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Sample records for stz induced diabetes

  1. Metformin ameliorates insulitis in STZ-induced diabetic mice

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    Guo-Jun Jiang; Xue Han; Yu-Long Tao; Ya-Ping Deng; Jia-Wen Yu; Jian Cai; Guo-Fei Ren; Yuan-Nan Sun

    2017-01-01

    Background & Aims Metformin is currently the most widely used first-line hypoglycemic agent for diabetes mellitus. Besides glucose-lowering action, there is increasingly interest in the potential anti-inflammatory action of this drug. In the present study, we investigated the actions of metformin on experimental insulitis using STZ-induced diabetic mice. Methods Mice with acute diabetes induced by STZ were administered metformin by gavage. Changes of blood glucose and body weight, and the dai...

  2. Metformin ameliorates insulitis in STZ-induced diabetic mice

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    Guo-Jun Jiang

    2017-04-01

    Full Text Available Background & Aims Metformin is currently the most widely used first-line hypoglycemic agent for diabetes mellitus. Besides glucose-lowering action, there is increasingly interest in the potential anti-inflammatory action of this drug. In the present study, we investigated the actions of metformin on experimental insulitis using STZ-induced diabetic mice. Methods Mice with acute diabetes induced by STZ were administered metformin by gavage. Changes of blood glucose and body weight, and the daily amount of food and water intake were measured. Pancreatic tissues were collected for histologic analyses. Pathological assessment and immunohistochemistry analysis were used to determine the effect of metformin on insulitis. Inflammatory cytokines in the pancreas and insulin levels were measured through ELISA analysis. Results Metformin significantly reduced blood glucose levels and improved aberrant water intake behavior in experimental diabetic mice. No significant differences were observed in terms of body weight and food intake behavior in metformin-treated animals. In the STZ-induced model of diabetes, we found the appearance of pronounced insulitis. However, metformin administration reduced the severity of insulitis assessed by blind pathological scoring. In addition, metformin treatment improved insulin levels in experimental diabetic mice. ELISA assay revealed decreased levels of inflammatory response marker IL-1β and TNF-α in the pancreatic tissues following metformin treatment. Conclusion Metformin attenuated insulitis in the STZ-induced mice model of diabetes. This islet-protective effect might be partly correlated with the anti-inflammatory action of metformin.

  3. 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.

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

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

    2012-09-01

    Rebaudioside A (Reb A), a major constituent of Stevia rebaudiana, was recently proposed as an insulinotropic agent. The aim of this investigation was to evaluate the antihyperglycemic effect of Reb A on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male Albino Wistar rats, weighing 180-200 g, by a single intraperitoneal injection at a dose of STZ (40 mg/kg body weight). Diabetic rats showed significant (Pdiabetic rats significantly (Pdiabetic rats. Thus, the results show that Reb A possesses an antihyperglycemic activity and provide evidence for its traditional usage in the control of diabetes.

  5. Anti-diabetic activity of peony seed oil, a new resource food in STZ-induced diabetic mice.

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    Su, Jianhui; Wang, Hongxin; Ma, Caoyang; Lou, Zaixiang; Liu, Chengxiang; Tanver Rahman, MdRamim; Gao, Chuanzhong; Nie, Rongjing

    2015-09-01

    This study was conducted to investigate the components of a new resource food in China, peony seed oil (PSO) by GC-MS (gas chromatography-mass spectrometry), its inhibitory effects on carbohydrate hydrolyzing enzymes in vitro and its anti-diabetic effects on mice induced by streptozotocin (STZ). The results showed that peony seed oil showed weak anti-α-amylase activity; however, strong anti-α-glucosidase activity was noted. The GC-MS analysis of the oil showed 9 constituents of which α-linolenic acid was found to be the major component (38.66%), followed by linoleic acid (26.34%) and oleic acid (23.65%). The anti-diabetic potential of peony seed oil was tested in STZ induced diabetic mice. Administration of peony seed oil and glibenclamide reduced the blood glucose level and the area under curve (AUC) in STZ induced diabetic mice. There were significant increases in body weight, liver glycogen content, serum insulin level, high-density lipoprotein cholesterol (HDL-C) and decreases in glycosylated hemoglobin (HbA1C), total serum cholesterol (TC), and triglyceride (TG) in test groups as compared to the untreated diabetic groups. In vivo antioxidant studies on STZ induced diabetic mice revealed the reduction of malondialdehyde (MDA) and increase of glutathione peroxides (GSH-px), superoxide dismutase (SOD), and glutathione (GSH). The results provided a sound rationale for future clinical trials of oral administration of peony seed oil to alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice.

  6. Biomechanical and morphological remodelings of gastrointestinal tract in STZ-induced diabetic rats

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    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 normal group (CON, 9 rats) were used in the study. Blood glucose and body weight was regularly measured. After 60 days of experiment, morphometric properties and residual strains were studied in esophageal, duodenal, jejunal, ileal, colonic and rectal segments. Stress-strain of the wall was also studied......, jejunal, colonic wall in circumferential direction and the esophageal, colonic wall in longitudinal direction increased in DM group compared those with CON group (Pdiabetes induces morphometric and biomechanical remodeling in the gastrointestinal tract which is likely...

  7. Determination of micronutrients and oxidative stress status in the blood of STZ-induced experimental diabetic rat models.

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

    2014-11-01

    This study aims to research the effect of streptozotocin (STZ) at different doses on the serum micronutrients and oxidative stress status in diabetic rat models. Twenty male rats averaged 250 g and 3-4 months old were used as experimental models. They were put in four groups composed of five rats each. Diabetic was induced by administering STZ 55 and 65 mg/kg intraperitonally. The serum micronutrients including minerals and vitamins (Cu, Zn, Mg, Fe, vitamins D, E, and C) and oxidative stress (malondialdehyde, MDA) were determined. Cu, Zn, and Vitamin D3 levels were found to increase significantly in STZ groups (p micronutrients were affected significantly.

  8. Novel hydrogen sulfide-releasing compound, S-propargyl-cysteine, prevents STZ-induced diabetic nephropathy

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    Qian, Xin [Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai (China); Li, Xinghui [Departments of Physiology and Pathophysiology, Shanghai College of Medicine, Fudan University, Shanghai (China); Ma, Fenfen; Luo, Shanshan [Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai (China); Ge, Ruowen [Departmentof Biological Sciences, National University of Singapore (Singapore); Zhu, Yizhun, E-mail: zhuyz@fudan.edu.cn [Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai (China); Departmentof Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore (Singapore)

    2016-05-13

    In this work, we demonstrated for the first time that S-propargyl-cysteine (SPRC, also named as ZYZ-802), a novel hydrogen sulfide (H{sub 2}S)-releasing compound, had renoprotective effects on streptozotocin (STZ)-induced diabetic kidney injury. SPRC treatment significantly reduced the level of creatinine, kidney to body weight ratio and in particular, markedly decreased 24-h urine microalbuminuria excretion. SPRC suppressed the mRNA expression of fibronectin and type IV collagen. In vitro, SPRC inhibited mesangial cells over-proliferation and hypertrophy induced by high glucose. Additionally, SPRC attenuated inflammation in diabetic kidneys. SPRC also reduced transforming growth factor β1 (TGF-β1) signaling and expression of phosphorylated Smad3 (p-Smad3) pathway. Moreover, SPRC inhibited phosphorylation of ERK, p38 protein. Taken together, SPRC was demonstrated to be a potential therapeutic candidate to suppress diabetic nephropathy. - Highlights: • We synthesized a novel hydrogen sulfide-releasing compound, S-propargyl-cysteine (SPRC). • SPRC was preliminarily demonstrated to prevent STZ-induced diabetic nephropathy (DN). • SPRC may exert potential therapeutic candidate to suppress DN.

  9. Podocyte-specific deletion of Rac1 leads to aggravation of renal injury in STZ-induced diabetic mice

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    Ishizaka, Masanori [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Gohda, Tomohito, E-mail: goda@juntendo.ac.jp [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Takagi, Miyuki; Omote, Keisuke; Sonoda, Yuji [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Oliva Trejo, Juan Alejandro [Laboratory for Kidney Research (TMK Project), Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8397 (Japan); Asao, Rin; Hidaka, Teruo [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Asanuma, Katsuhiko [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Laboratory for Kidney Research (TMK Project), Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8397 (Japan); Horikoshi, Satoshi [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Tomino, Yasuhiko [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Medical Corporation SHOWAKAI, 3-12-12 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023 (Japan)

    2015-11-20

    Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal architecture, as well as the regulation of cell migration and growth. However, renal injury in mice with podocyte-specific deletion of Rac1 has yet to be elucidated fully due to conflicting findings. Herein, we identified a possible role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was significantly higher than that in the wild type (WT) group at any week of age. A more marked ACR increase was observed in STZ/KO group than STZ/WT group, although ACR did increase with weeks of age in both diabetic groups. The kidney sections from diabetic mice revealed a glomerular hypertrophy with mesangial expansion, but there was no appreciable difference in glomerular findings under a light microscope between STZ/WT and STZ/KO mice. However, an electron microscopy analysis revealed that regardless of the presence or absence of diabetes, both KO (KO and STZ/KO) groups had a higher rate of foot process effacement compared with both WT (WT and STZ/WT) groups. The expression levels of the slit diaphragm protein, podocin, was reduced with the induction of diabetes, and the levels in the STZ/KO group experienced a further reduction compared with the STZ/WT group. The number of WT1-positive cells in the STZ/KO group was more significantly decreased than that in the other three groups. In contrast, the numbers of cleaved caspase 3- and TUNEL-positive cells in the glomeruli of the STZ/KO group were more increased than those in the STZ/WT group. Thus, this study provides evidence that podocyte-specific deletion of Rac1 results in morphological alteration in podocytes, and that the induction of apoptosis or decreased expression of the slit diaphragm proteins by hyperglycemic stimuli are associated with the progression of diabetic nephropathy.

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

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

    2011-08-15

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

  11. Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ-Induced Diabetic Mice

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    Xiuli Zhang

    2016-08-01

    Full Text Available Diabetic nephropathy (DN is a serious diabetic complication with renal hypertrophy and expansion of extracellular matrices in renal fibrosis. Epithelial-to-mesenchymal transition (EMT of renal tubular epithelial cells may be involved in the main mechanism. Berberine (BBR has been shown to have antifibrotic effects in liver, kidney and lung. However, the mechanism of cytoprotective effects of BBR in DN is still unclear. In this study, we investigated the curative effects of BBR on tubulointerstitial fibrosis in streptozotocin (STZ-induced diabetic mice and the high glucose (HG-induced EMT in NRK 52E cells. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2 signaling pathway in the diabetic kidneys. Further revealed that BBR abrogated HG-induced EMT and oxidative stress in relation not only with the activation of Nrf2 and two Nrf2-targeted antioxidative genes (NQO-1 and HO-1, but also with the suppressing the activation of TGF-β/Smad signaling pathway. Importantly, knockdown Nrf2 with siRNA not only abolished the BBR-induced expression of HO-1 and NQO-1 but also removed the inhibitory effect of BBR on HG-induced activation of TGF-β/Smad signaling as well as the anti-fibrosis effects. The data from present study suggest that BBR can ameliorate tubulointerstitial fibrosis in DN by activating Nrf2 pathway and inhibiting TGF-β/Smad/EMT signaling activity.

  12. Anti-inflammatory role of sesamin in STZ induced mice model of diabetic retinopathy.

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    Ahmad, Saif; ElSherbiny, Nehal M; Jamal, Mohammad Sarwar; Alzahrani, Faisal A; Haque, Rizwanul; Khan, Raziuddin; Zaidi, Syed Kashif; AlQahtani, Mohammed H; Liou, Gregory I; Bhatia, Kanchan

    2016-06-15

    Diabetic retinopathy (DR) is the common cause of diabetic vascular complications that leads to the blindness in the working age population throughout the world. Free radicals mediated oxidative stress and inflammation play a significant role in pathophysiology of DR. To find a new and safe drug to treat DR is still challenging and for that purpose the natural compounds may be therapeutic agents. Here we show that sesamin (SES), which is the main component of sesame seed and its oil, and has been reported as potent antioxidant and neuroprotective, could be a therapeutic agent in DR. In the present study, we investigated protective effect of SES in Streptozotocin (STZ) induced DR in mice. The mice were divided into three groups (Control, DR and DR+SES) for the study. After two weeks post-diabetic establishment, mice were treated with SES (30mg/kg BW, i.p, alternate day) for four weeks. Mice body weight and blood glucose level were measured from each group. The microglial activation of retina was determined by immunohistochemistry analysis by using Iba-1 as a microglia marker. Retinal mRNA levels of Iba-1, tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and Intercellular Adhesion Molecule 1 (ICAM-1) were examined by qRT-PCR. The level of iNOS protein expression was examined by immunoblotting. Together these data demonstrate that SES treatment lowered the progression of diabetic retinal injury by: 1) decreasing blood glucose level, 2) suppressing microglia activation, 3) reducing retinal TNF-α and ICAM-1 levels and 4) quenching iNOS expression. In conclusion, the results suggest that SES treatment may be of therapeutic benefit in reducing the progression of DR by ameliorating hyperglycemia and inflammation in diabetic retina. Published by Elsevier B.V.

  13. The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats

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    Abbasali Abbasnezhad

    2015-06-01

    Full Text Available Objective: Oxidative stress plays an important role in the etiology of diabetic complications. Diabetes impairs hippocampus neurogenesis, synaptic plasticity, and learning. The aim of this study was to investigate the effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in STZ-induced diabetic rats' hippocampus. Materials and Methods: Diabetes induced by 60 mg/kg STZ, i.p, and the rats were divided into five experimental groups (n=8-10 in each group including control (received 0.5 ml normal saline, untreated STZ-diabetic (received 0.5 ml normal saline, and treated rats received Nigella sativa extract (200 and 400 mg/kg or metformin (300 mg/kg by gavage for 42 days. Serum glucose concentration and body weight as well as hippocampus tissue malondialdehyde and thiollevels were determined by calorimetric assay. Results: Serum glucose level in the diabetic rats treated with 200 mg/kg Nigella sativaextract at the days 24 and 45 decreased in comparison to untreated diabetic group (p

  14. Antidiabetic activities of polysaccharides from Anoectochilus roxburghii and Anoectochilus formosanus in STZ-induced diabetic mice.

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    Tang, Tingting; Duan, Xiaoyu; Ke, Yu; Zhang, Lan; Shen, Yingbin; Hu, Bin; Liu, Aiping; Chen, Hong; Li, Cheng; Wu, Wenjuan; Shen, Li; Liu, Yuntao

    2018-02-10

    Six polysaccharides were extracted from different parts (whole plants, roots and leaves) of Anoectochilus roxburghii and Anoectochilus formosanus (ARPs, ARPs-1, ARPs-2, AFPs, AFPs-1 and AFPs-2). Their primary characteristics were identified and their antidiabetic activities were evaluated in STZ-induced diabetic mice. Root polysaccharides (ARPs-1and AFPs-1) and leaf polysaccharides (ARPs-2 and AFPs-2) were distinct from each other in terms of the Mws, monosaccharide compositions and functional groups. Notably, the primary structures of ARPs and AFPs were similar to those of ARPs-1and AFPs-1, respectively. In animal experiment, after feeding with polysaccharides samples, the body weight, blood glucose, glycogen, insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondiadehyde (MDA) and antioxidant enzyme activities in liver and kidney of mice were tested to investigate the antidiabetic activities. All polysaccharides exhibited varying antidiabetic activities (antihyperglycemic, antioxidant and antihyperlipidemic activities), which were closely related to their primary characteristics. Furthermore, root polysaccharides with higher Mws and glucose content in both A. roxburghii and A. formosanus, exhibited better antidiabetic activities than leaf polysaccharides, and ARPs which showed the best antidiabetic activities had the potential to be used as functional food or medicine for diabetes treatment. Copyright © 2017. Published by Elsevier B.V.

  15. MiR-124 is Related to Podocytic Adhesive Capacity Damage in STZ-Induced Uninephrectomized Diabetic Rats

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    Dong Li

    2013-10-01

    Full Text Available Background: Diabetic nephropathy (DN is the leading cause of end-stage renal disease. Podocyte plays a key role in the pathogenesis of DN. Adhesive capacity damage of podocytes is characteristic in DN. Emerging evidence suggests that microRNAs (miRNAs play crucial roles in controlling many cell adhesion molecules thus contribute to normal cell adhesion. The roles of miRNA in podocytic adhesive capacity damage in diabetic conditions remain largely unknown. Methods: Diabetes was induced by tail vein injection of streptozotocin (STZ into uninephrectomized male Wistar rats. Comparative miRNA expression array and real-time PCR analyses were conducted in sham group at week 0 (W0, n = 3 and STZ-induced uninephrectomized diabetic rats at week 1 (W1, n = 3 and week 2 (W2, n = 3 to demonstrate the greatest increased miRNA in renal cortex. At week 2, STZ-induced uninephrectomized diabetic rats were treated with vehicle (Group U, n = 9, chemically modified antisense RNA oligonucleotide (ASO complementary to the mature miR-124 (Group O, n = 8, miR-124 mismatch control sequence (Group M, n = 8. Urine specimens were obtained for measurement of urine albumin concentration and urinary podocyte specific protein (nephrin and podocin quantitation. Expression of integrin α3 were detected by immunohistochemistry and western blotting. Results: MiRNAs are differentially regulated in renal cortex of STZ-induced uninephrectomized diabetic rats relative to sham rats. Among the up-regulated miRNAs, miR-124 expression demonstrated the greatest increase. Administration of miR-124 ASO for two weeks significantly reduced urinary podocytic nephrin, podocin and albumin excretion and up-regulate integrin α3 expression. Conclusion: MiR-124 is related to podocytic adhesive capacity damage and may be implicated in the pathogenesis of DN.

  16. Chromane isolated from leaves of Dillenia indica improves the neuronal dysfunction in STZ-induced diabetic neuropathy.

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    Kaur, Navpreet; Kishore, Lalit; Singh, Randhir

    2017-07-12

    According to the Indian traditional medicine, Dillenia indica L. has shown therapeutic efficacy in various diseases. Fruits and leaves of the plant possess anti-oxidant and anti-inflammatory properties. Reactive oxygen species, formation of advanced glycation end products (AGEs) and apoptosis are implicated in the pathogenesis of diabetic neuropathy. The aim of the present study was to explore the effect of D. indica and its isolate, chromane (CR), on thermal and mechanical hyperalgesia, allodynia, MNCV and oxidative-nitrosative stress in streptozotocin-induced experimental diabetes. Diabetes was induced by intraperitoneal administration of Streptozotocin (STZ; 65mg/kg) for the development of diabetic neuropathy. Chronic treatment with DAE (100, 200 and 400mg/kg, p.o.) and CR (5 and 10mg/kg, p.o.) for 30 days was started from the 60th day of STZ administration. Development of neuropathy was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with increased formation of AGEs and reactive oxygen species. significantly attenuated behavioral and biochemical changes associated with diabetic neuropathy. Present study suggested that DAE and CR ameliorated hyperglycemia and diabetic neuropathic pain via modulation of oxidative-nitrosative stress and reduction in AGEs formation in the diabetic rats. Thus D. indica might be beneficial in chronic diabetics, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Bio-optic signatures for advanced glycation end products in the skin in streptozotocin (STZ) Induced Diabetes (Conference Presentation)

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    Saidian, Mayer; Ponticorvo, Adrien; Rowland, Rebecca A.; Balbado, Melisa L.; Lentsch, Griffin; Balu, Mihaela; Alexander, Micheal; Shiri, Li; Lakey, Jonathan R. T.; Durkin, Anthony J.; Kohen, Roni; Tromberg, Bruce J.

    2017-02-01

    Type 1diabetes (T1D) is an autoimmune disorder that occurs due to the rapid destruction of insulin-producing beta cells, leading to insulin deficiency and the inability to regulate blood glucose levels and leads to destructive secondary complications. Advanced glycation end (AGEs) products, the result of the cross-linking of reducing sugars and proteins within the tissues, are one of the key causes of major complications associated with diabetes such as renal failure, blindness, nerve damage and vascular changes. Non-invasive techniques to detect AGEs are important for preventing the harmful effects of AGEs during diabetes mellitus. In this study, we utilized multiphoton microscopy to image biopsies taken from control rats and compared them to biopsies taken from streptozotocin (STZ) induced adult male diabetic rats. This was done at two and four weeks after the induction of hyperglycemia (>400 mg/dL) specifically to evaluate the effects of glycation on collagen. We chose to use an in-situ multiphoton microscopy method that combines multiphoton auto-florescence (AF) and second harmonic generation (SHG) to detect the microscopic influence of glycation. Initial results show high auto-florescence levels were present on the collagen, as a result of the accumulation of AGEs only two weeks after the STZ injection and considerably higher levels were present four weeks after the STZ injection. Future projects could involve evaluating advanced glycation end products in a clinical trial of diabetic patients.

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

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    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.

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

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    Kilari, Eswar Kumar; Putta, Swathi

    2017-03-01

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

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

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    Lu Guan-Yi

    2010-12-01

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

  1. Ophiocordyceps formosana improves hyperglycemia and depression-like behavior in an STZ-induced diabetic mouse model.

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    Huang, Chao-Wei; Hong, Tzu-Wen; Wang, Ying-Jing; Chen, Ko-Chien; Pei, Ju-Chun; Chuang, Tai-Yuan; Lai, Wen-Sung; Tsai, Sheng-Hong; Chu, Richard; Chen, Wei-Cheng; Sheen, Lee-Yan; Takahashi, Satoru; Ding, Shih-Torng; Shen, Tang-Long

    2016-08-24

    A newly defined Cordyceps species, Ophiocordyceps formosana (O. formosana) has been implicated in multitudinous bioactivities, including lowering glucose and cholesterol levels and modulating the immune system. However, few literatures demonstrate sufficient evidence to support these proposed functions. Although the use of Cordyceps spp. has been previously addressed to improve insulin insensitivity and improve the detrimental symptoms of depression; its mechanistic nature remains unsettled. Herein, we reveal the effects of O. formosana in ameliorating hyperglycemia accompanied with depression. Diabetes was induced in mice by employing streptozotocin(STZ), a chemical that is toxic to insulin-producing β cells of the pancreas. These streptozotocin (STZ)-induced diabetic mice showed combined symptoms of hyperglycemia and depressive behaviors. Twenty-four STZ-induced mice were randomly divided into 3 groups subjected to oral gavage with 100 μL solution of either PBS or 25 mg/mL Ophiocordyceps formosana extract (OFE) or 2 mg/mL rosiglitazone (Rosi, positive control group). Treatments were administered once per day for 28 days. An additional 6 mice without STZ induction were treated with PBS to serve as the control group. Insulin sensitivity was measured by a glucose tolerance test and levels of adiponectin in plasma and adipose tissue were also quantified. Behavioral tests were conducted and levels of monoamines in various brain regions relating to depression were evaluated. HPLC analysis uncovered three major constituents, adenosine, D-mannitol and cordycepin, within O. formosana similar to other prestigious medicinal Cordyceps spp.. STZ-induced diabetic mice demonstrated decreased body weight and subcutaneous adipose tissue, while these symptoms were recovered in mice receiving OFE treatment. Moreover, the OFE group displayed improved insulin sensitivity and elevated adiponectin within the plasma and adipose tissue. The anti-depressive effect of OFE was

  2. Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice

    OpenAIRE

    Yan Zhang; Liying Wu; Zhongsu Ma; Jia Cheng; Jingbo Liu

    2015-01-01

    Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs) on streptozotocin (STZ)-induced diabetic mice. The results revealed that treatment with 300 mg/kg or 500 mg/kg of CSFs significantly reduced the body weight loss, water consumption, and especially the blood glucose (BG) concentration of diabetic mi...

  3. Colonic PDGFRα Overexpression Accompanied Forkhead Transcription Factor FOXO3 Up-Regulation in STZ-Induced Diabetic Mice

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    Hongli Lu

    2017-08-01

    Full Text Available Background: Colonic transit disorder-induced constipation is a major complication in diabetic patients. PDGFRα+ (platelet-derived growth factor receptor α-positive cells play critical roles in the inhibitory regulation of colonic motility, and FOXO3 (forkhead transcription factor 3 has a broad range of biological functions. The present study was designed to investigate the relationship between FOXO3 and PDGFRα+ cell proliferation in streptozotocin (STZ-induced diabetic mice. Methods: The major experimental techniques used in this paper are immunohistochemistry, quantitative RT-RCR and Western blotting for the evaluation of specific protein expression; ChIP assay for identifying the interaction between FOXO3 protein and the PDGFRα promotor; and lentiviral transfection for the overexpression of short hairpin RNAs (shRNAs to down-regulate FOXO3. Results: In proximal colonic smooth muscle tissue of STZ-induced diabetic mice, there was a significant increase in PDGFRα and Ki67 immunoreactivity. PDGFRα mRNA and protein expression levels were both significantly increased in colonic smooth muscle tissue, but PDGFRβ expression was unchanged. Meanwhile, the expression of PDGF ligands, including both PDGFα and PDGFβ, was significantly increased in diabetic colonic smooth muscle tissue. In whole cell and nuclear extracts, the expression of FOXO3 protein was also significantly increased; however, the expression of P-FOXO3 (phosphorylated FOXO3 protein was significantly decreased. When NIH cells were incubated with 50 mmol/L glucose for 12 h, 24 h and 48 h, the expression of PDGFRα significantly increased, and in whole cell and nuclear extracts, the expression of FOXO3 protein was significantly increased. However, the expression of P-FOXO3 protein was significantly decreased. FOXO3 could bind to a site on the PDGFRα promoter, and the basal expression of PDGFRα was significantly reduced when endogenous FOXO3 expression was knocked down with FOXO3

  4. Evaluation of antidiabetic potential of selected traditional Chinese medicines in STZ-induced diabetic mice.

    Science.gov (United States)

    He, Kai; Li, Xuegang; Chen, Xin; Ye, Xiaoli; Huang, Jing; Jin, Yanan; Li, Panpan; Deng, Yafei; Jin, Qing; Shi, Qing; Shu, Hejing

    2011-10-11

    Traditional Chinese medicine (TCM) has been used for treating complex chronic diseases owing to their fewer side-effects, better patient tolerance and relatively less cost. The present work was carried out to study the anti-diabetic efficacy and mechanisms of 34 TCMs. Streptozotocin (STZ)-diabetic mice were orally administrated with corresponding herbal solution once a day for 4 weeks. At the end of experiment, the level of plasma glucose, malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the serum aldose reductase (AR) were determined, the effects of TCM extract on α-glucosidase and angiotensin-converting enzyme (ACE) in vitro were also evaluated. 13 out of the 34 herbs showed a statistically significant plasma glucose lowering action compared with the diabetic control group. Biochemical analysis revealed that Atractylodes macrocephala, Codonopsis pilosula, Dioscorea opposite, Flos lonicerae and Pueraria lobata may retard the progression of diabetes via reduce the blood glucose level and prevent the increase of AR activity. Other tested herbs, such as Ramulus cinnamomi, Cinnamomum cassia, and Eucommia ulmoides, showed the antidiabetic ability by either prevent the decrease in SOD activity or suppress the increase of MDA. Zymologic assay reveals that Pueraria lobata and Anemarrhena asphodeloides showed the highest inhibition against α-glucosidase and ACE respectively. Interestingly, the post-treatment glucose levels and AR activity were positively correlated with kidney/body weight of 34 herbs treated diabetic mice (p = 0.02, 0.04 respectively). Several potential antidiabetic herbs derived from Chinese traditional pharmacopeia such as Dioscorea opposite, Pueraria lobata, Codonopsis pilosula and Ramulus cinnamomi, have been found to exert a beneficial action on diabetes and diabetic complications via multi-mechanisms. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Evaluation of the Effect of Hydroalcoholic Extract of Citrullus colocynthis in Normoglycemic and Streptozocine (STZ Induced Diabetic Male Rats

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    MR Nikbakht

    2006-07-01

    Full Text Available Introduction & Objective: Adverse side effects of chemical drugs for treatment of diabetes persuaded the using of medical plants. Citrullus colocynthis is a plant which has been used traditionally for treatment of diabetes. The purpose of this study was to evaluate the effect of hydroalcholic extract of Citrullus colocynthis fruit on normoglycemic and streptozocine induced diabetic rats. Materials & Methods: 45 male Wistar rats weighing, 250-350 gr, have been selected and randomly divided in seven groups. Group1 without any drugs usage, group 2 that received normal saline (IV and distilled water (oral, group 3 received only streptozocine (IV, group 4 received only the extract of Citrullus colocynthis (1000 mg/kg, groups 5, 6 and 7 received 500, 1000 and 1500 mg/kg of Citrullus colocynthis extract after injection of STZ and induction of diabetes. Diabetes was induced by intravenous injection (45 mg/kg of STZ. Blood sampling was provided directly from animal heart and blood sugar was measured. The collected data were analyzed by SPSS software using students t-test and ANOVA. Results: Mean of normal blood sugar in control group was 156.5±15.7 mg/dl which defined as normal blood sugar. Streptozocine significantly increased blood sugar (p<0.05. The Citrullus colocynthis extract with 500 mg/kg dosage has not significantly reduced the blood sugar but is dosage of 1000 and 1500 mg/kg significantly decreased the blood sugar in a dose-dependent mode (p<0.05. Results also showed that the extract in dosage of 1000 mg/kg did not have a significant effect on normoglycemic animals. Conclusion: Results of this study indicate that the extract of Citrullus colocynthis fruit dose-dependently reduced the blood glucose level in streptozocine-induced diabetic rats but did not have significant effect on normal blood sugar.

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

    Science.gov (United States)

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

    2011-01-01

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

  7. Investigation of metabolic changes in STZ-induced diabetic rats with hyperpolarized [1-13C]acetate

    DEFF Research Database (Denmark)

    Koellisch, Ulrich; Laustsen, Christoffer; Nørlinger, Thomas S

    2015-01-01

    In the metabolism of acetate several enzymes are involved, which play an important role in free fatty acid oxidation. Fatty acid metabolism is altered in diabetes patients and therefore acetate might serve as a marker for pathological changes in the fuel selection of cells, as these changes occur...... in diabetes patients. Acetylcarnitine is a metabolic product of acetate, which enables its transport into the mitochondria for energy production. This study investigates whether the ratio of acetylcarnitine to acetate, measured by noninvasive hyperpolarized [1-(13)C]acetate magnetic resonance spectroscopy......, could serve as a marker for myocardial, hepatic, and renal metabolic changes in rats with Streptozotocin (STZ)-induced diabetes in vivo. We demonstrate that the conversion of acetate to acetylcarnitine could be detected and quantified in all three organs of interest. More interestingly, we found...

  8. Ghrelin ameliorates nerve growth factor Dysmetabolism and inflammation in STZ-induced diabetic rats.

    Science.gov (United States)

    Zhao, Yuxing; Shen, Zhaoxing; Zhang, Dongling; Luo, Huiqiong; Chen, Jinliang; Sun, Yue; Xiao, Qian

    2017-06-01

    Diabetic encephalopathy is characterized by cognitive impairment and neuroinflammation, deficient neurotrophic support, and neuronal and synaptic loss. Ghrelin, a 28 amino acid peptide, is associated with neuromodulation and cognitive improvement, which has been considered as a potential protective agent for several neurodegenerative diseases. Here we sought to investigate the role of ghrelin in preventing diabetic-related neuropathology. We found that ghrelin attenuated astrocytic activation and reduced levels of interleukin-6 and tumor necrosis factor-α in streptozotocin-induced diabetic rats. In addition, ghrelin inhibited p38 mitogen-associated protein kinase activation. The upregulation of nerve growth factor (NGF) precursor and matrix metalloproteinase (MMP)-9 and downregulation of mature NGF and MMP-7 in the diabetic brain were reversed by ghrelin. Treatment with ghrelin elevated synaptophysin expression and synaptic density in diabetic rats. Taken together, our results demonstrate that ghrelin ameliorates diabetes-related neurodegeneration by preventing NGF dysmetabolism and synaptic degeneration through regulating MMP levels as well as inhibiting neuroinflammation.

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

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    Mohammad Badavi

    2013-12-01

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

  10. Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.

    Science.gov (United States)

    Yin, Weiqin; Xu, Shiqing; Wang, Zai; Liu, Honglin; Peng, Liang; Fang, Qing; Deng, Tingting; Zhang, Wenjian; Lou, Jinning

    2018-01-01

    GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced. The results showed that rhGLP-1 reduced urinary albumin without influencing the body weight and food intake. rhGLP-1 could increased the serum C-peptide slightly but not lower fasting blood glucose significantly. In diabetic nephropathy rats, beside glomerular sclerosis, tubulointerstitial fibrosis was very serious. These lesions could be alleviated by rhGLP-1. rhGLP-1 decreased the expression of profibrotic factors collagen I, α-SMA, fibronectin, and inflammation factors MCP-1 and TNFα in tubular tissue and human proximal tubular cells (HK-2 cells). Furthermore, rhGLP-1 significantly inhibited the phosphorylation of NF-κB, MAPK in both diabetic tubular tissue and HK-2 cells. The inhibition of the expression of TNFα, MCP-1, collagen I and α-SMA in HK-2 cells by GLP-1 could be mimicked by blocking NF-κB or MAPK. These results indicate that rhGLP-1 exhibit renoprotective effect by alleviation of tubulointerstitial injury via inhibiting phosphorylation of MAPK and NF-κB. Therefore, rhGLP-1 may be a potential drug for treatment of diabetic nephropathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The effect of exercise on the peripheral nerve in streptozotocin (STZ)-induced diabetic rats.

    Science.gov (United States)

    Jin, Heung Yong; Lee, Kyung Ae; Park, Tae Sun

    2015-04-01

    The exact effectiveness of supportive care activities, such as exercise, in diabetes patients has yet to be elucidated in the diabetic peripheral neuropathy (DPN) field. Therefore, this study was designed to investigate the effect of regular exercise on the peripheral nerves of streptozotocin-induced diabetic rats. The animals were divided as follows into six groups according to exercise combination and glucose control: Normal group, normal group with exercise (EXE), diabetic group (DM), DM group with EXE, DM+glucose control with insulin (INS), and DM+INS+EXE. Animals in the exercise groups were made to walk on a treadmill machine everyday for 30 min at a setting of 8 m/min without inclination. After 8 weeks, sensory parameters were evaluated, and after 16 weeks, biochemicals and peripheral nerves were quantified by immunohistochemistry and compared among experimental groups. The resulting data showed that fasting blood glucose levels and HbA1c levels were not influenced significantly by exercise in normal and DM groups. However, the current perception threshold and the von Frey stimulation test revealed higher thresholds in the DM+INS+EXE group than in the DM+INS group (PExercise alone was not associated with a significant protective effect on the peripheral nerve in the normal or DM groups; however, a beneficial effect from exercise was observed when hyperglycemia was controlled with insulin in the DM group. These findings suggest that exercise has a potential protective effect against DPN based on the preferential effort for glucose control, although exercise alone cannot prevent peripheral nerve damage from hyperglycemia.

  12. [Effect of combination of insulin and selenium on insulin signal transduction in cardiac muscle of STZ-induced diabetic rats].

    Science.gov (United States)

    Xu, Tian-Jiao; Yuan, Bing-Xiang; Zou, Ya-Min

    2011-03-01

    This study is to investigate the effect of low doses of insulin (1 u x kg(-1)) and selenium (180 microg x kg(-1)) in combination on general physiological parameters and insulin signal molecules in cardiac muscle of STZ-induced diabetic rats. The levels of blood glucose were estimated using One Touch SureStep Blood Glucose meter. HbA1c levels were estimated using microcolumn assay. TG and TC were estimated using enzymatic assay. The levels of PI3K and GLUT4 in cardiac muscle were examined by immunoblotting and immunohistochemistry. The result showed that insulin in combination with selenium could significantly lower blood glucose and blood lipid levels and markedly restored the PI3K and GLUT4 levels in cardiac muscle. It could be concluded that there was cooperation between insulin and selenium, and that treatment of diabetic rats with combined doses of insulin and selenium increased cardiac glucose uptake by upregulating the level of PI3K-mediated GLUT4 in cardiac muscle, eventually ameliorating myocardial dysfunction.

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

    Science.gov (United States)

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

    2012-01-01

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

  14. RNA-Seq analysis of glycosylation related gene expression in STZ-induced diabetic rat kidney inner medulla

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    Xiaoqian eQian

    2015-10-01

    Full Text Available The UT-A1 urea transporter is crucial to the kidney’s ability to generate concentrated urine. Native UT-A1 from kidney inner medulla (IM is a heavily glycosylated protein with two glycosylation forms of 97 and 117 kDa. In diabetes, UT-A1 protein abundance, particularly the 117 kD isoform, is significantly increased corresponding to an increased urea permeability in perfused IM collecting ducts, which plays an important role in preventing the osmotic diuresis caused by glucosuria. However, how the glycan carbohydrate structure change and the glycan related enzymes regulate kidney urea transport activity, particularly under diabetic condition, is largely unknown. In this study, using sugar-specific binding lectins, we found that the carbohydrate structure of UT-A1 is changed with increased amounts of sialic acid, fucose, and increased glycan branching under diabetic conditions. These changes were accompanied by altered UT-A1 association with the galectin proteins, α-galactoside glycan binding proteins. To explore the molecular basis of the alterations of glycan structures, the highly sensitive next generation sequencing (NGS technology, Illumina RNA-seq, was employed to analyze genes involved in the process of UT-A1 glycosylation using streptozotocin (STZ - induced diabetic rat kidney. Differential gene expression analysis combining quantitative PCR revealed that expression of a number of important glycosylation related genes were changed under diabetic conditions. These genes include the glycosyltransferase genes Mgat4a, the sialylation enzymes St3gal1 and St3gal4 and glycan binding protein galectin-3, -5, -8 and -9. In contrast, although highly expressed in kidney IM, the glycosyltransferase genes Mgat1, Mgat2, and fucosyltransferase Fut8, did not show any changes. Conclusions: In diabetes, not only is UT-A1 protein abundance increased but the protein’s glycan structure is also significantly changed. UT-A1 protein becomes highly sialylated

  15. Attenuation of diabetic nephropathy by Sanziguben Granule inhibiting EMT through Nrf2-mediated anti-oxidative effects in streptozotocin (STZ)-induced diabetic rats.

    Science.gov (United States)

    Zhang, Chenxue; Li, Qian; Lai, Sisi; Yang, Lei; Shi, Guoqi; Wang, Qing; Luo, Zijie; Zhao, Ruizhi; Yu, Yang

    2017-06-09

    Diabetic nephropathy (DN) is an acute and serious diabetic complication characterized by renal hypertrophy and renal fibrosis with the expansion of extracellular matrices. Diabetic nephropathy has become a major cause of end-stage kidney disease. Sanziguben Granule (SZGB) is a compound prescription which has been widely applied in clinical medicine for the prevention and treatment of diabetic nephropathy as well as for acute and chronic kidney injuries. However, the mechanism of protective effects of SZGB in DN remains unclear. In this research, we investigated the effects of SZGB on renal interstitial fibrosis, antioxidant proficiency, and apoptosis in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by performing a right uninephrectomy along with a single intraperitoneal injection of STZ. Rats were divided into six groups including sham, DN, SZGB-D, SZGB-Z, SZGB-G and fosinopril. SZGB and fosinopril were given to rats by gavage for 12 weeks. Samples from urine, blood and kidneys were collected for biochemical, histological, immunohistochemical and western blot analyses. We found that rats treated with SZGB showed reduced 24-h urinary protein excretion along with reduced serum total cholesterol (TC) and triglyceride (TG) levels. SZGB was also shown to prevent the disruption of catalase activity and reduce serum urea, creatinine, and renal malondialdehyde while increasing glutathione levels. Moreover, SZGB administration markedly improved the expression levels of E-cadherin, 4-HNE, Nrf2, HO-1, and Bcl-2, while it decreased the expression levels of Vimentin, α-SMA and Cleaved caspase-3 in the kidneys of diabetic rats. The renoprotective effects of SZGB was believed to be mediated by its antioxidant capacity, and SZGB treatment attenuated renal fibrosis through stimulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Therefore, it is suggested that SZGB can restrain epithelial

  16. Effect of L-carnitine administration on serum insulin and adiponectin levels, and AMPK, APPL1 and PPARγ gene expression in STZ-induced diabetic rat liver

    Directory of Open Access Journals (Sweden)

    B. Shahouzehi

    2017-12-01

    Full Text Available Diabetes is considered as a metabolic disease in which insulin secretion and functions are disturbed and characterized by hyperglycemia. L-carnitine is synthesized in most mammals and plays critical role in fatty acid oxidation and energy production. Data about the L-carnitine hypoglycemic effects are controversial. We evaluated long-term oral L-carnitine administration effects on blood glucose, insulin and adiponectin levels, as well as expression of AMPK, APPL1 and PPARγ genes in liver of STZ-induced diabetic rats. Group 1 (control, did not receive any treatment, group 2 received 50 mg/kg STZ by i.p injection, group 3 received single dose of 50 mg/kg STZ by i.p injection and also 600 mg/kg/day L-carnitine orally for 5 weeks. Our results showed that L-carnitine long-term oral supplementation significantly reduced blood glucose and normalized insulin levels in diabetic rats. Also, we found that L-carnitine significantly increased AMPK and APPL1 expression, and showed a mild elevation of PPARγ expression. In sum, we suggest that long-term L-carnitine supplementation has beneficial effects on diabetic rats which showed hypoglycemic effects. Probably the beneficial effects of L-carnitine are contributed to the upregulation of insulin sensitizers such as AMPK and adiponectin.

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

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    Zhong-Cheng Xin

    2013-05-01

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

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

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    Hua-Yu Liu

    2014-01-01

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

  19. Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice.

    Science.gov (United States)

    Zhang, Yan; Wu, Liying; Ma, Zhongsu; Cheng, Jia; Liu, Jingbo

    2015-12-23

    Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs) on streptozotocin (STZ)-induced diabetic mice. The results revealed that treatment with 300 mg/kg or 500 mg/kg of CSFs significantly reduced the body weight loss, water consumption, and especially the blood glucose (BG) concentration of diabetic mice, which indicated their potential anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the anti-oxidant effects. Besides, several serum lipid values including total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C) were reduced and the high density lipoprotein cholesterol level (HDL-C) was increased. The anti-diabetic, anti-oxidant and anti-hyperlipidemic effect of the CSFs suggest a potential therapeutic treatment for diabetic conditions.

  20. Anti neuroinflammatory effect of Vildagliptin in ischaemia-reperfusion induced cerebral infarction in normal and STZ induced type-II diabetic rats

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    Kaleru Purnachander

    2016-03-01

    Full Text Available Diabetes is one of the major risk factor for cerebral ischemic stroke. Increased base line levels of oxidative stress in diabetes will lead to cerebral ischemic damage. In pathological conditions such as cerebral ischemia/reperfusion injury, free radicals cause oxidative stress and inflammation leading to increased injury of brain. Inflammation is one of the major pathological mechanisms involved in cerebral ischemia and reperfusion injury. Vildagliptin newer anti-diabetic drug of the class DPP-4 inhibitors is reported to have anti-inflammatory properties apart from its antihyperglycemic activity. Therefore the aim of the present study is to evaluate the anti-inflammatory effect of Vildagliptin against cerebral infarction induced ischemia reperfusion injury in normal and STZ induced diabetic Wistar rats. Cerebral infarction was induced by bilateral common carotid artery occlusion followed by 4 hr reperfusion. Percent infarction, inflammatory markers such as MPO, TNF-α, IL-6 and IL-10 were analysed. Treatment with Vildagliptin for a period of four weeks produced significant reduction in percent cerebral infarct volume. Vildagliptin at 10 mg/kg dose, showed significant reduction in markers like MPO, TNF-α, IL-6 and IL-1β in diabetic group when compared to normal group and in contrast significant increase in anti-inflammatory marker like IL-10 levels. Vildagliptin showed significant cerebroprotective effect by antiinflammatory mechanisms.

  1. Anti-Glycemic and Anti-Hepatotoxic Effects of Mangosteen Vinegar Rind from Garcinia mangostana Against HFD/STZ-Induced Type II Diabetes in Mice

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    Karim Naymul

    2018-06-01

    Full Text Available This study focuses on anti-glycemic and anti-hepatotoxic effects of mangosteen vinegar rind (MVR on five weeks high-fat diet (HFD / single dose streptozotocin (STZ 30 mg/kg BW induced male ICR diabetic mice. Mice were randomly divided into five groups (n=6, normal control, diabetic control, and diabetic groups treated with MVR 100, 200 mg/kg BW and glibenclamide 60 mg/kg BW for one week. After the treatment, lipid profile, glycogen and bilirubin contents, oxidative damage (malondialdehyde, MDA, aspartate aminotransferase (AST and alanine aminotransferase (ALT activities, antioxidant enzymes: superoxide dismutase (SOD, catalase (CAT were measured in plasma and/or liver tissues. MVR and glibenclamide treatment to HFD/STZ-induced diabetic mice significantly reduced their plasma glucose, plasma lipid profile, and hepatic lipid profile (P<0.05. Increased hepatic glycogen content indicates improvement of insulin sensitivity. Moreover, oxidative damage markers were ameliorated in MVR- and glibenclamide-treated groups compared to the diabetic control group. MVR with phenolic compounds content of 75 mg GAE/g dry weight and antioxidant potential of 303 mmol/L Trolox/g dry weight acted as a hepatoprotective agent against oxidative damage.

  2. Polyploidy Analysis and Attenuation of Oxidative Stress in Hepatic Tissue of STZ-Induced Diabetic Rats Treated with an Aqueous Extract of Vochysia rufa

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    Izabela Barbosa Moraes

    2015-01-01

    Full Text Available Diabetes mellitus (DM is characterized by hyperglycemia and alterations in the metabolism of lipids, carbohydrates, and proteins. Due to its hypoglycemic effect Vochysia rufa is frequently used in Uberlandia, Brazil, to treat DM. Despite its popularity, there is little information about its effect on hepatic tissue. Therefore, we evaluated the histoarchitecture, oxidative stress parameters, and polyploidy of liver tissue from streptozotocin- (STZ- induced diabetic rats treated with aqueous extract of Vochysia rufa (AEV. Histology was determined by fixing the livers, processing, and staining with HE. Oxidative stress was determined by evaluating CAT, GPx, and SOD activity in liver homogenates and hepatic mitochondria fraction and by measuring GST, GSH levels and lipid peroxidation (MDA. Polyploidy was determined by subjecting isolated hepatocyte nuclei to flow cytometry. In the diabetic group, GST activity and GSH rates decreased whereas liver homogenate analysis showed that GPx, SOD activity and MDA increased. AEV treatment restored all parameters to normal levels. The oxidative stress analysis of hepatic mitochondria fraction showed similar results. Lower polyploid cell populations were found in the diabetic rat livers, even after glibenclamide treatment. Thus, AEV treatment efficiently reduced hepatic oxidative stress caused by STZ-induced diabetes and produced no morphological changes in the histological analysis.

  3. Ameliorating effect of Semecarpus anacardium Linn. nut milk extract on altered glucose metabolism in high fat diet STZ induced type 2 diabetic rats.

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

    2012-12-01

    To explore the protective effect of the drug Semecarpus anacardium (S. anacardium)on altered glucose metabolism in diabetic rats. Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ) (35 mg/kg b.w.). Seven days after STZ induction, diabetic rats received nut milk extract of S. anacardium Linn. nut milk extract orally at a dosage of 200 mg/kg daily for 4 weeks. The effect of nut milk extract of S. anacardium on blood glucose, plasma insulin, glucose metabolising enzymes and GSK were studied. Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA - β and decrease in HOMA -IR. The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes. The drug also effectively ameliorated the alterations in GSK-3 mRNA expression. Overall, the present study demonstrates the possible mechanism of glucose regulation of S. anacardium suggestive of its therapeutic potential for the management of diabetes mellitus. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2012-03-01

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

  5. Hypoglycemic effect of the polyphenols rich extract from Rose rugosa Thunb on high fat diet and STZ induced diabetic rats.

    Science.gov (United States)

    Liu, Liu; Tang, Dan; Zhao, Haiqing; Xin, Xuelei; Aisa, Haji Akber

    2017-03-22

    Rosa rugosa Thunb is a traditional Uygur medicine that has been used in the treatment of diabetes in Uygur ancient recipe for hundreds of years. However, the mechanism of Rosa rugosa Thunb activity is still unclear. This study was designed to address this issue by studying the polyphenols enriched extract (RPE) of Rosa rugosa Thunb in diabetic rats. RPE were tested in the inhibition of α-glucosidase and oxidative stress in vitro. RPE was administrated at dosages of 37.5, 75 and 150mg/kg body weight in the type 2 diabetic rats, which were made by high fat diet feeding plus a low dose of STZ injection (30mg/kg). The therapeutic effect was evaluated four weeks later. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and insulin signal pathway (PI3K/AKT) were examined to determine insulin sensitivity. Blood glucose levels and body weight were measured weekly in the study. In vitro, RPE exhibited an activity in the inhibition of α-glucosidase and had an excellent antioxidant activity in the liver of diabetic rats. RPE significantly decreased the fasting blood glucose, improved insulin sensitivity (HOMA-IR), OGTT, ITT and blood lipid profile. The glycogen synthesis and hexokinase activity were increased together with the improved signaling activity of insulin as indicated by p-IRS, p-IR, p-AKT, and p-GSK-3β. The results suggest that RPE reduced blood glucose in type 2 diabetic rats by improvement of insulin sensitivity. The effect is likely achieved by inhibition of oxidative stress and α-glucosidase. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. The Research on the Relationship of RAGE, LRP-1, and Aβ Accumulation in the Hippocampus, Prefrontal Lobe, and Amygdala of STZ-Induced Diabetic Rats.

