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Sample records for diabetic rat models

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

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    Yusuke Kemmochi

    2013-01-01

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

  2. 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.

  3. 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.

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

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    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.

  5. 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.

  6. Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model

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    Mi Young Lee

    2011-04-01

    Full Text Available BackgroundWhile there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.MethodsThirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5, spironolactone-treated (n=10, losartan-treated (n=9, and combination of spironolactone- and losartan-treated (n=9.ResultsAt week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.ConclusionThese results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

  7. Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic Nephropathy

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    Li-Hao Chen

    2012-05-01

    Full Text Available Background/Aims: While experimental models that emulate diabetic nephropathy are valuable tools for elucidating pathogenetic mechanisms and developing novel therapies, existing models imperfectly recapitulate human disease. In diabetes, hyperglycemia and hemodynamic forces act in concert to induce renal injury. Accordingly, in the present study, we combined streptozotocin-induced diabetes with surgical ablation of 5/6 of the kidney mass with the aim of evaluating their additive effects on renal function and glomerular morphology. Methods: Female F344 rats were randomized to undergo subtotal nephrectomy (SNx either at baseline or following 4 weeks of diabetes. Results: In comparison to sham rats, rats with diabetes or rats after SNx surgery, diabetic subtotally nephrectomized (DM-SNx rats demonstrated an increase in systolic blood pressure, glomerular volume and mesangial matrix. Albuminuria was synergistically increased by hyperglycemia and renal mass ablation associated with decreased nephrin expression. In contrast, glomerular capillary rarefaction and glomerular filtration rate were similarly reduced in SNx and DM-SNx rats. Conclusion: The DM-SNx rat recapitulates some of the features of human disease, most notably augmented albuminuria. Since this model avoids the deletion or overexpression of gene(s linked to the pathogenesis of nephropathy, the DM-SNx rat model represents a complementary tool for the trial of novel therapies.

  8. Protective effects of leflunomide on renal lesions in a rat model if diabetic nephropathy.

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    Zhang, Qing; Ji, Yongqiang; Lv, Wei; He, Tianwei; Wang, Jianping

    2016-01-01

    Diabetic nephropathy is one of the most common chronic complications of diabetes with poor efficacy of clinical treatment. This study investigated the protective effects of leflunomide, a new immunosuppressant, on tubulointerstitial lesions in a rat model of diabetic nephropathy. Diabetes was induced with streptozotocin (STZ, 50 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 8 weeks with low (5 mg/kg) and high dose (10 mg/kg) of leflunomide, and benazepril hydrochloride (4 mg/kg) as a positive control. In diabetic rats, the 24-h urine volume, urine protein and microalbumin, blood creatinine and urea nitrogen significantly increased, which were attenuated by leflunomide treatment in a dose-dependent manner (all p diabetic rats were mitigated by leflunomide treatment. Immunohistochemistry study and real-time polymerase chain reaction results demonstrated that osteopontin (OPN), transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin and CD68 expression in the renal tubulointerstitial region were significantly increased in the diabetic rats, while these increases were inhibited by leflunomide treatment. These findings suggest that leflunomide protects the kidney injury of diabetic rats might through its inhibition of OPN/TGF-β1 mediated extracellular matrix deposition and tubulointerstitial fibrosis, as well as its inhibition on tubular epithelial-myofibroblast transdifferentiation.

  9. Autoimmunity in type 1 diabetes mellitus: a rat model

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    Liu, Z.

    1987-01-01

    In this study, we have sought to isolate in vitro, from acutely diabetic BB rats, cytotoxic T lymphocytes, which exhibit specific cytotoxicity toward islet cells. Thoracic duct lymphocytes (TDL) from acutely diabetic BB rats cultured with irradiated MHC matched (RT1.u) islet cells and dendritic cells in vitro were shown to be specifically cytotoxic to MHC matched and mismatched allogeneic (RT1.1) and xenogeneic (hamster) islet target cells in a 3 H-leucine release assay. Two cell lines (V1A8 and V1D11) derived from the TDL culture showed similar patterns of non-MHC restricted islet cell killing which could be blocked by islet cells and cultured rat insulinoma cells (RIN5mF) but not by non-islet cells of various tissue origins. Both V1A8 and V1D11 were not cytotoxic to Natural Killer (NK) sensitive target cells, G1TC and YAC-1. Conventional surface markers for rat helper and suppressor/cytotoxic T cells were not detectable on either cell lines. The V1D11 cell line was positive for W 3/13 (rat T/NK marker) on OX-19 (rat T/macrophage marker), whereas the V1A8 cell line was only positive for W 3/13

  10. Sodium salicylate reduced insulin resistance in the retina of a type 2 diabetic rat model.

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    Jiang, Youde; Thakran, Shalini; Bheemreddy, Rajini; Coppess, William; Walker, Robert J; Steinle, Jena J

    2015-01-01

    Sodium salicylate has been reported to reduce markers of diabetic retinopathy in a type 1 rat model. Because rates of type 2 diabetes are on the rise, we wanted to determine whether salicylate could improve insulin resistance in a type 2 rat model, as well as improve retinal function. We treated lean and obese BBZDR/Wor type 2 diabetic rats with salicylate in their chow for 2 months. Prior to salicylate treatment, rats underwent an electroretinogram to measure retinal function. After 2 months of treatment, rats underwent an additional electroretinogram prior to sacrifice. In addition to the animal model, we also treated retinal endothelial cells (REC) and rat Müller cells with salicylate and performed the same analyses as done for the rat retinal lysates. To investigate the role of salicylate in insulin signaling, we measured TNFα and caspase 3 levels by ELISA, as well as performed Western blotting for insulin receptor substrate 1, insulin receptor, SOCS3, and pro- and anti-apoptotic markers. Data demonstrated that salicylate significantly improved retinal function, as well as reduced TNFα and SOCS3-induced insulin resistance in all samples. Overall, results suggest that salicylate is effective in reducing insulin resistance in the retina of type 2 diabetic rat models.

  11. Sodium Salicylate Reduced Insulin Resistance in the Retina of a Type 2 Diabetic Rat Model

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    Jiang, Youde; Thakran, Shalini; Bheemreddy, Rajini; Coppess, William; Walker, Robert J.; Steinle, Jena J.

    2015-01-01

    Sodium salicylate has been reported to reduce markers of diabetic retinopathy in a type 1 rat model. Because rates of type 2 diabetes are on the rise, we wanted to determine whether salicylate could improve insulin resistance in a type 2 rat model, as well as improve retinal function. We treated lean and obese BBZDR/Wor type 2 diabetic rats with salicylate in their chow for 2 months. Prior to salicylate treatment, rats underwent an electroretinogram to measure retinal function. After 2 months of treatment, rats underwent an additional electroretinogram prior to sacrifice. In addition to the animal model, we also treated retinal endothelial cells (REC) and rat Müller cells with salicylate and performed the same analyses as done for the rat retinal lysates. To investigate the role of salicylate in insulin signaling, we measured TNFα and caspase 3 levels by ELISA, as well as performed Western blotting for insulin receptor substrate 1, insulin receptor, SOCS3, and pro- and anti-apoptotic markers. Data demonstrated that salicylate significantly improved retinal function, as well as reduced TNFα and SOCS3-induced insulin resistance in all samples. Overall, results suggest that salicylate is effective in reducing insulin resistance in the retina of type 2 diabetic rat models. PMID:25874611

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

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

    1994-01-01

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

  13. Improvement of insulin secretion in rat models of diabetes after ACEI/ARB therapy

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    Tian Jingyan; Li Fengying; Liu Yun; Long Hongmei; Li Weiyi; Wang Xiao; Zhang Hongli; Li Guo; Luo Min

    2009-01-01

    Objective To study the effect of ACEI/ARB therapy on the secretion of insulin and glucagon as well as serum lipid peroxidation marker 8-iso PGF-2α levels in streptozoticin (STZ) induced diabetic rat models.Methods Twenty-four rat models of STZ induced diabetes were prepared (random blood sugar>16.7 mmol/L). Of which, 8 models were fed enalaprial 5mg/kg/d, 8 models were fed losartan 10μg/kg/d and 8 models left unterated. Fasting serum insulin,glucagon (with RIA) and 8-iso PGF-2α (with ELISA) levels were measured in these models and 8 control rats three weeks later. Intravenous glucose tolerance test (IVGTT) were performed in 12 rats (3 animals in each group) six weeks later. Results: Serum levels of insulin in the treated models were higher than those in the non-treated models but without significance (P>0.05). Serum levels of glucagon and 8-iso PGF-2α levels in the treated models were significantly lower than those in the non-treated models (P 6 x ) in the treated models. Conclusion: ACEI/ARB treatment could improve the secretion of insulin in rat models of diabetes, which might be beneficial for controlling the progression of the disease. This phenomenon is consistent with the result of clinical study. (authors)

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

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

    2013-01-01

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

  15. [Causes of death in STZ-induced rat models of diabetes mellitus].

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    Wang, Yan-Jiang; Xie, Xi-Sheng; Feng, Sheng-Gang; Long, Qiong-Xian; Ai, Na; Wang, Bao-Fu

    2014-07-01

    To identify conditions that may improve the successful rate of STZ-induced rat models of diabetes mellitus (DM). 100 male SD rats were randomly divided into control group (n = 10) and experimental group (n = 90). Rats in the experimental group were treated with intraperitoneal injection of STZ 65 mg/kg once, and were then categorized into succeeded DM model group and failed group. Their body masses and levels of fasting blood glucose (FBG), urine glucose (UG), urine protein (UP), urine routine, renal function, liver function, blood lipids and kidney hypertrophy index (KHI) were monitored and compared. Dead rats were dissected to observe diseased organs. Pathological changes of those diseased organs were examined by HE staining. DM rat models were established through a single intraperitoneal injection of STZ, with a success rate of 58.89%. During the experiment, 43.33% of rats died. Compared with the rats in the failed group, the DM rat models had significantly higher levels of body mass, food intake, water intake, urine output, FBG, creatinine, blood urea nitrogen, KHI, urinary tract infections, and mortality; but lower levels of total protein, albumin and cholesterol and triglyceride (P causes of 11 dead rats were not clear. DM rat models can be established through a single intraperitoneal injection of STZ 65 mg/kg, but with high mortality rate. The deaths may be associated with infection, malnutrition, suffocation of lymphatic circulation, toxicity of STZ, and changes in environmental and climate conditions.

  16. The combination of colesevelam with sitagliptin enhances glycemic control in diabetic ZDF rat model

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    Shang, Quan; Liu, Matthew K; Saumoy, Monica

    2012-01-01

    . In the present study, we tested whether adding sitagliptin (Januvia) (SIT), which prolongs bioactive GLP-1 half life, to COL would further enhance glycemic control. Male Zucker diabetic fatty (ZDF) rats were assigned to four groups: diabetic model without treatment (the model), the model treated with 2% COL or 0...... to levels similar to the model. Histological examination of the pancreatic ß-cell islets showed that islet sizes were larger, proliferation enhanced, and cell apoptosis reduced in the COL+SIT but not the SIT alone group compared with the model. We hypothesize that the combination of COL with SIT extends...

  17. Anti-diabetic effects of the acetone fraction of Senna singueana stem bark in a type 2 diabetes rat model.

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    Ibrahim, Mohammed Auwal; Islam, M Shahidul

    2014-04-28

    Senna singueana is currently used in the traditional treatment of diabetes mellitus in Nigeria. The present study examined the anti-diabetic activity of the Senna singueana acetone fraction (SSAF) of stem bark in a type 2 diabetes (T2D) rat model. Crude ethyl acetate extract of the Senna singueana stem bark was fractionated with various solvents and the acetone fraction was selected for in vivo studies based on the high α-glucosidase and α-amylase inhibitory activities. In the in vivo study, male Sprague-Dawley rats were induced with T2D and treated with the SSAF at 150 and 300 mg/kg body weight. Several T2D-related parameters were measured in the study. After 4 weeks of intervention, non-fasting blood glucose concentrations were significantly decreased and the glucose tolerance ability was significantly improved in the SSAF treated groups compared to the diabetic control group. Serum insulin concentrations, pancreatic β-cell function (HOMA-β) and liver glycogen were significantly (Pdiabetic rats compared to the diabetic control group. Though insignificantly (P>0.05), other T2D-induced abnormalities such as food and fluid intake, body weight, serum lipids, serum fructosamine level and peripheral insulin resistance (HOMA-IR) were also partially ameliorated by the SSAF treatment. Data of this study suggest that orally administered SSAF could ameliorate most of the T2D-induced abnormalities in a T2D model of rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Effects of Astragalus polysaccharides on memory impairment in a diabetic rat model

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    Dun C

    2016-07-01

    Full Text Available Changping Dun,1 Junqian Liu,1 Fucheng Qiu,1 Xueda Wu,2 Yakun Wang,3 Yongyan Zhao,4 Ping Gu1 1Department of Neurology, the First Hospital of Hebei Medical University, 2Department of Cardiac Surgery, the Second Hospital of Hebei Medical University, 3Department of Endocrinology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 4Department of Nursing, Maternal and Child Health Hospital of Tangshan City, Tangshan, People’s Republic of China Objective: Astragalus polysaccharides (APS are active constituents of Astragalus membranaceus. In this study, we aimed to investigate the effects of APS on memory impairment in a diabetic rat model and their mechanisms. Methods: A diabetic model was established in 50 male Wistar rats with streptozotocin intraperitoneal injection. A blood glucose level higher than 16.7 mmol/L obtained 72 hours after the injection was regarded as a successful diabetic model. The modeled rats were divided into model group, high, medium, and low doses of APS, and piracetam groups (positive control. A group of ten rats without streptozotocin-induced diabetes were used as a normal control. After respective consecutive 8-week treatments, the levels of blood fasting plasma glucose, insulin, hemoglobin A1c, memory performance, hippocampal malondialdehyde, and superoxide dismutase were determined. Results: After the 8-week APS treatment, serum fasting plasma glucose, hemoglobin A1c, and insulin levels were decreased compared with those of the model group (P<0.05. Importantly, memory impairment in the diabetic model was reversed by APS treatments. In addition, hippocampal malondialdehyde concentration was lowered, whereas that of superoxide dismutase was higher after APS treatments. Conclusion: APS are important active components responsible for memory improvement in rats with streptozotocin-induced diabetes. The potential mechanism of action is associated with the effects of APS on glucose and lipid metabolism, and

  19. [Establishment of rat model with diabetes mellitus and concomitant periodontitis and the carotid artery lesions in the model rats].

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    Ren, X Y; Wang, C; Liu, X; Li, H; Gao, J H; Ge, X J

    2017-12-09

    Objectives: To establish SD rat model with type 2 diabetes mellitus (DM) and concomitant chronic periodontitis (CP) and to evaluate the influence of periodontitis on the vascular lesions of type 2 diabetes rats. Methods: Totally 241 clean level SD rats were randomly divided into four groups, group A (normal control, NC, n= 27), group B (DM, n= 34), group C (CP, n= 90) and group D (DM+CP, n= 90). The rats of DM group were fed with high-fat and high-sugar diet for 8 to 10 weeks, and then were multiply injected with small dose streptozotocin under the condition of ice bath. Blood sugar levels after the injection were dynamically monitored at 72 h, 1 week, 2 weeks and 4 weeks, respectively. The CP model was established by means of ligation. Bilateral maxillary first and second molars were selected and ligated using 0.2 mm orthodontic wires binding with 4-0 surgical suture soaked with Porphyromonas gingivalis (Pg) suspension. After a period of 14 weeks, all the rats were put to death. Maxillary samples were subjected to methylene blue staining to observe alveolar bone loss. Bilateral carotid artery specimens were collected. The left carotid artery specimens were used to detect the prevalence of Pg using quantitative real-time PCR. The right carotid artery specimens were used to observe pathological changes. Results: Blood sugar levels of rats in group B and D increased and changed sharply after Streptozotocin injection with in 1 week. Symptoms of 'more drink, more food and body weight loss' appeared. The fasting blood glucose (FBG) was more than 7.8 mmol/L and (or) the random blood glucose (RBG) was more than 17.8 mmol/L. Both FBG and RBG became stable after 2 to 3 weeks. Levels of HbA1C in group B and D ([7.32±0.45]%, [9.41±0.45]%) were significantly higher than that of group A ([4.02±0.45]%) ( Pdiabetes vascular lesions.

  20. Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat

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    Ghupurjan Gheni

    2015-01-01

    Full Text Available We recently established a novel animal model of obese type 2 diabetes (T2D, the Zucker fatty diabetes mellitus (ZFDM rat strain harboring the fatty mutation (fa in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6–8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10–12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain.

  1. 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.

  2. Recombinant fibromodulin has therapeutic effects on diabetic nephropathy by down-regulating transforming growth factor-β1 in streptozotocin-induced diabetic rat model

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    Maryam Foroutan Jazi

    2016-03-01

    Conclusion:Intraperitoneal injection of adenoviral vectors expressing fibromodulin  reduced TGF-β1 level in diabetic rat models. The molecular mechanisms involved in this process require further study.

  3. 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.

  4. Naringin prevents bone loss in a rat model of type 1 Diabetes mellitus.

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    Rivoira, M; Rodríguez, V; Picotto, G; Battaglino, R; Tolosa de Talamoni, N

    2018-01-01

    The aim of this work was to know whether naringin (NA) could prevent the bone complications in a model of streptozotocin (STZ) induced diabetes. Rats were divided in: 1) controls, 2) STZ-rats, 3) STZ-rats treated with 40 mg NA/kg, and 4) STZ-rats treated with 80 mg NA/kg. BMD and BMC were performed by DEXA. Bone histomorphometry and histology as well as TRAP staining were done in tibia. Osteocalcin (OCN) was determined in bone and serum. Glutathione content and SOD and catalase activities were assayed in bone marrow from femur. The data showed that NA80 increased the BMD and BMC from the long bones of STZ-rats. Both NA40 and NA80 normalized the trabecular number and the trabecular separations. An increase in the number of adipocytes and TRAP(+) cells in tibia from STZ-rats was blocked by NA. NA40 treatment increased the number of OCN(+) cells, but only the NA80 treatment allowed to reach the control values. NA normalized the SOD and catalase activities in bone marrow of femur from STZ-rats. In conclusion, NA avoids alterations in the physical properties and microstructure of bone from STZ-rats probably by stimulation of osteoblastogenesis, inhibition of the osteoclastogenesis and adipogenesis via blocking the oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Electrophysiological characterization of spinal neurons in different models of diabetes type 1- and type 2-induced neuropathy in rats.

    Science.gov (United States)

    Schuelert, N; Gorodetskaya, N; Just, S; Doods, H; Corradini, L

    2015-04-16

    Diabetic polyneuropathy (DPN) is a devastating complication of diabetes. The underlying pathogenesis of DPN is still elusive and an effective treatment devoid of side effects presents a challenge. There is evidence that in type-1 and -2 diabetes, metabolic and morphological changes lead to peripheral nerve damage and altered central nociceptive transmission, which may contribute to neuropathic pain symptoms. We characterized the electrophysiological response properties of spinal wide dynamic range (WDR) neurons in three diabetic models. The streptozotocin (STZ) model was used as a drug-induced model of type-1 diabetes, and the BioBreeding/Worcester (BB/Wor) and Zucker diabetic fatty (ZDF) rat models were used for genetic DPN models. Data were compared to the respective control group (BB/Wor diabetic-resistant, Zucker lean (ZL) and saline-injected Wistar rat). Response properties of WDR neurons to mechanical stimulation and spontaneous activity were assessed. We found abnormal response properties of spinal WDR neurons in all diabetic rats but not controls. Profound differences between models were observed. In BB/Wor diabetic rats evoked responses were increased, while in ZDF rats spontaneous activity was increased and in STZ rats mainly after discharges were increased. The abnormal response properties of neurons might indicate differential pathological, diabetes-induced, changes in spinal neuronal transmission. This study shows for the first time that specific electrophysiological response properties are characteristic for certain models of DPN and that these might reflect the diverse and complex symptomatology of DPN in the clinic. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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

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    Charitra N Grama

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

  7. Utilization of the Zucker Diabetic Fatty (ZDF) Rat Model for Investigating Hypoglycemia-related Toxicities.

    Science.gov (United States)

    Tirmenstein, Mark; Horvath, Joseph; Graziano, Michael; Mangipudy, Raja; Dorr, Thomas; Colman, Karyn; Zinker, Bradley; Kirby, Mark; Cheng, Peter T W; Patrone, Laura; Kozlosky, John; Reilly, Timothy P; Wang, Victor; Janovitz, Evan

    2015-08-01

    Glucokinase (GK) catalyzes the initial step in glycolysis and is a key regulator of glucose homeostasis. Therefore, glucokinase activators (GKa) have potential benefit in treating type 2 diabetes. Administration of a Bristol-Myers Squibb GKa (BMS-820132) to healthy euglycemic Sprague-Dawley (SD) rats and beagle dogs in 1 mo toxicology studies resulted in marked and extended hypoglycemia with associated clinical signs of toxicity and degenerative histopathological changes in the stomach, sciatic nerve, myocardium, and skeletal muscles at exposures comparable to those expected at therapeutic clinical exposures. To investigate whether these adverse effects were secondary to exaggerated pharmacology (prolonged hypoglycemia), BMS-820132 was administered daily to male Zucker diabetic fatty (ZDF) rats for 1 mo. ZDF rats are markedly hyperglycemic and insulin resistant. BMS-820132 did not induce hypoglycemia, clinical signs of hypoglycemia, or any of the histopathologic adverse effects observed in the 1 mo toxicology studies at exposures that exceeded those observed in SD rats and dogs. This indicates that the toxicity observed in euglycemic animals was secondary to the exaggerated pharmacology of potent GK activation. This study indicates that ZDF rats, with conventional toxicity studies, are a useful disease model for testing antidiabetic agents and determining toxicities that are independent of prolonged hypoglycemia. © 2015 by The Author(s).

  8. The efficacy of Prosopis glandulosa as antidiabetic treatment in rat models of diabetes and insulin resistance.

    Science.gov (United States)

    George, C; Lochner, A; Huisamen, B

    2011-09-01

    Diabetes mellitus is rampantly increasing and the need for therapeutics is crucial. In recognition of this, untested antidiabetic agents are flooding the market. Diavite™ which is a product consisting solely of the dried and ground pods of Prosopis glandulosa (Torr.) [Fabaceae] is currently marketed as a food supplement with glucose stabilizing properties. However, these are anecdotal claims lacking scientific evidence. The aim of this study was to determine the efficacy of Prosopis glandulosa as an antidiabetic agent. Male Wistar rats were rendered (a) type 1 diabetic after an intraperitoneal injection of STZ (40 mg/kg) and (b) insulin resistant after a 16-week high caloric diet (DIO). Zucker fa/fa ZDF rats were used in a pilot study. Half of each group of animals was placed on Prosopis glandulosa treatment (100mg/kg/day) for 8 weeks and the remaining animals served as age-matched controls. At the time of sacrifice, blood was collected for glucose and insulin level determination, the pancreata of the STZ rats were harvested for histological analysis and cardiomyocytes prepared from the DIO and Zucker fa/fa hearts for determination of insulin sensitivity. Type 1 diabetic model: Prosopis glandulosa treatment resulted in significant increased insulin levels (pProsopis glandulosa treatment resulted in increased small β-cells (pProsopis glandulosa treatment partially preventing this. Zucker fa/fa rats: Prosopis glandulosa treatment significantly reduced fasting glucose levels (pProsopis glandulosa treatment resulted in an increased basal (pProsopis glandulosa treatment moderately lowers glucose levels in different animal models of diabetes, stimulates insulin secretion, leads to the formation of small β-cells and improves insulin sensitivity of isolated cardiomyocytes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes

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    Valentina K. Bayrasheva

    2016-01-01

    Full Text Available Type 2 diabetes (DM2 could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ as well as STZ in high doses with preliminary nicotinamide (NA administration. However, STZ could induce tubulotoxicity. Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg or NA (230 mg/kg followed by STZ (65 mg/kg. Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study, metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1 were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.

  10. Evaluation of the Zucker diabetic fatty (ZDF rat as a model for human disease based on urinary peptidomic profiles.

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    Justyna Siwy

    Full Text Available Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD and cardiovascular disease (CVD biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin or related to disease development (collagen. Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level.

  11. Costimulation and autoimmune diabetes in BB rats

    NARCIS (Netherlands)

    Beaudette-Zlatanova, BC; Whalen, B; Zipris, D; Yagita, H; Rozing, J; Groen, H; Benjamin, CD; Hunig, T; Drexhage, HA; Ansari, MJ; Leif, J; Mordes, JP; Greiner, DL; Sayegh, MH; Rossini, AA

    Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55-120 days of age. We observed that two anti-CD28

  12. Effect of canagliflozin and metformin on cortical neurotransmitters in a diabetic rat model.

    Science.gov (United States)

    Arafa, Nadia M S; Marie, Mohamed-Assem S; AlAzimi, Sara Abdullah Mubarak

    2016-10-25

    The rapid economic development in the Arabian Gulf has resulted in lifestyle changes that have increased the prevalence of obesity and type 2 diabetes, with the greatest increases observed in Kuwait. Dyslipidemia and diabetes are risk factors for disruptions in cortical neurotransmitter homeostasis. This study investigated the effect of the antidiabetic medications canagliflozin (CAN) and metformin (MET) on the levels of cortical neurotransmitters in a diabetic rat model. The rats were assigned to the control (C) group, the diabetic group that did not receive treatment (D) or the diabetic group treated with either CAN (10 mg/kg) or MET (100 mg/kg) for 2 or 4 weeks. Blood and urine glucose levels and cortical acetylcholinesterase (AChE) activity were assayed, and amino acid and monoamine levels were measured using HPLC. The diabetic group exhibited a significant increase in AChE activity and a decrease in monoamine and amino acid neurotransmitter levels. In the CAN group, AChE was significantly lower than that in the D and D + MET groups after 2 weeks of treatment. In addition, a significant increase in some cortical monoamines and amino acids was observed in the D + MET and D + CAN groups compared with the D group. Histopathological analysis revealed the presence of severe focal hemorrhage, neuronal degeneration, and cerebral blood vessel congestion, with gliosis in the cerebrum of rats in the D group. The CAN-treated group exhibited severe cerebral blood vessel congestion after 2 weeks of treatment and focal gliosis in the cerebrum after 4 weeks of treatment. Focal gliosis in the cerebrum of rats in the MET-treated group was observed after 2 and 4 weeks of treatment. We conclude that the effect of CAN and MET on neurotransmitters is potentially mediated by their antihyperglycemic and antihyperlipidemic effects. In addition, the effects of CAN on neurotransmitters might be associated with its receptor activity, and the effect of MET on neurotransmitters

  13. Hematological changes in opium addicted diabetic rats.

    Science.gov (United States)

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

    2013-01-01

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

  14. A Canola Oil-Supplemented Diet Prevents Type I Diabetes-Caused Lipotoxicity and Renal Dysfunction in a Rat Model.

    Science.gov (United States)

    Cano-Europa, Edgar; Ortiz-Butron, Rocio; Camargo, Estela Melendez; Esteves-Carmona, María Miriam; Oliart-Ros, Rosa Maria; Blas-Valdivia, Vanessa; Franco-Colin, Margarita

    2016-11-01

    We investigated the effect of a canola oil-supplemented diet on the metabolic state and diabetic renal function of a type I diabetes experimental model. Male Sprague-Dawley rats were randomly divided into four groups: (1) normoglycemic+chow diet, (2) normoglycemic+a canola oil-supplemented chow diet, (3) diabetic+chow diet, and (4) diabetic+a canola oil-supplemented chow diet. For 15 weeks, animals were fed a diet of Purina rat chow alone or supplemented with 30% canola oil. Energetic intake, water intake, body weight, and adipose tissue fat pad were measured; renal function, electrolyte balance, glomerular filtration rate, and the plasmatic concentration of free fatty acids, cholesterol, triglycerides, and glucose were evaluated. The mesenteric, retroperitoneal, and epididymal fat pads were dissected and weighed. The kidneys were used for lipid peroxidation (LP) and reactive oxygen species (ROS) quantifications. Diabetic rats fed with a canola oil-supplemented diet had higher body weights, were less hyperphagic, and their mesenteric, retroperitoneal, and epididymal fat pads weighed more than diabetic rats on an unsupplemented diet. The canola oil-supplemented diet decreased plasmatic concentrations of free fatty acids, triglycerides, and cholesterol; showed improved osmolarity, water clearances, and creatinine depuration; and had decreased LP and ROS. A canola oil-supplemented diet decreases hyperphagia and prevents lipotoxicity and renal dysfunction in a type I diabetes mellitus model.

  15. Wound treatment on a diabetic rat model by a 808 nm diode laser

    International Nuclear Information System (INIS)

    Lau, Pik Suan; Bidin, Noriah; Krishnan, Ganesan; AnaybBaleg, Sana Mohammed; Baktiar, Harzi; Marsin, Faridah M; Sum, Mohamad Bin Md; Nassir, Zaleha; Chong, Pek Lian; Hamid, Asmah

    2015-01-01

    This paper presents a study on the effect of laser irradiation on wound healing. 808 nm diode laser was employed to facilitate the healing of impaired wounds in experimental diabetes using a rat model. Diabetes was induced in male rats by a streptozotocin injection with a dose of 60 mg kg −1 . The disease was verified via measurement of the blood glucose level, which was set having 20 mmol L −1 stability. The rats were randomly distributed into two groups; one served as a control group and the other group was treated with the laser. The power density of the laser used was 0.5 W cm −2 and the wounds were treated for 8 d with the contact time of one second daily. The energy density used was 0.5 J cm −2 . The healing progress was recorded via a digital camera. The recorded images were then transferred into Inspector Matrox and image J programs for the accurate measurement of the healing area. The tissue details of the wound were studied through histology. The wound contraction rate of laser therapy group was found to be two times faster than control group. This indicates that the 808 nm diode laser can accelerate the wound healing process. (paper)

  16. Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract

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    Madhoosudan A. Patil

    2014-01-01

    Full Text Available Type 2 diabetes (T2D generally follows prediabetes (PD conditions such as impaired fasting glucose (IFG and/or impaired glucose tolerance (IGT. Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70% of nSTZ injected pups developed IGT (nSTZ-PD by two months but not cataract even after seven months, remaining (30% nSTZ rats developed hyperglycemia (nSTZ-D by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities.

  17. The superoxide dismutase mimetic tempol blunts diabetes-induced upregulation of NADPH oxidase and endoplasmic reticulum stress in a rat model of diabetic nephropathy.

    Science.gov (United States)

    De Blasio, Miles J; Ramalingam, Anand; Cao, Anh H; Prakoso, Darnel; Ye, Ji-Ming; Pickering, Raelene; Watson, Anna M D; de Haan, Judy B; Kaye, David M; Ritchie, Rebecca H

    2017-07-15

    Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes. An additional age-matched group of rats was administered with citrate vehicle as controls. After 4 weeks of untreated diabetes, rats received tempol (1.5mM/kg/day subcutaneously, n=8), ramipril (1mg/kg/day in drinking water, n=8) or remained untreated for an additional 4 weeks (n=7). After 8 weeks of diabetes in total, kidneys were collected for histological analysis, gene expression and protein abundance. Tempol and ramipril blunted diabetes-induced upregulation of NADPH oxidase isoforms (Nox4, Nox2, p47 phox ), accompanied by an amelioration of diabetes-induced glomerular injury (podocin, nephrin, Kim-1), tubulo-interstitial fibrosis (TGFβ1, TGFβ-R2, pSMAD3, α-SMA) and pro-inflammatory cytokines (TNFα, MCP-1, ANX-A1, FPR2) expression. In addition, the diabetes-induced renal ER stress, evidenced by increased expression of GRP-78 chaperone and stress-associated markers ATF4, TRB3, as well as XBP1s, phospho-p38 mitogen-activated protein kinase (MAPK) and 3-nitrotyrosination, were all attenuated by tempol and ramipril. These observations suggest that antioxidant approaches that blunt NADPH upregulation may attenuate diabetic nephropathy, at least in part by negatively regulating ER stress and inflammation, and hence ameliorating kidney damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus.

    Science.gov (United States)

    Lenzen, S; Tiedge, M; Elsner, M; Lortz, S; Weiss, H; Jörns, A; Klöppel, G; Wedekind, D; Prokop, C M; Hedrich, H J

    2001-09-01

    We describe a new Type I (insulin-dependent) diabetes mellitus rat model (LEW.1AR1/Ztm-iddm) which arose through a spontaneous mutation in a congenic Lewis rat strain with a defined MHC haplotype (RT1.Aa B/Du Cu). The development of diabetes was characterised using biochemical, immunological and morphological methods. Diabetes appeared in the rats with an incidence of 20 % without major sex preference at 58+/-2 days. The disease was characterised by hyperglycaemia, glycosuria, ketonuria and polyuria. In peripheral blood, the proportion of T lymphocytes was in the normal range expressing the RT6.1 differentiation antigen. Islets were heavily infiltrated with B and T lymphocytes, macrophages and NK cells with beta cells rapidly destroyed through apoptosis in areas of insulitis. This Type I diabetic rat develops a spontaneous insulin-dependent autoimmune diabetes through beta cell apoptosis. It could prove to be a valuable new animal model for clarifying the mechanisms involved in the development of autoimmune diabetes.

  19. Combined Microencapsulated Islet Transplantation and Revascularization of Aortorenal Bypass in a Diabetic Nephropathy Rat Model

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    Yunqiang He

    2016-01-01

    Full Text Available Objective. Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS in diabetic nephropathy (DN patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model. Methods. A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group. The levels of blood glucose and urine protein were measured, and changes in renal pathology were observed. The expression of monocyte chemoattractant protein-1 (MCP-1 in graft vessels was assessed by immunohistochemical staining. Histopathological staining was performed to assess the pathological changes of glomeruli and tubules. Results. The levels of urine protein and the expression of MCP-1 in graft vessels were decreased after islet transplantation. The injury of glomerular basement membrane and podocytes was significantly ameliorated. Conclusions. The combined strategy of revascularization and microencapsulated islet transplantation had multiple protective effects on diabetic nephropathy, including preventing atherosclerosis in the graft vessels and alleviating injury to the glomerular filtration barrier. This combined strategy may be helpful for DN patients with RAS.

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

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    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

  1. Nutritional correlates and dynamics of diabetes in the Nile rat (Arvicanthis niloticus: a novel model for diet-induced type 2 diabetes and the metabolic syndrome

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    Maslova Ekaterina

    2010-04-01

    Full Text Available Abstract Background The prevalence of Metabolic Syndrome and related chronic diseases, among them non-insulin-dependent (type 2 diabetes mellitus, are on the rise in the United States and throughout the world. Animal models that respond to environmental stressors, such as diet, are useful for investigating the outcome and development of these related diseases. Objective Within this context, growth and energy relationships were characterized in the Nile rat, an exotic African rodent, as a potential animal model for diet-induced type 2 diabetes mellitus and Metabolic Syndrome. Methods Compiled data from several studies established the relationship between age, body weight gain (including abdominal adiposity, food and water consumption, and blood glucose levels as determinants of diabetes in male and female Nile rats. Glucose Tolerance Testing, insulin, HbA1c, blood pressure measurements and plasma lipids further characterized the diabetes in relation to criteria of the Metabolic Syndrome, while diet modification with high-fat, low-fiber or food restriction attempted to modulate the disease. Results The Nile rat fed lab chow demonstrates signs of the Metabolic Syndrome that evolve into diet-induced non-insulin-dependent (type 2 diabetes mellitus characterized by hyperinsulinemia with rising blood glucose (insulin resistance, abdominal adiposity, and impaired glucose clearance that precedes increased food and water intake, as well as elevated HbA1c, marked elevation in plasma triglycerides and cholesterol, microalbuminuria, and hypertension. Males are more prone than females with rapid progression to diabetes depending on the challenge diet. In males diabetes segregated into early-onset and late-onset groups, the former related to more rapid growth and greater growth efficiency for the calories consumed. Interestingly, no correlation was found between blood glucose and body mass index (overall adiposity in older male Nile rats in long term studies

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

    Science.gov (United States)

    Leung, Joanne Y T; Pang, Catherine C Y

    2014-07-01

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

  3. Effects of Bariatric Surgery on Serum Bile Acid Composition and Conjugation in a Diabetic Rat Model.

    Science.gov (United States)

    Wu, Qunzheng; Zhang, Xiang; Zhong, Mingwei; Han, Haifeng; Liu, Shaozhuang; Liu, Teng; Wei, Meng; Guo, Wei; Xie, Haibin; Hu, Sanyuan; Zhang, Guangyong

    2016-10-01

    Serum bile acids (BAs) are elevated following bariatric surgery and have emerged as a potential glucose-lowering beneficial factor. The change of BA components and its underlying mechanisms may be of great significance during bariatric surgery. The aim of this study is to investigate the effects of different bariatric procedures on serum BA composition and explore the potential mechanisms using a diabetic rat model. Duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham operation were performed in diabetic rats induced by high-fat diet (HFD) and streptozotocin (STZ). Body weight, food intake, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were measured at indicated time points. Serum BAs composition and the expression of cholesterol 7α hydroxylase (CYP7A1), bile acid: CoA synthase (BACS) and bile acid-CoA: amino acid N-acyltransferase (BAAT) at both transcriptional and protein levels in the liver were evaluated at 12 weeks postoperatively. Compared with sham group, DJB and SG both achieved rapid and sustained improvements in glucose tolerance and insulin sensitivity. They also resulted in increased serum BAs, especially the taurine-conjugated BAs by elevated conjugation. No obvious difference was detected between DJB and SG except that SG achieved decreased weight gain and food intake. The preferentially elevated serum taurine-conjugated BAs were similar after different bariatric surgeries, and the enhanced conjugation of BAs in the liver might account for the changed serum BAs profiles.

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

    Science.gov (United States)

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

    2017-08-01

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

  5. Potential impact of Paracentrotus lividus extract on diabetic rat models induced by high fat diet/streptozotocin

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    Amel M. Soliman

    2016-10-01

    Full Text Available Antioxidant therapy has been thought to be effectual for the prevention and treatment of various diseases including diabetes. Therefore, the present study was designed to investigate the potency of Paracentrotus lividus extract (PLE for alleviating the complications that resulted after induction of the diabetic rat models (T1DM and T2DM using high fat diet (HFD/streptozotocin (STZ. Thirty six male Wistar albino rats were assigned into normal control, T1DM and T2DM untreated, and PLE treated diabetic rat groups. Induction of T1DM was performed by streptozotocin injection (60 mg/kg of dissolved in sodium citrate buffer, 0.1 mol/L, i.p. T2DM induction through 4 weeks of high fat diet (HFD intervention was followed by a single low dosage of STZ (30 mg/kg dissolved in 0.1 mol/L citrate buffer at pH 4.5, i.p. Both diabetic rat models showed a significant increase in serum; levels of fasting glucose, total protein, bilirubin, activities of arginase, transaminases (AST and ALT, alkaline phosphatase (ALP, γ glutamyl transferase (GGT, lipid profile parameters, and liver malondialdehyde (MDA. However, T1DM and T2DM rats have decreased levels of serum insulin, and liver glucose 6 phosphate dehydrogenase (G6PD, glutathione reduced (GSH, nitric oxide (NO, and antioxidant enzymes. Furthermore, the present study showed the hypoglycemic, hypolipidemic, and antioxidant potency of the PLE as confirmed by its ability for ameliorating most of the alterations caused in the studied parameters of diabetic rats. In conclusion, PLE may be useful as therapy against oxidative stress and liver damage in both types of diabetes mellitus and is therefore recommended for further studies.

  6. Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model.

    Science.gov (United States)

    Piccolo, Brian D; Graham, James L; Stanhope, Kimber L; Fiehn, Oliver; Havel, Peter J; Adams, Sean H

    2016-06-01

    Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e., prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-β-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset. Copyright © 2016 the American Physiological Society.

  7. Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes.

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    Shima, Takeru; Matsui, Takashi; Jesmin, Subrina; Okamoto, Masahiro; Soya, Mariko; Inoue, Koshiro; Liu, Yu-Fan; Torres-Aleman, Ignacio; McEwen, Bruce S; Soya, Hideaki

    2017-03-01

    Type 2 diabetes is likely to be an independent risk factor for hippocampal-based memory dysfunction, although this complication has yet to be investigated in detail. As dysregulated glycometabolism in peripheral tissues is a key symptom of type 2 diabetes, it is hypothesised that diabetes-mediated memory dysfunction is also caused by hippocampal glycometabolic dysfunction. If so, such dysfunction should also be ameliorated with moderate exercise by normalising hippocampal glycometabolism, since 4 weeks of moderate exercise enhances memory function and local hippocampal glycogen levels in normal animals. The hippocampal glycometabolism in OLETF rats (model of human type 2 diabetes) was assessed and, subsequently, the effects of exercise on memory function and hippocampal glycometabolism were investigated. OLETF rats, which have memory dysfunction, exhibited higher levels of glycogen in the hippocampus than did control rats, and breakdown of hippocampal glycogen with a single bout of exercise remained unimpaired. However, OLETF rats expressed lower levels of hippocampal monocarboxylate transporter 2 (MCT2, a transporter for lactate to neurons). Four weeks of moderate exercise improved spatial memory accompanied by further increase in hippocampal glycogen levels and restoration of MCT2 expression independent of neurotrophic factor and clinical symptoms in OLETF rats. Our findings are the first to describe detailed profiles of glycometabolism in the type 2 diabetic hippocampus and to show that 4 weeks of moderate exercise improves memory dysfunction in type 2 diabetes via amelioration of dysregulated hippocampal glycometabolism. Dysregulated hippocampal lactate-transport-related glycometabolism is a possible aetiology of type-2-diabetes-mediated memory dysfunction.

  8. Melatonin supplementation plus exercise behavior ameliorate insulin resistance, hypertension and fatigue in a rat model of type 2 diabetes mellitus.

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    Rahman, Md Mahbubur; Kwon, Han-Sol; Kim, Myung-Jin; Go, Hyeon-Kyu; Oak, Min-Ho; Kim, Do-Hyung

    2017-08-01

    The objective was to investigate the effects of melatonin and exercise on insulin resistance (IR), hypertension and fatigue syndrome in a rat model of type 2 diabetes mellitus (T2DM). Rats were divided into 5 groups namely normal control (NC), T2DM control group (DC), diabetes plus exercise (DE), diabetes plus oral melatonin supplement (DM) and diabetes plus melatonin and exercise (DME) groups. Melatonin was administered orally 5mg/kg twice daily and 40min swimming/day 5days/week were regimented after diabetes induction. Blood pressure, fasting blood glucose, insulin, IR, serum leptin, lipid profiles, inflammatory cytokines, lipid peroxidation increased significantly (Pmelatonin ameliorated markedly hypertension, IR, biochemical alteration induced by diabetes and significantly increased exercise performance (PMelatonin supplementation in combination with exercise behavior may ameliorate IR, hypertension and exercise performance or fatigue possibly by improving antioxidative activities, hyperlipidemia, inflammatory cytokines via up-regulation of GLUT4, PGC-1 α and mitochondrial biogenesis in T2DM rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Adipose-Derived Stem Cell-Derived Exosomes Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes.

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    Chen, Fengzhi; Zhang, Haibo; Wang, Zhiqiang; Ding, Wei; Zeng, Qinyu; Liu, Wenbing; Huang, Can; He, Shuhua; Wei, Anyang

    2017-09-01

    The efficacy of adipose-derived stem cells (ADSCs) in alleviating erectile dysfunction (ED) of diabetic rats has been demonstrated mainly through a paracrine effect. However, exosomes (EXOs), which are important bioactive substance vectors secreted by ADSCs, have never been associated with ED. To investigate the effect of ADSC-derived EXOs on erectile function in a type 2 diabetic ED rat model. EXOs were isolated from the supernatants of cultured ADSCs by ultracentrifugation. We constructed a type 2 diabetic rat model using a high-fat diet and low-dose streptozotocin administered by intraperitoneal injection. In total, 24 diabetic rats were randomly assigned to three groups and were treated with an intracavernous injection of ADSC-derived EXOs, ADSCs, or phosphate buffered saline. Another eight age-matched rats underwent sham operation and composed the normal control group. Intracavernous pressure and mean arterial pressure testing and histologic and western blot analyses were performed 4 weeks after the intracavernous injection. ADSC-derived EXOs and ADSCs administered by intracavernous injection led to an increase in the ratio of intracavernous pressure to mean arterial pressure compared with that for phosphate buffered saline treatment. Histologic and western blot analyses demonstrated an increased ratio of smooth muscle to collagen, increased expression of an endothelial marker (CD31), a smooth muscle marker (α-smooth muscle actin), and antiapoptotic protein Bcl-2 and decreased the expression of the apoptotic protein cleaved caspase-3 and apoptosis of endothelial and smooth muscle cells in the corpus cavernosum tissue after EXO or ADSC injection compared with values for the phosphate buffered saline treatment. The present results are expected to provide a scientific foundation for clinical application in the near future. Although the results demonstrated that intracavernous injection of ADSC-derived EXOs could ameliorate ED of diabetic rats, the optimum dose

  10. The Nile Rat (Arvicanthis niloticus as a Superior Carbohydrate-Sensitive Model for Type 2 Diabetes Mellitus (T2DM

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    Avinaash Subramaniam

    2018-02-01

    Full Text Available Type II diabetes mellitus (T2DM is a multifactorial disease involving complex genetic and environmental interactions. No single animal model has so far mirrored all the characteristics or complications of diabetes in humans. Since this disease represents a chronic nutritional insult based on a diet bearing a high glycemic load, the ideal model should recapitulate the underlying dietary issues. Most rodent models have three shortcomings: (1 they are genetically or chemically modified to produce diabetes; (2 unlike humans, most require high-fat feeding; (3 and they take too long to develop diabetes. By contrast, Nile rats develop diabetes rapidly (8–10 weeks with high-carbohydrate (hiCHO diets, similar to humans, and are protected by high fat (with low glycemic load intake. This review describes diabetes progression in the Nile rat, including various aspects of breeding, feeding, and handling for best experimental outcomes. The diabetes is characterized by a striking genetic permissiveness influencing hyperphagia and hyperinsulinemia; random blood glucose is the best index of disease progression; and kidney failure with chronic morbidity and death are outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty liver disease (NAFLD, also described in diabetic humans, results from hepatic triglyceride and cholesterol accumulation associated with rising blood glucose. Protection is afforded by low glycemic load diets rich in certain fibers or polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify the nutritional factors and underlying genetic and molecular mechanisms that characterize human T2DM.

  11. The effects of hydroalcoholic extract of Juglans regia leaf on histological changes of Langerhans islet in diabetic rats model

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    Jamshid Mohammadi

    2012-12-01

    Full Text Available Background: It has been shown that the Juglans regia leaves have hypoglycemic, diuretic and blood pressure reduction properties. The objective of the present study was to examine the histopathology effects of Juglans regia leaves on diabetes mellitus in rats. Material and Methods: Forty-eight Wistar rats (150- 200 g were randomized into six groups of 8 animals. Groups III, IV, V and VI received intraperitoneal injection of streptozotocin to make diabetic model. Blood glucose was measured by glucometer after 72 hours. After 10 days, Group II, IV and V received 400, 200 and 400 mg/kg Juglans regia extract, respectively and group VI treated with 4 mg/kg glybenclamid for four weeks. Group I were fed with normal diet and group III received distilled water (diabetic control. The body weight and blood glucose were measured in every week. The number of β cells and diameter of islets of Langerhans were determined using hematoxylin-floxin staining. The collected data was analyzed by the SPSS software using one-way ANOVA. Results: The number of β cells and diameter of islets decreased significantly in diabetic control compare to the normal group. Treatment with 400 mg/kg of Juglans regia extract showed a significant decrease in blood glucose, a significant increase in diameter of islets and number of β cells compared to diabetic control group. The pancreas / body weight ratio increased in diabetic rats compare to the treatment group. Conclusion: The administration of Juglans regia extract can cause recovery of β cells number and improve the size of islets of Langerhans in diabetic model rats.

