streptozocin.

  20. THE BENEFICIAL EFFECT OF ASIATICOSIDE ON EXPERIMENTAL NEUROPATHY IN DIABETIC RATS

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    Chonlathip Thipkaew

    2012-01-01

    Full Text Available Though diabetic neuropathy produces high impact on quality of life, annual cost and morbidities, the therapeutic efficacy is still not in a satisfaction level. Based on the crucial role of oxidative stress on the pathophysiology of diabetic neuropathy and the improvement of this condition induced by antioxidant, we hypothesized that asiaticoside, a substance possessing antioxidant activity, could provide beneficial effect. Therefore, we aimed to determine the effect of asiaticoside on the recovery of sciatic nerve in experimental neuropathy in diabetic rats. Young adult male Wistar rats at 8 weeks old, weighing approximate 180-220 g, were orally given asiaticoside at doses of 0.1 and 1 mg kg-1 BW at a period of 5 days before and 3 weeks after sciatic nerve crush injury. Motor and sensory functions were observed every 3 day until the end of the experiment by using Deminacelli method, walking pattern, muscle power and foot reflex withdrawal test, respectively. Our results showed that both doses of asiaticoside could significantly reverse the enhanced withdrawal threshold intensity elicited by electrical stimuli. However, the rats received asiaticoside at dose of 1 mg kg-1 BW provided optimum benefit. However, no other significant effects were observed. Asiaticoside administration in an experimental model of neuropathy in diabetic rats mitigates some functional impairment of sciatic nerve. Though our data show only the beneficial effect of asiaticoside on the foot withdrawal reflex, it is very much important because it involve the protective mechanism against painful stimuli. Therefore, it is worth for further investigation in order to confirm the improvement of sensori-motor functions and determined the both therapeutic window and possible underlying mechanism."

  1. N-acetylcysteine attenuates ischemia/reperfusion-induced cardiocyte apoptosis in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Li Ma; Shanglong Yao; Kezhong Li

    2006-01-01

    Objective: To study the effects of N-acetylcysteine (NAC) on iscbemia/ reperfusion (I/R)-induced myocyte apoptosis in diabetic rats. Methods:The I/R heart model was made by ligation of the left anterior descending coronary artery (LAD) close to its origin. The LAD was occluded for 30 min followed by removal of ligation to allow subsequent reperfusion for 3 h. 72 rats were randomly divided into two groups: non-diabetic group (C, n = 36) and diabetic group (D, n = 36).The animals in C group were randomly reassigned into sham-ope rated group (CS, n = 12) , I/R group (C I/R, n = 12) and treated with NAC group (CN, n = 12). The rats in D group were also reassigned to sham-operated group (DS, n = 12) , I/R group (DI/R, n = 12) and treated with NAC group (DN, n = 12). Malondialdehyde (MDA) and creatine kinase isoenzyme-MB (CK-MB) were measured. Infarct size(IS/AAR%), the apoptosis index(AI) by TUNEL staining, the number of the cells positive for Caspase-3 and positive expression index (PEI) were calculated. Results:After I/R, the IS/AAR%, CK-MB, MDA, AI and Caspase-3 PEI were higher in diabetic group than those in non-diabetic group. Treatment with NAC decreased the above parameters in both non-diabetic and diabetic rats, but the parameters in diabetic rats were higher than those in non-diabetic rats. Conclusion:Diabetic rat hearts are more susceptible to I/R-induced myocardial necrosis and myocyte apoptosis. NAC can decrease the infarct size and attenuate cardiomyocyte apoptosis in both non-diabetic and diabetic rats, but the therapeutic effects are less effective in diabetic rats than those in non-diabetic rats.