    Science.gov (United States)

    Ma, Lou-Yan; Fei, Yu-Lang; Wang, Xiao-Ye; Wu, Song-Di; Du, Jun-Hui; Zhu, Mei; Jin, Long; Li, Ming; Li, Hai-Long; Zhai, Jia-Jia; Ji, Lu-Peng; Ma, Ran-Ran; Liu, Song-Fang; Li, Mo; Ma, Li; Ma, Xiao-Rui; Qu, Qiu-Min; Lv, Ya-Li

    2017-05-01

    Diabetes mellitus (DM) has been regarded as an important risk factor for Alzheimer's disease (AD), and diabetic patients and animals have shown cognitive dysfunction. More research has shown that the amyloid-β (Aβ), which is a hallmark of AD, was found deposited in the hippocampus of diabetic rats. This Aβ accumulation is regulated by the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP-1). However, the expression of RAGE and LRP-1 in diabetic rats is not very clear. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether the expression of RAGE and LRP-1 is related to Aβ 1-42 deposition at the hippocampus, prefrontal lobe, and amygdala in DM. We found that diabetic rats had longer escape latency and less frequency of entrance into the target zone than that of the control group (P RAGE increased (P RAGE positively (P RAGE, and LRP-1 were not changed in the amygdala between the diabetic rats and the control group. These findings indicated that upregulating RAGE and/or downregulating LRP-1 at the hippocampus and the prefrontal lobe contributed to the Aβ 1-42 accumulation and then further promoted the cognitive impairment of diabetic rats.

  7. Effect of Resistance Exercise Training Associated with Skeletal Muscle Hypertrophy on Serum Pro-Inflammatory Cytokines in STZ-induced Diabetes

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    Mahdieh Molanouri Shamsi

    2016-06-01

    Full Text Available Skeletal muscle atrophy is associated with type 1 diabetes. Effects of resistance exercise training associated with skeletal muscle hypertrophy on serum inflammatory cytokines was exactly not clarified. Protein levels of inflammatory cytokines IL-6, TNF-α, and interleukin-1beta (IL-1β in serum of healthy and streptozotocin (STZ- induced diabetic rats subjected to resistance exercise training were assessed in this study. Rats were divided into the control, training, control diabetic and diabetic training groups. Training groups performed the resistance training consisted of climbing a 1 m ladder with increasing weight added to the tail. Proteins levels of IL-6, TNF-α and IL-1β in serum were measured by the ELIZA method. The results of this study indicated that resistance training induced skeletal muscle hypertrophy in diabetic samples (P<0.05. Also, Resistance training decrease IL-6 protein levels in serum. Inflammatory cytokines could act as stress factors in diabetes. It seems that this kind of exercise training individually could not change cytokines levels in serum.

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

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    Nur Akmal Ishak

    2013-01-01

    Full Text Available Curculigo latifolia fruit is used as alternative sweetener while root is used as alternative treatment for diuretic and urinary problems. The antidiabetic and hypolipidemic activities of C. latifolia fruit:root aqueous extract in high fat diet (HFD and 40 mg streptozotocin (STZ induced diabetic rats through expression of genes involved in glucose and lipid metabolisms were investigated. Diabetic rats were treated with C. latifolia fruit:root extract for 4 weeks. Plasma glucose, insulin, adiponectin, lipid profiles, alanine aminotransferase (ALT, gamma glutamyltransferase (GGT, urea, and creatinine levels were measured before and after treatments. Regulations of selected genes involved in glucose and lipid metabolisms were determined. Results showed the significant (P<0.05 increase in body weight, high density lipoprotein (HDL, insulin, and adiponectin levels and decreased glucose, total cholesterol (TC, triglycerides (TG, low density lipoprotein (LDL, urea, creatinine, ALT, and GGT levels in diabetic rats after 4 weeks treatment. Furthermore, C. latifolia fruit:root extract significantly increased the expression of IRS-1, IGF-1, GLUT4, PPARα, PPARγ, AdipoR1, AdipoR2, leptin, LPL, and lipase genes in adipose and muscle tissues in diabetic rats. These results suggest that C. latifolia fruit:root extract exerts antidiabetic and hypolipidemic effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats.

  9. L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

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    Xia Yunqiu

    2011-11-01

    Full Text Available Abstract Background There are an increasing number of patients suffering from fatty liver caused by type 2 diabetes. We intended to study the preventive and therapeutic effect of L-carnitine (LC on nonalcoholic fatty liver disease (NAFLD in streptozotocin (STZ-induced type 2 diabetic mice and to explore its possible mechanism. Methods Thirty male Kungming mice were randomly divided into five groups: control group, diabetic group, pre-treatment group (125 mg/kg BW, low-dose (125 mg/kg BW therapeutic group and high-dose (250 mg/kg BW therapeutic group. The morphology of hepatocytes was observed by light and electron microscopy. LC and ALC (acetyl L-carnitine concentrations in the liver were determined by high-performance liquid chromatography (HPLC. Moreover, liver weight, insulin levels and free fatty acid (FFA and triglyceride (TG levels in the liver and plasma were measured. Results Average liver LC and ALC levels were 33.7% and 20% lower, respectively, in diabetic mice compared to control mice (P Conclusion LC supplements ameliorated fatty liver in type 2 diabetic mice by increasing fatty acid oxidation and decreasing the LC/ALC ratio in the liver. Therefore, oral administration of LC protected mitochondrial function in liver.

  10. A Soxhlet Extract of Gongronema latifolium Retains Moderate Blood Glucose Lowering Effect and Produces Structural Recovery in the Pancreas of STZ-Induced Diabetic Rats

    Science.gov (United States)

    Al-Hindi, Bassel; Yusoff, Nor A.; Atangwho, Item J.; Ahmad, Mariam; Asmawi, Mohd Z.; Yam, Mun F.

    2016-01-01

    Background: Gongronema latifolium Benth. (GL) possesses considerable glucose lowering effects able to be utilized on a large-scale. This paper investigates the effects of a Soxhlet extract on hyperglycemia, Langerhans islets and glucose uptake by abdominal muscles. Methods: Ethanol and a Soxhlet apparatus were used to obtain GL ethanolic Soxhlet extract (GLES). It was then administered to randomly-segregated male Sprague-Dawley, normal and STZ-induced diabetic rats, using oral gavage to evaluate blood glucose levels (BGLs), serum lipid profile, insulin levels and the pancreas post-treatment. Results: GLES significantly (p Soxhlet extraction of Gongronema latifolium probably leads to the destruction of active heat-liable compounds. PMID:29083373

  11. Active and passive mechanical properties of isolated arterioles from STZ-induced diabetic rats. Effect of aminoguanidine treatment.

    Science.gov (United States)

    Hill, M A; Ege, E A

    1994-12-01

    Studies were performed to examine the effect of experimental diabetes (4-6 weeks duration) on both the passive elastic and active myogenic properties of isolated skeletal muscle arterioles. Studies were conducted on untreated streptozotocin (60 mg/kg)-induced diabetic rats and in similar rats treated daily with either amino-guanidine (25 mg/kg) or methylguanidine (25 mg/kg). First-order cremaster muscle arterioles were isolated, cannulated, and pressurized in the absence of intraluminal flow. Video microscopy was used to determine relationships between arteriolar diameter and intraluminal pressure both in the active and passive (o mmol/l Ca(2+)-2 mmol/l EGTA superfusated) tes. The measurements were used to calculate active myogenic responses, arteriolar distensibility, and stress-strain relationships. Under passive conditions, arterioles from untreated diabetic animals appeared to be stiffer and less distensible compared with similar arterioles from control animals. Under active conditions, i.e., in the presence of extracellular Ca2+, arterioles from the untreated diabetic group showed impaired myogenic reactivity as evidenced by a significant (P < 0.001) reduction in the negative slope of the pressure-diameter relationship over a physiological range of intraluminal pressures. Chronic treatment with aminoguanidine prevented the diabetes-induced changes in the active and passive properties of the isolated arterioles while treatment with methylguanidine appeared ineffective. Vasodilator responses to topically applied acetylcholine (10(-8) to 5 x 10(-6) mol/l) were significantly impaired in diabetic animals irrespective of treatment with aminoguanidine. The data indicate that experimental diabetes is associated with a decreased passive distensibility, or stiffening, of skeletal muscle arterioles that, in addition, may contribute to impaired active myogenic responses.

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

    Science.gov (United States)

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

    2014-01-01

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

  13. A Soxhlet Extract of Gongronema latifolium Retains Moderate Blood Glucose Lowering Effect and Produces Structural Recovery in the Pancreas of STZ-Induced Diabetic Rats

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    Bassel Al-Hindi

    2016-04-01

    Full Text Available Background: Gongronema latifolium Benth. (GL possesses considerable glucose lowering effects able to be utilized on a large-scale. This paper investigates the effects of a Soxhlet extract on hyperglycemia, Langerhans islets and glucose uptake by abdominal muscles. Methods: Ethanol and a Soxhlet apparatus were used to obtain GL ethanolic Soxhlet extract (GLES. It was then administered to randomly-segregated male Sprague-Dawley, normal and STZ-induced diabetic rats, using oral gavage to evaluate blood glucose levels (BGLs, serum lipid profile, insulin levels and the pancreas post-treatment. Results: GLES significantly (p < 0.05 decreased BGLs of normal rats in glucose tolerance testing at a dose of 2 g/kg b.w. but failed to do so in diabetic rats undergoing acute 7-h treatment. Given twice-daily, 1 g/kg b.w. of GLES moderately controlled diabetic BGLs starting from day 10. After 14 days of treatment, 1 g/kg and 0.5 g/kg b.w. of GLES caused 44% and 50% respective increases in the average area of Langerhans islets compared to DC. Using isolated rat abdominal muscle, GLES was found to be a mild insulin-sensitizer. GC-MS analysis revealed the presence of the known glucose-lowering phytosterol, Sitostenone. Conclusion: Despite retaining moderate antidiabetic activity, Soxhlet extraction of Gongronema latifolium probably leads to the destruction of active heat-liable compounds.

  14. Effect of Elderberry (Sambucus nigra L. Extract Supplementation in STZ-Induced Diabetic Rats Fed with a High-Fat Diet

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    Ângelo C. Salvador

    2016-12-01

    Full Text Available Elderberry (Sambucus nigra L. lipophilic and polar extract dietary supplementation effects were evaluated according to diabetes management indices, using an in vivo model. A research pipeline was constructed, that ranged from extract preparation, partial chemical characterization and toxicity evaluation, to examining the elderberry extract dietary supplementation effects on biofluid and tissues. Extracts toxicity was screened using an Aliivibrio fischeri bioluminescence model. A concentration of up to 60 mg/L was selected, and rat doses for oral supplementation were computed applying the interspecies correlation between A. fischeri and rats. Wistar type 2 diabetic rats, induced by streptozotocin (STZ, were fed a high-fat diet and supplemented for 4 weeks at doses of 190 and 350 mg/kg body weight/day of lipophilic and polar extract, respectively. As far as we know, lipophilic elderberry extract supplementation was assessed for the first time, while polar extract was administrated at higher doses and for a shorter period compared to previous studies, aiming to evaluate subacute supplementation effects. The polar extract modulated glucose metabolism by correcting hyperglycemia, while the lipophilic extract lowered insulin secretion. Both extracts lowered insulin resistance, without remarkable alterations to hematological indices, sera lipids and sera and tissular trace element homeostasis. In conclusion, elderberries are a potential source of bioactive compounds for formulations to be used as co-adjuvants in diabetes management.

  15. Interaction of glimepiride with prokinetic drugs on some of gastrointestinal functions in STZ-induced diabetic mice

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    Mohamed A. Fouad

    2013-06-01

    Conclusion: Use of metoclopramide, domperidone or erythromycin with glimepiride may guard against the risk of gastrointestinal motility disturbance associated with glimepiride treated diabetic patients and may enhance the absorption of carbohydrates. The dose of glimepiride may be safely decreased when combined with erythromycin or metoclopramide.

  16. Effect of berberin on the regulatin of GFAP+ astrecyte in the hippocampus of STZ diabetic rats

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    Hamid Kalalian-Moghaddam

    2015-05-01

    Full Text Available Background: Diabetes mellitus increases the risk of central nervous system (CNS disorders such as stroke, seizures, dementia, and cognitive impairment. Berberine, a natural isoquinolne alkaloid, is reported to exhibit beneficial effect in various neurodegenerative and neuropsychiatric disorders. Moreover astrocytes are proving critical for normal CNS function, and alterations in their activity and impaired oxidative stress could contribute to diabetes-related cognitive dysfunction. Metabolic and oxidative insults often cause rapid changes in glial cells. Key indicators of this response are increased synthesis of glial fibrillary acidic protein (GFAP as an astrocytic marker. Therefore, this study was conducted to determine the effect of berberine on glial reactivity of hippocampus in (STZ-induced diabetes rats. Materials and Methods: Experimental groups included: The control, control berberine treated (100 mg/kg.8 weeks, diabetic and diabetic berberine treated (50,100 mg/kg for 8 weeks groups. The effects of berberine on glial reactivity of hippocampus evaluated in (STZ-induced diabetics rats, using GFAP immunohistochemistry test. Data were analyzed by using Prism-5, one way ANOVA and Tukey tests. Results: Eight weeks after diabetes induction we observed an increase in GFAP immune staining in the hippocampus of STZ-diabetic rats relative to levels in the control brains. In contrast, chronic treatment with berberine (50 and 100 mg/kg, p.o., once daily lowered hyperglycemia, and prevents the up regulation of GFAP in brain of diabetic rats. Conclusion: the present study demonstrates treatment with berberine resulted in an obvious reduction of GFAP+ immunoreactive astrocytes in hippocampus of STZ -induced diabetic rats.

  17. Changes in Iron Metabolism and Oxidative Status in STZ-Induced Diabetic Rats Treated with Bis(maltolato Oxovanadium (IV as an Antidiabetic Agent

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    Cristina Sánchez-González

    2014-01-01

    Full Text Available The role of vanadium as a micronutrient and hypoglycaemic agent has yet to be fully clarified. The present study was undertaken to investigate changes in the metabolism of iron and in antioxidant defences of diabetic STZ rats following treatment with vanadium. Four groups were examined: control; diabetic; diabetic treated with 1 mgV/day; and Diabetic treated with 3 mgV/day. The vanadium was supplied in drinking water as bis(maltolato oxovanadium (IV (BMOV. The experiment had a duration of five weeks. Iron was measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, and femur. Superoxide dismutase, catalase, NAD(PH: quinone-oxidoreductase-1 (NQO1 activity, and protein carbonyl group levels in the liver were determined. In the diabetic rats, higher levels of Fe absorbed, Fe content in kidney, muscle, and femur, and NQO1 activity were recorded, together with decreased catalase activity, in comparison with the control rats. In the rats treated with 3 mgV/day, there was a significant decrease in fasting glycaemia, Fe content in the liver, spleen, and heart, catalase activity, and levels of protein carbonyl groups in comparison with the diabetic group. In conclusion BMOV was a dose-dependent hypoglycaemic agent. Treatment with 3 mgV/day provoked increased Fe deposits in the tissues, which promoted a protein oxidative damage in the liver.

  18. Dillenia indica L. attenuates diabetic nephropathy via inhibition of advanced glycation end products accumulation in STZ-nicotinamide induced diabetic rats.

    Science.gov (United States)

    Kaur, Navpreet; Kishore, Lalit; Singh, Randhir

    2018-01-01

    The present study was aimed to evaluate advanced glycation end products (AGEs) inhibitory activity of alcohol and hydro-alcohol extract (DAE and DHE) of Dillenia indica L. (Family: Dilleniaceae) and its potential in treatment of diabetic nephropathy by targeting markers of oxidative stress. D. indica was evaluated for its in vitro inhibitory activity against formation of AGEs by using bovine serum albumin. Diabetes was induced in male Wistar rats by streptozotocin (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration. Diabetic rats were treated with different doses of extracts (100, 200 and 400 mg/kg) to analyze their nephroprotective effect. Tissue antioxidant enzymes level was measured along with the formation of AGEs in kidney to assess the effect of D. indica in ameliorating oxidative stress. D. indica showed significant inhibition of AGEs formation in vitro. D. indica produced significant attenuation in the glycemic status, renal parameter, lipid profile and level of antioxidant enzymes proving efficacy in diabetic nephropathy. Moreover, D. indica produced significant reduction in the formation of AGEs in kidneys. The present study concludes that D. indica as a possible therapeutic agent against diabetic nephropathy.

  19. Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats.

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    Raul Hernandes Bortolin

    Full Text Available Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM, and T1DM plus zinc supplementation (T1DMS. Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus, and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic

  20. Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE-/- mice.

    Science.gov (United States)

    Ganguly, Rituparna; Sahu, Soumyadip; Ohanyan, Vahagn; Haney, Rebecca; Chavez, Ronaldo J; Shah, Shivani; Yalamanchili, Siri; Raman, Priya

    2017-03-27

    Increasing evidence suggests thrombospondin-1 (TSP-1), a potent proatherogenic matricellular protein, as a putative link between hyperglycemia and atherosclerotic complications in diabetes. We previously reported that the micronutrient chromium picolinate (CrP), with long-standing cardiovascular benefits, inhibits TSP-1 expression in glucose-stimulated human aortic smooth muscle cells in vitro. Here, we investigated the atheroprotective action of orally administered CrP in type 1 diabetic apolipoprotein E-deficient (ApoE-/-) mice and elucidated the role of TSP-1 in this process. CrP decreased lipid burden and neointimal thickness in aortic root lesions of hyperglycemic ApoE-/- mice; also, smooth muscle cell (SMC), macrophage and leukocyte abundance was prevented coupled with reduced cell proliferation. Attenuated lesion progression was accompanied with inhibition of hyperglycemia-induced TSP-1 expression and reduced protein O-glycosylation following CrP treatment; also, PCNA and vimentin (SMC synthetic marker) expression were reduced while SM-MHC (SMC contractile marker) levels were increased. To confirm a direct role of TSP-1 in diabetic atherosclerosis, hyperglycemic TSP-1-/-/ApoE-/- double knockout mice were compared with age-matched hyperglycemic ApoE-/- littermates. Lack of TSP-1 prevented lesion formation in hyperglycemic ApoE-/- mice, mimicking the atheroprotective phenotype of CrP-treated mice. These results suggest that therapeutic TSP-1 inhibition may have important atheroprotective potential in diabetic vascular disease.

  1. Effects of hydro-alcoholic extract of Prangos ferulacea (L. Lindle on histopathology of pancreas and diabetes treatment in STZ- induced diabetic rats

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    Khosro Soltani band

    2011-12-01

    Conclusion: The roots´ hydro-alcoholic extract of P.f seems to be capable to regenerate the islets of Langerhans in the treated rats in comparison with the untreated diabetic rats. This property can be due to some components of the plant that can increase insulin secretion.

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

    African Journals Online (AJOL)

    This study evaluated the liver status of STZ- induced diabetic rats treated with aqueous root-bark extract of T. tetraptera for 35 days. Twenty-four (24) rats in four groups (normal control, diabetic control, T. tetraptera treated STZ induced diabetic rats at 150 mg/kg b. w. and T. tetraptera treated STZ-diabetic rats at 300 mg/kg ...

  3. Renal injury is accelerated by global hypoxia-inducible factor 1 alpha deficiency in a mouse model of STZ-induced diabetes

    Czech Academy of Sciences Publication Activity Database

    Bohuslavová, Romana; Čerychová, Radka; Nepomucká, Kateřina; Pavlínková, Gabriela

    2017-01-01

    Roč. 17, č. 1 (2017), č. článku 48. ISSN 1472-6823 Institutional support: RVO:86652036 Keywords : Diabetic complications * Diabetic nephropathy * Hypoxia Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.275, year: 2016

  4. Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats.

    Science.gov (United States)

    Molanouri Shamsi, M; Mahdavi, M; Quinn, L S; Gharakhanlou, R; Isanegad, A

    2016-09-01

    Impairment of adipose tissue and skeletal muscles accrued following type 1 diabetes is associated with protein misfolding and loss of adipose mass and skeletal muscle atrophy. Resistance training can maintain muscle mass by changing both inflammatory cytokines and stress factors in adipose tissue and skeletal muscle. The purpose of this study was to determine the effects of a 5-week ladder climbing resistance training program on the expression of Hsp70 and inflammatory cytokines in adipose tissue and fast-twitch flexor hallucis longus (FHL) and slow-twitch soleus muscles in healthy and streptozotocin-induced diabetic rats. Induction of diabetes reduced body mass, while resistance training preserved FHL muscle weight in diabetic rats without any changes in body mass. Diabetes increased Hsp70 protein content in skeletal muscles, adipose tissue, and serum. Hsp70 protein levels were decreased in normal and diabetic rats by resistance training in the FHL, but not soleus muscle. Furthermore, resistance training decreased inflammatory cytokines in FHL skeletal muscle. On the other hand, Hsp70 and inflammatory cytokine protein levels were increased by training in adipose tissue. Also, significant positive correlations between inflammatory cytokines in adipose tissue and skeletal muscles with Hsp70 protein levels were observed. In conclusion, we found that in diabetic rats, resistance training decreased inflammatory cytokines and Hsp70 protein levels in fast skeletal muscle, increased adipose tissue inflammatory cytokines and Hsp70, and preserved FHL muscle mass. These results suggest that resistance training can maintain skeletal muscle mass in diabetes by changing inflammatory cytokines and stress factors such as Hsp70 in skeletal muscle and adipose tissue.

  5. [Study on hypoglycemic effect and mechanism of total flavonoids of Propolis in STZ diabetic rats].

    Science.gov (United States)

    Yang, Ming; Sui, Dian-jun; Chen, Wen-xue; Yang, Ming; Yu, De-wei

    2014-09-01

    To study hypoglycemic effect and mechanism of the total flavonoids of Propolis (TFP) in the STZ diabetic rats. The model of type 2 diabetic rats was induced by high-fat diet feeding for 4 weeks combined with intraperitoneal injection of streptozotocin (STZ). Then the rats without above-mentioned treatment were selected as the normal control group,the diabetic rats were randomly divided into four groups by blood glucose, the model control group, high doses (240 mg/kg), medium doses (120 mg/kg) and low doses (60 mg/kg) TFP groups. The TFP preparation was intragastric administration given to rats in TFP groups. The model control rats were treated intragastric administration with 0.5% sodium carboxymethyl cellulose (CMC-Na) for 4 weeks. The rats were fed with high fat diet during treatment. 12 hours after the last administration, glucose (GLU), total cholesterol (TC), triglyceride (TG), high density lipoprotein( HDL-C), low density lipoprotein LDL-C), glycated hemoglobin (GHb), serum insulin INS), C-peptide (C-P), superoxide dismutase( SOD), malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-alpha (TNF-alpha), free fatty acid (FFA), nitric oxide (NO), and hepatic glycogen were determined. Compared with the normal group, the levels of GLU, TC, TG, HDL-C, FFA, TNF-alpha, NO, MDA and GHb in serum were increased significantly in the model control group (P < 0.05-P < 0.001), the levels of HDL-C, INS, C-P, SOD and GSH in serum and hepatic glycogen in hepatic tissue were decreased significantly (P < 0.01 or P < 0.001). The levels of all above indexes of high and medium doses groups were improved significantly compared with the model control group (P < 0.05-P < 0.01). TFP can significantly decrease the level of blood glucose,improve the glucose and lipid metabolism and inhibit insulin resistance in STZ diabetic rats.

  6. Effect of an aqueous extract of Cucurbita ficifolia Bouché on the glutathione redox cycle in mice with STZ-induced diabetes.

    Science.gov (United States)

    Díaz-Flores, M; Angeles-Mejia, S; Baiza-Gutman, L A; Medina-Navarro, R; Hernández-Saavedra, D; Ortega-Camarillo, C; Roman-Ramos, R; Cruz, M; Alarcon-Aguilar, F J

    2012-10-31

    Cucurbita ficifolia is used in Mexican traditional medicine as an anti-diabetic and anti-inflammatory agent and its actions can be mediated by antioxidant mechanisms. Disturbance in the homeostasis of glutathione has been implicated in the etiology and progression of diabetes mellitus and its complications. It was evaluated, the effect of an aqueous extract of Cucurbita ficifolia on glycemia, plasma lipid peroxidation; as well as levels of reduced (GSH) and oxidized (GSSG) glutathione and activities of enzymes involved in glutathione redox cycle: glutathione peroxidase (GPx) and glutathione reductase (GR) in liver, pancreas, kidney and heart homogenates of streptozotocin-induced diabetic mice. Increased blood glucose and lipid peroxidation, together with decreased of GSH concentration, GSH/GSSG ratio and its redox potential (E(h)), and enhanced activity of GPx and GR in liver, pancreas and kidney were the salient features observed in diabetic mice. Administration of the aqueous extract of Cucurbita ficifolia to diabetic mice for 30 days, used at a dose of 200 mg/kg, resulted in a significant reduction in glycemia, polydipsia, hyperphagia and plasma lipid peroxidation. Moreover, GSH was increased in liver, pancreas and kidney, and GSSG was reduced in liver, pancreas and heart, therefore GSH/GSSG ratio and its E(h) were restored. Also, the activities involved in the glutathione cycle were decreased, reaching similar values to controls. An aqueous extract of Cucurbita ficifolia with hypoglycemic action, improve GSH redox state, increasing glutathione pool, GSH, GSH/GSSG ratio and its E(h), mechanism that can explain, at least in part, its antioxidant properties, supporting its use as an alternative treatment for the control of diabetes mellitus, and prevent the induction of complications by oxidative stress. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  9. Effect of Chinese medicine Qidengmingmu capsule on the STZ induced hyperglycemia rat's blood-retinal barrier

    Directory of Open Access Journals (Sweden)

    Fu-Wen Zhang

    2013-06-01

    Full Text Available AIM: To observe retinal vessel leakage of streptozotocin(STZinduced diabetic rat, and the effect of traditional Chinese medicine on it. METHODS: We induced diabetic rat model by peritoneal injection of STZ, after the blood glucose raised, we used Evans blue to trace the leakage of blood-retina barrier(BRBevery month. After blood glucose rose three months later, we treated the Chinese medicine group diabetic rat with Qidengmingmu capsule. There were three groups of different dose, low dose group of 125mg/kg, middle dose group of 250mg/kg, high dose group of 500mg/kg. The control group was treated with calcium dobesilate(200mg/kg. After three months treated by medicine, the leakage of rat blood-retina barrier was evaluated. RESULTS: The damage of BRB and visual function occurred at two week after the blood glucose rose, and the damage aggravated with the continuing of high diabetic. But after the Chinese medicine treated three months, the rat's retina vessel leakage was reduced. CONCLUSION: BRB break down and visual acuity damage appears in early phase of STZ diabetic rat and get worse as the hyperglycemia keep on. The Chinese medicine Qidengmingmu capsule can prevent the vessel leakage by damage of BRB.

  10. Comparison of sensory tests and neuronal quantity of peripheral nerves between streptozotocin (STZ)-induced diabetic rats and paclitaxel (PAC)-treated rats.

    Science.gov (United States)

    Jin, Heung Yong; Lee, Na Young; Ko, Hyun A; Lee, Kyung Ae; Park, Tae Sun

    Although diabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are different disease entities, they share similar neuropathic symptoms that impede quality of life for these patients. Despite having very similar downstream effects, there have been no direct comparisons between DPN and CIPN with respect to symptom severity and therapeutic responses. We compared peripheral nerve damage due to hyperglycemia with that caused by paclitaxel (PAC) treatment as represented by biochemical parameters, diverse sensory tests, and immunohistochemistry of cutaneous and sciatic nerves. The therapeutic effects of alpha-lipoic acid and DA-9801 were also compared in the two models. Animals were divided into seven groups (n = 7-10) as follows: normal, diabetes (DM), DM + alpha-lipoic acid 100 mg/kg (ALA), DM + DA-9801 (100 mg/kg), paclitaxel-treated rat (PAC), PAC + ALA (100 mg/kg), and PAC + DA-9801 (100 mg/kg). The sensory thresholds of animals to mechanical, heat, and pressure stimuli were altered by both hyperglycemia and PAC when compared with controls, and the responses to sensory tests were different between both groups. There were no significant differences in the biochemical markers of blood glutathione between DM and PAC groups (p > .05). Quantitative comparisons of peripheral nerves by intraepidermal nerve fiber density (IENFD) analysis indicated that the DM and PAC groups were similar (6.18 ± 1.03 vs. 5.01 ± 2.57). IENFD was significantly improved after ALA and DA-9801 treatment in diabetic animals (7.6 ± 1.28, 7.7 ± 1.28, respectively, p PAC-treated groups (6.05 ± 1.76, 5.66 ± 1.26, respectively, p > .05). Sciatic nerves were less damaged in the PAC-treated groups compared with the DM groups with respect to axonal diameter and area (8.60 ± 1.14 μm vs. 6.66 ± 1.07 μm, and 59.04 ± 15.16 μm2 vs. 35.71 ± 11.2 μm2, respectively, p < .05

  11. Heterogeneous Downregulation of Angiotensin II AT1-A and AT1-B Receptors in Arterioles in STZ-Induced Diabetic Rat Kidneys

    Directory of Open Access Journals (Sweden)

    Zsolt Razga

    2014-01-01

    Full Text Available Introduction. The renin granulation of kidney arterioles is enhanced in diabetes despite the fact that the level of angiotensin II in the diabetic kidney is elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in afferent and efferent arteriole’s renin-positive and renin-negative smooth muscle cells (SMC was estimated. Method. Immunohistochemistry at the electron microscopic level was combined with 3D stereological sampling techniques. Results. In diabetes the enhanced downregulation of AT1-B receptors in the renin-positive than in the renin-negative SMCs in both arterioles was resulted: the significant difference in the number of AT1 (AT1-A + AT1-B receptors between the two types of SMCs in the normal rats was further increased in diabetes and in contrast with the significant difference observed between the afferent and efferent arterioles in the normal animals, there was no such difference in diabetes. Conclusions. The enhanced downregulation of the AT1-B receptors in the renin-negative SMCs in the efferent arterioles demonstrates that the regulation of the glomerular filtration rate by the pre- and postglomerular arterioles is changed in diabetes. The enhanced downregulation of the AT1-B receptors in the renin-positive SMCs in the arterioles may result in an enhanced level of renin granulation in the arterioles.

  12. Abnormal Expressions of Age, RAGE, TGF- b1 and TGF- b1 Receptor in Colonic Wall Contributed to STZ-Induced Diabetic Colon Remodeling

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Gregersen, Hans

    2016-01-01

    glycation end product (AGE) and AGE receptor (RAGE) were up-regulated in the diabetic colon wall (2). However, it lacks data in relation to the association between AGE, RAGE, transforming growth factor- b1 (TGF-b1) and TGFb1 receptor expressions with colon morphological and biomechanical remodeling...... glucose level was measured. The parameters of morphometric and biomechanical properties of colonic segments were obtained from diabetic (DM) and normal (Con) rats. The expressions of AGE, RAGE, TGF- b1 and TGF- b1 receptor were detected in different layers of the colon by immunohistochemistry. In order...... to determine the expressions of AGE, RAGE, TGF- b1 and TGF- b1 receptor in association with other parameters, and to see interrelation among AGE, RAGE, TGF- b1 and TGF- b1 receptor expressions, the multiple linear regression analysis was done. Results: The expressions of AGE, RAGE, TGF-b1 and TGF- b1 receptor...

  13. COMPARATIVE EVALUATION OF HYPOGLYCEMIC EFFECTS OF TWO DIFFERENT PARTS OF BAUHUNIA PURPUREA LINN. PLANT IN STZ-INDUCED DIABETIC ALBINO WISTAR RATS

    Directory of Open Access Journals (Sweden)

    A. K. Brahmachari

    2015-12-01

    Full Text Available The present work was undertaken to study the comparative phytochemical profiles and hypoglycemic effects of Bauhinia purpurea Linn. Barks (BPBE and leaves ethanolic extracts (BPLE in albino wistar rats to validate their ethno medical use in hyperglycemia as well as to explore the better option. Phytochemicals in ethanolic extracts were analyzed by standard natural product chemistry methods. Diabetes was developed in rats by single intraperitoneal injection of Streptozotocin @ 60mg/ Kg bw. Diabetic albino wister rats (n=3 of either sex (150-200gm bw were orally fed with the extracts once daily for 4 weeks. Glibenclamide @ 0.5mg/Kg bw was used as a positive control for comparison. Fasting blood glucose level at 0, 14th and 28th day and hemoglobin and glycosylated hemoglobin on 28th day of experiment were analyzed. Our results show that the extracts contain alkaloids, flavonoids, glycosides, terpenoids, tannins and phenolics. Rats treated with plant extracts show better glucose modulation, decreased hemoglobin glycosylation and improved hemoglobin concentration as compared to diabetic control. The hypoglycemic effect of only BPBE at 420 mgkg-1 on 14th and 28th day is comparable to that of standard drug glibenclamide (P>0.01. The bark extract has been observed to be more potent hypoglycemic agent than leave extract.

  14. Ethanol extract of mango (Mangifera indica L.) peel inhibits α-amylase and α-glucosidase activities, and ameliorates diabetes related biochemical parameters in streptozotocin (STZ)-induced diabetic rats.

    Science.gov (United States)

    Gondi, Mahendranath; Prasada Rao, U J S

    2015-12-01

    Peel is a major by-product during processing of mango fruit into pulp. Recent report indicates that the whole peel powder ameliorated diabetes. In the present study, ethanolic extract of mango peel was analysed for its bioactive compounds, evaluated for α-amylase and α-glucosidase inhibitory properties, oral glucose tolerance test, antioxidant properties, plasma insulin level and biochemical parameters related to diabetes. In addition to gallic and protocatechuic acids, the extract also had chlorogenic and ferulic acids, which were not reported earlier in mango peel extracts. The peel extract inhibited α-amylase and α-glucosidase activities, with IC50 values of 4.0 and 3.5 μg/ml. Ethanolic extract of peel showed better glucose utilization in oral glucose tolerance test. Treatment of streptozotocin-induced diabetic rats with the extract decreased fasting blood glucose, fructosamine and glycated hemoglobin levels, and increased plasma insulin level. Peel extract treatment decreased malondialdehyde level, but increased the activities of antioxidant enzymes significantly in liver and kidney compared to diabetic rats. These beneficial effects were comparable to metformin, but better than gallic acid treated diabetic rats. The beneficial effects of peel extract may be through different mechanism like increased plasma insulin levels, decreased oxidative stress and inhibition of carbohydrate hydrolyzing enzyme activities by its bioactive compounds. Thus, results suggest that the peel extract can be a potential source of nutraceutical or can be used in functional foods and this is the first report on antidiabetic properties of mango peel extract.

  15. ICV STZ induced impairment in memory and neuronal mitochondrial function: A protective role of nicotinic receptor.

    Science.gov (United States)

    Saxena, Gunjan; Patro, Ishan K; Nath, Chandishwar

    2011-10-10

    The present study was planned to evaluate the cholinergic influence on mitochondrial activity and neurodegeneration associated with impaired memory in intracerebroventricular (ICV) streptozotocin (STZ) treated rats. STZ (3mg/kg), administered ICV twice with an interval of 48h between the two doses, showed significant impairment in spatial memory tested by water maze test 14 days after first dose without altering blood glucose level and locomotor activity. Animals were sacrificed on 21st day of ICV administration. STZ significantly increased malondialdehyde (MDA), reactive oxygen species (ROS), Ca(2+) ion influx, caspase-3 activity and decreased glutathione (GSH) level. Acetylcholinesterase inhibitors tacrine and donepezil (5mg/kg, PO) pretreatment significantly prevented STZ induced memory deficit, oxidative stress, Ca(2+) influx and caspase-3 activity. Carbachol, a muscarinic cholinergic agonist (0.01mg/kg, SC) did not show any significant effect on ROS generation, Ca(2+) ion influx and caspase-3 activity. While nicotinic cholinergic agonist, nicotine, significantly attenuated ICV STZ induced mitochondrial dysfunction and caspase-3 activity. The results indicate that instead of muscarinic receptors nicotinic receptors may be involved in neuroprotection by maintaining mitochondrial functions. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.

    Science.gov (United States)

    Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

    2017-08-05

    Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing.

  17. Renal Protective Effects of Low Molecular Weight of Inonotus obliquus Polysaccharide (LIOP on HFD/STZ-Induced Nephropathy in Mice

    Directory of Open Access Journals (Sweden)

    Yen-Jung Chou

    2016-09-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM. Inonotus obliquus (IO is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP, from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10–100 kDa, LIOP (300 mg/kg had progressively increased their sensitivity to glucose (less insulin tolerance, reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-β on renal cortex in mice. Consistently, three days of LIOP (100 μg/mL incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1, while the levels of NF-κB and TGF-β expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF

  18. Testicular cytoprotective activities of Curcuma longa in STZ-induced ...

    African Journals Online (AJOL)

    Its major component is the curcumin that is found to be a natural antioxidant. Diabetes affects large number of young men of reproductive age. It is among a number of disorders associated with oxidative stress. There has been a relationship established between the reduction in glucose load and insulin resistance reduction ...

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

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    N erfani majd

    2016-12-01

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

  20. Exercise and Beta-Glucan Consumption (Saccharomyces cerevisiae) Improve the Metabolic Profile and Reduce the Atherogenic Index in Type 2 Diabetic Rats (HFD/STZ).

    Science.gov (United States)

    Andrade, Eric Francelino; Lima, Andressa Ribeiro Veiga; Nunes, Ingrid Edwiges; Orlando, Débora Ribeiro; Gondim, Paula Novato; Zangeronimo, Márcio Gilberto; Alves, Fernando Henrique Ferrari; Pereira, Luciano José

    2016-12-17

    Physical activity and the ingestion of dietary fiber are non-drug alternatives commonly used as adjuvants to glycemic control in diabetic individuals. Among these fibers, we can highlight beta-glucans. However, few studies have compared isolated and synergic effects of physical exercise and beta-glucan ingestion, especially in type 2 diabetic rats. Therefore, we evaluated the effects beta-glucan (Saccharomyces cerevisiae) consumption, associated or not to exercise, on metabolic parameters of diabetic Wistar rats. The diabetes mellitus (DM) was induced by high-fat diet (HFD) associated with a low dose of streptozotocin (STZ-35 mg/kg). Trained groups were submitted to eight weeks of exercise in aquatic environment. In the last 28 days of experiment, animals received 30 mg/kg/day of beta-glucan by gavage. Isolated use of beta-glucan decreased glucose levels in fasting, Glycated hemoglobin (HbA1c), triglycerides (TAG), total cholesterol (TC), low-density lipoprotein (LDL-C), the atherogenic index of plasma. Exercise alone also decreased blood glucose levels, HbA1c, and renal lesions. An additive effect for reducing the atherogenic index of plasma and renal lesions was observed when both treatments were combined. It was concluded that both beta-glucan and exercise improved metabolic parameters in type 2 (HFD/STZ) diabetic rats.

  1. Effects of black hoof medicinal mushroom, phellinus linteus (Agaricomycetes), polysaccharide extract in streptozotocin-induced diabetic rats

    NARCIS (Netherlands)

    Yamaç, Mustafa; Zeytinoğlu, Melih; Şentürk, Hakan; Kartkaya, Kazim; Kanbak, Göngör; Bayramoğlu, Gökhan; Oğlakci, Ayşegül; Griensven, van Leo J.L.D.

    2016-01-01

    In this article we report the healing effects of a Phellinus linteus fruiting body hot water extract (PLE) in streptozotocin (STZ)–induced diabetic rats. PLE was given before and after STZ. The preprotective, protective, and postprotective effects of PLE on STZ-induced oxidative stress were

  2. Intranasal insulin improves cerebral blood flow, Nrf-2 expression and BDNF in STZ (ICV)-induced memory impaired rats.

    Science.gov (United States)

    Rajasekar, N; Nath, Chandishwar; Hanif, Kashif; Shukla, Rakesh

    2017-03-15

    Insulin/insulin receptor signaling is involved in cognitive functions. Clinical studies have shown that intranasal insulin administration improves memory functions. However, the molecular mechanisms associated with improvement in memory functions are largely unexplored. Therefore, we investigated the protective effect of intranasal insulin in intracerebroventricular (ICV) streptozotocin (STZ) induced memory impairment in rats. Rats were injected with STZ (3mg/kg, ICV) bilaterally twice, on days 1 and 3 and intranasal insulin (2IU/rat/day) was given for 14days. Memory was assessed by Morris water maze test. Cerebral blood flow (CBF) was measured by laser-Doppler flowmetry. The biochemical and molecular studies were done in cortex and hippocampus of rat brain. STZ (ICV) administration caused memory impairment along with the reduction of CBF, ATP level, and Nrf-2 expression. Treatment with intranasal insulin significantly improved memory functions as well as restored CBF, ATP content and Nrf-2 expression in STZ injected rats. STZ administration stimulated oxidative-nitrosative stress as evidenced by a significant increase in ROS, malondialdehyde, NO level and inducible nitric oxide synthase expression and the decrease in glutathione level; which was normalized by intranasal insulin delivery. STZ-induced cholinergic dysfunction (AChE activity and α7-nAChR expression), and mitochondrial hypofunction was largely prevented by treatment with intranasal insulin. Intranasal insulin delivery successfully restored BDNF level and pCREB expression in STZ injected rats. The study shows the beneficial effects of intranasal insulin against STZ-induced memory impairment, which attributed to improved CBF, cholinergic function, brain energy metabolism, BDNF, Nrf-2 expression and antioxidative action. Copyright © 2016. Published by Elsevier Inc.

  3. Protective Effect of Flowerbuds of Lonicera Japonica Extract on Diabetes Mellitus Type 2 and Associated Vascular Complications in STZ-HFD Treated Rats

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    Chiragkumar Amrutlal Prajapati

    2015-12-01

    Full Text Available Objective: To study the protective effect of Lonicera Japonica Alcoholic Extract (LJALE on Diabetes Mellitus  II (DM and associated vascular complications.Methods: Induction of Diabetes Mellitus II with 35 mg / kg STZ-HFD leads to excessive level of 11β-HSD1 enzyme. It has been found that flower buds of Lonicera Japonica (LJ has also been traditionally indicated for treatment of diabetes. Chlorogenic Acid (CA is a major bioactive component in the flower buds of LJ has received more attention because of its 11β-HSD1 inhibitory action.11β-HSD1 regulates glucocorticoid action at the pre-receptor stage by converting cortisone to cortisol. Elevated glucocorticoids are a key risk factor for metabolic diseases. LJALE was prepared with help of Microwave Assisted Extraction (MAE method.  STZ-HFD-induced diabetic rats were treated with LJALE (200 mg/kg, 500 mg/kg and Metformin (50 mg/kg. It was given for 4 weeks.Result: LJALE treated Diabetic rats showed significant decreased in blood glucose levels, plasma insulin, serum cortisol as well significant increased hepatic glycogen, 11β-HSD1 index compare to diabetic control rats. LJALE (500 mg/kg treatment showed the return of islets close to good vascular pattern. LJALE treatment restored endothelium dysfunction.Conclusions: From all results it is reasonable to conclude that LJALE (500 mg/kg may be used in treatment of diabetes and diabetes associated vascular dysfunction.Keywords:  Diabetes Mellitus, 11β-HSD1, CA, LJALE

  4. The Effect of Alium Satium Extract on the Glomerular Diameter of STZ -induced Sprague dawley Rats

    Directory of Open Access Journals (Sweden)

    Susilorini Susilorini

    2013-06-01

    Full Text Available Hyperglycemia exert toxic effect in kidney.The aim of this study was to investigate the short term effect of ethanolic extract of garlic in preventing nephropathy following streptozotocin (STZ induced rats. Twenty male Sprague dawley rats were randomly divided into 4 group, all group induced induced by single dose intraperitoneal injection of 40 mg kg-1 of streptozotocin (STZ. Treatment with 3 doses ethanolic extract of garlic (0,1; 0,25; 0,5 mg kg-1 day-1 was followed for 14 days, then the left kidneys were excised and histhopathological studies were carried out using scanner 3D Hitech and Panoramic view software. Statistical analysis have been done using non parametric analysis Kruskall Wallis. The study revealed that glomerular diameter of the treatment rats was significantly different from the control group (p=0,0001. Increasing doses didn’t make difference. The ethanolic extract of garlic (Allium sativum influences the diameter glomeruli but increasing doses has no effect on the glomerular diameter.

  5. Impairment of insulin-stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic Rats

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    Deng Jen-Ying

    2009-08-01

    Full Text Available Abstract In this study, we established systemic in-vivo evidence from molecular to organism level to explain how diabetes can aggravate myocardial ischemia-reperfusion (I/R injury and revealed the role of insulin signaling (with specific focus on Akt/GLUT4 signaling molecules. The myocardial I/R injury was induced by the left main coronary artery occlusion for 1 hr and then 3 hr reperfusion in control, streptozotocin (STZ-induced insulinopenic diabetes, and insulin-treated diabetic rats. The diabetic rats showed a significant decrease in heart rate, and a prolonged isovolumic relaxation (tau which lead to decrease in cardiac output (CO without changing total peripheral resistance (TPR. The phosphorylated Akt and glucose transporter 4 (GLUT 4 protein levels were dramatically reduced in both I/R and non-I/R diabetic rat hearts. Insulin treatment in diabetes showed improvement of contractile function as well as partially increased Akt phosphorylation and GLUT 4 protein levels. In the animals subjected to I/R, the mortality rates were 25%, 65%, and 33% in the control, diabetic, and insulin-treated diabetic group respectively. The I/R-induced arrhythmias and myocardial infarction did not differ significantly between the control and the diabetic groups. Consistent with its anti-hyperglycemic effects, insulin significantly reduced I/R-induced arrhythmias but had no effect on I/R-induced infarctions. Diabetic rat with I/R exhibited the worse hemodynamic outcome, which included systolic and diastolic dysfunctions. Insulin treatment only partially improved diastolic functions and elevated P-Akt and GLUT 4 protein levels. Our results indicate that cardiac contractile dysfunction caused by a defect in insulin-stimulated Akt/GLUT4 may be a major reason for the high mortality rate in I/R injured diabetic rats.

  6. Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice.

    Science.gov (United States)

    Zhao, Shan-shan; Yang, Wei-na; Jin, Hui; Ma, Kai-ge; Feng, Gai-feng

    2015-12-01

    Puerarin (PUE), an isoflavone purified from the root of Pueraria lobata (Chinese herb), has been reported to attenuate learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). In the present study, we tested PUE in a sporadic AD (SAD) mouse model which was induced by the intracerebroventricular injection of streptozotocin (STZ). The mice were administrated PUE (25, 50, or 100mg/kg/d) for 28 days. Learning and memory abilities were assessed by the Morris water maze test. After behavioral test, the biochemical parameters of oxidative stress (glutathione peroxidase (GSH-Px), superoxide dismutases (SOD), and malondialdehyde (MDA)) were measured in the cerebral cortex and hippocampus. The SAD mice exhibited significantly decreased learning and memory ability, while PUE attenuated these impairments. The activities of GSH-Px and SOD were decreased while MDA was increased in the SAD animals. After PUE treatment, the activities of GSH-Px and SOD were elevated, and the level of MDA was decreased. The middle dose PUE was more effective than others. These results indicate that PUE attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. PUE may be a promising therapeutic agent for SAD. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Severe Hypoglycemia-Induced Fatal Cardiac Arrhythmias Are Augmented by Diabetes and Attenuated by Recurrent Hypoglycemia.

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    Reno, Candace M; VanderWeele, Jennifer; Bayles, Justin; Litvin, Marina; Skinner, Allie; Jordan, Andrew; Daphna-Iken, Dorit; Fisher, Simon J

    2017-12-01

    We previously demonstrated that insulin-mediated severe hypoglycemia induces lethal cardiac arrhythmias. However, whether chronic diabetes and insulin deficiency exacerbates, and whether recurrent antecedent hypoglycemia ameliorates, susceptibility to arrhythmias remains unknown. Thus, adult Sprague-Dawley rats were randomized into four groups: 1) nondiabetic (NONDIAB), 2) streptozotocin-induced insulin deficiency (STZ), 3) STZ with antecedent recurrent (3 days) hypoglycemia (∼40-45 mg/dL, 90 min) (STZ+RH), and 4) insulin-treated STZ (STZ+Ins). Following treatment protocols, all rats underwent hyperinsulinemic (0.2 units ⋅ kg-1 ⋅ min-1), severe hypoglycemic (10-15 mg/dL) clamps for 3 h with continuous electrocardiographic recordings. During matched nadirs of severe hypoglycemia, rats in the STZ+RH group required a 1.7-fold higher glucose infusion rate than those in the STZ group, consistent with the blunted epinephrine response. Second-degree heart block was increased 12- and 6.8-fold in the STZ and STZ+Ins groups, respectively, compared with the NONDIAB group, yet this decreased 5.4-fold in the STZ+RH group compared with the STZ group. Incidence of third-degree heart block in the STZ+RH group was 5.6%, 7.8-fold less than the incidence in the STZ group (44%). Mortality due to severe hypoglycemia was 5% in the STZ+RH group, 6.2-fold less than that in the STZ group (31%). In summary, severe hypoglycemia-induced cardiac arrhythmias were increased by insulin deficiency and diabetes and reduced by antecedent recurrent hypoglycemia. In this model, recurrent moderate hypoglycemia reduced fatal severe hypoglycemia-induced cardiac arrhythmias. © 2017 by the American Diabetes Association.

  8. Lutein attenuates oxidative stress markers and ameliorates glucose homeostasis through polyol pathway in heart and kidney of STZ-induced hyperglycemic rat model.