  12. Ethanol at Low Concentration Attenuates Diabetes Induced Lung Injury in Rats Model

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    Jun-Feng Hu

    2014-01-01

    Full Text Available To observe the changes of lung injury when diabetic rats were treated with low concentration of ethanol (EtOH and analyze the related mechanisms, male Sprague-Dawley (SD rats were divided into control, diabetic (DM, and EtOH+DM groups. Diabetic rat was mimicked by injection of streptozotocin intraperitoneally. Fasting blood glucose (FBG level, lung weight (LW, body weight (BW, and LW/BW were measured. The changes of lung tissue and Type II alveolar cell were detected. Pulmonary malondialdehyde (MDA content and superoxide dismutase (SOD activity were measured; meanwhile, ALDH2 mRNA and protein expressions were detected by RT-PCR and western blotting, respectively. Compared with control group, in DM group, SOD activity was decreased; FBG level, LW/BW, MDA content, ALDH2 mRNA, and protein expressions were decreased. Compared with DM group, in EtOH+DM group, SOD activity, ALDH2 mRNA, and protein expressions were increased; LW/BW and MDA content were decreased. The structures of lung tissue and lamellar bodies were collapsed in DM group; the injury was attenuated in EtOH+DM group. Our findings suggested that, in diabetic rat, pulmonary ALDH2 expression was decreased accompanying lung injury. EtOH at low concentration decreased diabetes induced lung injury through activating ALDH2 expression.

  13. Replacing white rice with pre-germinated brown rice mildly ameliorates hyperglycemia and imbalance of adipocytokine levels in type 2 diabetes model rats.

    Science.gov (United States)

    Torimitsu, Mariko; Nagase, Ryouhei; Yanagi, Megumi; Homma, Miyuki; Sasai, Yousuke; Ito, Yukihiko; Hayamizu, Kousuke; Nonaka, Shouta; Hosono, Takashi; Kise, Mitsuo; Seki, Taiichiro; Ariga, Toyohiko

    2010-01-01

    Pre-germinated brown rice (PR) has been developed industrially in order to enhance the nutritional functions of its source material, brown rice (BR). The present study was aimed at clarifying the effect of PR on the type 2 diabetes mellitus. We employed Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of type-2 diabetes mellitus. OLETF rats were fed on either PR or white rice (WR) from the age of 4 to 35 wk. Age-matched male Long-Evans Tokushima Otsuka (LETO) rats as a non-diabetic control were also fed on WR. The HbA(1c) level in OLETF rats was significantly higher than that in LETO rats. However, the level was lower in PR-fed OLETF rats than in WR-fed OLETF rats. The plasma concentrations of TNF-α and PAI-1 in OLETF rats were higher than those in LETO rats. However, both elevated levels were decreased by the PR-feeding, but not by the WR-feeding. On the other hand, the plasma adiponectin concentration in OLETF rats was lower than that in LETO rats. The decrease in adiponectin level of OLETF rats was ameliorated by PR-feeding. The size of adipocytes in PR-fed OLETF rats was smaller than that in WR-fed OLETF rats. In summary, intake of PR instead of WR ameliorates both insulin resistance and imbalance of the levels of plasma adipocytokines leading to diabetic complications.

  14. Cardioprotective and anti-hypertensive effects of Prosopis glandulosa in rat models of pre-diabetes.

    Science.gov (United States)

    Huisamen, B; George, C; Dietrich, D; Genade, S

    2013-03-01

    Obesity and type 2 diabetes present with two debilitating complications, namely, hypertension and heart disease. The dried and ground pods of Prosopis glandulosa (commonly known as the Honey mesquite tree) which is part of the Fabaceae (or legume) family are currently marketed in South Africa as a food supplement with blood glucose-stabilising and anti-hypertensive properties. We previously determined its hypoglycaemic effects, and in the current study we determined the efficacy of P glandulosa as anti-hypertensive agent and its myocardial protective ability. Male Wistar rats were rendered either pre-diabetic (diet-induced obesity: DIO) or hypertensive (high-fat diet: HFD). DIO animals were treated with P glandulosa (100 mg/kg/day for the last eight weeks of a 16-week period) and compared to age-matched controls. Hearts were perfused ex vivo to determine infarct size. Biometric parameters were determined at the time of sacrifice. Cardiac-specific insulin receptor knock-out (CIRKO) mice were similarly treated with P glandulosa and infarct size was determined. HFD animals were treated with P glandulosa from the onset of the diet or from weeks 12-16, using captopril (50 mg/kg/day) as the positive control. Blood pressure was monitored weekly. DIO rats and CIRKO mice: P glandulosa ingestion significantly reduced infarct size after ischaemia-reperfusion. Proteins of the PI-3-kinase/PKB/Akt survival pathway were affected in a manner supporting cardioprotection. HFD model: P glandulosa treatment both prevented and corrected the development of hypertension, which was also reflected in alleviation of water retention. P glandulosa was cardioprotective and infarct sparing as well as anti-hypertensive without affecting the body weight or the intra-peritoneal fat depots of the animals. Changes in the PI-3-kinase/PKB/Akt pathway may be causal to protection. Results indicated water retention, possibly coupled to vasoconstriction in the HFD animals, while ingestion of P glandulosa

  15. Total parenteral nutrition in diabetic rats

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  16. Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes.

    Science.gov (United States)

    Ibrahim, Ahmed S; El-Remessy, Azza B; Matragoon, Suraporn; Zhang, Wenbo; Patel, Yogin; Khan, Sohail; Al-Gayyar, Mohammed M; El-Shishtawy, Mamdouh M; Liou, Gregory I

    2011-04-01

    During diabetes, retinal microglial cells are activated to release inflammatory cytokines that initiate neuronal loss and blood-retinal barrier breakdown seen in diabetic retinopathy (DR). The mechanism by which diabetes activates microglia to release those inflammatory mediators is unclear and was therefore elucidated. Microglia activation was characterized in streptozocin-injected rats and in isolated microglial cells using immunofluorescence, enzyme-linked immunosorbent assay, RT-PCR, and Western blot analyses. In 8-week diabetic retina, phospho-extracellular signal-related kinase (ERK) and P38 mitogen-activated protein kinases were localized in microglia, but not in Mueller cells or astrocytes. At the same time, Amadori-glycated albumin (AGA)-like epitopes were featured in the regions of microglia distribution, implicating a pathogenic effect on microglial activation. To test this, diabetic rats were treated intravitreally with A717, a specific AGA-neutralizing antibody, or murine IgG. Relative to nondiabetic rats, diabetic rats (IgG-treated) manifested 3.9- and 7.9-fold increases in Iba-1 and tumor necrosis factor (TNF)-α mRNAs, respectively. Treatment of diabetic rats with A717 significantly attenuated overexpression of these mRNAs. Intravitreal injection of AGA per se in normal rats resulted in increases of Iba-1 expression and TNF-α release. Guided by these results, a cultured retinal microglia model was developed to study microglial response after AGA treatment and the mechanistic basis behind this response. The results showed that formation of reactive oxygen species and subsequent activation of ERK and P38, but not Jun NH2-terminal kinase, are molecular events underpinning retinal microglial TNF-α release during AGA treatment. These results provide new insights in understanding the pathogenesis of early DR, showing that the accumulated AGA within the diabetic retina elicits the microglial activation and secretion of TNF-α. Thus, intervention trials

  17. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    International Nuclear Information System (INIS)

    Ergaz, Zivanit; Shoshani-Dror, Dana; Guillemin, Claire; Neeman-azulay, Meytal; Fudim, Liza; Weksler-Zangen, Sarah; Stodgell, Christopher J.; Miller, Richard K.; Ornoy, Asher

    2012-01-01

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

  18. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il [Hebrew University Hadassah Medical School, Jerusalem (Israel); Shoshani-Dror, Dana [Hebrew University Hadassah Medical School, Jerusalem (Israel); Guillemin, Claire [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Neeman-azulay, Meytal; Fudim, Liza [Hebrew University Hadassah Medical School, Jerusalem (Israel); Weksler-Zangen, Sarah [Diabetes Research Unit, Hebrew University Hadassah Medical School and Hospital, Jerusalem (Israel); Stodgell, Christopher J.; Miller, Richard K. [Department of Obstetrics and Gynecology, University of Rochester, Rochester, MN (United States); Ornoy, Asher [Hebrew University Hadassah Medical School, Jerusalem (Israel)

    2012-12-01

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

  19. Effects of insulin-mimetic vanadyl-poly(gamma-glutamic acid) complex on diabetic rat model.

    Science.gov (United States)

    Hu, Rongzhang; He, Chengliang; Liu, Jian; Wu, Yelin; Li, Jing; Feng, Zhen; Huang, Jing; Xi, Xu Guang; Wu, Zirong

    2010-07-01

    Poly-gamma-glutamic acid (gamma-PGA) prepared by fermentation of microbe was used as drug carrier for vanadium sulfate to obtain vanadyl-poly-gamma-glutamic acid (VO-gamma-PGA) complex. The FI-IR spectrum of the complex demonstrated that the expected VO-gamma-PGA complex is formed by the coordination of VO(2+) through the side chain carboxylic groups of the gamma-PGA. Studies of the complex in treating type I diabetes were carried out on alloxan induced diabetes rats. The results of treating the rats in 2 weeks and then stopping administration for 10 days showed that VO-gamma-PGA can effectively lower blood glucose levels of diabetic rats during administration. But after ceasing treatment there were no differences between groups in blood glucose level and water intake. The results of oral glucose tolerance and some serum parameters also demonstrated that VO-gamma-PGA was more effective than vanadium sulfate in treating diabetic rats. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  20. Aortic superoxide production at the early hyperglycemic stage in a rat type 2 diabetes model and the effects of pravastatin.

    Science.gov (United States)

    Kikuchi, Chigusa; Kajikuri, Junko; Hori, Eisei; Nagami, Chie; Matsunaga, Tamihide; Kimura, Kazunori; Itoh, Takeo

    2014-01-01

    Endothelium-derived superoxide induces vascular dysfunctions. The aim of this study was to examine the activity of protein kinase C (PKC) isoforms and endothelial nitric oxide synthase (eNOS), which leads to vascular superoxide production in type 2 diabetes, in addition to the effects of pravastatin. We studied these mechanisms in Otsuka Long-Evans Tokushima Fatty (OLETF) rats (type 2 diabetes model) at the early hyperglycemic stage (vs. non-diabetic Long-Evans Tokushima Otsuka [LETO] rats). Superoxide production and catalase activity were measured in aortas, as were the protein expressions of PKCδ and phospho-Ser(1177) eNOS. Superoxide production was increased in OLETF rats, and this increase was inhibited by the selective conventional PKC (cPKC) inhibitor Gö6976 and by the non-selective cPKC and novel PKC inhibitor GF109203X. Phospho-Ser(1177) eNOS was significantly increased in OLETF rats, whereas the protein expressions of PKCδ and phosopho-Thr(505) PKCδ and catalase activity were all greatly reduced. Pravastatin administration to OLETF rats in vivo had normalizing effects on all of these variables. The increment in superoxide production seen in OLETF rats (but not the production in pravastatin-treated OLETF rats) was abolished by high concentration of N(ω)-nitro-L-arginine methyl ester (electron transport inhibitor of eNOS), by sepiapterin (precursor of tetrahydrobiopterin), and by LY294002 (phosphatidylinositol 3-kinase [PI3-kinase] inhibitor). In OLETF rats at the early hyperglycemic stage, aortic superoxide production is increased owing to activation of uncoupled eNOS through phosphorylation by PI3-kinase/Akt. This may be related to the observed reduction in PKCδ/catalase activities. Pravastatin inhibited endothelial superoxide production via normalization of PKCδ/catalase activities.

  1. Appropriate Insulin Level in Selecting Fortified Diet-Fed, Streptozotocin-Treated Rat Model of Type 2 Diabetes for Anti-Diabetic Studies

    Science.gov (United States)

    Umar, Ismaila A.; James, Dorcas B.; Inuwa, Hajiya M.

    2017-01-01

    Background Pathophysiological investigation of disease in a suitable animal model is a classical approach towards development of a credible therapeutic strategy. This study examined appropriate insulin level in selecting animal model for type 2 diabetes (T2D) studies. Method Albino Wistar rats (150-200g) were divided into two groups fed with commercially available normal-diet-feed (NDF) and water or fortified diet feed (FDF) (10g NDF per gram of margarine) with 20% fructose solution as drinking water. After 6 weeks of dietary regimen both groups were divided into 5 sub-groups and injected intraperitoneally with a graded dose of streptozotocin (STZ) (0, 25, 35, 45 & 55mg/kg bw.). Result The result showed that the FDF-fed rats increased significantly in body weight, basal serum insulin, total cholesterol, triglycerides and blood glucose levels as compared to NDF-fed rats. Ten days post STZ induction, the groups treated with STZ (45 & 55 mg/kg) developed frank hyperglycaemia with insulin, a severe deficiency typical of diabetes type 1. The NDF25 and NDF35 groups with 75.7% and 64.4% serum insulin respectively presented relative normoglycemia, whereas the FDF35 (85.8% serum insulin) were notably hyperglycaemia (>300 mg/dL) throughout the 6weeks post diabetes confirmation. These FDF35 rats were sensitive to glibenclamide, metformin and pioglitazone in lowering hyperglycaemia, hypertriglyceridemia and hypercholesterolemia Conclusion The hyperglycaemia stability of the FDF35 rats (85.5% insulin) together with their sensitivity to 3 different hypoglycaemic drugs strongly suggests their suitability as a non-genetic model of T2D. Hence the study shows that circulating serum insulin ≥ 85.8% with overt hyperglycaemia may be utilized as the benchmark in selecting rat models for T2D studies. PMID:28129400

  2. Preserving Duodenal-Jejunal (Foregut) Transit Does Not Impair Glucose Tolerance and Diabetes Remission Following Gastric Bypass in Type 2 Diabetes Sprague-Dawley Rat Model.

    Science.gov (United States)

    Dolo, Ponnie R; Yao, Libin; Li, Chao; Zhu, Xiaocheng; Shi, Linsen; Widjaja, Jason

    2017-11-02

    Possible mechanisms underlying diabetes remission following Roux-en-Y gastric bypass (RYGB) include eradication of putative factor(s) with duodenal-jejunal bypass. The objective of this study is to observe the effects of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass rat model. In order to verify the effect of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass, 22 type 2 diabetes Sprague-Dawley rat models established through high-fat diet and low-dose streptozotocin (STZ) administered intraperitoneally were assigned to one of three groups: gastric bypass with duodenal-jejunal transit (GB-DJT n = 8), gastric bypass without duodenal-jejunal transit (RYGB n = 8), and sham (n = 6). Body weight, food intake, blood glucose, as well as meal-stimulated insulin, and incretin hormone responses were assessed to ascertain the effect of surgery in all groups. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted three and 7 weeks after surgery. Comparing our GB-DJT to the RYGB group, we saw no differences in the mean decline in body weight, food intake, and blood glucose 8 weeks after surgery. GB-DJT group exhibited immediate and sustained glucose control throughout the study. Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels were also significantly increased from preoperative level in the GB-DJT group (p transit does not impede glucose tolerance and diabetes remission after gastric bypass in type-2 diabetes Sprague-Dawley rat model.

  3. Combined Effects of a Dietary Fiber Mixture and Wheat Albumin in a Rat Model of Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Kubo, Kazuhiro; Koido, Ayano; Kitano, Misako; Yamamoto, Hirotaka; Saito, Morio

    2016-01-01

    As bioactive ingredients of functional foods, dietary fiber and wheat albumin (WA) are known to suppress hyperglycemia in patients with type 2 diabetes mellitus. The combined effects of these bioactive ingredients were examined using an animal model of type 2 diabetes mellitus. First, oral starch tolerance tests (OSTTs) with the simultaneous intake of a dietary fiber mixture (DF) and WA were performed as an acute study. Male Goto-Kakizaki rats received a soluble starch solution [700 mg/kg body weight (bw)] containing DF and/or WA (each 300 mg/kg bw). In these OSTTs, the combined intake of DF and WA suppressed hyperglycemia much more effectively than each separate intake. Second, in a chronic intake study, diets containing DF and/or WA were administered to male Zucker diabetic fatty rats over 84 d. The combined effects of DF and WA were not observed in glycosylated hemoglobin concentration levels or fasting blood glucose levels, but appeared as an improvement in liver lipid contents. Variations in the liver lipid contents were similarly reflected in those of the plasma lipid concentrations. In conclusion, this study found that the simultaneous intake of bioactive DF and WA improved the postprandial hyperglycemia and the chronic lipid metabolism disorders in rat models of type 2 diabetes mellitus.

  4. The establishment of a rat diabetic model and the functional measurement of its α, β, D cells of pancreas

    International Nuclear Information System (INIS)

    Zhang Guangzheng; Shen Jiangfan; Kang Aijuan; Yuan Jimin; Zhu Cuiying

    1992-01-01

    A diabetic model with alloxan in Will's rat has been established and the function of α, β, D cells of its pancreas were studied. The plasma level of glucagon, somatostatin and insulin in portal and caval vein were measured by RIA. The results showed that the glucagon and somatostatin were significantly increased, while the insulin was decreased. The results demonstrated that the changes of somatostatin was somewhat related also to diabetes and the experimental studies have supported this concept that the increasing of somatostatin level will inhibit the increasing of glucagon and thereby the hyperglycemia would be alleviated

  5. Kinetic analysis of the rate of corneal wound healing in Otsuka long-evans Tokushima Fatty rats, a model of type 2 diabetes mellitus.

    Science.gov (United States)

    Nagai, Noriaki; Murao, Takatoshi; Okamoto, Norio; Ito, Yoshimasa

    2010-01-01

    Diabetic keratopathy is a well-known ocular complication secondary to type 2 diabetes mellitus. In this study, we performed a kinetic analysis of corneal wound healing in Long-Evans rats (normal rat) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Corneal wound healing in 7-week-old normal rats was mostly complete 24 h after corneal epithelial abrasion, and the process of corneal wound healing took place according to an equation with a first-order rate constant. The rate of corneal wound healing in normal rats decreased with aging. The process of corneal wound healing in 38- and 60-week-old normal and OLETF rats occurred in two phases with rate constants for the first and second phases represented as alpha and beta, respectively. The alpha and beta values in 38- and 60-week-old OLETF rats were lower than those in normal rats of the corresponding age. Furthermore, a close relationship was observed between the corneal wound healing rate constant and plasma glucose levels in OLETF rats. The present studies suggest the sequence of events that occur following damage to the corneal surface in OLETF rats as a model animal for a human type 2 diabetes mellitus.

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

    OpenAIRE

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

    2013-01-01

    Curcumin, the active principle present in the yellow spice turmeric, has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Previously we have reported that dietary curcumin delays diabetes-induced cataract in rats. However, low peroral bioavailability is a major limiting factor for the success of clinical utilization of curcumin. In this study, we have administered curcumin encapsulated nanoparticles ...

  7. Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.

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    Goichi Yanai

    Full Text Available Islet transplantation is a minimally invasive treatment for severe diabetes. However, it often requires multiple donors to accomplish insulin-independence and the long-term results are not yet satisfying. Therefore, novel ways to overcome these problems have been explored. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types, promote angiogenesis and modulate inflammation, thereby studied as an enhancer of islet function and engraftment. Electrofusion is an efficient method of cell fusion and nuclear reprogramming occurs in hybrid cells between different cell types. Therefore, we hypothesized that electrofusion between MSC and islet cells may yield robust islet cells for diabetes therapy. We establish a method of electrofusion between dispersed islet cells and MSCs in rats. The fusion cells maintained glucose-responsive insulin release for 20 days in vitro. Renal subcapsular transplantation of fusion cells prepared from suboptimal islet mass (1,000 islets that did not correct hyperglycemia even if co-transplanted with MSCs, caused slow but consistent lowering of blood glucose with significant weight gain within the observation period in streptozotocin-induced diabetic rats. In the fusion cells between rat islet cells and mouse MSCs, RT-PCR showed new expression of both rat MSC-related genes and mouse β-cell-related genes, indicating bidirectional reprogramming of both β-cell and MSCs nuclei. Moreover, decreased caspase3 expression and new expression of Ki-67 in the islet cell nuclei suggested alleviated apoptosis and gain of proliferative capability, respectively. These results show that electrofusion between MSCs and islet cells yield special cells with β-cell function and robustness of MSCs and seems feasible for novel therapeutic strategy for diabetes

  8. Investigation of pharmacological responses to anti-diabetic drugs in female Spontaneously Diabetic Torii (SDT) fatty rats, a new nonalcoholic steatohepatitis (NASH) model.

    Science.gov (United States)

    Toriniwa, Yasufumi; Saito, Tomoyuki; Miyajima, Katsuhiro; Ishii, Yukihito; Uno, Kinuko; Maekawa, Tatsuya; Matsui, Tohru; Kume, Shinichi; Yamada, Takahisa; Ohta, Takeshi

    2018-04-10

    Nonalcoholic steatohepatitis (NASH) is a progressive liver disease, and some patients develop hepatic cirrhosis/carcinoma. Animal models play key roles in the development of new therapies for NASH. In this study, the pharmacological effects of metformin and pioglitazone were investigated in female Spontaneously Diabetic Torii (SDT) fatty rats to verify the utility of this model. The anti-diabetic drugs were administered to SDT fatty rats fed a cholesterol-enriched diet from 4 to 25 weeks, and changes in food intake, body weight, and blood chemistry parameters were evaluated every 4 weeks. The hepatic lipid content, mRNA expression in relation to lipid synthesis, inflammation, and fibrosis, and histopathological analyses were performed at 25 weeks. Pioglitazone improved hyperglycemia, hyperlipidemia, and abnormalities in hepatic parameters. The insulin levels were lower than those in the control rats before 16 weeks. Plasma glucose levels in the metformin-treated rats were lower than those in the control rats, and plasma triglyceride and alanine aminotransferase levels temporarily decreased. The lipid content and some mRNA expression in relation to fibrosis in the liver decreased with pioglitazone treatment, and the mRNA expression of microsomal triglyceride transfer protein increased. Hepatic fibrosis observed in the SDT fatty rats improved with pioglitazone treatment; however, the effect with metformin treatment was partial. These results in both drugs are in line with results in the human study, suggesting that the SDT fatty rat is useful for developing new anti-NASH drugs that show potential to regulate glucose/lipid metabolism.

  9. Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they reliable models to study Type 2 Diabetes mellitus?

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    Wilson Mitsuo Tatagiba Kuwabara

    Full Text Available Type 2 Diabetes mellitus (T2DM is an evident growing disease that affects different cultures throughout the world. T2DM occurs under the influence of three main factors: the genetic background, environmental and behavioral components. Obesity is strongly associated to the development of T2DM in the occident, while in the orient most of the diabetic patients are considered lean. Genetics may be a key factor in the development of T2DM in societies where obesity is not a recurrent public health problem. Herein, two different models of rats were used to understand their differences and reliability as experimental models to study the pathophysiology of T2DM, in two different approaches: the genetic (GK rats and the environmental (HFD-induced obese rats influences. GK rats were resistant to weight gain even though food/energy consumption (relative to body weight was higher in this group. HFD, on the other hand, induced obesity in Wistar rats. White adipose tissue (WAT expansion in this group was accompanied by immune cells infiltration, inflammation and insulin resistance. GK rats also presented WAT inflammation and insulin resistance; however, no immune cells infiltration was observed in the WAT of this group. Liver of HFD group presented fat accumulation without differences in inflammatory cytokines content, while liver of GK rats didn't present fat accumulation, but showed an increase of IL-6 and IL-10 content and glycogen. Also, GK rats showed increased plasma GOT and GPT. Soleus muscle of HFD presented normal insulin signaling, contrary to GK rats, which presented higher content of basal phosphorylation of GSK-3β. Our results demonstrated that HFD developed a mild insulin resistance in Wistar rats, but was not sufficient to develop T2DM. In contrast, GK rats presented all the typical hallmarks of T2DM, such as insulin resistance, defective insulin production, fasting hyperglycemia/hyperinsulinemia and lipid plasma alteration. Thus, on the given

  10. Novel lean type 2 diabetic rat model using gestational low-protein programming

    Science.gov (United States)

    Type 2 diabetes (T2D) in lean individuals is not well studied and up to 26% of diabetes occurs in these individuals. Although the cause is not well understood, it has been primarily attributed to nutritional issues during early development. Our objective was to develop a lean T2D model using gestati...

  11. Grapefruit Derived Flavonoid Naringin Improves Ketoacidosis and Lipid Peroxidation in Type 1 Diabetes Rat Model.

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    Alfred N Murunga

    Full Text Available Hypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known.To investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats.Sprague-Dawley rats divided into 5 groups (n = 7 were orally treated daily with 3.0 ml/kg body weight (BW/day of distilled water (group 1 or 50 mg/kg BW of naringin (groups 2 and 4, respectively. Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW twice daily, respectively.Stretozotocin (STZ only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA, acetoacetate, β-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI, hepatic glycogen content, malondialdehyde, β-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG compared to the STZ only-treated group.Naringin is not hypoglycemic but ameliorates ketoacidosis and oxidative stress. Naringin supplements could therefore mitigate complications of diabetic ketoacidosis.

  12. Ethyl acetate fraction of Aframomum melegueta fruit ameliorates pancreatic β-cell dysfunction and major diabetes-related parameters in a type 2 diabetes model of rats.

    Science.gov (United States)

    Mohammed, Aminu; Koorbanally, Neil Anthony; Islam, Md Shahidul

    2015-12-04

    In West Africa, various preparations of the fruit, seed and leaf of Aframomum melegueta K. Schum. are reputably used for the management of diabetes mellitus (DM) and other metabolic disorders. The present study evaluated the anti-diabetic effects of A. melegueta ethyl acetate fraction (AMEF) from fruit ethanolic extract in a type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were orally treated with 150 or 300 mg/kg body weight (bw) of the AMEF once daily for four weeks. At the end of the intervention, diabetic untreated animals showed significantly higher serum glucose, serum fructosamine, LDH, CK-MB, serum lipids, liver glycogen, insulin resistance (HOMA-IR), AI, CRI and lower serum insulin, pancreatic β-cell function (HOMA- β) and glucose tolerance ability compared to the normal animals. Histopathological examination of their pancreas revealed corresponding pathological changes in the islets and β-cells. These alterations were reverted to near-normal after the treatment of AMEF at 150 and 300 mg/kg bw when, the effects were more pronounced at 300 mg/kg bw compared to the 150 mg/kg bw. The results of our study suggest that AMEF treatment at 300 mg/kg bw showed potent anti-diabetic effect in a T2D model of rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Antihyperglycemic, hypolipidemic, hepatoprotective and antioxidative effects of dietary clove (Szyzgium aromaticum) bud powder in a high-fat diet/streptozotocin-induced diabetes rat model.

    Science.gov (United States)

    Adefegha, Stephen A; Oboh, Ganiyu; Adefegha, Omowunmi M; Boligon, Aline A; Athayde, Margareth L

    2014-10-01

    Syzygium aromaticum (L.) Merr. & Perry (clove) bud is an important spice used in the preparation of several delicacies and in folklore for diabetes management. The present study was convened to assess the effects of dietary clove bud powder (CBP) on biochemical parameters in a type 2 diabetes rat model, induced by a combination of high-fat diet and low-dose streptozotocin (35 mg kg⁻¹) for 30 days. Diabetic rats were placed on dietary regimen containing 20-40 g kg⁻¹ clove bud powder. The results revealed that there was no significant (P > 0.05) difference in the average feed intake and weight changes between the rat groups. Furthermore, supplementation with CBP gradually reduced blood glucose level in diabetic rat compared to control diabetic rats without CBP supplementation (DBC). Moreover, reduced activity of α-glucosidase was observed in CBP and metformin-treated rat groups when compared to that of the DBC rat group. In addition, the DBC group had significantly (P alkaline phosphatase) and showed elevated levels of antioxidant status (glutathione, ascorbic acid, superoxide dismutase and catalase). The results suggest that the clove bud diet may attenuate hyperglycemia, hyperlipidemia, hepatotoxicity and oxidative stress in the type 2 diabetic condition. © 2014 Society of Chemical Industry.

  14. The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes.

    Science.gov (United States)

    Neuschäfer-Rube, Frank; Lieske, Stefanie; Kuna, Manuela; Henkel, Janin; Perry, Rachel J; Erion, Derek M; Pesta, Dominik; Willmes, Diana M; Brachs, Sebastian; von Loeffelholz, Christian; Tolkachov, Alexander; Schupp, Michael; Pathe-Neuschäfer-Rube, Andrea; Pfeiffer, Andreas F H; Shulman, Gerald I; Püschel, Gerhard P; Birkenfeld, Andreas L

    2014-03-01

    Reduced expression of the INDY (I'm not dead yet) tricarboxylate carrier increased the life span in different species by mechanisms akin to caloric restriction. Mammalian INDY homolog (mIndy, SLC13A5) gene expression seems to be regulated by hormonal and/or nutritional factors. The underlying mechanisms are still unknown. The current study revealed that mIndy expression and [(14)C]-citrate uptake was induced by physiological concentrations of glucagon via a cAMP-dependent and cAMP-responsive element-binding protein (CREB)-dependent mechanism in primary rat hepatocytes. The promoter sequence of mIndy located upstream of the most frequent transcription start site was determined by 5'-rapid amplification of cDNA ends. In silico analysis identified a CREB-binding site within this promoter fragment of mIndy. Functional relevance for the CREB-binding site was demonstrated with reporter gene constructs that were induced by CREB activation when under the control of a fragment of a wild-type promoter, whereas promoter activity was lost after site-directed mutagenesis of the CREB-binding site. Moreover, CREB binding to this promoter element was confirmed by chromatin immunoprecipitation in rat liver. In vivo studies revealed that mIndy was induced in livers of fasted as well as in high-fat-diet-streptozotocin diabetic rats, in which CREB is constitutively activated. mIndy induction was completely prevented when CREB was depleted in these rats by antisense oligonucleotides. Together, these data suggest that mIndy is a CREB-dependent glucagon target gene that is induced in fasting and in type 2 diabetes. Increased mIndy expression might contribute to the metabolic consequences of diabetes in the liver.

  15. Effects of Brown Seaweed (Sargassum polycystum Extracts on Kidney, Liver, and Pancreas of Type 2 Diabetic Rat Model

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    Mahsa Motshakeri

    2014-01-01

    Full Text Available The edible seaweed Sargassum polycystum (SP is traditionally used against several human diseases. This investigation evaluated the effects of two dietary doses of SP ethanolic and aqueous extracts on the pancreatic, hepatic, and renal morphology of type 2 diabetic rats (T2DM. T2DM was induced by feeding rats on high calorie diet followed by a low dose streptozotocin. Changes in the diabetic rat organs in SP treated groups with different doses of extracts were compared with normal rats, diabetic control rats, and metformin treated rats. After 22 days of treatment, the pathological lesions of the livers and kidneys in the diabetic rats were quantitatively and qualitatively alleviated (P<0.05 by both the SP extracts at 150 mg/kg body weight and by metformin. All the treated diabetic groups revealed marked improvement in the histopathology of the pancreas compared with the control diabetic group. Oral administration of 300 mg/kg body weight of aqueous and ethanolic extracts of SP and metformin revealed pancreas protective or restorative effects. The seaweed extracts at 150 mg/kg body weight reduced the liver and kidney damages in the diabetic rats and may exert tissue repair or restoration of the pancreatic islets in experimentally induced diabetes to produce the beneficial homeostatic effects.

  16. Emodin Protects against Diabetic Cardiomyopathy by Regulating the AKT/GSK-3β Signaling Pathway in the Rat Model

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    Zhiqin Wu

    2014-09-01

    Full Text Available Diabetes mellitus (DM has been recognized as a major health problem. Emodin (Emo has been reported to exhibit protective effects against diabetic nephropathy. However, little has been known about the effect of Emo on diabetic cardiomyopathy (DCM. A type 2 DM model was induced in rats by low dose streptozotocin (STZ combined with high energy intake. We found that Emo-treated groups displayed significantly higher body weight (BW and lower heart weight (HW/BW. Furthermore, Emo could significantly decrease blood glucose, total cholesterol (TG levels, and triglyceride (TC levels in diabetic rats. Moreover, the Emo-treated group showed a marked increase in heart rate (HR and showed lower left ventricular end-diastolic diameter (LVEDD, left ventricular end-systolic diameter (LVESD, left ventricular posterior wall thickness (LWPWT, and interventricular septal diastolic wall thickness (IVSD. Emo induced a significant increase in phosphorylation of Akt and GSK-3β in myocardium. These results suggest that Emo may have great therapeutic potential in the treatment of DCM by Akt/GSK-3β signaling pathway.

  17. Oral administration of green algae, Euglena gracilis, inhibits hyperglycemia in OLETF rats, a model of spontaneous type 2 diabetes.

    Science.gov (United States)

    Shimada, Ryoko; Fujita, Miho; Yuasa, Masahiro; Sawamura, Hiromi; Watanabe, Toshiaki; Nakashima, Ayaka; Suzuki, Kengo

    2016-11-09

    In the present study, the effects of Euglena and paramylon on hyperglycemia were examined in Otsuka Long-Evans Tokushima fatty (OLETF; type 2 diabetes mellitus model) rats. OLETF rats were fed an AIN-93 M diet containing cellulose, Euglena, or paramylon for 10 weeks. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. An oral glucose-tolerance test (OGTT) was performed at 0 and 10 weeks. OLETF control rats were obese because of bulimia and showed abdominal fat accumulation and hyperglycemia. Euglena supplementation improved hyperglycemia and decreased food intake, body weight gain, and abdominal fat. However, there were no changes in the paramylon-supplemented group compared to the OLETF control group. Triglyceride concentrations in the serum and liver were lower in Euglena-supplemented rats than in OLETF control rats. There was a correlation between hepatic triglyceride concentration and the area under the curve (AUC) of OGTT at 10 weeks. This suggests that the improvement in glycemic control in the Euglena-supplemented group may depend on substances other than paramylon present in Euglena.

  18. Effect of Turmeric Etanol Extract (Curcuma Longa L) on Low Density Lipoprotein Level and Liver Histopathology Image in Type 1 Diabetes Mellitus Rat Model Induced by Streptozotocin

    OpenAIRE

    Herlina Pratiwi; Djoko Winarso; Nunung Handoyo

    2017-01-01

    This study was conducted to determine levels of LDL and liver damage in rats (Rattus norvegicus) models of type 1 diabetes mellitus inducted by streptozotocin (STZ) with etanol extract of turmeric (Curcuma Longa L) therapy. Animals used rat (Rattus norvegicus) 3-month-old males who were divided into 5 groups, each group consisting of four mice. The group was divided according to treatment: negative control (not induced by STZ), the positive control group (STZ induced), groups of rats DM 1 wit...

  19. Study of TNF-α, IL-1β and LPS levels in the gingival crevicular fluid of a rat model of diabetes mellitus and periodontitis.

    Science.gov (United States)

    Jiang, Zhu-Ling; Cui, Yu-Qiong; Gao, Rui; Li, Ying; Fu, Zhao-Chen; Zhang, Bin; Guan, Cheng-Chao

    2013-01-01

    In this study, we sought to investigate the dynamic changes in the levels of TNF-α, IL-1β and LPS in the gingival crevicular fluid (GCF) in a rat model of diabetes mellitus (DM) and periodontitis (PD). Additionally, we evaluated alveolar bone loss and the histopathological response associated with experimental diabetes mellitus and experimental periodontitis. DM and PD were induced together in 15 rats (group 1) by streptozotocin injection and ligature induction. Periodontitis alone was produced by ligature induction in 15 rats (group 2), diabetes alone was produced by streptozotocin injection in 15 rats (group 3), and fifteen systemically and periodontally healthy rats were used as controls (group 4). The gingival TNF-α, IL-1β and LPS levels were measured by using ELISA method. Periodontal destruction was assessed by measuring the alveolar bone loss. Periodontal inflammation was quantified by histopathological grading in H&E stained samples. Higher levels of TNF-α, IL1-β and LPS, increased alveolar bone loss and more serve histopathology were found in group 1 compared with group 2, group 3 and group 4 (pperiodontal tissues. The resorption values of alveolar bone and the histological inflammation were more severe in rats with periodontitis and diabetes mellitus than in those with periodontitis alone, diabetes mellitus alone and control rats. Our findings are consistent with the hypothesis that hyperglycemia contributes to the heightened inflammatory response associated with periodontitis.

  20. Concentration of Zinc, Copper, Iron, Calcium, and Magnesium in the Serum, Tissues, and Urine of Streptozotocin-Induced Mild Diabetic Rat Model.

    Science.gov (United States)

    Gómez, Tahiry; Bequer, Leticia; Mollineda, Angel; Molina, José L; Álvarez, Alain; Lavastida, Mayrelis; Clapés, Sonia

    2017-10-01

    The present study aimed to investigate, in the streptozotocin-induced mild diabetic rat model, the zinc (Zn), copper (Cu), iron (Fe), calcium (Ca), and magnesium (Mg) concentration in serum, liver, and kidney tissues, and urine samples from adult Wistar rats treated neonatally with streptozotocin (STZ). Diabetes was induced by subcutaneous administration of streptozotocin (100 mg/Kg) in female Wistar rats of 2 days old (STZ, n = 10). Control group (CG, n = 10) received only sodium-citrate buffer. The mineral concentrations were measured by atomic absorption spectrophotometry. The validity and accuracy were checked by conventional methods. STZ neonatal injection successfully leaded to mild diabetes in the adult rats. Serum concentrations of Zn, Cu, Fe, Ca, and Mg showed no changes (p > 0.05) due to diabetes. The Zn, Fe, Ca, and Mg concentrations in liver and kidney tissues were not different (p > 0.05) between STZ and CG. The mean values of Cu were higher (p Urine minerals concentrations (Zn, Cu, Fe and Ca) in STZ-rats group were lower (p urine were higher (p  0.7; p < 0.001). Observed changes in mineral metabolism of STZ-induced mild diabetes model could be due to the endocrine imbalance associated with the diabetic condition.

  1. Investigation of antioxidant defense mechanisms of Citrullus Colocynthis fruits and N-acetylcysteine in the diabetes mellitus model on rats

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    H. R. Lamazian

    2016-10-01

    Full Text Available The aim of study: to investigate the presence and mechanisms of antioxidant activity in dry extract of Citrullus Colocynthis fruits and N-acetylcysteine. Materials and methods. MDA, SOD, catalase, glutathione were studied in liver homogenate of streptozotocin-induced diabetic rats (group "model", groups X1 and X2 - rats with diabetes who were given a plant extract per os at a dose of 200 mg / kg and 400 mg / kg respectively, X3 - rats with diabetes who were given NAC per os at a dose of1.5 g / kg and healthy rats (group "Control". Fatty acid composition of erythrocyte and heart homogenate was determined by a gas chromatography. Results. In "Model" the growth of MDA, reduction of SOD and catalase were observed. In X1 and X2 groups MDA concentration and SOD activity decreased in relative to "Model" and "Control" and catalase activity, on the contrary, increased reaching the level of "Control" and even higher (X2. Glutathione concentration also decreased and this negative effect was increasing with increasing of plant extract dose. NAC caused a decrease of MDA in relative to "Model", normalized levels of SOD and catalase and effectively increased the concentration of glutathione compared with "Model". 9 fatty acids (FA, 4 of which belong to the unsaturated one (oleic, linoleic, linolenic, arachidonic and 5 - to saturated one (myristic, pentadecanoic, palmitic, margarine (heptadecanoic, stearic were identified in heart homogenate and erythrocytes of rats. The plant extract significantly changes the ratio of fatty acids in the myocardium (increases the level of stearic and linoleic FA and decreases the level of pentadecanoic and arachidonic FA and in erythrocytes (decreases the level of linoleic and linolenic FA and increases the level of saturated FA, practically without disturbing the balance between saturated and unsaturated FA. The quantitative composition of saturated FA doesn’t change statistically in the group X3 in relative to "Control

  2. The impact of bodyweight and body condition on behavioral testing for painful diabetic neuropathy in the streptozotocin rat model.

    Science.gov (United States)

    Hoybergs, Yves M J J; Biermans, Ria L V; Meert, Theo F

    2008-05-02

    The streptozotocin (STZ)-induced diabetes model is widely used for the induction of neuropathy in the rat. In this model, diabetic animals often display chronic illness, which raises objections not only on ethical but also on scientific grounds. In this study, the investigators set out to determine the impact of bodyweight and body condition (BC) on behavioral testing in the rat. Animals were allocated to four different groups as a function of their bodyweight, in particular one control group and three experimental groups with different starting weights (low bodyweight [LBW], medium bodyweight [MBW] and high bodyweight [HBW]), the groups having been rendered diabetic with an intraperitoneal injection of STZ (65mg/kg). Bodyweight, blood glucose, body condition and thresholds for mechanical hyperalgesia and tactile allodynia were measured or evaluated over a 68-day period. Animals with a LBW at the start of the experiment showed a gradual increase in BW with a decrease in mechanical nociceptive thresholds, while MBW and HBW animals presented a decrease in both thresholds and BW. The body condition score (BCS) decreased in all STZ-treated groups over time. Since correlations between mechanical thresholds and BW were similar between the control group and the HBW and MBW groups, the loss in BW clearly contributed to the decrease in thresholds. In the LBW group, thresholds and BW correlated negatively, so that the decrease in thresholds was mainly caused by the development of a painful neuropathy. From an ethical and a scientific point of view, in the STZ-induced diabetic neuropathy model, animals should be chosen on the basis of bodyweight and it must also be ensured that STZ is correctly dosed.

  3. Hesperidin produces cardioprotective activity via PPAR-γ pathway in ischemic heart disease model in diabetic rats.

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    Yogeeta O Agrawal

    Full Text Available The present study investigated the effect of hesperidin, a natural flavonoid, in cardiac ischemia and reperfusion (I/R injury in diabetic rats. Male Wistar rats with diabetes were divided into five groups and were orally administered saline once daily (IR-sham and IR-control, Hesperidin (100 mg/kg/day; IR-Hesperidin, GW9962 (PPAR-γ receptor antagonist, or combination of both for 14 days. On the 15th day, in the IR-control and IR-treatment groups, rats were subjected to left anterior descending (LAD coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical, histopathological, ultrastructural and immunohistochemistry. In the IR-control group, significant ventricular dysfunctions were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in cardiac injury markers lactate dehydrogenase activity, CK-MB and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and TNF-α were observed. Hesperidin pretreatment significantly improved mean arterial pressure, reduced left ventricular end-diastolic pressure, and improved both inotropic and lusitropic function of the heart (+LVdP/dt and -LVdP/dt as compared to IR-control. Furthermore, hesperidin treatment significantly decreased the level of thiobarbituric acid reactive substances and reversed the activity of lactate dehydrogenase towards normal value. Hesperidin showed anti-apoptotic effects by upregulating Bcl-2 protein and decreasing Bax protein expression. Additionally, histopathological and ultrastructural studies reconfirmed the protective action of hesperidin. On the other hand, GW9662, selective PPAR-γ receptor antagonist, produced opposite effects and attenuated the hesperidin induced improvements. The study for the first time evidence the involvement of PPAR-γ pathway in the cardioprotective activity of

  4. MDA and Histologic Profile of Pancreatic Diabetic-Rats Model Administered With Extract of Glycine max (L. Merr.

    Directory of Open Access Journals (Sweden)

    Luh Putu Gina

    2016-03-01

    Full Text Available Diabetes Mellitus is characterized by leveling up glucose in human blood and affects increasing of free radicals in body as well as leading to cellular oxidative stress. Experimentally, this condition is able to be characterized by increasing malondialdehyde (MDA level in cell and histological changing in pancreas appearance. Consumption of antioxidant substances was reported able to reduce the MDA quantity as free radicals. Black soybean or Glycine max (L Merr. was reported contains important antioxidant agents such as anthocyanin and isoflavone. This paper discloses recent investigation on application of black soybean water extract to reduce the MDA level on diabetes mellitus-rat model induced by STZ (DM and also reports the pancreas histological changing of the DM rats. Investigation revealed that black soybean water extract significantly affect decreasing of MDA level by 4.9%, 27.1% and 45.7% in three different doses theraphy (500, 750, and 1000 mg/kg BW. Histologically, it also clearly indicates repairing of pancreas tissue of the DM rats.

  5. Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model

    Directory of Open Access Journals (Sweden)

    A. Schaschkow

    2016-01-01

    Full Text Available Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC injection in a basal and bolus scheme using insulin pens (injection or pumps (preimplanted SC catheter. Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin at the same dosage (4 IU/200 g/day on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed.

  6. Multi-modal proteomic analysis of retinal protein expression alterations in a rat model of diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Heather D VanGuilder

    Full Text Available BACKGROUND: As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies. METHODOLOGY/PRINCIPAL FINDINGS: A multi-modal proteomic approach of antibody (Luminex-, electrophoresis (DIGE-, and LC-MS (iTRAQ-based quantitation methods was used to maximize coverage of the retinal proteome. Transcriptomic profiling through microarray analysis was included to identify additional targets and assess potential regulation of protein expression changes at the mRNA level. The proteomic approaches proved complementary, with limited overlap in proteomic coverage. Alterations in pro-inflammatory, signaling and crystallin family proteins were confirmed by orthogonal methods in multiple independent animal cohorts. In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5 while other proteins (Cp, Cryba3, Lgals3, Stat3 were only partially normalized and Fgf2 and Crybb2 expression remained elevated. CONCLUSIONS/SIGNIFICANCE: These results expand the understanding of the changes in retinal protein expression occurring with diabetes and their responsiveness to normalization of blood glucose through insulin therapy. These proteins, especially those not normalized by insulin therapy, may also be useful in preclinical drug development studies.

  7. Duodenal-jejunal bypass surgery suppresses hepatic de novo lipogenesis and alleviates liver fat accumulation in a diabetic rat model.

    Science.gov (United States)

    Han, Haifeng; Hu, Chunxiao; Wang, Lei; Zhang, Guangyong; Liu, Shaozhuang; Li, Feng; Sun, Dong; Hu, Sanyuan

    2014-12-01

    Duodenal-jejunal bypass (DJB) surgery can induce rapid and durable remission of type 2 diabetes mellitus (T2DM), but the intrinsic mechanisms remain to be elucidated. Recent studies indicated that improved hepatic insulin resistance and insulin signaling transduction might contribute to the diabetic control after DJB. Given the important role of liver adiposity in hepatic insulin resistance, this study was aimed at investigating the effects of DJB on glucose homeostasis and liver fat accumulation in a T2DM rat model induced by high-fat diet (HFD) and small dose of streptozotocin (STZ). Forty adult male diabetic rats induced by HFD and small dose of STZ were randomly assigned to sham and DJB groups. Body weight, calorie intake, hormone levels, glucose, and lipid parameters were measured at indicated time points. Subsequently, hepatic triglycerides (TG) content and the protein levels of sterol regulatory element binding protein-1 (SREBP-1), carbohydrate response element binding protein (ChREBP), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were evaluated at 2 and 8 weeks postoperatively. Compared with sham group, DJB induced rapid and significant improvements in glucose homeostasis and insulin sensitivity independently of weight loss and calorie restriction. The DJB-operated rats exhibited lower liver TG content and decreased hepatic SREBP-1, ChREBP, ACC, and FAS at 8 weeks postoperatively. DJB alleviated hepatic fat accumulation and downregulated the key transcriptional regulators and enzymes involved in hepatic de novo lipogenesis, which might contribute to improved hepatic insulin sensitivity and glucose homeostasis after DJB.

  8. Different patterns between mechanical and electrical activities: an approach to investigate gastric motility in a model of long-term diabetic rats

    International Nuclear Information System (INIS)

    Marques, Rozemeire G; Spadella, Cesar T; Americo, Madileine F; Corá, Luciana A; Oliveira, Ricardo B; Miranda, Jose Ricardo A

    2014-01-01

    The relationship between time-courses of mechanical and electrical events in longstanding diabetes was investigated in rats. Magnetic markers and electrodes were surgically implanted in the gastric serosa of male rats. Simultaneous recordings were obtained by AC biosusceptometry, electromyography and electrogastrography one, three and six months after injections of saline (control) or alloxan (diabetic). Frequency and amplitude of contraction, abnormal rhythmic index and half-bandwidth were obtained (ANOVA P < 0.05). Antral hypomotility and gastric motility instability were observed in the signal waveform of diabetic rats at the three time points of study. The mean frequency (4.4 ± 0.4 cpm) was strictly similar, but the mechanical and electrical correlation was lowest for diabetics groups. Decreases in mechanical amplitude were observed for all diabetic groups compared with control; also the ranges of frequency were much wider in diabetes. The half-bandwidth increased since the first month in mechanical recordings and only after the third month in electrical. In diabetic animals, about 40% of gastric activity was abnormal (against 12% in control) and may reach 60% in the sixth month of mechanical recordings. The multi-instrumental approach showed a more substantial deterioration in mechanical activity and created an integrative view of gastric motility for longstanding diabetic model. (paper)

  9. Thymectomy should be the first choice in the protection of diabetes-prone BB rats for breeding purposes

    NARCIS (Netherlands)

    Visser, Jeroen; Klatter, F; Hillebrands, JL; Jansen, Ar; Vijfschaft, L; Rozing, J

    2004-01-01

    Diabetes-prone (DP)-BB rats spontaneously develop diabetes and are widely used as an animal model for the study of type I diabetes. Since DP-BB rats develop diabetes before or at the time of breeding, such rats used for breeding need to be protected against diabetes development by the transfer of

  10. Evaluation of the Hypoglycaemic Activity of Petiveria alliacea (Guinea Hen Weed) Extracts in Normoglycaemic and Diabetic Rat Models.