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    Sharavana, Gurunathan; Joseph, G S; Baskaran, Vallikannan

    2017-12-01

    Lutein's role on chronic hyperglycemia-induced oxidative stress and associated glucose homeostasis in heart and kidney is limited. Purpose of the study is to investigate the effect of lutein on cardiac and renal polyol pathway enzymes and oxidative stress markers under hyperglycemia-induced oxidative stress condition using streptozotocin (STZ)-injected rat model. STZ-induced hyperglycemic (fasting blood glucose ≥11 mM) male Wistar rats were divided into two groups (n = 11/group). Group 1 received micellar lutein (39 nmol/day/rat) and group 2 (negative control) received micelle without lutein for 8 weeks. A separate group (no STZ injected) served as a positive control (n = 11/group). Oral glucose tolerance test (OGTT), biweekly urine glucose and activities of aldose reductase (AR) and sorbitol dehydrogenase (SDH) enzymes were assessed. Activities of antioxidant enzymes and antioxidant level were also evaluated. Lutein-administered hyperglycemic rats showed better glucose tolerance as evidenced with OGTT and biweekly urine glucose when compared to negative control. Activities of AR and SDH were decreased in heart and kidney of lutein-fed hyperglycemic rats. Also, they had significantly (p < 0.05) decreased malondialdehyde levels (66, 34, and 33 %) and increased reduced glutathione level (81, 18 and 92 %) in serum, heart and kidney, respectively. Altered antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase were also affected in serum, heart and kidney of lutein-fed diabetic group. Lutein prevented cardiac and renal injury in STZ-induced hyperglycemic rats due to potential amelioration of altered activities in polyol pathway and oxidative stress markers.

  9. Protective Effect of Urtica dioica L. (Urticaceae) on Morphometric and Morphologic Alterations of Seminiferous Tubules in STZ Diabetic Rats.

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    Golalipour, Mohammad Jafar; Kabiri Balajadeh, Babak; Ghafari, Soraya; Azarhosh, Ramin; Khori, Vahid

    2011-09-01

    Urtica dioica L. has been known as a medicinal plant in the world. This study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on seminiferous tubules of diabetic rats. Animals were allocated to control, diabetic and protective groups. Treated animals received extract of U. dioica (100 mg/ kg/ day) IP for the first 5 days and STZ injection on the 6th day. After 5 weeks, testes removed and stained with H&E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization, and decrease in sperm concentration observed in diabetic in comparison with control and protective groups. External seminiferous tubular diameter and seminiferous epithelial height significantly reduced (Pdioica, before induction of diabetes; has protective role on seminiferous tubules alterations.

  10. 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.

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

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

    2014-05-01

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

  12. Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats.

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    Cheng, Juei-Tang; Huang, Ching-Chiu; Liu, I-Min; Tzeng, Thing-Fong; Chang, Chih Jen

    2006-03-01

    To better understand the insulin-independent plasma glucose-lowering action of metformin, we used streptozotocin (STZ)-induced diabetic rats to investigate the possible mechanisms. Oral intake of metformin decreased the plasma glucose of STZ-induced diabetic rats with a parallel increase of plasma beta-endorphin-like immunoreactivity (BER). Mediation of opioid mu-receptors in the action of metformin was identified by the blockade of receptors with antagonist in STZ-induced diabetic rats and the failure of action in opioid mu-receptor knockout diabetic mice. Release of BER from adrenal glands by metformin was characterized, using bilateral adrenalectomy and the release of BER from isolated adrenal medulla of STZ-induced diabetic rats. Repeated treatment with metformin in STZ-induced diabetic rats increased the mRNA and protein levels of GLUT-4 in soleus muscle that was blocked by naloxonazine. Reduction of the mRNA or protein levels of hepatic PEPCK was also impeded in the same group of STZ-induced diabetic rats. In conclusion, our results provide novel mechanisms for the plasma glucose-lowering action of metformin, via an increase of beta-endorphin secretion from adrenal glands to stimulate opioid mu-receptor linkage, leading to an increase of GLUT-4 gene expression and an attenuation of hepatic PEPCK gene expression in STZ-induced diabetic rats.

  13. Exercise and Beta-Glucan Consumption (Saccharomyces cerevisiae Improve the Metabolic Profile and Reduce the Atherogenic Index in Type 2 Diabetic Rats (HFD/STZ

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    Eric Francelino Andrade

    2016-12-01

    Full Text Available Physical activity and the ingestion of dietary fiber are non-drug alternatives commonly used as adjuvants to glycemic control in diabetic individuals. Among these fibers, we can highlight beta-glucans. However, few studies have compared isolated and synergic effects of physical exercise and beta-glucan ingestion, especially in type 2 diabetic rats. Therefore, we evaluated the effects beta-glucan (Saccharomyces cerevisiae consumption, associated or not to exercise, on metabolic parameters of diabetic Wistar rats. The diabetes mellitus (DM was induced by high-fat diet (HFD associated with a low dose of streptozotocin (STZ—35 mg/kg. Trained groups were submitted to eight weeks of exercise in aquatic environment. In the last 28 days of experiment, animals received 30 mg/kg/day of beta-glucan by gavage. Isolated use of beta-glucan decreased glucose levels in fasting, Glycated hemoglobin (HbA1c, triglycerides (TAG, total cholesterol (TC, low-density lipoprotein (LDL-C, the atherogenic index of plasma. Exercise alone also decreased blood glucose levels, HbA1c, and renal lesions. An additive effect for reducing the atherogenic index of plasma and renal lesions was observed when both treatments were combined. It was concluded that both beta-glucan and exercise improved metabolic parameters in type 2 (HFD/STZ diabetic rats.

  14. Thujone improves glucose homeostasis in streptozotocin-induced diabetic rats through activation of Akt/GSK-3AND#946; signaling pathway

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    Hakam Hasan Alkhateeb

    2015-01-01

    Objective: Thujone, a main constituent of medicinal herbs, has been shown to have antidiabetic properties. Therefore the primary objective of this study was to investigate the mechanism(s) by which thujone ameliorates diabetes and insulin resistance in streptozotocin (STZ)-induced diabetic rats. Methods: Male Sprague-Dawley rats were rendered diabetic by a single intraperitoneal injection of STZ (55 mg/kg). Thereafter, rats were randomly divided into three groups: normal control rats; STZ...

  15. Anti-diabetic effect of Murraya koenigii leaves on streptozotocin induced diabetic rats.

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    Arulselvan, P; Senthilkumar, G P; Sathish Kumar, D; Subramanian, S

    2006-10-01

    The present study was aimed to evaluate the anti-hyperglycemic efficacy of Murraya koenigii in STZ-induced diabetic rats. Oral administration of ethanolic extract of M. koenigii at a dose of 200 mg/kg/ b.w./day for a period of 30 days significantly decreased the levels of blood glucose, glycosylated hemoglobin, urea, uric acid and creatinine in diabetic treated group of animals. Determination of plasma insulin level revealed the insulin stimulatory effect of the extract. The results suggest that M. koenigii possesses statistically significant hypoglycemic potential in STZ-induced diabetic rats. The M. koenigii extract appeared to be more effective than glibenclamide, a known antidiabetic drug.

  16. Carnosine Prevents Apoptosis of Glomerular Cells and Podocyte Loss in STZ Diabetic Rats

    NARCIS (Netherlands)

    Riedl, Eva; Pfister, Frederick; Braunagel, Margarita; Brinkkoetter, Paul; Sternik, Paula; Deinzer, Martina; Bakker, Stephan J. L.; Henning, Rob H.; van den Born, Jacob; Kraemer, Bernhard K.; Navis, Gerjan; Hammes, Hans-Peter; Yard, Benito; Koeppel, Hannes

    2011-01-01

    Background/Aims: We identified carnosinase-1 (CN-1) as risk-factor for diabetic nephropathy (DN). Carnosine, the substrate for CN-1, supposedly is a protective factor regarding diabetic complications. In this study, we hypothesized that carnosine administration to diabetic rats might protect the

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

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

    2016-12-01

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

  18. Protective role of Urtica dioica L. (Urticaceae) extract on hepatocytes morphometric changes in STZ diabetic Wistar rats.

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    Golalipour, Mohammad Jafar; Ghafari, Soraya; Afshar, Mohammad

    2010-09-01

    The present investigation was carried out to evaluate the protective effect of the hydroalcoholic extract of Urtica dioica leaves on the quantitative morphometric changes in the liver of streptozotocin-induced diabetic rats. Thirty male Wistar rats were divided into control (G1), diabetic (G2), diabetic + Urtica dioica (G3) groups. The control group received only sham injections of intraperitoneal saline; the diabetic group received intraperitoneal saline for 5 days followed by streptozotocin (80 mg/kg) on the 6th day; and the diabetic + Urtica dioica group received 100 mg/kg Urtica dioica intraperitoneal (7) injections for 5 days and streptozotocin injection on the 6th day. After five weeks, the animals were sacrificed and whole livers removed. Liver specimens were used for quantitative morphometric analysis after hematoxylin and eosin staining. All data were statistically analyzed by one-way ANOVA and expressed as the mean with standard error of means. In the G3 (diabetic + Urtica diocia) group, the mean surface area of hepatocytes in the periportal zone (Z1) was greater than in G2 (diabetic) and G1 (control) groups, but this difference was not significant. No alteration was observed in the surface area of hepatocytes in the perivenous zone (Z3) in the diabetic + Urtica dioica (G3) group compared to the diabetic (G2) group. The mean nuclear area of hepatocytes of the rats in the diabetic + Urtica dioica (G3) group was higher in Z1 and lower in Z3 than that of rats in the diabetic (G2) group. The mean diameter of hepatocyte nuclei in the diabetic + Urtica dioica (G3) group was lower than that of diabetic (G2) and control (G1) groups in both Z1 and Z3. This study revealed that the administration of extract of Urtica dioica leaves before induction of diabetic with streptozotocin has a protective effect on the morphometric alterations of hepatocytes in the periportal and perivenous zones of the liver lobule in rats.

  19. Acute bout of exercise induced prolonged muscle glucose transporter-4 translocation and delayed counter-regulatory hormone response in type 1 diabetes.

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    Koji Sato

    Full Text Available Previous studies have demonstrated that an acute bout of aerobic exercise induces a subsequent delayed onset of hypoglycemia among patients with type 1 diabetes. However, the mechanisms of exercise-induced hypoglycemia in type 1 diabetes are still unclear. Streptozotocin (STZ was injected to 6-week-old male Wistar rats, and three days after STZ injection, animals were randomly assigned into 2 groups: STZ with insulin only (STZ and STZ with insulin and exercise (STZ+EX. Normal Wistar rats with exercise were used as control (CON+EX. Insulin was intraperitoneally injected (0.5 U/kg to both STZ groups (-0.5 h, and a bout of aerobic exercise (15 m/min for 30 min was conducted at euglycemic conditions (0 h. Blood was collected at 0, 1, 3, and 5 h after exercise from the carotid artery. While the blood glucose level was stable during the post-exercise period (0-5 h in the STZ and CON+EX groups, it decreased significantly only in the STZ+EX group at 3 h. Plasma glucagon, adrenalin, and noradrenalin levels significantly increased at 1 h in the STZ group, whereas significant hormonal responses were observed at 5 h in the STZ+EX group. In skeletal muscle glucose metabolism-related pathway, the level of glucose transporter-4 (GLUT-4 translocation was significantly higher at 1 h in the CON and STZ groups. However, in the STZ+EX group, these activations were maintained by 5 h, indicating a sustained glucose metabolism in the STZ+EX group. A single bout of aerobic exercise induced a delayed onset of hypoglycemia in STZ-treated rats. A prolonged enhancement of GLUT-4 translocation and delayed counter-regulatory hormone responses may have contributed to the induction of hypoglycemia.

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

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    Schaan B.D.

    2004-01-01

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

  1. Antidiabetic Effect of Fresh Nopal (Opuntia ficus-indica) in Low-Dose Streptozotocin-Induced Diabetic Rats Fed a High-Fat Diet.

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    Hwang, Seung Hwan; Kang, Il-Jun; Lim, Soon Sung

    2017-01-01

    The objective of the present study was to evaluate α-glucosidase inhibitory and antidiabetic effects of Nopal water extract (NPWE) and Nopal dry power (NADP) in low-dose streptozotocin- (STZ-) induced diabetic rats fed a high-fat diet (HFD). The type 2 diabetic rat model was induced by HFD and low-dose STZ. The rats were divided into four groups as follows: (1) nondiabetic rats fed a regular diet (RD-Control); (2) low-dose STZ-induced diabetic rats fed HFD (HF-STZ-Control); (3) low-dose STZ-induced diabetic rats fed HFD and supplemented with NPWE (100 mg/kg body weight, HF-STZ-NPWE); and (4) low-dose STZ-induced diabetic rats fed HFD and supplemented with comparison medication (rosiglitazone, 10 mg/kg, body weight, HF-STZ-Rosiglitazone). In results, NPWE and NADP had IC50 values of 67.33 and 86.68 μg/mL, both of which exhibit inhibitory activities but lower than that of acarbose (38.05 μg/mL) while NPWE group significantly decreased blood glucose levels compared to control and NPDP group on glucose tolerance in the high-fat diet fed rats model (P < 0.05). Also, the blood glucose levels of HR-STZ-NPWE group were significantly lower (P < 0.05) than HR-STZ-Control group on low-dose STZ-induced diabetic rats fed HFD. Based on these findings, we suggested that NPWE could be considered for the prevention and/or treatment of blood glucose and a potential use as a dietary supplement.

  2. Antidiabetic Effect of Fresh Nopal (Opuntia ficus-indica in Low-Dose Streptozotocin-Induced Diabetic Rats Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Seung Hwan Hwang

    2017-01-01

    Full Text Available The objective of the present study was to evaluate α-glucosidase inhibitory and antidiabetic effects of Nopal water extract (NPWE and Nopal dry power (NADP in low-dose streptozotocin- (STZ- induced diabetic rats fed a high-fat diet (HFD. The type 2 diabetic rat model was induced by HFD and low-dose STZ. The rats were divided into four groups as follows: (1 nondiabetic rats fed a regular diet (RD-Control; (2 low-dose STZ-induced diabetic rats fed HFD (HF-STZ-Control; (3 low-dose STZ-induced diabetic rats fed HFD and supplemented with NPWE (100 mg/kg body weight, HF-STZ-NPWE; and (4 low-dose STZ-induced diabetic rats fed HFD and supplemented with comparison medication (rosiglitazone, 10 mg/kg, body weight, HF-STZ-Rosiglitazone. In results, NPWE and NADP had IC50 values of 67.33 and 86.68 μg/mL, both of which exhibit inhibitory activities but lower than that of acarbose (38.05 μg/mL while NPWE group significantly decreased blood glucose levels compared to control and NPDP group on glucose tolerance in the high-fat diet fed rats model (P<0.05. Also, the blood glucose levels of HR-STZ-NPWE group were significantly lower (P<0.05 than HR-STZ-Control group on low-dose STZ-induced diabetic rats fed HFD. Based on these findings, we suggested that NPWE could be considered for the prevention and/or treatment of blood glucose and a potential use as a dietary supplement.

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

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    Malone Michael A

    2006-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  5. Impact of the controlled release of a connexin 43 peptide on corneal wound closure in an STZ model of type I diabetes.

    Directory of Open Access Journals (Sweden)

    Keith Moore

    Full Text Available The alpha-carboxy terminus 1 (αCT1 peptide is a synthetically produced mimetic modified from the DDLEI C-terminus sequence of connexin 43 (Cx43. Previous research using various wound healing models have found promising therapeutic effects when applying the drug, resulting in increased wound healing rates and reduced scarring. Previous data suggested a rapid metabolism rate in vitro, creating an interest in long term release. Using a streptozotocin (STZ type I diabetic rat model with a surgically induced corneal injury, we delivered αCT1 both directly, in a pluronic gel solution, and in a sustained system, using polymeric alginate-poly-l-ornithine (A-PLO microcapsules (MC. Fluorescent staining of wound area over a 5 day period indicated a significant increase in wound closure rates for both αCT1 and αCT1 MC treated groups, withαCT1 MC groups showing the most rapid wound closure overall. Analysis of inflammatory reaction to the treatment groups indicated significantly lower levels of both Interferon Inducible T-Cell Alpha Chemoattractant (ITAC and Tumor Necrosis Factor Alpha (TNFα markers using confocal quantification and ELISA assays. Additional analysis examining genes selected from the EMT pathway using RT-PCR and Western blotting suggested αCT1 modification of Transforming Growth Factor Beta 2 (TGFβ2, Keratin 8 (Krt8, Estrogen Receptor 1 (Esr1, and Glucose Transporter 4 (Glut4 over a 14 day period. Combined, this data indicated a possible suppression of the inflammatory response by αCT1, leading to increased wound healing rates.

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

    Science.gov (United States)

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

    2006-10-01

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

  7. In vivo evidences of Curcuma longa on oxidative stress in STZ ...

    African Journals Online (AJOL)

    ... mildly with a significance of: (p<0.05) in comparison to control group and with the diabetic group being critically lower than those in control group. This suggested that Curcuma longa may be promising in enhancing sperm health parameters. Keywords: Turmeric, oxidative stress, semen, STZ-induced diabetes, antioxidant ...

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

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    Daye Cheng

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

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    Mohammad Ashafaq

    2014-01-01

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

  11. 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...... before and after insulin therapy in HF/HS-STZ rats. HbA1c%, TGs, cholesterol, high-density lipoprotein and adiponectin were analyzed by conventional methods adapted for rats. RESULTS: Insulin therapy lowered HbA1c (P

  12. Protective Action of Carica papaya on β-Cells in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Miranda-Osorio, Pedro H; Castell-Rodríguez, Andrés E; Vargas-Mancilla, Juan; Tovilla-Zárate, Carlos A; Ble-Castillo, Jorge L; Aguilar-Domínguez, Dora E; Juárez-Rojop, Isela E; Díaz-Zagoya, Juan C

    2016-04-27

    The aim of the present study was to investigate the effect of C. papaya L. leaf extract (CPLE) on pancreatic islets in streptozotocin (STZ)-induced diabetic rats, as well as on cultured normal pancreatic cells with STZ in the medium. CPLE (3-125 mg/Kg) was administered orally for 20 days, while a group of diabetic rats received 5 IU/Kg/day of insulin. At the end of the treatment the rats were sacrificed. Blood was obtained to assess glucose and insulin levels. The pancreas was dissected to evaluate β cells by immunohistochemistry. In addition, normal pancreatic cells were cultured in a medium that included CPLE (3-12 mg). One half of the cultured cells received simultaneously CPLE and STZ (6 mg), while the other half received CPLE and five days later the STZ. After three days of incubation, insulin was assayed in the incubation medium. The CPLE administered to diabetic rats improved the fasting glycemia and preserved the number and structure of pancreatic islets. However, when CPLE was added to pancreatic cells in culture along with STZ, the insulin concentration was higher in comparison with the cells that only received STZ. In conclusion, the CPLE preserves the integrity of pancreatic islets, improves the basal insulin secretion and protects cultured cells from the adverse effects of STZ.

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

    Science.gov (United States)

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

    2016-05-01

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

  14. 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.

  15. 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...

  16. Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Montilla, Pedro; Barcos, Montserrat; Munoz, Maria C; Bujalance, Inmaculada; Munoz-Castaneda, Juan R; Tunez, Isaac

    2005-09-30

    We have studied the effects of red wine on brain oxidative stress and nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats with a single intraperitonally injection of STZ (50 mg/kg). Two weeks before and four weeks after injection, red wine was given orally in both normal and diabetic rats. Blood samples were taken from the neck vascular trunk in order to determine the glucose, triglycerides, total cholesterol, HDL-cholesterol (HDL-c), atherogenic index (AI), total protein, blood urea nitrogen (BUN), creatinine, insulin, lipid peroxidation products, reduced glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. As well, we estimated the lipid peroxidtion, GSH and SOD, GSH-Px and catalase activities in brain and renal homogenates, and the excretion of albumin, proteins and glucose in urine over 24 h period. The administration of STZ caused significant increases in levels of glycosuria, proteinuria, albuminuria, glycemia, total cholesterol and AI, as well as in lipid peroxidation products in the brain, plasma and kidney, whereas it decreased the GSH content and SOD, GSH-Px and catalase activities. Treatment with red wine significantly prevented the changes induced by STZ. These data suggested that red wine has a protective effect against brain oxidative stress, diabetic nephropathy and diabetes induced by STZ, as well as it protects against hypercholesterolemia and atherogenic risk.

  17. Food deprivation depletes gastric mucus glycoprotein in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Igarashi, S; Kume, E; Narita, H; Kinoshita, M

    2000-09-01

    Fasting causes gastric mucosal damage in streptozotocin (STZ)-induced diabetic rats, but its pathogenic mechanism remains to be elucidated. The aim of the present study was to investigate the alteration of gastric mucosal mucin, one of the gastric defensive factors against the development of such damage. Diabetes was induced in rats by intravenous injection of STZ (65 mg/kg). The experiments were performed using 4-week STZ-diabetic rats with blood glucose levels above 350 mg/dl. The amount of gastric mucus glycoprotein was determined by gel filtration, and the distribution of neutral and acidic mucins in the stomach epithelium was examined by histochemical analysis. In normal rats, 24-h fasting neither affected the gastric mucin content nor caused any macroscopic gastric mucosal injury. In contrast, starvation significantly reduced the amount of total gastric mucus glycoprotein prior to the formation of mucosal lesions in the STZ-diabetic rats. Nine hours after food deprivation, the gastric damage developed in about 70% of the diabetic rats, the amount of mucus glycoprotein markedly decreased, and both the neutral and acidic mucins diminished in the epithelium. Taken together, in STZ-diabetic rats, fasting by itself depletes gastric mucus glycoprotein, and this depletion may be involved in the pathogenic mechanism of the formation of gastric mucosal lesions.

  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

    Directory of Open Access Journals (Sweden)

    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. Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

    OpenAIRE

    Jin, Hai-Rong; Kim, Woo Jean; Song, Jae Sook; Piao, Shuguang; Choi, Min Ji; Tumurbaatar, Munkhbayar; Shin, Sun Hwa; Yin, Guo Nan; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu

    2011-01-01

    OBJECTIVE Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals. RESEARCH DESIGN AND METHODS Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-...

  1. Ghrelin and insulin gene expression changes in streptozotocin-induced diabetic rats after rosiglitazone pretreatment

    Directory of Open Access Journals (Sweden)

    S Yildirim

    2009-06-01

    Full Text Available The aim of the study was to evaluate the effect of rosiglitazone treatment on islet ghrelin and insulin gene expressions in streptozotocin (STZ-induced diabetic rats. Animals were divided into four groups. 1. Intact controls. 2. Rosiglitazonetreated controls. 3. STZ-induced diabetes. 4. Rosiglitazonetreated diabetes. Rosiglitazone was given for 7 days at a dose of 20 mg/kg body weight. Ghrelin and insulin gene expressions were investigated by immunohistochemistry and in situ hybridization. There was no statistically significant difference in body weight between STZ-induced diabetic rats and rosiglitazone-treated diabetic rats during the experimental period. Furthermore, there were no significant differences in blood glucose levels and insulin immunoreactive cell numbers between STZ-induced diabetic rats and rosiglitazone- treated diabetic rats. There was a tendency towards a reduction of ghrelin gene expression in diabetic animals compared with intact controls. We found, in addition, that ghrelin immunoreactive and ghrelin mRNA expressing cells were frequent in the epithelial lining of the ducts suggesting ductal epithelium might be the source of the regenerating islet ghrelin cells, as is known for other islet cells. The results show that short-term rosiglitazone pretreatment had no significant effect on ghrelin and insulin gene expressions.

  2. 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.

  3. Effect Of Keren Fruit Extract (Muntingia calabura On Blood Glucose Levels Of Rats (Rattus novergicus Which Induced By Streptozotocin (STZ

    Directory of Open Access Journals (Sweden)

    Vembriarto Jati Pramono

    2015-06-01

    control, group II (positive control, group III, IV, and V were given kersen fruit extract 100 mg/kg BW, 200 mg/kg BW, and 400 mg/kg BW respectively. Rats of groups I-V were induced with streptozotocin (STZ. Blood sugar values were analyzed using Analysis of Variance Repeated method (Repated ANOVA. The results showed blood glucose levels before treatment, week-0, and week-2 in the group I (133 mg/dL, 164 mg/dL, 105 mg/dL, group II (136 mg/dL, 362 mg/dL, 431 mg/dL, group III (133 mg/dL, 513 mg/dL, 109 mg/dL, group IV (100 mg/dL, 376 mg/dL, 153 mg/dL, and group V (83 mg/dL, 225 mg/dL, 169 mg/dL. Respectively based on statistical analysis showed a significant decreasies of blood sugar levels of the group III so that kersen extract with the dose of 100 mg / kg has the potential to antidiabetic.

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

    Science.gov (United States)

    Ravi, Kasiappan; Rajasekaran, Subbaih; Subramanian, Sorimuthu

    2005-09-01

    Abnormalities in lipid profile are one of the most common complications in diabetes mellitus, which is found in about 40% of diabetics. In the present study, anti-hyperlipidemic efficacy of Eugenia jambolana seed kernel (EJs-kernel) was evaluated in streptozotocin (STZ)-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide. The effect of oral administration of ethanolic extract of EJs-kernel (100 mg/kg body weight) was examined on the levels of cholesterol, phospholipids, triglycerides and free fatty acids in the plasma, liver and kidney tissues of STZ (55 mg/kg body weight)-induced diabetic rats. The plasma lipoproteins and tissues fatty acid composition were also monitored. STZ-induced diabetic rats, showed significant increase in the levels of cholesterol, phospholipids, triglycerides and free fatty acids which were considerably restored to near normal in EJs-kernel or glibenclamide treated animals. The plasma lipoproteins (HDL, LDL, VLDL-cholesterol) and fatty acid composition were altered in STZ-induced diabetic rats and these levels were also reverted back to near normalcy by EJs-kernel or glibenclamide treatment. It may be concluded that, EJs-kernel possesses hypolipidemic effect, which may be due to the presence of flavonoids, saponins, glycosides and triterpenoids in the extract. The hypolipidemic effect mediated by EJs-kernel may also be anticipated to have biological significance and provide a scientific rationale for the use of EJs-kernel as an anti-diabetic plant.

  5. Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Rodrigo Mello Gomes

    2017-06-01

    Full Text Available Background/Aims: Trichilia catigua A. Juss., known as “catuaba” in Brazil, has been popularly used as a tonic for fatigue, impotence and memory deficits. Previously, our group demonstrated that the ethyl-acetate fraction (EAF of T. catigua has antioxidant and anti-inflammatory effects. The present study evaluated the anti-diabetic activity of EAF in type 1 diabetic rats. Methods: Male Wistar rats were divided into four groups (N: non-diabetic group, D: type 1 diabetic group, NC: non-diabetic + EAF group and DC: type 1 diabetic + EAF group. The latter two groups were treated with 200 mg/kg EAF. Type 1 diabetes was induced by intravenous streptozotocin (STZ injection (35 mg/kg. Starting two days after STZ injection, EAF was administered daily by gavage for 8 weeks. Results: EAF attenuated body mass loss and reduced food and water intake. EAF improved hyperglycaemia and other biochemical parameters, such as alkaline phosphatase (ALP, alanine aminotransferase (ALT and aspartate aminotransferase (AST. Furthermore, the number of pancreatic β-cells and the size of the islets had increased by β-cell proliferation in the DC group. EAF promoted reduction in kidney tissue damage in STZ-induced diabetic rats by reduction of renal fibrosis. Conclusion: The present study showed that EAF improves glucose homeostasis and endocrine pancreas morphology and inhibits the development of diabetic nephropathy in STZ-induced diabetic rats.

  6. Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats.

    Science.gov (United States)

    Gomes, Rodrigo Mello; de Paulo, Luis Fernando; Bonato Panizzon, Cynthia Priscilla do Nascimento; Neves, Camila Quaglio; Cordeiro, Bruna Colombo; Zanoni, Jacqueline Nelisis; Francisco, Flávio Andrade; Piovan, Silvano; de Freitas Mathias, Paulo Cezar; Longhini, Renata; de Mello, João Carlos Palazzo; de Oliveira, Júlio Cezar; Pedrino, Gustavo Rodrigues; da Silva Reis, Angela Adamski; Cecchini, Alessandra Lourenço; Marçal Natali, Maria Raquel

    2017-01-01

    Trichilia catigua A. Juss., known as "catuaba" in Brazil, has been popularly used as a tonic for fatigue, impotence and memory deficits. Previously, our group demonstrated that the ethyl-acetate fraction (EAF) of T. catigua has antioxidant and anti-inflammatory effects. The present study evaluated the anti-diabetic activity of EAF in type 1 diabetic rats. Male Wistar rats were divided into four groups (N: non-diabetic group, D: type 1 diabetic group, NC: non-diabetic + EAF group and DC: type 1 diabetic + EAF group). The latter two groups were treated with 200 mg/kg EAF. Type 1 diabetes was induced by intravenous streptozotocin (STZ) injection (35 mg/kg). Starting two days after STZ injection, EAF was administered daily by gavage for 8 weeks. EAF attenuated body mass loss and reduced food and water intake. EAF improved hyperglycaemia and other biochemical parameters, such as alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, the number of pancreatic β-cells and the size of the islets had increased by β-cell proliferation in the DC group. EAF promoted reduction in kidney tissue damage in STZ-induced diabetic rats by reduction of renal fibrosis. The present study showed that EAF improves glucose homeostasis and endocrine pancreas morphology and inhibits the development of diabetic nephropathy in STZ-induced diabetic rats. © 2017 The Author(s). Published by S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2011-01-01

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

  8. Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Alvarado-Vásquez, Noé; Lascurain, Ricardo; Cerón, Eduarda; Vanda, Beatriz; Carvajal-Sandoval, Guillermo; Tapia, Aurora; Guevara, Jorge; Montaño, Luis Felipe; Zenteno, Edgar

    2006-06-13

    Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (Pdiabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (Pcorporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.

  9. Administration of Zinc plus Cyclo-(His-Pro) Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes.

    Science.gov (United States)

    Choi, Bo Young; Kim, In Yeol; Kim, Jin Hee; Lee, Bo Eun; Lee, Song Hee; Kho, A Ra; Sohn, Min; Suh, Sang Won

    2017-01-01

    The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro) (ZC) on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ)-induced diabetes. ZC (27 mg/kg) was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase) or 45 (late phase) days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs) and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes.

  10. Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropathy.

    Science.gov (United States)

    Nørgaard, Sisse A; Sand, Fredrik W; Sørensen, Dorte B; Abelson, Klas Sp; Søndergaard, Henrik

    2018-01-01

    The streptozotocin (STZ)-induced diabetic mouse is a widely used model of diabetes and diabetic nephropathy (DN). However, it is a well-known issue that this model is challenged by high weight loss, which despite supportive measures often results in high euthanization rates. To overcome these issues, we hypothesized that supplementing STZ-induced diabetic mice with water-softened chow in addition to normal chow would reduce weight loss, lower the need for supportive treatment, and reduce the number of mice reaching the humane endpoint of 20% weight loss. In a 15 week STZ-induced DN study we demonstrated that diabetic male mice receiving softened chow had reduced acute weight loss following STZ treatment ( p = 0.045) and additionally fewer mice were euthanized due to weight loss. By supplementing the diabetic mice with softened chow, no mice reached 20% weight loss whereas 37.5% of the mice without this supplement reached this humane endpoint ( p = 0.0027). Excretion of corticosterone metabolites in faeces was reduced in diabetic mice on softened chow ( p = 0.0007), suggesting lower levels of general stress. Finally, it was demonstrated that the water-softened chow supplement did not significantly affect the induction of key disease parameters, i.e. %HbA1C and albuminuria nor result in abnormal teeth wear. In conclusion, supplementation of softened food is refining the STZ-induced diabetic mouse model significantly by reducing stress, weight loss and the number of animals sacrificed due to humane endpoints, while maintaining the key phenotypes of diabetes and nephropathy.

  11. Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats.

    Science.gov (United States)

    Reno, Candace M; Tanoli, Tariq; Bree, Adam; Daphna-Iken, Dorit; Cui, Chen; Maloney, Susan E; Wozniak, David F; Fisher, Simon J

    2013-06-15

    Brain damage due to severe hypoglycemia occurs in insulin-treated people with diabetes. This study tests the hypothesis that chronic insulin therapy that normalizes elevated blood glucose in diabetic rats would be neuroprotective against brain damage induced by an acute episode of severe hypoglycemia. Male Sprague-Dawley rats were split into three groups: 1) control, non-diabetic; 2) STZ-diabetic; and 3) insulin-treated STZ-diabetic. After 3 wk of chronic treatment, unrestrained awake rats underwent acute hyperinsulinemic severe hypoglycemic (10-15 mg/dl) clamps for 1 h. Rats were subsequently analyzed for brain damage and cognitive function. Severe hypoglycemia induced 15-fold more neuronal damage in STZ-diabetic rats compared with nondiabetic rats. Chronic insulin treatment of diabetic rats, which nearly normalized glucose levels, markedly reduced neuronal damage induced by severe hypoglycemia. Fortunately, no cognitive defects associated with the hypoglycemia-induced brain damage were observed in any group. In conclusion, antecedent blood glucose control represents a major modifiable therapeutic intervention that can afford diabetic subjects neuroprotection against severe hypoglycemia-induced brain damage.

  12. Diabetes Impairs Wnt3 Protein-induced Neurogenesis in Olfactory Bulbs via Glutamate Transporter 1 Inhibition.

    Science.gov (United States)

    Wakabayashi, Tamami; Hidaka, Ryo; Fujimaki, Shin; Asashima, Makoto; Kuwabara, Tomoko

    2016-07-15

    Diabetes is associated with impaired cognitive function. Streptozotocin (STZ)-induced diabetic rats exhibit a loss of neurogenesis and deficits in behavioral tasks involving spatial learning and memory; thus, impaired adult hippocampal neurogenesis may contribute to diabetes-associated cognitive deficits. Recent studies have demonstrated that adult neurogenesis generally occurs in the dentate gyrus of the hippocampus, the subventricular zone, and the olfactory bulbs (OB) and is defective in patients with diabetes. We hypothesized that OB neurogenesis and associated behaviors would be affected in diabetes. In this study, we show that inhibition of Wnt3-induced neurogenesis in the OB causes several behavioral deficits in STZ-induced diabetic rats, including impaired odor discrimination, cognitive dysfunction, and increased anxiety. Notably, the sodium- and chloride-dependent GABA transporters and excitatory amino acid transporters that localize to GABAergic and glutamatergic terminals decreased in the OB of diabetic rats. Moreover, GAT1 inhibitor administration also hindered Wnt3-induced neurogenesis in vitro Collectively, these data suggest that STZ-induced diabetes adversely affects OB neurogenesis via GABA and glutamate transporter systems, leading to functional impairments in olfactory performance. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. The protective effect of dietary flavonoid fraction from Acanthophora spicifera on streptozotocin induced oxidative stress in diabetic rats

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    Lavakumar Vuppalapati

    2016-06-01

    Full Text Available The present investigation was considered in arraying of antidiabetic and antioxidant activity from dietary flavonoid loaded fraction of Acanthophora spicifera (A. spicifera, Family: Rhodomelaceae on streptozotocin (STZ induced oxidative stress rats. The testings were acted upon male rats, which were alienated into five groups: control group, diabetic group (single dose of 65 mg/kg, streptozotocin (STZ i.p., diabetic with insulin (6 IU, and diabetic with flavonoid rich fraction groups (FRF at 50 and 100 mg/kg body weight, given orally for 21 days. The blood glucose level was determined at different week intermissions. The antioxidant consequences of FRF on STZ-induced diabetic rats were determined by the estimations of the oxidative stress marker like malonyldialdehyde and antioxidant enzymes such as superoxide dismutase, catalase and glutathione in tissue homogenates of heart, liver and kidney. FRF treatment of diabetic rats significantly (P < 0.05 diminishes the blood glucose altitudes to normal in contrast with diabetic rats. However, FRF administration, significantly decreased the malonyldialdehyde (MDA and increased the activities of superoxide dismutase (SOD, catalase (CAT and glutathione levels (GSH in diabetic rats. The outcome designates that FRF fraction from red algae A. spicifera was potent anti diabetic and antioxidant asset against STZ induced diabetes and oxidative tissue breakups.

  14. Effects of Caffeine and Lycopene in Experimentally Induced Diabetes Mellitus.

    Science.gov (United States)

    Ozmen, Ozlem; Topsakal, Senay; Haligur, Mehmet; Aydogan, Ahmet; Dincoglu, Dilnur

    2016-04-01

    Diabetes mellitus (DM) is a global epidemic with increasing prevalence. The disease is chronic in nature, and patients must use antidiabetic drugs or insulin during their lifespan. Because of the difficulty of using injectable insulin preparations, patients and practitioners prefer to use oral antidiabetic drugs for prophylaxis and treatment. There are, however, numerous adverse effects of antidiabetic drugs and rapidly increasing attention is being paid to new nutraceutical drugs with fewer adverse effects. The purpose of this study was to evaluate the effects of caffeine and lycopene on streptozotocin (STZ)-induced DM in rats. Caffeine and lycopene were administered to the study groups by oral gavages for 1 month whereafter experimental diabetes was induced in 90 rats in 6 groups. There were no pathological effects of lycopene and caffeine on the pancreas. Marked vacuolization and degeneration were observed in STZ-treated groups. Caffeine and lycopene decreased the pathological findings and lowered the blood and urine glucose levels in the rats with STZ-induced DM, whereas these compounds increased serum insulin levels. This study showed that caffeine and lycopene provided protective effects against experimentally induced DM. The protective effects of lycopene were observed to be much greater than those of caffeine.

  15. Bacterial Flora Changes in Conjunctiva of Rats with Streptozotocin-Induced Type I Diabetes.

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    Chao Yang

    Full Text Available The microbiota of both humans and animals plays an important role in their health and the development of disease. Therefore, the bacterial flora of the conjunctiva may also be associated with some diseases. However, there are no reports on the alteration of bacterial flora in conjunctiva of diabetic rats in the literature. Therefore, we investigated the changes in bacterial flora in bulbar conjunctiva of rats with streptozotocin (STZ-induced type I diabetes.A high dose of STZ (60 mg/kg, i.p. was injected into Sprague-Dawley (SD rats to induce type I diabetes mellitus (T1DM. The diabetic rats were raised in the animal laboratory and at 8 months post-injection of STZ swab samples were taken from the bulbar conjunctiva for cultivation of aerobic bacteria. The bacterial isolates were identified by Gram staining and biochemical features. The identified bacteria from both diabetic and healthy rats were then compared.The diabetic and healthy rats had different bacterial flora present in their bulbar conjunctiva. In total, 10 and 8 bacterial species were found in the STZ and control groups, respectively, with only three species (Enterococcus faecium, Enterococcus gallinarum and Escherichia coli shared between the two groups. Gram-positive bacteria were common in both groups and the most abundant was Enterococcus faecium. However, after the development of T1DM, the bacterial flora in the rat bulbar conjunctiva changed considerably, with a reduced complexity evident.STZ-induced diabetes caused alterations of bacterial flora in the bulbar conjunctiva in rats, with some bacterial species disappearing and others emerging. Our results indicate that the conjunctival bacterial flora in diabetic humans should be surveyed for potential diagnostic markers or countermeasures to prevent eye infections in T1DM patients.

  16. Urtica dioica leaves modulates muscarinic cholinergic system in the hippocampus of streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Patel, Sita Sharan; Parashar, Arun; Udayabanu, Malairaman

    2015-06-01

    Diabetes mellitus is a chronic metabolic disorder and has been associated with cognitive dysfunction. In our earlier study, chronic Urtica dioica (UD) treatment significantly ameliorated diabetes induced associative and spatial memory deficit in mice. The present study was designed to explore the effect of UD leaves extract on muscarinic cholinergic system, which has long been known to be involved in cognition. Streptozotocin (STZ) (50 mg/kg, i.p., consecutively for 5 days) was used to induce diabetes followed by treatment with UD extract (50 mg/kg, oral) or rosiglitazone (5 mg/kg, oral) for 8 weeks. STZ-induced diabetic mice showed significant reduction in hippocampal muscarinic acetylcholine receptor-1 and choline acetyltransferase expressions. Chronic diabetes significantly up-regulated the protein expression of acetylcholinesterase associated with oxidative stress in hippocampus. Besides, STZ-induced diabetic mice showed hypolocomotion with up-regulation of muscarinic acetylcholine receptor-4 expression in striatum. Chronic UD treatment significantly attenuated the cholinergic dysfunction and oxidative stress in the hippocampus of diabetic mice. UD had no effect on locomotor activity and muscarinic acetylcholine receptor-4 expression in striatum. In conclusion, UD leaves extract has potential to reverse diabetes mediated alteration in muscarinic cholinergic system in hippocampus and thereby improve memory functions.

  17. Influence of the low thyroid state in diabetes mellitus on cardiac function and inotropic responsiveness to alpha 1-adrenoceptor stimulation: comparison with the role of hypothyroidism alone

    NARCIS (Netherlands)

    Beenen, O. H.; Pfaffendorf, M.; van Zwieten, P. A.

    1996-01-01

    The hypothyroid state accompanying diabetes mellitus has been suggested to be partly responsible for the diabetes-induced metabolic, hemodynamic, and pharmacological cardiovascular changes. We assessed the effectivity of streptozotocin (STZ) to induce diabetes mellitus and a hypothyroid state.

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

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    Jing Wang

    2014-05-01

    Full Text Available Diabetic nephropathy (DN has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS in streptozotocin (STZ-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the β2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications.

  19. 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.

  20. [Differentially expressed genes in diabetes-induced embryopathy].

    Science.gov (United States)

    Ma, Xiang-Dong; Ma, Xing; Wu, Xiao-Ming; Chen, Bi-Liang; Wang, De-Tang

    2009-03-01

    To determine molecular mechanism in hyperglycemia induced congenital neural tube defects, yolk sac cells were harvested at gestational day 12 from streptozotocin (STZ) -induced diabetic rats with congenital neural tube defects in offspring, STZ-induced diabetic rats without neural tube defects and normal control group. We analyzed gene expression profiles in yolk sac cells using a DNA microarray technique. Changes in apoptotic and MAP Kinase signaling pathways were detected by Western blotting analyses. Comparison of genes in yolk sac cells with a total of 1 200 genes in the control cells, 79 genes differently expressed between the two groups were detected. Forty-two of them were up-regulated and 37 were down-regulated. There was strong characteristic apoptotic DNA ladder in yolk sac cells in embryopathic offspring from experimentally-induced diabetic rats. The activity of ERK1/2 was dramatically decreased and the activity of JNK1/2 was significantly increased. Differentially expressed genes, MAP Kinase, and apoptotic signal pathways play very important roles in hyperglycemia induced neural tube defects. We hope that these could provide useful hallmark to rapid identification of early diabetic embryopathy.

  1. Candesartan restores pressure-induced vasodilation and prevents skin pressure ulcer formation in diabetic mice.

    Science.gov (United States)

    Danigo, Aurore; Nasser, Mohamad; Bessaguet, Flavien; Javellaud, James; Oudart, Nicole; Achard, Jean-Michel; Demiot, Claire

    2015-02-18

    Angiotensin II type 1 receptor (AT1R) blockers have beneficial effects on neurovascular complications in diabetes and in organ's protection against ischemic episodes. The present study examines whether the AT1R blocker candesartan (1) has a beneficial effect on diabetes-induced alteration of pressure-induced vasodilation (PIV, a cutaneous physiological neurovascular mechanism which could delay the occurrence of tissue ischemia), and (2) could be protective against skin pressure ulcer formation. Male Swiss mice aged 5-6 weeks were randomly assigned to four experimental groups. In two groups, diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 200 mg.kg(-1)). After 6 weeks, control and STZ mice received either no treatment or candesartan (1 mg/kg-daily in drinking water) during 2 weeks. At the end of treatment (8 weeks of diabetes duration), C-fiber mediated nociception threshold, endothelium-dependent vasodilation and PIV were assessed. Pressure ulcers (PUs) were then induced by pinching the dorsal skin between two magnetic plates for three hours. Skin ulcer area development was assessed during three days, and histological examination of the depth of the skin lesion was performed at day three. After 8 weeks of diabetes, the skin neurovascular functions (C-fiber nociception, endothelium-dependent vasodilation and PIV) were markedly altered in STZ-treated mice, but were fully restored by treatment with candesartan. Whereas in diabetes mice exposure of the skin to pressure induced wide and deep necrotic lesions, treatment with candersartan restored their ability to resist to pressure-induced ulceration as efficiently as the control mice. Candesartan decreases the vulnerability to pressure-induced ulceration and restores skin neurovascular functions in mice with STZ-induced established diabetes.

  2. Protective effects of methanolic extract of Juglans regia L. leaf on streptozotocin-induced diabetic peripheral neuropathy in rats.

    Science.gov (United States)

    Nasiry, Davood; Khalatbary, Ali Reza; Ahmadvand, Hassan; Talebpour Amiri, Fereshteh; Akbari, Esmaeil

    2017-10-02

    Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against

  3. Effect of Resveratrol on Leptin and Sirtuin 2 Expression in the Kidneys in Streptozotocin-induced Diabetic Rats.

    Science.gov (United States)

    Yaylali, Ashi; Ergin, Kemal; Ceçen, Serpil

    2015-08-01

    To investigate the effect of resveratrol (RSV) on the histopathology and leptin and sirtuin 2 expression levels of the kidneys in streptozotocin (STZ)-induced diabetic rats. The study was carried out with 33 young, healthy, female Wistar Albino rats. STZ was given (50 mg/kg, intraperitoneal, single dose) to the rats to induce and constitute a diabetes model. After 1 month of STZ, resveratrol (10 mg/kg) was given for 15 days. Then the kidneys were evaluated histopathologically and the leptin and sirtuin 2 expressions were analyzed immunohistochemically. High glucose and fewer weight levels were seen in the STZ-induced diabetes mellitus group. The glucose levels in the RSV-administered diabetic group showed a tendency to decrease but not significantly. Decreased signs of histopathologic kidney damage was seen in the RSV-administered diabetic group, and an increased expression of leptin was seen in the diabetic kidney tissues. There were no significant differences of sirtuin 2 expression levels among the groups. It was observed that resveratrol caused changes in the diabetic kidney histology and leptin expression level. Resveratrol may be effective, with its antioxidant and antidiabetic effects, in the prevention of kidney damage caused by long-term hyperglycemia.

  4. The histopathological and morphometric investigation of the effects of systemically administered boric acid on alveolar bone loss in ligature-induced periodontitis in diabetic rats.

    Science.gov (United States)

    Balci Yuce, Hatice; Toker, Hulya; Goze, Fahrettin

    2014-11-01

    The purpose of this study was to evaluate the effects of systemically administered boric acid on alveolar bone loss, histopathological changes and oxidant/antioxidant status in ligature-induced periodontitis in diabetic rats. Forty-four Wistar rats were divided into six experimental groups: (1) non-ligated (NL, n = 6) group, (2) ligature only (LO, n = 6) group, (3) Streptozotocin only (STZ, n = 8) group, (4) STZ and ligature (STZ+LO, n = 8) group, (5) STZ, ligature and systemic administration of 15 mg/kg/day boric acid for 15 days (BA15, n = 8) group and (6) STZ, ligature and systemic administration of 30 mg/kg/day boric acid for 15 days (BA30, n = 8) group. Diabetes mellitus was induced by 60 mg/kg streptozotocin. Silk ligatures were placed at the gingival margin of lower first molars of the mandibular quadrant. The study duration was 15 days after diabetes induction and the animals were sacrificed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were histopathologically examined. Serum total antioxidant status (TAS), total oxidant status (TOS), calcium (Ca) and magnesium (Mg) levels and oxidative stress index (OSI) were evaluated. Primary outcome was alveolar bone loss. Seconder outcome (osteoblast number) was also measured. At the end of 15 days, the alveolar bone loss was significantly higher in the STZ+LO group compared to the other groups (p boric acid and STZ+LO 30 mg/kg boric acid groups (p > 0.05). Systemically administered boric acid significantly decreased alveolar bone loss compared to the STZ+LO group (p 0.05). The OSI values of the BA30 group were significantly lower than the STZ+LO group (p 0.05). Within the limits of this study, it can be suggested that BA, when administered systemically, may reduce alveolar bone loss in the diabetic rat model.

  5. Minocycline Attenuates Kidney Injury in a Rat Model of Streptozotocin-Induced Diabetic Nephropathy.

    Science.gov (United States)

    Yuan, Hongping; Zhang, Xiaoxuan; Zheng, Wei; Zhou, Hui; Zhang, Bo-Yin; Zhao, Dongxu

    2016-01-01

    The effects of minocycline on the development of diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats were evaluated in this study. The diabetes rats with DN were induced by STZ (55 mg/kg) injection. The experiment included 5 groups 1) normal, 2) normal plus minocycline for 16 weeks, 3) DN plus vehicle, 4) DN plus minocycline 16 weeks and 5) DN plus minocycline for 8 weeks. The pathological changes were analyzed by hematoxylin and eosin (H&E) staining and the apoptotic cells were stained by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The mRNA expression of caspase-3, Bax and Bcl-2 in the kidney tissues was detected by quantitative RT-PCR. The biochemical parameters of blood and urine were determined by biochemical analyzer. Treatment with minocycline reduced the urine volume, 24-h urine protein, serum creatinine (Scr), blood urea nitrogen (BUN) but not blood alanine aminotransferase (ALT) in the DN rats. Furthermore, treatment with minocycline improved the pathological score of STZ-injured kidney and reduced the numbers of apoptotic cells in the kidney of DN rats. Moreover, minocycline mitigated the expression of caspase-3 and Bax mRNA, but increased Bcl-2 expression in the kidney of DN rats. These data indicated that minocycline improved the STZ-induced kidney damages, at least partially by protection form long-term hyperglycemia-induced kidney cell apoptosis.

  6. A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment

    Science.gov (United States)

    Ackart, David F.; Richardson, Michael A.; DiLisio, James E.; Pulford, Bruce; Basaraba, Randall J.

    2017-01-01

    ABSTRACT Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species. PMID:28093504

  7. A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment.

    Science.gov (United States)

    Podell, Brendan K; Ackart, David F; Richardson, Michael A; DiLisio, James E; Pulford, Bruce; Basaraba, Randall J

    2017-02-01

    Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species. © 2017. Published by

  8. Curcumin ameliorates macrophage infiltration by inhibiting NF-κB activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Suzuki Kenji

    2011-06-01

    Full Text Available Abstract Background Chronic inflammation plays an important role in the progression of diabetic nephropathy (DN and that the infiltration of macrophages in glomerulus has been implicated in the development of glomerular injury. We hypothesized that the plant polyphenolic compound curcumin, which is known to exert potent anti-inflammatory effect, would ameliorate macrophage infiltration in streptozotocin (STZ-induced diabetic rats. Methods Diabetes was induced with STZ (55 mg/kg by intraperitoneal injection in rats. Three weeks after STZ injection, rats were divided into three groups, namely, control, diabetic, and diabetic treated with curcumin at 100 mg/kg/day, p.o., for 8 weeks. The rats were sacrificed 11 weeks after induction of diabetes. The excised kidney was used to assess macrophage infiltration and expression of various inflammatory markers. Results At 11 weeks after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, blood urea nitrogen and proteinuria, along with marked reduction in the body weight. All of these abnormalities were significantly reversed by curcumin. Hyperglycemia induced the degradation of IκBα and NF-κB activation and as a result increased infiltration of macrophages (52% as well as increased proinflammatory cytokines: TNF-α and IL-1β. Curcumin treatment significantly reduced macrophage infiltration in the kidneys of diabetic rats, suppressed the expression of above proinflammatory cytokines and degradation of IκBα. In addition, curcumin treatment also markedly decreased ICAM-1, MCP-1 and TGF-β1 protein expression. Moreover, at nuclear level curcumin inhibited the NF-κB activity. Conclusion Our results suggested that curcumin treatment protect against the development of DN in rats by reducing macrophage infiltration through the inhibition of NF-κB activation in STZ-induced diabetic rats.

  9. Bioflavonoids Effects of Ginger on Glomerular Podocyte Apoptosis in Streptozotocin-Induced Diabetic Rat

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    Hajhosieni Laleh

    2014-04-01

    Full Text Available Objective: Ginger is a strong antioxidant and long-term treatment of streptozotocin (STZ-diabetic animals, and it has been shown to reduce oxidative stress. Prevalence oxidative stress among urban life and changes in antioxidant capacity are considered asplay an important role in the pathogenesis of chronic diabetes mellitus. Materials and Methods: Wistar male rat (n = 40 were divided into three groups, control group (n = 10 and Ginger Quercetin group that received 100 mg/kg (gavage, (n = 10, and diabetic group, which received 55 mg/kg intra peritoneal (IP STZ (n = 20, which was subdivided to two groups of 10; STZ group and treatment group. Treatment group received 55 mg/kg (IP STZ plus100 mg/kg ginger, daily for, 8 weeks, respectively; however, the control group just received an equal volume of distilled water daily (IP. Diabetes was induced by a single (IP injection of STZ (55 mg/kg. Animals were kept in standard condition. In 28 day after inducing diabetic 5 cc blood were collected for total antioxidant capacity, malondialdehyde and oxidized low density lipoprotein levels and kidney tissues of rat in whole groups were removed then prepared for apoptosis analysis by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL method. Results: Apoptotic cells significantly decreased in group that has received 100 mg/kg ginger (P < 0.05 in comparison to experimental groups (P < 0.05. Conclusion: Since in our study 100 mg/kg ginger have significantly preventive effect on kidney cells damages by reducing number of apoptotic cells in kidney and hence it seems that using it can be effective for treatment in diabetic rat.

  10. Streptozotocin-induced diabetes decreases conducted vasoconstrictor response in mouse cremaster arterioles

    DEFF Research Database (Denmark)

    Rai, A; Riemann, M; Gustafsson, F

    2008-01-01

    A conducted vasomotor response (CVR) is characterized by the spread of vasoconstriction or vasodilatation both up- and downstream from a local stimulation site in the microcirculation. It is believed to coordinate vasomotor responses within the microcirculation, and to contribute to the control....... The mouse cremasteric arterioles were stimulated locally with KCl and the resulting local response as well as conducted responses at 500 microm and 1000 microm were measured in control and STZ treated mice. Diabetes (n=8) induced by intraperitoneal injection of STZ in a dose of 100 mg/kg (mean blood glucose...

  11. Mechanism for blockade of angiotensin subtype 1 receptors to lower plasma glucose in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Chan, P; Liu, I-M; Tzeng, T-F; Yang, T-L; Cheng, J-T

    2007-01-01

    We investigated the mechanism(s) by which valsartan, a selective antagonist of angiotensin subtype 1 (AT(1)) receptor, decreased plasma glucose in streptozotocin (STZ)-induced diabetic rats. The plasma glucose concentration was assessed by the glucose oxidase method. The concentration of beta-endorphin in plasma or medium incubating adrenal medulla was measured using an enzyme-linked immunosorbent assay. The mRNA levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver were detected by Northern blotting analysis, while the protein levels of GLUT4 in isolated soleus muscle and hepatic PEPCK were investigated using Western blotting analysis. A single intravenous injection of valsartan dose-dependently increased plasma beta-endorphin-like immunoreactivity (BER) in parallel with the lowering of plasma glucose concentration in STZ-induced diabetic rats. Naloxone and naloxonazine inhibited the plasma glucose-lowering action of valsartan at doses sufficient to block opioid micro-receptors. In contrast to its action in wild-type diabetic mice, valsartan failed to modify plasma glucose in opioid micro-receptor knockout diabetic mice. Bilateral adrenalectomy in STZ-induced diabetic rats eliminated both the plasma glucose-lowering action and the plasma BER-elevating action of valsartan. In the isolated adrenal medulla of STZ-induced diabetic rats, angiotensin II (Ang II) or valsartan did not affect spontaneous BER secretion. Activation of cholinergic receptors by 1.0 micromol/l acetylcholine (ACh) enhanced BER secretion from the isolated adrenal medulla of STZ-induced diabetic rats, but not in the presence of 1.0 nmol/l Ang II, while valsartan reversed this inhibition by Ang II in a concentration-dependent manner. Treatment of STZ-induced diabetic rats with valsartan (0.2 mg/kg) three times daily for 3 days resulted in an increase in gene expression of GLUT4 in soleus muscle and impeded the

  12. Early visual deficits in streptozotocin-induced diabetic long evans rats.

    Science.gov (United States)

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

    2013-02-15

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

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

    African Journals Online (AJOL)

    Animal were maintained under lard-fructose diet for 3 days after STZ injection and Blood glucose level was measured to evaluate the stability. Only rats with blood glucose level greater than. 200 mg/dl 72 h after administration of STZ were selected to constitute the group of diabetic animals. Animal treatment. Five groups of ...

  14. Correction of protein metabolic disorders by composite extract of Musa paradisiaca and Coccinia indica in streptozotocin-induced diabetic albino rat: an approach through the pancreas.

    Science.gov (United States)

    Mallick, Chhanda; De, Debasis; Ghosh, Debidas

    2009-04-01

    The study focused on the ability of the extracts of Musa paradisiaca and Coccinia indica on protein metabolic disorders in streptozotocin (STZ)-induced diabetes. Wistar strain rats were divided into 6 groups as control, control + composite extract treated, STZ-induced diabetes, diabetic + composite extract treated, composite extract-pretreated diabetes, and composite extract-pretreated diabetes + composite extract treated. Protein metabolic status was assessed by serum levels of urea, uric acid, albumin, and creatinine along with urine urea and albumin levels. Diabetic therapeutic ability was assessed by blood glucose, glycated hemoglobin, and serum insulin levels. Histology of the pancreas, liver, and kidney was evaluated. Indices of protein metabolic disorders were deviated from control in STZ-induced diabetes, which were protected significantly after the treatment of composite extract of M. paradisiaca and C. indica. This protection was more prominent when the extract-pretreated animals were subjected to diabetes induction by STZ. The composite extract has a protective therapeutic effect against diabetes through beta-cell regeneration capacity.

  15. Antidiabetic effect of polysaccharides from Pleurotus ostreatus in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Zhang, Yan; Hu, Tao; Zhou, Hongli; Zhang, Yang; Jin, Gang; Yang, Yu

    2016-02-01

    This study was performed to evaluate the effects of total polysaccharides extracted from Pleurotus ostreatus on type 2 diabetes. Rats were administered with high-fat diet and streptozotocin (STZ) to induce diabetes. The rats were then treated with 100, 200, and 400 mg/kg/d POP or vehicle for 4 weeks. Our experiments indicated that POP reduces hyperglycemia and hyperlipidemia levels, improves insulin resistance, and increases glycogen storage by activating GSK3 phosphorylation and GLUT4 translocation. Moreover, POP reduces the risk of oxidative damage by increasing superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase(GSH-Px) activities and decreasing malonaldehyde(MDA) level. These results suggest that POP exerts antidiabetic effect on STZ-induced diabetic rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β-endorphin in type I-like diabetic rats.

    Science.gov (United States)

    Hsu, Chia-Chen; Lin, Mang Hung; Cheng, Juei Tang; Wu, Ming Chang

    2017-05-01

    Diosmin is one of the flavonoids contained in citrus and has been demonstrated to improve glucose metabolism in diabetic disorders. However, the mechanism(s) of diosmin in glucose regulation remain obscure. Therefore, we investigated the potential mechanism(s) for the antihyperglycaemic action of diosmin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Diosmin lowered hyperglycaemia in a dose-dependent manner in STZ-diabetic rats. This action was inhibited by naloxone at a dose sufficient to block opioid receptors. Additionally, we determined the changes in plasma β-endorphin-like immunoreactivity (BER) using enzyme-linked immunosorbent assay (ELISA). Diosmin also increased BER dose-dependently in the same manner. Repeated treatment of STZ-diabetic rats with diosmin for 1 week resulted in an increase in the expression of the glucose transporter subtype 4 (GLUT 4) in the soleus muscle and a reduction in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. These effects were also inhibited by naloxone at a dose sufficient to block opioid receptors. Bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of diosmin, including both the reduction in hyperglycemia and the elevation of plasma BER. In conclusion, our results suggest that diosmin may act on the adrenal glands to enhance the secretion of β-endorphin, which can stimulate the opioid receptors to attenuate hepatic gluconeogenesis and increase glucose uptake in soleus muscle, resulting in reduced hyperglycemia in STZ-diabetic rats. © 2017 John Wiley & Sons Australia, Ltd.

  17. Neuroprotective effect of Amorphophallus campanulatus in STZ ...

    African Journals Online (AJOL)

    3 mg/kg, ICV) day one and 3rd day after surgery. Surgery was performed on anesthetized rats by the help of stereotaxic apparatus. STZ induced AD rats were treated with petroleum ether extract of AC (100, 200 and 500 mg/kg, p.o.) for 14 days.

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

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    Tian W

    2015-09-01

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

  19. Hypolipidemic Activity of Eryngium carlinae on Streptozotocin-Induced Diabetic Rats

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    Ruth Noriega-Cisneros

    2012-01-01

    Full Text Available Diabetes mellitus (DM is a significant risk factor for the development of cardiovascular complications. This study was undertaken to investigate the effect of chronic administration of ethanolic extract of Eryngium carlinae on glucose, creatinine, uric acid, total cholesterol, and triglycerides levels in serum of streptozotocin- (STZ- induced diabetic rats. Triglycerides, total cholesterol, and uric acid levels increased in serum from diabetic rats. The treatment with E. carlinae prevented these changes. The administration of E. carlinae extract reduced the levels of creatinine, uric acid, total cholesterol, and triglycerides. Thus administration of E. carlinae is able to reduce hyperlipidemia related to the cardiovascular risk in diabetes mellitus.

  20. Calcium dobesilate attenuates vascular injury and the progression of diabetic retinopathy in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Padilla, Eugenia; Ganado, Patricia; Sanz, Mercedes; Zeini, Miriam; Ruiz, Emilio; Triviño, Alberto; Ramírez, Ana I; Salazar, Juan J; Ramírez, Jose M; Rojas, Blanca; Hoz, Rosa de; Tejerina, Teresa

    2005-01-01

    Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats. Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections. Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBE-treated group (71.8 +/- 4.5%, 53.3 +/- 0.5%, 67.4 +/- 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 +/- 0.05 g, 1.70 +/- 0.08 g, 1.13 +/- 0.05 g in group 0, 1 and 2 respectively) and caffeine-induced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats. We showed that long-term treatment with DOBE attenuated the progression of diabetic retinopathy and the alterations in vascular reactivity in streptozotocin-induced diabetic rats. Copyright 2004 John Wiley & Sons, Ltd.

  1. Administration of Lupinus albus gamma conglutin (Cγ) to n5 STZ rats augmented Ins-1 gene expression and pancreatic insulin content.

    Science.gov (United States)

    Vargas-Guerrero, Belinda; García-López, Pedro M; Martínez-Ayala, Alma L; Domínguez-Rosales, José A; Gurrola-Díaz, Carmen M

    2014-09-01

    Several studies support the health-promoting benefits of lupins, particularly lupin proteins. It has been demonstrated that Lupinus albus gamma conglutin (Cγ) protein lowered blood glucose levels; thus, Cγ showed promise as a new anti-diabetic compound for type 2 diabetes (T2D) treatment. The aim of this study was to evaluate the effect of Cγ on Ins-1 gene expression and on pancreatic insulin content in streptozotocin-mediated diabetic rats. Cγ was isolated from Lupinus albus seeds. Its identification was confirmed with polyacrylamide gel electrophoresis under native and denaturing conditions. We used streptozotocin (STZ) to induce T2D on the 5th day of life of newborn male Wistar rats (n5-STZ). After 20 weeks post-induction, these animals (glycemia > 200 mg/dL) were randomly assigned to three groups that received the following one-week treatments: vehicle, 0.90% w/v NaCl (n5 STZ-Ctrl); glibenclamide, 10 mg/kg (n5 STZ-Glib); or Cγ, 120 mg/kg (n5 STZ-Cγ). Glucose and insulin levels were measured before and after treatment. Ins-1 gene expression was quantified using real time polymerase chain reaction and the pancreatic insulin content was evaluated with immunohistochemistry. Post-treatment, the n5 STZ-Cγ and n5 STZ-Glib groups showed reductions in glucose, increments in serum insulin, and increases in Ins-1 gene expression and beta cell insulin content compared to the n5 STZ-Ctrl group. The results showed that Cγ had beneficial effects on Ins-1 gene expression and pancreatic insulin content. These biological effects of Cγ strengthen its promising potential as a nutraceutical and/or new agent for controlling hyperglycemia.

  2. Sapium ellipticum (Hochst. Pax Ethanol Leaf Extract Maintains Lipid Homeostasis in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Osasenaga Mcdonald Ighodaro

    2017-01-01

    Full Text Available Dyslipidemia is a common metabolic disorder especially in diabetes mellitus (DM. In this study, the ability of Sapium ellipticum (SE leaf extract to restore lipid homeostasis in streptozotocin-induced diabetes was examined. DM was induced in experimental rats (Wistar strains using single intraperitoneal dose (55 mg/kg body weight BW of streptozotocin (STZ. Treatment of diabetic rats with SE was oral (p.o, at doses of 400 and 800 mg kg−1 BW, twice daily at 8 h interval for 21 days. Lipid parameters were analyzed in the serum of rats using test kits. SE caused a significant (P≤0.05 reduction in STZ-induced hypercholesterolemia in a dose dependent pattern (13.7 and 17.89%. These effects were comparable to that provided by metformin (15.45%, a standard antidiabetic drug. Similar pattern was noted with serum triglycerides (TG (10.63 and 19.06% and LDL (31.47 and 25.97%. Adipose tissue TG level was improved to near normal. Besides, the cardiovascular risk predictors in terms of atherogenic index of plasma (AIP and LDL/HDL ratio were lowered by 57.85 and 44.12%, respectively. However, the extract failed to significantly reverse the STZ-induced decline in serum HDL. Overall, with AIP value of 0.28 and LDL/HDL ratio of 0.91, SE demonstrated the potential to maintain lipid homeostasis in the diabetics.

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

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    Esmaeal Tamaddonfard

    2013-01-01

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

  4. Ameliorative potential of rutin in combination with nimesulide in STZ model of diabetic neuropathy: targeting Nrf2/HO-1/NF-kB and COX signalling pathway.

    Science.gov (United States)

    Mittal, Ruchika; Kumar, Anil; Singh, Dhirendra Pratap; Bishnoi, Mahendra; Nag, Tapas Chandra

    2017-11-01

    Emerging role of Nrf-2/HO-1 in pathogenesis of diabetic neuropathy has been suggested. Diabetic neuropathy is one of the most common complications of diabetes and more than 50% patients of diabetes develop diabetic neuropathy. Rutin has been well documented to show protective effect in various complications, e.g., diabetic neuropathy. However, its mechanistic insight is still not completely understood. The present study has been designed to explore the protective effect of rutin and its interaction with COX-2 inhibitor, nimesulide in diabetic neuropathy. DN (diabetic neuropathy) rats were maintained with or without rutin (100 and 200 mg/kg), nimesulide (5 and 10 mg/kg), and their combinations for 8 weeks. Body weight, serum glucose, pain assessment (mechanical allodynia, cold allodynia, mechanical hyperalgesia, and thermal hyperalgesia), and motor nerve conduction velocity (MNCV) were measured in all groups. Oxidative damage was assessed through biochemical estimation and mitochondrial ROS production, followed by inflammatory and apoptotic markers (TNF-α, caspase-3, Nrf-2, HO-1, and NF-kBp65) for their activity, protein, and gene expression. The structural changes were also reported through transmission electron microscope. Streptozotocin injection (55 mg/kg) induced diabetes reduced body weight, reduced the threshold for pain in various pain assessment parameters. Oxidative damage (increased MDA, decreased SOD, catalase, and GSH levels) increased mitochondrial ROS production followed by increased expression of inflammatory markers and decreased expression of Nrf-2/HO-1 in sciatic nerve. Treatment with rutin (100 and 200 mg/kg) and nimesulide (5 and 10 mg/kg) significantly attenuates these alterations as compared to DN control rats. Furthermore, combination of rutin (200 mg/kg) and nimesulide (10 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone in streptozotocin-treated rats. The present study

  5. Effect of Calendula officinalis hydroalcoholic extract on passive avoidance learning and memory in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Moradkhani, Shirin; Salehi, Iraj; Abdolmaleki, Somayeh; Komaki, Alireza

    2015-01-01

    Medicinal plants, owing to their different mechanisms such as antioxidants effects, may improve learning and memory impairments in diabetic rats. Calendula officinalis (CO), has a significant antioxidant activity. To examine the effect of hydroalcoholic extract of CO on passive avoidance learning (PAL) and memory in streptozotocin (STZ)-induced diabetic male rats. A total of 32 adult male Wistar rats were randomly allocated to four groups: Control, diabetic, control + extract of CO and diabetic control + extract of CO groups with free access to regular rat diet. Diabetes in diabetic rats was induced by single intraperitoneal injection of 60 mg/kg STZ. After confirmation of diabetes, oral administration of 300 mg/kg CO extract to extract-treated groups have been done. PAL was tested 8 weeks after onset of treatment, and blood glucose and body weight were measured in all groups at the beginning and end of the experiment. The statistical analysis of data was performed by ANOVA followed by least significant difference post-hoc analysis. Diabetes decreased learning and memory. Effect of CO extract in retention test (after 24 and 48 h) has been shown a significant decrease in step-through latency and increase in time spent in the dark compartment part. Also the extract partially improved hyperglycemia and reduced body weight. Taken together, CO extract can improve PAL and memory impairments in STZ-diabetic rats. This improvement may be due to its antioxidant, anticholinergic activities or its power to reduce hyperglycemia.

  6. Effect of naringerin on biochemical parameters in the streptozotocin-induced diabetic rats

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    Ana Angélica Henrique Fernandes

    2009-02-01

    Full Text Available Amongst the numerous co-adjuvant therapies which could influence the incidence and progression of diabetic complications, antioxidants and flavonoids are currently being tested in clinical trials. We investigated the effect of naringerin on biochemical parameters in streptozotocin-induced (STZ - 60 mg/kg, i.p. diabetic rats. Male rats were divided into four groups: G1: untreated controls; G2: normal rats receiving naringerin; G3: untreated diabetics; G4: diabetics rats receiving naringerin. The naringerin (50mg/kg, i.p, decreased the hyperglycaemia and hyperlipidaemia associated with STZ-diabetes. The concentrations of serum insulin in treated diabetic rats tended to be increased. Naringerin treatment prevents STZ-induced changes in the activities of ALT, AST and LDH in the liver and heart, indicating the protective effect of naringerin against the hepatic and cardiac toxicity caused by STZ. The glycogen level in cardiac and hepatic tissues elevated with naringerin in diabetic rats. The naringerin can improve the glucose and lipid metabolism and is beneficial in preventing diabetic complications.Dentre as numerosas terapias para minimizar as complicações diabéticas, os antioxidantes e flavonoides são testados na clínica médica. Foi analisado o efeito da naringerina sobre os parâmetros bioquímicos em ratos diabéticos induzidos por estreptozotocina (STZ - 60mg/kg, i.p.. Ratos machos foram divididos em 4 grupos: G1: controle não tratado; G2: ratos normais que receberam naringerina; G3: diabéticos não tratados; G4: ratos diabéticos que receberam naringerina. Naringerina (50mg/kg, i.p., decresceu a hiperglicemia e a hiperlipidemia em ratos diabéticos. A concentração sérica de insulina em ratos tratados tendeu aumentar. A naringerina preveniu as alterações, provocadas pela estreptozotocina, na atividade hepática e cardíaca de ALT, AST e LDH, indicando o efeito protetor da naringerina sobre estes tecidos, contra toxicidade

  7. Protective Effects of Beta Glucan and Gliclazide on Brain Tissue and Sciatic Nerve of Diabetic Rats Induced by Streptozosin

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    Harun Alp

    2012-01-01

    Full Text Available There have not been yet enough studies about effects of beta glucan and gliclazide on oxidative stress created by streptozotocin in the brain and sciatic nerve of diabetic rats. The aim of this paper was to investigate the antioxidant effects of gliclazide and beta glucan on oxidative stress and lipid peroxidation created by streptozotosin in brain and sciatic nerve. Total of 42 rats were divided into 6 groups including control, diabetic untreated (DM (only STZ, diabetic, STZ (DM + beta glucan, STZ (DM + gliclazide, only beta glucan treated (no diabetic, and only gliclazide treated (no diabetic. The brain and sciatic nerve tissue samples were analyzed for malondialdehyde (MDA, total oxidant status (TOS, total antioxidant status (TAS, oxidative stress index (OSI, and paraoxonase (PON-1 levels. We found a significant increase in MDA, TOS, and OSI along with a reduction in TAS level, catalase, and PON-1 activities in brain and sciatic nerve of streptozotocin-induced diabetic rats. Also, this study shows that in terms of these parameters both gliclazide and beta glucan have a neuroprotective effect on the brain and sciatic nerve of the streptozotocin-induced diabetic rat. Our conclusion was that gliclazide and beta glucan have antioxidant effects on the brain and sciatic nerve of the streptozotocin-induced diabetic rat.

  8. Goettingen Minipigs (GMP: Comparison of Two Different Models for Inducing Diabetes

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    Strauss Armin

    2012-03-01

    Full Text Available Abstract Purpose Preclinical experiments on large animals are indispensable for evaluating the effectiveness of diabetes therapies. Miniature swine are well suited for such studies due to their physiological and pathophysiological responses. Methods We compare two methods for inducing diabetes in Goettingen minipigs (GMP, in five with the beta cell toxin streptozotocin (STZ and in five other GMP by total pancreatectomy (PE. Glucose homeostasis was assessed with the intravenous glucose-tolerance test (IVGTT and continual monitoring of interstitial glucose levels. At conclusion of the observation period, the pancreata were examined histologically. Three non-diabetic GMP served as control group. Results The IVGTT revealed markedly diabetic profiles in both GMP groups. STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive cells in the pancreas. PE-GMP survived the total pancreatectomy only with intensive postoperative care. Conclusions Although both methods reliably induced diabetes in GMP, the PE-GMP clearly had more health problems and required a greater expenditure of time and resources. The PE-GMP model, however, was better at eliminating endogenous insulin and C-peptide than the STZ-GMP model.

  9. Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Arokiyaraj, S; Balamurugan, R; Augustian, P

    2011-10-01

    To evaluate the antihyperglycemic activity of ethyl acetate extract of Hypericum perforatum (H. perforatum) in streptozotocin (STZ)-induced diabetic rats. Acute toxicity and oral glucose tolerance test were performed in normal rats. Male albino rats were rendered diabetic by STZ (40 mg/kg, intraperitoneally). H. perforatum ethyl acetate extract was orally administered to diabetic rats at 50, 100 and 200 mg/kg doses for 15 days to determine the antihyperglycemic activity. Biochemical parameters were determined at the end of the treatment. H. perforatum ethyl acetate extract showed dose dependant fall in fasting blood glucose (FBG). After 30 min of extract administration, FBG was reduced significantly when compared with normal rats. H. perforatum ethyl acetate extract produced significant reduction in plasma glucose level, serum total cholesterol, triglycerides, glucose-6-phosphatase levels. Tissue glycogen content, HDL-cholesterol, glucose-6-phosphate dehydrogenase were significantly increased compared with diabetic control. No death or lethal effect was observed in the toxic study. The results demonstrate that H. perforatum ethyl acetate extract possesses potent antihyperglycemic activity in STZ induced diabetic rats.

  10. Consumption of Dietary Resistant Starch Partially Corrected the Growth Pattern Despite Hyperglycemia and Compromised Kidney Function in Streptozotocin-Induced Diabetic Rats.

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    Koh, Gar Yee; Rowling, Matthew J; Schalinske, Kevin L; Grapentine, Kelly; Loo, Yi Ting

    2016-10-12

    We previously demonstrated that feeding of dietary resistant starch (RS) prior to the induction of diabetes delayed the progression of diabetic nephropathy and maintained vitamin D balance in streptozotocin (STZ)-induced type 1 diabetic (T1D) rats. Here, we examined the impact of RS on kidney function and vitamin D homeostasis following STZ injection. Male Sprague-Dawley rats were administered STZ and fed a standard diet containing cornstarch or 20, 10, or 5% RS for 4 weeks. T1D rats fed 10 and 20% RS, but not 5% RS, gained more weight than cornstarch-fed rats. Yet, renal health and glucose metabolism were not improved by RS. Our data suggest that RS normalized growth patterns in T1D rats after diabetes induction in a dose-dependent manner despite having no effect on blood glucose and vitamin D balances. Future interventions should focus on the preventative strategies with RS in T1D.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Anti-diabetic activity of traditional Indian gold containing preparation: Shadguna Balijarita Makaradhwaja on streptozotocin induced diabetic rats.

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    Khedekar, Sanjay; Rukkudin, Galib; Ravishankar, Basavaiah; Prajapati, Pradeepkumar

    2016-01-01

    Makaradhwaja a gold containing mercurial preparation used for diabetes mellitus in indigenous system of medicine. It is a popular aphrodisiac and rejuvenator traditional medicine. It is prepared by using processed gold, mercury and sulfur in different ratios by applying intermittent heating pattern in Valuka Yantra. The aim of the study was to evaluate anti-diabetic effect of Shadguna Balijarita Makaradhwaja (SBM) on streptozotocin (STZ) induced diabetic rats. Diabetes was induced to normal rats by injecting STZ in dose 40 mg/kg. Powdered SBM and dried extract of Tinospora cordifolia were mixed with honey and administered orally for 20 days at dose 2.63 mg/kg and 42.34 mg/kg body weight, respectively. The effects of treatment on body weight changes and blood glucose levels were quantified on day 1, 5, 10, 15 and 21 of the experiments. On the 21(st) day, animals were sacrificed and gross histopathological changes in liver, kidney and pancreas were illustrated. Blood sugar level, glyacated hemoglobin, blood urea, serum cholesterol, serum creatinine, serum triglyceride and serum protein were estimated with standard methods. The study was conducted in the year 2011. Test drug observed significant decrease (P diabetic control rats. Blood sugar level of test drug group shown a significant decrease (279.11 ± 57.95) compared with diabetic rats. The present study demonstrates that SBM and dried extract of T. cordifolia with honey significantly reduces the blood glucose level and shows anti-diabetic effect.

  13. Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle.

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    de Carvalho, Afonso Kopczynski; da Silva, Sabrina; Serafini, Edenir; de Souza, Daniela Roxo; Farias, Hemelin Resende; de Bem Silveira, Gustavo; Silveira, Paulo Cesar Lock; de Souza, Claudio Teodoro; Portela, Luis Valmor; Muller, Alexandre Pastoris

    2017-04-01

    Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. We investigated the effect of a prior 30 days voluntary exercise protocol on STZ-diabetic CF1 mice. Glycemia, and the liver and skeletal muscle glycogen, mitochondrial function, and redox status were analyzed up to 5 days after STZ injection. Animals were engaged in the following groups: Sedentary vehicle (Sed Veh), Sedentary STZ (Sed STZ), Exercise Vehicle (Ex Veh), and Exercise STZ (Ex STZ). Exercise prevented fasting hyperglycemia in the Ex STZ group. In the liver, there was decreased on glycogen level in Sed STZ group but not in EX STZ group. STZ groups showed decreased mitochondrial oxygen consumption compared to vehicle groups, whereas mitochondrial H2 O2 production was not different between groups. Addition of ADP to the medium did not decrease H2 O2 production in Sed STZ mice. Exercise increased GSH level. Sed STZ group increased nitrite levels compared to other groups. In quadriceps muscle, glycogen level was similar between groups. The Sed STZ group displayed decreased O2 consumption, and exercise prevented this reduction. The H2 O2 production was higher in Ex STZ when compared to other groups. Also, GSH level decreased whereas nitrite levels increased in the Sed STZ compared to other groups. The PGC1 α levels increased in Sed STZ, Ex Veh, and Ex STZ groups. In summary, prior exercise training prevents hyperglycemia in STZ-mice diabetic associated with increased liver glycogen storage, and oxygen consumption by the mitochondria of skeletal muscle implying in increased oxidative/biogenesis capacity, and improved redox status of both tissues. J. Cell. Biochem. 118: 678-685, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

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    Sachin L Badole

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

  15. Differential Expression of Nerve Injury-Induced Protein 1 (Ninjurin 1) in In Vivo and In Vitro Models for Diabetic Erectile Dysfunction

    OpenAIRE

    Kim, Do Kyung; Yin, Guo Nan; Ryu,Ji Kan; Suh, Jun?Kyu

    2012-01-01

    Purpose Endothelial dysfunction and peripheral neuropathy are important mechanisms responsible for diabetes-induced erectile dysfunction (ED). Nerve injury-induced protein 1 (Ninjurin 1) is known to be related to neuroinflammatory processes and is also reported to induce vascular regression during the developmental period. In the present study, we determined the differential expression of Ninjurin 1 in penile tissue of streptozotocin (STZ)-induced diabetic mice with ED. Materials and Methods ...

  16. Intracavernous delivery of a designed angiopoietin-1 variant rescues erectile function by enhancing endothelial regeneration in the streptozotocin-induced diabetic mouse.

    Science.gov (United States)

    Jin, Hai-Rong; Kim, Woo Jean; Song, Jae Sook; Piao, Shuguang; Choi, Min Ji; Tumurbaatar, Munkhbayar; Shin, Sun Hwa; Yin, Guo Nan; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu

    2011-03-01

    Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals. Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days -3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test. Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47(phox) and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1-treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1-induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin. These findings support the concept of cavernous endothelial regeneration by use of the recombinant Ang1 protein as

  17. The protective effects of Ziziphus vulgaris L. fruits on biochemical and histological abnormalities induced by diabetes in rats.

    Science.gov (United States)

    Goli-malekabadi, Najmeh; Asgary, Sedigheh; Rashidi, Bahman; Rafieian-Kopaei, Mahmood; Ghannadian, Mostafa; Hajian, Shabnam; Sahebkar, Amirhossein

    2014-09-01

    Diabetes mellitus arises from a deficient production and action of insulin. Ziziphus vulgaris L. (jujube) is a medicinal plant that is known to have anti-diabetic actions. The aim of the present study was to investigate the protective effects of jujube fruit powder and extract against biochemical imbalances in streptozotocin (STZ)-induced diabetes. Diabetes was induced in rats using intraperitoneal injection of STZ at a dose of 60 mg/kg body weight (bw). Jujube powder (1 g/kg bw) and extract (1 g/kg bw) were administered daily via gavage, from two weeks prior to three weeks after STZ injection. Serum concentrations of glucose, insulin, and lipids and histological changes of the pancreas tissue were assessed at the end of study. The kaempferol content of jujube extract was found to be 0.013 ± 0.0005% (w/w). Two weeks of supplementation with jujube powder resulted in a significant reduction of serum glucose levels compared with the non-diabetic control group prior to STZ treatment. Both jujube preparations prevented serum insulin decrease following STZ treatment, increased antioxidant capacity, and reduced total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde levels. Jujube powder reduced serum low-density lipoprotein cholesterol and C-reactive protein concentrations while jujube extract had no effect on these parameters. Histopathological examination revealed a significant attenuation of pancreatic inflammation in the jujube-treated animals. The present findings suggest a protective role of jujube supplementation, in particular in the powdered form, against diabetes-induced biochemical and histopathological abnormalities.

  18. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh

    Crocus sativus L. (saffron) has many biological effects such as antioxidant property. The present study investigated the immunomodulatory effects of the aqueous saffron extract on streptozotocin (STZ)-induced diabetic rats. In this study, the rats were divided into the following groups of 9 animals each: control, untreated diabetic, three saffron extract-treated diabetic groups. Diabetes was induced by STZ in rats. Saffron was administered 3 days after STZ administration; these injections were continued to the end of the study (4 weeks). At the end of the 4-week period, blood was drawn for biochemical assays and the abdominal aorta was removed for detecting the inflammatory cytokines expression. We found that saffron decreased blood glucose, malondialdehyde, nitric oxide, total lipids, triglycerides, cholesterol levels significantly (psaffron-treated diabetic groups compared with the untreated groups, in a dose dependent manner (psaffron-treated diabetic rats inhibited the expression of inflammatory cytokines in the abdominal aorta versus the untreated diabetic rats. Our results validate the use of saffron as a treatment against diabetes mellitus and its vascular complications. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  19. Effect of coenzyme Q10 alone and its combination with metformin on streptozotocin-nicotinamide-induced diabetic nephropathy in rats.

    Science.gov (United States)

    Maheshwari, Rajesh A; Balaraman, R; Sen, Ashim K; Seth, A K

    2014-01-01

    This study was aimed to investigate the therapeutic potential of coenzyme Q10 and its combination with metformin on streptozotocin (STZ)-nicotinamide-induced diabetic nephropathy (DN). Type 2 diabetes in rats was induced with STZ-nicotinamide. The diabetic rats were treated with coenzyme Q10 (10 mg/kg, p.o.) alone or coenzyme Q10 + metformin. Various parameters of renal function tests such as serum creatinine, urea, uric acid, and markers of oxidative stress such as renal malondialdehyde (MDA) level, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) activity, transforming growth factor-β (TGF-β), and nitrite content were estimated in renal tissues. All treated animal were subjected to histopathological changes of kidney. Diabetic rats showed a significant reduction in renal function, which was reflected with an increase in serum urea, serum creatinine, uric acid. In addition, STZ-nicotinamide caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity and glutathione (GSH) level. Moreover, TNF-α, MPO activity, TGF-β, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-α, MPO activity, TGF-β and nitrite content along with histopathological changes. This finding suggests that the treatment with coenzyme Q10 or metformin showed significant renoprotective effect against STZ-nicotinamide-induced DN. However, concomitant administration of both showed a better renoprotective effect than coenzyme Q10 or metformin alone treatment.

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

    Science.gov (United States)

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

    2013-03-01

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

  1. Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity

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    Pauza Mary E

    2008-03-01

    Full Text Available Abstract A common complication associated with diabetes is painful or painless diabetic peripheral neuropathy (DPN. The mechanisms and determinants responsible for these peripheral neuropathies are poorly understood. Using both streptozotocin (STZ-induced and transgene-mediated murine models of type 1 diabetes (T1D, we demonstrate that Transient Receptor Potential Vanilloid 1 (TRPV1 expression varies with the neuropathic phenotype. We have found that both STZ- and transgene-mediated T1D are associated with two distinct phases of thermal pain sensitivity that parallel changes in TRPV1 as determined by paw withdrawal latency (PWL. An early phase of hyperalgesia and a late phase of hypoalgesia are evident. TRPV1-mediated whole cell currents are larger and smaller in dorsal root ganglion (DRG neurons collected from hyperalgesic and hypoalgesic mice. Resiniferatoxin (RTX binding, a measure of TRPV1 expression is increased and decreased in DRG and paw skin of hyperalgesic and hypoalgesic mice, respectively. Immunohistochemical labeling of spinal cord lamina I and II, dorsal root ganglion (DRG, and paw skin from hyperalgesic and hypoalgesic mice reveal increased and decreased TRPV1 expression, respectively. A role for TRPV1 in thermal DPN is further suggested by the failure of STZ treatment to influence thermal nociception in TRPV1 deficient mice. These findings demonstrate that altered TRPV1 expression and function contribute to diabetes-induced changes in thermal perception.

  2. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

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    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  3. Favorable effects of vildagliptin on metabolic and cognitive dysfunctions in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    El Batsh, Maha M; El Batch, Manal M; Shafik, Noha M; Younos, Ibrahim H

    2015-12-15

    Progression of diabetes mellitus is accompanied by metabolic disorders together with psychological deficits including cognitive dysfunctions. Herein, we used a murine streptozotocin (STZ)-induced diabetes to investigate the beneficial effects of vildagliptin not only on metabolic abnormalities, but also on diabetes-induced cognitive decline. Sixty rats were divided randomly and equally into 2 groups; one remains normal and the other serves as STZ- induced diabetic. Both groups were further divided equally into 2 groups; one received vehicle and the other received oral vildagliptin for 8 weeks. Cognitive behavior was assessed using novel object recognition test. Blood samples were collected to measure metabolic parameters and dipeptidyl peptidase (DPP)-IV activity. Brains were removed and investigated for the levels of inflammatory and oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α), in addition to brain-derived neurotrophic factor (BDNF) and relative expression of nuclear factor kappa B (NF-κB)/p65. Treatment of STZ-induced diabetic rats with vildagliptin increased their body weight and corrected diabetes-induced memory and learning impairment. Moreover, vildagliptin significantly decreased serum levels of glucose and lipids (except high density lipoprotein) together with brain MDA, TNF-α, serum DPP-IV activities and NF-κB/p65 gene expression. On the other hand, vildagliptin significantly increased brain BDNF, SOD as well as serum insulin. Results suggested that vildagliptin has a protective role in counteracting both metabolic abnormalities and memory deficits in diabetic rats, possibly via its anti-hyperglycemic, anti-inflammatory, antioxidant effects, together with reduction of brain NF-κB/p65 over expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms.

    OpenAIRE

    Aragno Manuela; Mastrocola Raffaella; Ghé Corrado; Arnoletti Elisa; Bassino Eleonora; Alloatti Giuseppe; Muccioli Giampiero

    2012-01-01

    Abstract Background The aim of this study was to investigate whether obestatin (OB), a peptide mediator encoded by the ghrelin gene exerting a protective effect in ischemic reperfused heart, is able to reduce cardiac dysfunctions in adult diabetic rats. Methods Diabetes was induced by STZ injection (50 mg/kg) in Wistar rats (DM). OB was administered (25 μg/kg) twice a day for 6 weeks. Non-diabetic (ND) rats and DM rats were distributed into four groups: untreated ND, OB-treated ND, untreated ...

  5. TRAIL and DcR1 Expressions Are Differentially Regulated in the Pancreatic Islets of STZ- versus CY-Applied NOD Mice

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    Ercument Dirice

    2011-01-01

    Full Text Available TNF-related apoptosis-inducing ligand (TRAIL is an important component of the immune system. Although it is well acknowledged that it also has an important role in Type 1 Diabetes (T1D development, this presumed role has not yet been clearly revealed. Streptozotocin (STZ and Cyclophosphamide (CY are frequently used agents for establishment or acceleration of T1D disease in experimental models, including the non-obese diabetic (NOD mice. Although such disease models are very suitable for diabetes research, different expression patterns for various T1D-related molecules may be expected, depending on the action mechanism of the applied agent. We accelerated diabetes in female NOD mice using STZ or CY and analyzed the expression profiles of TRAIL ligand and receptors throughout disease development. TRAIL ligand expression followed a completely different pattern in STZ- versus CY-accelerated disease, displaying a prominent increase in the former, while appearing at reduced levels in the latter. Decoy receptor 1 (DcR1 expression also increased significantly in the pancreatic islets in STZ-induced disease. Specific increases observed in TRAIL ligand and DcR1 expressions may be part of a defensive strategy of the beta islets against the infiltrating leukocytes, while the immune-suppressive agent CY may partly hold down this defense, contributing further to diabetes development.

  6. Effect of vanadium treatment on tissue distribution of biotrace elements in normal and streptozotocin-induced diabetic rats. Simultaneous analysis of V and Zn using radioactive multitracer

    Energy Technology Data Exchange (ETDEWEB)

    Yasui, Hiroyuki; Takino, Toshikazu; Fugono, Jun; Sakurai, Hiromu [Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto (Japan); Hirunuma, Rieko; Enomoto, Shuichi [Radioisotope Technology Division, Cyclotron Center, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama (Japan)

    2001-05-01

    Because vanadium ions such as vanadyl (VO{sup 2+}) and vanadate (VO{sup 3-}) ions were demonstrated to normalize blood glucose levels of diabetic animals and patients, the action mechanism of vanadium treatment has been of interest. In this study, we focused on understanding interactions among trace elements in diabetic rats, in which a multitracer technique was used. The effects of vanadyl sulfate (VS)-treatment on the tissue distribution of trace vanadium ({sup 48}V) and zinc ({sup 65}Zn) in normal and streptozotocin (STZ)-induced diabetic rats were examined, and were evaluated in terms of the uptake ratio. The uptake ratio of both elements in tissues significantly changed between STZ-rats and those treated with VS. These results indicated that vanadium treatment in STZ-rats alters the tissue distribution of endogenous elements, suggesting the importance of the relationship between biotrace elements and pathophysiology. (author)

  7. Streptozotocin produces oxidative stress, inflammation and decreases BDNF concentrations to induce apoptosis of RIN5F cells and type 2 diabetes mellitus in Wistar rats.

    Science.gov (United States)

    Bathina, Siresha; Srinivas, Nanduri; Das, Undurti N

    2017-04-29

    Neurodegenerative disorders, such as deficits in learning, memory and cognition and Alzheimer's disease are associated with diabetes mellitus. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor and is known to possess anti-obesity, anti-diabetic actions and is believed to have a role in memory and Alzheimer's disease. To investigate whether STZ can reduce BDNF production by rat insulinoma (RIN5F) cells in vitro and decrease BDNF levels in the pancreas, liver and brain in vivo. Streptozotocin (STZ)-induced cytotoxicity to RIN5F cells in vitro and type 2 DM in Wistar rats was employed in the present study. Cell viability, activities of various anti-oxidants and secretion of BDNF by RIN5F cells in vitro were measured using MTT assay, biochemical methods and ELISA respectively. In STZ-induced type 2 DM rats: plasma glucose, interleukin-6 and tumor necrosis factor-α levels and BDNF protein expression in the pancreas, liver and brain tissues were measured. In addition, neuronal count and morphology in the hippocampus and hypothalamus areas was assessed. STZ-induced suppression of RIN5F cell viability was abrogated by BDNF. STZ suppressed BDNF secretion by RIN5F cells in vitro. STZ-induced type 2 DM rats showed hyperglycemia, enhanced plasma IL-6 and TNF-αlevels and reduced plasma and pancreas, liver and brain tissues (P stress compared to untreated control. Hypothalamic and hippocampal neuron in STZ-treated animals showed a decrease in the number of neurons and morphological changes suggesting of STZ cytotoxicity. The results of the present study suggest that STZ is not only cytotoxic to pancreatic beta cells but also to hypothalamic and hippocampal neurons by inducing oxidative stress. STZ ability to suppress BDNF production by pancreas, liver and brain tissues suggests that impaired memory, learning, and cognitive dysfunction seen in diabetes mellitus could be due to BDNF deficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 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.

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

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    Jianmin Ran

    2014-01-01

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

  10. Diabetes Induced Changes in Podocyte Morphology and Gene Expression Evaluated Using GFP Transgenic Podocytes.

    Science.gov (United States)

    Xu, Jianxiang; Zheng, Shirong; Kralik, Patricia M; Krishnan, Laxminarayanan; Huang, Hui; Hoying, James B; Cai, Lu; Carlson, Edward C; Tan, Yi; Epstein, Paul N

    2016-01-01

    The effect of diabetes in vivo has not been examined on isolated podocytes. To achieve this, GFP was expressed constitutively in podocytes of PGFP transgenic mice which were bred to OVE mice to produce diabetic OVE-GFP mice. Viewing GFP fluorescence, foot processes of OVE-GFP podocytes were visually and measurably effaced, which did not occur with less severe STZ diabetes. Over 300,000 podocytes were purified from each PGFP mouse but only 49,000 podocytes per diabetic OVE-GFP mouse. The low yield from OVE-GFP mice appeared to be due to more fragile state of most OVE-GFP diabetic podocytes which did not survive the isolation process. Diabetic podocytes that were isolated had high levels of the lipid peroxidation product 4-HNE and they were more sensitive to death due to oxidative stress. Gene array analysis of OVE-GFP podocytes showed strong diabetes induction of genes involved in inflammation. Four CXC chemokines were induced at least 3-fold and the chemokine CXCL1 was shown for the first time to be specifically induced in podocytes by OVE, dbdb and STZ diabetes.

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

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    Lu, Hung-Jen; Tzeng, Thing-Fong; Liou, Shorong-Shii; Da Lin, Sheng; Wu, Ming-Chang; Liu, I-Min

    2014-03-26

    Ruscogenin is a major steroid sapogenin in the traditional Chinese herb Ophiopogon japonicus that have multiple bioactivities. Recent studies have demonstrated that ruscogenin is involved in down-regulation of intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) activation in anti-inflammatory pathways. We hypothesized that ruscogenin protects against diabetic nephropathy (DN) by inhibiting NF-κB-mediated inflammatory pathway. To test this hypothesis, the present study was to examine the effects of ruscogenin in rats with streptozotocin (STZ)-induced DN. Diabetes was induced with STZ (60 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats in the treatment group were orally dosed with 0.3, 1.0 or 3.0 mg/kg ruscogenin for 8 weeks. The normal rats were chosen as nondiabetic control group. The rats were sacrificed 10 weeks after induction of diabetes. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for pathology histology, immunohistochemistry, and Western blot analyses. Ruscogenin administration did not lower the levels of plasma glucose and glycosylated hemoglobin in STZ-diabetic rats. Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, blood urea nitrogen and proteinuria, along with marked elevation in the ratio of kidney weight to body weight, that were reversed by ruscogenin. Ruscogenin treatment was found to markedly improve histological architecture in the diabetic kidney. Renal NF-κB activity, as wells as protein expression and infiltration of macrophages were increased in diabetic kidneys, accompanied by an increase in protein content of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in kidney tissues. All of the above abnormalities were reversed by ruscogenin treatment, which also decreased the expression of transforming growth factor-β1 and fibronectin in the

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

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    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

  13. Danhong Huayu Koufuye Prevents Diabetic Retinopathy in Streptozotocin-Induced Diabetic Rats via Antioxidation and Anti-Inflammation

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    Wenpei Chen

    2017-01-01

    Full Text Available Danhong Huayu Koufuye (DHK, a traditional Chinese prescription, is used to treat central retinal vein occlusion clinically. We previously reported that DHK prevented diabetic retinopathy (DR in rats. Moreover, we found that it protected endothelial cells from hyperglycemia-induced apoptosis through antioxidation and anti-inflammation. Here, we investigated whether antioxidative and anti-inflammatory activities of DHK contributed to its therapeutic effect on DR in streptozotocin- (STZ- induced diabetic rats. DHK significantly blocked the breakdown of the blood-retinal barrier (BRB and increased the thickness of the inner nuclear layer (INL, as well as suppressed the swelling of the ganglion cell layer (GCL in diabetic retinas. DHK remarkably increased the activities of superoxide dismutase (SOD and glutathione peroxidase (GPx in plasma, and decreased serum level of nitric oxide (NO. Moreover, DHK markedly reduced the serum levels of vascular endothelial growth factor (VEGF and intercellular adhesion molecule-1 (ICAM-1. Furthermore, DHK significantly downregulated protein expressions of VEGF and inducible NO synthase (iNOS and mRNA expression of ICAM-1 in retinas. These results suggest that the antioxidative and anti-inflammatory activities of DHK may be important mechanisms involved in the protective effect of DHK on DR in STZ-induced diabetic rats.

  14. Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus.