    Science.gov (United States)

    Christie, S-L; Levy, A

    2013-11-01

    Petiveria alliacea (P alliacea) has ethno-traditional use as a hypoglycaemic agent in Jamaica and is yet to be scientifically validated as such. Therefore, extracts of aerial parts of the plant were evaluated for hypoglycaemic activity in normoglycaemic and diabetic rats. Aqueous and hexane extracts prepared from leaves of P alliacea were tested for hypoglycaemic activity. An acute administration of the extracts (200 and 400 mg/kg body weight) was evaluated in normoglycaemic rats. Additionally, the hypoglycaemic effect of sub-chronic administration was assessed in streptozotocin-induced diabetic rats. Blood glucose was recorded using a glucometer and test strips. Data were analysed using Student's t-test (p ≤ 0.05). The aqueous and hexane extracts demonstrated no significant reduction of fasting blood glucose (FBG) and no significant improvement of glucose tolerance in normal rats. The aqueous extract (400 mg/kg body weight) increased FBG from 4.75 ± 0.28 mmol/L to 5.88 ± 0.46 when compared to control (p ≤ 0.001). In diabetic rats, the hexane extract (400 mg/kg body weight) caused reduction of FBG after two weeks of treatment (p ≤ 0.010), but this was not sustained. The aqueous extract showed no reduction of FBG in diabetic rats. The aqueous extract of P alliacea demonstrated a hyperglycaemic effect in normoglycaemic rats and showed no hypoglycaemic activity in diabetic rats. The hexane extract caused no hypoglycaemic action in normal rats and failed to sustain an initial hypoglycaemic action in diabetic rats. This study presents evidence that does not support significant hypoglycaemic activity of P alliacea; this could hold significant implications for its use in ethno-traditional medicine.

  11. X-ray lethality in diabetic rats

    International Nuclear Information System (INIS)

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

    1978-01-01

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

  12. Validation of the antidiabetic effects of Vernonia amygdalina delile leaf fractions in fortified diet-fed streptozotocin-treated rat model of type-2 diabetes

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    Stanley Irobekhian Reuben Okoduwa

    2017-01-01

    Full Text Available Background: Vernonia amygdalina (VA is used in the traditional management of diabetes in Nigeria. Previous scientific verification of VA is on Type-1 diabetes model, in spite of the continuous increase in Type-2 diabetes (T2D among adults. This study aimed to validate the antidiabetic effects of VA leaf fraction (VALF in a unique T2D rat model. Materials and Methods: Methanol crude extract of VA leaf was fractionated with solvents of increasing order of polarity (n-hexane, chloroform, ethyl-acetate, n- butanol and water. The antidiabetic activities of the fractions were evaluated in vivo in T2D model rats. Albino Wistar rats were induced with T2D and treated with the VALF. Several T2D-related parameters were measured. Results: T2D rats showed significant increase in serum levels of fasting blood glucose (FBG, liver and kidney biomarkers. At 28-day post-oral treatment with the VALF, FBG levels were significantly (P < 0.05 reduced (n- hexane [29.3%], chloroform [66.7%], ethyl acetate [36.2%], n- butanol [45.59%] and aqueous [39.3%]. The glucose tolerance ability was significantly improved in the chloroform fraction (Vernonia amygdalina chloroform fraction [VAc]-treated groups compared to the other fractions-treated group and diabetic control group. Furthermore, the VAc was found to be most effective as it ameliorates most of the alterations caused in the studied parameters in diabetic rats when compared with n- hexane, ethyl acetate, n- butanol and aqueous fractions. Conclusion: The study validates the anti-diabetic effects of VALF in fortified diet-fed streptozotocin-treated rat model of T2D, and suggests that the VAc is a potential candidate for development of a more effective drug for the management of T2D.

  13. Antidiabetic and Synergistic Effects of Anthocyanin Fraction from Berberis integerrima Fruit on Streptozotocin-Induced Diabetic Rats Model

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    Zahra Sabahi

    2016-03-01

    Full Text Available Diabetes mellitus is a complex endocrine disorder. There is a serious attempt to identify antidiabetic compounds from natural sources to use with other drugs for reduction of diabetes complications. Present study is based on the investigation of antihyperglycemic effect of anthocyanin fraction of Berberis integerrima Bunge (AFBI fruits on some physiological parameters (glucose level, glycogen content, and body weight in normal and streptozotocin-induced (STZ-induced diabetic rats and evaluation of synergic effect of this fraction with metformin and glibenclamide. Male Sprague dawley rats were divided into nine groups: healthy control group, diabetic control group, diabetic groups treated with anthocyanin fraction (200, 400 and 1000 mg/kg, respectively; diabetic groups treated with glibenclamide and metformin separately, diabetic groups treated with glibenclamide + anthocyanin fraction (1000 mg/kg, metformin + anthocyanin fraction (1000 mg/kg. Treatment of diabetic rats with AFBI (400, 1000mg/kg significantly decreased blood glucose as compared with control. Moreover, AFBI (400, 1000mg/kg significantly increased liver glycogen and body weight compared to control. Nevertheless, there were no synergistic effects between anthocyanin fraction and metformin or glibenclamide on blood glucose, liver glycogen, and body weight. The results of this study indicate that AFBI possesses hypoglycemic effects and may be considered for evaluation in future diabetes clinical studies.

  14. The effect of Bongardia Chrysogonum on prostate tissue in a rat model of STZ-induced diabetes.

    Science.gov (United States)

    Dokuyucu, Recep; Gozukara, Kerem Han; Ozcan, Oguzhan; Sefil, Nebihat Kaplan; Nacar, Ahmet; Dokuyucu, Ahmet; Inci, Mehmet

    2016-01-01

    Bongardia chrysogonum is widely used in Turkey for treating urinary tract infections and prostate hypertrophy, and it also has potent hypoglycemic effects and aids glucose homeostasis. Because of the inflammatory conditions in diabetes mellitus (DM), the prostate tissue of men with diabetes is particularly susceptible to developing hypoplasia, and DM produces characteristic pathological changes in prostate tissue. Here, we examined the effects of B. chrysogonum on the prostate tissue of rats with streptozotocin (STZ)-induced diabetes. The glucose levels were statistically significantly higher in the diabetic rats than in healthy controls (P prostate tissue of the non-diabetic rats. In the diabetic group, the glandular lumens were filled with cellular debris and leucocytic infiltrate, and the glandular epithelium was degenerated and thickened. In the diabetic group treated with B. chrysogonum, the epithelium was better preserved and less debris was seen in the glandular lumen. To our knowledge, this is the first study to histologically prove the effects of B. chrysogonum on prostate tissue in diabetes. Our findings may be useful in developing B. chrysogonum into a therapeutic agent against diabetes and benign prostate hyperplasia.

  15. Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus

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    Ping Wang

    2017-01-01

    Full Text Available Glucokinase (GK plays a critical role in the control of whole-body glucose homeostasis. We investigated the possible effects of a novel glucokinase activator (GKA, HMS5552, to the GK in rats with type 2 diabetes mellitus (T2DM. Male Sprague-Dawley (SD rats were divided into four groups: control group, diabetic group, low-dose (10 mg/kg HMS5552-treated diabetic group (HMS-L, and high-dose (30 mg/kg HMS5552-treated diabetic group (HMS-H. HMS5552 was administered intragastrically to the T2DM rats for one month. The levels of total cholesterol, triglyceride, fasting plasma insulin (FINS, and glucagon (FG were determined, and an oral glucose tolerance test was performed. The expression patterns of proteins and genes associated with insulin resistance and GK activity were assayed. Compared with diabetic rats, the FINS level was significantly decreased in the HMS5552-treated diabetic rats. HMS5552 treatment significantly lowered the blood glucose levels and improved GK activity and insulin resistance. The immunohistochemistry, western blot, and semiquantitative RT-PCR results further demonstrated the effects of HMS5552 on the liver and pancreas. Our data suggest that the novel GKA, HMS5552, exerts antidiabetic effects on the liver and pancreas by improving GK activity and insulin resistance, which holds promise as a novel drug for the treatment of T2DM patients.

  16. Comparison of the effect of topical versus systemic L-arginine on wound healing in acute incisional diabetic rat model

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    Alireza Zandifar

    2015-01-01

    Full Text Available Background: Diabetes is associated with endothelial dysfunction and impaired wound healing. The amino acid L-arginine is the only substrate for nitric oxide (NO synthesis. The purpose of this study was to compare the topical versus systemic L-arginine treatment on total nitrite (NO x and vascular endothelial growth factor (VEGF concentrations in wound fluid and rate of wound healing in an acute incisional diabetic wound model. Materials and Methods: A total of 56 Sprague-Dawley rats were used of which 32 were rendered diabetic. Animals underwent a dorsal skin incision. Dm-sys-arg group (N = 8, diabetic and Norm-sys-arg group (N = 8, normoglycemic were gavaged with L-arginine. Dm-sys-control group (N = 8, diabetic and Norm-sys-control group (N = 8, normoglycemic were gavaged with water. Dm-top-arg group (N = 8, diabetic and norm-top-arg group (N = 8, normoglycemic received topical L-arginine gel. Dm-top-control group (N = 8, diabetic received gel vehicle. On the day 5 the amount of NO x in wound fluid was measured by Griess reaction. VEGF/total protein in wound fluids was also measured on day 5 using enzyme-linked immunosorbent assay. All wound tissue specimens were fixed and stained to be evaluated for rate of healing. Data were analyzed using SPSS software (version 18.0, Chicago, IL, USA through One-way analysis of variance test and Tukey′s post-hoc. Results: In dm-sys-arg group, the level of NO x on day 5 was significantly more than dm-top-arg group (P < 0.05. VEGF content in L-arginine treated groups were significantly more than controls (P < 0.05. Rate of diabetic wound healing in dm-sys-arg group was significantly more than dm-top-arg group. Conclusion: Systemic L-arginine is more efficient than topical L-arginine in wound healing. This process is mediated at least in part, by increasing VEGF and NO in the wound fluid.

  17. High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.

    Science.gov (United States)

    Dower, Ken; Zhao, Shanrong; Schlerman, Franklin J; Savary, Leigh; Campanholle, Gabriela; Johnson, Bryce G; Xi, Li; Nguyen, Vuong; Zhan, Yutian; Lech, Matthew P; Wang, Ju; Nie, Qing; Karsdal, Morten A; Genovese, Federica; Boucher, Germaine; Brown, Thomas P; Zhang, Baohong; Homer, Bruce L; Martinez, Robert V

    2017-01-01

    ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model's suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy.

  18. induced diabetic rats

    African Journals Online (AJOL)

    Dr. Parker

    2014-02-05

    Feb 5, 2014 ... Eucalyptus globulus (Myrtaceae), Xylopia aethiopica (Annonaceae). INTRODUCTION. Diabetes mellitus is a chronic metabolic disorder of car- bohydrate, proteins and fats occurring in the endocrine system (Jarald et al., 2008) as a result of absolute or relative deficiency of insulin secretion as in the case of.

  19. Levetiracetam ameliorates ovarian function in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Akman, Levent; Erbas, Oytun; Akdemir, Ali; Yavasoglu, Altug; Taskiran, Dilek; Kazandi, Mert

    2015-01-01

    Diabetes mellitus can adversely affect gonadal function. In the present study, we aimed to investigate the protective effects and mechanism of action of levetiracetam (LEV) on the ovaries in a streptozotocin (STZ)-induced diabetes model in rats. Twenty-one adult female rats were assigned to three groups as control, diabetes group treated with 1 mL/kg/d saline (STZ + SP) and diabetes group treated with 600 mg/kg/d LEV (STZ + LEV). Following 4 weeks treatment, blood samples were collected for biochemical analysis and ovariectomy was performed for histopathological examination. Plasma anti-Mullerian hormone (AMH), glutathione and total anti-oxidant capacity values were significantly lower whereas lipid peroxides and transforming growth factor-β (TGF-β) values were significantly higher in STZ + SP group compared to control. LEV treatment successfully decreased lipid peroxidation and TGF-β levels, and also increased anti-oxidant parameters and AMH levels in diabetic rats. Saline-treated rats significantly displayed ovarian degeneration and decreased counts of follicles. However, treatment of diabetic rats with LEV effectively prevented the degenerative changes and follicle loss. Also, LEV suppressed ovarian nuclear factor-kappa B (NF-kB) immunoexpression in diabetic rats. Taken together, we propose that LEV can ameliorate the adverse effects of diabetes on ovarian function via decreasing NF-kB expression and oxidative stress and increasing anti-oxidant status in rats.

  20. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    Science.gov (United States)

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  1. Effect of Turmeric Etanol Extract (Curcuma Longa L on Low Density Lipoprotein Level and Liver Histopathology Image in Type 1 Diabetes Mellitus Rat Model Induced by Streptozotocin

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    Herlina Pratiwi

    2017-02-01

    Full Text Available This study was conducted to determine levels of LDL and liver damage in rats (Rattus norvegicus models of type 1 diabetes mellitus inducted by streptozotocin (STZ with etanol extract of turmeric (Curcuma Longa L therapy. Animals used rat (Rattus norvegicus 3-month-old males who were divided into 5 groups, each group consisting of four mice. The group was divided according to treatment: negative control (not induced by STZ, the positive control group (STZ induced, groups of rats DM 1 with etanol turmeric extract therapy a dose of 1.2 g / kg, groups of rats DM 1 with etanol turmeric extract therapy a dose of 1.8 g / kg, and groups of rats DM 1 with etanol turmeric extract therapy a dose of 2.7 g / kg. LDL levels measured by direct method and the severity of liver damage was observed through histopatology picture. The results showed that the etanol extract of turmeric dose of 2.7 g / kg in a rats model of type 1 diabetes mellitus can lower LDL levels up to 59.55%, and reduced the severity of fatty liver with reduced fat vacuoles. The conclusion from this study that the etanol extract of turmeric contains antioxidants that can lower LDL levels and reduced the severity of fatty liver in type 1 diabetes mellitus.

  2. Effects of PEMF on microcirculation and angiogenesis in a model of acute hindlimb ischemia in diabetic rats.

    Science.gov (United States)

    Pan, Yunhu; Dong, Yushu; Hou, Wugang; Ji, Zhiyu; Zhi, Kailin; Yin, Zhongmin; Wen, Hua; Chen, Yitan

    2013-04-01

    Hindlimb ischemia is a major complication of diabetic patients due to poor neovascularization. Therapy with pulsed electromagnetic fields (PEMF) can promote angiogenesis in ischemic lesions. However, the efficacy and therapeutic mechanisms of PEMF in diabetes-related hindlimb ischemia are unclear. Sprague-Dawley rats were injected with streptozocin to induce diabetes, and 10 weeks later diabetic rats were subjected to surgical induction of acute hindlimb ischemia. The rats were randomized and treated with PEMF, and the blood perfusion of individual rats was determined longitudinally by laser Doppler perfusion imaging (LDPI). The neovascular density was examined using immunofluorescent analysis of CD31 expression and alkaline phosphatase (AP) staining. The levels of VEGF, VEGFR, FGF-2, and FGFR1 expression, and ERK 1/2 and P38 phosphorylation in the muscles were characterized using enzyme-linked immunosorbent assay (ELISA) and Western blot assays. The values of LDPI in the PEMF-treated rats at 14 and 28 days post surgery were significantly greater than those in the controls, accompanied by significantly elevated levels of anti-CD31 and AP staining. The relative levels of FGF-2 and FGFR1, but not VEGF and VEGFR expression, and ERK1/2, but not P38 phosphorylation, in the muscles of the PEMF-treated rats were significantly higher than those in the controls. Our data indicated that PEMF enhanced acute hindlimb ischemia-related perfusion and angiogenesis, associated with up-regulating FGF-2 expression and activating the ERK1/2 pathway in diabetic rats. Therefore, PEMF may be valuable for the treatment of diabetic patients with ischemic injury. Copyright © 2012 Wiley Periodicals, Inc.

  3. Efficacy of integrative medicine in deficiency of both qi and yin in the rat model of type 2 diabetes

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    Jing Zhao

    2015-10-01

    Conclusions: A rat model of T2DM with both qi and yin deficiency was successfully replicated. CHF appeared to be more efficacious than IM and PIO in the rat model of qi and yin deficiency pattern of T2DM, though IM and PIO were each found to have their merits and drawbacks in attenuating T2DM indicators in the rat model.

  4. Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes.

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    Aisha S Ahmed

    Full Text Available Metabolic diseases such as diabetes mellitus type-II (DM-II may increase the risk of suffering painful connective tissue disorders and tendon ruptures. The pathomechanisms, however, by which diabetes adversely affects connective tissue matrix metabolism and regeneration, still need better definition. Our aim was to study the effect of DM-II on expressional changes of neuro- and angiotrophic mediators and receptors in intact and healing Achilles tendon. The right Achilles tendon was transected in 5 male DM-II Goto-Kakizaki (GK and 4 age-matched Wistar control rats. The left Achilles tendons were left intact. At week 2 post-injury, NGF, BDNF, TSP, and receptors TrkA, TrkB and Nk1 gene expression was studied by quantitative RT-PCR (qRT-PCR and their protein distribution by immunohistochemistry in intact and injured tendons. The expression of tendon-related markers, Scleraxis (SCX and Tenomodulin (TNMD, was evaluated by qRT-PCR in intact and injured tendons. Injured tendons of diabetic GK rats exhibited significantly down-regulated Ngf and Tsp1 mRNA and corresponding protein levels, and down-regulated Trka gene expression compared to injured Wistar controls. Intact tendons of DM-II GK rats displayed reduced mRNA levels for Ngf, Tsp1 and Trkb compared to corresponding intact non-diabetic tendons. Up-regulated Scx and Tnmd gene expression was observed in injured tendons of normal and diabetic GK rats compared to intact Wistar controls. However, these molecules were not up-regulated in injured DM-II GK rats compared to their corresponding controls. Our results suggest that DM-II has detrimental effects on neuro- and angiotrophic pathways, and such effects may reflect the compromised repair seen in diabetic Achilles tendon. Thus, novel approaches for regeneration of injured, including tendinopathic, and surgically repaired diabetic tendons may include therapeutic molecular modulation of neurotrophic pathways such as NGF and its receptors.

  5. Selective Activation of AMPK β1-Containing Isoforms Improves Kidney Function in a Rat Model of Diabetic Nephropathy.

    Science.gov (United States)

    Salatto, Christopher T; Miller, Russell A; Cameron, Kimberly O; Cokorinos, Emily; Reyes, Allan; Ward, Jessica; Calabrese, Matthew F; Kurumbail, Ravi G; Rajamohan, Francis; Kalgutkar, Amit S; Tess, David A; Shavnya, Andre; Genung, Nathan E; Edmonds, David J; Jatkar, Aditi; Maciejewski, Benjamin S; Amaro, Marina; Gandhok, Harmeet; Monetti, Mara; Cialdea, Katherine; Bollinger, Eliza; Kreeger, John M; Coskran, Timothy M; Opsahl, Alan C; Boucher, Germaine G; Birnbaum, Morris J; DaSilva-Jardine, Paul; Rolph, Tim

    2017-05-01

    Diabetic nephropathy remains an area of high unmet medical need, with current therapies that slow down, but do not prevent, the progression of disease. A reduced phosphorylation state of adenosine monophosphate-activated protein kinase (AMPK) has been correlated with diminished kidney function in both humans and animal models of renal disease. Here, we describe the identification of novel, potent, small molecule activators of AMPK that selectively activate AMPK heterotrimers containing the β 1 subunit. After confirming that human and rodent kidney predominately express AMPK β 1, we explore the effects of pharmacological activation of AMPK in the ZSF1 rat model of diabetic nephropathy. Chronic administration of these direct activators elevates the phosphorylation of AMPK in the kidney, without impacting blood glucose levels, and reduces the progression of proteinuria to a greater degree than the current standard of care, angiotensin-converting enzyme inhibitor ramipril. Further analyses of urine biomarkers and kidney tissue gene expression reveal AMPK activation leads to the modulation of multiple pathways implicated in kidney injury, including cellular hypertrophy, fibrosis, and oxidative stress. These results support the need for further investigation into the potential beneficial effects of AMPK activation in kidney disease. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes.

    Science.gov (United States)

    Karachalias, N; Babaei-Jadidi, R; Rabbani, N; Thornalley, P J

    2010-07-01

    The aim of this study was to quantify protein damage by glycation, oxidation and nitration in a rat model of diabetes at the sites of development of microvascular complications, including the effects of thiamine and benfotiamine therapy. Diabetes was induced in male Sprague-Dawley rats by 55 mg/kg streptozotocin and moderated by insulin (2 U twice daily). Diabetic and control rats were given thiamine or benfotiamine (7 or 70 mg kg(-1) day(-1)) over 24 weeks. Plasma, urine and tissues were collected and analysed for protein damage by stable isotopic dilution analysis MS. There were two- to fourfold increases in fructosyl-lysine and AGE content of glomerular, retinal, sciatic nerve and plasma protein in diabetes. Increases in AGEs were reversed by thiamine and benfotiamine therapy but increases in fructosyl-lysine were not. Methionine sulfoxide content of plasma protein and 3-nitrotyrosine content of sciatic nerve protein were increased in diabetes. Plasma glycation free adducts were increased up to twofold in diabetes; the increases were reversed by thiamine. Urinary excretion of glycation, oxidation and nitration free adducts was increased by seven- to 27-fold in diabetes. These increases were reversed by thiamine and benfotiamine therapy. AGEs, particularly arginine-derived hydroimidazolones, accumulate at sites of microvascular complication development and have markedly increased urinary excretion rates in experimental diabetes. Thiamine and benfotiamine supplementation prevented tissue accumulation and increased urinary excretion of protein glycation, oxidation and nitration adducts. Similar effects may contribute to the reversal of early-stage clinical diabetic nephropathy by thiamine.

  7. Promise(s of mesenchymal stem cells as an in vitro model system to depict pre-diabetic/diabetic milieu in WNIN/GR-Ob mutant rats.

    Directory of Open Access Journals (Sweden)

    Soundarya L Madhira

    Full Text Available BACKGROUND: Development of model systems have helped to a large extent, in bridging gap to understand the mechanism(s of disease including diabetes. Interestingly, WNIN/GR-Ob rats (Mutants, established at National Centre for Laboratory Animals (NCLAS of National Institute of Nutrition (NIN, form a suitable model system to study obesity with Type 2 diabetes (T2D demonstrating several secondary complications (cataract, cardiovascular complications, infertility, nephropathy etc. The present study has been carried out to explore the potent application(s of multipotent stem cells such as bone marrow mesenchymal stem cells (BM-MSCs, to portray features of pre-diabetic/T2D vis-à-vis featuring obesity, with impaired glucose tolerance (IGT, hyperinsulinemia (HI and insulin resistance (IR seen with Mutant rats akin to human situation. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of BM-MSCs (third passage from Mutants, its lean littermate (Lean and parental control (Control were characterized for: proliferation markers, disease memory to mark obesity/T2D/HI/IR which included phased gene expression studies for adipogenic/pancreatic lineages, inflammatory markers and differentiation ability to form mature adipocytes/Insulin-like cellular aggregates (ILCAs. The data showed that BM-MSCs from Mutant demonstrated a state of disease memory, depicted by an upregulated expression of inflammatory markers (IL-6, TNFα; increased stem cell recruitment (Oct-4, Sox-2 and proliferation rates (CD90+/CD29+, PDA, 'S' phase of cell cycle by FACS and BrdU incorporation; accelerated preadipocyte induction (Dact-1, PPARγ2 with a quantitative increase in mature adipocyte formation (Leptin; ILCAs, which were non-responsive to high glucose did confer the Obese/T2D memory in Mutants. Further, these observations were in compliance with the anthropometric data. CONCLUSIONS: Given the ease of accessibility and availability of MSCs, the present study form the basis to report for

  8. Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    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.

  9. Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model.

    Science.gov (United States)

    Ranasinghe, Priyanga; Perera, Sanja; Gunatilake, Mangala; Abeywardene, Eranga; Gunapala, Nuwan; Premakumara, Sirimal; Perera, Kamal; Lokuhetty, Dilani; Katulanda, Prasad

    2012-04-01

    To evaluate short- and long-term effects of Cinnamomum zeylanicum on food consumption, body weight, glycemic control, and lipids in healthy and diabetes-induced rats. The study was conducted in two phases (Phase I and Phase II), using Sprague-Dawley rats in four groups. Phase I evaluated acute effects on fasting blood glucose (FBG) (Groups 1 and 2) and on post-oral glucose (Groups 3 and 4) blood glucose. Groups 1 and 3 received distilled-water and Groups 2 and 4 received cinnamon-extracts. Phase II evaluated effects on food consumption, body weight, blood glucose, and lipids over 1 month. Group A (n = 8, distilled-water) and Group B (n = 8, cinnamon-extracts) were healthy rats, while Group C (n = 5, distilled-water) and Group D (n = 5, cinnamon-extracts) were diabetes-induced rats. Serum lipid profile and HbA1c were measured on D-0 and D-30. FBG, 2-h post-prandial blood glucose, body weight, and food consumption were measured on every fifth day. There was no significant difference in serial blood glucose values in cinnamon-treated group from time 0 (P > 0.05). Following oral glucose, the cinnamon group demonstrated a faster decline in blood glucose compared to controls (P cinnamon-extracts in FBG and 2-h post-prandial blood glucose from D0 to D30 was shown only in diabetes-induced rats. In cinnamon-extracts administered groups, total and LDL cholesterol levels were lower on D30 in both healthy and diabetes-induced animals (P < 0.001). C. zeylanicum lowered blood glucose, reduced food intake, and improved lipid parameters in diabetes-induced rats.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes. METHODS: Wild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection...... measured with ELISA-based techniques. RESULTS: Diabetes-induced formation of AGEs in mesenteric arteries and endothelial dysfunction were reduced by Glo1 overexpression. Despite the absence of advanced nephrotic lesions, early markers of renal dysfunction (i.e. increased glomerular volume, decreased...... and early renal impairment in experimental diabetes. Modulating the GLO-I pathway therefore may provide a novel approach to prevent vascular complications in diabetes....

  11. Investigation into Hypoglycemic, Antihyperlipidemic, and Renoprotective Potentials of Dennettia tripetala (Pepper Fruit Seed in a Rat Model of Diabetes

    Directory of Open Access Journals (Sweden)

    Innocent Anioke

    2017-01-01

    Full Text Available This study investigated the hypoglycemic, antihyperlipidemic, and renoprotective potentials of Dennettia tripetala (DT in a rat model of diabetes. The hypoglycemic activity in crude methanol seed extract of DT (CMEDT and methanol seed fraction of DT (MFDT measured by glucose oxidase method was increased by 47.37% and 28.72%, respectively, after 8 hours of administration. After 10 days of treatment, CMEDT and MFDT gave a good glycemic control with the highest percentage reduction of 75.82% and 71.34% in glucose level, respectively, which is closely compared with 79.91% in glibenclamide. Using the enzymatic assay and Friedewald’s equation, there was a significant reduction in serum level of total cholesterol (TC, triglyceride (TG, very-low-density lipoprotein (VLDL, and low-density lipoprotein (LDL and a significant increase in high-density lipoprotein (HDL (p<0.05 following treatment with CMEDT and MFDT, when compared with the untreated group, although results varied in dosed groups, with high dose of MFDT showing a better lipid-lowering activity. High dose of MFDT improved lipid metabolism and increased percentage protection against atherogenesis by 44%. However, neither CMEDT nor MFDT ameliorated the renal biochemical alteration in urea and creatinine. Thus, the study demonstrates hypoglycemic and antihyperlipidemic potentials of DT seed in diabetes.

  12. Effects of insulin therapy on weight gain and fat distribution in the HF/HS-STZ rat model of type 2 diabetes

    DEFF Research Database (Denmark)

    Skovsø, Søs; Damgaard, J; Fels, J J

    2015-01-01

    BACKGROUND/OBJECTIVES: Insulin therapy is required for many patients with the obesity-related disorder type 2 diabetes, but is also associated with weight gain. The specific location of adipose tissue location matters to cardiovascular disease (CVD) risk. We investigated effects of exogenous...... insulin on fat distribution in the high-fat/high-sucrose fed rat treated with streptozotocin (HF/HS-STZ) rat model of type 2 diabetes. We also examined effects of insulin therapy on circulating CVD markers, including adiponectin, triglycerides (TGs), total cholesterol and high-density lipoprotein....... SUBJECTS/METHODS: Male SD rats were HF/HS fed for 5 weeks followed by STZ treatment to mimic the hallmarks of human obesity-associated insulin resistance followed by hyperglycemia. Magnetic resonance imaging and computed tomography were used to determine total fat, abdominal fat distribution and liver fat...

  13. Chronic administration of ethanol leaf extract of Moringa oleifera Lam. (Moringaceae) may compromise glycaemic efficacy of Sitagliptin with no significant effect in retinopathy in a diabetic rat model.

    Science.gov (United States)

    Olurishe, Comfort; Kwanashie, Helen; Zezi, Abdulkadiri; Danjuma, Nuhu; Mohammed, Bisalla

    2016-12-24

    Moringa oleifera Lam. (Moringaceae) has gained awareness for its antidiabetic effect, and is used as alternative therapy or concurrently with orthodox medicines such as sitagliptin in diabetes mellitus. This is without ascertaining the possibility of drug-herb interactions, which could either lead to enhanced antidiabetic efficacy, increased toxicity, or compromised glycaemic control with negative consequence in diabetic retinopathy. To investigate the effect, of sitagliptin (50mg/kg), Moringa oleifera (300mg/kg) leaf extract, and a combination of both on glycaemic control parameters, lenticular opacity and changes in retinal microvasculature in alloxan (150mg/kg i.p) induced diabetic rat model. Seven groups of eight rats per group were used, with groups I, II and VII as normal (NC), diabetic (DC) and post-prandial controls (PPC). Groups III to VI were diabetic rats on sitagliptin (III), M. oleifera (IV), sitagliptin and M. oleifera (SM) (V), for 42 days with 2 weeks delayed treatment in a post-prandial hyperglycaemic group (PPSM) (VI). Glycaemic control parameters, insulin levels, body weights, and effects of retinal microvasculature on lenticular opacity/morphology were investigated. A significant decrease in fasting blood glucose (FBG) levels was displayed in SM group from day 14(60%) (poleifera showed a progressive decrease in anti-hyperglycaemic effect of sitagliptin, and although it delayed the onset of lenticular opacity (i.e. cataract-like changes) it did not prevent the progression nor ameliorated pathologic lesions in the retina. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Oxidative stress in normal and diabetic rats.

    Science.gov (United States)

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (pE far greater (pvitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected.

  15. Studies on the antidiabetic effects of Mangifera indica stem-barks and leaves on nondiabetic, type 1 and type 2 diabetic model rats

    Directory of Open Access Journals (Sweden)

    Amrita Bhowmik

    2009-06-01

    Full Text Available Mangifera indica Linn, locally known as mango tree has been claimed to possess antidiabetic properties by many investigators. The present study was undertaken to screen the hypo- and antihyperglycemic activity of both ethanol and water extracts of leaves and stem-barks of M. indica in nondiabetic and diabetic model rats in different prandial states. The results showed that all of the extracts had significant antihyperglycemic effect in type 2 model rats when fed simultaneously with glucose load (p< 0.05-0.01; p< 0.005-0.001. Moreover, the ethanol extract of stem-barks showed significant antihyperglycemic effect when the extract was fed 30 min prior to the glucose load (p< 0.01. Investigations were carried out to evaluate the effect of M. indica on glucose absorption using a rat intestinal preparation in situ. The ethanol extracts of stem-barks reduced glucose absorption gradually during the whole perfusion period in type 2 rats.

  16. in Alloxan-induced Diabetic Rats

    African Journals Online (AJOL)

    HP

    extract of its leaves [7,8]. Despite the fact that ethanolic extract of Carica papaya leaf is used in the treatment of diabetes in Nigeria [6], there is dearth of information on its efficacy. Therefore, this study was aimed at evaluating the anti- diabetic effect of ethanolic extract of Carica papaya leaves in alloxan-induced diabetic rats.

  17. Hydrogen sulfide accelerates wound healing in diabetic rats.

    Science.gov (United States)

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

    2015-01-01

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

  18. 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...

  19. Prediction of Methionine and Homocysteine levels in Zucker diabetic fatty (ZDF) rats as a T2DM animal model after consumption of a Methionine-rich diet.

    Science.gov (United States)

    Han, Nayoung; Chae, Jung-Woo; Jeon, Jihyun; Lee, Jaeyeon; Back, Hyun-Moon; Song, Byungjeong; Kwon, Kwang-Il; Kim, Sang Kyum; Yun, Hwi-Yeol

    2018-01-01

    Although alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fatty (ZDF) rats, as a representative T2DM animal model. The model building and simulation were performed using NONMEM® (ver. 7.3.0) assisted by Perl-Speaks-NONMEM (PsN, ver. 4.3.0). Model parameters were derived using first-order conditional estimation method with interactions permitted among the parameters (FOCE-INTER). NCA was conducted using Phoenix (ver. 6.4.0). For all tests, we considered a P -value < 0.05 to reflect statistical significance. Our model featured seven compartments that considered all parts of the cycle by applying non-linear mixed effects model. Conversion of S-adenosyl-L-homocysteine (SAH) to homocysteine increased and the metabolism of homocysteine was reduced under diabetic conditions, and consequently homocysteine accumulated in the elimination phase.Using our model, we performed simulations to compare the changes in plasma methionine and homocysteine concentrations between ZDF and normal rats, by multiple administrations of the methionine-rich diet of 1 mmol/kg, daily for 60 days. The levels of methionine and homocysteine were elevated approximately two- and three-fold, respectively, in ZDF rats, while there were no changes observed in the normal control rats. These results can be interpreted to mean that both methionine and homocysteine will accumulate in patients with T2DM, who regularly consume high-methionine foods.

  20. Amaranthus caudatus Stimulates Insulin Secretion in Goto-Kakizaki Rats, a Model of Diabetes Mellitus Type 2

    Science.gov (United States)

    Zambrana, Silvia; Lundqvist, Lena C. E.; Veliz, Virginia; Catrina, Sergiu-Bogdan; Gonzales, Eduardo; Östenson, Claes-Göran

    2018-01-01

    Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats. A single oral administration of AC extract (2000 mg/kg body weight) improved glucose tolerance during Oral Glucose Tolerance Tests (OGTT) in both GK rats and in W rats. Long-term treatment (21 days) with AC (1000 mg/kg b.w.) improved the glucose tolerance evaluated by the area under the curve (AUC) of glucose levels during the OGTT, in both GK and W rats. The HbA1c levels were reduced in both GK (19.83%) and W rats (10.7%). This effect was secondary to an increase in serum insulin levels in both GK and W rats and confirmed in pancreatic islets, isolated from treated animals, where the chronic AC exposure increased the insulin production 4.1-fold in GK and 3.7-fold in W rat islets. Furthermore, the effect of AC on in vitro glucose-dependent insulin secretion (16.7 mM glucose) was concentration-dependent up to 50 mg/mL, with 8.5-fold increase in GK and 5.7-fold in W rat islets, and the insulin secretion in perifused GK and W rat islets increased 31 and nine times, respectively. The mechanism of action of AC on insulin secretion was shown to involve calcium, PKA and PKC activation, and G-protein coupled-exocytosis since the AC effect was reduced 38% by nifedipine (L-type channel inhibitor), 77% by H89 (PKA inhibitor), 79% by Calphostine-C (PKC inhibitor) and 20% by pertussis toxin (G-protein suppressor). PMID:29342984

  1. Studies on the antidiabetic effects of Mangifera indica stem-barks and leaves on nondiabetic, type 1 and type 2 diabetic model rats

    Directory of Open Access Journals (Sweden)

    Amrita Bhowmik, Liakot Ali Khan, Masfida Akhter and Begum Rokeya

    2009-12-01

    Full Text Available Mangifera indica Linn, locally known as mango tree has been claimed to possess antidiabetic properties by many investigators. The present study was undertaken to screen the hypoglycemic and antihyperglycemic activity of both ethanol and water extracts of leaves and stem-barks of M. indica in nondiabetic and diabetic model rats in different prandial state. The results showed that all of the extracts had significant antihyperglycemic effect in type 2 diabetic model rats when fed simultaneously with glucose load (p<0.05-0.01; p<0.005-0.001. Moreover, the ethanol extract of stem-barks showed significant antihyperglycemic effect when the extract was fed 30 min prior to the glucose load (p<0.01. Investigations were carried out to evaluate the effect of M. indica on glucose absorption using a rat intestinal preparation in situ. The ethanol extracts of stem-barks reduced glucose absorption gradually during the whole perfusion period in type 2 diabetic rats.

  2. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.

    Science.gov (United States)

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

    2012-01-15

    We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, Pdiabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), Pnerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, Pdiabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. 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.

  4. Enhancing effects of sericin on corneal wound healing in Otsuka Long-Evans Tokushima fatty rats as a model of human type 2 diabetes.

    Science.gov (United States)

    Nagai, Noriaki; Murao, Takatoshi; Ito, Yoshimasa; Okamoto, Norio; Sasaki, Masahiro

    2009-09-01

    The protein sericin is the main constituent of silk. We investigated the effects of sericin on corneal wound healing in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for human type 2 diabetes. Corneal wounds were prepared by removal of the corneal epithelium, and documented using a TRC-50X equipped with a digital camera. Sericin solutions were instilled into the eyes of rats five times a day following corneal abrasion. Plasma glucose and triglycerides were determined using an Accutrend GCT. Cholesterol and insulin were measured using a Cholesterol E-Test Kit and ELISA Insulin Kit, respectively. The plasma levels of glucose, triglycerides, cholesterol and insulin in 38-week-old OLETF rats were significantly higher than in Long-Evans Tokushima Otsuka (LETO) rats used as normal controls, and the rate of corneal wound healing in OLETF rats was slower than in LETO rats. The corneal wounds of rats instilled with saline showed almost complete healing by 72 h after corneal epithelial abrasion. On the other hand, the corneal healing rate of OLETF rats instilled with 10% sericin solution was significantly higher than that of LETO rats instilled with saline, and the wounds showed almost complete healing at 48 h after abrasion. The corneal healing rate increased with increasing sericin concentration. The present study demonstrates that the corneal wound healing rate in OLETF rat is slower than in LETO rats, and the instillation of sericin solution has a potent effect in promoting wound healing and wound-size reduction in LETO and OLETF rats.

  5. Deterioration of plasticity and metabolic homeostasis in the brain of the UCD-T2DM rat model of naturally occurring type-2 diabetes

    OpenAIRE

    Agrawal, Rahul; Zhuang, Yumei; Cummings, Bethany P.; Stanhope, Kimber L.; Graham, James L.; Havel, Peter J.; Gomez-Pinilla, Fernando

    2014-01-01

    The rising prevalence of type-2 diabetes (T2DM) is becoming a pressing issue based on emerging reports that T2DM can also adversely impact mental health. We have utilized the UCD-T2DM rat model in which the onset of T2DM develops spontaneously across time and can serve to understand the pathophysiology of diabetes in humans. An increased insulin resistance index and plasma glucose levels manifested the onset of T2DM. There was a decrease in hippocampal insulin receptor (InR) signaling in the ...

  6. Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress in Rats

    Directory of Open Access Journals (Sweden)

    Siti Hajar Abdul Aziz

    2016-01-01

    Full Text Available This study attempts to develop an experimental gestational diabetes mellitus (GDM animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0. Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin, lipid profiles (total cholesterol, triglycerides, HDL, and LDL, genes affecting insulin signaling (IRS-2, AKT-1, and PCK-1, glucose transporters (GLUT-2 and GLUT-4, proinflammatory cytokines (IL-6, TNF-α, and antioxidants (SOD, CAT, and GPX on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations.

  7. Antidepressant effect of taurine in diabetic rats.

    Science.gov (United States)

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

    2012-10-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  9. Renal iron overload in rats with diabetic nephropathy.

    Science.gov (United States)

    Dominguez, Jesus H; Liu, Yunlong; Kelly, Katherine J

    2015-12-01

    Diabetic nephropathy (DN) remains incurable and is the main cause of end-stage renal disease. We approached the pathophysiology of DN with systems biology, and a comprehensive profile of renal transcripts was obtained with RNA-Seq in ZS (F1 hybrids of Zucker and spontaneously hypertensive heart failure) rats, a model of diabetic nephropathy. We included sham-operated lean control rats (LS), sham-operated diabetic (DS), and diabetic rats with induced renal ischemia (DI). Diabetic nephropathy in DI was accelerated by the single episode of renal ischemia. This progressive renal decline was associated with renal iron accumulation, although serum and urinary iron levels were far lower in DI than in LS. Furthermore, obese/diabetic ZS rats have severe dyslipidemia, a condition that has been linked to hepatic iron overload. Hence, we tested and found that the fatty acids oleic acid and palmitate stimulated iron accumulation in renal tubular cells in vitro. Renal mRNAs encoding several key proteins that promote iron accumulation were increased in DI. Moreover, renal mRNAs encoding the antioxidant proteins superoxide dismutase, catalase, and most of the glutathione synthetic system were suppressed, which would magnify the prooxidant effects of renal iron loads. Substantial renal iron loads occur in obese/diabetic rats. We propose that in diabetes, specific renal gene activation is partly responsible for iron accumulation. This state might be further aggravated by lipid-stimulated iron uptake. We suggest that progressive renal iron overload may further advance renal injury in obese/diabetic ZS rats. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  10. A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects.

    Science.gov (United States)

    Elburki, M S; Moore, D D; Terezakis, N G; Zhang, Y; Lee, H-M; Johnson, F; Golub, L M

    2017-04-01

    Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a "bidirectional manner", the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (CMC) 2.24. Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30 mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (n = 6 rats/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography; MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor-α], were measured in gingival tissue extracts and serum by ELISA. Systemic administration of CMC 2.24 to diabetic rats with endotoxin-induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the pathologically excessive

  11. Defects in Antigen-Presenting Cells in the BB-DP Rat Model of Diabetes

    NARCIS (Netherlands)

    V. Sommandas (Vinod)

    2008-01-01

    textabstractType-1 diabetes is the result of a T cell mediated immune response against the insulin-producing β cells in the islet of Langerhans. In humans, until now, the disease is only clearly detectable at the onset of the disease. Therefore studies to identify initial factors involved in

  12. Nanoparticle mediated PPARγ gene delivery on dental implants improves osseointegration via mitochondrial biogenesis in diabetes mellitus rat model.

    Science.gov (United States)

    Lee, Young-Hee; Kim, Jeong-Seok; Kim, Ji-Eun; Lee, Min-Ho; Jeon, Jae-Gyu; Park, Il-Song; Yi, Ho-Keun

    2017-07-01

    Diabetes mellitus (DM) has a detrimental effect on osseointegration, stability and longevity of implants due to osteoporosis. In this study, PPARγ-loaded dental implants were investigated for the improvement of osseointegration and peri-implantitis. Chitosan gold nanoparticles conjugated with PPARγ cDNA were introduced on titanium mini-implant surfaces for PPARγ release to rat mandibular. DM-induced rat mandible showed structural changes such as decreased bone mass and increased inflammatory molecules, and diminution of PPARγ expression and bone formation molecules compared to normal rats. PPARγ induced bone formation via reduction of inflammatory molecules even under glucose oxidative stress. Furthermore, PPARγ strongly activated mitochondrial biogenesis and cell viability via p-AMK and Wnt/β-catenin signaling. Consequently, PPARγ gene delivery on regional dental implants contributed osseointegration, new bone formation and mineralization in DM-induced rats. This study demonstrates that PPARγ can be used as a therapeutic gene with dental implantation in diabetic patients since regional PPARγ expression enhances osseointegration and implant longevity. Copyright © 2017. Published by Elsevier Inc.

  13. 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...... an increase of 33% in kidney weight when compared to controls. The adrenergic antagonist treated diabetic groups had a significantly lower increase of 15%. Postnephrectomized renal growth was not affected by adrenergic antagonists. The total renal content of EGF was comparable in the saline-treated diabetic...... was not affected by adrenergic blocking agents. These results provide evidence for fundamental differences between diabetes-related renal growth and that observed in compensation to nephrectomy and suggest a connection between adrenergic activity, renal growth, and EGF in diabetes....

  14. Cardioprotective and anti-hypertensive effects of Prosopis glandulosa in rat models of pre-diabetes

    OpenAIRE

    Huisamen, B; George, C; Genade, S; Dietrich, D

    2013-01-01

    Aim Obesity and type 2 diabetes present with two debilitating complications, namely, hypertension and heart disease. The dried and ground pods of Prosopis glandulosa (commonly known as the Honey mesquite tree) which is part of the Fabaceae (or legume) family are currently marketed in South Africa as a food supplement with blood glucose-stabilising and anti-hypertensive properties. We previously determined its hypoglycaemic effects, and in the current study we determined the efficacy of P glan...

  15. Syphacia muris infection delays the onset of hyperglycemia in WBN/Kob-Leprfa rats, a new type 2 diabetes mellitus model

    Directory of Open Access Journals (Sweden)

    Taira K.

    2015-02-01

    Full Text Available Diabetes mellitus is one of the most common endocrine disorders and its continuous global increase is due to factors as population growth, urbanization, aging, and increasing prevalence of obesity and physical inactivity. The effect of pinworm infection on the development of hyperglycemia was examined in WBN/K-Lepf (fa/fa rats, a new model of the obese type 2 diabetes mellitus (T2DM with pancreatitis. The rats were orally administered Syphacia muris eggs (infected group and distilled water (control group. Hyperglycemia onset in the infected group was significantly delayed compared to the control group. Neither body weight nor intake of food and water were affected by S. muris infection. This study demonstrated that S. muris infection delayed the onset of T2DM in fa/fa rats and suggested that elucidation of the underlying mechanism and relevant pathways in the helminth-mediated protection may lead to the development of a new strategy to prevent diabetes mellitus.

  16. Dioscorea esculenta-induced increase in muscle sex steroid hormones is associated with enhanced insulin sensitivity in a type 2 diabetes rat model.

    Science.gov (United States)

    Sato, Koji; Fujita, Satoshi; Iemitsu, Motoyuki

    2017-02-01

    The effects of chronic Dioscorea esculenta administration and exercise training on muscle sex steroid hormone levels and insulin resistance in type 2 diabetes rats was assessed. Twenty-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were assigned randomly to the control, D. esculenta treatment, D. esculenta with 5α-reductase inhibitor treatment, or the exercise training groups (running at 25 m/min for 1 h, 5 d/wk; n = 10 each group). Eight weeks of D. esculenta treatment or exercise training significantly attenuated the increase in plasma insulin and fasting glucose levels. Plasma and muscle concentrations of dehydroepiandrosterone and 5α-dihydrotestosterone (DHT) and the expression of 5α-reductase increased significantly in the D. esculenta-treated and exercise training groups, and both treatments led to the upregulation of glucose transporter-4 translocation with concomitant increases in PKB and PKC-ζ/λ phosphorylation. Furthermore, the glucose metabolic clearance rate, which represents insulin sensitivity, increased significantly in both the D. esculenta-treated and exercise training groups. These effects were suppressed by administration of the DHT synthetic inhibitor. Together, these findings suggest that the D. esculenta-induced increase in muscle sex steroid hormone levels helps decrease insulin resistance in type 2 diabetes.-Sato, K., Fujita, S., Iemitsu, M. Dioscorea esculenta-induced increase in muscle sex steroid hormones is associated with enhanced insulin sensitivity in a type 2 diabetes rat model. © FASEB.