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    Lee, C-T; Lien, Y-H H; Lai, L-W; Chen, J-B; Lin, C-R; Chen, H-C

    2006-05-01

    Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P diabetic rats. Sodium chloride cotransporter was also increased (207 +/- 10%). No change was found in paracellin-1 (cortex: 108 +/- 8%; medulla: 110 +/- 10%). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 +/- 10%) and TRPV5 (211 +/- 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 +/- 7%; medulla: 99 +/- 7%). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.

  15. Antidiabetic effect of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats

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    B. Jayaprasad

    2016-03-01

    Full Text Available Diabetes has been increasing at an alarming rate around the world, and experts have relied on remedies from the utilization of ancient drugs that are essentially derived from plants. The present study aimed to evaluate the antidiabetic potential of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats. Diabetes was induced in male albino Wistar rats by single intraperitoneal injection of streptozotocin (STZ (50 mg/kg b.w.. The diabetic rats were administered orally with C. swietenia bark (CSB methanolic (CSBMEt and aqueous (CSBAEt (250 mg/kg b.w. extracts and glibenclamide (600 µg/kg b.w. by intragastric intubation for 45 days. The result showed a heavy loss in weight, increase in blood glucose and glycosylated hemoglobin level, and decline in plasma insulin and total hemoglobin content. Furthermore, glucose-6-phosphatase and fructose-1,6-bis phosphatase were found to be increased whereas hexokinase and glycogen contents were decreased in STZ induced diabetic rats. CSBAEt, CSBMEt and glibenclamide treated diabetic rats showed moderate reduction in blood glucose and glycosylated hemoglobin levels; in addition, plasma insulin and hemoglobin levels were elevated. The altered activities of carbohydrate metabolizing enzymes and liver glycogen were improved remarkably. CSBMEt results were comparable to the standard drug glibenclamide. The present findings support the usage of the plant extracts for the traditional treatment of diabetes.

  16. Investigating the effects of Capparis Spinosa on hepatic gluconeogenesis and lipid content in streptozotocin-induced diabetic rats.

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    Jalali, Mohammad Taha; Mohammadtaghvaei, Narges; Larky, Damoon Ashtary

    2016-12-01

    The present study aimed to investigate the effects of administration of Capparis spinosa (CS) fruit aqueous extract on liver metabolism in streptozotocin (STZ)-induced diabetic rats. The aqueous extract of CS was orally administered at a dose of 20mg/kg for 28 consecutive days and then its effects on blood glucose, lipid and insulin levels in normal and STZ diabetic rats were comparatively investigated. Furthermore, the effects of CS on the activity and expression of the key enzymes of gluconeogenesis and hepatic lipid content were investigated. The results showed that administration of CS extract in the STZ diabetic rats significantly decreased blood glucose level, while no significant influence on the insulin level. In addition, CS significantly decreased blood and liver triglyceride and cholesterol content in STZ diabetic rats. Furthermore, CS administration significantly reduced the mRNA expression and enzyme activities of glucose-6- phosphatase and phosphoenolpyruvate carboxykinase in liver tissues. Our findings demonstrated the beneficial effects of CS on blood glucose and lipid levels in an insulin- independent manner. This study also showed that CS improved the circulating levels of triglyceride and cholesterol. In addition, direct inhibition of gluconeogenesis in liver may be a probable mechanism of action of this plant. Since CS also decreased liver lipid content, we suggest that CS administration might be a beneficial therapeutic approach for metabolic syndrome and fatty liver. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Protective effects of allicin on streptozotocin-induced diabetic nephropathy in rats.

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    Huang, Hong; Jiang, Ying; Mao, Genxiang; Yuan, Fang; Zheng, Hexin; Ruan, Yuan; Wu, Tianfeng

    2017-03-01

    Studies in animal models have shown that allicin, a major biologically active component of garlic, can play a role in the prevention of tissue fibrosis in the liver, lung and heart, mainly related to the inhibition of fibroblast proliferation, fibrogenic cytokine secretion and extracellular matrix synthesis. This study aimed to investigate the protective effects of allicin on renal damage in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were administered allicin (15, 30 and 45 mg · kg -1  · day -1 ) via daily intra-gastric gavage for 12 weeks. The levels of fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (sCr), lipid and 24 h urine albumin excretion (UAE) were measured at the end of weeks 4, 8 and 12. The renal histopathology and the expression levels of collagen I, transforming growth factor β1 (TGF-β1) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) were measured using immunohistochemistry and/or western blotting. In 12 week STZ-induced diabetic rats, severe hyperglycemia and albuminuria were markedly developed. Treatment with allicin for 12 weeks ameliorated diabetes-induced morphological alterations of the kidney and decreased FBG, BUN, sCr, triglyceride (TG) and 24 h UAE in diabetic rats. The expression levels of collagen I, TGF-β1 and p-ERK1/2 were significantly decreased by allicin treatment. These results suggested that allicin may play a protective role in diabetic nephropathy via the TGF-β1/ERK pathway in diabetic rats. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  18. High fat diet attenuates hyperglycemia, body composition changes, and bone loss in male streptozotocin-induced type 1 diabetic mice.

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    Carvalho, Adriana Lelis; DeMambro, Victoria E; Guntur, Anyonya R; Le, Phuong; Nagano, Kenichi; Baron, Roland; de Paula, Francisco José Albuquerque; Motyl, Katherine J

    2018-02-01

    There is a growing and alarming prevalence of obesity and the metabolic syndrome in type I diabetic patients (T1DM), particularly in adolescence. In general, low bone mass, higher fracture risk, and increased marrow adipose tissue (MAT) are features of diabetic osteopathy in insulin-deficient subjects. On the other hand, type 2 diabetes (T2DM) is associated with normal or high bone mass, a greater risk of peripheral fractures, and no change in MAT. Therefore, we sought to determine the effect of weight gain on bone turnover in insulin-deficient mice. We evaluated the impact of a 6-week high-fat (HFD) rich in medium chain fatty acids or low-fat diet (LFD) on bone mass and MAT in a streptozotocin (STZ)-induced model using male C57BL/6J mice at 8 weeks of age. Dietary intervention was initiated after diabetes confirmation. At the endpoint, lower non-fasting glucose levels were observed in diabetic mice fed with high fat diet compared to diabetic mice fed the low fat diet (STZ-LFD). Compared to euglycemic controls, the STZ-LFD had marked polydipsia and polyphagia, as well as reduced lean mass, fat mass, and bone parameters. Interestingly, STZ-HFD mice had higher bone mass, namely less cortical bone loss and more trabecular bone than STZ-LFD. Thus, we found that a HFD, rich in medium chain fatty acids, protects against bone loss in a T1DM mouse model. Whether this may also translate to T1DM patients who are overweight or obese in respect to maintenance of bone mass remains to be determined through longitudinal studies. © 2017 Wiley Periodicals, Inc.

  19. Streptozotocin-induced diabetes increases amyloid plaque deposition in AD transgenic mice through modulating AGEs/RAGE/NF-κB pathway.

    Science.gov (United States)

    Wang, Xu; Yu, Song; Hu, Jiang-Ping; Wang, Chun-Yan; Wang, Yue; Liu, Hai-Xing; Liu, Yu-Li

    2014-08-01

    An increasing number of studies have demonstrated of that diabetes mellitus (DM) is associated with an increased prevalence of Alzheimer disease (AD), the underlying mechanisms are still obscure. We developed a streptozotocin (STZ)-induced diabetic AD transgenic mouse model and evaluated the effect of hyperglycemia on senile plaque formation. Our data showed that administration of STZ increased the level of blood glucose and increased the advanced glycation end products (AGEs) in brain tissue, and further enhanced the expression levels of the receptor for AGEs (RAGE) and the nuclear factor-kappa B (NF-κB) in the brain, and accelerated the senile plaque formation in the transgenic mice. Our results showed that STZ-induced insulin-deficient hyperglycemia caused the pathophysiology of AD in APP/PS1 transgenic mice by modulating the AGEs/RAGE/NF-κB pathway. Our study suggests that there is a close linkage of DM and cerebral amyloidosis in the pathogenesis of AD.

  20. Improvement of Insulin Secretion and Pancreatic β-cell Function in Streptozotocin-induced Diabetic Rats Treated with Aloe vera Extract.

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    Noor, Ayesha; Gunasekaran, S; Vijayalakshmi, M A

    2017-12-01

    Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Plant extracts and their products are being used as an alternative system of medicine for the treatment of diabetes. Aloe vera has been traditionally used to treat several diseases and it exhibits antioxidant, anti-inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar diabetic rats were used in this study to understand the potential protective effect of A. vera extract on the pancreatic islets. The aim of the present study was to evaluate the A. vera extract on improvement of insulin secretion and pancreatic β-cell function by morphometric analysis of pancreatic islets in STZ-induced diabetic Wistar rats. After acclimatization, male Wistar rats, maintained as per the Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines, were randomly divided into four groups of six rats each. Fasting plasma glucose and insulin levels were assessed. The effect of A. vera extract in STZ-induced diabetic rats on the pancreatic islets by morphometric analysis was evaluated. Oral administration of A. vera extract (300 mg/kg) daily to diabetic rats for 3 weeks showed restoration of blood glucose levels to normal levels with a concomitant increase in insulin levels upon feeding with A. vera extract in STZ-induced diabetic rats. Morphometric analysis of pancreatic sections revealed quantitative and qualitative gain in terms of number, diameter, volume, and area of the pancreatic islets of diabetic rats treated with A. vera extract when compared to the untreated diabetic rats. A. vera extract exerts antidiabetic effects by improving insulin secretion and pancreatic β-cell function by restoring pancreatic islet mass in STZ-induced diabetic Wistar rats. Fasting plasma glucose (FPG) and insulin levels were restored to normal levels in diabetic rats treated with Aloe vera extractIslets of pancreas were qualitatively and quantitatively restored to

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

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    Lotfipour, Shahrdad; Smith, Maree T

    2018-01-01

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

  2. Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

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    Singh, Gurpreet; Sharma, Bhupesh; Jaggi, Amteshwar Singh; Singh, Nirmal

    2014-09-01

    The study was designed to investigate the efficacy of bosentan a dual endothelin (ETA and ETB) receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia. Diabetes was induced in rats by administration of a single dose (50mg/kg, i.p.) of streptozotocin (STZ). Drug treatment was started after 1 month of STZ administration and treatment was continued until the end of the study. Morris water maze (MWM) test was employed for testing spatial learning and memory. Endothelial function was measured on isolated aortic rings using student physiograph. Serum glucose, body weight, serum nitrite/nitrate, brain thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH) levels, and brain acetylcholinesterase activity were also tested. STZ treatment resulted in significant development of cognitive and vascular endothelial deficits, manifested in the terms of endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate levels along with increase in serum glucose, brain acetylcholinesterase activity, TBARS, and decreased GSH levels. Treatment of bosentan attenuated diabetes induced impairment of learning, memory, endothelial function, and various biochemical parameters. It may be concluded that bosentan has shown efficacy in STZ induced cognitive and vascular endothelial deficits. Thus, endothelin receptors can be considered as a potential pharmacological target for the management of experimental diabetes induced vascular endothelial dysfunction and associated dementia. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. ADMA reduction does not protect mice with streptozotocin-induced diabetes mellitus from development of diabetic nephropathy.

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    Rodionov, Roman N; Heinrich, Annett; Brilloff, Silke; Jarzebska, Natalia; Martens-Lobenhoffer, Jens; Bode-Böger, Stefanie M; Todorov, Vladimir T; Hugo, Christian P M; Weiss, Norbert; Hohenstein, Bernd

    2017-11-01

    Cardiovascular disease is the major cause of morbidity and mortality in the world. Diabetes and its complications, such as diabetic nephropathy, dramatically increase cardiovascular risk. Association studies suggest that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, plays a role in the pathogenesis of diabetic nephropathy. The major pathway of ADMA catabolism is hydrolysis by dimethylarginine dimethylaminohydrolase 1 (DDAH1). The goal of this study was to test the hypothesis that lowering ADMA by overexpression of DDAH1 protects from development of diabetic nephropathy. Diabetes was induced with streptozotocin (STZ) in wild type and DDAH1 transgenic mice. Healthy mice served as controls. Mice were sacrificed after 20 weeks of diabetes. ADMA levels were assessed by isotope-dilution tandem mass spectrometry, creatinine by standard laboratory methods and albumin by ELISA. Kidney tissues were stained for markers of glomerular cells, cell matrix, inflammation and cell proliferation. STZ led to development of diabetes in all injected mice. Transgenic overexpression of DDAH1 led to a decrease in plasma ADMA levels in healthy animals. Diabetic state itself did not lead to elevation of plasma ADMA levels. Diabetic mice of both genotypes developed albuminuria (27 and 25 vs. 9 and 6 μg albumin/mg creatinine) (p diabetes led to the development of early features of diabetic nephropathy. Overexpression of DDAH1 and lowering of systemic ADMA levels did not prevent these changes, indicating that ADMA is not the major mediator of the early diabetic changes reflected by this experimental model. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Inhibiting microRNA-144 abates oxidative stress and reduces apoptosis in hearts of streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Yu, Manli; Liu, Yu; Zhang, Bili; Shi, Yicheng; Cui, Ling; Zhao, Xianxian

    2015-01-01

    Hyperglycemia-induced reactive oxygen species (ROS) generation contributes to the development of diabetic cardiomyopathy. However, little is known about the role of microRNAs in the regulation of ROS formation and myocardial apoptosis in streptozotocin (STZ)-induced diabetic mice. It was observed that microRNA-144 (miR-144) level was lower in heart tissues of STZ-induced diabetic mice. High glucose exposure also reduced miR-144 levels in cultured cardiomyocytes. Moreover, miR-144 modulated high glucose-induced oxidative stress in cultured cardiomyocytes by directly targeting nuclear factor-erythroid 2-related factor 2 (Nrf2), which was a central regulator of cellular response to oxidative stress. The miR-144 mimics aggravated high glucose-induced ROS formation and apoptosis in cardiomyocytes, which could be attenuated by treatment with Dh404, an activator of Nrf2. Meanwhile, inhibition of miR-144 suppressed ROS formation and apoptosis induced by high glucose in cultured cardiomyocytes. What was more important is that reduced myocardial oxidative stress and apoptosis and improved cardiac function were identified in STZ-induced diabetic mice when treated with miR-144 antagomir. Although miR-144 cannot explain the increased oxidative stress in STZ, therapeutic interventions directed at decreasing miR-144 may help to decrease oxidative stress in these hearts. Inhibition of miR-144 might have clinical potential to abate oxidative stress as well as to reduce cardiomyocyte apoptosis and improve cardiac function in diabetic cardiomyopathy. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-08-01

    Diabetes is associated with long-term complications in the brain and reduced cognitive ability. Vitamin D3 (VD3 ) appears to be involved in the amelioration of hyperglycaemia in streptozotocin (STZ)-induced diabetic rats. Our aim was to analyse the potential of VD3 in avoiding brain damage through evaluation of acetylcholinesterase (AChE), Na(+) K(+) -adenosine triphosphatase (ATPase) and delta aminolevulinate dehydratase (δ-ALA-D) activities and thiobarbituric acid reactive substance (TBARS) levels from cerebral cortex, as well as memory in STZ-induced diabetic rats. Animals were divided into eight groups (n = 5): control/saline, control/metformin (Metf), control/VD3 , control/Metf + VD3 , diabetic/saline, diabetic/Metf, diabetic/VD3 and diabetic/Metf + VD3 . Thirty days after treatment, animals were submitted to contextual fear-conditioning and open-field behavioural tests, after which they were sacrificed and the cerebral cortex was dissected. Our results demonstrate a significant memory deficit, an increase in AChE activity and TBARS levels and a decrease in δ-ALA-D and Na(+) K(+) -ATPase activities in diabetic rats when compared with the controls. Treatment of diabetic rats with Metf and VD3 prevented the increase in AChE activity when compared with the diabetic/saline group. In treated diabetic rats, the decrease in Na(+) K(+) -ATPase was reverted when compared with non-treated rats, but the increase in δ-ALA-D activity was not. VD3 prevented diabetes-induced TBARS level and improved memory. Our results show that VD3 can avoid cognitive deficit through prevention of changes in important enzymes such as Na(+) K(+) -ATPase and AChE in cerebral cortex in type 1 diabetic rats. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Zanthoxylum alkylamides activate phosphorylated AMPK and ameliorate glycolipid metabolism in the streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Ren, Tingyuan; Zhu, Yuping; Kan, Jianquan

    2017-01-01

    This study aimed to evaluate the effects of Zanthoxylum alkylamides on the glycolipid metabolism of rats with streptozotocin (STZ)-induced diabetes. Diabetic rats were given daily oral treatments of 2, 4, or 8 mg/kg bw alkylamides for 28 days. Alkylamides significantly decreased fasting blood glucose and fructosamine content, as well as relieved organ enlargement caused by diabetes. The serum and liver triglyceride, malondialdehyde, and free fatty-acid contents of rats with STZ-induced diabetes were significantly reduced. Total cholesterol in the liver also significantly decreased. Quantitative polymerase chain reaction (Q-PCR) and Western blot detected insignificantly increased (P > 0.05) mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK) in the skeletal muscle of diabetic rats. However, AMPK and p-AMPK (Thr172) protein expression levels significantly increased. The mRNA and protein expression levels of silencing information regulator 1 significantly increased. The mRNA expression levels of acetyl-CoA-carboxylase (ACC) and protein p-ACC (Ser79) also increased. The mRNA and protein expression levels of glucose transporter type 4 (GLUT4) were significantly upregulated in the skeletal muscle cell membranes of diabetic rats. Results indicated that alkylamides activated the AMPK-signaling pathway. Thus, inhibiting ACC activity reduced fatty-acid synthesis. The rapid translocation of GLUT4 mediated increased glucose transport rate and reduced blood glucose. Therefore, alkylamides can ameliorate glucose and lipid metabolism disorders in diabetic rats by activating the AMPK pathway.

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

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    Subbuswamy K. Prabu

    2011-05-01

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

  8. GABAergic effect of valeric acid from Valeriana wallichii in amelioration of ICV STZ induced dementia in rats

    Directory of Open Access Journals (Sweden)

    Shilpa Vishwakarma

    Full Text Available ABSTRACT Valeriana wallichii DC., Caprifoliaceae, is used to have anti-ulcer, anti-spasmodic, anti-epileptic, memory enhancer, anti-anxiety, anti-rheumatic, sedative, anti-asthmatic and diuretic activities. V. wallichii is reported to contain valpotriates, valeric acid, valerenic acid, valechlorine, valerianine, resins and alkaloids. Valeric acid, found in V. wallichii appears similar in structure to the neurotransmitter GABA. Valeric acid also acts as an NMDA-receptor antagonist. The aim of present study was to investigate the neuroprotective effect of V. wallichii containing valeric acid and its possible mechanism of action in amelioration of intracerebroventricular streptozotocin induced neurodegeneration in Wistar rats. The rhizomes of V. wallichii were powdered coarsely and extracted by percolation method using dichloromethane. Wistar rats (220–250 g of either sex were divided into 5 groups, comprising 6 animals each. Valeric acid was isolated from plant extract and characterized using FT-IR. Picrotoxin (2 mg/kg was used as GABA-A antagonist. Intracerebroventricular streptozotocin administration caused significant (p < 0.05 increase in escape latency, retention transfer latency on morris water maze on 17th, 18th, 19th and 20th day and elevated plus maze on 19th and 20th day respectively, as compared to normal untreated rats. Treatment with V. wallichii extract 100 and 200 mg/kg and valeric acid 20 and 40 mg/kg significantly decreased the escape latency and retention transfer latency, as compared to intracerebroventricular-streptozotocin group. Plant extract and valeric acid also decreased the level of lipid peroxidation and restored glutathione level in rat brains. Administration of picrotoxin significantly reversed the effects produced by plant extract and valeric acid in intracerebroventricular-streptozotocin treated rats. The findings may conclude that valeric acid present in V. wallichii has significant GABAergic effect in

  9. Effect of Commiphora mukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats.

    Science.gov (United States)

    Ramesh, B; Karuna, R; Sreenivasa, Reddy S; Haritha, K; Sai, Mangala D; Sasi, Bhusana Rao B; Saralakumari, D

    2012-11-01

    To study the antioxidant efficacy of Commiphora mukul (C. mukul) gum resin ethanolic extract in streptozotocin (STZ) induced diabetic rats. THE MALE WISTAR ALBINO RATS WERE RANDOMLY DIVIDED INTO FOUR GROUPS OF EIGHT ANIMALS EACH: Control group (C), CM-treated control group (C+CMEE), Diabetic control group (D), CM- treated diabetic group (D+CMEE). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg/ bwt). After being confirmed the diabetic rats were treated with C. mukul gum resin ethanolic extract (CMEE) for 60 days. The biochemical estimations like antioxidant, oxidative stress marker enzymes and hepatic marker enzymes of tissues were performed. The diabetic rats showed increased level of enzymatic activities aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) in liver and kidney and oxidative markers like lipid peroxidation (LPO) and protein oxidation (PO) in pancreas and heart. Antioxidant enzyme activities were significantly decreased in the pancreas and heart compared to control group. Administration of CMEE (200 mg/kg bw) to diabetic rats for 60 days significantly reversed the above parameters towards normalcy. In conclusion, our data indicate the preventive role of C. mukul against STZ-induced diabetic oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of diabetes and aggravated antioxidant status.

  10. Effect of traditional plant medicines (Cinnamomum zeylanicum and Syzygium cumini on oxidative stress and insulin resistance in streptozotocin-induced diabetic rats

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    Khaled Sharafeldin

    2015-10-01

    Both CZ and SC possessed antioxidant activity as shown by elevated SOD and GPx activities and reduction in LPO. CZ and SC are functioning to improve the level of insulin, hyperglycemia, hyperlipidemia, oxidative stress and kidney and liver dysfunctions in STZ-induced diabetic rats.

  11. Effect of aqueous and alcoholic extract of Sesbania sesban (Linn Merr. root on glycemic control in streptozotocin-induced diabetic mice

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    Manjusha Choudhary

    2014-01-01

    Full Text Available Aim: The present study was carried out to investigate the hypoglycemic effects of the aqueous and ethanolic extracts of Sesbania sesban (SS (Merr. roots, which is widely used in inflammation, fever, ulcers, leucoderma and diabetes in various parts of India. Materials and Methods: SS extracts were administered orally at doses (500 and 1000 mg/kg to normal and streptozotocin (STZ induced Type-2 diabetic mice. The fasting blood glucose (FBG, biochemical parameters in serum viz., blood glucose, serum insulin, cholesterol, triglyceride (TG, high-density lipoprotein (HDL cholesterol, urea, creatinine and total protein, change in body weight, internal organs weight, food intake, water intake and glycogen level in liver were performed for the evaluation of hypoglycemic effects. Results: Both doses of aqueous and ethanolic SS extracts caused a marked decrease of FBG in STZ induced Type-2 diabetic mice. Both extracts decreased the cholesterol, TG, urea, creatinine level and increased the insulin, HDL cholesterol and total protein level. Decrease in body weight and glycogen level induced by STZ was restored. Increase in water and food intake induced by STZ was decreased. Conclusions: The results suggest that aqueous and ethanolic extracts of SS may have hypoglycemic potential for the Type-2 diabetes and support the traditional use of the roots of plant as a hypoglycemic agent.

  12. Protective effect of rosmarinic acid against oxidative stress biomarkers in liver and kidney of strepotozotocin-induced diabetic rats.

    Science.gov (United States)

    Mushtaq, Nadia; Schmatz, Roberta; Ahmed, Mushtaq; Pereira, Luciane Belmonte; da Costa, Pauline; Reichert, Karine Paula; Dalenogare, Diéssica; Pelinson, Luana Paula; Vieira, Juliano Marchi; Stefanello, Naiara; de Oliveira, Lizielle Souza; Mulinacci, Nadia; Bellumori, Maria; Morsch, Vera Maria; Schetinger, Maria Rosa

    2015-12-01

    In the present study, we investigated the efficiency of rosmarinic acid (RA) in preventing the alteration of oxidative parameters in the liver and kidney of diabetic rats induced by streptozotocin (STZ). The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol, and diabetic/RA 10 mg/kg. After 3 weeks of treatment, we found that TBARS levels in liver and kidney were significantly increased in the diabetic/saline group and the administration of RA prevented this increase in the liver and kidney (P < 0.05). Diabetes caused a significant decrease in the activity of superoxide dismutase (SOD) and catalase (CAT) in the diabetes/saline group (P < 0.05). However, the treatment with 10 mg/kg RA (antioxidant) prevented this alteration in SOD and CAT activity in the diabetic RA group (P < 0.05). In addition, RA reverses the decrease in ascorbic acid and non-protein-thiol (NPSH) levels in diabetic rats. The treatment with RA also prevented the decrease in the Delta-aminolevulinic acid dehydratase (ALA-D) activity in the liver and kidney of diabetic rats. Furthermore, RA did not have any effect on glycemic levels. These results indicate that RA effectively reduced the oxidative stress induced by STZ, suggesting that RA is a potential candidate for the prevention and treatment of pathological conditions in diabetic models.

  13. The Antioxidant Potential of Azadirachta indica Ameliorates Cardioprotection Following Diabetic Mellitus-Induced Microangiopathy.

    Science.gov (United States)

    Gupta, Naveen Kumar; Srivastva, Nidhi; Bubber, Parvesh; Puri, Sanjeev

    2016-05-01

    Cardiac complications associated with diabetes mellitus have become major cause of concern. Antidiabetic drugs, with varied mode of action, are although available, apprehensions exist for their limited action or side effects upon prolonged use. Efforts are therefore inclined toward finding other alternatives. The present study was, thus, undertaken to evaluate the cardioprotective effect of Azadirachta indica (AI) on microangiopathic changes in rat model of diabetes. Diabetes was induced in male rats by single intraperitoneal injection of streptozotocin (60 mg/kg body weight). Seven days after glucose levels are stabilized, aqueous leaf extract of AI (ALE) (600 mg/kg(1) body weight) was administered orally to diabetic animals every day for 7 days. High blood glucose characterizing diabetes in these animals was found to show increased lipid peroxidation (LPO), altered antioxidant biomarkers together with microangiopathic alterations. The treatment of diabetic rats with ALE reduced the levels of blood glucose, LPO, and restored the activities of antioxidant enzyme. Light and transmission electron microscopic analysis revealed reduced necrotic areas and inflammation in tissue architecture of ALE treated heart in comparison to untreated diabetic group. AI provides cardioprotection by ameliorating oxidative stress in rat model of diabetic mellitus. The streptozotocin (STZ) treatment (60 mg/kg body weight) to animals induced diabetic changes such as elevated blood glucose levels, decreased body weight, altered lipid profiles together with development of proxidant state evidenced by elevated levels of lipid peroxidation (LPO), depletion in reduced glutathione (GSH) levels and altered antioxidant enzymes with consequent microangiopathic alterations in heart tissue evinced by localization of necrotic and inflamed areas in heart tissueThe treatment of animals with Azadirachta indica leaf extract (ALE) (600 mg/kg body weight) post-STZ treatment significantly reversed the

  14. Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition

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    Ruangvejvorachai Preecha

    2010-10-01

    Full Text Available Abstract Background Curcumin, an Asian spice and food-coloring agent, is known for its anti-oxidant properties. We propose that curcumin can improve diabetes-induced endothelial dysfunction through superoxide reduction. Methods Diabetes (DM was induced in rats by streptozotocin (STZ. Daily curcumin oral feeding was started six weeks after the STZ injection. Twelve weeks after STZ injection, mesenteric arteriolar responses were recorded in real time using intravital fluorescence videomicroscopy. Superoxide and vascular protein kinase C (PKC-βII were examined by hydroethidine and immunofluorescence, respectively. Results The dilatory response to acetylcholine (ACh significantly decreased in DM arterioles as compared to control arterioles. There was no difference among groups when sodium nitroprusside (SNP was used. ACh responses were significantly improved by both low and high doses (30 and 300 mg/kg, respectively of curcumin supplementation. An oxygen radical-sensitive fluorescent probe, hydroethidine, was used to detect intracellular superoxide anion (O2●- production. O2●- production was markedly increased in DM arterioles, but it was significantly reduced by supplementation of either low or high doses of curcumin. In addition, with a high dose of curcumin, diabetes-induced vascular PKC-βII expression was diminished. Conclusion Therefore, it is suggested that curcumin supplementation could improve diabetes-induced endothelial dysfunction significantly in relation to its potential to decrease superoxide production and PKC inhibition.

  15. Antidiabetic and antihyperlipidemic activities of Forsythia suspensa (Thunb.) Vahl (fruit) in streptozotocin-induced diabetes mice.

    Science.gov (United States)

    Zhang, Yanyan; Feng, Fu; Chen, Ting; Li, Zhongwen; Shen, Qingwu W

    2016-11-04

    The fruit of Forsythia suspense (Thunb.) Vahl, a well-known Chinese Materia Medica, has been traditionally used in traditional Chinese medicine for the treatment of diabetes and some other diseases, but the rational for the usage of this plant is unclear. The aim of this study was to investigate the therapeutic effect and potential mechanism of the fruit of F. suspensa using streptozotocin (STZ)-induced diabetic mice. Crude methanol extract of F. suspense fruit was fractionated with different solvents and the ethyl acetate fraction (EAF) was selected for in vivo studies based on the in vitro α-amylase and HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl coenzyme A) inhibiting activities. For in vivo study, diabetes mellitus was induced in mice with STZ. Diabetic mice were orally administrated with 50, 100 and 200mg/kg body weight of EAF for 4 weeks. Mouse body weight, blood glucose, glucose tolerance, biochemical parameters and gene expression related to pancreas and liver function were analyzed after EAF administration. After 4 weeks of EAF intervention, a significant decrease in blood glucose, triglyceride, creatinine total cholesterol, acid phosphatase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and hepatic lipid (triglycerides and cholesterol) content as well as a significant increase in body weight, insulin secretion and glucose tolerance was observed in EAF treated diabetic mice. qRT-PCR analysis revealed that EAF antagonized STZ-induced alteration of the expression of rate-limiting enzymes (glucokinase and phosphorenolpyruvate carboxykinase) in liver and insulin secretion related genes insulin-1, insulin-2 and duodenal homeobox factor-1 in pancreas. The ethyl acetate extract of Forsythia suspense (Thunb.) Vahl fruit has potency to develop an antihyperglycemic and antihyperlipidemic agent for the treatment of diabetes mellitus via modulation of oxidative stress, the hepatic glucose metabolism and pancreatic insulin secretion. Copyright

  16. Anti-diabetic and anti-oxidant potential of aged garlic extract (AGE) in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Thomson, Martha; Al-Qattan, Khaled K; Js, Divya; Ali, Muslim

    2016-01-19

    Although aged garlic extract (AGE) shares some active components with fresh garlic and in spite of its palatability and milder side effects, the anti-diabetic and related anti-oxidant properties of AGE have not been investigated extensively, and the reported findings are inconsistent. This study investigated the anti-diabetic effects of 3 incremental doses of AGE in streptozotocin (STZ)-induced diabetic rats (fasting blood sugar > 20 mM). Diabetic rats were divided into a control diabetic group (CD) and AGE-treated diabetic group (AGE-D). The AGE-D was divided into 3 groups and accordingly treated with AGE i.p. at 100, 300 and 600 mg/kg daily for 8 weeks. A control normal group (CN) was also included for reference. Compared to the CN group, the CD group showed significant loss of body weight (over 50 %); and decreased serum insulin concentration (10 fold) and total anti-oxidant level and catalase activity (45-70 %) in serum, kidney and liver. Conversely, the CD rats had an elevated blood glucose (nearly 4 fold), serum cholesterol (nearly 2 fold) and triglycerides (>2 fold), erythrocyte glycated hemoglobin (GHb, 3 fold) and kidney and liver lipid peroxidation (MDA levels). Treatment with AGE positively reversed the diabetic changes in the targeted parameters to levels significantly lower than those measured in the CD group and the degrees of attenuation were almost dose dependent especially with the two higher doses. AGE exhibits a dose-dependent ameliorative action on indicators of diabetes in STZ-induced diabetic rats.

  17. Alleviating effects of morin against experimentally-induced diabetic osteopenia

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    Abuohashish Hatem M

    2013-02-01

    Full Text Available Abstract Background Plant flavonoids are emerging as potent therapeutic drugs effective against a wide range of aging diseases particularly bone metabolic disorders. Morin (3,5,7,20,40-pentahydroxyflavone, a member of flavonols, is an important bioactive compound by interacting with nucleic acids, enzymes and protein. The present study was designed to investigate the putative beneficial effect of morin on diabetic osteopenia in rats. Methods Streptozotocin (STZ-induced diabetic model was used by considering 300 mg/dl fasting glucose level as diabetic. Morin (15 and 30 mg/kg was treated for five consecutive weeks to diabetic rats. Serum levels of glucose, insulin, deoxypyridinoline cross links (DPD, osteocalcin (OC, bone specific alkaline phosphatase (BALP, telopeptides of collagen type I (CTX, interleukin 1 beta (IL-1β, interleukin 6 (IL-6, tumor necrosis factor alpha (TNF-α, thiobarbituric acid reactive substance (TBARS and reduced glutathione (GSH were estimated. Femoral bones were taken for micro CT scan to measure trabecular bone mineral density (BMD and other morphometric parameters. Results Significant bone loss was documented as the level of bone turnover parameters including DPD, OC, BALP and CTX were increased in serum of diabetic rats. Morin treatment significantly attenuated these elevated levels. Bone micro-CT scan of diabetic rats showed a significant impairment in trabecular bone microarchitecture, density and other morphometric parameters. These impairments were significantly ameliorated by morin administration. Serum levels of glucose, TBARS, IL-1β, IL-6 and TNF-α were significantly elevated, while the level of insulin and GSH was decreased in diabetic rats. These serum changes in diabetic rats were bring back to normal values after 5 weeks morin treatment. Conclusion These findings revealed the protective effect of morin against diabetic induced osteopenia. We believed that this effect is through its both the anti

  18. Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats.

    Science.gov (United States)

    Hofni, Amal; El-Moselhy, Mohamed A; Taye, Ashraf; Khalifa, Mohamed M

    2014-12-05

    Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg). The diabetic rats were orally treated with spironolactone (50 mg/kg/day) and/or candesartan (1 mg/kg/day) for 8 weeks. Administration of STZ caused a marked elevation in the serum level of creatinine, urea and urinary albumin-creatinine ratio (ACR). This was associated with upregulated renal protein levels of nuclear factor-kappa B (NF-κB), transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) alongside increasing the renal superoxide anion (O2(-)) production, malondialdehyde (MDA) level and the systolic blood pressure. There was a marked decrease in nitric oxide (NO) bioavailability and antioxidant enzyme capacity. The combined therapy of spironolactone and candesartan significantly normalized the oxidative stress and fibrotic/inflammatory alterations. Additionally, the elevated blood pressure was attenuated by administration of candesartan alone or in combination. This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy. In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice

    Science.gov (United States)

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P. R.

    2016-01-01

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin−Sca-1+cKit+ (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10–12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P mobilization by G-CSF or AMD3100 was either increased or unaffected (P mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy. PMID:27188595

  20. Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy.

    Science.gov (United States)

    Brouwers, Bas; Pruniau, Vincent P E G; Cauwelier, Elisa J G; Schuit, Frans; Lerut, Evelyne; Ectors, Nadine; Declercq, Jeroen; Creemers, John W M

    2013-09-20

    Streptozotocin (STZ) is widely used as diabetogenic agent in animal models for diabetic nephropathy (DN). However, it is also directly cytotoxic to kidneys, making it difficult to distinguish between DN-related and STZ-induced nephropathy. Therefore, an improved protocol to generate mice for DN studies, with a quick and robust achievement of the diabetic state, without direct kidney toxicity is required. To investigate the mechanism leading to STZ-induced nephropathy, kidney damage was induced with a high dose of STZ. This resulted in delayed gastric emptying, at least partially caused by impaired desacyl ghrelin clearance. STZ uptake in the kidneys is to a large extent mediated by the sodium/glucose cotransporters (Sglts) because the Sglt inhibitor phlorizin could reduce STZ uptake in the kidneys. Consequently, the direct toxic effects in the kidney and the gastric dilatation were resolved without interfering with the β-cell toxicity. Furthermore, pancreatic STZ uptake was increased, hereby decreasing the threshold for β-cell toxicity, allowing for single low non-nephrotoxic STZ doses (70 mg/kg). In conclusion, this study provides novel insights into the mechanism of STZ toxicity in kidneys and suggests a more efficient regime to induce DN with little or no toxic side effects.

  1. Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Srinivasan, Subramani; Sathish, Gajendren; Jayanthi, Mahadevan; Muthukumaran, Jayachandran; Muruganathan, Udaiyar; Ramachandran, Vinayagam

    2014-01-01

    Epidemiological studies have demonstrated that diabetes mellitus is a serious health burden for both governments and healthcare providers. This study was hypothesized to evaluate the antihyperglycemic potential of eugenol by determine the activities of key enzymes of glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg body weight (b.w.)). Eugenol was administered to diabetic rats intragastrically at 2.5, 5, and 10 mg/kg b.w. for 30 days. The dose 10 mg/kg b.w. significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and liver marker enzymes (AST, ALT, and ALP), creatine kinase and blood urea nitrogen in serum and blood of diabetic rats were significantly reverted to near normal levels by the administration of eugenol. Further, eugenol administration to diabetic rats improved body weight and hepatic glycogen content demonstrated the antihyperglycemic potential of eugenol in diabetic rats. The present findings suggest that eugenol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes, and it is sensible to broaden the scale of use of eugenol in a trial to alleviate the adverse effects of diabetes.

  2. The Hypoglycemic, Hypolipidemic, and Anti-Diabetic Nephritic Activities of Zeaxanthin in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats.

    Science.gov (United States)

    Kou, Ling; Du, Mingzhao; Zhang, Chaopu; Dai, Zhiyin; Li, Xuan; Zhang, Baohai

    2017-07-01

    Zeaxanthin (ZA), an important compound found in Lycium barbarum, shows various pharmacodynamic effects. In our present study, a high-fat, high-sucrose diet and streptozotocin (STZ)-induced diabetic rat model was used to investigate the antidiabetic activities of ZA. After a 4-week administration of 200 and 400 mg/kg of ZA and 100 mg/kg of metformin hydrochloride, various blood biochemical indexes were detected. ZA strongly normalized the reduced bodyweight and enhanced fasting blood glucose in diabetic rats. The positive data obtained from the oral glucose tolerance test further confirmed its antidiabetic effects. ZA displayed significant hypolipidemic activities indicated by its modulation of serum levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. The antidiabetic nephropathy of ZA was confirmed by its regulation of pathological kidney structures, urine levels of n-acetyl-β-d-glucosaminidase and albuminuria, and serum levels of urea nitrogen. ZA inhibited the serum levels of inflammatory factors including interleukin-2 (IL-2), IL-6, tumor necrosis factor-α, and nuclear factor kappa B, further confirming its renal protection. Moreover, the serum imbalances in superoxide dismutase, glutathione peroxidase, methane dicarboxylic aldehyde, and catalase were normalized by ZA, suggesting its antioxidant properties. Altogether, ZA produced hypoglycemic, hypolipidemic, and antidiabetic nephritic effects in a diet-STZ-induced diabetic rat model.

  3. Brain aging and AD-like pathology in streptozotocin-induced diabetic rats.

    Science.gov (United States)

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

    2014-01-01

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

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

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    Jian-Qin Wang

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    OpenAIRE

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

    2013-01-01

    PURPOSE: Recent reports suggest that the hypoglycaemic effects of the triterpenes involve inhibition of glucose transport in the small intestine. Therefore, the effects of Syzygium spp-derived triterpenes oleanolic acid (OA) and maslinic acid (MA) were evaluated on carbohydrate hydrolyzing enzymes in STZ-induced diabetic rats and consequences on postprandial hyperglycaemia after carbohydrate loading. METHODS: We determined using Western blot analysis the expressions of α-amylase and α-glucosi...

  7. Effects of alpha-tocopherol on gingival expression of inducible nitric ...

    African Journals Online (AJOL)

    2015-09-01

    or insulin on the number of gingival inducible nitric oxide synthase (iNOS) positive cells in rats with experimental periodontitis with or without streptozotocin (STZ)-induced diabetes. Materials and Methods: A total of 60 ...

  8. Potential antidiabetic and hypolipidemic effects of propolis extract in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    El-Sayed, El-Sayed M; Abo-Salem, Osama M; Aly, Hamdy A; Mansour, Ahmed M

    2009-04-01

    Free radicals have been implicated in the pathogenesis of diabetes mellitus leading to various complications including atherosclerosis. Propolis was reported to have oxygen radical scavenging activity. The present study was designed to investigate the possible antidiabetic, hypolipidemic and antioxidant effects of ethanolic extract of propolis (EEP). Type capital I, Ukrainian diabetes was induced in rats by injection of streptozotocin (STZ) in a dose of 60 mg/kg bwt, i.p. for 3 consecutive days. After 5 weeks of STZ injection, there were an apparent reduction in the animal body weight amounting to 21% and significant increases in serum glucose (184%), triglycerides (63%), total cholesterol (43%) and low density lipoprotein-cholesterol (LDL-C) (148%) with a concomitant decrease in serum high density lipoprotein-cholesterol (HDL-C) (51%) as compared to the control normal group. In addition, there was significant elevation in pancreatic lipid peroxides measured as malondialdehyde (MDA) and serum nitric oxide (NO) amounting to 185% and 224%, respectively with marked reduction in serum reduced glutathione (GSH) and catalase (CAT) (66% and 31%, respectively) and pancreatic superoxide dismutase (SOD) (54%) in STZ-treated rats. On the other hand, oral daily treatment of animals with EEP in a dose of 200 mg/kg bwt for a period of 5 weeks ameliorated STZ-induced alterations in the animal body weight as well as in serum glucose, lipids, lipoproteins, NO, GSH & CAT and pancreatic MDA & SOD. In conclusion, propolis extract offers promising antidiabetic and hypolipidemic effects that may be mainly attributed to its potent antioxidant potential. Further studies will be needed in future in order to determine which one(or more) of its active constituents has the main antidiabetic and hypolipidemic effects.

  9. Chronic Inhibition of PDE5 Limits Pro-Inflammatory Monocyte-Macrophage Polarization in Streptozotocin-Induced Diabetic Mice.

    Directory of Open Access Journals (Sweden)

    Mary Anna Venneri

    Full Text Available Diabetes mellitus is characterized by changes in endothelial cells that alter monocyte recruitment, increase classic (M1-type tissue macrophage infiltration and lead to self-sustained inflammation. Our and other groups recently showed that chronic inhibition of phosphodiesterase-5 (PDE5i affects circulating cytokine levels in patients with diabetes; whether PDE5i also affects circulating monocytes and tissue inflammatory cell infiltration remains to be established. Using murine streptozotocin (STZ-induced diabetes and in human vitro cell-cell adhesion models we show that chronic hyperglycemia induces changes in myeloid and endothelial cells that alter monocyte recruitment and lead to self-sustained inflammation. Continuous PDE5i with sildenafil (SILD expanded tissue anti-inflammatory TIE2-expressing monocytes (TEMs, which are known to limit inflammation and promote tissue repair. Specifically, SILD: 1 normalizes the frequency of circulating pro-inflammatory monocytes triggered by hyperglycemia (53.7 ± 7.9% of CD11b+Gr-1+ cells in STZ vs. 30.4 ± 8.3% in STZ+SILD and 27.1 ± 1.6% in CTRL, P<0.01; 2 prevents STZ-induced tissue inflammatory infiltration (4-fold increase in F4/80+ macrophages in diabetic vs. control mice by increasing renal and heart anti-inflammatory TEMs (30.9 ± 3.6% in STZ+SILD vs. 6.9 ± 2.7% in STZ, P <0.01, and 11.6 ± 2.9% in CTRL mice; 3 reduces vascular inflammatory proteins (iNOS, COX2, VCAM-1 promoting tissue protection; 4 lowers monocyte adhesion to human endothelial cells in vitro through the TIE2 receptor. All these changes occurred independently from changes of glycemic status. In summary, we demonstrate that circulating renal and cardiac TEMs are defective in chronic hyperglycemia and that SILD normalizes their levels by facilitating the shift from classic (M1-like to alternative (M2-like/TEM macrophage polarization. Restoration of tissue TEMs with PDE5i could represent an additional pharmacological tool to prevent

  10. Anti-Diabetic Potential of the Leaves of Anisomeles malabarica in Streptozotocin Induced Diabetic Rats.

    Science.gov (United States)

    Kotha, Peddanna; Badri, Kameswara Rao; Nagalapuram, Ramya; Allagadda, Rajasekhar; Chippada, Appa Rao

    2017-01-01

    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. 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. 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. The results of our study suggest that Anisomeles malabarica has potential anti-diabetic activity in STZ induced diabetic rats. © 2017 The Author(s). Published by S. Karger AG, Basel.

  11. Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats

    Science.gov (United States)

    Aseer, Kanikkai Raja; Kim, Sang Woo; Choi, Myung-Sook; Yun, Jong Won

    2015-01-01

    Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels. PMID:26110898

  12. The Antidiabetic Activity of Curry Leaves “Murraya Koenigii” on the Glucose Levels, Kidneys, and Islets of Langerhans of Rats with Streptozotocin Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Imad M Al-Ani

    2017-08-01

    Full Text Available Background: The aims of this study were to explore the antihyperglycemic effect of curry leaves, Murraya koenigii "MK" aqueous extract, and to examine its possible protective effects on the islets of Langerhans and kidneys of streptozotocin (STZ diabetic rats. Methods: Thirty healthy adult male Sprague Dawley rats were randomized into five groups (n=6; normal control, normal treated with "MK" control, diabetic control (non-treated with "MK", diabetic treated with 200 mg/kg MK aqueous leaf extract and diabetic treated with 400 mg/kg MK aqueous leaf extract. Blood glucose levels and body weight were monitored gravimetrically. The animals were sacrificed on the 30th day; the kidney and pancreatic tissues were processed for histological studies. Results: The diabetic group showed considerable loss of body weight and increase in blood glucose levels and degeneration of the glomeruli and renal convoluted tubules and atrophied islets with disintegration of β-cells. Treatment of diabetic rats with MK extract showed significant (p < 0.001 improvement in blood glucose levels and body weight gain. The MK extract also caused an improvement in tissue injury induced by STZ injection in the kidney and islets of Langerhans. Conclusions: These findings highlighted the beneficial effects of MK aqueous extract against cellular oxidative damage in STZ-induced diabetic rats.

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

    National Research Council Canada - National Science Library

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

    2015-01-01

    .... Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats...

  14. Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats.

    Science.gov (United States)

    Qiu, Xuefeng; Lin, Haocheng; Wang, Yajing; Yu, Wen; Chen, Yun; Wang, Run; Dai, Yutian

    2011-02-01

    Erectile dysfunction (ED) is a frequent complication of diabetes mellitus. The efficacy of common ED therapies is low for diabetes-associated ED. To explore the effects of transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) on improving erectile function of streptozocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were injected either with STZ to induce diabetes or with citrate buffer as controls. Rat BM-MSCs were harvested and labeled with CM-DiI (Chloromethylbenzamido derivatives of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), and then transplanted into corporal cavernosum of STZ-induced diabetic rats. Four weeks after transplantation, all rats were analyzed for erectile function and penile histology. Erectile function was evaluated by the ratio between intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrostimulation of cavernous nerve. Fate of transplanted BM-MSCs was identified using immunofluorescence staining. Smooth muscle and endothelium in corpora cavernosum were assessed using immunohistochemistry. After BM-MSCs transplantation, the ICP/MAP ratio was increased significantly compared with diabetic controls. Content of smooth muscle and endothelium in corporal cavernosa of BM-MSCs transplanted rats was significantly increased compared to diabetic controls. Immunofluorescence analysis demonstrated that CM-DiI-labeled BM-MSCs could stay in corporal cavernosa for at least 4 weeks and some of them expressed von Willebrand Factor, CD31, calponin, or α-smooth muscle actin, cells markers for endothelial cells or smooth muscle cells, respectively. Intracavernous transplantation of BM-MSCs had beneficial effects on erectile function of diabetic rats and increased the content of endothelium and smooth muscle in corporal cavernosum. © 2010 International Society for Sexual Medicine.

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

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2013-08-01

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

  16. The Protective Effect of Hydroalcoholic Extract of Rosa canina (Dog Rose) Fruit on Liver Function and Structure in Streptozotocin-Induced Diabetes in Rats.

    Science.gov (United States)

    Taghizadeh, Mohsen; Rashidi, Ali Akbar; Taherian, Ali Akbar; Vakili, Zarichehr; Mehran, Mehdi

    2017-11-02

    This study was conducted to evaluate the hepatoprotective effects of Rosa canina (R. canina) extract on streptozotocin- (STZ-) induced diabetes in rats by measuring the fasting blood glucose (FBG), total antioxidant capacity (TAC), and liver enzyme activity, including serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Forty adult male Wistar rats were randomly divided into four groups and treated daily for 42 days as follows: group I (control) received saline as a vehicle; group II (diabetic) received saline; groups III and IV (diabetic) treated with 250 and 500 mg/kg body weight (BW) per day R. canina extract, respectively. Diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (50 mg/kg BW). At the end of the study, blood samples were collected via heart puncture and sera were used for estimation of the mentioned parameters. Then all the rats were sacrificed and their livers used for histopathological evaluations. In the untreated diabetic group, the results showed a significant increase in FBG, ALT, and AST levels compared to the other groups (p .05). In the treated groups, administration of R. canina extract significantly improved the mentioned parameters in a dose-dependent manner (p < .05). Histological evaluations indicated that R. canina extract ameliorated defective liver caused by STZ. It can be concluded that R. canina extract has a hepatoprotective effect in STZ-induced diabetes in rats.

  17. Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sagara, M; Satoh, J; Zhu, X P; Takahashi, K; Fukuzawa, M; Muto, G; Muto, Y; Toyota, T

    1994-06-01

    We previously reported that the in vivo production of the tumor necrosis factor alpha (TNF) was significantly enhanced after the onset of diabetes in spontaneous type 1 and 2 diabetic animals. In this report we confirmed the enhanced production of TNF in streptozotocin (STZ)-induced diabetes and then attempted to suppress the enhanced TNF production with N-acetylcysteine (NAC), a precursor of glutathione synthesis. The lipopolysaccharide-induced serum TNF activities were significantly enhanced in STZ-induced diabetic rats (6-18 weeks of age) compared with those of nondiabetic rats throughout the 12-week experiment. A single, oral administration of NAC (200 or 1000 mg/kg body wt) significantly suppressed the enhanced TNF production in the diabetic rats compared with that in untreated rats in a dose-dependent manner. On the other hand, in the long-term (6 or 12 weeks) administrations, smaller doses of NAC (50 or 200 mg/kg/day) also significantly inhibited the enhanced production of TNF regardless of the dose of NAC. NAC administration, however, did not suppress the TNF production of nondiabetic rats. The long-term NAC administration affected neither body weight nor levels of serum glucose, fructosamine, albumin, and triglyceride. These results show that NAC administration significantly suppressed the enhanced TNF production in diabetic rats and indicate that NAC might be useful in preventing TNF-mediated pathological conditions in diabetes.

  18. Influence of streptozotocin-induced diabetes in rats on the lithium content of tissue and the effect of dietary lithium supplements on this diabetic condition.

    Science.gov (United States)

    Hu, M; Wu, Y; Wu, H

    1999-05-01

    To study the effects of lithium supplementation on the diabetic condition, we measured the lithium concentration in the liver, kidney, and muscle from streptozotocin (STZ)-induced diabetic male Sprague-Dawley (SD) rats that were either treated or untreated with peroral lithium carbonate (0.3 mg/mL). The data showed that the lithium content of the liver and muscle was significantly lower in STZ rats than in normal control rats (0.22 +/- 0.05 v 1.30 +/- 0.15, P lithium carbonate supplementation, we found that (1) the lithium content of the liver and muscle returned to the normal range, (2) the extent of STZ-mediated destruction of beta cells in the pancreas decreased, (3) fasting blood glucose (FBG) and 2-hour postprandial blood glucose (PBG) decreased (P superoxide dismutase (RBC-SOD) and glutathione (GSH) returned to normal, and (5) hepatic LPO decreased and glutathione peroxidase (GSH-Px) increased. These results suggest that the restoration of lithium to control levels in the liver and muscle of diabetic animals is associated not only with decreased blood glucose but also with reduced oxidative stress, and consequently with the protection of insulin-secreting pancreatic islet cells.

  19. Effect of vanadyl sulfate on the status of lipid parameters and on stomach and spleen tissues of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Tunali, Sevim; Yanardag, Refiye

    2006-03-01

    Diabetes mellitus is a significant risk factor for cardiovascular complications. Experimental evidence suggests that oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. This study was undertaken to investigate the effect of vanadyl sulfate on blood glucose, serum and tissue lipid profiles and on stomach and spleen tissues in STZ-induced diabetic rats. In this study, male 6-6.5-month-old Swiss albino rats were used. Rats were randomly divided into four groups. Group I: control animals (normal, nondiabetic animals) (n = 13); Group II: vanadyl sulfate controls (n = 5); Group III: streptozotocin (STZ)-diabetic, untreated animals (n = 11); and Group IV: STZ diabetic animals given vanadyl sulfate (n = 11). Experimental diabetes was induced by intraperitoneal (i.p.) injection of STZ in a single dose of 65 mg kg(-1) body weight. Vanadyl sulfate was administered by gavage at a dose of 100 mg kg(-1). The levels of cholesterol, phospholipid, high density lipoprotein-cholesterol (HDL-), low density lipoprotein-cholesterol (LDL-), very low density lipoprotein-cholesterol (VLDL-), triglycerides and lipid peroxidation (LPO) in serum and cholesterol in liver were assayed according to standard procedures. The levels of lipid peroxidation, glutathione (GSH) and nonenzymatic glycosylation (NEG) in stomach and lipid peroxidation and glutathione (GSH) in spleen tissues were analyzed. After 60 days of treatment, serum cholesterol, LDL-cholesterol, triglyceride, phospholipid, VLDL-cholesterol, LPO, blood glucose levels, stomach LPO and NEG, spleen LPO significantly increased, but serum HDL-cholesterol, stomach GSH and spleen GSH levels significantly decreased in the diabetic group. On the other hand, treatment with vanadyl sulfate reversed these effects. These results reveal that diabetes mellitus increased oxidative damage in stomach and spleen tissues and vanadyl sulfate has an ameliorating effect on the oxidative stress via its antioxidant property. The

  20. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Rashid, Kahkashan; Sil, Parames C., E-mail: parames@jcbose.ac.in

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  1. Effect of Kaempferol isolated from seeds of Eruca sativa on changes of pain sensitivity in Streptozotocin-induced diabetic neuropathy.

    Science.gov (United States)

    Kishore, Lalit; Kaur, Navpreet; Singh, Randhir

    2017-11-20

    Generation of excessive reactive oxygen species (ROS) and advanced glycation end products (AGEs), and cellular apoptosis are implicated in the pathogenesis of diabetic neuropathy. Present study was aimed to explore the effect of Eruca sativa and Kaempferol (KP) on hyperalgesia (thermal and mechanical); tactile allodynia, motor nerve conduction velocity (MNCV) and oxidative-nitrosative stress in streptozotocin (STZ) induced experimental diabetes. Neuropathy developed in diabetic rats was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with excess formation of AGEs and ROS. Chronic treatment with E. sativa hydroalcoholic extract (EHA; 100, 200 and 400 mg/kg) and KP (5 and 10 mg/kg) for 30 days starting from the 60th day of STZ administration significantly ameliorated behavioral and biochemical changes linked to diabetic neuropathy. Present study suggested that EHA and KP corrected hyperglycemia and reversed the pain response partially in diabetic rats along via modulating oxidative and nitrosative stress along with reduction of AGEs formation in diabetic rats. Thus E. sativa might be beneficial in chronic diabetes, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain.

  2. Anti-diabetic effect of Cyclo-His-Pro (CHP)-enriched yeast ...

    African Journals Online (AJOL)

    The present study was designed to investigate the hypoglycemic effects of the daily oral dose of 0.50 to 0.75 g/kg of yeast hydrolysate (YH) containing high Cyclo-His-Pro (51.0 mg CHP/g YH) on normal and streptozotocin (STZ)-induced diabetic rats for 14 days. In STZ-induced diabetic rats, after administrations of the YH for ...

  3. Streptozotocin-induced type-1-diabetes disease onset in Sprague-Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity.

    Science.gov (United States)

    Patterson, Elaine; Marques, Tatiana M; O'Sullivan, Orla; Fitzgerald, Patrick; Fitzgerald, Gerald F; Cotter, Paul D; Dinan, Timothy G; Cryan, John F; Stanton, Catherine; Ross, R Paul

    2015-01-01

    There is a growing appreciation that microbiota composition can significantly affect host health and play a role in disease onset and progression. This study assessed the impact of streptozotocin (STZ)-induced type-1-diabetes (T1D) on intestinal microbiota composition and diversity in Sprague-Dawley rats, compared with healthy controls over time. T1D was induced by injection of a single dose (60 mg STZ kg(-1)) of STZ, administered via the intraperitoneal cavity. Total DNA was isolated from faecal pellets at weeks 0 (pre-STZ injection), 1, 2 and 4 and from caecal content at week 5 from both healthy and T1D groups. High-throughput 16S rRNA sequencing was employed to investigate intestinal microbiota composition. The data revealed that although intestinal microbiota composition between the groups was similar at week 0, a dramatic impact of T1D development on the microbiota was apparent post-STZ injection and for up to 5 weeks. Most notably, T1D onset was associated with a shift in the Bacteroidetes : Firmicutes ratio (Pmicrobiota composition and reduced microbial diversity over time. © 2015 The Authors.

  4. Effect of insulin on naturally occurring gingivitis rats with diabetes.

    Science.gov (United States)

    Hayashi, A; Shinohara, M; Ohura, K

    1999-04-01

    It is well known that diabetes mellitus aggravates both the severity and progression of periodontal disease. We sought to further explore biologic mechanisms of this relationship using naturally occurring gingivitis rats (ODUS/Odu) rendered diabetic by 65 mg/kg intravenous injection of streptozotocin (STZ). Insulin was administered daily to one group of the rats beginning 4 weeks after STZ injection (STZ-insulin group). Others received no insulin (STZ group). A third group that received no STZ was kept as controls. Eight weeks after STZ injection, sterilized liquid paraffin was injected peritoneally into all three groups, and peritoneal macrophages were collected 4 days later. Macrophage chemotaxis was measured by the membrane filter method using a 48-well microchemotaxis chamber with zymosan activated serum used as a chemotactic stimulant. Blood glucose levels, body weight, plaque indices, pocket depths, serum triglyceride and hemoglobin A1C levels were also determined. We found that blood glucose levels, body weight and triglycerides recovered to normal values in the STZ-insulin group. Further, control of blood glucose resulted in diminished plaque indices, and pocket depths returned to values seen in the controls. Chemotaxis and phagocytosis of peritoneal macrophages improved slightly in the STZ-insulin group, but did not return to levels seen in the pretreatment state. Although insulin resulted in some improvement in leukocyte function damaged by induced diabetes mellitus, recovery was incomplete.

  5. Anti-hepatotoxic activities of Hibiscus sabdariffa L. in animal model of streptozotocin diabetes-induced liver damage.

    Science.gov (United States)

    Adeyemi, David O; Ukwenya, Victor O; Obuotor, Efere M; Adewole, Stephen O

    2014-07-30

    Flavonoid-rich aqueous fraction of methanolic extract of Hibiscus sabdariffa calyx was evaluated for its anti-hepatotoxic activities in streptozotocin-induced diabetic Wistar rats. Diabetes Mellitus was induced in Wistar rats by a single i.p injection of 80 mg/kg b.w. streptozotocin (STZ) dissolved in 0.1 M citrate buffer (pH 6.3). The ameliorative effects of the extract on STZ-diabetes induced liver damage was evident from the histopathological analysis and the biochemical parameters evaluated in the serum and liver homogenates. Reduced levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (3.76 ± 0.38 μM, 0.42 ± 0.04 U/L, 41.08 ± 3.04 U/ml, 0.82 ± 0.04 U/L respectively) in the liver of diabetic rats were restored to a near normal level in the Hibiscus sabdariffa-treated rats (6.87 ± 0.51 μM, 0.72 ± 0.06 U/L, 87.92 ± 5.26 U/ml, 1.37 ± 0.06 U/L respectively). Elevated levels of aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) in the serum of diabetic rats were also restored in Hibiscus sabdariffa -treated rats. Examination of stained liver sections revealed hepatic fibrosis and excessive glycogen deposition in the diabetic rats. These pathological changes were ameliorated in the extract-treated rats. The anti-hepatotoxic activity of Hibiscus sabdariffa extract in STZ diabetic rats could be partly related to its antioxidant activity and the presence of flavonnoids.

  6. Distal tubule bicarbonate reabsorption in intact and remnant diabetic kidneys.

    Science.gov (United States)

    Levine, D Z; Iacovitti, M; Burns, K D

    2000-02-01

    In the diabetic patient, hyperkalemia and hyperchloremic metabolic acidosis has been attributed to one or more of the following factors associated with diabetic nephropathy: hypoaldosteronism, altered potassium homeostasis, or a distal tubular (DT) defect in hydrogen ion secretion. To evaluate maximal in vivo DT acidification in streptozotocin (STZ) diabetes, unidirectional bicarbonate reabsorption (JHCO3) was measured in DTs after acid loading and in surviving DT after 2/3 nephrectomy (Nx). Acid gavage induced hyperchloremic metabolic acidosis in four groups of rats: diabetic rats with hyperglycemia two (a) and (b) eight weeks after STZ injection, (c) diabetic rats with tight glucose control two weeks after STZ injection and insulin pump implantation; and (d) control nondiabetic rats. Another group of diabetic rats underwent (e) Nx one week after STZ injection; these rats were neither acid loaded nor pump implanted. In the acidotic rats, the plasma potassium concentration, the plasma and urine acid-base parameters in the three STZ diabetic groups was not different from control rats, whereas JHCO3 fluxes were brisk without important differences between groups. In Nx rats, although the plasma potassium concentration and acid-base status were normal, surviving JHCO3 fluxes were still brisk and not different from the acid-loaded rats. These in vivo measurements indicate there is no impairment in DT unidirectional bicarbonate reabsorption in the intact or remnant STZ diabetic kidney.

  7. Duration of streptozotocin-induced diabetes differentially affects p38-mitogen-activated protein kinase (MAPK phosphorylation in renal and vascular dysfunction

    Directory of Open Access Journals (Sweden)

    Gupta Akanksha

    2005-03-01

    Full Text Available Abstract Background In the present study we tested the hypothesis that progression of streptozotocin (STZ-induced diabetes (14-days to 28-days would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK phosphorylation in kidneys and thoracic aorta. Methods Male Sprague Dawley rats (350–400 g were randomized into three groups: sham (N = 6, 14-days diabetic (N = 6 and 28-days diabetic rats (N = 6. Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V. on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were noted. At both 14-days and 28-days post diabetes blood samples were collected and kidney cortex, medulla and aorta were harvested from each rat. Results The diabetic rats lost body weight at both 14-days (-10% and 28-days (-13% more significantly as compared to sham (+10% group. Glucose levels were significantly elevated in the diabetic rats at both 14-days and 28-days post-STZ administration. Renal dysfunction as evidenced by renal hypertrophy, increased plasma creatinine concentration and reduced renal blood flow was observed in 14-days and 28-days diabetes. Vascular dysfunction as evidenced by decreased carotid blood flow was observed in 14-days and 28-days diabetes. We observed an up-regulation of inducible nitric oxide synthase (iNOS, prepro endothelin-1 (preproET-1 and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group. Conclusion The study provides evidence that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes.

  8. Changes in Oxidative Stress and Antioxidant Enzyme Activities in Streptozotocin-Induced Diabetes Mellitus in Rats: Role of Alhagi maurorum Extracts.

    Science.gov (United States)

    Sheweita, S A; Mashaly, S; Newairy, A A; Abdou, H M; Eweda, S M

    2016-01-01

    Alhagi maurorum (camel thorn plant) is a promising medicinal plant due to the presence of flavonoids and phenolic compounds as major contents of its constituents. No previous study has been conducted before on A. maurorum extracts as an antioxidative stress and/or antidiabetic herb in STZ-induced DM in rats. Therefore, four groups of rats were allocated as control (C), STZ-induced DM (D), and STZ-induced DM supplemented with 300 mg/kg BW of either aqueous extract (WE) or ethanolic extract (EE) of A. maurorum. The plasma levels of glucose, TG, TC, LDL-C and VLDL-C, MDA, and bilirubin and the activities of transaminases and GR were significantly increased in the diabetic group. Also, diabetic rats showed severe glucose intolerance and histopathological changes in their livers. In addition, levels of insulin, total proteins, GSH, and HDL-C and the activities of SOD, GPx, and GST were significantly decreased in the diabetic rats compared to those of the control group. The ingestion of A. maurorum extracts lowered the blood glucose levels during the OGTT compared to the diabetic rats and restored all tested parameters to their normal levels with the exception of insulin level that could not be restored. It is concluded that A. maurorum extracts decreased elevated blood glucose levels and hyperlipidemia and suppressed oxidative stress caused by diabetes mellitus in rats.

  9. Effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Siamak Asri-Rezaei

    2015-08-01

    Full Text Available Objectives:Crocin is one of constituents of saffron and has antioxidant property. Zinc chloride is one of the common compounds of zinc with antioxidant activity. The present study was aimed to investigate separate and combined treatment effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in diabetic rats. Materials and Methods:Diabetes was induced by intraperitoneal (i.p. injection of 50 mg/kg of streptozotocin (STZ and was confirmed by blood glucose levels higher than 250 mg/dL. After confirmation of diabetes, injections (i.p. of crocin and zinc chloride were performed for six weeks. At the end of the experiment, blood levels of zinc, glucose, insulin, malodialdehyde (MDA, and total antioxidant capacity (TAC were measured. ‎ Results:Crocin (25 and 50 mg/kg and zinc chloride (5 mg/kg significantly recovered the decreased levels of zinc, insulin, and TAC and improved the increased levels of glucose and MDA in STZ-induced diabetic rats. In a combination treatment performed with an ineffective dose of crocin (12.5 mg/kg and a low dose of zinc chloride (1.25 mg/kg, improving effects were observed on the above-mentioned biochemical parameters.‎ Conclusions: The results indicated that separate and combined treatments with crocin and zinc chloride produced improving effects on the blood levels of zinc, glucose, insulin, MDA and TAC in STZ-induced diabetic rats.‎

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

    Science.gov (United States)

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

    2015-07-18

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

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

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    V Sabitha

    2011-01-01

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

  12. Essential pathogenic role of endogenous IL-18 in murine diabetes induced by multiple low doses of streptozotocin. Prevention of hyperglycemia and insulitis by a recombinant IL-18-binding protein: Fc construct

    DEFF Research Database (Denmark)

    Nicoletti, Ferdinando; Di Marco, Roberto; Papaccio, Gianpaolo

    2003-01-01

    to day 14 exhibited clinical and histological signs of STZ-induced diabetes similar to those of control mice treated with IgG. The protective effect of IL-18 bp:Fc was accompanied by modified ex vivo immune responses, in that spleen cells and peritoneal macrophages contained fewer IFN-gamma secreting...

  13. Effects of the Hydroalcoholic Extract of Zingiber officinale on Arginase I Activity and Expression in the Retina of Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Lamuchi-Deli, Nasrin; Aberomand, Mohammad; Babaahmadi-Rezaei, Hossein; Mohammadzadeh, Ghorban

    2017-04-01

    Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes. This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats. In this experimental study, 16 male Wistar rats weighing 200 - 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively. Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P extract reduced arginase I activity and expression (P extract. Serum insulin was significantly increased in diabetic rats treated with 400 mg/kg of the extract compared to diabetic controls (P extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina.

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

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    Abdulrahman L. Al-Malki

    2015-01-01

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

  15. The antidiabetic effect of low doses of Moringa oleifera Lam. seeds on streptozotocin induced diabetes and diabetic nephropathy in male rats.

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

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    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.

  18. Antidiabetic and Antidyslipidemic Activities of the Aqueous Extract of Cochlospermum planchonii Leaves in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Abraham, Bamisaye Fisayo; Olarewaju, Sulyman Abdulhakeem; Ronke, Abegunde; Oladipo, Ajani Emmanuel

    2017-11-01

    Diabetes mellitus is considered one of the 5 principal causes of death in the world and is recognized as a global public health issue because of its multifactorial facets affecting essential biochemical processes in the body. This study investigated the antidiabetic and antidyslipidemic activities of the aqueous extract of Cochlospermum planchonii (C. planchonii) leaves in streptozotocin (STZ)-induced diabetic rats. Thirty adult female rats (Rattus norvegicus) weighing 153±3.41g were randomized into 6 groups of 5 animals each. STZ-induced diabetic rats were orally administered 50, 100, and 200 mg/kg body weight of the extract, respectively, once a day, and their blood glucose levels as well as variations of diabetes-associated biomarkers including alpha amylase, glucose-6-phosphate dehydrogenase (G6PDH), and lipid profile by the extract were monitored for 21 days. The results were expressed as means±SEMs and compared with repeated measures using SPSS, Data Editor, version 16.0. The aqueous extract of C. planchonii leaves significantly reduced the blood glucose level in a dose-dependent manner, with the highest dose producing a 74.52% reduction after 21 days of administration, which compared significantly (Pextract. In addition, the aqueous extract of C. planchonii leaves significantly attenuated the decrease in the activity of G6PDH and the increase in the activity of α-AMY in the liver of the STZ-induced diabetic rats. Overall, the aqueous extract of C. planchonii leaves could be used to manage diabetes and other related complications.

  19. Histological and gene expression analysis of the effects of pulsed low-level laser therapy on wound healing of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sharifian, Zanelabedien; Bayat, Mohammad; Alidoust, Morteza; Farahani, Reza Masteri; Bayat, Maryam; Rezaie, Fatemealsadat; Bayat, Homa

    2014-05-01

    Diabetes mellitus (DM) is associated with poor wound healing. Studies have shown accelerated wound healing following pulsed low-level laser therapy (LLLT) in non-diabetic animals. The present study aims to evaluate the effect of pulsed LLLT on wound healing in streptozotocin-induced diabetic (STZ-D) rats. We divided 48 rats into two groups of non-diabetic and diabetic. Type 1 DM was induced in the diabetic rat group by injections of STZ. Two, full-thickness skin incisions were made on the dorsal region of each rat. One month after the STZ injection, wounds of the non-diabetic and diabetic rats were submitted to a pulsed, infrared 890-nm laser with an 80-Hz frequency and 0.2 J/cm(2) for each wound point. Control wounds did not receive LLLT. Animals were sacrificed on days 4, 7, and 15 post-injury for histomorphometry and reverse transcription polymerase chain reaction (RT-PCR) analyses of basic fibroblast growth factor (bFGF) gene expression. Pulsed LLLT significantly increased the numbers of macrophages, fibroblasts, and blood vessel sections compared to the corresponding control groups. Semi-quantitative analysis of bFGF gene expression at 48 h post-injury revealed a significant increase in gene expression in both non-diabetic and diabetic rats following LLLT (the ANOVA test). Pulsed LLLT at 0.2 J/cm(2) accelerated the wound healing process in both non-diabetic and diabetic rats as measured by histological characteristics and semi-quantitative bFGF gene expression.

  20. Effect of streptozotocin-induced diabetes on lipids metabolism in the salivary glands.

    Science.gov (United States)

    Matczuk, Jan; Zalewska, Anna; Łukaszuk, Bartłomiej; Garbowska, Marta; Chabowski, Adrian; Żendzian-Piotrowska, Małgorzata; Kurek, Krzysztof

    2016-11-01

    Diabetes is one of the most common metabolic diseases. Moreover, previous studies indicate that diabetes may cause changes in the salivary glands phenotype and in the composition of saliva itself. Therefore, the main objective of this study was to determine the effects of streptozotocin induced diabetes on lipid profile of the rat salivary glands. Male Wistar rats were divided into two groups: control and STZ-induced diabetes. At the end of the experiment all animals were sacrificed and samples of the parotid and submandibular salivary glands were excised. Major lipid fractions concentrations were determined by means of chromatography (TLC and GC). We observed a significant increase (∼3.5 fold) in the level of triacylglycerol in both the parotid and submandibular salivary glands of diabetic rats. The abovementioned changes were accompanied by significant, although less dramatic (i.e. from -60% to -90%), decrements in the levels of other lipid classes (phospholipids, free fatty acids and diacylglycerol). In our study we have showed, presumably for the first time, that streptozotocin induced diabetes causes decrement in PH content with subsequent atrophy and malfunction in both parotid and submandibular salivary glands. Another novel finding of our research is that diabetic rats were characterized by an increased TG accumulation in both parotid and submandibular salivary glands. The later one could be a clinical manifestation of diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice.

    Science.gov (United States)

    Rossi, Claudia; Marzano, Valeria; Consalvo, Ada; Zucchelli, Mirco; Levi Mortera, Stefano; Casagrande, Viviana; Mavilio, Maria; Sacchetta, Paolo; Federici, Massimo; Menghini, Rossella; Urbani, Andrea; Ciavardelli, Domenico

    2017-11-13

    The tissue inhibitor of metalloproteinase TIMP3 is a stromal protein that restrains the activity of both protease and receptor in the extracellular matrix and has been found to be down-regulated in diabetic nephropathy (DN), the leading cause of end-stage renal disease in developed countries. In order to gain deeper insights on the association of loss of TIMP3 and DN, we performed differential proteomic analysis of kidney and blood metabolic profiling of wild-type and Timp3-knockout mice before and after streptozotocin (STZ) treatment, widely used to induce insulin deficiency and hyperglycemia. Kidney proteomic data and blood metabolic profiles suggest significant alterations of peroxisomal and mitochondrial fatty acids β-oxidation in Timp3-knockout mice compared to wild-type mice under basal condition. These alterations were exacerbated in response to STZ treatment. Proteomic and metabolomic approaches showed that loss of TIMP3 alone or in combination with STZ treatment results in significant alterations of kidney lipid metabolism and peripheral acylcarnitine levels, supporting the idea that loss of TIMP3 may generate a phenotype more prone to DN.

  2. Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

    Science.gov (United States)

    Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

    2016-02-01

    Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Two types of

  3. A fluorescent homogeneous assay for myeloperoxidase measurement in biological samples. A positive correlation between myeloperoxidase-generated HOCl level and oxidative status in STZ-diabetic rats.

    Science.gov (United States)

    Stocker, Pierre; Cassien, Mathieu; Vidal, Nicolas; Thétiot-Laurent, Sophie; Pietri, Sylvia

    2017-08-01

    Myeloperoxidase (MPO) is a key enzyme derived from leukocytes which is associated with the initiation and progression of many inflammatory diseases. Increased levels of MPO may contribute to cellular dysfunction and tissues injury by producing highly reactive oxidants such as hypochlorous acid (HOCl). Myeloperoxidase-generated HOCl is therefore considered as a relevant biomarker of oxidative stress-related damage and its quantitation is of great importance to the study of disease progression. In this context, the current study describes a rapid, sensitive and homogeneous fluorescence-based method for detecting the MPO chlorination activity in biological samples. This assay utilizes 7-hydroxy-2-oxo-2H-chromene-8-carbaldehyde oxime as a selective probe for HOCl detection, and is adapted to 96-well microplates to allow high-throughput quantitation of active MPO. The ability of the method to monitor HOCl release was further investigated in hyperglycemic streptozotocin-treated diabetic rats. The data proved that the present assay has a reliable performance when quantitating the active MPO in the plasma of diabetic animals, a feature of inflammatory disease found concomitant with an elevation of protein carbonyls levels and lipid peroxidation and which was negatively correlated with the ratio of reduced-to-oxidized glutathione. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

    Science.gov (United States)

    Jin, Hai-Rong; Kim, Woo Jean; Song, Jae Sook; Piao, Shuguang; Choi, Min Ji; Tumurbaatar, Munkhbayar; Shin, Sun Hwa; Yin, Guo Nan; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu

    2011-01-01

    OBJECTIVE Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals. RESEARCH DESIGN AND METHODS Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test. RESULTS Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47phox and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin. CONCLUSIONS These findings support the concept of cavernous

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

    Directory of Open Access Journals (Sweden)

    Amir Farshid

    2016-11-01

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

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

    Science.gov (United States)

    El-Akabawy, Gehan; El-Kholy, Wael

    2014-05-01

    Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. The Effect of Simvastatin on Glucose Homeostasis in Streptozotocin Induced Type 2 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Lulu Wang

    2013-01-01

    Full Text Available Objective. To investigate the effect of simvastatin on glucose homeostasis in streptozotocin induced type 2 diabetic rats. Methods. Forty male Wistar rats were randomly divided into four groups. Normal control rats were fed with standard diet, others were fed with high-fat diet. Diabetic rats were induced by a single intraperitoneal injection of STZ. The simvastatin intervention rats were fed with simvastatin during the experiment process, and the simvastatin treatment rats were fed with simvastatin after diabetes rats were induced. We measured body weight, fasting plasma glucose, cholesterol, high-density lipoprotein cholesterol, and triglyceride after an overnight fast. Results. The FPG was higher in diabetic rats when compared to normal control ones; the simvastatin intervention rats had a higher FPG compared to the diabetic rats and were more easily be induced to diabetes at the end of 4 weeks, FPG level of simvastatin treatment rats was increased compared with diabetic model rats after 12 weeks. Conclusion. These data indicate that simvastatin intervention rats may cause hyperglycemia by impairing the function of islet β cells and have an adverse effect on glucose homeostasis, especially on FPG level.

  8. Diosgenin reorganises hyperglycaemia and distorted tissue lipid profile in high-fat diet-streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Naidu, Parim Brahma; Ponmurugan, Ponnusamy; Begum, Mustapha Sabana; Mohan, Karthick; Meriga, Balaji; RavindarNaik, Ramavat; Saravanan, Ganapathy

    2015-12-01

    Diabetes is often connected with significant morbidity, mortality and also has a pivotal role in the development of cardiovascular diseases. Diet intervention, particularly naturaceutical antioxidants have anti-diabetic potential and avert oxidative damage linked with diabetic pathogenesis. The present study investigated the effects of diosgenin, a saponin from fenugreek, on the changes in lipid profile in plasma, liver, heart and brain in high-fat diet-streptozotocin (HFD-STZ)-induced diabetic rats. Diosgenin was administered to HFD-STZ induced diabetic rats by orally at 60 mg kg(-1) body weight for 30 days to assess its effects on body weight gain, glucose, insulin, insulin resistance and cholesterol, triglycerides, free fatty acids and phospholipids in plasma, liver, heart and brain. The levels of body weight, glucose, insulin, insulin resistance, cholesterol, triglycerides, free fatty acids, phospholipids, VLDL-C and LDL-C were increased significantly (P lipid profile in plasma and tissues. The traditional plant fenugreek and its constituents mediate its anti-diabetic potential through mitigating hyperglycaemic status, altering insulin resistance by alleviating metabolic dysregulation of lipid profile in both plasma and tissues. © 2014 Society of Chemical Industry.

  9. GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Inoue, Tomoaki; Inoguchi, Toyoshi; Sonoda, Noriyuki; Hendarto, Hari; Makimura, Hiroaki; Sasaki, Shuji; Yokomizo, Hisashi; Fujimura, Yoshinori; Miura, Daisuke; Takayanagi, Ryoichi

    2015-05-01

    Accumulating evidence has implicated that GLP-1 may have a beneficial effect on cardiovascular but the mechanism is not fully understood. Here we show that GLP-1 analog, liraglutide, inhibits cardiac steatosis, oxidative stress and apoptosis in streptozotocin (STZ)-induced type 1 diabetic rats, via activation of AMPK-Sirt1 pathway. Diabetic rats were treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Myocardial steatosis (detected by oil red O staining and myocardial triglyceride and diacylglycerol (DAG) contents assay), expression of protein kinase C (PKC), heart NAD(P)H oxidase activity, oxidative stress markers (8-hydroxy-2'-deoxyguanosine staining), apoptosis (TUNEL analysis) and genes that affect apoptosis and lipid metabolism were evaluated. Administration of liraglutide did not affect plasma glucose and insulin levels or body weights in STZ-induced diabetic rats, but normalized myocardial steatosis, expression of PKC, NAD(P)H oxidase activity, oxidative stress markers and apoptosis, all of which were significantly increased in diabetic hearts. Additionally, expression of genes mediating lipid uptake, synthesis and oxidation were increased in the diabetic hearts, and these increases were all reduced by liraglutide. In addition, liraglutide increased expression of Sirt1 and phosphorylated AMPK in the diabetic hearts. Liraglutide may have a beneficial effect on cardiac steatosis, DAG-PKC-NAD(P)H pathway, oxidative stress and apoptosis via activation of AMPK-Sirt1 pathway, independently of a glucose-lowering effect. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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    Eren Çerman

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

  11. Hpyerglycemic and anti-diabetic nephritis activities of polysaccharides separated from Auricularia auricular in diet-streptozotocin-induced diabetic rats.

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    Hu, Xinyu; Liu, Chungang; Wang, Xue; Jia, Dongxu; Lu, Wenqian; Sun, Xiaoqi; Liu, Yang; Yuan, Lijia

    2017-01-01

    Due to substantial morbidity and complications including nephropathy, a search for alternative treatment of diabetes mellitus is urgently required. The present study aimed to investigate the hypoglycemic and anti-diabetic nephropathy activities of polysaccharides separated from Auricularia auricular (AAP). Diet streptozotocin (STZ)-induced diabetic Sprague-Dawley rats were orally treated with metformin (100 mg/kg; positive control) and AAP (100 and 400 mg/kg) for four weeks, and parameters in the serum and liver associated with blood glucose, free radicals and nephropathy were determined. Similar to metformin, AAP treatment strongly reduced blood glucose levels by promoting glucose metabolism. The anti-oxidative activity of AAP, which was indicated by the modulation of superoxide dismutase, glutathione peroxidase, reactive oxygen species and methane dicarboxylic aldehyde levels in serum, was observed in diabetic rats. Furthermore, the regulatory effects of AAP on blood urea nitrogen, creatinine, uric protein and inflammatory-related factors revealed its protection against diabetic nephropathy. The present data suggests that AAP-mediated anti-diabetic and anti-nephritic effects are partially associated with their modulations on the anti-oxidative system and nuclear factor kappa B-related signaling pathway. In conclusion, AAP has potential to be a novel source of treatments for diabetes.

  12. The Histological, Histomorphometrical and Histochemical Changes of Testicular Tissue in the Metformin Treated and Untreated Streptozotocin-Induced Adult Diabetic Rats

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    Davoud Kianifard

    2011-03-01

    Full Text Available In this investigation, diabetes was induced in adult male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin (STZ at 45 mg kg-1 of body weight. A group comprised of 8 diabetic rats was treated with metformin at 100 mg kg-1 of body weight for reducing the elevated blood glucose level. The results revealed that, in the untreated diabetic rats, the body and testicular weight reduced in comparison with the control rats (P < 0.05 , the metformin treated diabetic rats showed body weight loss in comparison with the control group (P < 0.05. In the untreated diabetic rats, the blood glucose level significantly increased in comparison with control and metformin treated diabetic rats. Histomorphological examinations revealed a reduction in testicular capsule diameter, seminiferous tubules (STs and germinal epithelium height, increase of amorphous material of interstitial tissue, germ cell depletion, decrease in cellular population and activity and disruption of spermatogenesis in the untreated diabetic rats in comparison with control group. In metformin treated diabetic rats, the histomorphological alterations were seen in lesser part in comparison with untreated diabetic group. The results from this study proved that, there was a direct relationship between increased levels of blood glucose as a result of STZ-induced diabetes and the histomorphological changes of testicular tissue.

  13. Antidiabetic, hypolipidemic and hepatoprotective effects ofArctium lapparoot's hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice.

    Science.gov (United States)

    Ahangarpour, Akram; Heidari, Hamid; Oroojan, Ali Akbar; Mirzavandi, Farhang; Nasr Esfehani, Khalil; Dehghan Mohammadi, Zeinab

    2017-01-01

    Arctium lappa (burdock), (A. lappa) root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ)-induced type2 diabetes in mice. In this investigation, 70 adult male NMRI mice (30-35g) randomly divided into 7 groups (n=10) as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg) as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated. Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL) and increased the level of other lipids, glucose, and hepatic enzymes significantly (plappa root extract, at specific doses, has an anti-diabetic effect through its hypolipidemic and insulinotropic properties. Hence, this plant extract may be beneficial in the treatment of diabetes.

  14. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice

    Science.gov (United States)

    Ahangarpour, Akram; Heidari, Hamid; Oroojan, Ali Akbar; Mirzavandi, Farhang; Nasr Esfehani, Khalil; Dehghan Mohammadi, Zeinab

    2017-01-01

    Objective: Arctium lappa (burdock), (A. lappa) root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ)-induced type2 diabetes in mice. Materials and Methods: In this investigation, 70 adult male NMRI mice (30-35g) randomly divided into 7 groups (n=10) as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg) as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated. Results: Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL) and increased the level of other lipids, glucose, and hepatic enzymes significantly (plappa root extract, at specific doses, has an anti-diabetic effect through its hypolipidemic and insulinotropic properties. Hence, this plant extract may be beneficial in the treatment of diabetes. PMID:28348972

  15. Hypoglycemic Effects of Achillea Wilhelmsii in Normal and Streptozotocin Induced Diabetic Rats

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    H Sadeghi

    2009-04-01

    Full Text Available ABSTRACT Introduction & Objective: Diabetes mellitus is a syndrome, initially characterized by a loss of glucose homeostasis resulting from defects in Insulin secretion, insulin action both is resulting in impaired metabolism of glucose and other energy yielding fuels as lipids and protein. Several medicinal herbs have been described with hypoglycemic effects. These include: Allium Sativum, Trigonella Foenum, Marus nigra, Ocimum Sanctum, and Astragalus Ovinus. The main purpose of the present study was to determine the effect of Achillea Wilhelmsii C. Koch on blood glucose levels of diabetic rats induced by stereptozotocine (STZ. Materials & Methods: In this experimental research, forty-eight male Wistar rats were divided into two groups: non-diabetic (normal and STZ-induced diabetic mice. Each group was further divided into four groups: control (induced by normal saline and treatment received 100, 200.and 300 mg/kg aqueous- alcoholic extract of Achillea Wilhelmsii C. Koch daily for one month. The blood glucose level was measured and Data were analyzed by t-test and ANOVA. Results: At the end of first month, significant decrease was observed in blood glucose level in diabetic rats which received 100 mg/kg (p<0/001, 200mg/kg(p<0/01, 300mg/kg (p<0/001 of aqueous alcoholic extract of Achillea Wilhelmsii C. Koch in comparison with control groups. The extract had not have any significant effects on the blood glucose level of normal groups except in those which received 300mg/kg of the extract. Conclusion: The results of this study showed that aqueous- alcoholic extract of Achillea Wilhelmsii C. Koch have a significant effect on reducing the blood glucose level of diabetic rats.

  16. Mechanism Investigation of the Improvement of Chang Run Tong on the Colonic Remodeling in Streptozotocin-Induced Diabetic Rats

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    Hong Sha

    2016-01-01

    Full Text Available Previous study demonstrated that Chang Run Tong (CRT could partly restore the colon remodeling in streptozotocin- (STZ- induced diabetic rats. Here we investigated the mechanisms of such effects of CRT. Diabetes was induced by a single injection of 40 mg/kg of STZ. CRT was poured into the stomach by gastric lavage once daily for 60 days. The remodeling parameters were obtained from diabetic (DM, CRT treated diabetic (T1, 50 g/kg; T2, 25 g/kg, and normal (Con rats. Expressions of advanced glycation end product (AGE, AGE receptor, transforming growth factor-β1 (TGF-β1, and TGF-β1 receptor in the colon wall were immunochemically detected and quantitatively analyzed. The association between the expressions of those proteins and the remodeling parameters was analyzed. The expressions of those proteins were significantly higher in different colon layers in the DM group (P0.05. The corrective effect on the expressions of those proteins is likely to be one molecular pathway for the improvement of CRT on the diabetes-induced colon remodeling.

  17. Effects of parsley (Petroselinum crispum) extract versus glibornuride on the liver of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Ozsoy-Sacan, Ozlem; Yanardag, Refiye; Orak, Haci; Ozgey, Yasemin; Yarat, Aysen; Tunali, Tugba

    2006-03-08

    Parsley (Petroselinum crispum) is one of the medicinal herbs used by diabetics in Turkey. The aim of this study is to investigate the effects of parsley (2g/kg) and glibornuride (5mg/kg) on the liver tissue of streptozotocin-induced diabetic rats. Swiss albino rats were divided into six groups: control; control+parsley; control+glibornuride; diabetic; diabetic+parsley; diabetic+glibornuride. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Parsley extract and glibornuride were given daily to both diabetic and control rats separately, until the end of the experiment, at day 42. The drugs were administered to one diabetic and one control group from days 14 to 42. On day 42, liver tissues were taken from each rat. In STZ-diabetic group, blood glucose levels, serum alkaline phosphatase activity, uric acid, sialic acid, sodium and potassium levels, liver lipid peroxidation (LPO), and non-enzymatic glycosylation (NEG) levels increased, while liver glutathione (GSH) levels and body weight decreased. In the diabetic group given parsley, blood glucose, serum alkaline phosphatase activity, sialic acid, uric acid, potassium and sodium levels, and liver LPO and NEG levels decreased, but GSH levels increased. The diabetic group, given glibornuride, blood glucose, serum alkaline phosphatase activity, serum sialic acid, uric acid, potassium, and liver NEG levels decreased, but liver LPO, GSH, serum sodium levels, and body weight increased. It was concluded that probably, due to its antioxidant property, parsley extract has a protective effect comparable to glibornuride against hepatotoxicity caused by diabetes.

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

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

    1991-01-01

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

  19. Streptozotocin, Type I Diabetes Severity and Bone

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    Motyl Katherine

    2009-01-01

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

  20. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-03-01

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

  1. Effect of pre-germinated brown rice intake on diabetic neuropathy in streptozotocin-induced diabetic rats

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    Ariga Toshio

    2007-11-01

    Full Text Available Abstract Background To study the effects of a pre-germinated brown rice diet (PR on diabetic neuropathy in streptozotocin (STZ-induced diabetic rats. Methods The effects of a PR diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with those fed brown rice (BR or white rice (WR diets with respect to the following parameters: blood-glucose level, motor-nerve conduction velocity (NCV, sciatic-nerve Na+/K+-ATPase activity, and serum homocysteine-thiolactonase (HTase activity. Results Compared with diabetic rats fed BR or WR diets, those fed a PR diet demonstrated significantly lower blood-glucose levels (p +/K+-ATPase activity (1.6- and 1.7-fold higher, respectively. The PR diet was also able to normalize decreased serum homocysteine levels normally seen in diabetic rats. The increased Na+/K+-ATPase activity observed in rats fed PR diets was associated with elevations in HTase activity (r = 0.913, p in vitro effect of the total lipid extract from PR bran (TLp on the Na+/K+-ATPase and HTase activity was also examined. Incubation of homocysteine thiolactone (HT with low-density lipoprotein (LDL in vitro resulted in generation of HT-modified LDL, which possessed high potency to inhibit Na+/K+-ATPase activity in the sciatic nerve membrane. The inhibitory effect of HT-modified LDL on Na+/K+-ATPase activity disappeared when TLp was added to the incubation mixture. Furthermore, TLp directly activated the HTase associated with high-density lipoprotein (HDL. Conclusion PR treatment shows efficacy for protecting diabetic deterioration and for improving physiological parameters of diabetic neuropathy in rats, as compared with a BR or WR diet. This effect may be induced by a mechanism whereby PR intake mitigates diabetic neuropathy by one or more factors in the total lipid fraction. The active lipid fraction is able to protect the Na+/K+-ATPase of the sciatic-nerve membrane from the toxicity of HT-modified LDL and to directly

  2. Effect of pre-germinated brown rice intake on diabetic neuropathy in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Usuki, Seigo; Ito, Yukihiko; Morikawa, Keiko; Kise, Mitsuo; Ariga, Toshio; Rivner, Michael; Yu, Robert K

    2007-11-23

    To study the effects of a pre-germinated brown rice diet (PR) on diabetic neuropathy in streptozotocin (STZ)-induced diabetic rats. The effects of a PR diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with those fed brown rice (BR) or white rice (WR) diets with respect to the following parameters: blood-glucose level, motor-nerve conduction velocity (NCV), sciatic-nerve Na+/K+-ATPase activity, and serum homocysteine-thiolactonase (HTase) activity. Compared with diabetic rats fed BR or WR diets, those fed a PR diet demonstrated significantly lower blood-glucose levels (p < 0.001), improved NCV (1.2- and 1.3-fold higher, respectively), and increased Na+/K+-ATPase activity (1.6- and 1.7-fold higher, respectively). The PR diet was also able to normalize decreased serum homocysteine levels normally seen in diabetic rats. The increased Na+/K+-ATPase activity observed in rats fed PR diets was associated with elevations in HTase activity (r = 0.913, p < 0.001). The in vitro effect of the total lipid extract from PR bran (TLp) on the Na+/K+-ATPase and HTase activity was also examined. Incubation of homocysteine thiolactone (HT) with low-density lipoprotein (LDL) in vitro resulted in generation of HT-modified LDL, which possessed high potency to inhibit Na+/K+-ATPase activity in the sciatic nerve membrane. The inhibitory effect of HT-modified LDL on Na+/K+-ATPase activity disappeared when TLp was added to the incubation mixture. Furthermore, TLp directly activated the HTase associated with high-density lipoprotein (HDL). PR treatment shows efficacy for protecting diabetic deterioration and for improving physiological parameters of diabetic neuropathy in rats, as compared with a BR or WR diet. This effect may be induced by a mechanism whereby PR intake mitigates diabetic neuropathy by one or more factors in the total lipid fraction. The active lipid fraction is able to protect the Na+/K+-ATPase of the sciatic-nerve membrane from the

  3. 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.

  4. Neural Degeneration in the Retina of the Streptozotocin-Induced Type 1 Diabetes Model

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    Yoko Ozawa

    2011-01-01

    Full Text Available Diabetic retinopathy, a vision-threatening disease, has been regarded as a vascular disorder. However, impaired oscillatory potentials (OPs in the electroretinogram (ERG and visual dysfunction are recorded before severe vascular lesions appear. Here, we review the molecular mechanisms underlying the retinal neural degeneration observed in the streptozotocin-(STZ- induced type 1 diabetes model. The renin-angiotensin system (RAS and reactive oxygen species (ROS both cause OP impairment and reduced levels of synaptophysin, a synaptic vesicle protein for neurotransmitter release, most likely through excessive protein degradation by the ubiquitin-proteasome system. ROS also decrease brain-derived neurotrophic factor (BDNF and inner retinal neuronal cells. The influence of both RAS and ROS on synaptophysin suggests that RAS-ROS crosstalk occurs in the diabetic retina. Therefore, suppressors of RAS or ROS, such as angiotensin II type 1 receptor blockers or the antioxidant lutein, respectively, are potential candidates for neuroprotective and preventive therapies to improve the visual prognosis.

  5. The impact of low-dose insulin on peripheral nerve insulin receptor signaling in streptozotocin-induced diabetic rats.

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    Kazuhiro Sugimoto

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

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

    Science.gov (United States)

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

    2013-01-01

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

  7. Mediation of beta-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals.

    Science.gov (United States)

    Yu, Bu Chin; Chang, Cheng Kuei; Su, Chih Fen; Cheng, Juei Tang

    2008-06-01

    In the present study, we investigated the mechanism(s) for glucose-lowering action of andrographolide in streptozotocin-induced diabetic rats (STZ-diabetic rats). Andrographolide lowered plasma glucose concentrations in a dose-dependent manner and increased plasma beta-endorphin-like immunoreactivity (BER) dose-dependently in diabetic rats. Both of these responses to andrographolide were abolished by the pretreatment of animals with prazosin or N-(2-(2-cyclopropylmethoxy) ethyl) 5-choro-alpha-dimethyl-1H-indole-3-thylamine (RS17053) at doses sufficient to block alpha1-adrenoceptors (ARs). Also, andrographolide enhanced BER release from isolated rat adrenal medulla in a concentration-related manner that could be abolished by alpha1-ARs antagonists. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of andrographolide, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Andrographolide failed to lower plasma glucose in the presence of opioid micro-receptor antagonists and in the opioid micro-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with andrographolide resulted in the reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver and an increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle. These effects were also blocked by opioid micro-receptor antagonists. In conclusion, our results suggest that andrographolide may activate alpha1-ARs to enhance the secretion of beta-endorphin which can stimulate the opioid micro-receptors to reduce hepatic gluconeogenesis and to enhance the glucose uptake in soleus muscle, resulting in a decrease of plasma glucose in STZ-diabetic rats. However, the roles of other endogenous opioid peptides or the mixture of several opioid peptides in the activation of opioid micro-receptors associated with the plasma glucose-lowering action of andrographolide, should be considered and need more investigation in the future.

  8. Protective Effects of Fufang Xueshuantong on Diabetic Retinopathy in Rats

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    Huihui Duan

    2013-01-01

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

  9. Effect of the Total Extract of Averrhoacarambola (Oxalidaceae Root on the Expression Levels of TLR4 and NF-κB in Streptozotocin-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Xiaohui Xu

    2015-07-01

    Full Text Available Background: Averrhoacarambola L., which is a folk medicine used in diabetes mellitus (DM in ancient China, has been reported to have anti-diabetic efficacy. Aims: The aim of this study was to evaluate the hypoglycemic effect of the extract of Averrhoacarambola L. root (EACR on the regulation of the Toll-like receptor 4 (TLR4-Nuclear-factor kappa B (NF-κB pathway in B pathway in streptozotocin (STZ-induced diabetic mice. Methods: the mice were injected with STZ (120 mg/kg body weight via a tail vein. After 72 h, the mice with FBG = 11.1 mmol/L were confirmed as having diabetes. Subsequently, the mice were treated intragastrically with EACR (300, 600, 1200 mg/kg body weight/d and metformin (320 mg/kg body weight/d for 14 days. Results: As a result the serum fasting blood glucose (FBG, interleukin-6 (IL-6 and tumor necrosis factor-a (TNF-a levels were decreased following EACR administration. Immunohistochemical analysis revealed that the pancreatic tissue expression levels of TLR4 and NF-κB were downregulated after EACR administration. EACR suppressed pancreatic mRNA expression level of TLR4 and blocked the downstream NF-κB pathway in the pancreas. According to Western blot analysis EACR suppressed pancreatic TLR4 and NF-κB protein expression levels. Histopathological examination of the pancreas showed that STZ-induced pancreas lesions were alleviated by the EACR treatment. Conclusion: These findings suggest that the modulation of the IL-6 and TNF-a inflammatory cytokines and the suppression of the TLR4-NF-κB pathway are most likely involved in the anti-hyperglycemic effect of EACR in STZ-induced diabetic mice.

  10. 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.