  17. Energy balance of pregnant diabetic rats.

    Science.gov (United States)

    Yamada, Ruth; Griggio, Mauro A; Luz, Jacqueline

    2002-05-01

    Pregnancy and diabetes lead to metabolic alterations in the energy balance that may not be completely independent. The objective of the present study was to look at the alterations induced by type 1 diabetes mellitus on the energy balance of pregnant rats and the offspring. Diabetes was induced by streptozotocin injection 15 d before the starting of pregnancy. The rats had their energy balance variables followed for 21 d. Protein, fat and energy content of dams was determined from samples of the carcasses. Pregnancy led to increased energy intake, energy gain and energy expenditure as well as higher gross food efficiency than non-pregnant counterparts. Diabetes increased metabolizable energy intake but not the energy gain of the animals: they had very high energy expenditure, so that diabetes blocked the improvement in gross food efficiency shown during pregnancy. Offspring from diabetic dams were born with lower body weight. Pregnant animals did not present the usual energy storage as seen by lower energy gain of diabetic dams as well as by the lower fat content in the carcasses of pregnant diabetic rats. It is concluded that diabetes impairs the energy variables usually enhanced by pregnancy alone.

  18. Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model

    International Nuclear Information System (INIS)

    Wu, Jiangchun; Wang, Ruobing; Ye, Zhouheng; Sun, Xuejun; Chen, Zeli; Xia, Fangzhou; Sun, Qinglei; Liu, Lin

    2015-01-01

    As the commonest complication of diabetes mellitus (DM), diabetic retinopathy (DR) is a neuro-vascular disease with chronic inflammatory. Methane could exert potential therapeutic interest in inflammatory pathologies in previous studies. Our study aims to evaluate the protective effects of methane-rich saline on DR and investigate the potential role of related MicroRNA (miRNA) in diabetic rats. Streptozotocin-induced diabetic Sprague–Dawley rats were injected intraperitoneally with methane-rich or normal saline (5 ml/kg) daily for eight weeks. Morphology changes and blood-retinal barrier (BRB) permeability were assessed by hematoxylin eosin staining and Evans blue leakage. Retinal inflammatory cytokines levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL1-β) were evaluated by immunohistochemistry. Retinal protein expressions of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined by western blotting. Retinal miRNA expressions were examined by miRNA-specific microarray, verified by quantitative RT-PCR and predicted by GO enrichment and KEGG pathway analysis. There was no significant changes in blood glucose level and body weight of diabetic rats with methane-rich or normal saline treatment, but the decreased retinal thickness, retinal ganglial cell loss and BRB breakdown were all significantly suppressed by methane treatment. DM-induced retinal overexpressions of TNF-α, IL-1β, GFAP and VEGF were also significantly ameliorated. Moreover, the methane treatment significantly up-regulated retinal levels of miR-192-5p (related to apoptosis and tyrosine kinase signaling pathway) and miR-335 (related to proliferation, oxidative stress and leukocyte). Methane exerts protective effect on DR via anti-inflammation, which may be related to the regulatory mechanism of miRNAs. - Highlights: • Methane exerts protective effect on diabetic retinopathy via anti-inflammation. • Therapeutic effect of methane is

  19. Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jiangchun; Wang, Ruobing [Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai (China); Ye, Zhouheng; Sun, Xuejun [Department of Navy Aeromedicine, Second Military Medical University, Shanghai (China); Chen, Zeli; Xia, Fangzhou; Sun, Qinglei [Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai (China); Liu, Lin, E-mail: linliu@sh163.net [Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai (China)

    2015-10-16

    As the commonest complication of diabetes mellitus (DM), diabetic retinopathy (DR) is a neuro-vascular disease with chronic inflammatory. Methane could exert potential therapeutic interest in inflammatory pathologies in previous studies. Our study aims to evaluate the protective effects of methane-rich saline on DR and investigate the potential role of related MicroRNA (miRNA) in diabetic rats. Streptozotocin-induced diabetic Sprague–Dawley rats were injected intraperitoneally with methane-rich or normal saline (5 ml/kg) daily for eight weeks. Morphology changes and blood-retinal barrier (BRB) permeability were assessed by hematoxylin eosin staining and Evans blue leakage. Retinal inflammatory cytokines levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL1-β) were evaluated by immunohistochemistry. Retinal protein expressions of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined by western blotting. Retinal miRNA expressions were examined by miRNA-specific microarray, verified by quantitative RT-PCR and predicted by GO enrichment and KEGG pathway analysis. There was no significant changes in blood glucose level and body weight of diabetic rats with methane-rich or normal saline treatment, but the decreased retinal thickness, retinal ganglial cell loss and BRB breakdown were all significantly suppressed by methane treatment. DM-induced retinal overexpressions of TNF-α, IL-1β, GFAP and VEGF were also significantly ameliorated. Moreover, the methane treatment significantly up-regulated retinal levels of miR-192-5p (related to apoptosis and tyrosine kinase signaling pathway) and miR-335 (related to proliferation, oxidative stress and leukocyte). Methane exerts protective effect on DR via anti-inflammation, which may be related to the regulatory mechanism of miRNAs. - Highlights: • Methane exerts protective effect on diabetic retinopathy via anti-inflammation. • Therapeutic effect of methane is

  20. Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model.

    Science.gov (United States)

    Li, Xue; Xie, Xiaoyun; Lian, Weishuai; Shi, Rongfeng; Han, Shilong; Zhang, Haijun; Lu, Ligong; Li, Maoquan

    2018-04-13

    Diabetic foot ulcers (DFU) increase the risks of infection and amputation in patients with diabetes mellitus (DM). The impaired function and senescence of endothelial progenitor cells (EPCs) and high glucose-induced ROS likely exacerbate DFUs. We assessed EPCs in 60 patients with DM in a hospital or primary care setting. We also evaluated the therapeutic effects of exosomes secreted from adipose-derived stem cells (ADSCs) on stress-mediated senescence of EPCs induced by high glucose. Additionally, the effects of exosomes and Nrf2 overexpression in ADSCs were investigated in vitro and in vivo in a diabetic rat model. We found that ADSCs that secreted exosomes promoted proliferation and angiopoiesis in EPCs in a high glucose environment and that overexpression of Nrf2 increased this protective effect. Wounds in the feet of diabetic rats had a significantly reduced ulcerated area when treated with exosomes from ADSCs overexpressing Nrf2. Increased granulation tissue formation, angiogenesis, and levels of growth factor expression as well as reduced levels of inflammation and oxidative stress-related proteins were detected in wound beds. Our data suggest that exosomes from ADSCs can potentially promote wound healing, particularly when overexpressing Nrf2 and therefore that the transplantation of exosomes may be suitable for clinical application in the treatment of DFUs.

  1. The Effect of Butter Oil on Avoidance Memory in Normal and Diabetic Rats

    OpenAIRE

    Zare, Khadije; Tabatabaei, Seyed Reza Fatemi; Shahriari, Ali; Jafari, Ramezan Ali

    2012-01-01

    Objective(s): Since diabetes mellitus is accompanied by cognitive impairment in diabetic patient and animal models and since lipids play important roles in neuronal membrane composition, structure and function; we intended to evaluate the effect of dietary butter oil on passive avoidance memory of streptoztosin (STZ)-induced diabetic rats in this study. Materials and Methods: Thirty six adult male rats were randomly allocated to four equal groups: normal (N) and diabetic control (D) groups wi...

  2. Study and analysis of oxidative stress and cell apoptosis in retinal tissue of diabetic model rats after total flavonoids of onion treatment

    Directory of Open Access Journals (Sweden)

    Wei Shi

    2017-05-01

    Full Text Available Objective: To study the effect of total flavonoids of onion treatment on oxidative stress and cell apoptosis in the retinal tissue of diabetic model rats. Methods: Male SD rats were selected as experimental animals and randomly divided into control group, diabetes group, lowdosage total flavonoids group (total flavonoids L group and high-dose total flavonoids (total flavonoids H group, intraperitoneal injection of streptozotocin was adopted to make diabetes model, and the total flavonoids L group and H group received lavage of 100 mg/kg and 200 mg/kg total flavonoids of onion for intervention. After 8 weeks of intervention, retinal tissue was collected and the degree of oxidative stress and cell apoptosis were determined. Results: P2X7, ROS, ﹣OH, O2﹣, H2O2, FADD, p-JNK, caspase-8 and caspase-3 levels in retinal tissue of diabetes group were significantly higher than those of control group while Mn-SOD, CAT, GSH, AsA, NGF, BDNF and CNTF levels were significantly lower than those of control group; P2X7, ROS, ﹣OH, O2﹣, H2O2, FADD, p-JNK, caspase-8 and caspase-3 levels in retinal tissue of total flavonoids L group and total flavonoids H group were significantly lower than those of diabetes group while Mn-SOD, CAT, GSH, AsA, NGF, BDNF and CNTF levels were significantly higher than those of diabetes group; P2X7, ROS, ﹣OH, O2﹣, H2O2, FADD, p-JNK, caspase-8 and caspase-3 levels in retinal tissue of total flavonoids H group were significantly lower than those of total flavonoids L group while Mn-SOD, CAT, GSH, AsA, NGF, BDNF and CNTF levels were significantly higher than those of total flavonoids L group. Conclusion: Total flavonoids of onion have inhibiting effect on the oxidative stress and cell apoptosis in retinal tissue of diabetic model rats.

  3. Garcinia kola seeds may prevent cognitive and motor dysfunctions in a type 1 diabetes mellitus rat model partly by mitigating neuroinflammation.

    Science.gov (United States)

    Seke Etet, Paul F; Farahna, Mohammed; Satti, Gwiria M H; Bushara, Yahia M; El-Tahir, Ahmed; Hamza, Muaawia A; Osman, Sayed Y; Dibia, Ambrose C; Vecchio, Lorella

    2017-04-15

    Background We reported recently that extracts of seeds of Garcinia kola, a plant with established hypoglycemic properties, prevented the loss of inflammation-sensible neuronal populations like Purkinje cells in a rat model of type 1 diabetes mellitus (T1DM). Here, we assessed G. kola extract ability to prevent the early cognitive and motor dysfunctions observed in this model. Methods Rats made diabetic by single injection of streptozotocin were treated daily with either vehicle solution (diabetic control group), insulin, or G. kola extract from the first to the 6th week post-injection. Then, cognitive and motor functions were assessed using holeboard and vertical pole behavioral tests, and animals were sacrificed. Brains were dissected out, cut, and processed for Nissl staining and immunohistochemistry. Results Hyperglycemia (209.26 %), body weight loss (-12.37 %), and T1DM-like cognitive and motor dysfunctions revealed behavioral tests in diabetic control animals were not observed in insulin and extract-treated animals. Similar, expressions of inflammation markers tumor necrosis factor (TNF), iba1 (CD68), and Glial fibrillary acidic protein (GFAP), as well as decreases of neuronal density in regions involved in cognitive and motor functions (-49.56 % motor cortex, -33.24 % medial septal nucleus, -41.8 % /-37.34 % cerebellar Purkinje /granular cell layers) were observed in diabetic controls but not in animals treated with insulin or G. kola. Conclusions Our results indicate that T1DM-like functional alterations are mediated, at least partly, by neuroinflammation and neuronal loss in this model. The prevention of the development of such alterations by early treatment with G. kola confirms the neuroprotective properties of the plant and warrant further mechanistic studies, considering the potential for human disease.

  4. Interleukin-1 beta induced transient diabetes mellitus in rats. A model of the initial events in the pathogenesis of insulin-dependent diabetes mellitus?

    DEFF Research Database (Denmark)

    Reimers, J I

    1998-01-01

    and molecular mechanisms of IL-1 beta on temperature and food intake used as control parameters for successful injection of rhIL-1 beta in rats, 3) the effects of one or more injection of IL-1 beta on rat beta cell function, 4) the molecular mechanisms leading to IL-1 beta induced beta cell inhibition in vivo...... studies suggested that IL-1 beta is distributed according to a two-compartment model with a first-order elimination. Interleukin-1 beta reached all the investigated organs in the rats, was accumulated in kidneys and was excreted in the urine. The data suggested that IL-1 beta also accumulated...

  5. The role of glycogen synthase kinase 3 beta in brain injury induced by myocardial ischemia/reperfusion injury in a rat model of diabetes mellitus.

    Science.gov (United States)

    Zhao, Bo; Gao, Wen-Wei; Liu, Ya-Jing; Jiang, Meng; Liu, Lian; Yuan, Quan; Hou, Jia-Bao; Xia, Zhong-Yuan

    2017-10-01

    Myocardial ischemia/reperfusion injury can lead to severe brain injury. Glycogen synthase kinase 3 beta is known to be involved in myo-cardial ischemia/reperfusion injury and diabetes mellitus. However, the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear. In this study, we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats. Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin. Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery. Post-conditioning comprised three cycles of ischemia/reperfusion. Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion, the structure of the brain was seriously damaged in the experimental rats compared with normal controls. Expression of Bax, interleukin-6, interleukin-8, terminal deoxynucleotidyl transferase dUTP nick end labeling, and cleaved caspase-3 in the brain was significantly increased, while expression of Bcl-2, interleukin-10, and phospho-glycogen synthase kinase 3 beta was decreased. Diabetes mellitus can aggravate inflammatory reactions and apoptosis. Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes. Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glyco-gen synthase kinase 3 beta. According to these results, glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.

  6. Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model

    Directory of Open Access Journals (Sweden)

    Pin-Fang Kang

    2016-01-01

    Full Text Available The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2 when diabetes mellitus (DM rat heart was subjected to ischemia/reperfusion (I/R intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH; cardiomyocyte in high glucose (HG condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker, atractyloside (mitoPTP opener, and wortmannin (PI3K inhibitor groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.

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

    Science.gov (United States)

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

    2014-10-01

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

  8. Ghrelin mitigates β-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat.

    Science.gov (United States)

    Baena-Nieto, Gloria; Lomas-Romero, Isabel M; Mateos, Rosa M; Leal-Cosme, Noelia; Perez-Arana, Gonzalo; Aguilar-Diosdado, Manuel; Segundo, Carmen; Lechuga-Sancho, Alfonso M

    2017-01-01

    Ghrelin is a peptide hormone with pleiotropic effects. It stimulates cell proliferation and inhibits apoptosis-mediated cell death. It prevents diabetes mellitus in several models of chemical, surgical and biological toxic insults to pancreas in both in vivo and in vitro models and promotes glucose-stimulated insulin secretion under cytotoxic conditions. It has not yet been tested in vivo in an autoimmune model of diabetes with a persistent insult to the β-cell. Given the immunomodulating effects of ghrelin and its trophic effects on β-cells, we hypothesized that ghrelin treatment during the early stages of insulitis would delay diabetes onset. BioBreeding/Worcester male rats received ghrelin (10 ng/kg/day) before insulitis development. Glucose metabolism was characterized by glucose and insulin tolerance tests. β-cell mass, islet area, islet number, β-cell clusters, proliferation and apoptosis and degree of insulitis were analysed by histomorphometry. A Kaplan-Meier survival curve was plotted and analysed applying the log-rank (Mantel-Cox) test. Ghrelin treatment significantly reduced the probability of developing diabetes in our model (p cell mass loss, enabling the maintenance of β-cell neogenesis and proliferation rates. Furthermore, ghrelin treatment did not induce any metabolic perturbations. These findings support the hypothesis that ghrelin delays the development of autoimmune diabetes by attenuating insulitis and supporting β-cell mass. Ghrelin promotes β-cell viability and function through diverse mechanisms that may have significant implications for diabetes prevention, therapy and also transplant success of both islets and complete pancreas. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Study on the protective effect of shengmai san (see text) on the myocardium in the type 2 diabetic cardiomyopathy model rat.

    Science.gov (United States)

    Ni, Qing; Wang, Jie; Li, En-Qing; Zhao, An-Bin; Yu, Bin; Wang, Min; Huang, Chun-Rong

    2011-09-01

    To study the effect of Shengmai San ((see text) Pulse-activating Powder) in protecting myocardium in the rat of the type 2 diabetic cardiomyopathy (DCM) model. The DCM rat model was established by combination of insulin resistance induced by a high-fat diet with intraperitoneal injection of high dose streptozotocin (50 mg/kg). And these rat models were randomly divided into three groups: a normal group (n = 12,one of them died), a model group (n = 15) and a Shengmai San group (treatment group, n = 15).The damage of the myocardium was assessed by electrocardiogram at the twelfth week after modeling, and the blood glucose, cholesterol and triglyceride levels were determined; the content of the left cardiac ventricle myocardial collagen was quantified by Masson staining test; the level of myocardial cell apoptosis was detected with TUNEL apoptosis detection kit; the damage extent of the myocardial sub-cellular structures was observed by electron microscopy; the expression levels of cardiac TSP-1 (Thrombospondin-1), TGF-beta1 (Transforming Growth F factor-beta) and TRB-3 (Tribbles homolog 3) proteins were detected by immunohistochemical method; the expression levels of cardiac TSP-1, A-TGF-beta1 and L-TGF-beta1 proteins were detected by Western blotting; and the expression levels of TSP-1 and TRB-3 mRNAs were detected by real-time quantitative PCR. Compared with the control group, the blood glucose, cholesterol, triglycerides levels in both the model groups and the Shengmai San group were significantly decreased; the myocardial tissue was less damaged and the collagen content was reduced in the Shengmai San group; the myocardial sub-cellular structure was injured to a lesser extent; the expression levels of myocardial TSP-1, TGF-beta1, TRB-3, and TSP-1, A-TGF-beta1, L-TGF-beta1 and chymase were decreased, and the expression levels of TSP-1 mRNA and TRB-3 mRNA were decreased in both the model groups and the Shengmai San group (the latter was better),. Shengmai San can

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

    Science.gov (United States)

    Prasad, K

    2000-06-01

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

  11. Evalution of the castrated male Sprague-Dawley rat as a model of the metabolic syndrome and type 2 diabetes.

    Science.gov (United States)

    Christoffersen, B; Raun, K; Svendsen, O; Fledelius, C; Golozoubova, V

    2006-08-01

    Low testosterone levels have been shown to be predictive for the development of the metabolic syndrome in men. The aim of this study was to describe effects of testosterone deficiency on metabolic syndrome-related parameters in male rats in order to evaluate the rat as a model for the human metabolic syndrome related to low testosterone levels. Male Sprague-Dawley rats were castrated or sham operated at 16 weeks of age and fed either a standard or a high energy diet. Measured parameters were: food intake, body weight, fat distribution, energy expenditure, physical activity and blood/plasma parameters related to glucose and lipid metabolism. Castration led to an increase in the amount of subcutaneous fat, but did not result in any changes in the visceral fat. Fasting blood glucose levels were increased and free fatty acids concentration decreased in the castrated rats from 2 weeks after castration and throughout the study, whereas no significant differences between the groups were found in any of the other parameters measured. A high-energy diet did not change the response to castration in male Sprague-Dawley rats. Compared to humans rats respond differently to testosterone deficiency. Only few of the features typical for the human metabolic syndrome were observed in castrated male Sprague-Dawley rats. Therefore, we conclude that with the present experimental setup the castrated rat is not an optimal model for studies on the influence of testosterone deficiency on body fat distribution and the development of other central components of the metabolic syndrome.

  12. Effects of streptozotocin-diabetes on the hippocampal NMDA receptor complex in rats

    NARCIS (Netherlands)

    Gispen, W.H.; Gardoni, F.; Kamal, A.; Bellone, C.; Biessels, G.J.; Ramakers, G.M.J.; Cattabeni, F.; Di Luca, M.

    2002-01-01

    In animal models of diabetes mellitus, such as the streptozotocin-diabetic rat (STZ-rat), spatial learning impairments develop in parallel with a reduced expression of long-term potentiation (LTP) and enhanced expression of long-term depression (LTD) in the hippocampus. This study examined the time

  13. Tangshen Formula Attenuates Colonic Structure Remodeling in Type 2 Diabetic Rats

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Zhang, Haojun

    2017-01-01

    Aim. This study investigated the effect and mechanism of the Chinese herbal medicine Tangshen Formula (TSF) on GI structure remodeling in the rat model of diabetes. Methods. Type 2 diabetic rats were used. Wet weight per unit length, layer thicknesses, levels of collagens I and III, nuclear factor...

  14. Infections that induce autoimmune diabetes in BBDR rats modulate CD4(+)CD25(+) T cell populations

    NARCIS (Netherlands)

    Zipris, D; Hillebrands, JL; Welsh, RM; Rozing, J; Xie, JX; Mordes, JP; Greiner, DL; Rossini, AA

    2003-01-01

    Viruses are believed to contribute to the pathogenesis of autoimmune type 1A diabetes in humans. This pathogenic process can be modeled in the BBDR rat, which develops pancreatic insulitis and type 1A-like diabetes after infection with Kilham's rat virus (RV). The mechanism is unknown, but does not

  15. Type 2 diabetes models

    DEFF Research Database (Denmark)

    Gram, Dorte Xenia

    2012-01-01

    This chapter deals with type 2 diabetes in vivo models and techniques suitable for testing new anti-diabetic compounds. In particular, the testing of TRP antagonist for beneficial effects against type 2 diabetes is considered. There are many choices of both in vitro techniques and in vivo models......, impaired glucose tolerance, impaired insulin secretion, and insulin resistance in vivo and should, thus, be sufficient to demonstrate preclinical proof of concept of a TRP antagonist in type 2 diabetes in rodents. The experiments are suggestions and could be replaced or supplemented by others....

  16. Renal antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats.

    Science.gov (United States)

    Castoldi, G; di Gioia, C R T; Bombardi, C; Preziuso, C; Leopizzi, M; Maestroni, S; Corradi, B; Zerbini, G; Stella, A

    2013-01-01

    Diabetic nephropathy is the main cause of end-stage renal disease. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a physiological tetrapeptide hydrolyzed by the angiotensin-converting enzyme (ACE), has antifibrotic effects in the cardiovascular system and in the kidney in experimental models of hypertension, heart failure and renal disease. The aim of the study was to evaluate the effect of Ac-SDKP in diabetic nephropathy and the potential additive effect of Ac-SDKP, when compared to ACE inhibitors alone, on the development of renal fibrosis. Diabetes was induced in 28 Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin. Control rats (n = 10) received only buffer solution. An ACE inhibitor (ramipril, 3 mg/kg/day) was administered to 11 diabetic rats. After 2 months, Ac-SDKP (1 mg/kg/day) was administered by osmotic minipumps for 8 weeks to 7 diabetic rats and to 6 diabetic rats treated with ramipril. Osmotic minipumps delivered saline solution in the corresponding sham-treated rats (diabetic rats, n = 10, and ramipril-treated diabetic rats, n = 5). Diabetic rats showed a significant increase in blood glucose level, urinary albumin excretion and renal fibrosis, and a reduction of glomerular nephrin expression with respect to control rats. Ac-SDKP administration significantly reduced renal fibrosis in diabetic rats, without significantly reducing urinary albumin excretion. Ramipril treatment caused a significant decrease in albuminuria and renal fibrosis and restored glomerular nephrin expression. Administration of Ac-SDKP, in addition to ramipril, further reduced renal fibrosis with respect to ramipril alone, while it did not improve the antiproteinuric effect of ramipril. Ac-SDKP administration reduces renal fibrosis in diabetic nephropathy. Addition of Ac-SDKP to ACE inhibition therapy improves the reduction of renal fibrosis with respect to ACE inhibition alone, suggesting a beneficial effect of this pharmacological association in

  17. GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

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    Quan Shi

    2017-11-01

    Full Text Available Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats.Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis.Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density.Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing

  18. Rare sugar d-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats

    Science.gov (United States)

    Hossain, Akram; Yamaguchi, Fuminori; Hirose, Kayoko; Matsunaga, Toru; Sui, Li; Hirata, Yuko; Noguchi, Chisato; Katagi, Ayako; Kamitori, Kazuyo; Dong, Youyi; Tsukamoto, Ikuko; Tokuda, Masaaki

    2015-01-01

    Background The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects. Aim Above mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats. Methods Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests. Results d-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue. Conclusion Our findings suggest that the rare sugar d-psicose could be beneficial for the

  19. Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats.

    Science.gov (United States)

    Hossain, Akram; Yamaguchi, Fuminori; Hirose, Kayoko; Matsunaga, Toru; Sui, Li; Hirata, Yuko; Noguchi, Chisato; Katagi, Ayako; Kamitori, Kazuyo; Dong, Youyi; Tsukamoto, Ikuko; Tokuda, Masaaki

    2015-01-01

    The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects. Above mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats. Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests. d-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue. Our findings suggest that the rare sugar d-psicose could be beneficial for the prevention and control of obesity and

  20. Atorvastatin induced increase in homologous angiotensin I converting enzyme (ACE2) mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    OpenAIRE

    Aguilar, Cristian; Departamento de Anatomía Patológica, Hospital Nacional Edgardo Rebagliati Martins. Lima, Perú. Médico, Residente de Anatomía Patológica, HNERM.; Ventura, Freddy; Departamento de Ciencias Básicas, facultad de Medicina, Universidad Nacional de Trujillo. Trujillo, Perú. Químico farmacéutico, Magíster en fisiología y Biofísica.; Rodríguez-Delfín, Luis; Departamento de Anatomía Patológica, Hospital Nacional Edgardo Rebagliati Martins. Lima, Perú. Laboratorio de Biología Molecular, Facultad de Biología, Universidad Nacional Pedro Ruiz Gallo. Chiclayo, Perú. Investigación y Diagnóstico en Genética y Biología Molecular “GEN MOL”. Trujillo, Perú. Biólogo, Doctor en Ciencias, área de Genética.

    2011-01-01

    Objectives. This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats. Materials and Methods. Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divided into 3 groups: (1) normal control rats, (2) diabetic rats and (3) diabetic rats treated orally with atorvastatin (50 mg/kg/day). After eight weeks of treatment, the hearts were removed for morpho...

  1. Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.

    Science.gov (United States)

    Davidson, Eric P; Coppey, Lawrence J; Shevalye, Hanna; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A

    2017-06-01

    This study investigated the efficacy of monotherapy versus combination of menhaden oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes. Male Sprague-Dawley rats (aged 12 weeks) were fed a high-fat diet for 8 weeks followed by 30 mg/kg streptozotocin. After 16 weeks of hyperglycemia, 12-week treatments consisting of menhaden oil, α-lipoic acid, enalapril, or their combination were initiated. Before and after treatments, we performed analyses of multiple neural and vascular endpoints including corneal sensitivity, corneal nerve density, vascular reactivity of epineurial arterioles, motor and sensory nerve conduction velocity, intraepidermal nerve fiber density, and thermal nociception. Before treatment, all the neural and vascular endpoints in diabetic rats were impaired. Treating diabetic rats with monotherapy was effective in improving neural and vascular deficits with menhaden oil being most efficacious. However, the combination therapy provided the greatest benefit and improved/reversed all nerve and vascular deficits. The effect of combination therapy on corneal relative sensitivity and structure (in mm/mm), primary endpoints for this study, for control, diabetic, and diabetic treated rats was 4.2 ± 1.4 and 7.5 ± 0.5, 12.1 ± 1.3* and 3.8 ± 0.2*, and 6.6 ± 2.3 and 7.3 ± 0.5, respectively (*P < 0.05 compared with control rats; P < 0.05 compared with diabetic rats). These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.

  2. A non-MHC locus essential for autoimmune type I diabetes in the Komeda Diabetes-Prone rat.

    OpenAIRE

    Yokoi, N; Kanazawa, M; Kitada, K; Tanaka, A; Kanazawa, Y; Suda, S; Ito, H; Serikawa, T; Komeda, K

    1997-01-01

    The Long-Evans Tokushima Lean (LETL) rat, characterized by rapid onset of insulin-dependent (type I) diabetes mellitus (IDDM), no sex difference in the incidence of IDDM, autoimmune destruction of pancreatic beta cells, and no significant T cell lymphopenia, is a desirable animal model for human IDDM. We have established a diabetes-prone substrain of the LETL rat, named Komeda Diabetes-Prone (KDP) rat, showing a 100% development of moderate to severe insulitis within 220 d of age. The cumulat...

  3. Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Renal Protection of in vivo administration of Tempol in streptozotocin-induced Diabetic Rats

    OpenAIRE

    Luan, Jiajie; Li, Weiping; Han, Jia; Zhang, Wen; Gong, Huiling; Ma, Rong

    2012-01-01

    The present study was carried out to investigate the protective effects of tempol on renal function and the underlying mechanism in streptozotocin-induced diabetic rats. The diabetic rats were randomly divided into Model group (without tempol) and Tempol group. Nondiabetic rats were served as Control group. The mRNA expression of canonical transient receptor potential 6 (TRPC6), transforming growth factor (TGF)-β1 and type IV collagen (Col IV) were examined. The malondialdehyde (MDA) level, a...

  6. Analysis of Maceaene and Macamide Contents of Petroleum Ether Extract of Black, Yellow, and Purple Lepidium Meyenii (Maca and Their Antioxidant Effect on Diabetes Mellitus Rat Model

    Directory of Open Access Journals (Sweden)

    Congyang Qiu

    Full Text Available ABSTRACT Maceaene and macamide contents as well as antioxidant effect of petroleum ether extract of black maca (BM, yellow maca (YM, and purple maca (PM on diabetes mellitus (DM rats were investigated. The results showed that seven, six, and five analogues of macamides were identified from the petroleum ether extracts of BM, YM, and PM, respectively. BM extract exhibited the highest contents of total macamides. Comparatively, the PM extract has the lowest macamide quantity. The maceaene contents in all the extracts showed no significant difference (p>0.05. Macamide contents in maca with the same color were not statistically different. Pharmacological results showed that 60-day oral administration of the petroleum ether extract of maca (100 mg/kg.d can significantly decrease lipid oxidation as indicated by the decreased thiobarbituric acid reactive substances (TBARS and carbonylated proteins (CP concentrations on DM rat model (P<0.05. Among them, oral administration of PM extract showed the lowest TBRAS and CP concentrations. All maca extracts can enhance antioxidant enzyme (SOD, superoxide dismutase; CAT, catalase activity of liver and red blood cells (RBC of DM rat. However, only oral administration of PM extract can increase SOD and CAT activity of both RBC and liver. The glutathion (GSH contents in plasma were significantly increased in DM rats treated with PM extract (p<0.05. But, oral administration of BM and YM extracts did not enhance GSH levels. Take together, the data suggested that PM extract exhibited the most potent antioxidant activity on DM rat model. And, maceaene and macamide in maca extract was not correlated with its antioxidant ability.

  7. Effects on Glycemic Control in Impaired Wound Healing in Spontaneously Diabetic Torii (SDT) Fatty Rats.

    Science.gov (United States)

    Katsuhiro, Miyajima; Hui Teoh, Soon; Yamashiro, Hideaki; Shinohara, Masami; Fatchiyah, Fatchiyah; Ohta, Takeshi; Yamada, Takahisa

    2018-02-01

    Impaired diabetic wound healing is an important issue in diabetic complications. The present study aims to evaluate the protective effect on glycemic control against impaired diabetic wound healing using a diabetic rat model. We investigated the wound healing process and effect on the impaired wound repair by glycemic control in the Spontaneously Diabetic Torii (SDT) fatty rat, which is a new animal model of obese type 2 diabetes and may be a good model for study impaired wound healing. Male SDT fatty rats at 15 weeks of age were administered orally with sodium glucose co-transporter (SGLT) 2 inhibitor for 3 weeks. Wounds were induced at 2 weeks after SGLT 2 inhibitor treatment, and the wound areas were periodically examined in morphological and histological analyses. The SDT fatty rats showed a delayed wound healing as compared with the normal rats, but a glycemic control improved the impaired wound healing. In histological analysis in the skin of SDT fatty rats showed severe infiltration of inflammatory cell, hemorrhage and many bacterial masses in the remaining and slight fibrosis of crust on skin tissue . Thought that this results skin performance to be a delay of crust formation and regeneration of epithelium; however, these findings were ameliorated in the SGLT 2 inhibitor treated group. Glycemic control is effective for treatment in diabetic wounds and the SDT fatty rat may be useful to investigate pathophysiological changes in impaired diabetic wound healing.

  8. EGb761, a Ginkgo biloba extract, is effective against atherosclerosis in vitro, and in a rat model of type 2 diabetes.

    Science.gov (United States)

    Lim, Soo; Yoon, Ji Won; Kang, Seon Mee; Choi, Sung Hee; Cho, Bong Jun; Kim, Min; Park, Ho Seon; Cho, Hyun Ju; Shin, Hayley; Kim, Young-Bum; Kim, Hyo Soo; Jang, Hak Chul; Park, Kyong Soo

    2011-01-01

    EGb761, a standardized Ginkgo biloba extract, has antioxidant and antiplatelet aggregation and thus might protect against atherosclerosis. However, molecular and functional properties of EGb761 and its major subcomponents have not been well characterized. We investigated the effect of EGb761 and its major subcomponents (bilobalide, kaemferol, and quercetin) on preventing atherosclerosis in vitro, and in a rat model of type 2 diabetes. EGb761 (100 and 200 mg/kg) or normal saline (control) were administered to Otsuka Long-Evans Tokushima Fatty rats, an obese insulin-resistant rat model, for 6 weeks (from 3 weeks before to 3 weeks after carotid artery injury). Immunohistochemical staining was performed to investigate cell proliferation and apoptosis in the injured arteries. Cell migration, caspase-3 activity and DNA fragmentation, monocyte adhesion, and ICAM-1/VCAM-1 levels were explored in vitro. Treatment with EGb761 dose-dependently reduced intima-media ratio, proliferation of vascular smooth muscle cells (VSMCs) and induced greater apoptosis than the controls. Proliferation and migration of VSMCs in vitro were also decreased by the treatment of EGb761. Glucose homeostasis and circulating adiponectin levels were improved, and plasma hsCRP concentrations were decreased in the treatment groups. Caspase-3 activity and DNA fragmentation increased while monocyte adhesion and ICAM-1/VCAM-1 levels decreased significantly. Among subcomponents of EGb761, kaemferol and quercetin reduced VSMC migration and increased caspase activity. EGb761 has a protective role in the development of atherosclerosis and is a potential therapeutic agent for preventing atherosclerosis.

  9. Regulation of insulin sensitivity, insulin production, and pancreatic β cell survival by angiotensin-(1-7) in a rat model of streptozotocin-induced diabetes mellitus.

    Science.gov (United States)

    He, Junhua; Yang, Zhiming; Yang, Huiyu; Wang, Li; Wu, Huilu; Fan, Yunjuan; Wang, Wei; Fan, Xin; Li, Xing

    2015-02-01

    The aim of this study is to determine the antidiabetic activity of Ang-(1-7), an important component of the renin-angiotensin system, in a rat model of streptozotocin (STZ)-induced type 2 diabetes mellitus (DM). A total of 36 male Wistar rats were randomly divided into 3 groups: control group fed standard laboratory diet, DM group fed high-fat diet and injected with STZ, and Ang-(1-7) group receiving injection of STZ followed by Ang-(1-7) treatment. Body weight, blood glucose levels, fasting serum Ang II and insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The pancreas was collected for histological examination and gene expression analysis. Notably, the Ang-(1-7) group showed a significant decrease in fasting blood glucose and serum Ang II levels and HOMA-IR values and increase in fasting serum insulin levels. Pancreatic β cells in the control and Ang-(1-7) groups were normally distributed in the center of pancreatic islets with large clear nuclei. In contrast, pancreatic β cells in the DM group had a marked shrinkage of the cytoplasm and condensation of nuclear chromatin. Ang-(1-7) treatment significantly facilitated insulin production by β cells in diabetic rats. The DM-associated elevation of inducible nitric oxide synthase (iNOS), caspase-3, caspase-9, caspase-8, and Bax and reduction of Bcl-2 was significantly reversed by Ang-(1-7) treatment. Taken together, Ang-(1-7) protects against STZ-induced DM through improvement of insulin resistance, insulin secretion, and pancreatic β cell survival, which is associated with reduction of iNOS expression and alteration of the Bcl-2 family. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yuan-Horng [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Charles, Chou C.-K. [Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan (China); Wang, Jyh-Seng [Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Tung, Chun-Liang [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Li, Ya-Ru; Lo, Kai [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Cheng, Tsun-Jen, E-mail: tcheng@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

    2014-12-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM{sub 2.5} exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM{sub 2.5} in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m{sup 3}, respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic

  11. Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats

    Directory of Open Access Journals (Sweden)

    Hossain A

    2015-01-01

    Full Text Available Akram Hossain,1,2 Fuminori Yamaguchi,1 Kayoko Hirose,1 Toru Matsunaga,3 Li Sui,1 Yuko Hirata,1 Chisato Noguchi,1 Ayako Katagi,1 Kazuyo Kamitori,1 Youyi Dong,1 Ikuko Tsukamoto,4 Masaaki Tokuda11Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan; 2Research and Development, Matsutani Chemical Industry Co., Ltd., Kitaitami, Itami-shi, Hyogo, Japan; 3Division of Hospital Pathology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan; 4Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, JapanBackground: The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, D-psicose (D-allulose, a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects.Aim: Above mentioned efficacy of D-psicose (D-allulose has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM model Otsuka Long-Evans Tokushima Fatty (OLETF rats with short-term treatment. In this study we investigated the long-term effect of D-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats.Methods: Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO, were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests.Results: D-Psicose prevented the commencement and progression of T2DM till 60 weeks through the

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

    Science.gov (United States)

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

    2017-12-01

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

  13. Effect of Consumption of Tribulus Terrestris on Serum Glucose and Lipid Levels in Diabetic Rats

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    M Roghani

    2010-03-01

    Full Text Available Introduction: The effect of Tribulus terrestris (TT on serum glucose and lipid levels was investigated in an experimental model of diabetes mellitus in rats. Methods: Female Wistar rats were divided into control, TT-treated control, diabetic, glibenclamide-treated, and TT-treated diabetic groups. For induction of diabetes, streptozotcin (STZ was administered (60 mg/Kg. Meanwhile, TT-treated groups received TT mixed with standard pelleted food at a weight ratio of 6.25% for 6 weeks. Serum glucose and lipid levels were determined before the study and at the 3rd and 4th week after the study. Results: Serum glucose was significantly lower in TT-treated diabetic rats at 3rd and 6th weeks as compared to untreated diabetics (p<0.01 and p<0.005, respectively. In addition, serum total cholesterol, triglyceride, and LDL-cholesterol showed a significant reduction in TT-treated diabetic rats as compared to untreated diabetics (p<0.05. On the other hand, HDL-cholesterol level did not change significantly in TT-treated diabetic group as compared to untreated diabetic group. Conclusions: Oral administration of TT has a significant hypoglycemic effect and in long term leads to appropriate changes in serum LDL-cholesterol, total cholesterol, and triglyceride levels, but does not affect HDL-cholesterol levels in diabetic rats.

  14. Effect of Petiveria alliacea Leaves Extract in Decreasing Serum Level of Blood Glucose Level Through Activation of AMPK-α1 in Diabetes Mellitus Rat Models

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    Arifa Mustika

    2017-03-01

    Full Text Available Singawalang (Petiveria alliaceae is a medicinal herb that is used traditionally as folk medicine for various diseases. The plant has been used as an antidiabetic agent in Indonesian society. Until now, the effect and mechanism of action of Petiveria alliaceae as antidiabetic agent is not clear. The aim of the study was to determine the effect of Petiveria alliaceae to blood glucose level and to identify expression of AMPK-α1 in rat liver. The research was experimental study with randomized and was conducted at Laboratory Pharmacology and Therapy, and Laboratory Patology Anatomy, Faculty of Medicine, Universitas Airlangga, on April until August 2015. Twenty five male rats were injected by Streptozotocin to create diabetic rat models and randomly divided into 5 groups. The group 1, 2 and 3 are treatment groups that were given the ethanol extract of Petiveria alliaceae at dose 90 mg/kgbw, 180 mg/kgbw, and 360 mg/kgbw, orally, once daily for fourteen days. The fourth group is a negative control who were given distilled water and the fifth group is a positive control who were given metformin at dose 150 mg/kgbw. On the 15th day, blood glucose level were measured by glucometer and the rats were sacrificed to collect the liver. Expression of AMPK-α1 were assessed by immunohistochemistry. Data were analyzed by ANAVA and Wilcoxon (α=0,05. The results have been showed that there were significant differences in glucose blood level between negative control with the group were given the extract at dose 90 mg/kgbw, 360 mg/kgbw and positive control, between dose 180 mg/kgbw with dose 360 mg/kgbw and positive control. A significant differences of expression of AMPK-α1 showed between dose 180 mg/kgbw with dose 360 mg/kgbw and positive control. The conclusion of this study was the extract ethanol of Singawalang leaves reduce blood glucose level in diabetes mellitus rat models through increase in the expression of AMPK-α1.

  15. Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes.

    Science.gov (United States)

    Go, Hyeon-Kyu; Rahman, Md Mahbubur; Kim, Gi-Beum; Na, Chong-Sam; Song, Choon-Ho; Kim, Jin-Shang; Kim, Shang-Jin; Kang, Hyung-Sub

    2015-10-15

    The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of β-cells maintaining normal insulin and glucose

  16. Deterioration of plasticity and metabolic homeostasis in the brain of the UCD-T2DM rat model of naturally occurring type-2 diabetes.

    Science.gov (United States)

    Agrawal, Rahul; Zhuang, Yumei; Cummings, Bethany P; Stanhope, Kimber L; Graham, James L; Havel, Peter J; Gomez-Pinilla, Fernando

    2014-09-01

    The rising prevalence of type-2 diabetes is becoming a pressing issue based on emerging reports that T2DM can also adversely impact mental health. We have utilized the UCD-T2DM rat model in which the onset of T2DM develops spontaneously across time and can serve to understand the pathophysiology of diabetes in humans. An increased insulin resistance index and plasma glucose levels manifested the onset of T2DM. There was a decrease in hippocampal insulin receptor signaling in the hippocampus, which correlated with peripheral insulin resistance index along the course of diabetes onset (r=-0.56, pT2DM increased the hippocampal levels of 4-hydroxynonenal (4-HNE; a marker of lipid peroxidation) in inverse proportion to the changes in the mitochondrial regulator PGC-1α. Disrupted energy homeostasis was further manifested by a concurrent reduction in energy metabolic markers, including TFAM, SIRT1, and AMPK phosphorylation. In addition, T2DM influenced brain plasticity as evidenced by a significant reduction of BDNF-TrkB signaling. These results suggest that the pathology of T2DM in the brain involves a progressive and coordinated disruption of insulin signaling, and energy homeostasis, with profound consequences for brain function and plasticity. All the described consequences of T2DM were attenuated by treatment with the glucagon-like peptide-1 receptor agonist, liraglutide. Similar results to those of liraglutide were obtained by exposing T2DM rats to a food energy restricted diet, which suggest that normalization of brain energy metabolism is a crucial factor to counteract central insulin sensitivity and synaptic plasticity associated with T2DM. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. [Red Blood Cells Raman Spectroscopy Comparison of Type Two Diabetes Patients and Rats].

    Science.gov (United States)

    Wang, Lei; Liu, Gui-dong; Mu, Xin; Xiao, Hong-bin; Qi, Chao; Zhang, Si-qi; Niu Wen-ying; Jiang, Guang-kun; Feng, Yue-nan; Bian, Jing-qi

    2015-10-01

    By using confocal Raman spectroscopy, Raman spectra were measured in normal rat red blood cells, normal human red blood cells, STZ induced diabetetic rats red blood cells, Alloxan induced diabetetic rats red blood cells and human type 2 diabetes red blood cells. Then principal component analysis (PCA) with support vector machine (SVM) classifier was used for data analysis, and then the distance between classes was used to judge the degree of close to two kinds of rat model with type 2 diabetes. The results found significant differences in the Raman spectra of red blood cell in diabetic and normal red blood cells. To diabetic red blood cells, the peak in the amide VI C=O deformation vibration band is obvious, and amide V N-H deformation vibration band spectral lines appear deviation. Belong to phospholipid fatty acyl C-C skeleton, the 1 130 cm(-1) spectral line is enhanced and the 1 088 cm(-1) spectral line is abated, which show diabetes red cell membrane permeability increased. Raman spectra of PCA combined with SVM can well separate 5 types of red blood cells. Classifier test results show that the classification accuracy is up to 100%. Through the class distance between the two induced method and human type 2 diabetes, it is found that STZ induced model is more close to human type 2 diabetes. In conclusion, Raman spectroscopy can be used for diagnosis of diabetes and rats STZ induced diabetes method is closer to human type 2 diabetes.

  18. Pig model for diabetes

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention relates to a transgenic pig comprising a mutated IAPP gene and displaying a phenotype associated with diabetes. The invention also relates to a transgenic blastocyst, embryo, fetus, donor cell and/or cell nucleusderived from said transgenic pig. The invention further relates...... to use of the transgenic pig as a model system for studying therapy, treatment and/or prevention of diabetes....

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

    Directory of Open Access Journals (Sweden)

    Takeshi Ohta

    2014-01-01

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

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

    Science.gov (United States)

    Grisé, Kenneth N; Olver, T Dylan; McDonald, Matthew W; Dey, Adwitia; Jiang, Mao; Lacefield, James C; Shoemaker, J Kevin; Noble, Earl G; Melling, C W James

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

    Science.gov (United States)

    Dain, Alejandro; Repossi, Gaston; Diaz-Gerevini, Gustavo T; Vanamala, Jairam; Das, Undurti N; Eynard, Aldo R

    2016-11-25

    Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory

  3. Histological and cognitive alterations in adult diabetic rats following an episode of juvenile diabetic ketoacidosis: Evidence of permanent cerebral injury.

    Science.gov (United States)

    Glaser, Nicole; Sasaki-Russell, Jennifer; Cohen, Michael; Little, Christopher; O'Donnell, Martha; Sall, Jeffrey

    2017-05-22

    Evidence suggests that diabetic ketoacidosis (DKA) may cause subtle cognitive alterations in children but the mechanisms are poorly understood. Acute DKA is associated with reactive astrogliosis and microglial activation in a rat model. Whether these inflammatory changes permanently alter brain histology is unknown. We aimed to determine whether DKA results in permanent alterations in brain histology and whether these changes are associated with cognitive deficits in a rat model. We induced diabetes in juvenile rats with streptozotocin at 4 weeks of age. We induced DKA in one group (n=21) at 5 weeks of age and compared this group to rats with diabetes without DKA episodes (n=13). Beginning at 7 weeks, rats underwent a series of cognitive tests to evaluate memory. At 15 weeks, rat brains were harvested and examined using immunohistochemistry (IHC). In tests of novel object recognition and social recognition, both groups performed similarly, however, the DKA group performed more poorly in object-place recognition tests, suggesting alterations in hippocampal function. IHC studies demonstrated increased glial fibrillary acidic protein staining intensity in the hippocampus of DKA rats suggesting astrogliosis, and decreased NeuN positive cell counts in the cortex suggesting neuron loss. These studies demonstrate that DKA results in permanent alterations in brain microstructure in a rat diabetes model. These structural changes are associated with deficits in hippocampal function. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Effect of Momordica charantia fruit extract on vascular complication in type 1 diabetic rats.

    Science.gov (United States)

    Abas, Razif; Othman, Faizah; Thent, Zar Chi

    2015-01-01

    Diabetes mellitus is one of the risk factors in the development of vascular complications. Decreased nitric oxide (NO) production and increased lipid peroxidation in diabetes mellitus are the dominant exaggerating factors. Mormodica charantia (MC) was proven to be useful in improving diabetes mellitus and its complications. In the present study, a total of 40 male Sprague-Dawley rats were used. Diabetes was induced by a single dose (50 mg/kg) of streptozotocin (STZ), intramuscularly. Following 4 weeks of STZ induction, the animals were equally divided into five groups (n = 8); Control group (Ctrl), control group treated with MC (Ctrl-MC), diabetic untreated group (DM-Ctrl), diabetic group treated with MC (DM-MC) and diabetic group treated with metformin 150 g/kg (DM-Met). Oral administration of the MC fruit extract (1.5 g/kg) was continued for 28 days. DM-MC group showed a significant decrease (P diabetic rat model.

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

    Directory of Open Access Journals (Sweden)

    Selvaraju Kavipriya

    2013-09-01

    Full Text Available 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.

  6. Renal protection of in vivo administration of tempol in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Luan, Jiajie; Li, Weiping; Han, Jia; Zhang, Wen; Gong, Huiling; Ma, Rong

    2012-01-01

    The present study was carried out to investigate the protective effects of tempol on renal function and the underlying mechanism in streptozotocin-induced diabetic rats. The diabetic rats were randomly divided into the model group (without tempol) and tempol group (1 mM tempol in drinking water for 6 weeks). Nondiabetic rats were served as the Control group. The mRNA expression of canonical transient receptor potential 6 (TRPC6), transforming growth factor (TGF)-β1, and type IV collagen (Col IV) were examined. The malondialdehyde (MDA) level, activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in renal tissues were measured to assess redox status in kidneys. We found that tempol significantly reduced 24-h urine output and urine albuminuria excretion in the diabetic rats. Compared with the model group, the concentration of MDA was significantly lower in the tempol group. In addition, diabetes decreased activities of SOD and GSH-Px and these responses were prevented by tempol treatment. Moreover, in diabetic rats, the mRNA expression levels of TGF-β1 and Col IV were upregulated. TRPC6 mRNA expression level was down-regulated in diabetic kidneys. However, all of these diabetic effects were significantly suppressed by tempol treatment. These results suggest that chronic treatment of diabetic rats with tempol can protect kidneys, possibly by reducing expression of TGF-β1, Col IV, and upregulating TRPC6 expression level.

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

    International Nuclear Information System (INIS)

    Chen Yingjian; Tu Xiaowen; Yin Qiuxia; Hu Chenjing

    2004-01-01

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

  8. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    International Nuclear Information System (INIS)

    Kodera, Ryo; Shikata, Kenichi; Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro; Usui, Hitomi Kataoka; Makino, Hirofumi

    2014-01-01

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose

  9. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kodera, Ryo, E-mail: kodera@cc.okayama-u.ac.jp [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikata, Kenichi [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Usui, Hitomi Kataoka [Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Makino, Hirofumi [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)

    2014-01-17

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose.

  10. Melatonin improves spatial navigation memory in male diabetic rats

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    Farrin Babaei-Balderlou

    2012-09-01

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

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

    Science.gov (United States)

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

    2017-11-04

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

  12. 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.

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

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    Qian Zhang

    2018-03-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  15. Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats.

    Science.gov (United States)

    Navarro-Alarcon, Miguel; Ruiz-Ojeda, Francisco J; Blanca-Herrera, Rosa M; Kaki, Abdullah; Adem, Abdu; Agil, Ahmad

    2014-03-01

    The use of melatonin, a neurohormone present in plants, represents an exciting approach for the maintenance of optimum health conditions. Melatonin administration ameliorates glucose homeostasis in Zucker diabetic fatty (ZDF) rats. The objective of this study was to investigate the effects of melatonin in diabetes in relation to the levels and regulation of plasma chromium (Cr), vanadium (V), and magnesium (Mg) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. At the age of 6 weeks, ZDF (n = 30) and ZL (n = 30) groups were each subdivided into three groups: control (C) (n = 10), vehicle-treated (V') (n = 10) and melatonin-treated (M) (10 mg kg(-1) per day; n = 10) groups for a 6 week period. After treatment, plasma mineral concentrations were measured by flame (Mg) and electrothermal (Cr and V) atomic absorption spectrometry. No significant differences were found between the C and V' groups (p > 0.05). Plasma Mg levels were significantly lower in C-ZDF vs. C-ZL rats, demonstrating the presence of hypomagnesemia in this diabetes mellitus model. Plasma V and Cr levels were significantly higher in M-ZDF vs. C-ZDF rats. Plasma Mg levels in ZDF rats were not affected by melatonin treatment (p > 0.05). Melatonin administration ameliorates the diabetic status of ZDF rats by enhancing plasma Cr and V concentrations. This appears to be the first report of a beneficial effect of melatonin treatment on plasma Cr and V regulation in ZDF rats.

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  17. Antinociceptive effect of black seed feeding in streptozotocin-diabetic rats

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    Mohammad reza Vaez mahdavi

    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 Nigella sativum (NS on formalin-induced nociceptive responses (standard formalin test in streptozotocin (STZ-induced diabetic rats.  Methods: For this purpose, STZ-diabetic rats received Nigella sativum mixed with standard rat chow at a weight ratio of 6.25% orally for a period of one month.  Results: It was found out that NS treatment did cause a significant reduction in blood glucose in diabetic rats and NS-treated diabetic rats exhibited a lower nociceptive score as compared to untreated-diabetic ones. Meanwhile, NS 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 NS feeding for treating painful diabetic neuropathy. 

  18. Antinociceptive effect of black seed feeding in streptozotocin-diabetic rats

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    Mohammad reza Vaez mahdavi

    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 Nigella sativum (NS on formalin-induced nociceptive responses (standard formalin test in streptozotocin (STZ-induced diabetic rats.  Methods: For this purpose, STZ-diabetic rats received Nigella sativum mixed with standard rat chow at a weight ratio of 6.25% orally for a period of one month.  Results: It was found out that NS treatment did cause a significant reduction in blood glucose in diabetic rats and NS-treated diabetic rats exhibited a lower nociceptive score as compared to untreated-diabetic ones. Meanwhile, NS 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 NS feeding for treating painful diabetic neuropathy.

  19. Total lymphoid irradiation prevents diabetes mellitus in the Bio-Breeding/Worcester (BB/W) rat

    International Nuclear Information System (INIS)

    Rossini, A.A.; Slavin, S.; Woda, B.A.; Geisberg, M.; Like, A.A.; Mordes, J.P.

    1984-01-01

    Total lymphoid irradiation (TLI) at doses of 2200 rads or greater prevented diabetes in susceptible BB/W rats. Two of 29 (7%) treated rats became diabetic compared with 23 of 39 (59%) controls. TLI did not, however, prevent insulitis or thyroiditis in nondiabetic rats, nor did it restore the depressed concanavalin-A responsiveness of BB rat lymphocytes. T-lymphocyte subset proportions were the same in both groups. TLI was associated with significant radiation-related mortality, and nondiabetic TLI-treated rats weighed significantly less than controls. It was concluded that TLI is effective in the prevention of BB rat diabetes. However, TLI fails to correct the subclinical immunologic abnormalities of the model and is associated with significant morbidity

  20. EGb761, a Ginkgo biloba extract, is effective against atherosclerosis in vitro, and in a rat model of type 2 diabetes.

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    Soo Lim

    Full Text Available BACKGROUND: EGb761, a standardized Ginkgo biloba extract, has antioxidant and antiplatelet aggregation and thus might protect against atherosclerosis. However, molecular and functional properties of EGb761 and its major subcomponents have not been well characterized. We investigated the effect of EGb761 and its major subcomponents (bilobalide, kaemferol, and quercetin on preventing atherosclerosis in vitro, and in a rat model of type 2 diabetes. METHODS AND RESULTS: EGb761 (100 and 200 mg/kg or normal saline (control were administered to Otsuka Long-Evans Tokushima Fatty rats, an obese insulin-resistant rat model, for 6 weeks (from 3 weeks before to 3 weeks after carotid artery injury. Immunohistochemical staining was performed to investigate cell proliferation and apoptosis in the injured arteries. Cell migration, caspase-3 activity and DNA fragmentation, monocyte adhesion, and ICAM-1/VCAM-1 levels were explored in vitro. Treatment with EGb761 dose-dependently reduced intima-media ratio, proliferation of vascular smooth muscle cells (VSMCs and induced greater apoptosis than the controls. Proliferation and migration of VSMCs in vitro were also decreased by the treatment of EGb761. Glucose homeostasis and circulating adiponectin levels were improved, and plasma hsCRP concentrations were decreased in the treatment groups. Caspase-3 activity and DNA fragmentation increased while monocyte adhesion and ICAM-1/VCAM-1 levels decreased significantly. Among subcomponents of EGb761, kaemferol and quercetin reduced VSMC migration and increased caspase activity. CONCLUSIONS: EGb761 has a protective role in the development of atherosclerosis and is a potential therapeutic agent for preventing atherosclerosis.

  1. Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats.

    Science.gov (United States)

    Coskun, Zeynep Mine; Bolkent, Sema

    2014-01-01

    The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ(9)-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Δ(9)-THC treated, (3) diabetic, and (4) diabetic+Δ(9)-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Δ(9)-THC and Δ(9)-THC treated diabetic groups received 3mg/kg/day of Δ(9)-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin-biotin-peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic+Δ(9)-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic+Δ(9)-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes+Δ(9)-THC group showed a decrease compared to the diabetic group. These results indicate that Δ(9)-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

  2. Penile alterations at early stage of type 1 diabetes in rats

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    Mingfang Tao

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

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

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    Chaoxing Yang

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

  4. Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in Streptozotocin-Induced Diabetic Rats

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    Mohammad Reza Hajizadeh

    2014-03-01

    Full Text Available Background: It has been proposed that oxidative stress may contribute to the development of testicular abnormalities in diabetes. Morus alba leaf extract (MAE has hypoglycemic and antioxidant properties. We, therefore, explored the impact of the administration of MAE on steroidogenesis in diabetic rats. Methods: To address this hypothesis, we measured the serum level of glucose, insulin, and free testosterone (Ts as well as oxidative stress parameters (including glutathione peroxidase, glutathione reductase, total antioxidant capacity, and malondialdehyde in the testis of control, untreated and MAE-treated (1 g/day/kg diabetic rats. In order to determine the likely mechanism of MAE action on Ts levels, we analyzed the quantitative mRNA expression level of the two key steroidogenic proteins, namely steroid acute regulatory protein (StAR and P450 cholesterol side-chain cleavage enzyme (P450scc, by real-time PCR. Results: The MAE-treated diabetic rats had significantly decreased glucose levels and on the other hand increased insulin and free Ts levels than the untreated diabetic rats. In addition, the administration of MAE to the diabetic rats restored the oxidative stress parameters toward control. Induction of diabetes decreased testicular StAR mRNA expression by 66% and MAE treatment enhanced mRNA expression to the same level of the control group. However, the expression of P540scc was not significantly decreased in the diabetic group as compared to the control group. Conclusion: Our findings indicated that MAE significantly increased Ts production in the diabetic rats, probably through the induction of StAR mRNA expression levels. Administration of MAE to experimental models of diabetes can effectively attenuate oxidative stress-mediated testosterone depletion. Please cite this article as: Hajizadeh MR, Eftekhar E, Zal F, Jaffarian A, Mostafavi-Pour Z. Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in

  5. The influence of nutrition (diet treatment in streptozotocin – induced diabetic rats

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    Chrcheva-Nikolovska Radmila

    2013-07-01

    Full Text Available The present study was designated to evaluate the effect of special antidiabetic diet treatment upon oxidative stress parameters in the initial stages of the development of diabetes. Male Wistar strain rats were used as an experimental model, divided into five groups: group 1, control rats; group 2, antidiabetic diet group; group 3, rats with induced diabetes mellitus – diabetic control; group 4, rats with induced diabetes mellitus and diet food, and group 5, rats with induced diabetes mellitus and insulin treatment.A significant decrease in superoxide dismutase (SOD and total glutathione (GSH activities were observed in the liver of diabetic rats when compared with control animals. There was simple evidence that elevation in glucose concentration depress natural antioxidant defense such as SOD and GSH. The observed decrease in SOD activity could result from inactivation by H2O2 or by glycation of the enzyme, which have been reported to occur in diabetes. The possible source of oxidative stress in diabetes includes shifts in redox balance resulting from altered carbohydrate and lipid metabolism, increased generation of reactive oxygen species, and decreased level of antioxidant defences such as GSH and SOD. The plasma level of aminotransferases (ALT, AST, creatine kinase (CK, lactate dehydrogenase (LDH and urea were significantly increased after induction of diabetes, in all groups under treatment. In contrast, rats fed special diet food, have shown slight different, but not significant changes. The decrease in total protein and albumin fraction may be due to microproteinuria and albuminuria, which are important clinical markers of diabetic nephro­pathy, and­/or may be due to increased protein catabolism.The findings of the present study suggest that special diet formula useful for prevention of progressive hyperglycaemia in age induced diabetes in dogs, could not restore the imbalance of cellular defence mechanism provoked by streptozotocin.

  6. WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy

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    Chengcheng Feng

    2018-01-01

    Full Text Available WenTong HuoXue Cream (WTHX-Cream has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN. This study investigated the gene and protein expression of the pain-related molecule PLC-β3 in the dorsal root ganglion (DRG of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats and DPN model (78 rats groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC-β3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC-β3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC-β3 mRNA and protein expression in the diabetic DRG of DPN rats.

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

    OpenAIRE

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting

    2010-01-01

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

  9. Neuroprotective effect of RYGB in Zucker fatty diabetic rats

    Science.gov (United States)

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

    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 measured. Peripheral nerve function was determined by the current perception threshold. Sciatic nerve blood flow (SNBF) and intraepidermal nerve fiber densities (IENFDs) also were evaluated. The results indicated that glucose tolerance and insulin sensitivity were significantly improved in the RYGB group. Fasting total GLP-1 were increased in the RYGB group. The increase seen in current perception threshold vales in RYGB group was reduced. The decreased IENFDs in sole skins of RYGB group were ameliorated by RYGB. In conclusion, the findings indicate that RYGB ameliorates the severity of DPN, which may be associated with increased GLP-1 and improved insulin sensitivity/action. PMID:25419361

  10. Effects of galangal extract on cognitive dysfunction and nerve pathological change in rats with diabetic encephalopathy

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    Dao-Rui Yu

    2016-09-01

    Full Text Available Objective: To evaluate the effects of galangal extract on cognitive dysfunction and nerve pathological change in rats with diabetic encephalopathy. Methods: Sixty male SD rats were given high sugar and fat diet except the control group. Fifty days later, the animals were injected with STZ 30 mg/kg through intraperitoneal to establish type 2 diabetes model. Rats were divided into control group, model group, Metformin group, oxiracetam group, galangal extract high and low dose group. After 4-week administration, Morris water maze was utilized to investigate the effects of different galangal extract on learning and memory ability in rats. After behavioral testing, the blood sugar level was detected. Meanwhile, spectrophotometer was used to measure the superoxide dismutase (SOD activity and maleic dialdehyde (MDA content of brain tissue. HE staining was used to observe the morphological changes in the hippocampus. Results: Galangal extract can significantly reduce swimming time and swimming distance of diabetic encephalopathy rat model, lower fasting blood glucose while increase body weight. At the same time, SOD activity and MDA content of rat brain were reduced. The morphology of neurons in hippocampus was improved and neuronal nuclear condensation was reduced correspondingly. Conclusions: Galangal extract can significantly improve cognitive ability in diabetic rats, reduce hippocampal pathological changes and have some prevention or treatment effects on of diabetes encephalopathy

  11. Effects of TNF-α blocking on experimental periodontitis and type 2 diabetes in obese diabetic Zucker rats

    DEFF Research Database (Denmark)

    Grauballe, Morten Christian Bay; Østergaard, Jakob Appel; Schou, Søren

    2015-01-01

    OBJECTIVE: Tumour necrosis factor α (TNF-α) is considered a key signalling modulator in the pathogenesis of both periodontitis (PD) and type 2 diabetes mellitus (DM2). This study aims at elucidating the effect of TNF-α blocking on the interplay between PD and DM2. METHODS: Obese diabetic Zucker...... rats and their lean littermates were divided into five treatment groups with or without periodontitis. Anti-TNF-α treatment was provided with Etanercept injections. Diabetic state was evaluated by oral glucose tolerance test, the homeostatic model assessment, free fatty acids and blood glucose...... treatment. CONCLUSION: In this study anti-TNF-α treatment improved glucose tolerance and compensated for the increased periodontal disease in obese diabetic Zucker. PD did not influence diabetic parameters assessed including complications of the rats kidneys....

  12. The effect of butter oil on avoidance memory in normal and diabetic rats.

    Science.gov (United States)

    Zare, Khadije; Tabatabaei, Seyed Reza Fatemi; Shahriari, Ali; Jafari, Ramezan Ali

    2012-07-01

    Since diabetes mellitus is accompanied by cognitive impairment in diabetic patient and animal models and since lipids play important roles in neuronal membrane composition, structure and function; we intended to evaluate the effect of dietary butter oil on passive avoidance memory of streptoztosin (STZ)-induced diabetic rats in this study. THIRTY SIX ADULT MALE RATS WERE RANDOMLY ALLOCATED TO FOUR EQUAL GROUPS: normal (N) and diabetic control (D) groups with free access to regular rat diet; but the diet of normal butter oil (NB) and diabetic butter oil (DB) groups was supplemented with 10% butter oil. Diabetes in D and DB groups was induced by intravenous (i.v.) injection of 50 mg/kg.bw of STZ. Passive avoidance memory and cholesterol of brain and hippocampal tissues has been measured six weeks after diabetes confirmation. Diabetes, especially in diabetic butter oil group decreased the abilities of learning and memory. The level of cholesterol in hippocampus was higher in NB (Pbutter oil may worsen cognitive impairment of diabetic animal. This may be related to the higher elevation of cholesterol in the hippocampus of diabetic animals.

  13. Up-regulation of Hsp72 and keratin16 mediates wound healing in streptozotocin diabetic rats

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    Rasha R. Ahmed

    2015-01-01

    Full Text Available BACKGROUND: Impaired wound healing is a complication of diabetes and a serious problem in clinical practice. We previously found that whey protein (WP was able to regulate wound healing normally in streptozotocin (STZ-dia-betic models. This subsequent study was designed to assess the effect of WP on heat shock protein-72 (Hsp72 and keratin16 (Krt16 expression during wound healing in diabetic rats. METHODS: WP at a dosage of 100 mg/kg of body weight was orally administered daily to wounded normal and STZ-diabetic rats for 8 days. RESULTS: At day 4, the WP-treated diabetic wound was significantly reduced compared to that in the corresponding control. Diabetic wounded rats developed severe inflammatory infiltration and moderate capillary dilatation and regeneration. Treated rats had mild necrotic formation, moderate infiltration, moderate to severe capillary dilatation and regeneration, in addition to moderate epidermal formation. Hsp72 and Krt16 densities showed low and dense activity in diabetic wounded and diabetic wounded treated groups, respectively. At day 8, WP-treatment of diabetic wounded animals revealed great amelioration with complete recovery and closure of the wound. Reactivity of Hsp72 and Krt16 was reversed, showing dense and low, or medium and low, activity in the diabetic wounded and diabetic wounded treated groups, respectively. Hsp72 expression in the pancreas was found to show dense reactivity with WP-treated diabetic wound rats. CONCLUSION: This data provides evidence for the potential impact of WP in the up-regulation of Hsp72 and Krt16 in T1D, resulting in an improved wound healing process in diabetic models.

  14. Expression of Endoplasmic Reticulum Stress-Related Factors in the Retinas of Diabetic Rats

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    Shu Yan

    2012-01-01

    Full Text Available Recent reports show that ER stress plays an important role in diabetic retinopathy (DR, but ER stress is a complicated process involving a network of signaling pathways and hundreds of factors, What factors involved in DR are not yet understood. We selected 89 ER stress factors from more than 200, A rat diabetes model was established by intraperitoneal injection of streptozotocin (STZ. The expression of 89 ER stress-related factors was found in the retinas of diabetic rats, at both 1- and 3-months after development of diabetes, by quantitative real-time polymerase chain reaction arrays. There were significant changes in expression levels of 13 and 12 ER stress-related factors in the diabetic rat retinas in the first and third month after the development of diabetes, Based on the array results, homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1(HERP, and synoviolin(HRD1 were studied further by immunofluorescence and Western blot. Immunofluorescence and Western blot analyses showed that the expression of HERP was reduced in the retinas of diabetic rats in first and third month. The expression of Hrd1 did not change significantly in the retinas of diabetic rats in the first month but was reduced in the third month.

  15. Metallothionein metabolism in the streptozotocin-diabetic rat

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  16. Lupine Alleviate Hyperglycemia in Streptozotocin Diabetic gamma- Irradiated Rats

    International Nuclear Information System (INIS)

    El-Sayed, S.M.

    2010-01-01

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

  17. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats

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    Xianchu Liu

    2016-04-01

    Full Text Available Objective(s:Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ-induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD. In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. Materials and Methods:Diabetic rats were treated with naringin (100 mg/kg/d for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD and malondialdehyde (MDA] and inflammatory cytokines (TNF-a, IL-1β, and IL-6 were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARγ were evaluated by real time (RT-PCR and Western blot analysis. Results:The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-α, IL-1β, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARγ expression. Conclusion: Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD.

  18. Bixa orellana (annatto) exerts a sustained hypoglycemic effect in experimental diabetes mellitus in rats

    OpenAIRE

    Teles, Flávio; Anjos, Felipe Silveira dos; Machado, Tarcilo; Lima, Roberta

    2014-01-01

    OBJECTIVE: Bixa orellana (annatto) is a natural pigment and food colorant that has been used for a variety of therapeutic purposes. It has been suggested that annatto could have the property of reducing blood glucose levels. However, most previous studies have demonstrated a hypoglycemic effect in non-diabetic animals. We evaluated the impact of annatto on blood glucose levels in an experimental model of diabetes mellitus. METHOD: Male Wistar rats were made diabetic by a single dose of60 mg/...

  19. The Sodium-Glucose Co-Transporter 2 Inhibitor Empagliflozin Improves Diabetes-Induced Vascular Dysfunction in the Streptozotocin Diabetes Rat Model by Interfering with Oxidative Stress and Glucotoxicity

    Science.gov (United States)

    Welschof, Philipp; Jansen, Thomas; Hausding, Michael; Mikhed, Yuliya; Stamm, Paul; Mader, Michael; Zinßius, Elena; Agdauletova, Saule; Gottschlich, Anna; Steven, Sebastian; Schulz, Eberhard; Bottari, Serge P.; Mayoux, Eric; Münzel, Thomas; Daiber, Andreas

    2014-01-01

    Objective In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress. Methods Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 7 weeks. Vascular function was assessed by isometric tension recording, oxidative stress parameters by chemiluminescence and fluorescence techniques, protein expression by Western blot, mRNA expression by RT-PCR, and islet function by insulin ELISA in serum and immunohistochemical staining of pancreatic tissue. Advanced glycation end products (AGE) signaling was assessed by dot blot analysis and mRNA expression of the AGE-receptor (RAGE). Results Treatment with empagliflozin reduced blood glucose levels, normalized endothelial function (aortic rings) and reduced oxidative stress in aortic vessels (dihydroethidium staining) and in blood (phorbol ester/zymosan A-stimulated chemiluminescence) of diabetic rats. Additionally, the pro-inflammatory phenotype and glucotoxicity (AGE/RAGE signaling) in diabetic animals was reversed by SGLT2i therapy. Conclusions Empagliflozin improves hyperglycemia and prevents the development of endothelial dysfunction, reduces oxidative stress and improves the metabolic situation in type 1 diabetic rats. These preclinical observations illustrate the therapeutic potential of this new class of antidiabetic drugs. PMID:25402275

  20. The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity.

    Directory of Open Access Journals (Sweden)

    Matthias Oelze

    Full Text Available OBJECTIVE: In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i, offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress. METHODS: Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg. One week after injection empagliflozin (10 and 30 mg/kg/d was administered via drinking water for 7 weeks. Vascular function was assessed by isometric tension recording, oxidative stress parameters by chemiluminescence and fluorescence techniques, protein expression by Western blot, mRNA expression by RT-PCR, and islet function by insulin ELISA in serum and immunohistochemical staining of pancreatic tissue. Advanced glycation end products (AGE signaling was assessed by dot blot analysis and mRNA expression of the AGE-receptor (RAGE. RESULTS: Treatment with empagliflozin reduced blood glucose levels, normalized endothelial function (aortic rings and reduced oxidative stress in aortic vessels (dihydroethidium staining and in blood (phorbol ester/zymosan A-stimulated chemiluminescence of diabetic rats. Additionally, the pro-inflammatory phenotype and glucotoxicity (AGE/RAGE signaling in diabetic animals was reversed by SGLT2i therapy. CONCLUSIONS: Empagliflozin improves hyperglycemia and prevents the development of endothelial dysfunction, reduces oxidative stress and improves the metabolic situation in type 1 diabetic rats. These preclinical observations illustrate the therapeutic potential of this new class of antidiabetic drugs.

  1. Intermittent Fasting Modulation of the Diabetic Syndrome in Streptozotocin-Injected Rats

    OpenAIRE

    Belkacemi, Louiza; Selselet-Attou, Ghalem; Hupkens, Emeline; Nguidjoe, Evrard; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J.

    2012-01-01

    This study investigates the effects of intermittent overnight fasting in streptozotocin-induced diabetic rats (STZ rats). Over 30 days, groups of 5-6 control or STZ rats were allowed free food access, starved overnight, or exposed to a restricted food supply comparable to that ingested by the intermittently fasting animals. Intermittent fasting improved glucose tolerance, increased plasma insulin, and lowered Homeostatis Model Assessment index. Caloric restriction failed to cause such benefic...

  2. Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats

    International Nuclear Information System (INIS)

    Myers, T.O.; Messina, E.J.; Rodrigues, A.M.; Gerritsen, M.E.

    1985-01-01

    Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous [1- 14 C]arachidonic acid by thoracic aortic rings and minced cremaster muscle. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis

  3. High-Salt Intake Ameliorates Hyperglycemia and Insulin Resistance in WBN/Kob-Leprfa/fa Rats: A New Model of Type 2 Diabetes Mellitus

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    Yoshiichi Takagi

    2018-01-01

    Full Text Available High-salt intake is a major risk factor for developing hypertension in type 2 diabetes mellitus, but its effects on glucose homeostasis are controversial. We previously found that high-salt intake induces severe hypertension in WBN/Kob diabetic fatty (WBKDF rats. In the present study, we examined the effects of a high-salt intake on glucose homeostasis in WBKDF rats. Male WBKDF rats and age-matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal-sodium (NS, 0.26% diet or high-sodium (HS, 8% diet for 7 weeks. Systolic blood pressure and urine volume were increased in WBKDF-HS and Wistar-HS. Body weight gain and food consumption were comparable between NS and HS in both strains. Plasma and urine glucose levels were significantly increased in WBKDF-NS but not in WBKDF-HS. HOMA-IR in WBKDF-HS was significantly lower compared with that in WBKDF-NS. The high plasma adiponectin level in WBKDF-NS compared with that in Wistar-NS was further enhanced in WBKDF-HS. Glycogen deposits and fat droplets in the livers of WBKDF-HS were reduced compared with those of WBKDF-NS. The present study demonstrated that HS intake ameliorated hyperglycemia and insulin resistance in WBKDF rats, which may be due to increased plasma levels of adiponectin.

  4. Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats

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    Zhiyan Tian

    2016-12-01

    Full Text Available Aims: To investigate the effects of resveratrol on cognitive impairment in streptozotocin (STZ-induced diabetic rats and to explore the mechanisms of that phenomenon. Methods: Sixty healthy male Sprague Dawley rats were randomly divided into four groups: normal control group (Con group, n = 15, Res group (normal Sprague Dawley rats treated with resveratrol, n = 15, diabetes mellitus group (DM group, n = 15 and DM + Res group (diabetic rats treat with resveratrol, n = 15. Streptozotocin (STZ was injected intraperitoneally to establish the diabetic model. One week after diabetic model induction, the animals in the Res group and the DM + Res group received resveratrol intraperitoneally once a day for consecutive 4 weeks. The Morris water maze test was applied to assess the effect of resveratrol on learning and memory. To explore the mechanisms of resveratrol on cognition, we detected the protein expression levels of Caspase-3, Bcl-2, Bax, NMDAR1 (N-Methyl-d-Aspartate receptor and BDNF (Brain Derived Neurotrophic Factor via western blotting analysis. Results: Resveratrol has no obvious effect on normal SD rats. Compared to Con group, cognitive ability was significantly impaired with increased expression of Caspase-3, Bax and down-regulation of Bcl-2, NMDAR1 and BDNF in diabetic rats. By contrast, resveratrol treatment improved the cognitive decline. Evidently, resveratrol treatment reversed diabetes-induced changes of protein expression. Conclusions: Resveratrol significantly ameliorates cognitive decline in STZ-induced diabetic model rats. The potential mechanism underlying the protective effect could be attributed to the inhibition of hippocampal apoptosis through the Bcl-2, Bax and Caspase-3 signaling pathways and improvement of synaptic dysfunction. BDNF may also play an indispensable role in this mechanism.

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

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    Samad Akbarzadeh

    2018-03-01

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

  6. Prediction of Methionine and Homocysteine levels in Zucker diabetic fatty (ZDF) rats as a T2DM animal model after consumption of a Methionine-rich diet

    OpenAIRE

    Han, Nayoung; Chae, Jung-woo; Jeon, Jihyun; Lee, Jaeyeon; Back, Hyun-moon; Song, Byungjeong; Kwon, Kwang-il; Kim, Sang Kyum; Yun, Hwi-yeol

    2018-01-01

    Background Although alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fat...

  7. Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

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    Luciane B. Ceretta

    2012-01-01

    Full Text Available Diabetes Mellitus (DM is associated with pathological changes in the central nervous system (SNC as well as alterations in oxidative stress. Thus, the main objective of this study was to evaluate the effects of the animal model of diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced in Wistar rats by using a single injection of alloxan (150 mg/kg, and fifteen days after induction, the rats memory was evaluated through the use of the object recognition task. The oxidative stress parameters and the activity of antioxidant enzymes, superoxide dismutase (SOD, and catalase (CAT were measured in the rat brain. The results showed that diabetic rats did not have alterations in their recognition memory. However, the results did show that diabetic rats had increases in the levels of superoxide in the prefrontal cortex, and in thiobarbituric acid reactive species (TBARS production in the prefrontal cortex and in the amygdala in submitochondrial particles. Also, there was an increase in protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the striatum and amygdala. The SOD activity was decreased in diabetic rats in the striatum and amygdala. However, the CAT activity was increased in the hippocampus taken from diabetic rats. In conclusion, our findings illustrate that the animal model of diabetes induced by alloxan did not cause alterations in the animals’ recognition memory, but it produced oxidants and an imbalance between SOD and CAT activities, which could contribute to the pathophysiology of diabetes.

  8. Analgesic synergism of gabapentin and carbamazepine in rat model ...

    African Journals Online (AJOL)

    Analgesic synergism of gabapentin and carbamazepine in rat model of diabetic neuropathic pain. Sinan Mohammed Abdullah AL-Mahmood, Shahrin Tarmizi Bin Che Abdullah, Nik Nur Fatnoon Nik Ahmad, Abdul Hadi Bin Mohamed, Tariq Abdul Razak ...

  9. Diabetes and hypertension in rodent models.

    Science.gov (United States)

    Klöting, I; Berg, S; Kovács, P; Voigt, B; Vogt, L; Schmidt, S

    1997-09-20

    As shown by ourselves and others, animals models closely resembling human complex diseases like IDDM in BB/OK and hypertension in SHR/Mol rats can be used to dissect a complex disease into discrete genetic factors as has been done for hypertension in (BB/OK x SHR/Mol) cross hybrids. Discrete genetic factors, so-called QTLs, were detected on chromosomes 1, 10, 18, 20, and X. To gain additional information about the physiologic effect of the mapped blood pressure QTLs, genetically defined regions of the SHR rat were transferred onto the genetic background of diabetes-prone BB/OK rats. Four new congenic BB.SHR rats named BB.Sa, BB.Bp2, BB.1K, and BB.Xs were generated and characterized telemetrically for blood pressure, heart rate, and motor activity. The data demonstrate clearly that each single blood pressure QTL of the SHR rat causes a significant increase of the systolic blood pressure and has a different influence on diastolic blood pressure, heart rate, and motor activity. The effects were modified differently by the diabetic state in BB.Sa, BB.Bp2, and BB.Xs rats carrying all diabetogenic genes of the BB/OK rats. The results demonstrate that these newly established congenic strains are a unique tool to study the physiological control of blood pressure by a single blood pressure QTL on the one hand and their interaction with hyperglycemia on the other. It is well within the bounds of possibility that diabetic congenics reflect the diabetic hypertension seen in diabetic patients. Because of the synteny conservation in gene order between different mammals, genes of the appropriate human region could therefore be candidate genes for hypertension in diabetics. Furthermore, these congenic strains can also be used to study interactions between a blood pressure QTL and various selected environmental conditions. In this way, one could learn which QTL can be influenced by environmental factors and to what extent. Another point is the study of gene interactions. Because

  10. Effects of compound K on hyperglycemia and insulin resistance in rats with type 2 diabetes mellitus.

    Science.gov (United States)

    Jiang, Shuang; Ren, Dayong; Li, Jianrui; Yuan, Guangxin; Li, Hongyu; Xu, Guangyu; Han, Xiao; Du, Peige; An, Liping

    2014-06-01

    Compound K (CK) is a final metabolite of panaxadiol ginsenosides from Panax ginseng. Although anti-diabetic activity of CK has been reported in recent years, the molecular mechanism of CK in the treatment of diabetes mellitus remains unclear. In the present investigation, we established a rat model of type 2 diabetes mellitus (T2DM) with insulin resistance using high-fat diet (HFD) and streptozotocin (STZ), and attempted to verify more details and exact mechanisms in the treatment of T2DM. CK was administered orally at three doses [300, 100 and 30 mg/kg bodyweight (b.w.)] to the diabetic rats. Bodyweight, food-intake, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity (ISI), total glycerin (TG), total cholesterol (TC), as well as oral glucose tolerance test (OGTT) were evaluated in normal and diabetic rats. According to our results, CK could improve bodyweight and food-intake of diabetic rats. CK exhibited dose-dependent reduction of FBG, TG and TC of diabetic rats. CK treatment also enhanced FINS and ISI. Meanwhile, the glucose tolerance observed in the present study was improved significantly by CK. It is concluded from the results that CK may have improving effects on hyperglycemia and insulin resistance of diabetic rats. Furthermore, research showed that CK could promote the expression of InsR, IRS1, PI3Kp85, pAkt and Glut4 in skeletal muscle tissue of diabetic rats. These results indicate that the hypoglycemic activity of CK is mediated by improvement of insulin sensitivity, which is closely related to PI3K/Akt signaling pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. 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.

  12. Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats.

    Science.gov (United States)

    Sun, Yan-Na; Liu, Li-Bo; Xue, Yi-Xue; Wang, Ping

    2015-04-01

    This study investigates the effect of insulin combined with idebenone on blood-brain barrier (BBB) permeability in experimental streptozotocin-induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ-associated proteins occludin, and zonula occludens (ZO)-1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end-products (RAGE) and nuclear factor-κB (NF-κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin-5, and ZO-1 and that the ROS/AGE/RAGE/NF-κB signal pathway might be involved in the process. © 2014 Wiley Periodicals, Inc.

  13. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes.

    Science.gov (United States)

    Kodera, Ryo; Shikata, Kenichi; Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro; Usui, Hitomi Kataoka; Makino, Hirofumi

    2014-01-17

    Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Five-week-old male Sprague-Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  14. Loss of coupling between calcium influx, energy consumption and insulin secretion associated with development of hyperglycaemia in the UCD-T2DM rat model of type 2 diabetes.

    Science.gov (United States)

    Rountree, A M; Reed, B J; Cummings, B P; Jung, S-R; Stanhope, K L; Graham, J L; Griffen, S C; Hull, R L; Havel, P J; Sweet, I R

    2013-04-01

    Previous studies on isolated islets have demonstrated tight coupling between calcium (Ca(2+)) influx and oxygen consumption rate (OCR) that is correlated with insulin secretion rate (ISR). To explain these observations, we have proposed a mechanism whereby the activation of a highly energetic process (Ca(2+)/metabolic coupling process [CMCP]) by Ca(2+) mediates the stimulation of ISR. The aim of the study was to test whether impairment of the CMCP could play a role in the development of type 2 diabetes. Glucose- and Ca(2+)-mediated changes in OCR and ISR in isolated islets were compared with the time course of changes of plasma insulin concentrations observed during the progression to hyperglycaemia in a rat model of type-2 diabetes (the University of California at Davis type 2 diabetes mellitus [UCD-T2DM] rat). Islets were isolated from UCD-T2DM rats before, 1 week, and 3 weeks after the onset of hyperglycaemia. Glucose stimulation of cytosolic Ca(2+) and OCR was similar for islets harvested before and 1 week after the onset of hyperglycaemia. In contrast, a loss of decrement in islet OCR and ISR in response to Ca(2+) channel blockade coincided with decreased fasting plasma insulin concentrations observed in rats 3 weeks after the onset of hyperglycaemia. These results suggest that phenotypic impairment of diabetic islets in the UCD-T2DM rat is downstream of Ca(2+) influx and involves unregulated stimulation of the CMCP. The continuously elevated levels of CMCP induced by chronic hyperglycaemia in these islets may mediate the loss of islet function.

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

    Directory of Open Access Journals (Sweden)

    Qinna NA

    2015-05-01

    altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents and insulin delivery systems. Keywords: protein delivery, animal model, diabetes mellitus, experimental, antidiabetic agents, streptozotocin 

  16. The effect of oral administration of Withania somnifera root on formalin-induced pain in diabetic rats

    Directory of Open Access Journals (Sweden)

    Mohsen Khalili

    2009-01-01

    Full Text Available Abstract  Introduction: Hyperalgesia is considered as one the marked signs of subchronic diabetes mellitus that could affect the life style of the patients. With c onsidering the potential anti-diabetic effect of the medicinal plant Withania somnifera (WS( ashwagandha, this study was designed to investigate the analgesic effect of WS on formalin-induced nociceptive responses (standard formalin test in diabetic rats. Methods: Rats were divided into control, WS-treated control, diabetic, sodium salicylate (SS-treated control and diabetic and WS-treated diabetic groups. For induction of diabetes, streptozotocin (STZ was used at a single dose. The treatment groups received oral administration of ashwagandha -mixed rat pellet (6.25% for two months.  Results: The results showed that diabetic rats exhibited a higher score of pain at both phases of the formalin test and WS-treated diabetic rats exhibited a lower nociceptive score at both phases of the test (p<0.05. Meanwhile, SS administration significantly reduced pain score only at chronic phase of the test in the diabetic group (p<0.01.   Discussion: Taken together, these results indicate that two-month administration of ashwagandha could attenuate nociceptive score in an experimental model of diabetes mellitus and this may be considered as a potential treatment for painful diabetic neuropathy.

  17. The effect of oral administration of Withania somnifera root on formalin-induced pain in diabetic rats

    Directory of Open Access Journals (Sweden)

    Mohsen Khalili

    2009-01-01

    Full Text Available   Abstract  Introduction: Hyperalgesia is considered as one the marked signs of subchronic diabetes mellitus that could affect the life style of the patients. With c onsidering the potential anti-diabetic effect of the medicinal plant Withania somnifera (WS( ashwagandha, this study was designed to investigate the analgesic effect of WS on formalin-induced nociceptive responses (standard formalin test in diabetic rats. Methods: Rats were divided into control, WS-treated control, diabetic, sodium salicylate (SS-treated control and diabetic and WS-treated diabetic groups. For induction of diabetes, streptozotocin (STZ was used at a single dose. The treatment groups received oral administration of ashwagandha -mixed rat pellet (6.25% for two months.  Results: The results showed that diabetic rats exhibited a higher score of pain at both phases of the formalin test and WS-treated diabetic rats exhibited a lower nociceptive score at both phases of the test (p<0.05. Meanwhile, SS administration significantly reduced pain score only at chronic phase of the test in the diabetic group (p<0.01.   Discussion: Taken together, these results indicate that two-month administration of ashwagandha could attenuate nociceptive score in an experimental model of diabetes mellitus and this may be considered as a potential treatment for painful diabetic neuropathy.  

  18. Evaluation of Protein Kinase Cβ and PPARγ Activity in Diabetic Rats Supplemented with Momordica charantia.

    Science.gov (United States)

    Chandru, Swetha; Vishwanath, Prashant; Devegowda, Devananda; Ramasamudra, Suresha Nagaraja; Prashant, Akila; Hathur, Basavanagowdappa

    2016-04-01

    The present study was taken up to compare and evaluate the effect of Momordica charantia supplementation with pioglitazone on PKC-β and PPAR-γ activity in kidneys of diabetic rats. The hypoglycaemic and lipid lowering effect of Momordica charantia were screened in laboratory animal model and its potency was compared with a Thiazolidinedione (TZD) group antidiabetic drug like pioglitazone. Adult healthy albino rats of Wistar strain aged 3-4months, weighing between 170-250gm of either sex were divided into 4 groups; Group 1 (normal controls), Group 2 (diabetic controls), Group 3 (diabetic rats treated with pioglitazone) and Group 4 (diabetic rats treated with bitter melon juice). Type 1 Diabetes was induced in rats by intraperitoneal injection of streptozotocin at a dose of 55 mg/kg body weight, following which glucose levels were estimated by Accu chek- active glucometer on day 0, 7, 14, 21 and 28 days to assess the efficacy of Bitter Melon Juice (BMJ) and pioglitazone. After 28 days of treatment, the rats were sacrificed and blood collected from abdominal vena cava was used for estimation of triglycerides by Glycerol 3 phosphate oxidase phenol aminophenazone method and cholesterol by Cholestrol oxidase phenol aminophenazone method. PKC-β and PPAR-γ were estimated in the dissected kidneys by using double sandwich ELISA based kits on an automated plate reader. BMJ significantly reduced blood glucose levels in group 4 as compared to diabetic controls (pdiabetic animal models. BMJ increases PPAR-γ activity and decreases PKC-β activity in kidneys of diabetic rats, thereby preventing the complications of diabetes mellitus. Fresh BMJ mimics action of pioglitazone belonging to TZD group thus showing a potential for further research in identifying the active molecules responsible for glucose and lipid lowering action.

  19. Associations among the cecal microbiome and bacterially-derived cecal xeno-metabolites during diabetes progression in the UC Davis-Type 2 diabetes rat model

    Science.gov (United States)

    The gut microbiome is altered in obesity and diabetes, but the molecular signals linking gut microbes and host metabolic regulation have not been established. Our aim was to identify gut microbe-derived xeno-metabolites that associate with alterations in the microbiome during the progression of a t...

  20. Intraperitoneal administration of the globular adiponectin gene ameliorates diabetic nephropathy in Wistar rats.

    Science.gov (United States)

    Yuan, Fang; Liu, Ying-Hong; Liu, Fu-You; Peng, You-Ming; Tian, Jun-Wei

    2014-06-01

    The present study investigated the potential effects of the long-term expression of exogenous adiponectin (ADPN) on normal and diabetic kidneys. Type 2 diabetes mellitus models were induced by high-lipid and high-sucrose feeding plus intraperitoneal injection of streptozotocin. The recombinant plasmid pIRES2-EGFP-gAd, which is able to co-express globular ADPN (gAd) and enhanced green fluorescent protein (EGFP), was intraperitoneally injected into rat models mediated by Lipofectamine. In total, 32 Wistar rats were randomly assigned into four groups: the normal control group, the diabetes group, the diabetes group treated with pIRES2-EGFP-gAd and the diabetes group treated with pIRES2-EGFP. After 12 weeks, serum biochemistry and urine albumin levels were measured. The kidneys were collected to assess the generation of reactive oxygen species (ROS) and the renal pathological changes were observed by light microcopy. The protein expression of endothelial nitric oxide synthase (eNOS), transforming growth factor-β1 (TGF-β1) and phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were determined by an immunohistochemical staining method and western blot analysis. Intraperitoneal injection of the human gAd gene via Lipofectamine resulted in abundant ADPN protein in the kidney. In the diabetic rats, the delivery of the exogenous gAd gene ameliorated the progression of diabetic nephropathy (DN). ADPN attenuated urine albumin excretion in the diabetic rats. ADPN also mitigated glomerular mesangial expansion, reduced the generation of ROS and prevented interstitial fibrosis. In addition, the expression of gAd inhibited the renal expression of TGF-β1, promoted the protein expression of eNOS and activated the opening of the AMPK signaling pathway in the renal tissues of the diabetic rats. Despite the effects of ADPN on DN being controversial, these observations indicate that the supplementation of ADPN is beneficial in ameliorating DN in rats.

  1. Effects of streptozotocin-induced diabetes on the pharmacology of rat conduit and resistance intrapulmonary arteries

    Directory of Open Access Journals (Sweden)

    Howarth Frank C

    2009-01-01

    Full Text Available Abstract Background Poor control of blood glucose in diabetes is known to promote vascular dysfunction and hypertension. Diabetes was recently shown to be linked to an increased prevalence of pulmonary hypertension. The aim of this study was to determine how the pharmacological reactivity of intrapulmonary arteries is altered in a rat model of diabetes. Methods Diabetes was induced in rats by the β-cell toxin, streptozotocin (STZ, 60 mg/kg, and isolated conduit and resistance intrapulmonary arteries studied 3–4 months later. Isometric tension responses to the vasoconstrictors phenylephrine, serotonin and PGF2α, and the vasodilators carbachol and glyceryl trinitrate, were compared in STZ-treated rats and age-matched controls. Results STZ-induced diabetes significantly blunted the maximum response of conduit, but not resistance pulmonary arteries to phenylephrine and serotonin, without a change in pEC50. Agonist responses were differentially reduced, with serotonin (46% smaller affected more than phenylephrine (32% smaller and responses to PGF2α unaltered. Vasoconstriction caused by K+-induced depolarisation remained normal in diabetic rats. Endothelium-dependent dilation to carbachol and endothelium-independent dilation to glyceryl trinitrate were also unaffected. Conclusion The small resistance pulmonary arteries are relatively resistant to STZ-induced diabetes. The impaired constrictor responsiveness of conduit vessels was agonist dependent, suggesting possible loss of receptor expression or function. The observed effects cannot account for pulmonary hypertension in diabetes, rather the impaired reactivity to vasoconstrictors would counteract the development of pulmonary hypertensive disease.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  3. 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.)

  4. Brain glycogen and its role in supporting glutamate and GABA homeostasis in a type 2 diabetes rat model

    DEFF Research Database (Denmark)

    Sickmann, Helle Mark; Waagepetersen, Helle S.; Schousboe, Arne

    2012-01-01

    The number of people suffering from diabetes is hastily increasing and the condition is associated with altered brain glucose homeostasis. Brain glycogen is located in astrocytes and being a carbohydrate reservoir it contributes to glucose homeostasis. Furthermore, glycogen has been indicated...

  5. MicroRNA-24 Attenuates Neointimal Hyperplasia in the Diabetic Rat Carotid Artery Injury Model by Inhibiting Wnt4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jian Yang

    2016-05-01

    Full Text Available The long-term stimulation of hyperglycemia greatly increases the incidence of vascular restenosis (RS after angioplasty. Neointimal hyperplasia after vascular injury is the pathological cause of RS, but its mechanism has not been elucidated. MicroRNA-24 (miR-24 has low expression in the injured carotid arteries of diabetic rats. However, the role of miR-24 in the vascular system is unknown. In this study, we explore whether over-expression of miR-24 could attenuate neointimal formation in streptozotocin (STZ-induced diabetic rats. Adenovirus (Ad-miR-24-GFP was used to deliver the miR-24 gene to injured carotid arteries in diabetic rats. The level of neointimal hyperplasia was examined by hematoxylin-eosin (HE staining. Vascular smooth muscle cell (VSMC proliferation in the neointima was evaluated by immunostaining for proliferating cell nuclear antigen (PCNA. The mRNA levels of miR-24, PCNA, wingless-type MMTV integration site family member 4 (Wnt4, disheveled-1 (Dvl-1, β-catenin and cell cycle-associated molecules (Cyclin D1, p21 were determined by Quantitative Real-Time PCR (qRT-PCR. PCNA, Wnt4, Dvl-1, β-catenin, Cyclin D1 and p21 protein levels were measured by Western blotting analysis. STZ administration decreased plasma insulin and increased fasting blood glucose in Sprague-Dawley (SD rats. The expression of miR-24 was decreased in the carotid artery after a balloon injury in diabetic rats, and adenoviral transfection (Ad-miR-24-GFP increased the expression of miR-24. Over-expression of miR-24 suppressed VSMC proliferation and neointimal hyperplasia in diabetic rats at 14 days. Furthermore, compared with Sham group, the mRNA and protein levels of PCNA, Wnt4, Dvl-1, β-catenin, and Cyclin D1 were strikingly up-regulated in the carotid arteries of diabetic rats after a balloon injury. Interestingly, up-regulation of miR-24 significantly reduced the mRNA and protein levels of these above molecules. In contrast, the change trend in p21 m

  6. Metabolic alteration in obese diabetes rats upon treatment with Centella asiatica extract.

    Science.gov (United States)

    Maulidiani; Abas, F; Khatib, A; Perumal, V; Suppaiah, V; Ismail, A; Hamid, M; Shaari, K; Lajis, N H

    2016-03-02

    'Pegaga' is a traditional Malay remedy for a wide range of complaints. Among the 'pegaga', Centella asiatica has been used as a remedy for diabetes mellitus. Thus, we decided to validate this claim by evaluating the in vivo antidiabetic property of C. asiatica (CA) on T2DM rat model using the holistic (1)H NMR-based metabolomics approach. In this study, an obese diabetic (mimic of T2DM condition) animal model was developed using Sprague-Dawley rats fed with a high-fat diet and induced into diabetic condition by the treatment of a low dose of streptozotocin (STZ). The effect of C. asiatica extract on the experimental animals was followed based on the changes observed in the urinary and serum metabolites, measured by (1)H NMR of urine and blood samples collected over the test period. A long-term treatment of obese diabetic rats with CA extract could reverse the glucose and lipid levels, as well as the tricarboxylic acid cycle and amino acid metabolic disorders, back towards normal states. Biochemical analysis also showed an increase of insulin production in diabetic rats upon treatment of CA extract. This study has provided evidence that clearly supported the traditional use of CA as a remedy for diabetes. NMR-based metabolomics was successfully applied to show that CA produced both anti-hyperglycemic and anti-hyperlipidemic effects on a rat model. In addition to increasing the insulin secretion, the CA extract also ameliorates the metabolic pathways affected in the induced diabetic rats. This study further revealed the potential usage of CA extract in managing diabetes mellitus and the results of this work may contribute towards the further understanding of the underlying molecular mechanism of this herbal remedy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. 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.