  11. Effect of spent turmeric on kidney glycoconjugates in streptozotocin-induced diabetic rats

    Science.gov (United States)

    2014-01-01

    Background Curcumin known to have number of medicinal use and masked the fiber containing ukonan like active polysaccharide in turmeric and its pharmacological effect will be addressed on diabetic nephropathy particularly the glycoconjugates of extracellular components viz., glycoproteins and glycosaminoglycans - heparan sulfate (HS). Methods Male Wistar rats were maintained on AIN-76 diet containing 10% spent turmeric and were grouped into control and STZ induced diabetes SFC/TFC and SFD/TFD, respectively. Diabetic status was monitored using blood and urine, and at the end, harvested kidneys were used to study the amelioration of glycoprotiens (collagen) and HS by enzymatic digestion, spectrophotometric, hydroxyproline and agarose electrophoretic methods. Results In the present study spent turmeric (10%) fed diabetic rats showed improved glomerular filtration rate (50%), kidney enlargement (60%) and other glycoconjugate metabolism in kidney. Increased collagen content in diabetic group was observed by hydroxyproline estimation (24%) and periodic acid-Schiff’s (PAS) staining. Furthermore, elevated activities of enzymes involved in the synthesis and degradation of glycosaminoglycans (GAGs) were significantly lowered in spent turmeric fed diabetic group. Improvement in total GAGs (43%) and sulfate content (18%) followed by fractionation of GAGs using specific enzymes led to HS (28%) in the spent turmeric fed diabetic group, when compared to starch fed diabetic group and was further confirmed by electrophoresis of GAG. Conclusion These results clearly indicate beneficial role of spent turmeric in controlling glycoconjugates such as glycoproteins and heparan sulfate related kidney complications during diabetes. PMID:26413492

  12. Chicken Embryos as a Potential New Model for Early Onset Type I Diabetes

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    Liheng Shi

    2014-01-01

    Full Text Available Diabetic retinopathy (DR is the leading cause of blindness among the American working population. The purpose of this study is to establish a new diabetic animal model using a cone-dominant avian species to address the distorted color vision and altered cone pathway responses in prediabetic and early diabetic patients. Chicken embryos were injected with either streptozotocin (STZ, high concentration of glucose (high-glucose, or vehicle at embryonic day 11. Cataracts occurred in varying degrees in both STZ- and high glucose-induced diabetic chick embryos at E18. Streptozotocin-diabetic chicken embryos had decreased levels of blood insulin, glucose transporter 4 (Glut4, and phosphorylated protein kinase B (pAKT. In STZ-injected E20 embryos, the ERG amplitudes of both a- and b-waves were significantly decreased, the implicit time of the a-wave was delayed, while that of the b-wave was significantly increased. Photoreceptors cultured from STZ-injected E18 embryos had a significant decrease in L-type voltage-gated calcium channel (L-VGCC currents, which was reflected in the decreased level of L-VGCCα1D subunit in the STZ-diabetic retinas. Through these independent lines of evidence, STZ-injection was able to induce pathological conditions in the chicken embryonic retina, and it is promising to use chickens as a potential new animal model for type I diabetes.

  13. Aire deficiency causes increased susceptibility to streptozotocin-induced murine type 1 diabetes.

    Science.gov (United States)

    Hässler, S; Peltonen, L; Sandler, S; Winqvist, O

    2008-06-01

    Aire-deficient mice are a model of the human monogenic disorder autoimmune polyendocrine syndrome type I (APS I) characterized by a progressive autoimmune destruction of multiple endocrine glands such as the adrenal cortex, the parathyroids and the beta-cells of the pancreas. The disease is caused by mutations in the autoimmune regulator (AIRE) gene, a putative transcription factor expressed in thymic medullary epithelial cells and in antigen-presenting cells of the myeloid lineage in peripheral lymphoid organs. As Aire(-/-) mice do not spontaneously develop endocrinopathies, we wanted to evaluate the autoimmune multiple low-dose streptozotocin (MLDSTZ) diabetes model in Aire(-/-) mice. Surprisingly, Aire heterozygote mice were most susceptible to MLDSTZ-induced diabetes, whereas Aire(-/-) mice displayed an intermediate sensitivity to diabetes. Furthermore, Aire(-/-) macrophages produced higher levels of TNF-alpha and lower levels of IL-10 following streptozotocin stimulation, and Aire(-/-) mice developed a higher frequency of islet cells autoantibodies as a sign of increased activation. However, the number of islet infiltrating F4/80(+) Aire(-/-) macrophages was significantly decreased which was attributed to an increased susceptibility to streptozotocin cytotoxicity of Aire(-/-) macrophages. In conclusion, Aire(-/-) macrophages display an increased activation after STZ stimuli, but suffer from increased susceptibility to STZ cytotoxicity. These results support an important function of Aire in the control of peripheral tolerance through myeloid antigen-presenting cells.

  14. Consumption of Polyphenol-Rich Zingiber Zerumbet Rhizome Extracts Protects against the Breakdown of the Blood-Retinal Barrier and Retinal Inflammation Induced by Diabetes

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    Thing-Fong Tzeng

    2015-09-01

    Full Text Available The present study investigates the amelioration of diabetic retinopathy (DR by Zingiber zerumbet rhizome ethanol extracts (ZZRext in streptozotocin-induced diabetic rats (STZ-diabetic rats. ZZRext contains high phenolic and flavonoid contents. STZ-diabetic rats were treated orally with ZZRext (200, 300 mg/kg per day for three months. Blood-retinal barrier (BRB breakdown and increased vascular permeability were found in diabetic rats, with downregulation of occludin, and claudin-5. ZZRext treatment effectively preserved the expression of occludin, and claudin-5, leading to less BRB breakdown and less vascular permeability. Retinal histopathological observation showed that the disarrangement and reduction in thickness of retinal layers were reversed in ZZRext-treated diabetic rats. Retinal gene expression of tumor necrosis factor-α, interleukin (IL-1β, IL-6, vascular endothelial growth factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in ZZRext-treated diabetic rats. Moreover, ZZRext treatment not only inhibited the nuclear factor κB (NF-κB activation, but also downregulated the protein expression of p38 mitogen-activated protein kinase (MAPK in diabetic retina. In conclusion, the results suggest that the retinal protective effects of ZZRext occur through improved retinal structural change and inhibiting retinal inflammation. The antiretinopathy property of ZZRext might be related to the downregulation of p38 MAPK and NF-κB signal transduction induced by diabetes.

  15. Anti-diabetic effects of Inonotus obliquus polysaccharides in streptozotocin-induced type 2 diabetic mice and potential mechanism via PI3K-Akt signal pathway.

    Science.gov (United States)

    Wang, Jia; Wang, Cong; Li, Shuqin; Li, Weiwei; Yuan, Guoqi; Pan, Yuxiang; Chen, Haixia

    2017-11-01

    Polysaccharides are the main components of mushroom Inonotus obliquus (I. obliquus) with antihyperglycemic activities. This study was aimed to investigate the anti-diabetic effects and the potential mechanism of I. obliquus polysaccharides (IOPS) in high fat diet and STZ-induced type 2 diabetic mice. Results showed that oral administration of IOPS (900mg/kg) could significantly restore the body and fat mass weight, reduce fasting blood glucose levels, improve glucose tolerance ability, increase hepatic glycogen level and ameliorate insulin resistance compared to those of the control diabetic mice (Pdiabetic mice. The results suggested that IOPS might be a promising functional food or drug candidate for diabetes treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

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    Xiuyuan Zhang

    2016-12-01

    Full Text Available Background/Aims: The endocannabinoid signalling (ECS system has been known to regulate glucose homeostasis. Previous studies have suggested that the cannabinoid 2 (CB2 receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance. Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD/streptozotocin (STZ-induced mice. Methods: Diabetes was induced in male ICR mice by HFD/STZ and exposed to a CB2 receptor agonist, SER601, for 2- or 4-weeks via subcutaneous implantation of osmotic minipumps. Glucose and insulin tolerance tests were performed at the end of treatment. Islets were isolated for assessment of β-cell function. Pancreases and skeletal muscles were also obtained for histological analyses. Results: Despite a lack of impact on glucose tolerance, substantial improvement on insulin sensitivity was observed in SER601-treated mice, which could partly be attributed to improved islet β-cell function, shown as increased glucose-induced insulin secretion and insulin content. No changes on islet macrophage infiltration or skeletal muscle fat deposition were detectable from SER601-treated mice. However, a major decrease in body weight was recorded at the end of 4-week SER601 exposure, accompanied by a lack of epididymal adipose mass in SER601-treated mice. Conclusion: Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity. Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.

  17. Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Zhang, Xiuyuan; Gao, Shan; Niu, Jinfeng; Li, Pan; Deng, Juan; Xu, Shixin; Wang, Zhihong; Wang, Weiwei; Kong, Deling; Li, Chen

    2016-01-01

    The endocannabinoid signalling (ECS) system has been known to regulate glucose homeostasis. Previous studies have suggested that the cannabinoid 2 (CB2) receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance. Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-induced mice. Diabetes was induced in male ICR mice by HFD/STZ and exposed to a CB2 receptor agonist, SER601, for 2- or 4-weeks via subcutaneous implantation of osmotic minipumps. Glucose and insulin tolerance tests were performed at the end of treatment. Islets were isolated for assessment of β-cell function. Pancreases and skeletal muscles were also obtained for histological analyses. Despite a lack of impact on glucose tolerance, substantial improvement on insulin sensitivity was observed in SER601-treated mice, which could partly be attributed to improved islet β-cell function, shown as increased glucose-induced insulin secretion and insulin content. No changes on islet macrophage infiltration or skeletal muscle fat deposition were detectable from SER601-treated mice. However, a major decrease in body weight was recorded at the end of 4-week SER601 exposure, accompanied by a lack of epididymal adipose mass in SER601-treated mice. Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity. Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes. © 2016 The Author(s) Published by S. Karger AG, Basel.

  18. Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia.

    Science.gov (United States)

    Xin, Ying; Jiang, Xin; Wang, Yishu; Su, Xuejin; Sun, Meiyu; Zhang, Lihong; Tan, Yi; Wintergerst, Kupper A; Li, Yan; Li, Yulin

    2016-01-01

    The two major obstacles in the successful transplantation of islets for diabetes treatment are inadequate supply of insulin-producing tissue and immune rejection. Induction of the differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) into insulin-producing cells (IPCs) for autologous transplantation may alleviate those limitations. hMSCs were isolated and induced to differentiate into IPCs through a three-stage differentiation protocol in a defined media with high glucose, nicotinamide, and exendin-4. The physiological characteristics and functions of IPCs were then evaluated. Next, about 3 × 10(6) differentiated cells were transplanted into the renal sub-capsular space of streptozotocin (STZ)-induced diabetic nude mice. Graft survival and function were assessed by immunohistochemistry, TUNEL staining and measurements of blood glucose levels in the mice. The differentiated IPCs were characterized by Dithizone (DTZ) positive staining, expression of pancreatic β-cell markers, and human insulin secretion in response to glucose stimulation. Moreover, 43% of the IPCs showed L-type Ca2+ channel activity and similar changes in intracellular Ca2+ in response to glucose stimulation as that seen in pancreatic β-cells in the process of glucose-stimulated insulin secretion. Transplantation of functional IPCs into the renal subcapsular space of STZ-induced diabetic nude mice ameliorated the hyperglycemia. Immunofluorescence staining revealed that transplanted IPCs sustainably expressed insulin, c-peptide, and PDX-1 without apparent apoptosis in vivo. IPCs derived from hMSCs in vitro can ameliorate STZ-induced diabetic hyperglycemia, which indicates that these hMSCs may be a promising approach to overcome the limitations of islet transplantation.

  19. Antihypertriglyceridemia and Anti-Inflammatory Activities of Monascus-Fermented Dioscorea in Streptozotocin-Induced Diabetic Rats

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    Yeu-Ching Shi

    2011-01-01

    Full Text Available The rice fermented by Monascus, called red mold rice (RMR, and has a long tradition in East Asia as a dietary staple. Monascus-fermented dioscorea called red mold dioscorea (RMD contains various metabolites to perform the ability of reducing oxidative stress and anti-inflammatory response. We used Wistar rats and induced diabetes by injecting streptozotocin (STZ, 65 mg/kg i.p.. RMD was administered daily starting six weeks after disease onset. Throughout the experimental period, significantly (<.05 lowered plasma glucose, triglyceride, cholesterol, free fatty acid and low density lipoprotein levels were observed in the RMD-treated groups. The RMD-treated diabetic rats showed higher activities of glutathione disulfide reductase, glutathione reductase, catalase and superoxide dismutase (<.05 in the pancreas compared with the diabetic control rats. RMD also inhibited diabetes-induced elevation in the levels of interleukin (IL-1β, IL-6, interferon-γ and tumor necrosis factor-α. Pancreatic β-cells damaged by STZ in the RMD supplemented groups were ameliorated. The results of this study clearly demonstrated that RMD possesses several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects, pancreatic β-cell protection and anti-inflammatory effects. Considering these observations, it appears that RMD may be a useful supplement to delay the development of diabetes and its complications.

  20. Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats

    DEFF Research Database (Denmark)

    Feigh, Michael; Hjuler, Sara T; Andreassen, Kim V

    2014-01-01

    We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present...... was enhanced in conjunction with protection of pancreatic insulin content. The results of the present study indicate that oral sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in obesity and type 2 diabetes....... study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ....... Oral sCT by gavage was delivered as once-daily administration with lead-in (2mg/kg) and maintenance (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight, blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of insulin sensitivity were investigated. Plasma...

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

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    Omotayo Owomofoyon Erejuwa

    2010-05-01

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

  2. Antihyperlipidemic Activity of the Ethyl-acetate Fraction of Stereospermum Suaveolens in Streptozotocin-induced Diabetic Rats.

    Science.gov (United States)

    Thirumalaisamy, Balasubramanian; Prabhakaran, Senthilkumar Gnanavadevel; Marimuthu, Karthikeyan; Chatterjee, Tapan Kumar

    2013-09-01

    Dyslipidemia in diabetes mellitus is a significant risk factor for the development of cardiovascular complications. The aim of this study was to evaluate the effect of the ethyl-acetate fraction of an ethanolic extract from Streospermum suaveolens on lipid metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitonial injection of STZ (50 mg/kg). Diabetic rats were treated with an ethyl-acetate fraction orally at doses of 200 and 400 mg/kg daily for 14 days. On the 15(th) day, serum lipid profiles, such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), were estimated in experimental rats. The atherogenic (AI) and the coronary risk (CRI) indices were also evaluated. The ethyl-acetate fraction at doses of 200 and 400 mg/kg significantly (Pethyl-acetate fraction of Stereospermum suaveolens exhibits a potent antihyperlipidemic activity in hyperglycemic rats and suggests that the plant may have therapeutic value in treating the diabetic complication of hyperlipidemia.

  3. Effects of adipose-derived stem cells plus insulin on erectile function in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Zhou, Feng; Hui, Yu; Xu, Yongde; Lei, Hongen; Yang, Bicheng; Guan, Ruili; Gao, Zhezhu; Xin, Zhongcheng; Hou, Jianquan

    2016-05-01

    Erectile dysfunction (ED) is a distressing complication in men with diabetes mellitus (DM). This study aimed to investigate the effects of adipose-derived stem cells (ADSCs) plus insulin on ED in streptozotocin (STZ)-induced diabetic rats. Forty-five eight-week-old male Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg/kg). Eight weeks after the induction, the determined diabetic rats were randomly distributed into four groups: rats in DM + PBS group received a one-time intracavernous (IC) injection of phosphate-buffered saline (PBS) solution, DM + ADSCs group received IC injection of ADSCs, DM + Insulin group received subcutaneous injection of neutral protamine Hagedorn twice a day, and DM + ADSCs + Insulin group received both ADSCs and neutral protamine Hagedorn treatments. Another 10 normal rats were served as control group and received IC injection of PBS. Four weeks after the treatments, intracavernous pressure, histopathological changes in penis, functional proteins of ADSCs, and penis were measured. We found that ADSCs expressed vascular endothelial growth factor, TIMP metallopeptidase inhibitor 1 (TIMP-1), and lipopolysaccharide-inducible CXC chemokine (LIX). ADSC injection partially restored cavernous endothelium and smooth muscle contents and nNOS-positive nerves, and reduced apoptosis in penis compared with PBS-treated diabetic rats. Insulin treatment could further modulate inflammatory response and reduce advanced glycation end-product accumulation in penis. Better than single therapy, ADSCs combined with insulin ameliorate ED and pathological changes in diabetic rats to near-normal levels.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Miguel Roehrs

    2014-01-01

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

  6. Bixin and norbixin have opposite effects on glycemia, lipidemia, and oxidative stress in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Roehrs, Miguel; Figueiredo, Cassieli Gehlen; Zanchi, Mariane Magalhães; Bochi, Guilherme Vargas; Moresco, Rafael Noal; Quatrin, Andréia; Somacal, Sabrina; Conte, Lisiane; Emanuelli, Tatiana

    2014-01-01

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

  7. Comparison of the effects of fresh leaf and peel extracts of walnut (Juglans regia L. on blood glucose and β-cells of streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Somaye Javidanpour

    2012-12-01

    Full Text Available There is some report about the hypoglycemic effect of Juglans rejia L. leaf in alloxan induced diabetic rats and hypoglycemic effect of its fruit peel administered intra peritoneally. Thirty male Wistar rats divided into five groups, to evaluate the hypoglycemic and pancreas β-cells regenerative effects of oral methanolic extracts of leaf and fruit peel of walnut. Rats were made diabetic by intravenous (IV injection of 50 mg kg-1 streptozotocin (STZ. Negative control group did not get STZ and any treatment. Positive control, leaf extract, peel extract and insulin groups were treated orally by extract solvent, 200 mg kg-1 leaf extract, 200 mg kg-1 peel extract and 5 IU kg-1 of subcutaneous neutral protamine Hagedorn (NPH insulin, respectively. Four weeks later, blood was collected for biochemical analysis and pancreases were removed for β-cells counts in histological sections. Diabetes leads to increase of fast blood sugar (FBS and HbA1c, and decrease of β-cell number and insulin. FBS decreased only in leaf extract group. HbA1c decreased in leaf extract and insulin groups. The β-cells number increased in leaf and peel extract groups. Insulin increased moderately in all treatment groups. We showed the proliferative properties of leaves and peel of Juglans regia L. methanolic extract in STZ- induced diabetic rats, which was accompanied by hypoglycemic effect of leaf extract.

  8. Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities.

    Science.gov (United States)

    Maciel, Roberto M; Carvalho, Fabiano B; Olabiyi, Ayodeji A; Schmatz, Roberta; Gutierres, Jessié M; Stefanello, Naiara; Zanini, Daniela; Rosa, Michelle M; Andrade, Cinthia M; Rubin, Maribel A; Schetinger, Maria Rosa; Morsch, Vera Maria; Danesi, Cristiane C; Lopes, Sonia T A

    2016-12-01

    The present study investigated the protective effect of quercetin (Querc) on memory, anxiety-like behavior and impairment of ectonucleotidases and acetylcholinesterase (AChE) activities in brain of streptozotocin-induced diabetic rats (STZ-diabetes). The type 1 diabetes mellitus was induced by an intraperitoneal injection of 70mg/kg of streptozotocin (STZ), diluted in 0.1M sodium-citrate buffer (pH 4.5). Querc was dissolved in 25% ethanol and administered by gavage at the doses of 5, 25 and 50mg/kg once a day during 40days. The animals were distributed in eight groups of ten animals as follows: vehicle, Querc 5mg/kg, Querc 25mg/kg, Querc 50mg/kg, diabetes, diabetes plus Querc 5mg/kg, diabetes plus Querc 25mg/kg and diabetes plus Querc 50mg/kg. Querc was able to prevent the impairment of memory and the anxiogenic-like behavior induced by STZ-diabetes. In addition, Querc prevents the decrease in the NTPDase and increase in the adenosine deaminase (ADA) activities in SN from cerebral cortex of STZ-diabetes. STZ-diabetes increased the AChE activity in SN from cerebral cortex and hippocampus. Querc 50mg/kg was more effective to prevent the increase in AChE activity in the brain of STZ-diabetes. Querc also prevented an increase in the malondialdehyde levels in all the brain structures. In conclusion, the present findings showed that Querc could prevent the impairment of the enzymes that regulate the purinergic and cholinergic extracellular signaling and improve the memory and anxiety-like behavior induced by STZ-diabetes. Copyright © 2016. Published by Elsevier Masson SAS.

  9. Efek Hipoglikemik Kecambah Beras Merah pada Tikus yang Diinduksi STZ-NA dengan Parameter Kadar Insulin, Indeks HOMA-IR dan HOMA β

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    Nurhidajah Nurhidajah

    2017-02-01

    Full Text Available The process of germination of grains such as rice, could increase some nutritional values of  amino acids and dietary fiber. Red rice and its sprouts are believed to be able to decrease blood glucose in patients with diabetes mellitus (DM. The aim of this study was to evaluate the hypoglycemic effect of red rice sprouts in STZ-NA induced diabetic rats on blood glucose level, insulin level, and HOMA-IR and HOMA-β index. This experimental study was conducted based on randomized post test only control group design using 24 male Wistar rats aged 2.5 months. Rats were divided into 4 groups, one group without induction of STZ-NA fed with a standard diet (control and three groups of STZ- NA induced with a standard diet, red rice and red rice germ. Experiments were conducted for 6 weeks. The results showed that sprouted red rice lowered blood glucose levels by 61.88 % and the value of HOMA-IR (insulin resistance parameters by 56.82%. Insulin level increased by 16.35 % and HOMA-β by 763.6 %. This study showed that red rice germ was able to decrease blood glucose levels and increase insulin resistance of DM rats and the strength of the pancreatic beta cells.   ABSTRAK Proses perkecambahan biji-bijian seperti beras, dapat meningkatkan beberapa nilai gizi seperti asam amino dan serat pangan. Beras merah dan kecambahnya diyakini mampu menurunkan glukosa darah pada penderita diabetes melitus (DM. Tujuan penelitian ini adalah mengevaluasi efek hipoglikemik kecambah beras merah pada tikus diabetes yang diinduksi STZ-NA terhadap kadar glukosa darah, insulin, serta indeks HOMA-IR dan HOMA β. Penelitian ini bersifat eksperimental in vivo pada hewan coba tikus Wistar jantan usia 2,5 bulan sebanyak 24 ekor dengan desain penelitian randomized post test only control group. Tikus dibagi menjadi 4 kelompok, masing-masing 1 kelompok tanpa induksi STZ-NA dengan diet standar dan 3 kelompok diinduksi STZ-NA dengan diet standar, beras merah dan kecambah beras merah

  10. EFFECT OF EXERCISE TRAINING OF DIFFERENT INTENSITIES ON ANTI-INFLAMMATORY REACTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

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    J.–S. Kim

    2014-07-01

    Full Text Available The study investigated the effect of high- and low-intensity exercise training on inflammatory reaction of blood and skeletal muscle in streptozotocin (STZ-induced diabetic male Sprague-Dawley rats (243 ± 7 g, 8 weeks. The rats completed treadmill running in either high-intensity exercise (6 weeks of exercise training, acute bouts of exercise or low-intensity exercise (6 weeks of exercise training. Non-running, sedentary rats served as controls. To induce diabetes mellitus, rats received a peritoneal injection of STZ (50 mg · kg-1. Rats were sacrificed immediately after an acute bout of exercise and 6 weeks of exercise training. Inflammatory factors were analyzed by ELISA and by immune blotting from the soleus and extensor digitorum longus muscles. In the serum, inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-4 and reactive oxygen species (ROS (nitric oxide and malondialdehyde increased in diabetic rats. However, all exercise training groups displayed reduced inflammatory cytokines and reactive oxygen species. In skeletal muscles, low-intensity exercise training, but not high intensity exercise, reduced the levels of COX-2, iNOS, and MMP-2, which were otherwise markedly elevated in the presence of STZ. Moreover, the levels of GLUT-4 and MyoD were effectively increased by different exercise intensity and exercise duration. Low-intensity exercise training appeared most effective to reduce diabetes-related inflammation. However, high-intensity training also reduced inflammatory factors in tissue-specific muscles. The data implicate regular exercise in protecting against chronic inflammatory diseases, such as diabetes.

  11. Diabetes promotes DMH-induced colorectal cancer by increasing the activity of glycolytic enzymes in rats.

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    Yanglei Jia

    Full Text Available The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats.

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

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    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.

  13. Effect of Chang Run Tong on the Biomechanical and Morphometric Remodeling of Colon and Rectum in STZ Induced Diabetic Rats

    DEFF Research Database (Denmark)

    Sha, Hong; Zhao, Dong; Zhao, Jingbo

    2013-01-01

    , low dosage: 25 g/kg/day) and normal (Con) rats. The experimental period was 60 d. The blood glucose level and body weight were measured. The circumferential length, wall thickness, and opening angle were measured from the segments in the no-load and zero-stress states. The residual strain was computed...

  14. Effect of Tangweian Jianji on the Biomechanical and Morphometric Remodeling of Colon and Rectum in STZ Induced Diabetic Rats

    DEFF Research Database (Denmark)

    Sha, Hong; Tong, Xiao-Lin; Liu, Gui-Fang

    2012-01-01

    was computed. Circumferential and longitudinal stresses and strains were computed from the length, diameter and pressure data and from the zero-stress state geometry for the colonic segment. RESULTS: The glucose and insulin levels did not differ among DM, TH and TL groups. Wet weight, wall thickness, cross......-sectional wall area, opening angle, and absolute values of residual strain of colonic and rectal segments in DM group were significantly higher than those in CON group (P

  15. Ophiocordyceps formosana improves hyperglycemia and depression-like behavior in an STZ-induced diabetic mouse model

    OpenAIRE

    Huang, Chao-Wei; Hong, Tzu-Wen; Wang, Ying-Jing; Chen, Ko-Chien; Pei, Ju-Chun; Chuang, Tai-Yuan; Lai, Wen-Sung; Tsai, Sheng-Hong; Chu, Richard; Chen, Wei-Cheng; Sheen, Lee-Yan; Takahashi, Satoru; Ding, Shih-Torng; Shen, Tang-Long

    2016-01-01

    Background A newly defined Cordyceps species, Ophiocordyceps formosana (O. formosana) has been implicated in multitudinous bioactivities, including lowering glucose and cholesterol levels and modulating the immune system. However, few literatures demonstrate sufficient evidence to support these proposed functions. Although the use of Cordyceps spp. has been previously addressed to improve insulin insensitivity and improve the detrimental symptoms of depression; its mechanistic nature remains ...

  16. The effect of leukocyte function of streptozotocin-induced diabetes in naturally occurring gingivitis rat.

    Science.gov (United States)

    Inoue, H; Shinohara, M; Ohura, K

    1997-12-01

    Although diabetes mellitus is known to aggravate periodontal disease, the precise relationship between these two entities is far from being completely understood. Further study of this relationship was therefore undertaken in the form of observation of both naturally occurring gingivitis in rats (ODUS/Odu) and effects produced by induction of experimental diabetes mellitus by injection of streptozotocin (STZ: 65 mg/kg, i.v.). At one and 3 mon after STZ injection, liquid paraffin was injected intraperitoneally. Four days thereafter, pocket probing depths of rats were measured and blood samples as well as peritoneal macrophages were collected from both experimental animals and non diabetic controls. Both chemotaxis and phagocytosis of macrophages were studied. At one and 3 mon after STZ injection, pocket probing depths of diabetic animals were significantly deeper than those of controls (p diabetic animals. At three months after STZ injection, there was a high degree of positive correlation between pocket probing depths, blood glucose levels, triglyceride, and hemoglobin A1c levels (p diabetic rats than it was in controls. Additionally, both phagocytosis ratios and phagocytosis indices of macrophages in the diabetes group were significantly more suppressed than those in controls in both experimental periods (p diabetic by STZ injection. Thus as host defense mechanisms become weakened, there is a corresponding progression of periodontal disease.

  17. PENGARUH PEMBERIAN KEFIR BENING TERHADAP KADAR GLUKOSA DARAH PADA TIKUS WISTAR HIPERGLIKEMIA YANG DIINDUKSI STREPTOZOTOCIN (STZ

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    Judiono Judiono

    2012-11-01

    Full Text Available ABSTRACT Background: Hyperglycemia in diabetes caused by excessive free-radicals, which in turn increases reactive oxygen species, reduced immune function and antioxidant, the beta cell damage. Objective: To validate the effects of plain kefir probiotic on blood glucose level in streptozotocin (STZ induced hyperglycemia Wistar rats. Methods: The experiment using randomized pretest-posttest control group design was carried-out on 48 male hyperglycemia Wistar rats induced by 40 mg/kg body-weight of STZ. Rats were divided randomly into four groups: (1 negative control fed ad libitum standard diet, (2 positive control induced by STZ, (3 insulin treated 0.76 UI/200 g body weight, and (4 plain kefir 3.6 cc per day. Kefir is prepared by the use of pasteurized skim milk fermented by kefir commercial inoculums. Blood glucose was measured with Super Glucocard II meter (Arkray, Kyoto, Japan. Results Kefir supplementation 3.6 cc per day had significantly effect on blood glucose reduction after… days. Results showed that blood glucose levels before and after the treatment in each group as follows: in negative control group, before and after the treatment were 92.7 ± 6.6 mgdL and 89.4 ± 5.3 mgdL, respectively; in positive control group, before and after treatment were 263.9 ± 61.7 mgdL and 290.9 ± 99.8 mgdL; in insulin group, before and after the treatment were 286.9 ± 73.2 mgdL and 168.3 ± 53.3 mgdL; and in kefir group, before and after the treatment were 234.0 ± 61.1 mgdL and 147.8 ± 52.6 mgdL. Conclusion: Kefir supplementation significantly reduced blood glucose in vivo. Isolation and identification of probiotic involved on biomolecular and to find out the role of specific probiotic originated from kefir in diabetes mellitus are very challenging to be implemented in clinical application. [Penel Gizi Makan 2009, 32(2: 129-136] Key words: probiotic, kefir, diabetes mellitus, hyperglicemia, streptozotocin

  18. Anti-diabetic activity of extract from Persea americana Mill. leaf via the activation of protein kinase B (PKB/Akt) in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Lima, C R; Vasconcelos, C F B; Costa-Silva, J H; Maranhão, C A; Costa, J; Batista, T M; Carneiro, E M; Soares, L A L; Ferreira, F; Wanderley, A G

    2012-05-07

    The leaves of Persea americana Mill. (Lauraceae) have been popularly used in the treatment of diabetes in countries in Latin America and Africa. To investigate the hypoglycaemic properties and to determine the molecular mechanism by which the hydroalcoholic extract of the leaves of Persea americana reduce blood glucose levels in streptozotocin (STZ)-induced diabetes in rats via the enzymatic pathway of protein kinase B (PKB/Akt). The hydroalcoholic extract of the leaves of Persea americana (0.15 and 0.3g/kg/day), vehicle and metformin (0.5g/kg/day) were administered orally to STZ-diabetic rats (n=7/group) for 4 weeks. Changes in body weight, food and water intake, fasting glucose levels and oral glucose tolerance were evaluated. Phosphorylation and the expression of PKB in the liver and soleus muscle were determined by Western blot. The hydroalcoholic extract of the leaves of Persea americana reduced blood glucose levels and improved the metabolic state of the animals. Additionally, PKB activation was observed in the liver and skeletal muscle of treated rats when compared with untreated rats. The results indicate that the hydroalcoholic extract of the leaves of Persea americana has anti-diabetic properties and possibly acts to regulate glucose uptake in liver and muscles by way of PKB/Akt activation, restoring the intracellular energy balance. Copyright © 2012. Published by Elsevier Ireland Ltd.

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

    Science.gov (United States)

    Juárez-Rojop, Isela Esther; Díaz-Zagoya, Juan C; Ble-Castillo, Jorge L; Miranda-Osorio, Pedro H; Castell-Rodríguez, Andrés E; Tovilla-Zárate, Carlos A; Rodríguez-Hernández, Arturo; Aguilar-Mariscal, Hidemi; Ramón-Frías, Teresa; Bermúdez-Ocaña, Deysi Y

    2012-11-28

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

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

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    Juárez-Rojop Isela Esther

    2012-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-11-04

    Cuscuta reflexa Roxb. (Convolvulaceae) is traditionally used to treat diabetes mellitus by tribal people of north-east India and Bangladesh. To evaluate the anti-diabetic effects of methanol and aqueous extracts of the aerial parts of Cuscuta reflexa Roxb. in normal, glucose loaded and Streptozotocin (STZ) induced diabetic rats. The methanol (MECR) and aqueous (AECR) extracts (200 and 400mg/kg body weight) were administered orally to normal and diabetic rats with Metformin and solvent control as comparison groups. Long term effects like FBG, OGTT, lipid profile, HbA1c, body weight, histopathology of major organs, etc. were investigated. MECR and AECR did not have hypoglycemic effects in normal rats. Both AECR and MECR (400mg/kg) treatments showed significant reduction in blood glucose during OGTT in diabetic rats at 3h. Single oral administration of methanol and aqueous extracts (400mg/kg) to diabetic rats significantly reduced (p400mg/kg body weight for 30 days to diabetic rats) showed a significant decrease (p<0.01) of blood glucose level to 60.00% as compared to other groups. The treatment also resulted an improvement in body weights, decreased HbA1c and restored lipid profile. Histopathological injury was not observed, rather repair of beta cells was seen in extract treated diabetic rats. Methanolic extract of C. reflexa has significant antidiabetic effects and improves metabolic alterations thereby justifying its traditional folkloric claims. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Effect of interleukin-6 (IL-6) on the vascular smooth muscle contraction in abdominal aorta of rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Tang, Wen-Bo; Zhou, Yu-Qin; Zhao, Ting; Shan, Jing-Li; Sun, Peng; Yang, Ting-Ting; Chang, Xin-Wen; Li, Sen; Wang, Paulus S; Xie, Dong-Ping

    2011-10-31

    Patients with type 1 diabetes are at a risk of hypertension. However, the mechanisms behind the findings are not completely known. The aim of the present study was to investigate involvement of interleukin-6 (IL-6) on the contraction of abdominal aorta in rats with type 1 diabetes. IL-6 levels in the plasma of rats with streptozotocin (STZ)-induced diabetes were determined by ELISA. The abdominal aorta was dissected free of fat and connective tissues and then cut into spiral rings. The endothelium-denuded strip was vertically suspended in tissue chambers containing 5 ml Krebs solution at 37 degrees C and bubbled continuously with 95% O2-5% CO2. The effects of phenylephrine (Phe) on the contractile responses of abdominal aorta were recorded. The effects of IL-6 and anti-rat IL-6 antibody on the Phe-induced response were also examined. Plasma levels of IL-6 increased time-dependently in rats with STZ-induced diabetes. Phe caused concentration-dependent contraction in aortic rings. Phe-induced contractions were higher in vascular strips of STZ-induced diabetic rats than that of control rats. Pretreatment of vascular strips with IL-6 for 1 h did not cause contraction but enhanced the contraction in response to Phe. Treatment of the vascular strips with an anti-IL-6 antibody for 1 h decreased the Phe-induced contractions. These results suggest that IL-6 causes vascular smooth muscle contraction in abdominal aorta of rats with type 1 diabetes.

  4. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice

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    Akram Ahangarpour

    2017-02-01

    Full Text Available Objective: Arctium lappa (burdock, (A. lappa root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ-induced type2 diabetes in mice.Materials and Methods: In this investigation, 70 adult male NMRI mice (30-35g randomly divided into 7 groups (n=10 as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated.Results: Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL and increased the level of other lipids, glucose, and hepatic enzymes significantly (p

  5. Positron emission tomography imaging of the glucagon-like peptide-1 receptor in healthy and streptozotocin-induced diabetic pigs

    Energy Technology Data Exchange (ETDEWEB)

    Nalin, Lovisa; Andreasson, Susanne; Wikstrand, Anna; Ryden, Anneli; Nyman, Goerel; Jensen-Waern, Marianne [Swedish University of Agricultural Sciences, Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Uppsala (Sweden); Selvaraju, Ram K.; Eriksson, Olof [Uppsala University, Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala (Sweden); Velikyan, Irina [Uppsala University, Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala (Sweden); Uppsala University, Department of Radiology, Oncology and Radiation Sciences, Uppsala (Sweden); Uppsala University Hospital, PET Centre, Centre for Medical Imaging, Uppsala (Sweden); Berglund, Marie [Uppsala University, Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala (Sweden); Uppsala University, Department of Radiology, Oncology and Radiation Sciences, Uppsala (Sweden); Lubberink, Mark [Uppsala University, Department of Radiology, Oncology and Radiation Sciences, Uppsala (Sweden); Kandeel, Fouad [Beckman Research Institute of the City of Hope, Duarte, CA (United States); Korsgren, Olle [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden)

    2014-09-15

    The glucagon-like peptide-1 receptor (GLP-1R) has been proposed as a target for molecular imaging of beta cells. The feasibility of non-invasive imaging and quantification of GLP-1R in pancreas using the positron emission tomography (PET) tracer [{sup 68}Ga]Ga-DO3A-VS-Cys{sup 40}-Exendin-4 in non-diabetic and streptozotocin (STZ)-induced diabetic pigs treated with insulin was investigated. Non-diabetic (n = 4) and STZ-induced diabetic pigs (n = 3) from the same litter were examined. Development of diabetes was confirmed by blood glucose values, clinical examinations and insulin staining of pancreatic sections post mortem. Tissue perfusion in the pancreas and kidneys was evaluated by [{sup 15}O]water PET/computed tomography (CT) scans. The in vivo receptor specificity of [{sup 68}Ga]Ga-DO3A-VS-Cys{sup 40}-Exendin-4 was assessed by administration of either tracer alone or by competition with 3-6.5 μg/kg of Exendin-4. Volume of distribution and occupancy in the pancreas were quantified with a single tissue compartment model. [{sup 15}O]water PET/CT examinations showed reduced perfusion in the pancreas and kidneys in diabetic pigs. [{sup 68}Ga]Ga-DO3A-VS-Cys{sup 40}-Exendin-4 uptake in the pancreas of both non-diabetic and diabetic pigs was almost completely abolished by co-injection of unlabeled Exendin-4 peptide. [{sup 68}Ga]Ga-DO3A-VS-Cys{sup 40}-Exendin-4 uptake did not differ between non-diabetic and diabetic pigs. In all animals, administration of the tracer resulted in an immediate increase in the heart rate (HR). Pancreatic uptake of [{sup 68}Ga]Ga-DO3A-VS-Cys{sup 40}-Exendin-4 was not reduced by destruction of beta cells in STZ-induced diabetic pigs. (orig.)

  6. Hypoglycemic activity of Cassia javanica Linn. in normal and streptozotocin-induced diabetic rats

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    Urmila C Kumavat

    2012-01-01

    Full Text Available In present work, one of the ornamentals and medicinally less known plant Cassia javanica has been explored for hypoglycemic potential. It aimed to check the hypoglycemic effect of C. javanica leaves on normal and streptozotocin (STZ-induced diabetic rats by acute and sub-acute studies. Prior to the hypoglycemic study, acute oral toxicity testing of drug was performed. Later, the effects of single and multiple doses of test drug were studied using various parameters. Dried powdered leaf material was used as an oral drug. The preliminary phytochemistry of drug was done by standard qualitative tests. Diabetes was induced in rats by single intraperitoneal injection of STZ. Single and multiple doses of test drug (0.5 g/kg body weight/day were given to normal and diabetic rats. The parameters studied were blood glucose, serum cholesterol, serum triglycerides, and serum proteins. The results of test drug were compared with standard hypoglycemic drug-glibenclamide (0.01 g/kg/day. Statistical analysis was done by ′Student′s ′t′ test′ and one way ANOVA test. In preliminary phytochemistry, antidiabetic compounds were detected. Unlike acute, subacute treatment of test drug showed highly significant reduction (37.62% in blood glucose level of diabetic rats in ten days. This effect was considerably good in comparison with standard drug (63.51%. The test drug and standard drug exhibited insignificant change in the abnormal levels of serum metabolites of diabetic rats. Preclinically, C. javanica was proved to be effective hypoglycemic agent.

  7. Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms

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    Aragno Manuela

    2012-10-01

    Full Text Available Abstract Background The aim of this study was to investigate whether obestatin (OB, a peptide mediator encoded by the ghrelin gene exerting a protective effect in ischemic reperfused heart, is able to reduce cardiac dysfunctions in adult diabetic rats. Methods Diabetes was induced by STZ injection (50 mg/kg in Wistar rats (DM. OB was administered (25 μg/kg twice a day for 6 weeks. Non-diabetic (ND rats and DM rats were distributed into four groups: untreated ND, OB-treated ND, untreated DM, OB-treated DM. Cardiac contractility and ß-adrenergic response were studied on isolated papillary muscles. Phosphorylation of AMPK, Akt, ERK1/2 and GSK3ß as well ß-1 adrenoreceptors levels were detected by western blot, while α-MHC was measured by RT-PCR. Results OB preserved papillary muscle contractility (85 vs 27% of ND, ß-adrenergic response (103 vs 65% of ND, as well ß1-adrenoreceptors and α-MHC levels in diabetic myocardial tissue. Moreover, OB up-regulated the survival kinases Akt and ERK1/2, and enhanced AMPK and GSK3ß phosphorylation. OB corrected oxidative unbalance, reduced pro-inflammatory cytokine TNF-α plasma levels, NFkB translocation and pro-fibrogenic factors expression in diabetic myocardium. Conclusions OB displays a significant beneficial effect against the alterations of contractility and ß-adrenergic response in the heart of STZ-treated diabetic rats, which was mainly associated with the ability of OB to up-regulate the transcription of ß1-adrenergic receptors and α-MHC; this protective effect was accompanied by the ability to restore oxidative balance and to promote phosphorylation/modulation of AMPK and pro-survival kinases such as Akt, ERK1/2 and GSK3ß.

  8. Evidence of Anti-hyperglycemic and Anti-oxidant Effect of Passiflora edulis flavicarpa (Sims. in Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Subash PANCHANATHAN

    2015-12-01

    Full Text Available Diabetes mellitus is a worldwide problem and has no distinct cure. The present study was designed to investigate the antidiabetic, antioxidant and antilipidemic effects of Passiflora edulis flavicarpa extract (PefEt against streptozotocin (STZ induced diabetic rats. A total of forty wistar rats were randomly divided into four groups (n = 10 male rats/group as control; control+PefEt; diabetic and diabetic + PefEt. Streptozotocin was administered as a single dose (50 mg/kg to induce diabetes. The effect of Passiflora edulis flavicarpa (PefEt-250 mg/kg bodyweight for four weeks on diabetic rats was investigated by evaluating various biochemical parameters. The levels of blood glucose, C-peptide, insulin; enzymatic antioxidants, total antioxidant status, oxidative markers (Malondialdehyde and Urinary 8-hydroxydeoxyguanosine and lipid profile were measured. Levels of glucose, MDA and urinary 8-OHdG were significantly decreased, while levels of antioxidants, C-peptide and insulin were significantly increased on administration of PefEt in the STZ-induced rats when compared to control groups. Therefore, it could be concluded that PefEt must be considered as an excellent herb for future studies on diabetes mellitus.

  9. Effects of Murraya koenigii leaf extract on impaired gastrointestinal motility in streptozotocin-induced diabetic rats.

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    Tembhurne, Sachin V; Sakarkar, Dinesh M

    2011-08-01

    The present study was to investigate the effects of Murraya koenigii leaf (MKL), an Indian herb, on glucose homeostasis, intestinal transit time, response to exogenous acetylcholine of smooth muscles of distal colon, and intestinal thiobarbituric acid reactive substance (TBARS) level in streptozotocin (STZ)-induced diabetic rats. Male adult Wistar rats were used in this study. Diabetes was induced in the rats by STZ (70 mg/kg, intravenously). The treatments of MKL extract (300 and 500 mg/kg) and glibenclamide were started after stabilization of blood glucose level (13 d after single dose of STZ), while the standard drug cisapride or vitamin E was given from the last week (8th week) of experimentation. At the end of the study, the rats were sacrificed and evaluated for gastrointestinal motility, the contractile response of distal colons and the TBARS content. The gastrointestinal motility was evaluated by measuring the intestinal transit rate of charcoal meal. The contractile response of distal colon was measured in terms of evaluating the dose-response curve with increasing doses of acetylcholine, and the TBARS content was measured by calculating the level of polyunsaturated fatty acid in homogenates of intestines of the diabetic rats. MKL significantly decreased the blood glucose level at the 30th (P<0.05) and 60th (P<0.01) day of MKL administration (300 and 500 mg/kg). The gastrointestinal motility significantly (P<0.05) reduced after 9 weeks in diabetic rats and it was correlated to the decrease of the percent response of acetylcholine on distal colons (P<0.01) and the increase of TBARS (as an index of oxidative stress) in intestines (P<0.05), while prior treatment with MKL (300 and 500 mg/kg) up to 9 weeks increased the gastrointestinal motility demonstrated by the increase in the activation of cholinergic response to acetylcholine on distal colons (P<0.05). The TBARS also decreased after 9-week treatment with MKL (P<0.05). The present study suggested that MKL

  10. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

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    Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Wang, Yunbiao [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102 (China); Xiong, Tao [College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025 (China); Ling, Xiao [Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012 (China); Zheng, Jianfeng [Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  11. Hypoglycemic effects of Zanthoxylum alkylamides by enhancing glucose metabolism and ameliorating pancreatic dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    You, Yuming; Ren, Ting; Zhang, Shiqi; Shirima, Gerald Gasper; Cheng, YaJiao; Liu, Xiong

    2015-09-01

    This study aimed to evaluate the hypoglycemic effect of Zanthoxylum alkylamides and explore the potential mechanism in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were orally treated with 3, 6, and 9 mg per kg bw alkylamides daily for 28 days. As the alkylamide dose increased, the relative weights of the liver and kidney, fasting blood glucose, and fructosamine levels were significantly decreased. The alkylamides also significantly increased the body weight and improved the oral glucose tolerance of the rats. Likewise, the alkylamides significantly increased the levels of liver and muscle glycogen and plasma insulin. These substances further alleviated the histopathological changes in the pancreas of the diabetic rats. The beneficial effects of high-dose alkylamides showed a comparable activity to the anti-diabetic drug glibenclamide. Western blot and real-time PCR results revealed that the alkylamide treatment significantly decreased the expression levels of the key enzymes (phosphoenolpyruvate caboxykinase and glucose-6-phosphatase) involved in gluconeogenesis and increased the glycolysis enzyme (glucokinase) in the liver, and enhanced the expression levels of pancreatic duodenal homeobox-1, glucokinase, and glucose transporter 2 in the pancreas. In addition, it was also observed that the alkylamides, unlike glibenclamide, increased the transient receptor potential cation channel subfamily V member 1 and decreased cannabinoid receptor 1 expressions in the liver and pancreas. Therefore, alkylamides can prevent STZ-induced hyperglycemia by altering the expression levels of the genes related to glucose metabolism and by ameliorating pancreatic dysfunction.

  12. Antidiabetic Effects of Carassius auratus Complex Formula in High Fat Diet Combined Streptozotocin-Induced Diabetic Mice

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    Zhi-Hong Wang

    2014-01-01

    Full Text Available Carassius auratus complex formula, including Carassius auratus, Rhizoma dioscoreae, Lycium chinense, and Rehmannia glutinosa Libosch, is a combination prescription of traditional Chinese medicine, which has always been used to treat diabetes mellitus in ancient China. In this study, we provided experimental evidence for the use of Carassius auratus complex formula in the treatment of high fat diet combined streptozotocin- (STZ- induced type 2 diabetes. Carassius auratus complex formula aqueous extract was prepared and the effects of it on blood glucose, serum insulin, adipose tissue weight, oral glucose tolerance test (OGTT, total cholesterol, and triglyceride (TG levels in mice were measured. Moreover, adiponectin, TG synthesis related gene expressions, and the inhibitory effect of aldose reductase (AR were performed to evaluate its antidiabetic effects. After the 8-week treatment, blood glucose, insulin levels, and adipose tissue weight were significantly decreased. OGTT and HOMA-IR index showed improved glucose tolerance. It could also lower plasma TG, TC, and liver TG levels. Furthermore, Carassius auratus complex formula could inhibit the activity of AR and restore adiponectin expression in serum. Based on these findings, it is suggested that Carassius auratus complex formula possesses potent anti-diabetic effects on high fat diet combined STZ-induced diabetic mice.

  13. Folic Acid Reduces Tau Phosphorylation by Regulating PP2A Methylation in Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Zheng, Miaoyan; Zou, Chen; Li, Mengyue; Huang, Guowei; Gao, Yuxia; Liu, Huan

    2017-04-19

    High incidence rate of Alzheimer's disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice. Diabetic mice induced by STZ, at the age of 10 weeks, were administered with three levels of folic acid: folic acid-deficient diet, diet with normal folic acid content, and 120 μg/kg folic acid diet for 8 weeks. Levels of serum folate and blood glucose were monitored. Tau phosphorylation, protein phosphatase 2A (PP2A) methylation, and Glycogen synthase kinase 3β (GSK-3β) phosphorylation were detected using Western blot. The S-adenosyl methionine:S-adenosyl homocysteine ratio (SAM:SAH) in brain tissues was also determined. DNA methyltransferase (DNMT) mRNA expression levels were detected using real-time PCR. Folic acid reduced tau hyperphosphorylation at Ser396 in the brain of diabetes mellitus (DM) mice. In addition, PP2A methylation and DNMT1 mRNA expression were significantly increased in DM mice post folic acid treatment. GSK-3β phosphorylation was not regulated by folic acid administration. Folic acid can reduce tau phosphorylation by regulating PP2A methylation in diabetic mice. These results support that folic acid can serve as a multitarget neuronal therapeutic agent for treating diabetes-associated cognitive dysfunction.

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

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    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.  

  15. Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina.