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

    Science.gov (United States)

    Whitney, Jennifer L; Bilkan, Christine Maric; Sandberg, Kathryn; Myers, Adam K; Mulroney, Susan E

    2013-01-01

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

  9. Molecular basis of bilirubin UDP-glucuronosyltransferase induction in spontaneously diabetic rats, acetone-treated rats and starved rats.

    Science.gov (United States)

    Braun, L; Coffey, M J; Puskás, F; Kardon, T; Nagy, G; Conley, A A; Burchell, B; Mandl, J

    1998-01-01

    The co-ordinated induction of several hepatic drug-metabolizing enzymes is a common feature in the regulation of drug biotransformation under normal and pathological conditions. In the present study the activity and expression of bilirubin UDP-glucuronosyltransferase (UGT1A1) were investigated in livers of BioBreeding/Worcester diabetic, fasted and acetone-treated rats. Bilirubin glucuronidation was stimulated by all three treatments; this was correlated with an increase in the UGT1A1 protein concentration in hepatic microsomes. Transcriptional induction of UGT1A1 was also observed in diabetes and starvation but not with acetone treatment, which apparently caused translational stabilization of the enzyme protein. The hormonal/metabolic alterations in diabetes and starvation might be a model for postnatal development. The sudden interruption of maternal glucose supply signals the enhanced expression of UGT1A1, giving a novel explanation for the physiological induction of bilirubin glucuronidation in newborn infants. PMID:9841869

  10. Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats

    DEFF Research Database (Denmark)

    Hartmann, Bolette; Thulesen, Jesper; Hare, Kristine Juul

    2002-01-01

    in the proximal part of the small intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight, blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2 in a model of adaptive intestinal growth reduces the growth response, providing strong evidence for a physiological......Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to induce intestinal growth by increasing villus height and crypt depth and by decreasing apoptosis, but a physiological effect of GLP-2 has not yet been demonstrated. Earlier, we found elevated levels of endogenous GLP-2...... in untreated streptozotocin diabetic rats associated with marked intestinal growth. In the present study, we investigated the role of endogenous GLP-2 for this adaptive response. We included four groups of six rats: (1) diabetic rats treated with saline, (2) diabetic rats treated with non-specific antibodies...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Broccoli (Brassica oleracea) Reduces Oxidative Damage to Pancreatic Tissue and Combats Hyperglycaemia in Diabetic Rats.

    Science.gov (United States)

    Suresh, Sithara; Waly, Mostafa Ibrahim; Rahman, Mohammad Shafiur; Guizani, Nejib; Al-Kindi, Mohamed Abdullah Badar; Al-Issaei, Halima Khalfan Ahmed; Al-Maskari, Sultan Nasser Mohd; Al-Ruqaishi, Bader Rashid Said; Al-Salami, Ahmed

    2017-12-01

    Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli ( Brassica oleracea ) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats. Streptozotocin (STZ) drug was used as a diabetogenic agent in a single intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level for each rat was measured twice a week. After 8 weeks, all animals were fasted overnight and sacrificed; pancreatic tissues were homogenized and used for measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and total antioxidant capacity (TAC) as well as histopathological examination for pancreatic tissues was examined. Diabetic rats showed significantly higher levels of DNA damage, GSH depletion, and impaired TAC levels in comparison to non-diabetics ( P <0.05). The treatment of diabetic rats with BE significantly reduced DNA damage and conserved GSH and TAC values ( P <0.01). BE attenuated pancreatic histopathological changes in diabetic rats. The results of this study indicated that BE reduced the STZ mediated hyperglycaemia and the STZ-induced oxidative injury to pancreas tissue. The used in vivo model confirmed the efficacy of BE as an anti-diabetic herbal medicine and provided insights into the capacity of BE to be used for phytoremediation purposes for human type 2 diabetes.

  13. Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in Rats.

    Directory of Open Access Journals (Sweden)

    TingTing Zhao

    Full Text Available Inflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF, a traditional Chinese medicine, on DN.Protective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined.We found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-κB signaling, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1β, TNFα, chemokine (MCP-1, and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-β/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-β/Smad3 and NF-κB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7.The present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-κB-driven renal inflammation and TGF-β/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN.

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Differences and similarities in development of corneal nerve damage and peripheral neuropathy and in diet-induced obesity and type 2 diabetic rats.

    Science.gov (United States)

    Davidson, Eric P; Coppey, Lawrence J; Kardon, Randy H; Yorek, Mark A

    2014-03-03

    Peripheral neuropathy has been shown to exist in prediabetic and diabetic patients and animal models. However, the development of peripheral neuropathy in prediabetes and posthyperglycemia is likely different. The purpose of this study was to examine the progression of peripheral neuropathy in diet-induced obese rats and high-fat-fed rats treated with a low dose of streptozotocin, a model for type 2 diabetes, using standard endpoints as well as corneal sensitivity and innervation. Diet-induced obese rats and high-fat/low-dose streptozotocin diabetic rats were used to examine standard peripheral neuropathy endpoints and innervation of the cornea and corneal epithelium using corneal and standard confocal microscopy, respectively, and corneal sensitivity using a Cochet-Bonnet esthesiometer at three different time points. Obese rats and to a greater extent diabetic rats were insulin resistant. Obese and diabetic rats had developed sensory nerve deficits, but only diabetic rats had motor nerve dysfunction as determined by measuring nerve conduction velocity, thermal nociception, and intraepidermal nerve fiber density. In the cornea there was a decrease in corneal nerve fiber length, innervation of the corneal epithelium, and corneal sensitivity in both diet-induced obese and diabetic rats. These studies demonstrate that changes in corneal nerve innervation and sensitivity occur in both obese and type 2 diabetic rat models that are consistent with development of peripheral neuropathy. Examination of corneal nerve changes may be valuable endpoints for exploring potential treatments for peripheral neuropathy in both prediabetes with insulin resistance and diabetes.

  16. Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters

    Directory of Open Access Journals (Sweden)

    Yuri Karen Sinzato

    2012-01-01

    Full Text Available The aim of this study was to assess placental changes and reproductive outcomes in neonatally induced mild diabetic dams and fetal development in their offspring. At birth, female rats were assigned either to control or diabetic group (100 mg of streptozotocin/Kg, subcutaneously. At adulthood, the female rats were mated. During pregnancy, the blood glucose levels and glucose and insulin tolerance tests were performed. At term, maternal reproductive outcomes, fetal and placental weight, and placental morphology were analyzed. Diabetic rats had smaller number of living fetuses, implantations and corpora lutea, and increased rate of embryonic loss. Placenta showed morphometric alterations in decidua area. Our results showed that mild diabetes was sufficient to trigger alterations in maternal organism leading to impaired decidua development contributing to failure in embryonic implantation and early embryonic losses. Regardless placental decidua alteration, the labyrinth, which is responsible for the maternal-fetal exchanges, showed no morphometric changes contributing to an appropriate fetal development, which was able to maintain normal fetal weight at term in mild diabetic rats. Thus, this experimental model of diabetes induction at the day of birth was more effective to reproduce the reproductive alterations of diabetic women.

  17. Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

    Science.gov (United States)

    Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

    2010-01-01

    Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

  18. 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.

  19. Diabetes alters aromatase enzyme levels in sciatic nerve and hippocampus tissues of rats.

    Science.gov (United States)

    Burul-Bozkurt, Nihan; Pekiner, Can; Kelicen, Pelin

    2010-04-01

    Diabetes mellitus (DM) is associated with increased risk of impaired cognitive function. Diabetic neuropathy is one of the most common and important complications of DM. Estrogens prevent neuronal loss in experimental models of neurodegeneration and accelerate nerve regeneration. Aromatase catalyzes the conversion of androgens to estrogens and expressed in a variety of tissues including neurons. Although insulin is known to regulate the activity of aromatase there is no study about the effects of diabetes on this enzyme. Present study was designed to investigate the effects of experimental diabetes on aromatase expression in nervous system. Gender-based differences were also investigated. Rats were injected with streptozotocin to induce diabetes. At the end of 4 and 12 weeks sciatic nerve and hippocampus homogenates were prepared and evaluated for aromatase proteins. Aromatase expressions in sciatic nerves of both genders were decreased in 4 weeks of diabetes, but in 12 weeks the enzyme levels were increased in females and reached to control levels in male animals. Aromatase levels were not altered in hippocampus at 4 weeks but increased at 12 weeks in female diabetic rats. No significant differences were observed at enzyme levels of hippocampus in male diabetic rats. Insulin therapy prevented all diabetes-induced changes. In conclusion, these results indicated for the first time that, DM altered the expression of aromatase both in central and peripheral nervous systems. Peripheral nervous system is more vulnerable to damage than central nervous system in diabetes. These effects of diabetes differ with gender and compensatory neuroprotective mechanisms are more efficient in female rats.

  20. Effects of TNF-α blocking on experimental periodontitis and type 2 diabetes in obese diabetic Zucker rats.

    Science.gov (United States)

    Grauballe, Morten Bay; Østergaard, Jakob Appel; Schou, Søren; Flyvbjerg, Allan; Holmstrup, Palle

    2015-09-01

    Tumour necrosis factor α (TNF-α) is considered a key signalling modulator in the pathogenesis of both periodontitis (PD) and type 2 diabetes mellitus (DM2). This study aims at elucidating the effect of TNF-α blocking on the interplay between PD and DM2. Obese diabetic Zucker rats and their lean littermates were divided into five treatment groups with or without periodontitis. Anti-TNF-α treatment was provided with Etanercept injections. Diabetic state was evaluated by oral glucose tolerance test, the homeostatic model assessment, free fatty acids and blood glucose. Systemic inflammation was assessed by measurement of interleukin (IL)-1β, IL-6 and TNF-α in plasma. Kidney complications were evaluated by real-time rtPCR, creatinine clearance rate, urinary albumin excretion and increase in weight. PD was evaluated by registration of alveolar bone level. After 4 weeks the diabetic state was modified by Etanercept treatment with lower insulin levels and lower homeostatic model assessment. Furthermore, while kidney complications were reduced by Etanercept treatment, PD had no effect. PD was influenced by diabetic state, but the impact was attenuated by Etanercept treatment. In this study anti-TNF-α treatment improved glucose tolerance and compensated for the increased periodontal disease in obese diabetic Zucker. PD did not influence diabetic parameters assessed including complications of the rats kidneys. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Ixeris dentata Extract Increases Salivary Secretion through the Regulation of Endoplasmic Reticulum Stress in a Diabetes-Induced Xerostomia Rat Model

    Directory of Open Access Journals (Sweden)

    Kashi Raj Bhattarai

    2018-04-01

    Full Text Available This study aimed to investigate the molecular mechanism of diabetes mellitus (DM-induced dry mouth and an application of natural products from Ixeris dentata (IXD, a recently suggested regulator of amylase secretion in salivary cells. Vehicle-treated or diabetic rats were orally treated with either water or an IXD extract for 10 days to observe the effect on salivary flow. We found that the IXD extract increased aquaporin 5 (AQP5 and alpha-amylase protein expression in the submandibular gland along with salivary flow rate. Similarly, the IXD extract and its purified compound increased amylase secretion in high glucose-exposed human salivary gland cells. Furthermore, increased endoplasmic reticulum stress response in the submandibular gland of diabetic rats was inhibited by treatment with the IXD extract, suggesting that IXD extract treatment improves the ER environment by increasing the protein folding capacity. Thus, pharmacological treatment with the IXD extract is suggested to relieve DM-induced dry mouth symptoms.

  2. [Nephro-protective effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats].

    Science.gov (United States)

    Kuang, Qiao-Ting; Zhao, Jing-Jing; Ye, Chun-Ling; Wang, Jing-Ru; Ye, Kai-He; Zhang, Xiao-Qi; Wang, Ying; Ye, Wen-Cai

    2012-01-01

    To investigate the nephro-protective effects of total triterpenoids from Psidium guajava leaves (TTPGL) on type 2 diabetic rats. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) and a high-fat diet. Diabetic rats were divided into five groups: diabetic model control, low-dose TTPGL-treated (60 mg/kg, L-TTPGL), medium-dose TTPGL-treated (120 mg/kg, M-TTPGL), high-dose TTPGL-treated (240 mg/kg, H-TTPGL) and rosiglitazone-treated (3 mg/kg, RSG). The rats received daily treatment for six weeks. At the end of the period,the levels of fasting blood glucose (FPG), fasting insulin (FINS), creatinine (Cr) and blood urea nitrogen (BUN) in serum were measured. Kidneys for histopathological evaluation were stained with Hematoxylin and Eosin (HE). Compared with normal control group, the level of FPG was increased, the insulin and insulin sensitivity index were decreased in the model group; The levels of BUN and Cr were increased with histopathological changes related to diabetic nephropathy in the kidney, which were the glomerular endothelium and mesangial cell proliferation, capillary narrowed, the base-membrane incrassation, glomerular swelling, cysts narrowed and tubules edema. Compared with the model group, the levels of FPG were decreased, serum insulin and insulin sensitivity index were increased significantly in M-TTPGL and H-TTPGL groups (P<0.01 or P<0.05); The levels of BUN and Cr were decreased significantly (P<0.01 or P<0.05) and the renal structural damages were improved significantly. TTPGL could decrease the level of blood glucose of diabetic rat effectively, increase the insulin sensitivity index and protect renal lesions in diabetic rats.

  3. Increased intraretinal PO2 in short-term diabetic rats.

    Science.gov (United States)

    Lau, Jennifer C M; Linsenmeier, Robert A

    2014-12-01

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

  4. The mechanism of hypercalciuria in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Guruprakash, G H; Krothapalli, R K; Rouse, D; Babino, H; Suki, W N

    1988-04-01

    Metabolic studies were performed in streptozotocin-induced diabetic (D) rats and normal control (C) rats to assess the role of hyperphagia in the hypercalciuria of diabetes. Urinary calcium excretion (UCaV) was significantly higher in D v C rats fed ad libitum. When D rats were pair-fed (calorie and mineral restriction) with C rats, UCaV declined but remained significantly higher than in C rats. When D rats were allowed their usual increased calorie intake but restricted to C rat mineral consumption, UCaV remained elevated. These findings suggested a tubular reabsorptive defect. In vivo microinjection studies were then performed to identify the site(s) of the tubular reabsorptive defect. Using 1.0 mmol/L Ca in the injectate, 45Ca recovery in the urine (CaR%) was significantly higher in D rats after intratubular injections into early and late proximal tubules and late distal but not early distal tubules. An additional load-dependent defect was revealed in the terminal nephron when the Ca concentration of the injectate was increased to 1.8 mmol/L. After early distal injection, CaR% was significantly increased in D v C rats. Infusion of PTH into thyroparathyroidectomized C and D rats enhanced Ca absorption to a similar degree but did not correct the reabsorptive defect in D rats. These results argue against a lack of end-organ responsiveness to PTH in diabetes or a low serum PTH level as the cause of the hypercalciuria. We conclude that hyperphagia contributes to the hypercalciuria of diabetes in the absence of increased Ca intake. Also, two tubular reabsorptive defects exist: one in the loop of Henle; the other, load-dependent in the terminal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Berberine alleviates ischemic arrhythmias via recovering depressed I(to) and I(Ca) currents in diabetic rats.

    Science.gov (United States)

    Wang, Li-Hong; Li, Xue-Lian; Li, Qiang; Fu, Ying; Yu, Hai-Jing; Sun, Yu-Qian; Zhang, Li; Shan, Hong-Li

    2012-02-15

    The present study was designed to elucidate the potential mechanism underlying that berberine suppressed ischemic arrhythmias in a rat model of diabetes mellitus (DM). Streptozotocin (STZ)-induced diabetic rats were subjected to ischemia by the occlusion of left anterior descending (LAD) coronary artery. Berberine was orally administered for 7 days before ischemic injury in diabetic rats. Whole-cell patch-clamp was performed to measure the transient outward K⁺ current (I(to)) and L-type Ca²⁺ current (I(Ca)). Results showed that oral administration of berberine (100 mg/kg) attenuated ischemia-induced arrhythmias in diabetic rats. Berberine significantly shortened the prolonged QTc interval from 214 ± 6ms to 189 ± 5ms in ischemic diabetic rats, and also restored the diminished I(to) and I(Ca) current densities in the same animal model rats. In conclusion, the ability of berberine to protect diabetic rats against cardiac arrhythmias makes it possible to be a prospective therapeutic agent in clinical management of cardiac disease secondary to diabetes. Copyright © 2011 Elsevier GmbH. All rights reserved.

  6. Prophylactic L-arginine and ibuprofen delay the development of tactile allodynia and suppress spinal miR-155 in a rat model of diabetic neuropathy.

    Science.gov (United States)

    El-Lithy, Ghada M; El-Bakly, Wesam M; Matboli, Marwa; Abd-Alkhalek, Hadwa A; Masoud, Somaia I; Hamza, May

    2016-11-01

    Diabetic neuropathy (DN) is a common complication of diabetes mellitus that is hardly reversible at the late stages. Since treatment of neuropathic pain is predominantly symptomatic, a prophylactic measure would be useful. Both ibuprofen and L-arginine exert antiallodynic effects on chronic constriction injury (CCI)-induced cold allodynia. Furthermore, ibuprofen is effective in CCI-induced mechanical allodynia. The aim of the study was to assess the antiallodynic effect of prophylactic ibuprofen and L-arginine in streptozotocin-induced DN in rats and to further investigate the role of spinal miR-155 and nitric oxide (NO) in this effect. Tactile allodynia was assessed weekly by von Frey filaments. Oral daily administration of ibuprofen, L-arginine and their combination, for 4 weeks starting 1 week after streptozotocin injection (ie, before the development of tactile allodynia), resulted in a significant decrease of tactile allodynia compared with the control diabetic group. This was evident in the fifth week of the experiment. The 3 treatments prevented the decrease in muscle fiber diameter and epidermal thickness, seen in the control diabetic group. Furthermore, ibuprofen, L-arginine and their combination prevented the increase in the spinal NO level and miRNA-155, seen in the control diabetic group. In conclusion, both ibuprofen and L-arginine delayed the development of behavioral and histologic changes of DN, with concomitant suppression of spinal miR-155 and NO level. L-arginine being tolerable may be useful prophylactically in diabetic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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.

  8. Protective effects of a coumarin derivative in diabetic rats.

    Science.gov (United States)

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

    2009-08-01

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

  9. Glucose cycling in islets from healthy and diabetic rats

    International Nuclear Information System (INIS)

    Khan, A.; Chandramouli, V.; Ostenson, C.G.; Loew, H.L.; Landau, B.R.; Efendic, S.

    1990-01-01

    Pancreatic islets from healthy (control) and neonatally streptozocin-induced diabetic (STZ-D) rats, a model for non-insulin-dependent diabetes mellitus, were incubated with 3 H 2 O and 5.5 or 16.7 mM glucose. At 5.5 mM glucose, no detectable [ 3 H]glucose was formed. At 16.7 mM, 2.2 patom.islet-1.h-1 of 3 H was incorporated into glucose by the control islets and 5.4 patom.islet-1.h-1 by STZ-D islets. About 75% of the 3 H was bound to carbon-2 of the glucose. Glucose utilization was 35.3 pmol.islet-1.h-1 by the control and 19.0 pmol.islet-1.h-1 by the STZ-D islets. Therefore, 4.5% of the glucose-6-phosphate formed by the control islets and 15.7% by the STZ-D islets was dephosphorylated. This presumably occurred in the beta-cells of the islets catalyzed by glucose-6-phosphatase. An increased glucose cycling, i.e., glucose----glucose-6-phosphate----glucose, in islets of STZ-D rats may contribute to the decreased insulin secretion found in these animals

  10. Cblb is a major susceptibility gene for rat type 1 diabetes mellitus.

    Science.gov (United States)

    Yokoi, Norihide; Komeda, Kajuro; Wang, He-Yao; Yano, Hideki; Kitada, Kazuhiro; Saitoh, Yuka; Seino, Yutaka; Yasuda, Kazuki; Serikawa, Tadao; Seino, Susumu

    2002-08-01

    The autoimmune disease type 1 diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) has a multifactorial etiology. So far, the major histocompatibility complex (MHC) is the only major susceptibility locus that has been identified for this disease and its animal models. The Komeda diabetes-prone (KDP) rat is a spontaneous animal model of human type 1 diabetes in which the major susceptibility locus Iddm/kdp1 accounts, in combination with MHC, for most of the genetic predisposition to diabetes. Here we report the positional cloning of Iddm/kdp1 and identify a nonsense mutation in Cblb, a member of the Cbl/Sli family of ubiquitin-protein ligases. Lymphocytes of the KDP rat infiltrate into pancreatic islets and several tissues including thyroid gland and kidney, indicating autoimmunity. Similar findings in Cblb-deficient mice are caused by enhanced T-cell activation. Transgenic complementation with wildtype Cblb significantly suppresses development of the KDP phenotype. Thus, Cblb functions as a negative regulator of autoimmunity and Cblb is a major susceptibility gene for type 1 diabetes in the rat. Impairment of the Cblb signaling pathway may contribute to human autoimmune diseases, including type 1 diabetes.

  11. Effect of magnesium sulfate on renal ischemia-reperfusion injury in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Akan, M; Ozbilgin, S; Boztas, N; Celik, A; Ozkardesler, S; Ergur, B U; Guneli, E; Sisman, A R; Akokay, P; Meseri, R

    2016-04-01

    Ischemia/reperfusion (I/R) injury is a major cause of acute organ dysfunction and I/R related acute renal failure is a common clinical problem. Diabetes mellitus is defined as a risk factor for the development of acute renal injury as diabetic nephropathy compromises the renal tolerance to ischemia. The aim of this study was to investigate the protective effect of magnesium sulfate in a diabetic rat renal I/R injury model. Diabetes mellitus was induced using streptozotocin. Thirty-five rats were divided into five groups: Group I: Nondiabetic sham group; Group II: Diabetic sham group; Group III: Diabetic I/R group; Group IV: Diabetic I/R + prophylactic (preischemic) MgSO4; and Group V: Diabetic I/R + therapeutic (following reperfusion) MgSO4 group. MgSO4 was administered 200 mg/kg intraperitoneally. Renal I/R (45 min ischemia + 4 h reperfusion) was induced in both kidneys. Histomorphological, immunohistochemical (caspase-3 and iNOS) and biochemical (BUN, Creatinine) methods were performed to assess the blood and tissue samples. Histomorphological injury scores and immunostaining intensities (for both caspase-3 and iNOS) were significantly lower in the MgSO4 administered groups (prophylactic and therapeutic) than in the Diabetic IR group. There were no significant differences in biochemical parameters (BUN, Cr) between the MgSO4 administered groups and the Diabetic IR group. In the present study, it was demonstrated by histomorphological and immunohistochemical methods that magnesium sulfate administration before ischemia or following reperfusion significantly reduced renal I/R injury in a diabetic rat model.

  12. 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.

  13. Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats.

    Science.gov (United States)

    Bagi, Cedo M; Edwards, Kristin; Berryman, Edwin

    2017-12-01

    Metabolic syndrome and osteoporosis share similar risk factors. Also, patients with diabetes have a higher risk of osteoporosis and fracture. Liver manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic syndrome are further aggravated in diabetics and often lead to liver failure. Our objective was to create a rat model of human metabolic syndrome and determine the long-term impact of early-onset T1D on bone structure and strength in obese growing rats. Male rats were given either standard chow and RO water (Controls) or a high-fat, high-cholesterol diet and sugar water containing 55% fructose and 45% glucose (HFD). A third group of rats received the HFD diet and a single dose of streptozotocin to induce type 1 diabetes (HFD/Sz). Body weight and glucose tolerance tests were conducted several times during the course of the study. Serum chemistry, liver enzymes, and biomarkers of bone metabolism were evaluated at 10 and 28 weeks. Shear wave elastography and histology were used to assess liver fibrosis. Cancellous bone structure and cortical bone geometry were evaluated by mCT and strength by the 3-point bending method. Body mass and fat accumulation was significantly higher in HFD and HFD/Sz rats compared to Controls. Rats in both the HFD and HFD/Sz groups developed NASH, although the change was more severe in diabetic rats. Although both groups of obese rats had larger bones, their cancellous structure and cortical thickness were reduced, resulting in diminished strength that was further aggravated by diabetes. The HFD and HFD/Sz rats recapitulate MeSy in humans with liver pathology consistent with NASH. Our data provide strong indication that obesity accompanied by type 1 diabetes significantly aggravates comorbidities of MeSy, including the development of osteopenia and weaker bones. The juvenile rat skeleton seems to be more vulnerable to damage imposed by obesity and diabetes and may offer a model to inform the underlying pathology associated

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

    Science.gov (United States)

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

    2005-02-22

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

  15. Brain effect of insulin and clonazepam in diabetic rats under depressive-like behavior.

    Science.gov (United States)

    Wayhs, Carlos Alberto Yasin; Mescka, Caroline Paula; Vanzin, Camila Simioni; Ribas, Graziela Schmitt; Guerreiro, Gilian; Nin, Maurício Schüler; Manfredini, Vanusa; Barros, Helena Maria Tannhauser; Vargas, Carmen Regla

    2013-12-01

    Diabetes mellitus is characterized by hyperglycemia resulting from defects on insulin secretion, insulin action, or both. It has recently become clear that the central nervous system is not spared from the deleterious effects of diabetes, since diabetic encephalopathy was recognized as a complication of this heterogeneous metabolic disorder. There is a well recognized association between depression and diabetes, once prevalence of depression in diabetic patients is higher than in general population, and clonazepam is being used to treat this complication. Oxidative stress is widely accepted as playing a key mediatory role in the development and progression of diabetes and its complications. In this work we analyzed DNA damage by comet assay and lipid damage in prefrontal cortex, hippocampus and striatum of streptozotocin-induced diabetic rats submitted to the forced swimming test. It was verified that the diabetic group presented DNA and lipid damage in the brain areas evaluated, when compared to the control groups. Additionally, a significant reduction of the DNA and lipid damage in animals treated with insulin and/or clonazepam was observed. These data suggest that the association of these two drugs could protect against DNA and lipid damage in diabetic rats submitted to the forced swimming test, an animal model of depression.

  16. Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals

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    Wang X

    2014-11-01

    Full Text Available Xi Wang,1 Debra C DuBois,1,2 Siddharth Sukumaran,2 Vivaswath Ayyar,1 William J Jusko,2,3 Richard R Almon1–3 1Department of Biological Sciences, 2Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA; 3New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA Abstract: Both obesity and chronic inflammation are often associated with insulin resistance and type 2 diabetes. The Zucker diabetic fatty (ZDF rat (fa/fa is an obese animal model frequently used in type 2 diabetes research. The current study determines whether chronic administration (from 5 weeks of age through 24 weeks of age of salsalate, a salicylate with anti-inflammatory properties, would be effective in mitigating diabetes disease progression in ZDF rats. Although a trend existed for lower blood glucose in the salsalate-treated group, significant differences were obscured by high animal-level variability. However, even in the non-drug-treated group, not all ZDF rats became diabetic as expected. Therefore, animals were parsed into two groups, regardless of drug treatment: normoglycemic ZDF rats, which maintained blood glucose profiles identical to nondiabetic Zucker lean rats (ZLRs, and hyperglycemic ZDF rats, which exhibited progressive elevation in blood glucose. To ascertain the differences between ZDF rats that became hyperglycemic and those that did not, relevant physiological indices and expression levels of adiponectin, tumor necrosis factor-α, interleukin-6, and glucocorticoid-induced leucine zipper messenger RNAs in adipose tissue were measured at sacrifice. Plasma C-reactive protein concentrations and expression levels of cytokine and glucocorticoid-induced leucine zipper messenger RNAs suggested more prevalent chronic inflammation in hyperglycemic animals. Early elevation of the insulin-sensitizing adipokine, adiponectin, was present in both ZDF groups, with the rate of its age-related decline

  17. Contribution of thrombin-reactive brain pericytes to blood-brain barrier dysfunction in an in vivo mouse model of obesity-associated diabetes and an in vitro rat model.

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    Takashi Machida

    Full Text Available Diabetic complications are characterized by the dysfunction of pericytes located around microvascular endothelial cells. The blood-brain barrier (BBB exhibits hyperpermeability with progression of diabetes. Therefore, brain pericytes at the BBB may be involved in diabetic complications of the central nervous system (CNS. We hypothesized that brain pericytes respond to increased brain thrombin levels in diabetes, leading to BBB dysfunction and diabetic CNS complications. Mice were fed a high-fat diet (HFD for 2 or 8 weeks to induce obesity. Transport of i.v.-administered sodium fluorescein and 125I-thrombin across the BBB were measured. We evaluated brain endothelial permeability and expression of tight junction proteins in the presence of thrombin-treated brain pericytes using a BBB model of co-cultured rat brain endothelial cells and pericytes. Mice fed a HFD for 8 weeks showed both increased weight gain and impaired glucose tolerance. In parallel, the brain influx rate of sodium fluorescein was significantly greater than that in mice fed a normal diet. HFD feeding inhibited the decline in brain thrombin levels occurring during 6 weeks of feeding. In the HFD fed mice, plasma thrombin levels were significantly increased, by up to 22%. 125I-thrombin was transported across the BBB in normal mice after i.v. injection, with uptake further enhanced by co-injection of unlabeled thrombin. Thrombin-treated brain pericytes increased brain endothelial permeability and caused decreased expression of zona occludens-1 (ZO-1 and occludin and morphological disorganization of ZO-1. Thrombin also increased mRNA expression of interleukin-1β and 6 and tumor necrosis factor-α in brain pericytes. Thrombin can be transported from circulating blood through the BBB, maintaining constant levels in the brain, where it can stimulate pericytes to induce BBB dysfunction. Thus, the brain pericyte-thrombin interaction may play a key role in causing BBB dysfunction in

  18. Positive effects of acarbose in the diabetic rat are not altered by feeding schedule.

    Science.gov (United States)

    Wright, B E; Vasselli, J R; Katovich, M J

    1998-03-01

    diabetic groups compared to vehicle-injected control groups. Acarbose treatment significantly reduced this rise, regardless of the feeding paradigm. Collectively, the results demonstrate that acarbose reduces diabetes-induced increases of blood glucose and glycated hemoglobin and that the glycemic effects of acarbose are most apparent during the absorptive period. Feeding paradigm (ad lib. versus meal fed) has little or no influence on acarbose's metabolic effects, indicating that large meals are not required to realize the beneficial effects of the drug. The meal-fed STZ-diabetic rat may be a good model with which to test meal-based diabetes treatments.

  19. CdSe/ZnS Quantum Dots-Labeled Mesenchymal Stem Cells for Targeted Fluorescence Imaging of Pancreas Tissues and Therapy of Type 1 Diabetic Rats.

    Science.gov (United States)

    Liu, Haoqi; Tang, Wei; Li, Chao; Lv, Pinlei; Wang, Zheng; Liu, Yanlei; Zhang, Cunlei; Bao, Yi; Chen, Haiyan; Meng, Xiangying; Song, Yan; Xia, Xiaoling; Pan, Fei; Cui, Daxiang; Shi, Yongquan

    2015-12-01

    Mesenchymal stem cells (MSCs) have been used for therapy of type 1 diabetes mellitus. However, the in vivo distribution and therapeutic effects of transplanted MSCs are not clarified well. Herein, we reported that CdSe/ZnS quantum dots-labeled MSCs were prepared for targeted fluorescence imaging and therapy of pancreas tissues in rat models with type 1 diabetes. CdSe/ZnS quantum dots were synthesized, their biocompatibility was evaluated, and then, the appropriate concentration of quantum dots was selected to label MSCs. CdSe/ZnS quantum dots-labeled MSCs were injected into mouse models with type 1 diabetes via tail vessel and then were observed by using the Bruker In-Vivo F PRO system, and the blood glucose levels were monitored for 8 weeks. Results showed that prepared CdSe/ZnS quantum dots owned good biocompatibility. Significant differences existed in distribution of quantum dots-labeled MSCs between normal control rats and diabetic rats (p quantum dots-labeled MSC injection. Statistical differences existed between the blood glucose levels of the diabetic rat control group and MSC-injected diabetic rat group (p < 0.01), and the MSC-injected diabetic rat group displayed lower blood glucose levels. In conclusion, CdSe/ZnS-labeled MSCs can target in vivo pancreas tissues in diabetic rats, and significantly reduce the blood glucose levels in diabetic rats, and own potential application in therapy of diabetic patients in the near future.

  20. Modulation of pancreatic β-cells in neonatally streptozotocin-induced type 2 diabetic rats by the ethanolic extract of Momordica charantia fruit pulp.

    Science.gov (United States)

    Hafizur, Rahman Md; Kabir, Nurul; Chishti, Sidra

    2011-02-01

    Effective doses of the Momordica charantia fruit pulp (MCF) ethanolic extract on pancreatic β-cells modulation in neonatally streptozotocin-induced type 2 diabetic rats were studied. Diabetic rats (n=8) were treated with MCF extract (400 mg kg(-1) day(-1)) or glibenclamide (5 mg kg(-1)) for 28 days. Control rats (n=11) and untreated diabetic rats (n=8) received only water. Fasting glucose, serum insulin (by ELISA) and β-cell function (HOMA %B by homeostasis model assessment) were measured. β- and α-cells were identified by immunostaining, nuclei by DAPI, and β-cell size and number by morphometry. Significant improvement of fasting blood glucose, serum insulin and β-cell function was observed with the MCF extract for the diabetic rat model. The islet size, total β-cell area and number of β-cells were increased to almost double in the diabetic rats treated with MCF extract as compared to the untreated diabetic rats. The number of α-cells did not change significantly. Insulin granules in β-cells were notably reduced in diabetic islets as compared to control islets. However, extract-treated diabetic rat β-cells were abundant with insulin granules, which was comparable to non-diabetic control islets. The modulation of pancreatic β-cells may be involved in the experimental observation of anti-diabetic effects of M. charantia extract.

  1. Evaluation of wound healing potential of Pterocarpus marsupium heart wood extract in normal and diabetic rats

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    Anil Kumar Singhal

    2012-01-01

    Full Text Available Aim: The aim of the present study is to evaluate and compare the cutaneous wound healing potential of Pterocarpus marsupium in normal and diabetic rats and make inference for the cutaneous wound healing potential by possible "mode of action" P. marsupium extract. Materials and Methods: The effect of heart wood extract of P. marsupium on wound healing has been studied in diabetic and normal animals. The effect has also been compared with standard (mupirocin ointment application. In the absence of specific animal model for cutaneous diabetic wound healing, we have used common model of wound healing (excision wound model in animals having diabetes (by administration of alloxan monohydrate 120 mg/kg i.p.. Statistics Analysis: Data were analyzed by using one-way ANOVA, followed by Tukey′s post hoc tests, using the Graph Pad Software (5.0 demo version, and P value <0.05 was considered to be significant. Results and Conclusion : Rats treated with 200 mg/kg/day of P. marsupium heart wood extract had high rate of wound contraction, significantly decreased epithelization period, and significant increase in dry weight, wet weight, and hydroxyproline content of the granulation tissue when compared with the diabetic control and normal control groups. Wound contraction together with increased tensile strength and hydroxyproline content support the use of P. marsupium heart wood extract in the management of wound healing in normal and diabetic rats.

  2. Hypoglycemic and antioxidative effects of fenugreek and termis seeds powder in streptozotocin-diabetic rats.

    Science.gov (United States)

    Marzouk, M; Soliman, A M; Omar, T Y

    2013-02-01

    Diabetes mellitus is a heterogeneous disease characterized by altered cellular metabolism. So, many traditional herbs are being used by diabetic patients to control this disease. In the present study, an attempt has been made to investigate the anti-diabetic and antioxidative effects of water suspension of Fenugreek (F), and Termis (T) seeds powder and their mixture (M) who were studied in Streptozotocin (STZ)-induced diabetic rats. Experimental diabetes was induced by injection a single dose of STZ (50 mg/kg, i.p.). Adult male albino rats were divided into five groups; normal control, diabetic control, diabetic-F supplement (1 g/kg b.wt.), diabetic-T supplement (1 g/kg b.wt.) and diabetic-M supplement 1 g/kg b.wt. of each seed powder concurrently for 30 days. Serum glucose, insulin, lipid profile, activities of serum marker enzymes of liver function as well as liver and muscle glycogen content were measured. The oxidative stress was assessed by blood reduced glutathione (GSH) content and enzyme activities of glutathione-S-transferase (GST) and catalase (CAT) in plasma. The increase in serum glucose, total lipid, triglycerides, total cholesterol, AST, ALT, ALP and decreased insulin, plasma, GSH, GST, CAT, as well as liver and muscle glycogen content were the salient features recorded in diabetic control rats. The F, T and M supplements significantly reverted the levels of the studied metabolites and enzymes activities to near normal control values. Co-administration of F and T seeds powder was considered as an effective agent in modulating the alterations in total lipid, AST, ALT, GSH and muscle glycogen. Our data suggest that F, T and M seeds powder supplementation may be beneficial for preventing diabetic complications in this animal model.

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

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    Yu Bai

    2016-07-01

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

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

    Science.gov (United States)

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

    2016-07-25

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

  5. Short-Term Caloric Restriction Does Not Reduce Bone Mineral Density in Rats with Early Type 2 Diabetes

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    Yun Kyung Jeon

    2014-03-01

    Full Text Available BackgroundThe effect of caloric restriction (CR in the setting of diabetes on bone metabolism has not yet been fully studied. The aim of this study is to determine if short-term CR alters bone mass and metabolism in Otsuka Long-Evans Tokushima fatty (OLETF rats, an animal model of type 2 diabetes.MethodsFour groups (n=5 were created: OLETF rats with food ad libitum (AL, OLETF rats with CR, Long-Evans Tokusima Otsuka (LETO rats with food AL, and LETO rats with CR. The CR condition was imposed on 24-week-old male rats using a 40% calorie reduction for 4 weeks. The effect of CR on femoral bone mineral density (BMD was assessed by dual-energy X-ray absorptiometry. Serum markers were measured by immunoassay.ResultsAfter 4 weeks of CR, body weight decreased in both strains. The BMD decreased in LETO rats and was maintained in OLETF rats. After adjustment for body weight, BMD remained lower in LETO rats (P=0.017 but not OLETF rats (P=0.410. Bone-specific alkaline phosphatase levels decreased in LETO rats (P=0.025 but not in OLEFT rats (P=0.347. Serum leptin levels were reduced after CR in both strains, but hyperleptinemia remained in OLETF rats (P=0.009. CR increased 25-hydroxyvitamin D levels in OLETF rats (P=0.009 but not in LETO rats (P=0.117. Additionally, interleukin-6 and tumor necrosis factor-α levels decreased only in OLETF rats (P=0.009.ConclusionShort-term CR and related weight loss were associated with decreases of femoral BMD in LETO rats while BMD was maintained in OLETF rats. Short-term CR may not alter bone mass and metabolism in type 2 diabetic rats.

  6. Short-term caloric restriction does not reduce bone mineral density in rats with early type 2 diabetes.

    Science.gov (United States)

    Jeon, Yun Kyung; Kim, Won Jin; Shin, Myung Jun; Chung, Hae-Young; Kim, Sang Soo; Kim, Bo Hyun; Kim, Seong-Jang; Kim, Yong Ki; Kim, In Joo

    2014-03-01

    The effect of caloric restriction (CR) in the setting of diabetes on bone metabolism has not yet been fully studied. The aim of this study is to determine if short-term CR alters bone mass and metabolism in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of type 2 diabetes. Four groups (n=5) were created: OLETF rats with food ad libitum (AL), OLETF rats with CR, Long-Evans Tokusima Otsuka (LETO) rats with food AL, and LETO rats with CR. The CR condition was imposed on 24-week-old male rats using a 40% calorie reduction for 4 weeks. The effect of CR on femoral bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry. Serum markers were measured by immunoassay. After 4 weeks of CR, body weight decreased in both strains. The BMD decreased in LETO rats and was maintained in OLETF rats. After adjustment for body weight, BMD remained lower in LETO rats (P=0.017) but not OLETF rats (P=0.410). Bone-specific alkaline phosphatase levels decreased in LETO rats (P=0.025) but not in OLEFT rats (P=0.347). Serum leptin levels were reduced after CR in both strains, but hyperleptinemia remained in OLETF rats (P=0.009). CR increased 25-hydroxyvitamin D levels in OLETF rats (P=0.009) but not in LETO rats (P=0.117). Additionally, interleukin-6 and tumor necrosis factor-α levels decreased only in OLETF rats (P=0.009). Short-term CR and related weight loss were associated with decreases of femoral BMD in LETO rats while BMD was maintained in OLETF rats. Short-term CR may not alter bone mass and metabolism in type 2 diabetic rats.

  7. Effect of vanadium on insulin and leptin in Zucker diabetic fatty rats.

    Science.gov (United States)

    Wang, J; Yuen, V G; McNeill, J H

    2001-02-01

    Vanadium exhibits a variety of insulin-mimetic actions in vitro and in vivo. The mechanism(s) of the effect of vanadium on leptin in Zucker diabetic fatty (ZDF) rats, a model of Type 2 diabetes, is unclear. Since insulin is a stimulator of leptin production and secretion and vanadium is an insulin-mimetic or insulin-enhancing agent, we studied how vanadium affected plasma leptin levels in vivo and the relationship between plasma insulin, leptin and body fat in ZDF rats. Zucker lean and ZDF rats at 9-week old were chronically treated with bis(ethylmaltolato)oxovanadium(IV) (BEOV), an organic vanadium compound, by oral gavage daily for 3 weeks. At termination, the total body fat was weighed and blood was collected for insulin, leptin and glucose assay. BEOV treatment (0.1 mmol/kg/day) significantly decreased plasma glucose levels in ZDF rats and did not change food intake and body fat content either in lean or ZDF rats. Following 3-week treatment, plasma insulin and leptin levels in BEOV treated ZDF rats were significantly higher, 1.5 and 0.5 fold than untreated rats, respectively. The correlation coefficients in ZDF rats showed that plasma leptin levels were correlated to plasma insulin levels, but not to body fat. These data indicate that plasma leptin levels parallel plasma insulin levels, and the effects of vanadium on leptin appear to be mediated by insulin in ZDF rats.

  8. The effects of diabetes on the rat parotid gland

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  9. Tempol effects on diabetic nephropathy in male rats.

    Science.gov (United States)

    Ranjbar, Akram; Ghasemi, Hassan; Hatami, Mahdi; Dadras, Farahanaz; Heidary Shayesteh, Tavakol; Khoshjou, Farhad

    2016-01-01

    Diabetic nephropathy (DN) is the most common cause of the chronic kidney disease in the world. Oxidative stress on the other hand has a major and well known role in its pathophysiology. The aim of the study is to figure out if tempol, a synthetic antioxidant agent, modifies DN and to determine its relevance to changes of serum oxidative biomarkers. Twenty-seven male rats were equally divided in to 4 groups (7 rats for each group). Group I (control or C), group II (diabetic or D), groups III (Tempol) which were given tempol (100 mg/kg/day) by gavages for 28 days and group IV (D&T) which includes diabetic rats that also received same dose of tempol. After treatment, blood samples were isolated. Enzymatic scavengers including catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, lipid peroxidation (LPO), total antioxidant capacity (TAC) and total thiol molecules (TTM) were measured. Blood urea nitrogen (BUN), creatinine (Cr) an albumin/Cr ratio were evaluated as well. Statistical differences were assessed with one-way analysis of variance (ANOVA) by SPSS followed by Tukey t test. Oxidative stress biomarkers modified and Alb/Cr ratio increased in diabetic group (II), however, they were altered to normal in group IV (D&T) compared with diabetic group (D). Tempol can modify oxidative stress biomarkers and presumably nephropathy in diabetic rats.

  10. Intermittent Fasting Modulation of the Diabetic Syndrome in Streptozotocin-Injected Rats

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    Louiza Belkacemi

    2012-01-01

    Full Text Available This study investigates the effects of intermittent overnight fasting in streptozotocin-induced diabetic rats (STZ rats. Over 30 days, groups of 5-6 control or STZ rats were allowed free food access, starved overnight, or exposed to a restricted food supply comparable to that ingested by the intermittently fasting animals. Intermittent fasting improved glucose tolerance, increased plasma insulin, and lowered Homeostatis Model Assessment index. Caloric restriction failed to cause such beneficial effects. The β-cell mass, as well as individual β-cell and islet area, was higher in intermittently fasting than in nonfasting STZ rats, whilst the percentage of apoptotic β-cells appeared lower in the former than latter STZ rats. In the calorie-restricted STZ rats, comparable findings were restricted to individual islet area and percentage of apoptotic cells. Hence, it is proposed that intermittent fasting could represent a possible approach to prevent or minimize disturbances of glucose homeostasis in human subjects.

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

    OpenAIRE

    PINHEIRO, MARCELO S.; RODRIGUES, LUHARA S.; S. NETO, LEILA; MORAES-SOUZA, RAFAIANNE Q.; SOARES, THAIGRA S.; AMÉRICO, MADILEINE F.; CAMPOS, KLEBER E.; DAMASCENO, DÉBORA C.; VOLPATO, GUSTAVO T.

    2017-01-01

    ABSTRACT Bauhinia holophylla, commonly known as “cow’s hoof”, is widely used in Brazilian folk medicine for the diabetes treatment. Therefore, the aim of this study was at evaluating the aqueous extract effect of Bauhinia holophylla leaves treatment on the streptozotocin-induced diabetic rats. Diabetes was induced by Streptozotocin (40 mg/Kg) in female Wistar rats. Oral administration of aqueous extract of Bauhinia holophylla leaves was given to non-diabetic and diabetic rats at a dose of 400...

  12. Effect of GLP-1 on the expression of NADPH oxidase subunits in the kidney of type 1 diabetic rats

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    Jin-jin LIU

    2013-09-01

    Full Text Available Objective To observe the effect of exenatide, a glucagon-like peptide-1 (GLP-1 receptor agonist, on the expression of NADPH oxidase subunits NOX4 and p22phox and connective tissue growth factor (CTGF in the kidney of streptozotocin (STZ-induced type 1 diabetic rats, and explore the protective effects and mechanisms of exenatide on the kidney of diabetic rats. Methods Thirty male Sprague-Dawley (SD rats were divided into control group (group A, n=7 and diabetic model group (n=23. Type 1 diabetic model was reproduced by intraperitoneal injection of streptozotocin. It was successful in 19 rats. Diabetic rats were randomly divided into diabetic control group (group B, n=10 and diabetic with treatment of exenatide group (group C, n=9. Rats in group C were injected subcutaneously with exenatide in dose of 5μg/kg twice daily. Rats in group A and B were given equivalent volume of normal saline by subcutaneous injection. All rats were sacrificed after eight weeks. The mRNA expression of renal p22phox and NOX4 were detected by real-time fluorescence quantitative PCR. The protein expression of CTGF was detected by immunohistochemical staining. Results The levels of blood glucose, lipids, creatinine, and urea nitrogen, the albumin excretion rate, kidney index, the mRNA expressions of renal NOX4 and p22phox, and the protein expression of renal CTGF were significantly increased in group B compared with that in group A (P0.05. Conclusion Exenatide can decrease the expressions of renal NOX4, p22phox and CTGF, decline the index of urinary protein, and alleviate the kidney hypertrophy in type 1 diabetic rats, implying that exenatide exerted a protective effect on the kidney.

  13. Effect of green tea on kidney tubules of diabetic rats.

    Science.gov (United States)

    Renno, Waleed M; Abdeen, Suad; Alkhalaf, Mousa; Asfar, Sami

    2008-09-01

    It has been documented that green tea (GT) and its catechin components improve renal failure and inhibit the growth of mesangial cells. In the present study we examined the long-term effect of GT extract on streptozotocin (STZ)-induced diabetic nephropathy and on the glycogen accumulation in the kidney tubules. Male Sprague-Dawley rats were randomly assigned to normal control groups (2, 6, 8 and 12 weeks) and five diabetic groups (n 10) of comparable age. A GT diabetic group received 16 % concentration of GT for 12 weeks post-diabetes induction as their sole source of drinking water. GT treatment significantly (P kidney tubules. These results indicate that in STZ diabetes, kidney function appears to be improved with GT consumption which also prevents glycogen accumulation in the renal tubules, probably by lowering blood levels of glucose. Therefore, GT could be beneficial additional therapy in the management of diabetic nephropathy.

  14. Comprehensive Experiment--Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    Science.gov (United States)

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a…

  15. Study of antidiabetic activity of white skinned sweet potato (Ipomoea batatas L.). Comparison of normal and streptozotocin induced diabetic rats and hereditary diabetic mice; Hakukansho (Ipomoea batatas L.) no kotonyobyo sayo. Seijo rat, streptozotocin tonyobyo rat, oyobi shizen hassho tonyobyo mausu ni taisuru sayo hikaku

    Energy Technology Data Exchange (ETDEWEB)

    Kusano, S.; Abe, H.; Okada, A. [Fuji Sangyo Co. Ltd., Kagawa (Japan)

    1998-09-01

    As a result of study on the effect of white skinned sweet potato (WSSP), it is found that the potato has potential hypoglycemic activity in streptozotocin (STZ) induced diabetic rats and hereditary diabetic mice (db/db). This report is the first one showing the antidiabetic effect of WSSP. Antidiabetic activity of WSSP in STZ induced diabetic rats and hereditary diabetic mice is shown. WSSP increases serum insulin levels of STZ induced diabetic rats like the tolbutamide treatment, and controls blood glucose after oral glucose load. WSSP decreases high blood glucose value with the decrease of insulin value in hereditary diabetic mice, and improves glucose tolerance. Those mice are models showing insulin resistance, and it is assumed from the effect on those diabetic models that blood glucose value is decreased by the improvement of insulin resistance. 37 refs., 4 figs., 2 tabs.

  16. 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.

    Science.gov (United States)

    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

    2010-12-01

    Impaired intestinal barrier function is observed in type 1 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 to type 1 diabetes. Since a hydrolysed casein (HC) diet prevents autoimmune diabetes onset in diabetes-prone (DP)-BioBreeding (BB) rats, we studied the role of the HC diet on intestinal barrier function and, therefore, prevention of autoimmune diabetes onset in this animal model. DP-BB rats were fed the HC diet from weaning onwards and monitored for autoimmune diabetes development. Intestinal permeability was assessed in vivo by lactulose-mannitol test and ex vivo by measuring transepithelial electrical resistance (TEER). Levels of serum zonulin, a physiological tight junction modulator, were measured by ELISA. Ileal mRNA expression of Myo9b, Cldn1, Cldn2 and Ocln (which encode the tight junction-related proteins myosin IXb, claudin-1, claudin-2 and occludin) and Il-10, Tgf-ß (also known as Il10 and Tgfb, respectively, which encode regulatory cytokines) was analysed by quantitative PCR. The HC diet reduced autoimmune diabetes by 50% in DP-BB rats. In DP-BB rats, prediabetic gut permeability negatively correlated with the moment of autoimmune diabetes onset. The improved intestinal barrier function that was induced by HC diet in DP-BB rats was visualised by decreasing lactulose:mannitol ratio, decreasing serum zonulin levels and increasing ileal TEER. The HC diet modified ileal mRNA expression of Myo9b, and Cldn1 and Cldn2, but left Ocln expression unaltered. Improved intestinal barrier function might be an important intermediate in the prevention of autoimmune diabetes by the HC diet in DP-BB rats. Effects on tight junctions, ileal cytokines and zonulin production might be important mechanisms for this effect.

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

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    Gomez R.

    2001-01-01

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

  18. Effect of Treadmill Exercise on Interleukin-15 Expression and Glucose Tolerance in Zucker Diabetic Fatty Rats

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    Hee-Jae Kim

    2013-10-01

    Full Text Available BackgroundInterleukin-15 (IL-15, a well-known myokine, is highly expressed in skeletal muscle and is involved in muscle-fat crosstalk. Recently, a role of skeletal muscle-derived IL-15 in the improvement of glucose homeostasis and insulin sensitivity has been proposed. However, little is known regarding the influence of endurance training on IL-15 expression in type 2 diabetic skeletal muscles. We investigated the effect of endurance exercise training on glucose tolerance and IL-15 expression in skeletal muscles using type 2 diabetic animal models.MethodsMale Zucker diabetic fatty (ZDF and ZDF lean control (ZLC rats were randomly divided into three groups: sedentary ZLC, sedentary ZDF (ZDF-Con, and exercised ZDF (ZDF-Ex. The ZDF-Ex rats were forced to run a motor-driven treadmill for 60 minutes once a day 5 times per week for 12 weeks. Intraperitoneal glucose tolerance test (IPGTT was performed after 12 weeks. Expression of IL-15 was measured using ELISA in extracted soleus (SOL and gastrocnemius medial muscles.ResultsAfter 12 weeks of treadmill training, reduction of body weight was observed in ZDF-Ex compared to ZDF-Con rats. Glucose tolerance using IPGTT in diabetic rats was significantly improved in ZDF-Ex rats. Furthermore, the expression of IL-15 was significantly increased (P<0.01 only in the SOL of ZDF-Ex rats compared to ZDF-Con. Additionally, IL-15 expression in SOL muscles was negatively correlated with change of body weight (R=-0.424, P=0.04.ConclusionThe present study results suggest that 12 weeks of progressive endurance training significantly improved glucose tolerance with concomitant increase of IL-15 expression in SOL muscles of type 2 diabetic rats.

  19. Hypoglycemic effect of instant aloe vera on the diabetic rats

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    Riyanto

    2017-09-01

    Full Text Available Instant aloe vera contains phenolic compounds which has antioxidative activity. However, this product is hygroscopic and damaged easily during storage. The critical condition of the instant occurs at the moisture content of 12.52 ± 0.24% (wb. Increasing the moisture content could accelerate oxidation of the phenolic compounds, thus decrease the antioxidative activity. Previous research showed that the antioxidative activity of instant aloe vera could lower the blood glucose. The purpose of this study was to evaluate the hypoglycemic activity of instant aloe vera during storage until the critical condition. The hypoglycemic effect was determined with the in vivo method using diabetic Wistar rats as experimental animals. The diabetic rats were fed with a standard feed combined with instant aloe vera which has been stored at various storage time i.e. 0, 2, 4, 6, 8 weeks and used normal rats fed without instant aloe vera as a control. The blood glucose was analyzed every week until 4 weeks. The research showed that the diabetic rats fed with standard feed without instant aloe vera had high blood glucose (219.40 mg/dL after 4 weeks treatment. Otherwise, the blood glucose of diabetic rats fed with instant aloe vera decreased from 214.00 mg/dL to 97.57 mg/dL after 4 weeks.

  20. Effects of an Antimutagenic 1,4-Dihydropyridine AV-153 on Expression of Nitric Oxide Synthases and DNA Repair-related Enzymes and Genes in Kidneys of Rats with a Streptozotocin Model of Diabetes Mellitus.

    Science.gov (United States)

    Ošiņa, Kristīne; Rostoka, Evita; Isajevs, Sergejs; Sokolovska, Jelizaveta; Sjakste, Tatjana; Sjakste, Nikolajs

    2016-11-01

    Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry. Development of DM significantly induced PARP1 protein expression, while AV-153 (0.5 mg/kg) administration decreased it. AV-153 increased the expression of Parp1 gene in the kidneys of both intact and diabetic animals. Expression of H2afx mRNA and γH2AX histone protein, a marker of DNA breakage, was not changed in diabetic animals, but AV-153 up-regulated the expression of the gene without any impact on the protein expression. Development of DM was followed by a significant increase in iNOS enzyme expression, while AV-153 down-regulated the enzyme expression up to normal levels. iNos gene expression was also found to be increased in diabetic animals, but unlike the protein, the expression of mRNA was found to be enhanced by AV-153 administration. Expression of both eNOS protein and eNos gene in the kidneys was down-regulated, and the administration of AV-153 normalized the expression level. The effects of the compound in the kidneys of diabetic animals appear to be beneficial, as a trend for the normalization of expression of NO synthases is observed. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  1. Impact of combined exercise training on cardiovascular autonomic control and mortality in diabetic ovariectomized rats.

    Science.gov (United States)

    Sanches, Iris C; Conti, Filipe F; Bernardes, Nathalia; Brito, Janaina de O; Galdini, Elia G; Cavaglieri, Cláudia R; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2015-09-15

    The purpose of this study was to compare the effects of aerobic, resistance, or combined exercise training on cardiovascular autonomic control and mortality in diabetic ovariectomized rats. Female Wistar rats were divided into one of five groups: euglycemic sedentary (ES), diabetic ovariectomized sedentary (DOS), diabetic ovariectomized aerobic-trained (DOTA), diabetic ovariectomized resistance-trained (DOTR), or diabetic ovariectomized aerobic+resistance-trained (DOTC). Arterial pressure (AP) was directly recorded and baroreflex sensitivity was evaluated by heart rate responses to AP changes. Cardiovascular autonomic modulation was evaluated by spectral analyses. No differences were observed in body weight and glycemia between diabetic rats. Animals in the DOTC and DOTA groups exhibited an increase in running time, whereas animals in the DOTC and DOTR groups showed greater strength. Trained groups exhibited improvement in total power and the high-frequency band of pulse interval and reduced mortality (vs. DOS). Animals in the DOTC (bradycardic and tachycardic responses) and DOTA (tachycardic responses) groups exhibited attenuation in baroreflex dysfunction that was observed in DOS and DOTR animals, and an improvement in AP variance. In conclusion, all training protocols led to reduced mortality, which may be due to an increase in physical capacity and to cardiovascular and autonomic benefits following training, regardless of any improvement in glycemic control. In this model, the aerobic and combined trainings seem to promote additional cardiovascular autonomic benefits when compared with resistance training alone. Copyright © 2015 the American Physiological Society.

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

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    Snehal Nitin Mestry

    2017-07-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

  4. Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats.

    Science.gov (United States)

    Abd El Sattar El Batran, Seham; El-Gengaihi, Souad E; El Shabrawy, Osama A

    2006-11-24

    Momordica charantia L. (MC) (Cucurbitaceae) commonly known as balsam pear, bitter gourd or karela, used in several purposes in traditional medicine is an important medicinal plant. Two sets of experiments were carried out, the first experiment indicated that the LD(50) for MC juice and alcoholic extracts were 91.9 and 362.34 mg/100g b.wt., respectively, of subcutaneously "s.c." injected mice. The toxic signs were recorded within the first 24 h post-injection. The second experiment was performed to evaluate the effect of MC juice and alcoholic extracts on blood glucose and other biochemical parameters in normal and diabetic rats. Both extracts induced a significant decrease in serum glucose levels in normal and diabetic rats. The two extracts did not show any significant effect in urea, creatinine, ALT, AST and AP in normal rat, while in diabetic rats the two extracts caused a significant decrease in serum urea, creatinine, ALT, AST, AP, cholesterol and triglyceride levels. Also, these results suggested that MC extracts possesses anti-diabetic, hepato-renal protective and hypolipidemic effect in alloxan-induced diabetic rats. Thus, MC is alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus.

  5. Evaluation of Topical Tocopherol Cream on Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats

    OpenAIRE

    Lin, Teoh Seong; Abd Latiff, Azian; Abd Hamid, Noor Aini; Wan Ngah, Wan Zurinah bt; Mazlan, Musalmah

    2012-01-01

    Diabetes is a common cause of delayed wound healing. The aim of the study was to determine the effect of topical administration of tocopherol cream on the wound healing process in diabetic rats. The study was conducted using 18 male Sprague Dawley rats which were divided into three groups: (I) diabetic rats receiving control cream (n = 6), (II) diabetic rats receiving 0.06% tocopherol cream (n = 6), and (III) diabetic rats receiving 0.29% tocopherol cream (n = 6). Four cutaneous wounds were c...

  6. Gut microbiota after Roux-en-Y gastric bypass and sleeve gastrectomy in a diabetic rat model: Increased diversity and associations of discriminant genera with metabolic changes.

    Science.gov (United States)

    Guo, Yan; Liu, Chao-Qian; Shan, Cheng-Xiang; Chen, Yue; Li, Hui-Hua; Huang, Zhi-Ping; Zou, Da-Jin

    2017-03-01

    Recent work with gut microbiota after bariatric surgery is limited, and the results have not been in agreement. Given the role of the gut microbiota in regulating host metabolism, we explored the effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the modifications of gut microbiota with regard to the potential influence of food intake and/or weight loss and examined their links with host metabolism. Zucker diabetic fatty rats were divided into the following groups: RYGB; sham-operated with pair-fed as RYGB; sham-operated fed ad libitum; and SG. The metabolic effects and gut microbiota profile were analyzed 10 weeks postoperatively. Associations between discriminating genera and metabolic markers after RYGB were explored. The 2 procedures induced similar glucose improvement and increased flora diversity after 10 weeks compared with sham-operated groups. RYGB induced a marked higher relative abundance of Proteobacteria/Gammaproteobacteria and Betaproteobacteria and increased emergence of Fusobacteria and Clostridium, whereas SG resulted in more abundant Actinobacteria compared with other groups. Most of the 12 discriminant genera correlated with changes in metabolic phenotype, but only 28.6% of these correlations were independent of weight, and 4 discriminant genera still negatively correlated with serum insulin level independent of food intake and weight loss after RYGB. These data demonstrate that RYGB and SG surgery produced similar diversity but different microbiota compositions changes in Zucker diabetic fatty rats. These findings stimulate deeper explorations of functions of the discriminate microbiota and the mechanisms linking postsurgical modulation of gut microbiota and improvements in insulin resistance. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Localization of human adipose-derived stem cells and their effect in repair of diabetic foot ulcers in rats.

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    Shi, Rongfeng; Jin, Yinpeng; Cao, Chuanwu; Han, Shilong; Shao, Xiaowen; Meng, Lingyu; Cheng, Jie; Zhang, Meiling; Zheng, Jiayi; Xu, Jun; Li, Maoquan

    2016-10-22

    Diabetic foot ulcer (DFU) is an intractable diabetic complication. Patients suffering from diabetes mellitus (DM) frequently present with infected DFUs. In this study, a wound healing model on diabetic rat foot was established to mimic the pathophysiology of clinical patients who suffer from DFUs. Our study aimed to explore the localization of human adipose-derived stem cells (hADSCs) and the role of these cells in the repair of foot ulcerated tissue in diabetic rats, and thus to estimate the possibilities of adipose-derived stem cells for diabetic wound therapy. Sprague-Dawley rats were used to establish diabetic models by streptozotocin injection. A full-thickness foot dorsal skin wound was created by a 5 mm skin biopsy punch and a Westcott scissor. These rats were randomly divided into two groups: the hADSC-treated group and the phosphate-buffered saline (PBS) control group. The hADSC or PBS treatment was delivered through the left femoral vein of rats. We evaluated the localization of hADSCs with fluorescence immunohistochemistry and the ulcer area and ulcerative histology were detected dynamically. The hADSCs had a positive effect on the full-thickness foot dorsal skin wound in diabetic rats with a significantly reduced ulcer area at day 15. More granulation tissue formation, angiogenesis, cellular proliferation, and higher levels of growth factors expression were also detected in wound beds. Our data suggest that hADSC transplantation has the potential to promote foot wound healing in diabetic rats, and transplantation of exogenous stem cells may be suitable for clinical application in the treatment of DFU.

  8. Regionally distinct alterations in the composition of the gut microbiota in rats with streptozotocin-induced diabetes.

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    Roland Wirth

    Full Text Available The aim of this study was to map the microbiota distribution along the gut and establish whether colon/faecal samples from diabetic rats adequately reflect the diabetic alterations in the microbiome. Streptozotocin-treated rats were used to model type 1 diabetes mellitus (T1D. Segments of the duodenum, ileum and colon were dissected, and the microbiome of the lumen material was analysed by using next-generation DNA sequencing, from phylum to genus level. The intestinal luminal contents were compared between diabetic, insulin-treated diabetic and healthy control rats. No significant differences in bacterial composition were found in the luminal contents from the duodenum of the experimental animal groups, whereas distinct patterns were seen in the ileum and colon, depending on the history of the luminal samples. Ileal samples from diabetic rats exhibited particularly striking alterations, while the richness and diversity obscured some of the modifications in the colon. Characteristic rearrangements in microbiome composition and diversity were detected after insulin treatment, though the normal gut flora was not restored. The Proteobacteria displayed more pronounced shifts than those of the predominant phyla (Firmicutes and Bacteroidetes in the rat model of T1D. Diabetes and insulin replacement affect the composition of the gut microbiota in different, gut region-specific manners. The luminal samples from the ileum appear more suitable for diagnostic purposes than the colon/faeces. The Proteobacteria should be at the focus of diagnosis and potential therapy. Klebsiella are recommended as biomarkers of T1D.

  9. A non-MHC locus essential for autoimmune type I diabetes in the Komeda Diabetes-Prone rat.

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    Yokoi, N; Kanazawa, M; Kitada, K; Tanaka, A; Kanazawa, Y; Suda, S; Ito, H; Serikawa, T; Komeda, K

    1997-10-15

    The Long-Evans Tokushima Lean (LETL) rat, characterized by rapid onset of insulin-dependent (type I) diabetes mellitus (IDDM), no sex difference in the incidence of IDDM, autoimmune destruction of pancreatic beta cells, and no significant T cell lymphopenia, is a desirable animal model for human IDDM. We have established a diabetes-prone substrain of the LETL rat, named Komeda Diabetes-Prone (KDP) rat, showing a 100% development of moderate to severe insulitis within 220 d of age. The cumulative frequency of IDDM was 70% at 120 d of age, and reached 82% within 220 d of age. Here, we performed the first genome-wide scan for non-MHC IDDM susceptibility genes in this strain. The analysis of three crosses has led to the revelation of a major IDDM susceptibility gene, termed Iddm/kdp1, on rat chromosome (Chr) 11. Homozygosity for the KDP allele at this locus is shown to be essential for the development of moderate to severe insulitis and the onset of IDDM. Comparative mapping suggests that the homologues of Iddm/ kdp1 are located on human Chr 3 and mouse Chr 16 and would therefore be different from previously reported IDDM susceptibility genes.

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

    OpenAIRE

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

    2017-01-01

    Abstract This study was aimed at investigating the antihyperglycemic and antidyslipidemic activity of Musa paradisiaca‐based diets in alloxan‐induced diabetic mellitus rats. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg b.w) in 48 randomly selected rats. The rats were randomly grouped into four as follows: normal rats fed Dioscorea rotundata‐based diet, diabetic control rats fed D. rotundata‐based diet, diabetic rats fed D. rotundata‐based diet and administe...

  11. Vascular mechanotransduction data in a rodent model of diabetes: Pressure-induced regulation of SHP2 and associated signaling in the rat inferior vena cava

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    Kevin M. Rice

    2017-12-01

    Full Text Available The effect of diabetes on vascular mechano-transductive response is of great concern. Given the higher rate of vein graft failures associated with diabetes, understanding the multiple cellular and molecular events associated with vascular remodeling is of vital importance. This article represents data related to a study published in Cardiovascular Diabetology [1] (Rice et al., 2006 and Open Journal of Endocrine and Metabolic Diseases [2] (Rice et al., 2015 evaluating the effect of pressurization on rat inferior venae cavae (IVC. Provided within this articles is information related to the method and processing of raw data related to our prior publish work and Data in Brief articles [3,4] (Rice et al., 2017, as well as the evaluation of alternation in SHP-2 signaling and associated proteins in response to mechanical force. IVC from lean and obese animals were exposed to a 30 min perfusion of 120 mm Hg pressure and evaluated for changes in expression of SHP2, BCL-3, BCL-XL, HSP 27, HSP 70, and PI3K p85, along with the phosphorylation of SHP-2 (Tyr 542.

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

    Science.gov (United States)

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

    2018-01-01

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

  13. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.

    Science.gov (United States)

    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Frederick, Kathy E; Parvin, Curtis A; Plurad, Santiago B; Levisetti, Matteo G

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.

  14. 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

  15. Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus.

    Science.gov (United States)

    Kusaka-Nakamura, M; Kishi, K; Miyazawa, A; Yagi, S; Sokabe, H

    1988-01-01

    Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.

  16. Attenuation of Diabetic Nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF Rats with a Combination of Chinese Herbs (Tangshen Formula

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    Haojun Zhang

    2011-01-01

    Full Text Available Diabetic nephropathy is one of the most significant microvascular complications in patients with type 2 diabetics. The concise mechanism of diabetic nephropathy is unknown and there is no successful treatment. The objective of study was to investigate effects of Chinese herbs (Tangshen Formula on diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF rats. OLETF rats and LETO rats were divided into four groups: LETO control, OLETF diabetics, OLETF diabetics treated with Tangshen Formula, and OLETF diabetics treated with Monopril. Body weight, blood glucose, and 24 h urinary proteins were measured once every four weeks. Blood samples and kidney tissues were obtained for analyses of total cholesterol, triglyceride, whole blood viscosity, plasma viscosity, and pathohistological examination at 36 and 56 weeksrespectively. Untreated OLETF rats displayed diabetic nephropathy over the study period. Treatment of OLETF rats with Tangshen Formula attenuated the increases in blood glucose, body weight, 24 h urinary protein content, serum total cholesterol, whole blood viscosity and plasma viscosity at certain time. Treatment with Tangshen Formula also reduced glomerulosclerotic index and interstitial fibrotic index seen in OLETF rats. In conclusion, Tangshen Formula could attenuate the development of diabetic nephropathy in OLETF rat diabetic model.

  17. Structure of the vitreoretinal border region in spontaneously diabetic BB rats

    DEFF Research Database (Denmark)

    Heegaard, S

    1993-01-01

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

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

    Science.gov (United States)

    Srinivasarao, Nelli; Swapna Rekha, Somesula; Muniandy, Sekaran

    2014-01-01

    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. PMID:25161691

  19. Morphological Changes of Gingiva in Streptozotocin Diabetic Rats

    Directory of Open Access Journals (Sweden)

    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.

  20. [Effect of the folic acid and vitamin B2 on the diabetes mellitus rats with diabetic nephropathy].

    Science.gov (United States)

    Xu, Rongxian; Fan, Yanfeng; Xiang, Jianjun; Zhan, Meirong

    2012-11-01

    To explore the relationship among the folic acid, vitamin B12 and diabetic nephropathy and to discuss the mechanism of the diabetic microangiopathy. We selected 80 SD rats, and then divided them into 2 groups randomly. Those were the control group and the model groups. During the process of this study, the control group was fed with the normal animal feeds; the model groups were fed with the high calorie diets for 10 weeks. At the end of the tenth week, the rats of the model group were induced to diabetes mellitus by intraperitoneal injection with streptozocin 30mg/kg, and then we divided the diabetes mellitus rats into 4 groups which measured the levels of the blood fat (total cholesterin, triglyceride), Fins, FBG, SOD, MDA, GSH-Px. Results (1) Through feeding the rats with the special feeds for a long time, and then injecting with streptozocin can make them develop to be the diabetes mellitus. The model groups' levels of the triglyceride, the cholesterin and the random blood glucose were (1.07 +/- 0.27), (2.29 +/- 0.42), (21.12 +/- 4.21) mmol/L, respectively, those were significantly higher than the control group's levels which were (1.11 +/- 0.20), (0.68 +/- 0.11), (5.73 +/- 0.26) mmol/L (P tissue was the most serious through the method of periodic acid-Schiff' s staining (PAS), and the level of the MDA was also highest (P What' s more, both of the folic acid and the vitamin B12 could reduce the increase of the 24hours urinary albumin, especially using the folic acid and the vitamin B12 together. Using the special feeds to feed the SD rats for ten weeks and then inject STZ (30 mg/kg) from abdominal cavity can make them develop to be the diabetes mellitus. The supplement with folic acid and vitamin B12 had the effect of protecting the capillary of the kidney from damage, and the mechanism may have something to do with the effect of anti-oxygenation.

  1. Effects of telmisartan on the expression of NADPH oxidase subunits in the myocardium of type 2 diabetic rats

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    Jia-wei LI

    2011-10-01

    Full Text Available Objective To explore the effect of telmisartan on the expression of NADPH oxidase subunits p22phox and NOX4 in the myocardiam of type 2 diabetic rats.Methods Thirty-six male Wistar rats were randomly divided into two groups: normal control group(group A,n=10,diabetic model group(n=26.Type 2 diabetic model was established by high-fat and high-sugar diet followed by intraperitoneal injection of a low dose of streptozotocin(STZ.After the model was reproduced successfully,20 diabetic rats were randomly divided into diabetic subgroup(group B,n=10 and telmisartan-treated subgroup(group C,n=10.Rats in group C were orally administered telmisartan(5mg/kg/d,and rats in group A and B were given equivalent volume of normal saline.All rats were sacrificed 12 weeks after treatment.The mRNA expressions of myocardial p22phox and NOX4 were detected by real-time fluorescence quantitative PCR,and the protein expressions of myocardial connective tissue growth factor(CTGF and copper-zinc-superoxide dismutase(Cu-Zn-SOD were detected by immunohistochemical staining.Results Compared with group A,the ratio of heart/body weight,the mRNA expression of myocardial p22phox and NOX4,and the protein expression of myocardial CTGF increased significantly in group B,and the protein expression of myocardial Cu-Zn-SOD decreased significantly(P 0.05.Conclusions Telmisartan can down-regulate the over-expression of myocardial NOX4 and p22phox mRNA in type 2 diabetic rats,lessen the myocardial damage induced by oxidative stress,thus plays a protective role in the myocardium of diabetic rats.

  2. Effects of diabetes mellitus on gastric motility in rats

    International Nuclear Information System (INIS)

    Rafsanjani, F.N.; Adeli, S.; Ardakani, Z.V.; Ardakani, J.V.; Ardakani, J.V.; Ghotbi, P.

    2009-01-01

    Diabetes mellitus is one of the most common endocrine diseases that affects most body organs. Peristaltic disorders and gastric distension have also been observed in diabetes. Because the effect of diabetes on gastric motility has not been fully examined, we decided to determine if gastric motility is also affected by diabetes in rat. This study was carried out at Kerman University of Medical Science, Kerman, Iran from October 2004 to February 2005. Three groups of male wistar rats (control, vehicle, diabetic) weighing 200-250 g were used. Diabetic state was induced by intraperitoneal injection of 45 mg/kg streptozotocin. Animals were anesthetized by intraperitoneal (IP) injection of 50 mg/kg thiopental sodium. After tracheostomy and laparatomy, a balloon was inserted into the stomach, which was attached to a pressure transducer system via a cannula and this whole system was connected to a physiograph. Acetylcholine (Ach) was the stimulant agent which was used intraperitoneally. There was no significant difference between basal intragastric pressures in three groups. Also there was no significant difference in the basal and Ach-stimulated intragastric pressure among the three groups. But Ach-stimulated intragastric pressure was more than the basal state in each group (control 28.3+-1.77 vs 14+-1.4, vehicle 30.8+-2.03 vs 15.9+-1.56 and diabetic 30.6+-0.05 vs 13.7+-0.84 mmHg). Although it has been shown that diabetes can change gastric acid and pepsin secretion in rats, no significant change in gastric motility could be shown. (author)

  3. Relationship between oxidative stress and diabetic osteopenia in premenopausal rats

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    Valéria Morgiana Gualberto Duarte

    2010-09-01

    Full Text Available The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship among lipid peroxidation index, antioxidant defense parameters and bone metabolism in a premenopausal diabetic model using measures including thiobarbituric acid-reactive substances concentration (TBARS and reduced glutathione (GSH content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD. Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15 and Group 2: diabetic rats (n = 15. Diabetes was induced by alloxan and confirmed by glycemia >250 mg/dL. The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (pA relação entre peroxidação lipídica, defesa antioxidante e osteopenia diabética permanece obscura. Este estudo avaliou a associação entre índice de peroxidação lipídica, parâmetro de defesa antioxidante e metabolismo ósseo em um modelo diabético pré-menopausa através de medidas como a concentração de substâncias reativas ao ácido tiobarbitúrico (SRAT e conteúdo de glutationa reduzida (GSH no homogenato cerebral, análises histomorfométricas, teste biomecânico e densidade mineral óssea (DMO. Ratos Wistar fêmeas com ciclo estral regular foram distribuídos em dois grupos: Grupo 1 - ratas controle (n = 15 e Grupo 2 - ratas diabéticas (n = 15. O diabetes foi induzido pela aloxana e confirmado pela glicemia >250 mg/dL. O índice de peroxidação lipídica, medido pela concentração de SRAT, demonstrou um aumento significativo (p<0.05 nos animais diabéticos, em relação aos animais controle. Entretanto, o parâmetro de defesa antioxidante, mensurado pelo conteúdo de GSH, foi reduzido significativamente (p<0.05 nos animais diabéticos. As análises histomorfométricas mostraram um aumento significativo (p<0.05 da separação trabecular do f

  4. Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

    Science.gov (United States)

    FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

    2016-01-01

    Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

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

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Scrophularia ningpoensis extract (SNE) on streptozotocin-induced diabetic rats. Methods: SNE was obtained by steeping the dried Scrophularia ningpoensis in water at 60 oC three times, each for 1 h, before first drying in an oven at 100 oC and then freeze-drying the last extract thus ...

  6. Insulin-mimetic activity of stevioside on diabetic rats: biochemical ...

    African Journals Online (AJOL)

    Biochemical, molecular and histopathological studies have been done to evaluate the therapeutic effect of stevioside on minimizing levels of glucose and its ... For mRNA expression, stevioside up-regulated the expressions of PK and IRS-1 genes, which are down-regulated in diabetic rats, and was very effective in the ...

  7. Suv39h1 Protects from Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

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    Bo Yang

    2014-04-01

    Full Text Available Background: Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R injury under diabetic condition has not been evaluated. Methods: To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis. Results: Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-κB. Conclusion: Overexpression of Suv39h1 results in the de-activation of proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore, Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under diabetic condition.

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

    Science.gov (United States)

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

    2008-04-01

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

  9. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

    Directory of Open Access Journals (Sweden)

    Saleh A. Bakheet

    2011-01-01

    Full Text Available We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients.

  10. Somatostatin ontogenesis in the gastrointestinal and pancreatic tract: study in normal rats and during a induced diabetes in neonates rats

    International Nuclear Information System (INIS)

    Cunha, M.C.

    1980-01-01

    The ontogenic studies of somatostatin of pancreas, ileum and duodenum of Wistar rats and the rats with induced diabetes were done. The radioimmunologic method to dose the somatostatin was used. (L.M.J.)

  11. Rat Genome and Model Resources.

    Science.gov (United States)

    Shimoyama, Mary; Smith, Jennifer R; Bryda, Elizabeth; Kuramoto, Takashi; Saba, Laura; Dwinell, Melinda

    2017-07-01

    Rats remain a major model for studying disease mechanisms and discovery, validation, and testing of new compounds to improve human health. The rat's value continues to grow as indicated by the more than 1.4 million publications (second to human) at PubMed documenting important discoveries using this model. Advanced sequencing technologies, genome modification techniques, and the development of embryonic stem cell protocols ensure the rat remains an important mammalian model for disease studies. The 2004 release of the reference genome has been followed by the production of complete genomes for more than two dozen individual strains utilizing NextGen sequencing technologies; their analyses have identified over 80 million variants. This explosion in genomic data has been accompanied by the ability to selectively edit the rat genome, leading to hundreds of new strains through multiple technologies. A number of resources have been developed to provide investigators with access to precision rat models, comprehensive datasets, and sophisticated software tools necessary for their research. Those profiled here include the Rat Genome Database, PhenoGen, Gene Editing Rat Resource Center, Rat Resource and Research Center, and the National BioResource Project for the Rat in Japan. © The Author 2017. Published by Oxford University Press.

  12. Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy.

    Science.gov (United States)

    Dagher, Zeina; Park, Yong Seek; Asnaghi, Veronica; Hoehn, Todd; Gerhardinger, Chiara; Lorenzi, Mara

    2004-09-01

    The polyol (sorbitol) pathway of glucose metabolism is activated in many cell types when intracellular glucose concentrations are high, and it can generate cellular stress through several mechanisms. The role of the polyol pathway in the pathogenesis of diabetic retinopathy has remained uncertain, in part because it has been examined preferentially in galactose-induced retinopathy and in part because inhibition studies may not have achieved full blockade of the pathway. Having observed that the streptozotocin-induced diabetic rat accurately models many cellular processes characteristic of human diabetic retinopathy, we tested in the diabetic rat if documented inhibition of the polyol pathway prevents a sequence of retinal vascular abnormalities also present in human diabetes. An inhibitor of aldose reductase, the rate-limiting enzyme in the pathway, prevented the early activation of complement in the wall of retinal vessels and the decreased levels of complement inhibitors in diabetic rats, as well as the later apoptosis of vascular pericytes and endothelial cells and the development of acellular capillaries. Both rat and human retinal endothelial cells showed aldose reductase immunoreactivity, and human retinas exposed to high glucose in organ culture increased the production of sorbitol by a degree similar to that observed in the rat. Excess aldose reductase activity can be a mechanism for human diabetic retinopathy.

  13. The effect of Stevia rebaudiana on serum omentin and visfatin level in STZ-induced diabetic rats.

    Science.gov (United States)

    Akbarzadeh, Samad; Eskandari, Fatemeh; Tangestani, Hadis; Bagherinejad, Somaieh Tangerami; Bargahi, Afshar; Bazzi, Parviz; Daneshi, Adel; Sahrapoor, Azam; O'Connor, William J; Rahbar, Ali Reza

    2015-03-01

    Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of β-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats.

  14. The Effect of Pycnogenol on Wound Healing in Diabetic Rats.

    Science.gov (United States)

    Dogan, Elif; Yanmaz, Latif; Gedikli, Semin; Ersoz, Ugur; Okumus, Zafer

    2017-04-01

    Pycnogenol (PYC), an extract of pine bark, is known to have photoprotective, antimicrobial, antioxidant, and anti-inflammatory properties. An in vivo study was conducted to evaluate the effects of PYC treatment on wound healing in 48 adult male Sprague-Dawley rats, of which 24 were injected with a single dose of alloxan to induce diabetes. Three (3) excisional skin wounds (1.3 cm x 1.3 cm x 2 mm) were created in each healthy and diabetic animal. One (1) wound in each animal was left untreated, 1 was treated daily with a cleanser (ethacridine lactate) and covered with silver sulfadiazine (SSD), and 1 was treated with PYC powder (30 mg). After measuring wound size, 6 animals from both groups were sacrificed on days 3, 7, 14, and 21 and tissue samples were taken for histopathological evaluation of acute and chronic inflammation, granulation tissue, fibroblast maturation, collagen deposition, epithelialization, and neovascularization using a scoring system of 0 = none, 1 = mild, 2 = moderate, and 3 = abundant. Because the wounds created were not uniform in size within and among the animals, healing was expressed as a percentage of the initial wound size for each animal. Data were compared using 2-way analysis of variance; histopathological lesion scores were reported in median values in univariate analysis, with P wound surface area was 1.69 ± 0.44 cm². On day 21, the average reduction in wound size was lower in diabetic than in healthy rats (47.42% versus 50.91%, P wounds (P Wound size reduction was also significantly different between PYC and the cleanser/SSD treatment depending on the rats' health status (P wound size for the healthy rats had decreased more than in the diabetic rats (mean 50.91% versus 47.42%). Although reepithelialization was complete in both groups by day 21, complete neovascularization was evident in the healthy rats but not in the diabetic rats. Overall, compared to the untreated control wounds, treatments with cleanser/SSD and PYC were

  15. 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.

  16. Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

    Directory of Open Access Journals (Sweden)

    D. C. Damasceno

    2014-01-01

    Full Text Available Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

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

    Science.gov (United States)

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

    2013-10-01

    Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permeability of glomerular basement membrane plays an important role in DN pathogenesis. This study was performed to assess the effect of arctiin, the lignan constituent from Arctium lappa L., on metabolic profile and aggravation of renal lesions in a rat model of streptozotocin (STZ)-induced DN. STZ-induced diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via intraperitoneal injection for 8 weeks. Blood glucose and 24-h urinary albumin content were measured, and kidney histopathological changes were monitored. RT-PCR and immunohistochemistry were used to detect the mRNA and protein levels of nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats, respectively. Treatment with arctiin significantly decreased the levels of 24-h urinary albumin, prevented the sclerosis of glomeruli and effectively restored the glomerular filtration barrier damage by up-regulating the expression of nephrin and podocin and down-regulating HPSE level. Our studies suggest that arctiin might be beneficial for DN. The effects of arctiin on attenuating albuminuria and glomerulosclerosis are possibly mediated by regulating the expression of nephrin and podocin and HPSE in STZ-induced diabetic rats. Copyright © 2012 John Wiley & Sons, Ltd.

  18. Effect of potent ethyl acetate fraction of Stereospermum suaveolens extract in streptozotocin-induced diabetic rats.

    Science.gov (United States)

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

    2012-01-01

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

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

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    T. Balasubramanian

    2012-01-01

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

  20. Thyroid hormone improves insulin signaling and reduces the activation of neurodegenerative pathway in the hippocampus of diabetic adult male rats.

    Science.gov (United States)

    Prieto-Almeida, Fernanda; Panveloski-Costa, Ana Carolina; Crunfli, Fernanda; da Silva Teixeira, Silvania; Nunes, Maria Tereza; Torrão, Andréada Silva

    2018-01-01

    Diabetes mellitus (DM) and impairments of glucose metabolism and insulin resistance in the brain have been suggested as a likely etiology of Alzheimer's disease (AD). Studies have shown that thyroid hormones (THs) improve insulin sensitivity in DM rats and act as mediators of the plasticity of the nervous system altering behavior and cognitive function. Based on these findings, this study aimed to evaluate the effects of diabetes and triiodothyronine (T3) treatment upon proteins associated with DM and AD in the central nervous system. Euglycemic and Diabetic (alloxan-induced) male Wistar rats were daily treated with T3 (1.5μg/100g body weight) or vehicle (saline) for a 4-week period and subdivided into the following groups: euglycemic treated with saline (Control=C); diabetic treated with saline (Diabetic=D); euglycemic treated with T3 (T3); diabetic treated with T3 (DT3). The expression of insulin signaling, neurodegenerative and neuron survival markers was evaluated in the hippocampus by immunoblotting, ELISA, and RT-PCR. T3 treatment decreased glycemia, restored the insulin signaling and reduced the activation of glycogen synthase kinase 3 (GSK3) and tau proteins content in the hippocampus of diabetic rats. The present data provide evidence that T3 treatment of diabetic rats is able to improve insulin sensitivity and reduce the activation of the neurodegenerative pathway in the brain, which might provide neuroprotection in this experimental model. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Hepatoprotective effect of tualang honey supplementation in streptozotocin-induced diabetic rats

    OpenAIRE

    OO Erejuwa; SA Sulaiman; MS Wahab; KNS Sirajudeen; MS Salleh; S Gurtu

    2012-01-01

    Summary: Hepatic dysfunction such as elevations of transaminases and alkaline phosphatase is associated with diabetes. We investigated the hepatoprotective effect of Malaysian tualang honey in streptozotocin (STZ; 60 mg/kg; ip)-induced diabetic rats by measuring serum AST, ALT and ALP activities. Non-diabetic and diabetic rats were administered distilled water or tualang honey orally for four weeks. Serum AST, ALP and ALT activities were significantly (p < 0.01) elevated in diabetic contro...

  2. Passive transfer of diabetes from BB/W to Wistar-Furth rats.

    OpenAIRE

    Koevary, S B; Williams, D E; Williams, R M; Chick, W L

    1985-01-01

    Autoimmune diabetes can be transferred to young, diabetes prone BB/W rats by injecting them intravenously with concanavalin A (Con A)-treated spleen cells from acute diabetic BB/W donors. This study describes the transfer of diabetes to the normal Wistar-Furth strain of rats using a similar procedure. For the successful transfer of diabetes it was necessary to immunosuppress recipient animals with a single intraperitoneal injection of cyclophosphamide 24-48 h before administering Con A-stimul...

  3. 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.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  5. Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats.

    Science.gov (United States)

    Arun, N; Nalini, N

    2002-01-01

    In the traditional system of medicine, Ayurveda, several spices and herbs are thought to possess medicinal properties. Among the spices, turmeric rhizomes (Curcuma longa. Linn.) are used as flavoring and coloring agents in the Indian diet everyday. In this research, we studied the effect of turmeric and its active principle, curcumin, on diabetes mellitus in a rat model. Alloxan was used to induce diabetes. Administration of turmeric or curcumin to diabetic rats reduced the blood sugar, Hb and glycosylated hemoglobin levels significantly. Turmeric and curcumin supplementation also reduced the oxidative stress encountered by the diabetic rats. This was demonstrated by the lower levels of TBARS (thiobarbituric acid reactive substances), which may have been due to the decreased influx of glucose into the polyol pathway leading to an increased NADPH/NADP ratio and elevated activity of the potent antioxdiant enzyme GPx. Moreover, the activity of SDH (sorbitol dehydrogenase), which catalyzes the conversion of sorbitol to fructose, was lowered significantly on treatment with turmeric or curcumin. These results also appeared to reveal that curcumin was more effective in attenuating diabetes mellitus related changes than turmeric.

  6. 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

  7. saRNA guided iNOS up-regulation improves erectile function of diabetic rats.

    Science.gov (United States)

    Wang, Tao; Li, Mingchao; Yuan, Huixin; Zhan, Yin; Xu, Hua; Wang, Shaogang; Yang, Weiming; Liu, Jihong; Ye, Zhangqun; Li, Long-Cheng

    2013-08-01

    Promoter targeted saRNAs mediate sequence specific up-regulation of gene expression. We explored the therapeutic effect of RNA activation mediated iNOS gene activation on improving erectile function in a rat model of diabetes mellitus. An optimal saRNA sequence specific for iNOS promoter was cloned into an adenoviral vector, resulting in AdU6/shiNOS and AdU6/shControl. The corresponding viruses were used to transduce cultured rat cavernous smooth muscle cells. Streptozotocin induced diabetes models were established in rats and used to test the effects of intracavernous delivery of iNOS saRNA viruses on erectile function. iNOS expression in the cavernous smooth muscle cells or penile tissue of treated rats was assessed by reverse transcriptase-polymerase chain reaction and Western blot. Cyclic guanosine monophosphate was analyzed by enzyme-linked immunosorbent assay. Intracavernous pressure in response to cavernous nerve stimulation was measured using a data acquisition system on post-injection days 1, 3, 5, 7, 10 and 14. Adenovirus mediated expression of iNOS saRNA caused sustained up-regulation of iNOS in cavernous smooth muscle cells. Intracavernous injection of AdU6/shiNOS activated iNOS expression in vivo and significantly increased peak intracavernous pressure in streptozotocin induced diabetic rats via nitric oxide/intracellular cyclic guanosine monophosphate activation. Results show that saRNA mediated iNOS over expression in the penis can restore erectile function in streptozocin diabetic rats via the nitric oxide-cyclic guanosine monophosphate pathway. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Anti-Diabetic Potential of the Leaves of Anisomeles malabarica in Streptozotocin Induced Diabetic Rats

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    Peddanna Kotha

    2017-10-01

    Full Text Available Background/Aims: Diabetes mellitus is a pandemic metabolic disorder that is affecting a majority of populations in recent years. There is a requirement for new drugs that are safer and cheaper due to the side effects associated with the available medications. Methods: We investigated the anti-diabetic activity of leaves of Anisomeles malabarica following bioactivity guided fractionation. The different solvent (hexane, ethyl acetate, methanol and water extracts of A. malabarica leaves were used in acute treatment studies to evaluate and identify the active fraction. The ethyl acetate extract was subjected to further fractionation using silica gel column chromatography and the compounds were identified by LC-SRM/MS and GC-MS. Additional chronic treatment studies were carried out using this active fraction (AMAF for 30 days in experimental diabetic rats. Fasting blood glucose (FBG, glycosylated hemoglobin (HbA1c, plasma insulin levels and glucose tolerance were measured along with insulin resistance/sensitivity indicators (HOMA-IR, HOMA-β and QUICKI to assess the beneficial effects of A. malabarica in the management of diabetes mellitus. Results: Among the different solvent extracts tested, ethyl acetate extract showed maximum (66% anti-hyperglycemic activity. The hexane and ethyl acetate (1: 1 fraction that has maximum anti-diabetic activity was identified as active fraction of A. malabarica (AMAF. The FBG, HbA1c, plasma insulin levels and insulin sensitivity/resistance indicators such as glucose tolerance, HOMA-IR, HOMA-β and QUICKI were significantly improved to near normal in diabetic rats treated with AMAF. Further, we identified key flavonoids and fatty acids as the anti-diabetic active principles from the AMAF of A. malabarica leaves. Conclusion: The results of our study suggest that Anisomeles malabarica has potential anti-diabetic activity in STZ induced diabetic rats.

  9. Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes.

    Science.gov (United States)

    Inceoglu, Bora; Wagner, Karen M; Yang, Jun; Bettaieb, Ahmed; Schebb, Nils H; Hwang, Sung Hee; Morisseau, Christophe; Haj, Fawaz G; Hammock, Bruce D

    2012-07-10

    The nerve damage occurring as a consequence of glucose toxicity in diabetes leads to neuropathic pain, among other problems. This pain dramatically reduces the quality of life in afflicted patients. The progressive damage to the peripheral nervous system is irreversible although strict control of hyperglycemia may prevent further damage. Current treatments include tricyclic antidepressants, anticonvulsants, and opioids, depending on the severity of the pain state. However, available therapeutics have drawbacks, arguing for the need to better understand the pathophysiology of neuropathic pain and develop novel treatments. Here we demonstrate that stabilization of a class of bioactive lipids, epoxygenated fatty acids (EpFAs), greatly reduces allodynia in rats caused by streptozocin-induced type I diabetes. Inhibitors of the soluble epoxide hydrolase (sEHI) elevated and stabilized the levels of plasma and spinal EpFAs, respectively, and generated dose-dependent antiallodynic effects more potently and efficaciously than gabapentin. In acute experiments, positive modulation of EpFAs did not display differences in insulin sensitivity, glucose tolerance, or insulin secretion, indicating the efficacy of sEHIs are not related to the glycemic status. Quantitative metabolomic analysis of a panel of 26 bioactive lipids demonstrated that sEHI-mediated antiallodynic effects coincided with a selective elevation of the levels of EpFAs in the plasma, and a decrease in degradation products coincided with the dihydroxy fatty acids in the spinal cord. Overall, these results argue that further efforts in understanding the spectrum of effects of EpFAs will yield novel opportunities in treating neuropathic pain.

  10. Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

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    Haider Raza

    2015-02-01

    Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

  11. Effects of high-fat diet and fructose-rich diet on obesity, dyslipidemia and hyperglycemia in the WBN/Kob-Leprfa rat, a new model of type 2 diabetes mellitus.

    Science.gov (United States)

    Namekawa, Junichi; Takagi, Yoshiichi; Wakabayashi, Kaoru; Nakamura, Yuki; Watanabe, Ayaka; Nagakubo, Dai; Shirai, Mitsuyuki; Asai, Fumitoshi

    2017-06-10

    Obesity and type 2 diabetes mellitus (T2DM) are occurring at epidemic-like rates, and these epidemics appear to have emerged largely from changes in daily diet. In the present study, we compared effects of high-fat diet (HFD) and fructose-rich diet (FRD) in WBN/Kob-Lepr fa (WBKDF) rats that spontaneously develop obesity, dyslipidemia and T2DM. After a 4-week feeding of each diet, WBKDF-HFD and WBKDF-FRD rats exhibited aggravated obesity and dyslipidemia compared with WBKDF rats fed standard diet (STD). In contrast, hyperglycemia developed in WBKDF-STD rats was significantly inhibited in WBKDF-FRD rats, but not in WBKDF-HFD rats. The present study demonstrated that the 4-week feeding of HFD and FRD caused diet-induced obesity with a distinct phenotype in the glucose metabolism in WBKDF rats.

  12. [Effect of protein intervention on amino acid metabolism spectrum of Qi and Yin deficiency type 2 diabetic rats].

    Science.gov (United States)

    Ma, Li-Na; Mao, Xin-Min; Ma, Xiao-Li; Li, Lin-Lin; Wang, Ye; Tao, Yi-Cun; Wang, Jing-Wei; Guo, Jia-Jia; Lan, Yi

    2016-11-01

    To study the effect of plant protein and animal protein on amino acid metabolism spectrum of Qi and Yin deficiency type 2 diabetic rats. 110 male SD rats were randomly divided into blank group (n=10), diabetic model group (n=20), disease-symptoms group (n=80). The rats of blank group received ordinary feeding, while other groups were fed with high sugar and fat diets. During the whole process of feeding, rats of disease-symptoms group were given with Qingpi-Fuzi (15.75 g•kg⁻¹) once a day through oral administration. Five weeks later, the rats were given with a low dose of STZ (40 mg•kg⁻¹) by intraperitoneal injection to establish experimental diabetic models. Then the models were randomly divided into disease-symptoms group 1 (Qi and Yin deficiency diabetic group, 15.75 g•kg⁻¹), disease-symptoms group 2 (plant protein group, 0.5 g•kg⁻¹), disease-symptoms group 3 (animal protein group, 0.5 g•kg⁻¹), disease-symptoms group 4 (berberine group, 0.1 g•kg⁻¹). The drugs were given for 4 weeks by gavage administration. After 4 weeks of protein intervention, the abdominal aortic blood was collected and serum was isolated to analyze its free amino acid by using AQC pre-column derivatization HPLC and fluorescence detector. Four weeks after the protein intervention, plant protein, animal protein and berberine had no obvious effect on body weight and blood sugar in type 2 diabetic rats. As compared with animal protein group, histidine and proline(PYin deficiency type 2 diabetic SD rats. Symbolic differential compounds could be found through metabonomics technology, providing experimental basis for early warning of type 2 diabetes and diagnosis of Qi and Yin deficiency syndrome. Copyright© by the Chinese Pharmaceutical Association.

  13. Mild Diabetes Models and Their Maternal-Fetal Repercussions

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    D. C. Damasceno

    2013-01-01

    Full Text Available The presence of diabetes in pregnancy leads to hormonal and metabolic changes making inappropriate intrauterine environment, favoring the onset of maternal and fetal complications. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons but also by the many uncontrollable variables. Thus, there is a need to develop appropriate experimental models. The diabetes induced in laboratory animals can be performed by different methods depending on dose, route of administration, and the strain and age of animal used. Many of these studies are carried out in neonatal period or during pregnancy, but the results presented are controversial. So this paper, addresses the review about the different models of mild diabetes induction using streptozotocin in pregnant rats and their repercussions on the maternal and fetal organisms to propose an adequate model for each approached issue.

  14. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    Science.gov (United States)

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy.

  15. Modelling diabetic nephropathy in mice.

    Science.gov (United States)

    Azushima, Kengo; Gurley, Susan B; Coffman, Thomas M

    2018-01-01

    Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the developed world. Accordingly, an urgent need exists for new, curative treatments as well as for biomarkers to stratify risk of DN among individuals with diabetes mellitus. A barrier to progress in these areas has been a lack of animal models that faithfully replicate the main features of human DN. Such models could be used to define the pathogenesis, identify drug targets and test new therapies. Owing to their tractability for genetic manipulation, mice are widely used to model human diseases, including DN. Questions have been raised, however, about the general utility of mouse models in human drug discovery. Standard mouse models of diabetes typically manifest only modest kidney abnormalities, whereas accelerated models, induced by superimposing genetic stressors, recapitulate key features of human DN. Incorporation of systems biology approaches and emerging data from genomics and metabolomics studies should enable further model refinement. Here, we discuss the current status of mouse models for DN, their limitations and opportunities for improvement. We emphasize that future efforts should focus on generating robust models that reproduce the major clinical and molecular phenotypes of human DN.

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

    International Nuclear Information System (INIS)

    Dallak, M.; Jaliah, B.I.

    2010-01-01

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

  17. 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...

  18. Biomechanical and morphological remodelings of gastrointestinal tract in STZ-induced diabetic rats

    DEFF Research Database (Denmark)

    Sha, Hong; Zhao, Jingbo; Liu, Gui-Fang

    2012-01-01

    AIM: The aim of the study was to investigate the biomechanical and morphometrical remodeling of gastrointestinal (GI) tract in streptozotocin (STZ) induced diabetic rats. METERIALS AND METHODS: Eighteen SD male rats of diabetic group(DM, a single tail vein injection 40mg/kg of STZ, 9 rats) and no...

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

    Science.gov (United States)

    Kilari, Eswar Kumar; Putta, Swathi

    2017-03-01

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

  20. Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Abdelaziz, Dalia H A; Ali, Sahar A; Mostafa, Mahmoud M A

    2015-06-01

    In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored. The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats. The aqueous suspension of P. dactylifera seeds (aqPDS) (1 g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase. Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248 ± 42 versus 508 ± 60 mg/dl), urea (32 ± 3.3 versus 48.3 ± 5.6 mg/dl), creatinine (2.2 ± 0.35 versus 3.8 ± 0.37 mg/dl), ALT (29.6 ± 3.9 versus 46.4 ± 5.9 IU/l), and AST (73.3 ± 13 versus 127.8 ± 18.7 IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats. The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.

  1. Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats.

    Science.gov (United States)

    Zhang, Jun; Bai, Xiaozhi; Zhao, Bin; Wang, Yunchuan; Su, Linlin; Chang, Peng; Wang, Xujie; Han, Shichao; Gao, Jianxin; Hu, Xiaolong; Hu, Dahai; Liu, Xiaoyan

    2016-05-01

    Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 × 10(6) allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection.

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

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ahad, Amjid [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Ganai, Ajaz Ahmad [Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Mujeeb, Mohd [Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Siddiqui, Waseem Ahmad, E-mail: was.sid121@gmail.com [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India)

    2014-08-15

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

  4. The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats

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    Sebastian Steven

    2017-10-01

    Full Text Available Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i, empagliflozin (Jardiance®, ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM. The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes. The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothelial dysfunction in Zucker diabetic fatty (ZDF rats. Male ZDF rats were used as a model of T2DM (35 diabetic ZDF‐Leprfa/fa and 16 ZDF-Lepr+/+ controls. Empagliflozin (10 and 30 mg/kg/d was administered via drinking water for 6 weeks. Treatment with empagliflozin restored glycemic control. Empagliflozin improved endothelial function (thoracic aorta and reduced oxidative stress in the aorta and in blood of diabetic rats. Inflammation and glucotoxicity (AGE/RAGE signaling were epigenetically prevented by SGLT2i treatment (ChIP. Linear regression analysis revealed a significant inverse correlation of endothelial function with HbA1c, whereas leukocyte-dependent oxidative burst and C-reactive protein (CRP were positively correlated with HbA1c. Viability of hyperglycemic endothelial cells was pleiotropically improved by SGLT2i. Empagliflozin reduces glucotoxicity and thereby prevents the development of endothelial dysfunction, reduces oxidative stress and exhibits anti-inflammatory effects in ZDF rats, despite persisting hyperlipidemia and hyperinsulinemia. Our preclinical observations provide insights into the mechanisms by which empagliflozin reduces cardiovascular mortality in humans (EMPA-REG trial.

  5. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats

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    Luciana Jorge

    2012-01-01

    Full Text Available 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.

  7. Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats

    Science.gov (United States)

    Jorge, Luciana; da Pureza, Demilto Y.; Dias, Danielle da Silva; 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. PMID:22203833

  8. Diabetic rats exercised prior to and during pregnancy: maternal reproductive outcome, biochemical profile, and frequency of fetal anomalies.

    Science.gov (United States)

    Damasceno, Débora Cristina; Silva, Hellen Pontes; Vaz, Geizi Fátima; Vasques-Silva, Francine Aparecida; Calderon, Iracema Mattos Paranhos; Rudge, Marilza Vieira Cunha; Campos, Kleber Eduardo; Volpato, Gustavo Tadeu

    2013-07-01

    The aim of this study was to evaluate the effects of exercise prior to or during pregnancy on maternal reproductive outcome, biochemical profile, and on fetal anomaly frequency in a rat pregnancy model utilizing chemically induced diabetes. Wistar rats (minimum n = 11 animals/group) were randomly assigned the following groups: group 1 (G1), sedentary, nondiabetic; G2, nondiabetic, exercised during pregnancy; G3, nondiabetic, exercised prior to and during pregnancy; G4, sedentary, diabetic; G5, diabetic, exercised during pregnancy; and G6, diabetic, exercised prior to and during pregnancy. A swimming program was utilized for moderate exercise. On day 21 of pregnancy, all rats were anesthetized to obtain blood for biochemical measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The nondiabetic rats exercised prior to pregnancy presented a reduced maternal weight gain. Besides, G2 and G3 groups showed decreased fetal weights at term pregnancy, indicating slight intrauterine growth restriction (IUGR). In the diabetic dams, the swimming program did not have antihyperglycemic effects. The exercise applied only during pregnancy caused severe IUGR, as confirmed by reduced fetal weight mean, fetal weight classification, and ossification sites. Nevertheless, exercise was not a teratogenic factor and improved the rats' lipid profiles, demonstrating that the exercise presented possible benefits, but there are also risks prior and during pregnancy, especially in diabetic pregnant women.

  9. The Effect of Food Hardness on the Development of Dental Caries in Alloxan-Induced Diabetic Rats

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    Yutaka Nakahara

    2013-01-01

    Full Text Available We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats.

  10. Effect of Simulated Intermittent Altitude on the Metabolic and Hematologic Parameters in Streptozotocin Induced Diabetic Rats

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    mehdi Faramoushi

    2016-04-01

    Full Text Available Background & objectives: Type II diabetes is a metabolic disorder accompanied with insulin resistance of the whole body cells and is considered be the fifth cause of death in the world. Adaptation to altitude can lead to tolerance to many diseases. Therefore, the aim of this study was to determine the effect of simulated intermittent altitude on the metabolic and hematologic parameters and liver function in streptozotocin induced diabetic rats. Methods: In the current experimental study, twenty four male Wistar rats weighing 220±20 gr were randomly divided into three groups; normal control group (NC, n=8, diabetic control group (D, n=8 received fat diet for 2 weeks then were injected with streptozotocin (37 mg/kg and diabetic+hypoxia group (D+H, n=8 including diabetic rat exposed to chronic intermittent hypoxia (PiO2≈106 mm Hg, simulated altitude≈3400 m, 14% oxygen for 8 weeks. Diabetic, hematologic and lipid parameters as well as ALT and AST activities were measured in peripheral blood. Results: Our findings showed that intermittent hypoxia significantly decreased serum total cholesterol, LDL ,VLDL and triglyceride in D+H group compared to D group (p<0.05. Serum levels of fasting blood glucose and homeostatic model assessment-insulin resistance HOMA-IR( index and ALT were decreased in D+H group vs. D group p<0.05. Also, hemoglubin and hematocrite level increased in D+H group in comparison to D group p<0.05. No significant difference was detected in red blood cell count in D+H vs. D group. Conclusion: Based on resultant data, it seems that intermittent exposure to hypoxia (simulated to chronic and intermittent lodgement in altitude can be used to control of type 2 diabetes by increasing hemoglobin, decreasing insulin resistance and improving liver function as well as lipid parameters.

  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. 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.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  14. 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

  15. Allopregnanolone suppresses diabetes-induced neuropathic pain and motor deficit through inhibition of GABAA receptor down-regulation in the spinal cord of diabetic rats

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    Samira Afrazi

    2014-05-01

    Full Text Available Objective(s:Painful diabetic neuropathy is associated with hyperexcitability and hyperactivity of spinal cord neurons. However, its underlying pathophysiological mechanisms have not been fully clarified. Induction of excitatory/inhibitory neurotransmission imbalance at the spinal cord seems to account for the abnormal neuronal activity in diabetes. Protective properties of neurosteroids have been demonstrated in numerous cellular and animal models of neurodegeneration. Materials and Methods: Here, the protective effects of allopregnanolone, a neurosteroid were investigated in an in vivo model of diabetic neuropathy. The tail-flick test was used to assess the nociceptive threshold. Diabetes was induced by injection of 50 mg/kg (IP streptozotocin. Seven weeks after the induction of diabetes, the dorsal half of the lumbar spinal cord was assayed for the expression of γ2 subunit of GABAA receptor using semiquantitative RT-PCR. Results: The data shows that allopregnanolone (5 and 20 mg/kg markedly ameliorated diabetes-induced thermal hyperalgesia and motor deficit. The weights of diabetic rats that received 5 and 20 mg/kg allopregnanolone did not significantly reduce during the time course of study. Furthermore, this neurosteroid could inhibit GABAA receptor down-regulation induced by diabetes in the rat spinal cord. Conclusion: The data revealed that allopregnanolone has preventive effects against hyperglycemic-induced neuropathic pain and motor deficit which are related to the inhibition of GABAA receptor down-regulation.

  16. Reproduction in Brattleboro rats with diabetes insipidus

    NARCIS (Netherlands)

    Boer, K.; Boer, G. J.; Swaab, D. F.

    1981-01-01

    The Brattleboro diabetes insipidus mutant is incapable of synthesizing vasopressin, but is activated in its production and release of oxytocin. In the homozygous female mutant, there were abnormally short and long oestrous cycles and reduced conception rates after mating with mutant males, a

  17. Altered magnesium transport in slices of kidney cortex from chemically-induced diabetic rats

    International Nuclear Information System (INIS)

    Hoskins, B.

    1981-01-01

    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

  18. Glycemic control with insulin prevents progression of dental caries and caries-related periodontitis in diabetic WBN/KobSlc rats.

    Science.gov (United States)

    Nakahara, Yutaka; Sano, Tomoya; Kodama, Yasushi; Ozaki, Kiyokazu; Matsuura, Tetsuro

    2013-07-01

    We have previously reported that dental caries progress in spontaneously and chemically induced diabetic rodent models. The aim of this study was to clarify the relationship between hyperglycemia and dental caries by evaluating the preventive effect of glycemic control with insulin on the progression of the lesions in diabetic rats. Male WBN/KobSlc rats aged 15 weeks were divided into groups of spontaneously diabetic rats (intact group), spontaneously diabetic rats with insulin treatment (INS group), alloxan-induced prolonged diabetic rats (AL group), and alloxan-induced prolonged diabetic rats with insulin treatment (AL + INS group). The animals were killed at 90 weeks of age, and their oral tissue was examined. Dental caries and periodontitis were frequently detected in the intact group, and the lesions were enhanced in the AL group (in which there was an increased duration of diabetes). Meanwhile, glycemic control with insulin reduced the incidence and severity of dental caries and periodontitis in the INS group, and the effects became more pronounced in the AL + INS group. In conclusion, glycemic control by insulin prevented the progression of dental caries and caries-related periodontitis in the diabetic rats.

  19. Antihyperglycemic and Antihyperlipidemic Activity of Plectranthus Amboinicus on Normal and Alloxan-Induced Diabetic Rats

    OpenAIRE

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

    2011-01-01

    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...

  20. Role of exercise training in cardiovascular autonomic dysfunction and mortality in diabetic ovariectomized rats

    OpenAIRE

    Souza, Silvia Beatriz Paulino Cavasin de [UNIFESP; Flues, Karin; Paulini, Janaina; Mostarda, Cristiano [UNIFESP; Rodrigues, Bruno; Souza, Leandro E.; Irigoyen, Maria Claudia [UNIFESP; De Angelis, Katia

    2007-01-01

    Diabetes and menopause markedly increase the risk of cardiovascular disease in women. the objective of the present study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction and on total mortality in diabetic female rats undergoing ovarian hormone deprivation. Female Wistar rats were divided into ovariectomized groups: sedentary and trained controls and sedentary and trained diabetic rats (streptozotocin, 50 mg/kg IV). Trained groups were submitted to an...

  1. 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.

  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. [Effect of total glucosides of paeony on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats].

    Science.gov (United States)

    Chang, Bao-Chao; Chen, Wei-Dong; Zhang, Yan; Yang, Ping; Liu, Lei; Wang, Jing

    2014-10-01

    The study is to explore the effect of total glucosides of paeony (TGP)on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats, and discuss the protection of TGP in diabetic nephropathy and possible mechanism. Ninety male SD rats of 8 weeks age were randomly divided into normal control group (n = 10) and model group (n = 80). Rats of the normal control group were fed with regular diet, while rats of the model group were fed with high-fat high-sugar diet and 4 weeks later were given an intraperitoneal injection of 35 mg x kg(-1) streptozotocin (STZ). The successfully induced type 2 diabetic rat models were then randomly divided into DM group, three TGP (50, 100, 200 mg x kg(-1) x d(-1)) treatment group and tripterygium wilfordii glycosides (8 mg x kg(-1) x d(-1)) control group. Rats of DM group and each treatment group were given high-fat high-sugar diet. At week 14, the levels of blood sugar, 24 hour urine protein, serum creatinine and blood urea nitrogen were tested. The rats were then sacrificed. Renal pathological changes were examined. Renal tissue Wnt-1 and β-catenin expressions were detected by immunohistochemical assay. Wnt-1 mRNA and β-catenin mRNA expression was semi-quantified by RT-PCR. Wnt-1 protein and β-catenin protein expression was semi-quantified by Western blot. The Result show that Wnt-1 and β-catenin expression increased in kidney of high-fat high-sugar induced type 2 diabetic rats. Compared with diabetic group, the level of serum creatinine, blood urea nitrogen, 24 h urine protein, mean glomerular area and mean glomerular volume were decreased, renal histopathology were improved, expression of Wnt-1 and β-catenin mRNA and protein was reduced in TGP group. Tripterygium wilfordii glycosides had the similar effect. In conclusion, these results showed that Wnt/β-catenin abnormal activation in kidney of type 2 diabetic rats, TGP can improve kidney damage in diabetic rats and delay the development of diabetic

  4. Islet transplantation in diabetic rats normalizes basal and exercise-induced energy metabolism

    NARCIS (Netherlands)

    Houwing, Harmina; Benthem, L.; Suylichem, P.T.R. van; Leest, J. van der; Strubbe, J.H.; Steffens, A.B.

    Transplantation of islets of Langerhans in diabetic rats normalizes resting glucose and insulin levels, but it remains unclear whether islet transplantation restores resting and exercise-induced energy metabolism. Therefore, we compared energy metabolism in islet transplanted rats with energy

  5. Effect of Huayu Tongluo Herbs on Reduction of Proteinuria via Inhibition of Wnt/β-Catenin Signaling Pathway in Diabetic Rats

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    Lu Bai

    2017-01-01

    Full Text Available The study investigated the expression of Wnt/β-catenin pathway in diabetic rats and the intervention effect of Huayu Tongluo herbs (HTH. Ten rats were randomly selected as control group and the remaining rats were established as diabetic models. The diabetic rats were randomly divided into model group and HTH treatment group. The intervention was intragastric administration in all rats for 20 weeks. At the end of every 4 weeks, fasting blood glucose and 24 h urinary total protein quantitatively were measured. At the end of the 20th week, biochemical parameters and body weight were tested. The kidney tissues were observed under light microscope and transmission electron microscopy. We examined Wnt/beta-catenin signaling pathway key proteins and renal interstitial fibrosis related molecular markers expression. The results showed that HTH could reduce urinary protein excretion and relieve renal pathological damage. Wnt4, p-GSK3β (S9, and β-catenin expression were decreased in the signaling pathway, but GSK3β level was not changed by HTH in diabetic rats. Furthermore, the expressions of TGF-β1 and ILK were decreased, but the level of E-cadherin was increased in diabetic rats after treatment with HTH. This study demonstrated that HTH could inhibit the high expression of Wnt/β-catenin pathway in kidney of diabetic rats. The effect might be one of the main ways to reduce urinary protein excretion.

  6. Decreased Neuronal Bursting and Phase Synchrony in the Hippocampus of Streptozotocin Diabetic Rats

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    Zhimei Qiao

    2014-01-01

    Full Text Available Diabetic encephalopathy is one of the complications of diabetes. Cognitive dysfunction is the main consequence. Previous findings from neuroanatomical and in vitro electrophysiological studies showed that the structure and function of the hippocampus is impaired in diabetes, which may underlie the cognitive dysfunction induced by diabetes. However the study of electrophysiological abnormality of hippocampal neurons in intact networks is sparse. In the current study, we recorded the spontaneous firing of neurons in hippocampal CA1 area in anesthetized streptozotozin (STZ-diabetic and age-matched control rats. Profound reduction in burst activity was found in diabetic rats. Compared to control rats, the intra-burst inter-spike intervals were prolonged significantly in diabetic rats, while the burst ratio and the mean number of spikes within a burst decreased significantly. Treatment with APP 17-mer peptide retarded the effects of diabetes on these parameters. In addition, the average PLV of diabetic rats was lower than that of control rats. These findings provide in vivo electrophysiological evidence for the impairment of hippocampal function in STZ-diabetic rats, and may have some implications in the mechanisms associated with cognitive deficits in diabetes.

  7. Δ9-Tetrahydrocannabinol Prevents Cardiovascular Dysfunction in STZ-Diabetic Wistar-Kyoto Rats

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    Rebecca K. Vella

    2017-01-01

    Full Text Available The aim of this study was to determine if chronic, low-dose administration of a nonspecific cannabinoid receptor agonist could provide cardioprotective effects in a model of type I diabetes mellitus. Diabetes was induced in eight-week-old male Wistar-Kyoto rats via a single intravenous dose of streptozotocin (65 mg kg−1. Following the induction of diabetes, Δ9-tetrahydrocannabinol was administered via intraperitoneal injection (0.15 mg kg−1 day−1 for an eight-week period until the animals reached sixteen weeks of age. Upon completion of the treatment regime, assessments of vascular reactivity and left ventricular function and electrophysiology were made, as were serum markers of oxidative stress and lipid peroxidation. Δ9-Tetrahydrocannabinol administration to diabetic animals significantly reduced blood glucose concentrations and attenuated pathological changes in serum markers of oxidative stress and lipid peroxidation. Positive changes to biochemical indices in diabetic animals conferred improvements in myocardial and vascular function. This study demonstrates that chronic, low-dose administration of Δ9-tetrahydrocannabinol can elicit antihyperglycaemic and antioxidant effects in diabetic animals, leading to improvements in end organ function of the cardiovascular system. Implications from this study suggest that cannabinoid receptors may be a potential new target for the treatment of diabetes-induced cardiovascular disease.

  8. Enamel hypoplasia in a litter of rats with alloxan-induced diabetes mellitus

    OpenAIRE

    Silva-Sousa,Yara Teresinha Corrêa; Peres,Luiz Cesar; Foss,Milton Cesar

    2003-01-01

    Enamel hypoplasia is an important clinical problem commonly seen in children born to diabetic women. We aimed to characterize the enamel hypoplasia in Wistar rats born to alloxan-induced diabetes mellitus rats. Groups consisted of pregnant rats supplemented (ISDR) or not (NISDR) with insulin and controls, in which sterile saline solution was administered instead of alloxan or insulin. The mandibular incisors of one-month-old rats born to these mothers were analyzed. Whitish defective enamel w...

  9. Study on cognitive impairment in diabetic rats by different behavioral experiments

    Science.gov (United States)

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

    2017-12-01

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

  10. 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

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

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

    Science.gov (United States)

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

    2017-12-01

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

  12. Diabetes mellitus in the BB/W rat. Insulitis in pancreatic islet grafts after transplantation in diabetic recipients.

    OpenAIRE

    Weringer, E. J.; Like, A. A.

    1986-01-01

    Spontaneous diabetes mellitus in the BioBreeding/Worcester (BB/W) rat is preceded by lymphocytic insulitis which destroys pancreatic beta cells. Cultured major histocompatibility complex identical pancreatic islets and adrenal cortex derived from diabetes-resistant BB/W donors were transplanted into diabetic recipients with hyperglycemia of variable duration. Islet grafts were the targets of BB/W immune attack and revealed lymphocytic insulitis after transplantation into diabetic recipients e...

  13. Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats.

    Science.gov (United States)

    Meena, Sunita; Rajput, Yudhishthir S; Pandey, Amit K; Sharma, Rajan; Singh, Raghvendar

    2016-08-01

    This study was designed to assess anti-diabetic potential of goat, camel, cow and buffalo milk in streptozotocin (STZ) induced type 1 diabetic albino wistar rats. A total of 48 rats were taken for the study where one group was kept as non-diabetic control group (8 rats) while others (40 rats) were made diabetic by STZ (50 mg/kg of body weight) injection. Among diabetic rats, a control group (8 rats) was kept and referred as diabetic control whereas other four groups (8 rats each) of diabetic rats were fed on 50 ml of goat or camel or cow or buffalo milk for 4 weeks. All the rats (non-diabetic and diabetic) were maintained on standard diet for four weeks. STZ administration resulted in enhancement of glucose, total cholesterol, triglyceride, low density lipoprotein, HbA1c and reduction in high density lipoprotein in plasma and lowering of antioxidative enzymes (catalase, glutathione peroxidase and superoxide dismutase) activities in pancreas, kidney, liver and RBCs, coupled with enhanced levels of TBARS and protein carbonyls in pancreas, kidney, liver and plasma. OGTT carried out at the end of 4 week milk feeding indicated that all milks helped in early maintenance of glucose level. All milks reduced atherogenic index. In camel milk fed diabetic group, insulin concentration enhanced to level noted for non-diabetic control while goat, cow and buffalo milk failed to restore insulin level. HbA1c level was also restored only in camel milk fed diabetic group. The level of antioxidative enzymes (catalase, GPx and SOD) in pancreas enhanced in all milk fed groups. Camel milk and to a reasonable extent goat milk reduced formation of TBARS and PCs in tissues and blood. It can be concluded that camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. Further, only camel milk completely ameliorated oxidative damage in pancreas and normalised insulin level.

  14. Effect of Urtica dioica Leaf Alcoholic and Aqueous Extracts on the Number and the Diameter of the Islets in Diabetic Rats.

    Science.gov (United States)

    Qujeq, Durdi; Tatar, Mohsen; Feizi, Farideh; Parsian, Hadi; Sohan Faraji, Alieh; Halalkhor, Sohrab

    2013-01-01

    Urtica dioica has been known as a plant that decreases blood glucose. Despite the importance of this plant in herbal medicine, relatively little research has been down on effects of this plant on islets yet. The objective of the current study was to evaluate the effect of dried Urtica dioica leaf alcoholic and aqueous extracts on the number and the diameter of the islets and histological parameters in streptozocin-induced diabetic rats. Six rats were used in each group. Group I: Normal rats were administered saline daily for 8 weeks. Group II: Diabetic rats were administered streptozotocin, 50 mg/kg of body weight; Group III: Diabetic rats were administered dried Urtica dioica leaf aqueous extracts for 8 weeks; Group IV: Diabetic rats were administered dried Urtica dioica leaf alcoholic extracts for 8 weeks. The animals, groups of diabetic and normal, were sacrificed by ether anaesthesia. Whole pancreas was dissected. The tissue samples were formalin fixed and paraffin embedded for microscopic examination. Histologic examination and grading were carried out on hematoxylin-eosin stained sections. The effects of administration of dried Urtica dioica leaf alcoholic and aqueous extracts to diabetic rats were determined by histopathologic examination. The pancreas from control rats showed normal pancreatic islets histoarchitecture. Our results also, indicate that the pancreas from diabetic rats show injury of pancreas tissue while the pancreas from diabetic rats treated with dried Urtica dioica leaf alcoholic and aqueous extracts show slight to moderate rearrangement of islets. According to our findings, dried Urtica dioica leaf alcoholic and aqueous extracts can cause a suitable repair of pancreatic tissue in streptozocin-induced diabetic experimental model.

  15. Pharmacological postconditioning with atorvastatin calcium attenuates myocardial ischemia/reperfusion injury in diabetic rats by phosphorylating GSK3β.

    Science.gov (United States)

    Chen, Linyan; Cai, Ping; Cheng, Zhendong; Zhang, Zaibao; Fang, Jun

    2017-07-01

    Diabetes is an independent risk factor for myocardial ischemia, and many epidemiological data and laboratory studies have revealed that diabetes significantly exacerbated myocardial ischemia/reperfusion injury and ameliorated protective effects. The present study aimed to determine whether pharmacological postconditioning with atorvastatin calcium lessened diabetic myocardial ischemia/reperfusion injury, and investigated the role of glycogen synthase kinase (GSK3β) in this. A total of 72 streptozotocin-induced diabetic rats were randomly divided into six groups, and 24 age-matched male non-diabetic Sprague-Dawley rats were randomly divided into two groups. Rats all received 40 min myocardial ischemia followed by 180 min reperfusion, except sham-operated groups. Compared with the non-diabetic ischemia/reperfusion model group, the diabetic ischemia/reperfusion group had a comparable myocardial infarct size, but a higher level of serum cardiac troponin I (cTnI) and morphological alterations to their myocardial cells. Compared with the diabetic ischemia/reperfusion group, the group that received pharmacological postconditioning with atorvastatin calcium had smaller myocardial infarct sizes, lower levels of cTnI, reduced morphological alterations to myocardial cells, higher levels of p-GSK3β, heat shock factor (HSF)-1 and heat shock protein (HSP)70. The cardioprotective effect conferred by atorvastatin calcium did not attenuate myocardial ischemia/reperfusion injury following application of TDZD-8, which phosphorylates and inactivates GSK3β. Pharmacological postconditioning with atorvastatin calcium may attenuate diabetic heart ischemia/reperfusion injury in the current context. The phosphorylation of GSK3β serves a critical role during the cardioprotection in diabetic rats, and p-GSK3β may accelerate HSP70 production partially by activating HSF-1 during myocardial ischemic/reperfusion injury.

  16. Modulation of heme oxygenase-1 expression and activity affects streptozotocin-induced diabetic nephropathy in rats.

    Science.gov (United States)

    Ali, Marwa A M; Heeba, Gehan H; El-Sheikh, Azza A K

    2017-10-01

    Heme oxygenase (HO)-1 has exhibited nephro-protective actions in different animal models; however, its full mechanistic potential in diabetic nephropathy (DN) has not yet been elucidated. Hence, the present study has been undertaken by inducing DN in rats using streptozotocin (50 mg/kg i.p.), with or without either HO-1 inducer; hemin (HM; 40 μmol/kg, s.c.), or HO-1 blocker; zinc protoporphyrin-IX (ZnPP; 50 μmol/kg, i.p.), for one month. Compared to control, rats with DN suffered from hyperglycemia and hyperlipidemia, with signs of renal damage, as assessed by distortion in renal histopathologic architecture and kidney function. Renal oxidative/nitrosative stress was evident by increased malondialdehyde, nitric oxide, myeloperoxidase, with decreased reduced glutathione, superoxide dismutase, and catalase. DN group also exhibited high renal expression of the pro-inflammatory cytokine; tumor necrosis factor (TNF)-α, and the apoptotic marker; caspase 3, assessed by Western blot. Renal HO-1 protein expression and activity were increased in DN rats compared to control. Administration of HM, but not ZnPP, to DN rats improved kidney function, histopathologic features, lipid profile, TNF-α, and caspase 3 expressions, with no effect on blood glucose level. HM increased, while ZnPP decreased renal HO-1 activity in DN rats. It is noteworthy that neither intervention affected HO-1 activity or renal oxidative capacity in non-diabetic rats. Interestingly, the expression of HO-1 was upregulated by both HM and ZnPP in DN rats. In conclusion, activation of HO-1 via HM ameliorated renal damage in STZ-induced DN in rats, probably through antioxidant, anti-nitrosative, anti-inflammatory, and anti-apoptotic mechanisms. © 2017 Société Française de Pharmacologie et de Thérapeutique.

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

    Directory of Open Access Journals (Sweden)

    I. Salehi

    2009-07-01

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

  18. Analysis of Heart Rate Variability and Cardiac Autonomic Nerve Remodeling in Streptozotocin-induced Diabetic Rats.

    Science.gov (United States)

    Li, X; Jiang, Y-H; Jiang, P; Lin, H-Q; Yang, J-L; Ma, D-f; Wang, X; Yang, C-H

    2015-05-01

    Diabetes mellitus (DM) is associated with both cardiovascular and autonomic nervous system dysfunction. Spectral analysis of heart rate variability (HRV) can be used to monitor changes in response to autonomic innervation and stimulation of the heart. In this study, conducted in a rat model of diabetes, HRV and changes in associated neurotransmitters and neurotrophic factors in the right atrium (RA) were monitored. Diabetes was induced by streptozotocin (STZ) (60 mg/kg) in male Wistar rats, and HRV data were collected for 10 weeks by telemetry. Time and frequency domains of HRV data were analyzed using established metrics. The levels of various neural enzymes in the RA were determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence to characterize autonomic nerve remodeling. Insulin and methycobal were used to block the effects of STZ. HRV parameters reflecting parasympathetic tone (SDNN, RMSSD and HF domains) sharply decreased in the first 3 weeks after STZ administration; measures of sympathetic tone (SDANN) increased. After a series of adjustments, cardiac autonomic nerve innervation reached a new equilibrium, with a dominance of sympathetic tone. RA levels of tyrosine hydroxylase (TH) increased, and choline acetyltransferase (ChAT) decreased, indicating autonomic nerve remodeling. Levels of growth associated protein-43 (GAP43) and nerve growth factor (NGF) increased during the period of diabetes-induced cardiac-nerve damage; however, the level of ciliary neurotrophic factor (CNTF) decreased. The physical condition and indexes of rats were normalized in different degree after administration of the insulin and methycobal, but not completely recovered. STZ-induced diabetes was associated with cardiac autonomic nerve dysfunction at both the organ and molecular levels. Parasympathetic nerves exhibited severe damage and/or weak recovery; remodeling of sympathetic nerves predominated during 10-weeks of STZ-induced diabetes. © Georg Thieme Verlag

  19. Quantitative-profiling of neurotransmitter abnormalities in the disease progression of experimental diabetic encephalopathy rat.

    Science.gov (United States)

    Zhou, Xueyan; Zhu, Qiuxiang; Han, Xiaowen; Chen, Renguo; Liu, Yaowu; Fan, Hongbin; Yin, Xiaoxing

    2015-11-01

    Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters. Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF, hippocampus, and cortex were all significantly down-regulated as early as 6 weeks in the STZ treatment group. In contrast, the glutamate (Glu) levels were decreased in CSF and the hippocampus, but unaffected in the serum and cortex of STZ-treated rats. As for γ-aminobutyric acid (GABA), it was down-regulated in serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated group. The mRNA expressions of neurotransmitter-related rate limiting enzymes (including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL-1β and TNF-α) were all increased in the DE rats. Our data suggest that DM induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and that neuroinflammation may underlay the nervous system dysfunction observed in the progression of DE.

  20. The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

    Science.gov (United States)

    Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

    2016-01-01

    Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin

  1. The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

    Directory of Open Access Journals (Sweden)

    Adriana Márquez-Ibarra

    Full Text Available Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance.Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups.Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of

  2. Effects of training and nitric oxide on diabetic nephropathy progression in type I diabetic rats.

    Science.gov (United States)

    Rodrigues, Adelson M; Bergamaschi, Cássia T; Araújo, Ronaldo C; Mouro, Margaret G; Rosa, Thiago S; Higa, Elisa M S

    2011-10-01

    The aim of the paper is to assess nitric oxide (NO) production during aerobic training and its role on the progression of diabetic nephropathy in rats. Induction of diabetes mellitus (DM) was achieved in adult male Wistar rats with streptozotocin. Half of the animals underwent training on a treadmill and the others (sedentary) stayed on a turned-off treadmill for the same period according to the following groups: sedentary control (CTL + SE); training control (CTL + EX); sedentary diabetic (DM + SE); and training diabetic (DM + EX) (n = 9 for all groups). The training on treadmill was carried out at a work rate of 16 m/min, 60 min/d, 5 d/week for eight weeks. Before and after the exercises, rats were placed in individual metabolic cages with standard chow and water ad libitum, for 24-h urine collection, followed by three hours' fasting blood sample withdrawal from the retro-orbital plexus, under anesthesia. Diabetic animals showed reduction of body weight, creatinine and urea depurations and NO excretion, increased blood glucose concentrations, albuminuria and thiobarbituric acid reactive substance (TBARS) excretion, when compared with the respective controls. All these alterations induced by DM were attenuated in the DM + EX versus DM + SE group. Analysis of insulin concentrations at the end of the protocol showed no significant change between the DM + SE and DM + EX groups. In conclusion, our data show that a routine physical exercise resulted in a better control of glycemia with an increased NO bioavailability and oxidative stress control, associated with an amelioration of renal function. We suggest aerobic training and the control of oxidative and nitrosative stress as useful non-pharmacological tools to delay the progression of diabetic nephropathy.

  3. Effect of tetrahydrocurcumin on lipid peroxidation and lipids in streptozotocin-nicotinamide-induced diabetic rats.

    Science.gov (United States)

    Murugan, Pidaran; Pari, Leelavinothan

    2006-08-01

    Hyperlipidaemia is an associated complication of diabetes mellitus. We recently reported that tetrahydrocurcumin lowered the blood glucose in diabetic rats. In the present study, we have investigated the effect of tetrahydrocurcumin, one of the active metabolites of curcumin on lipid profile and lipid peroxidation in streptozotocin-nicotinamide-induced diabetic rats. Tetrahydrocurcumin 80 mg/kg body weight was administered orally to diabetic rats for 45 days, resulted a significant reduction in blood glucose and significant increase in plasma insulin in diabetic rats, which proved its antidiabetic effect. Tetrahydrocurcumin also caused a significant reduction in lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxides) and lipids (cholesterol, triglycerides, free fatty acids and phospholipids) in serum and tissues, suggesting its role in protection against lipid peroxidation and its antihyperlipidemic effect. Tetrahydrocurcumin showed a better effect when compared with curcumin. Results of the present study indicate that tetrahydrocurcumin showed antihyperlipidaemic effect in addition to its antidiabetic effect in type 2 diabetic rats.

  4. Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats.

    Science.gov (United States)

    Mansouri, Esrafil; Khorsandi, Layasadat; Abedi, Hassan Ali

    2014-06-01

    Diabetes plays an important role in the induction of the liver injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal properties against oxidative stress. In this study we evaluated antioxidant effects of GSP on liver in streptozotocin-induced diabetic rats. Thirty male Sprague-Dawley rats were divided into three groups: control, untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were administered via oral gavage (200 mg/kg) for 4 weeks. GSP produced significant hepatoprotective effects by decreasing activities of serum aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde and bilirubin (PGSP significantly ameliorated structural changes induced in liver of diabetic rats. GSP have protective effects against hepatic tissue injury due to antioxidant properties.

  5. Alterações pulmonares em um modelo de diabetes mellitus em ratos: o efeito da terapia antioxidante Lung alterations in a rat model of diabetes mellitus: effects of antioxidant therapy

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Forgiarini Junior

    2010-10-01

    Full Text Available OBJETIVO: Avaliar as alterações estruturais no pulmão de ratos com diabetes mellitus (DM através da quantificação do estresse oxidativo e do dano ao DNA, assim como determinar os efeitos de superóxido dismutase (SOD exógena nessas alterações. MÉTODOS: Estudo experimental controlado com 40 ratos Wistar, divididos em quatro grupos (10 animais cada: grupo controle, grupo SOD (sem DM e tratados com SOD, grupo DM (com DM induzido por estreptozotocina, e grupo DM+SOD (com DM induzido por estreptozotocina e tratados com SOD. Os animais foram avaliados por um período de 60 dias, iniciado a partir do dia em que os animais com diabetes induzido por estreptozotocina apresentaram glicemia > 250 mg/dL. Nos últimos 7 dias do período, os animais nos grupos tratados receberam SOD. Ao final do tempo de estudo, amostras de tecido pulmonar foram coletadas para análise histopatológica e avaliação do estresse oxidativo e do dano ao DNA. RESULTADOS: Não houve diferenças significativas entre os grupos em relação ao dano ao DNA. Houve um aumento significativo na matriz extracelular e hiperplasia do endotélio capilar no grupo DM quando comparado com os grupos controle e SOD. Também houve mudanças significativas em pneumócitos tipo II e macrófagos intravasculares, sugerindo um processo inflamatório no grupo DM. Entretanto, uma redução na matriz extracelular, endotélio capilar normal e pneumócitos tipo II normais foram encontrados no grupo com DM+SOD. CONCLUSÕES: A administração exógena de SOD pode reverter alterações nos pulmões de animais com DM induzido.OBJECTIVE: To evaluate structural alterations of the lung in rats with diabetes mellitus (DM, by quantifying oxidative stress and DNA damage, as well as to determine the effects that exogenous superoxide dismutase (SOD has on such alterations. METHODS: A controlled experimental study involving 40 male Wistar rats, divided into four groups (10 animals each: control; SOD

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

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

    2018-01-01

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

  7. Abnormal levels of histone methylation in the retinas of diabetic rats are reversed by minocycline treatment

    DEFF Research Database (Denmark)

    Wang, Wenjun; Sidoli, Simone; Zhang, Wenquan

    2017-01-01

    In this study we quantified the alterations of retinal histone post-translational modifications (PTMs) in diabetic rats using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach. Some diabetic rats were subsequently treated with minocycline, a tetracycline antibiotic, which has...... been shown to inhibit the diabetes-induced chronic inflammation in the retinas of rodents. We quantified 266 differentially modified histone peptides, including 48 out of 83 methylation marks with significantly different abundancein retinas of diabetic rats as compared to non-diabetic controls. About...... 67% of these marks had their relative abundance restored to non-diabetic levels after minocycline treatment. Mono-and di-methylation states of histone H4 lysine 20 (H4K20me1/me2), markers related to DNA damage response, were found to be up-regulated in the retinas of diabetic rats and restored...

  8. Increase of beta-endorphin secretion by syringin, an active principle of Eleutherococcus senticosus, to produce antihyperglycemic action in type 1-like diabetic rats.

    Science.gov (United States)

    Niu, H-S; Hsu, F-L; Liu, I-M; Cheng, J-T

    2007-12-01

    We employed streptozotocin-induced diabetic rats (STZ-diabetic rats) as type 1 diabetes-like animal models to investigate the mechanism(s) of antihyperglycemic action produced by syringin, an active principle purified from the rhizome and root part S of ELEUTHEROCOCCUS SENTICOSUS (Araliaceae). Bolus intravenous (i. v.) injection of syringin dose-dependently decreased the plasma glucose of STZ-diabetic rats in 30 minutes in a way parallel to the increase of plasma beta-endorphin-like immunoreactivity (BER). Syringin enhanced BER release from the isolated adrenal medulla of STZ-diabetic rats in a concentration-dependent manner from 0.001 to 10 micromol/l. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of syringin (1 mg/kg, i. v.) including the plasma glucose-lowering effect and the plasma BER-elevating effect. Also, syringin failed to lower plasma glucose in the presence of micro-opioid receptor antagonists and/or in the micro-opioid receptor knockout diabetic mice. In conclusion, the obtained results suggest that syringin can enhance the secretion of beta-endorphin from adrenal medulla to stimulate peripheral micro-opioid receptors resulting in a decrease of plasma glucose in diabetic rats lacking insulin.

  9. Effects of total glucosides of paeony on oxidative stress in the kidney from diabetic rats.

    Science.gov (United States)

    Su, Jing; Zhang, Pei; Zhang, Jing-Jing; Qi, Xiang-Ming; Wu, Yong-Gui; Shen, Ji-Jia

    2010-03-01

    TGP, extracted from the traditional Chinese herb root of Paeonia lactiflora pall, has been shown to have therapeutic effect in experimental diabetic nephropathy. However, its mechanism is not fully understood. In this study, the effects of TGP on oxidative stress were investigated in the kidney of diabetic rats induced by streptozotocin. TGP (50, 100, 200mg/kg) was orally administered once a day for 8 weeks. TGP treatment in all three doses significantly lowered 24 h urinary albumin excretion rate in diabetic rats and attenuated glomerular volume. TGP treatment with 100 and 200mg/kg significantly reduced indices for tubulointerstitial injury in diabetic rats. The level of MDA was significantly increased in the kidney of diabetic rats and attenuated by TGP treatment at the dose of 200mg/kg. TGP treatment in a dose-dependent manner decreased the level of 3-NT protein of the kidney which increased under diabetes. T-AOC was significantly reduced in diabetic rat kidney and remarkably increased by TGP treatment at the dose of 100 and 200mg/kg. Activity of antioxidant enzyme such as SOD, CAT was markedly elevated by TGP treatment with 200mg/kg. Western blot analysis showed that p-p38 MAPK and NF-kappaB p65 protein expression increased in diabetic rat kidney, which were significantly decreased by TGP treatment. It seems likely that oxidative stress is increased in the diabetic rat kidneys, while TGP can prevent diabetes-associated renal damage against oxidative stress.

  10. Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression

    Directory of Open Access Journals (Sweden)

    Mustafa S. Atta

    2017-04-01

    Full Text Available Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM. Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ works against diabetes-induced testicular deteriorations in rats. Wistar male rats (n = 60 were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg, Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg orally once daily, and TQ (non-diabetic rats treated with TQ for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO and malondialdehyde (MDA levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH levels and superoxide dismutase (SOD activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS and nuclear factor kappa-B (NF-κB and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats.

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

    Science.gov (United States)

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

    2017-09-01

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

  12. Phytopharmacological evaluation of Byesukar for hypoglycaemic activity and its effect on lipid profile and hepatic enzymes of glucose metabolism in diabetic rats.

    Science.gov (United States)

    Guruvayoorappan, C; Sudha, G

    2008-01-01

    Many anti-diabetic herbal preparations have been recommended in alternative systems of medicine for the treatment of diabetes. No systematic study has been done on the anti-diabetic efficacy of Byesukar, a polyherbal formulation to treat diabetes. The anti-diabetic efficacy of byesukar ethanol extract was evaluated in an animal model of diabetes induced by alloxan. Male Wistar rats were divided in to four groups. Group 1 was normal control group; group 2 and 3 received alloxan. After inducing experimental diabetes group 2 served as diabetic control; group 3 received byesukar (500 mg/kg body weight) orally for 30 consecutive days. Group 4 were normal rats which received byesukar extract alone. The effect of byesukar on glucose level in diabetic rats was studied and the level of glucose metabolizing enzymes (Hexokinase, glucose-6-phosphatase and fructose 1, 6-bisphosphatase) in the liver and kidney were estimated. The effect of byesukar on the serum and tissue lipid profile (Cholesterol, triglycerides, phospholipids and free fatty acids) were also estimated in diabetic rats. Our results indicate that treatment with byesukar resulted in significant reduction of blood glucose, tissue glucose-6-phosphatase and fructose 1, 6- bisphosphatase activity. The decreased tissue hexokinase activity in diabetes state was found to be significantly increased by byesukar treatment. Also the byesukar treated diabetic rats showed a significant decrease in the tissue lipid profile compared to the diabetic rats. In conclusion the decreased blood glucose accompanied with decreased lipid profile and changes in the activities of the glucose metabolizing enzymes shows the antidiabetic effect of byesukar.

  13. Berberine inhibits hepatic gluconeogenesis via the LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Jiang, Shu-Jun; Dong, Hui; Li, Jing-Bin; Xu, Li-Jun; Zou, Xin; Wang, Kai-Fu; Lu, Fu-Er; Yi, Ping

    2015-07-07

    To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model. The 40 rats were