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    Lahouaoui, Hasna; Coutanson, Christine; Cooper, Howard M; Bennis, Mohamed; Dkhissi-Benyahya, Ouria

    2016-01-01

    Diabetic retinopathy is one of the most common consequences of diabetes that affects millions of working-age adults worldwide and leads to progressive degeneration of the retina, visual loss, and blindness. Diabetes is associated with circadian disruption of the central and peripheral circadian clocks, but the mechanisms responsible for such alterations are unknown. Using a streptozotocin (STZ)-induced model of diabetes, we investigated whether diabetes alters 1) the circadian regulation of clock genes in the retina and in the central clocks, 2) the light response of clock genes in the retina, and/or 3) light-driven retinal dopamine (DA), a major output marker of the retinal clock. To quantify circadian expression of clock and clock-controlled genes, retinas and suprachiasmatic nucleus (SCN) from the same animals were collected every 4 h in circadian conditions, 12 weeks post-diabetes. Induction of Per1, Per2, and c-fos mRNAs was quantified in the retina after the administration of a pulse of monochromatic light (480 nm, 1.17×10(14) photons/cm(2)/s, 15 min) at circadian time 16. Gene expression was assessed with real-time reverse transcription PCR (RT-PCR). Pooled retinas from the control and STZ-diabetic mice were collected 2 h after light ON and light OFF (Zeitgeber time (ZT)2 and ZT14), and DA and its metabolite were analyzed with high-performance liquid chromatography (HPLC). We found variable effects of diabetes on the expression of clock genes in the retina and only slight differences in phase and/or amplitude in the SCN. c-fos and Per1 induction by a 480 nm light pulse was abolished in diabetic animals at 12 weeks post-induction of diabetes in comparison with the control mice, suggesting a deficit in light-induced neuronal activation of the retinal clock. Finally, we quantified a 56% reduction in the total number of tyrosine hydroxylase (TH) immunopositive cells, associated with a decrease in DA levels during the subjective day (ZT2). These findings

  16. Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina

    Science.gov (United States)

    Lahouaoui, Hasna; Coutanson, Christine; Cooper, Howard M.; Bennis, Mohamed

    2016-01-01

    Purpose Diabetic retinopathy is one of the most common consequences of diabetes that affects millions of working-age adults worldwide and leads to progressive degeneration of the retina, visual loss, and blindness. Diabetes is associated with circadian disruption of the central and peripheral circadian clocks, but the mechanisms responsible for such alterations are unknown. Using a streptozotocin (STZ)-induced model of diabetes, we investigated whether diabetes alters 1) the circadian regulation of clock genes in the retina and in the central clocks, 2) the light response of clock genes in the retina, and/or 3) light-driven retinal dopamine (DA), a major output marker of the retinal clock. Methods To quantify circadian expression of clock and clock-controlled genes, retinas and suprachiasmatic nucleus (SCN) from the same animals were collected every 4 h in circadian conditions, 12 weeks post-diabetes. Induction of Per1, Per2, and c-fos mRNAs was quantified in the retina after the administration of a pulse of monochromatic light (480 nm, 1.17×1014 photons/cm2/s, 15 min) at circadian time 16. Gene expression was assessed with real-time reverse transcription PCR (RT–PCR). Pooled retinas from the control and STZ-diabetic mice were collected 2 h after light ON and light OFF (Zeitgeber time (ZT)2 and ZT14), and DA and its metabolite were analyzed with high-performance liquid chromatography (HPLC). Results We found variable effects of diabetes on the expression of clock genes in the retina and only slight differences in phase and/or amplitude in the SCN. c-fos and Per1 induction by a 480 nm light pulse was abolished in diabetic animals at 12 weeks post-induction of diabetes in comparison with the control mice, suggesting a deficit in light-induced neuronal activation of the retinal clock. Finally, we quantified a 56% reduction in the total number of tyrosine hydroxylase (TH) immunopositive cells, associated with a decrease in DA levels during the subjective day (ZT2

  17. Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats.

    Science.gov (United States)

    Ahmed, Osama M; Hassan, Mohamed A; Abdel-Twab, Sanaa M; Abdel Azeem, Manal N

    2017-10-01

    The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade, there has been an interest in the expansion of anti-diabetic drugs especially those of natural sources. Thus, the aim of this study was to assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the anti-oxidant activities of navel orange hydroethanolic extract and its constituting flavonoids naringin and naringenin on nicotineamide (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16h-fasted rats were intraperitoneally injected with STZ at dose of 50mg/kg body weight (b. w.), 15min after the intraperitoneal administration of NA (120mg/kg b. w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel orange peel hydroethanolic extract, naringin and narengenin at dose level of 100mg/kg b. w./day for 4 weeks. The treatments with navel orange peel hydroethanolic extract, naringin and narengenin potentially alleviated the lowered serum insulin and C-peptide levels, the depleted liver glycogen content, the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities, the deteriorated serum lipid profile, and the suppressed liver antioxidant defense system of NA/STZ-induced type 2 diabetic rats. The treatments also enhanced the mRNA expression of insulin receptor β-subunit, GLUT4 and adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via their insulinotropic effects and insulin improving action which in turn may be mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in adipose tissue. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo.

    Science.gov (United States)

    Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

    2017-03-01

    The aim of this study was to observe whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5 F) cells against streptozotocin (STZ)-induced apoptosis in vitro and type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) in vivo and if so, what would be the mechanism of this action. RIN5 F cells were used for the in vitro study, whereas the in vivo study was performed in Wistar rats. STZ was used to induce apoptosis of RIN5 F cells in vitro and T1- and T2DM in vivo. The effect of PUFAs: γ-linolenic acid (GLA), arachidonic acid (AA) of ω-6 series, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of ω-3 series; cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors and antiinflammatory metabolite of AA and DHA, lipoxin A4 (LXA4), and resolvin D2 and protectin, respectively against STZ-induced cytotoxicity to RIN5 F cells in vitro and LXA4 against T1- and T2DM in vivo was studied. Changes in the antioxidant content, lipid peroxides, nitric oxide, and expression of PDX1, P65, nuclear factor-κb (NF-κb), and IKB genes in STZ-treated RIN5 F cells in vitro and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue of T1- and T2DM and LPCLN2 (lipocalin 2), NF-κb, IKB I in adipose tissue of T2DM after LXA4 treatment were studied. Plasma glucose, insulin, and tumor necrosis factor (TNF)-α levels also were measured in STZ-induced T1- and T2DM Wistar rats. Among all PUFAs tested, AA and EPA are the most effective against STZ-induced cytotoxicity to RIN5 F cells in vitro. Neither COX nor LOX inhibitors blocked the cytoprotective action of AA in vitro and T1- and T2DM by STZ. LXA4 production by RIN5 F cells in vitro and plasma LXA4 levels in STZ-induced T1- and T2DM animals were decreased by STZ that reverted to normal after AA treatment. AA prevented both T1- and T2DM induced by STZ. Antiinflammatory metabolite of AA and LXA4 prevented both T1- and T2DM induced by STZ. The expression of Pdx1, NF-κb, IKB genes in the

  19. Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

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    Cheng-Chia Tsai

    2014-01-01

    Full Text Available The present study investigated the merit of ginseng in the improvement of heart failure in diabetic rats and the role of peroxisome proliferator-activated receptors δ (PPARδ. We used streptozotocin-induced diabetic rat (STZ-rat to screen the effects of ginseng on cardiac performance and PPARδ expression. Changes of body weight, water intake, and food intake were compared in three groups of age-matched rats; the normal control (Wistar rats received vehicle, STZ-rats received vehicle and ginseng-treated STZ-rats. We also determined cardiac performances in addition to blood glucose level in these animals. The protein levels of PPARδ in hearts were identified using Western blotting analysis. In STZ-rats, cardiac performances were decreased but the food intake, water intake, and blood glucose were higher than the vehicle-treated control. After a 7-day treatment of ginseng in STZ-rats, cardiac output was markedly enhanced without changes in diabetic parameters. This treatment with ginseng also increased the PPARδ expression in hearts of STZ-rats. The related signal of cardiac contractility, troponin I phosphorylation, was also raised. Ginseng-induced increasing of cardiac output was reversed by the cotreatment with PPARδ antagonist GSK0660. Thus, we suggest that ginseng could improve heart failure through the increased PPARδ expression in STZ-rats.

  20. Antidiabetic and antioxidant effects of Annona muricata (Annonaceae), aqueous extract on streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Florence, Ngueguim Tsofack; Benoit, Massa Zibi; Jonas, Kouamouo; Alexandra, Tchuidjang; Désiré, Dzeufiet Djomeni Paul; Pierre, Kamtchouing; Théophile, Dimo

    2014-02-03

    The leaves of Annona muricata are used in Cameroon to manage diabetes and its complications. The aim of this study was to evaluate the antidiabetic, antioxidant activities and the potential toxicity of aqueous extract of Annona muricata in streptozotocin-induced diabetic rats. Oral administration of Annona muricata aqueous extract (100mg/kg or 200mg/kg) was studied in normal and streptozotocin-induced diabetic rats. In long term treatment, 2 weeks after streptozotocin-induced diabetic rats, animals received plant extract during 28 consecutive days. For a protective effect, extract was administered 3 days prior to streptozotocin exposure and animals were observed 2 weeks without treatment. The plant extract was not effective in normal rats. In diabetic rats, single administration of the extract significantly reduced blood glucose levels by 75% and 58.22% respectively at the dose of 100mg/kg and 200mg/kg as compared to the initial value. Treatment of normal rats 3 days prior to diabetes induction showed that, Annona muricata extract has no effect within 72h following STZ injection. However, after 14 days post-treatment, the extract at the dose of 100mg/kg significantly reduced blood glucose levels as compared with initial value and diabetic control rats. Immunohistochemical staining of pancreatic β-cells of diabetic rats treated with the dose of 100mg/kg expressed strong staining for β-cell compared to diabetic control. In a long-term study daily administration of Annona muricata aqueous extract for 28 days to diabetic rats, reduced blood glucose levels, serum creatinine, MDA, AST, ALT activity, and nitrite levels LDL-cholesterol. Total cholesterol, triglycerides, SOD, and CAT activity contents were restored. These different results show that the antidiabetic activity of Annona muricata aqueous extract can be explained by its hypolipidaemic effect, its antioxidant and protective action on pancreatic β-cells, which in turn improve glucose metabolism. © 2013

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

    Science.gov (United States)

    Heo, Myoung; Kim, Eunjung

    2013-08-01

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

  2. Comparison of Experimental Diabetic Periodontitis Induced by Porphyromonas gingivalis in Mice

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    Qi Wang

    2016-01-01

    Full Text Available Periodontitis is one of the severe complications in diabetic patients and gingival epithelium plays an initial role on the onset and progression of this disease. However the potential mechanism is yet sufficiently understood. Meanwhile, the research on the correlational experimental animal models was also insufficient. Here, we established periodontitis with type 2 diabetes in db/db and Tallyho/JngJ (TH mice and periodontitis with type 1 diabetes in streptozotocin induced diabetes C57BL/6J (STZ-C57 mice by oral infection of periodontal pathogen Porphyromonas gingivalis W50. We demonstrated that periodontal infected mice with high blood glucose levels showed dramatically more alveolar bone loss than their counterparts, in which infected db/db mice exhibited the most bone defects. No contrary impact could be observed between this periodontal infection and onset and severity of diabetes. The expressions of PTPN2 were inhibited whereas the expression of JAK1, STAT1, and STAT3 increased dramatically in gingival epithelia and the serum TNF-α also significantly increased in the mice with diabetic periodontitis. Our results indicated that the variations of inflammation-related protein expressions in gingival epithelia might lead to the phenotype differences in the mice with diabetic periodontitis.

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

    Science.gov (United States)

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

    2013-12-01

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

  4. Physical exercise reverses spatial memory deficit and induces hippocampal astrocyte plasticity in diabetic rats.

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    de Senna, Priscylla Nunes; Bagatini, Pamela Brambilla; Galland, Fabiana; Bobermin, Larissa; do Nascimento, Patrícia Severo; Nardin, Patrícia; Tramontina, Ana Carolina; Gonçalves, Carlos Alberto; Achaval, Matilde; Xavier, Léder Leal

    2017-01-15

    Physical exercise can induce brain plasticity and reduce the cognitive decline observed in type 1 diabetes mellitus (T1DM). We investigated the effects of physical exercise to prevent or reverse spatial memory deficits produced by diabetes and some biochemical and immunohistochemical changes in hippocampal astrocytes of T1DM model. In this study, 56 male Wistar rats were divided in four groups: trained control (TC), non-trained control (NTC), trained diabetic (TD) and non-trained diabetic (NTD). 27 days after streptozotocin-induced (STZ) diabetes, the exercise groups were submitted to 5 weeks of aerobic exercise. All groups were assessed in place recognition (PR) test before and after training. The glial fibrillary acidic protein (GFAP) positive astrocytes were evaluated using planar morphology, optical densitometry and Sholl's concentric circles method. Glucose and glutamate uptake, reduced glutathione (GSH) and glutamine synthetase (GS) levels were measured using biochemical assays. Our main results are: 1-Exercise reverses spatial memory impairments generated by T1DM; 2-Exercise increases GSH and GS in TC but not in TD rats; 3-Exercise increases density of GFAP positive astrocytes in the TC and TD groups and increases astrocytic ramification in TD animals. Our findings indicate that physical exercise reverses the cognitive deficits present in T1DM and induces important biochemical and immunohistochemical astrocytic changes. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Effect of rutin on diabetic-induced erectile dysfunction: Possible involvement of testicular biomarkers in male rats.

    Science.gov (United States)

    Al-Roujeaie, A S; Abuohashish, H M; Ahmed, M M; Alkhamees, O A

    2017-10-01

    The present study aimed to investigate effects of rutin on diabetic-induced impairments of sexual behaviour, spermatogenesis and oxidative testicular damage. Diabetes was induced by a single injection of STZ (65 mg/kg) in male adult Wistar rats. Two weeks later, rutin (50 and 100 mg kg-1  day-1 ) was treated to normal and diabetic rats for 5 weeks. Sexual behaviour of the animals was observed by taking stimulus females. At the end of the study, sperm count, motility and viability were recorded. Serum levels of glucose, inflammatory markers and testosterone were also estimated. In penile tissue, cGMP levels were measured, while lipid peroxidation and antioxidant molecules and enzyme activities were determined. Finally, histopathological changes were evaluated in a cross-section of testis. Diabetic-induced alterations in male sexual behaviour and sperm count, motility and viability were markedly corrected following 5 weeks of rutin treatment to the diabetic animals. Rutin also attenuated the inhibited serum testosterone and penile cGMP content, while improved diabetic-associated inflammation and testicular lipid peroxidation and oxidative stress. Histopathological evaluation revealed damaged testicular tissues in diabetic rats, which was protected following rutin treatment. In conclusion, treatment with rutin improved sexual functionality and also protects against diabetic-induced testicular damage. © 2016 Blackwell Verlag GmbH.

  6. Pyruvate administration reduces recurrent/moderate hypoglycemia-induced cortical neuron death in diabetic rats.

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    Full Text Available Recurrent/moderate (R/M hypoglycemia is common in type 1 diabetes patients. Moderate hypoglycemia is not life-threatening, but if experienced recurrently it may present several clinical complications. Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. We therefore hypothesized that pyruvate may be able to improve the outcome in diabetic rats subjected to insulin-induced R/M hypoglycemia by terminating hypoglycemia with glucose plus pyruvate, as compared with delivering just glucose alone. In an effort to mimic juvenile type 1 diabetes the experiments were conducted in one-month-old young rats that were rendered diabetic by streptozotocin (STZ, 50mg/kg, i.p. injection. One week after STZ injection, rats were subjected to moderate hypoglycemia by insulin injection (10 U/kg, i.p. without anesthesia for five consecutive days. Pyruvate (500 mg/kg was given by intraperitoneal injection after each R/M hypoglycemia. Three hours after last R/M hypoglycemia, zinc accumulation was evaluated. Three days after R/M hypoglycemia, neuronal death, oxidative stress, microglial activation and GSH concentrations in the cerebral cortex were analyzed. Sparse neuronal death was observed in the cortex. Zinc accumulation, oxidative injury, microglial activation and GSH loss in the cortex after R/M hypoglycemia were all reduced by pyruvate injection. These findings suggest that when delivered alongside glucose, pyruvate may significantly improve the outcome after R/M hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.

  7. Non-Obese Diabetic Mice Rapidly Develop Dramatic Sympathetic Neuritic Dystrophy

    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.

    2003-01-01

    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. PMID:14578206

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

    Science.gov (United States)

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

    2017-12-01

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

  9. Altered Macrophage and Dendritic Cell Response in Mif−/− Mice Reveals a Role of Mif for Inflammatory-Th1 Response in Type 1 Diabetes

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    Yuriko Itzel Sánchez-Zamora

    2016-01-01

    Full Text Available Macrophage migration inhibitory factor (Mif is highly expressed in type 1 diabetes mellitus (T1DM. However, there is limited information about how Mif influences the activation of macrophages (Mφ and dendritic cells (DC in T1DM. To address this issue, we induced T1DM by administering multiple low doses of streptozotocin (STZ to Mif−/− or wild-type (Wt BALB/c mice. We found that Mif−/− mice treated with STZ (Mif−/−STZ developed lower levels of hyperglycemia, inflammatory cytokines, and specific pancreatic islet antigen- (PIAg- IgG and displayed reduced cellular infiltration into the pancreatic islets compared to Wt mice treated with STZ (WtSTZ. Moreover, Mφ and DC from Mif−/−STZ displayed lower expression of MHC-II, costimulatory molecules CD80, CD86, and CD40, Toll-like receptor- (TLR- 2, and TLR-4 than WtSTZ. These changes were associated with a reduced capacity of Mφ and DC from Mif−/−STZ to induce proliferation in ovalbumin-specific T cells. All the deficiencies observed in Mif−/−STZ were recovered by exogenous administration of recombinant Mif. These findings suggest that Mif plays a role in the molecular mechanisms of Mφ and DC activation and drives T cell responses involved in the pathology of T1DM. Therefore, Mif is a potential therapeutic target to reduce the pathology of T1DM.

  10. Altered Macrophage and Dendritic Cell Response in Mif−/− Mice Reveals a Role of Mif for Inflammatory-Th1 Response in Type 1 Diabetes

    Science.gov (United States)

    Vazquez-Mendoza, Alicia

    2016-01-01

    Macrophage migration inhibitory factor (Mif) is highly expressed in type 1 diabetes mellitus (T1DM). However, there is limited information about how Mif influences the activation of macrophages (Mφ) and dendritic cells (DC) in T1DM. To address this issue, we induced T1DM by administering multiple low doses of streptozotocin (STZ) to Mif−/− or wild-type (Wt) BALB/c mice. We found that Mif−/− mice treated with STZ (Mif−/−STZ) developed lower levels of hyperglycemia, inflammatory cytokines, and specific pancreatic islet antigen- (PIAg-) IgG and displayed reduced cellular infiltration into the pancreatic islets compared to Wt mice treated with STZ (WtSTZ). Moreover, Mφ and DC from Mif−/−STZ displayed lower expression of MHC-II, costimulatory molecules CD80, CD86, and CD40, Toll-like receptor- (TLR-) 2, and TLR-4 than WtSTZ. These changes were associated with a reduced capacity of Mφ and DC from Mif−/−STZ to induce proliferation in ovalbumin-specific T cells. All the deficiencies observed in Mif−/−STZ were recovered by exogenous administration of recombinant Mif. These findings suggest that Mif plays a role in the molecular mechanisms of Mφ and DC activation and drives T cell responses involved in the pathology of T1DM. Therefore, Mif is a potential therapeutic target to reduce the pathology of T1DM. PMID:27699180

  11. Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice.

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    Zhou, Jun; Xu, Gang; Yan, Junyan; Li, Kaicheng; Bai, Zhaoshuai; Cheng, Weinan; Huang, Kaixun

    2015-04-22

    Rehmannia glutinosa (Gaertn.) DC. (RG) has been widely used as traditional Chinese herbal medicine for treatment of diabetes and its complications. The polysaccharide fraction of RG has been proposed to possess hypoglycemic effect by intraperitoneal administration, however, the mechanisms responsible for the hypoglycemic effect of RG polysaccharide (RGP) remain poorly understood. Here we studied the anti-hyperglycemic and anti-hyperlipidemic effect of oral administration of a purified RGP and its underlying mechanisms in streptozotocin (STZ)-induced diabetic mice. The preliminary structure of RGP was determined by GC and FT-IR. Mice were injected with STZ to induce type 1 diabetes. RGP at doses of 20, 40 and 80 mg/kg/day was orally administered to mice for 4 weeks, and metformin was used as positive control. After 4 weeks, the blood biochemical parameters, the pancreatic insulin contents, in vitro insulin secretion, the hepatic glycogen contents and mRNA expression of phosphoenolpyruvate carboxyl kinase (PEPCK) were assayed. RGP was composed of rhamnose, arabinose, mannose, glucose and galactose in the molar ratio of 1.00:1.26:0.73:16.45:30.40 with the average molecular weight of 63.5 kDa. RGP administration significantly decreased the blood levels of glucose, total cholesterol, triglycerides, low density lipoprotein-cholesterol, and increased the blood levels of high density lipoprotein-cholesterol and insulin in diabetic mice, concurrent with increases in body weights and pancreatic insulin contents. The in vitro study revealed that RGP significantly enhanced both basal and glucose-stimulated insulin secretions, as well as islet insulin contents in the pancreatic islets of diabetic mice. Moreover, RGP reversed the increased mRNA expression of PEPCK and the reduced glycogen contents in the liver of diabetic mice. Furthermore, RGP exhibited potent anti-inflammatory and anti-oxidative activities, as evidenced by the decreased blood levels of TNF-α, IL-6, monocyte

  12. Zataria multiflora essential oil reduces diabetic damages in ...

    African Journals Online (AJOL)

    diabetic effects were analyzed in the streptozotocin (STZ)-induced diabetic rats. The yield of EO was 3% and carvactol (53%), p-cymene (17%), and thymol (11%) were detected as the main EO components. The antioxidant and nitric oxide ...

  13. 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.

  14. The role of ghrelin on apoptosis, cell proliferation and oxidant-antioxidant system in the liver of neonatal diabetic rats.

    Science.gov (United States)

    Koyuturk, Meral; Sacan, Ozlem; Karabulut, Sezin; Turk, Neslihan; Bolkent, Sehnaz; Yanardag, Refiye; Bolkent, Sema

    2015-07-01

    Ghrelin is a multifunctional peptide hormone which stimulates appetite and regulates glucose metabolism and adipogenesis. The purpose of this study was to investigate whether ghrelin has protective effects in the liver of streptozocin (STZ) diabetic rats or not. Wistar-type neonatal rats were divided into four groups: I. Controls, II. Ghrelin administrated controls, III. STZ-diabetic rats, and IV. Ghrelin administrated diabetic rats. On the second day after birth, 100 mg/kg STZ was administered intraperitoneally in a single dose to induce diabetes in rats. 100 µg/kg/day ghrelin was administrated to rats subcutaneously for 4 weeks. Ghrelin administration improved histopathologic changes in STZ-diabetic liver. Obestatin immunoreactivity has been shown in livers of neonatal rats. The immunoreactivity of obestatin increased in diabetic rats and a decline was observed in ghrelin administrated diabetic rats. Caspase 8 and 3 immunoreactivities increased in diabetic rats; however, ghrelin administration differently affected caspases 8 and 3 immunoreactivities. Proliferating cell nuclear antigen immunoreactivities decreased in diabetic rats and in ghrelin administrated diabetic rats. Serum alanine (P diabetic rats compared to the diabetic rats. Gamma glutamyl transferase activity (P diabetic rats compared to the diabetic rats. The response of antioxidants including glutathione levels, catalase and superoxide dismutase activities were altered in ghrelin administrated diabetic rats. Our findings indicate that ghrelin administration affects hepatic functions in neonatal diabetic rats and might be considered as a therapeutic agent. © 2015 International Federation for Cell Biology.

  15. Low Dose Radiation Overcomes Diabetes-induced Suppression of Hippocampal Neuronal Cell Proliferation in Rats

    Science.gov (United States)

    Kim, Sang-Ki; Hong, Seong-Eon; Lee, Taeck-Hyun; Kim, Chang-Ju

    2006-01-01

    We investigated the effect of low dose radiation on diabetes induced suppression of neurogenesis in the hippocampal dentate gyrus of rat. After 0.01 Gy, 0.1 Gy, 1 Gy and 10 Gy radiation was delivered, the dentate gyrus of hippocampus of streptozotocin (STZ)-induced diabetic rats were evaluated using immunohistochemistry for 5-bromo-2-deoxyuridine (BrdU), caspase-3, and terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) staining. The number of BrdU positive cells in the non-diabetic rats, diabetic rats without radiation, diabetic rats with 0.01 Gy radiation, diabetic rats with 0.1 Gy radiation, diabetic rats with 1 Gy radiation and diabetic rats with 10 Gy radiation were 55.4±8.5/mm2, 33.3±6.4/mm2, 67.7±10.5/mm2, 66.6±10.0/mm2, 23.5±6.3/mm2and 14.3±7.2/mm2, respectively. The number of caspase-3 positive cells was 132.6±37.4/mm2, 378.6±99.1/mm2, 15.0±2.8/mm2, 57.1±16.9/mm2, 191.8±44.8/mm2and 450.4±58.3/mm2, respectively. The number of TUNEL-positive cells was 24.5±2.0/mm2, 21.7±4.0/mm2, 20.4±2.0/mm2, 18.96±2.1/mm2, 58.3±7.9/mm2, and 106.0±9.8/mm2, respectively. These results suggest low doses of radiation paradoxically improved diabetes induced neuronal cell suppression in the hippocampal dentate gyrus of rat. PMID:16778397

  16. Mori cortex prevents kidney damage through inhibiting expression of inflammatory factors in the glomerulus in streptozocin-induced diabetic rats

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    Lili Ma

    2017-06-01

    Full Text Available Objective(s: It has been widely reported that Mori cortex extract (MCE is used for the treatment of diabetes mellitus in traditional medicine. The present study was designed to investigate its mechanism of action in the treatment of diabetic nephropathy (DN. We assessed whether MCE preventive treatment ameliorates kidney damage in high-fat diet and streptozotocin (STZ-induced type 2 diabetic rats. Materials and Methods: Rats were fed a high-fat diet and injected with STZ. MCE was given to rats daily at 10 g/kg. Fasting blood glucose (FBG and postprandial plasma glucose were measured. Blood and urine biochemical parameters, renal tissue morphology, and inflammation were investigated. Results: Prevention with MCE significantly decreased FBG and homoeostasis model assessment (HOMA of IR (HOMA-IR levels and increased insulin levels in diabetic rats. MCE prevention significantly decreased levels of KW/BW, BUN, Cr, and 24 hr urinary protein. MCE inhibited glomerular basement membrane thickening, tubular epithelial cell hypertrophy, and glomerular capillary dilation. MCE also prevented the disappearance of bowman’s space and renal tubular lumen and decreased collagen deposition in rat kidney. Moreover, MCE reduced the levels of inflammatory factors (MCP-1 and TNF-α and fibrosis factors (collagen IV and fibronectin. Conclusion: MCE prevents DN through inhibition of inflammation and fibrosis in a rat model. It might provide a safe and effective way to prevent DN.

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

    Science.gov (United States)

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

    2013-02-01

    Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether the NF-κB signal transduction pathway was mobilized by CNTF. Neurite outgrowth of sensory neurons derived from streptozotocin (STZ)-induced diabetic rats was reduced compared to neurons from control rats and exposure to CNTF for 24 h enhanced neurite outgrowth. CNTF also activated NF-κB, as assessed by Western blotting for the NF-κB p50 subunit and reporter assays for NF-κB promoter activity. Conversely, blockade of NF-κB signaling using SN50 peptide inhibited CNTF-mediated neurite outgrowth. Studies in mice with STZ-induced diabetes demonstrated that systemic therapy with CNTF prevented functional indices of peripheral neuropathy along with deficiencies in dorsal root ganglion (DRG) NF-κB p50 expression and DNA binding activity. DRG neurons derived from STZ-diabetic mice also exhibited deficiencies in maximal oxygen consumption rate and associated spare respiratory capacity that were corrected by exposure to CNTF for 24 h in an NF-κB-dependent manner. We propose that the ability of CNTF to enhance axon regeneration and protect peripheral nerve from structural and functional indices of diabetic peripheral neuropathy is associated with targeting of mitochondrial function, in part via NF-κB activation, and improvement of cellular bioenergetics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Evaluation of the Antioxidant and Antiglycation Effects of Lactarius deterrimus and Castanea sativa Extracts on Hepatorenal Injury in Streptozotocin-Induced Diabetic Rats

    Science.gov (United States)

    Jovanović, Jelena Arambašić; Mihailović, Mirjana; Uskoković, Aleksandra S.; Grdović, Nevena; Dinić, Svetlana; Poznanović, Goran; Mujić, Ibrahim; Vidaković, Melita

    2017-01-01

    The present study aimed to investigate the beneficial effects of the treatment with extracts from the edible mushroom Lactarius deterrimus (Ld) and the chestnut Castanea sativa (Cs), separately and in combination (MIX Ld/Cs), on oxidative stress and advanced glycation end-product (AGE)-mediated hepatorenal injury in a rat model of streptozotocin (STZ)-induced diabetes by examining pathways responsible for maintenance of redox homeostasis. An experimental model of diabetes was induced in rats by the administration of 40 mg/kg STZ intraperitoneally (i.p.) for 5 consecutive days. The examined extracts were applied separately at a dose of 60 mg/kg i.p. and in combination (60 mg/kg each extract; i.p.) for 4 weeks, starting from the last day of STZ administration. The improvement of hepatorenal function in diabetic rats treated with the extracts was associated with an improved glycemic and lipid status and suppression of oxidative stress and thereby oxidative damage of lipids and DNA. Besides the fact that both extracts inhibited protein glycation and AGE formation in vitro, they also reduced non-enzymatic glycosylation in diabetic rats in vivo. The observed antiglycation activity of the examined extracts (separately and in combination) was accompanied with the inhibition of CML-mediated RAGE/NF-κB activation and reduction of enzymatic O-GlcNAcylation in liver and kidney tissues of diabetic rats. Taken together, these results reveal that the administration of chestnut and mushroom extracts, either individually or together, activates a coordinated cytoprotective response against diabetes-induced hepatorenal injury not only through recovery of the antioxidant defense system of the cell, but also through a marked antiglycation activity. PMID:29163175

  19. Evaluation of the Antioxidant and Antiglycation Effects ofLactarius deterrimusandCastanea sativaExtracts on Hepatorenal Injury in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Jovanović, Jelena Arambašić; Mihailović, Mirjana; Uskoković, Aleksandra S; Grdović, Nevena; Dinić, Svetlana; Poznanović, Goran; Mujić, Ibrahim; Vidaković, Melita

    2017-01-01

    The present study aimed to investigate the beneficial effects of the treatment with extracts from the edible mushroom Lactarius deterrimus (Ld) and the chestnut Castanea sativa (Cs), separately and in combination (MIX Ld/Cs), on oxidative stress and advanced glycation end-product (AGE)-mediated hepatorenal injury in a rat model of streptozotocin (STZ)-induced diabetes by examining pathways responsible for maintenance of redox homeostasis. An experimental model of diabetes was induced in rats by the administration of 40 mg/kg STZ intraperitoneally (i.p.) for 5 consecutive days. The examined extracts were applied separately at a dose of 60 mg/kg i.p. and in combination (60 mg/kg each extract; i.p.) for 4 weeks, starting from the last day of STZ administration. The improvement of hepatorenal function in diabetic rats treated with the extracts was associated with an improved glycemic and lipid status and suppression of oxidative stress and thereby oxidative damage of lipids and DNA. Besides the fact that both extracts inhibited protein glycation and AGE formation in vitro , they also reduced non-enzymatic glycosylation in diabetic rats in vivo. The observed antiglycation activity of the examined extracts (separately and in combination) was accompanied with the inhibition of CML-mediated RAGE/NF-κB activation and reduction of enzymatic O -GlcNAcylation in liver and kidney tissues of diabetic rats. Taken together, these results reveal that the administration of chestnut and mushroom extracts, either individually or together, activates a coordinated cytoprotective response against diabetes-induced hepatorenal injury not only through recovery of the antioxidant defense system of the cell, but also through a marked antiglycation activity.

  20. 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.

  1. Thalidomide Promotes Morphine Efficacy and Prevents Morphine-Induced Tolerance in Rats with Diabetic Neuropathy.

    Science.gov (United States)

    Zhao, Jianhui; Wang, Hong; Song, Tieying; Yang, Yunliang; Gu, Kunfeng; Ma, Pengyu; Zhang, Zaiwang; Shen, Limin; Liu, Jiabao; Wang, Wenli

    2016-12-01

    Opioid analgesics have less efficacy in diabetic neuropathy treatment, and tolerance often occurs after chronic usage. Given that thalidomide can potentiate the morphine efficacy in diabetic neuropathy treatment, we investigated the effects of intrathecal administrations of thalidomide on morphine tolerance during the treatment of diabetic neuropathy. We found that intrathecal administrations of thalidomide (25 mg/kg/ml) potentiated the analgesic effects of morphine on mechanical hyperalgesia and prevented the development of morphine tolerance. While this treatment regimen did not alter the protein levels of μ-opioid receptor (MOR) in the spinal cord of diabetic rats, chronic morphine treatment robustly increased MOR binding density in the synaptic plasma membranes fraction, but decreased it in the microsomal fraction. Furthermore, thalidomide was able to reverse the distribution of MOR altered by chronic morphine treatment. Finally, STZ-induced diabetes promoted PKC activation and enhanced TNFα level in the spinal cord, which were attenuated by intrathecal administrations of thalidomide. Taken together, these results suggested that thalidomide may potentiate morphine efficacy on diabetic neuropathy and prevent the development of morphine tolerance by suppressing PKC activation and TNFα level in the spinal cord.

  2. The effects of vanadium (V) absorbed by Coprinus comatus on bone in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Pei, Yi; Fu, Qin

    2011-09-01

    The purpose of this study was to evaluate the effects of vanadium absorbed by Coprinus comatus (VACC) treatment on bone in streptozotocin (STZ)-induced diabetic rats. Forty-five Wistar female rats used were divided into three groups: (1) normal rats (control), (2) diabetic rats, and (3) diabetic rats treated with VACC. Normal and diabetic rats were given physiological saline, and VACC-treated rats were administered VACC intragastrically at doses of 0.18 mg vanadium/kg body weight once daily. Treatments were performed over a 12-week period. At sacrifice, one tibia and one femur were removed, subjected to micro computed tomography (micro-CT) for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. Another femoral was used for mechanical testing. In addition, bone samples were collected to evaluate the content of mineral substances in bones. Treatment with VACC increased trabecular bone volume fraction in diabetic rats. Vanadium-treated animals had significant increases in ultimate load, trabecular thickness, and osteoblast surface. However, vanadium treatment did not seem to affect bone stiffness, bone energy absorption, trabecular separation, and osteoclast number. P levels in the femurs of diabetic rats treated with VACC were significantly higher than those of diabetic animals. Ca levels in diabetic and diabetic rats treated with vanadium showed no obvious changes. In conclusion, our results provide an important proof of concept that VACC may represent a powerful approach to treating or reversing diabetic osteopathy in humans.

  3. Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes.

    Science.gov (United States)

    Ziamajidi, Nasrin; Nasiri, Abolfazl; Abbasalipourkabir, Roghayeh; Sadeghi Moheb, Somayeh

    2017-12-01

    Allium sativum L. (Liliaceae) (garlic) is a medicinal plant that is widely used in herbal medicine. Nephropathy is a complication of diabetes that is induced by long-term hyperglycaemia. The effects of aqueous extract of garlic (AGE) on the expression of tumour necrosis factor-alpha (TNF-α) and oxidative stress status were studied in the kidneys of rats with streptozotocin (STZ) + nicotinamide-induced diabetes. Twenty-four Wistar rats were divided into four groups: control rats, rats with STZ + nicotinamide-induced diabetes that received a single dose of STZ (65 mg/kg) and nicotinamide (110 mg/kg) intraperitoneally, diabetic rats that were treated with garlic (2 g/kg/d, gavage), and normal rats that received garlic (2 g/kg/d, gavage). The glucose level was determined in the start of study, 7 d after induction of diabetes and 33 d after treatment with garlic. At the end of the treatment period, urea, uric acid and creatinine levels were estimated in sera. Malondialdehyde (MDA), total oxidant status (TOS), nitric oxide (NO) levels and TNF-α gene and protein expression were measured in the renal tissues of the rats. The glucose, uric acid, and urea levels increased in the serum of diabetic rats compared with control rats, and decreased in garlic-treated diabetic rats compared with diabetic rats (p garlic-treated diabetic rats compared with diabetic rats (p garlic, it was close to the normal level (p garlic extract has hypoglycaemic, antioxidant and anti-inflammatory properties; therefore, it can be useful for the alleviation of diabetic complications.

  4. Ulcer healing properties of different extracts of Origanum majorana in streptozotocin-nicotinamide induced diabetic rats

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    BP Pimple

    2012-08-01

    Full Text Available Objective: The aim of the present investigation was to evaluate the ulcer healing properties of different extracts of Origannum majorana, viz., hydrodistilled volatile oil (OMO, methanolic (OMM and aqueous extract (OMW in streptozotocin-nicotinamide induced diabetic rats. Methods: All the extracts were administered in different doses (100, 200 and 400 mg/kg, p.o. to investigate the ulcer healing potential. Streptozotocin (STZ; 65 mg/kg, i.p. along with nicotinamide (120 mg/kg, i.p. was used to induce non-insulin dependent diabetes mellitus in rats. Aspirin (200 mg/kg, i.p. was administered for initial 7 d to induce gastric ulcerations in the diabetic rats. Various biochemical markers of blood and tissue origin were estimated to compare the ulcer healing potential of these extracts. Results: The OMO and OMM exhibited dose dependent significant (P<0.01 ulcer healing property than the OMW. Additionally, the antidiabetic property of OMO and OMM was better than OMW. Conclusions: The OMO and OMM of Origanum majorana leaves can prove to be beneficial in the concomitant treatment of gastric ulcers and diabetes.

  5. Beneficial effect of the leaves of Murraya koenigii (Linn.) Spreng (Rutaceae) on diabetes-induced renal damage in vivo.

    Science.gov (United States)

    Yankuzo, Hassan; Ahmed, Qamar Uddin; Santosa, Rahajoe Imam; Akter, Seikh Farid Uddin; Talib, Norlewati A

    2011-04-26

    Murraya koenigii (Linn.) Spreng (curry leaf) is widely used as a nephroprotective agent in kidney's infirmities among diabetics by the traditional practitioners in Malaysia. However, the latter role of curry leaf has been grossly under reported and is yet to receive proper scientific evaluation. The present study was designed to investigate the beneficial effect of the leaves of Murraya koenigii (Linn.) on diabetes-induced renal damage in vivo with regard to prove its efficacy by local traditional practitioners in the treatment of kidney frailties in diabetics. Aqueous (AQ) extract of the leaves of Murraya koenigii (Linn.) was administered to both normal and streptozotocin (STZ) induced diabetic male rats (Sprague-Dawley strain). Animals were divided into six groups (n=6) and treated with variable dose levels of AQ extract (200 and 400mg/kg body weight/day) for 30 days. At the end of 30 days, animals were sacrificed, blood was collected, processed and stored at -70°C for the zestimation of serum urea and creatinine, changes in plasma antioxidant capacity by FRAP assay, and glutathione peroxidase levels, in the normal and STZ-induced diabetic rats. Histological changes of the kidneys of these animals were also evaluated by light microscopy to determine the beneficial effect of the leaves. Daily oral administration of variable dose levels of the AQ extract for 30 days, produced significant dose dependant decrease in serum urea and creatinine levels (pMurraya koenigii (Linn.) as adjuvant, in the treatment of pain disorders related to renal impairments among diabetics. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Antihyperglycemic Effect of Methanol Extract of Syzygium polyanthum (Wight. Leaf in Streptozotocin-Induced Diabetic Rats

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    Tri Widyawati

    2015-09-01

    Full Text Available Syzygium polyanthum (S. polyanthum, a plant belonging to Myrtaceae, is widely used in Indonesian and Malaysian cuisines. Diabetic patients in Indonesia also commonly use it as a traditional medicine. Hence, this study was conducted to investigate the antihyperglycemic effect of the methanol extract (ME of S. polyanthum leaf and its possible mechanisms of action. To test for hypoglycemic activity, ME was administered orally to normal male Sprague Dawley rats after a 12-h fast. To further test for antihyperglycemic activity, the same treatment was administered to glucose-loaded (intraperitoneal glucose tolerance test, IPGTT and streptozotocin (STZ-induced diabetic rats, respectively. Hypoglycemic test in normal rats did not show significant reduction in blood glucose levels (BGLs by the extract. Furthermore, IPGTT conducted on glucose-loaded normal rats also did not show significant reduction of BGLs. However, repeated administration of metformin and three doses of ME (250, 500 and 1000 mg/kg for six days caused significant reduction of fasting BGLs in STZ-induced diabetic rats. The possible mechanisms of action of S. polyanthum antihyperglycemic activity were assessed by measurement of intestinal glucose absorption and glucose uptake by isolated rat abdominal muscle. It was found that the extract not only inhibited glucose absorption from the intestine but also significantly increased glucose uptake in muscle tissue. A preliminary phytochemical qualitative analysis of ME indicated the presence of tannins, glycosides, flavonoids, alkaloids and saponins. Additionally, Gas Chromatography-Mass Spectrometry (GC-MS analysis detected squalene. In conclusion, S. polyanthum methanol leaf extract exerts its antihyperglycemic effect possibly by inhibiting glucose absorption from the intestine and promoting glucose uptake by the muscles.

  7. Characterization of upper thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in diabetic rats

    DEFF Research Database (Denmark)

    Ghorbani, Marie Louise M; Qin, Chao; Wu, Mingyuan

    2011-01-01

    The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes. Type 1 diabetes was induced with streptozotocin (50mg/kg) in 14 male Sprague-Dawley rats and citrate buffer was injected in 14 control rats. After 4-11weeks...

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

    OpenAIRE

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

  9. [Effect of secretory human calcitonin gene-related peptide recombinant AAV on penile erection in streptozotocin-induced diabetic rat].

    Science.gov (United States)

    Xing, Jun-ping; Cui, Xian-feng; Sun, Jian-hua; Qiu, Shu-dong

    2005-10-01

    To determine whether recombinant adeno-associated virus-mediated overexpression of hCGRP in the corpus cavernosum can affect the continuous production of hCGRP in the penile tissue and enhance erectile responses in STZ-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of 60 mg/kg streptozotocin in male SD rats. VssHGCMV-hCGRP, VssCMV-GFP and rAAV solution were injected into the corporal cavernosum of STZ-induced diabetic rats, respectively. The corporal tissue was obtained from groups of 8 rats on day 5 post-injection, and the expressions of CGRP and GFP in cavernosal tissue were detected using immunohistochemistry and laser scanning confocal microscopy, respectively. Cavemosal tissue cAMP and cGMP levels were measured using radioimmunoassay. On day 5 post-injection, intracavernous pressure induced by electrostimulation of penile dorsal nerves was measured and recorded with a biological signal processing system in each group rat. rAAV transduction efficiency of GFP reporter gene was measured by laser scanning confocal microscopy and was observed in the penile tissue, especially in the corporal cavernosum and the vessel 5 days after transfection with VssCMV-GFP. Immunohistochemistry showed that the CGRP increased in the corporal cavernosum. In addition, both cAMP and cGMP levels in the corpora cavernosa transfected with VssHGCMV-hCGRP were significantly increased, compared with controls [(48.4 +/- 6.5) nmol/L and (21.2 +/- 13.6) nmol/L vs (16.7 +/- 2.5) nmol/L and (0.42 +/- 0.12) nmol/L, respectively]. More importantly, 5 days after administration of VssHGCMV-hCGRP,a significant increase was observed in the erectile response to penile dorsal nerve stimulation in the diabetic rat [(60.5 +/- 4.5) mm Hg vs (22. 3 +/- 1.3) mm Hg]. This results demonstrate that rAAV-mediated transfer of the CGRP gene can increase production of endogenous CGRP, cAMP and cGMP in corpora cavernosa of STZ-induced diabetic rats. Moreover

  10. Immune tolerance induced by adoptive transfer of dendritic cells in an insulin-dependent diabetes mellitus murine model.

    Science.gov (United States)

    Zhang, Cheng-Liang; Zou, Xiao-Lei; Peng, Jia-Bei; Xiang, Ming

    2007-01-01

    To investigate the effect and underlying mechanisms of immune-tolerance induced by the adoptive transfer of bone marrow (BM)-derived dendritic cells (DC) in insulin-dependent diabetes mellitus (IDDM) mice. The IDDM model was established by a low dose of streptozotocin (STZ) in Balb/c mice. Two DC subpopulations were generated from the BM cells with granulocyte-macrophage colony-stimulating factor with or without interleukin-4. The purity and the T cell stimulatory capability of DC were identified. These cells were used to modulate autoimmune response in pre-diabetic mice. Blood glucose was examined weekly; pancreas tissues were taken for histopathological analysis, and CD4(+) T cells were isolated to detect lymphocyte proliferation by MTT assay and the ratio of CD4(+)CD25(+) T cells by fluorescence-activated cell sorting (FACS). The cytokine secretion was determined by ELISA analysis. Two DC subsets were generated from BM, which have phenotypes of mature DC (mDC) and immature DC (iDC), respectively. The level of blood glucose decreased significantly by transferring iDC (Ptransfer. Our data showed that iDC transfer was able to confer protection to mice from STZ-induced IDDM. The immune-tolerance to IDDM may be associated with promoting the production of CD4(+)CD25(+) T cells and inducing regulatory Th2 responses in vivo.

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

    Directory of Open Access Journals (Sweden)

    Tuğba Gürpınar

    2012-01-01

    Full Text Available Oxidative stress plays an important role in the development of complications in diabetes mellitus. Antioxidant therapy has been thought to decrease oxidative stress. The objective of the present study was to explore the effects of melatonin (MLT on oxidative stress in diabetic rat eye and brain tissue by using immunohistochemical methods. Diabetes was induced by streptozotocin, (STZ, 55 mg/kg/i.p in adult rats. MLT was given 10 mg/kg/i.p once a day for 2 weeks beginning from the sixth week. Six weeks later, rats were divided into three groups: control (CR, STZ-induced diabetic (STZ, and STZ-induced diabetic group received melatonin (STZ+MLT. Although no significant difference was observed with respect to antioxidant status, NOS activity tended to be higher in the untreated diabetic rats than in the treated rats. It was observed that MLT treatment improved the histopathological changes including apoptosis and oxidative stress in brain and eye in diabetic rat.

  12. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats.

    Science.gov (United States)

    Kandasamy, Neelamegam; Ashokkumar, Natarajan

    2014-09-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Effects of Ursolic Acid Derivatives on Caco-2 Cells and Their Alleviating Role in Streptozocin-Induced Type 2 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Panpan Wu

    2014-08-01

    Full Text Available In this study, the effect and mechanism of a series of ursolic acid (UA derivatives on glucose uptake were investigated in a Caco-2 cells model. Their effect on hyperglycemia, hyperlipidemia and oxidative stress were also demonstrated in streptozocin (STZ-induced diabetic rats. 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-ylamino]-2-deoxy-glucose (2-NBDG was used as a fluorescein in Caco-2 cells model to screen UA derivatives by glucose uptake and expression of glucose transporter protein (SGLT-1, GLUT-2. Moreover, STZ-induced diabetic rats were administered with these derivatives for 4 weeks of treatment. The fasting blood glucose (FBG, insulin levels, biochemical parameters, lipid levels, and oxidative stress markers were finally evaluated. The results of this study indicated that compounds 10 and 11 significantly inhibited 2-NBDG uptake under both Na+-dependent and Na+-independent conditions by decreasing SGLT-1 and GLUT-2 expression in the Caco-2 cells model. Further in vivo studies revealed that compound 10 significantly reduced hyperglycemia by increasing levels of serum insulin, total protein, and albumin, while the fasting blood glucose, body weight and food intake were restored much closer to those of normal rats. Compounds 10 and 11 showed hypolipidemic activity by decreasing the total amounts of cholesterol (TC and triglycerides (TG. Furthermore, compound 10 showed antioxidant potential which was confirmed by elevation of glutathione (GSH and superoxide dismutase (SOD and reduction of malondialdehyde (MDA levels in the liver and kidney of diabetic rats. It was concluded that compound 10 caused an apparent inhibition of intestinal glucose uptake in Caco-2 cells and hypoglycemia, hypolipidemia and augmented oxidative stress in STZ-induced diabetic rats. Thus, compound 10 could be developed as a potentially complementary therapeutic or prophylactic agent for diabetics mellitus and its complications.

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

    Science.gov (United States)

    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.

  15. Dysregulated LIF-STAT3 pathway is responsible for impaired embryo implantation in a Streptozotocin-induced diabetic mouse model

    Directory of Open Access Journals (Sweden)

    Tong-Song Wang

    2015-07-01

    Full Text Available The prevalence of diabetes is increasing worldwide with the trend of patients being young and creating a significant burden on health systems, including reproductive problems, but the effects of diabetes on embryo implantation are still poorly understood. Our study was to examine effects of diabetes on mouse embryo implantation, providing experimental basis for treating diabetes and its complications. Streptozotocin (STZ was applied to induce type 1 diabetes from day 2 of pregnancy or pseudopregnancy in mice. Embryo transfer was used to analyze effects of uterine environment on embryo implantation. Our results revealed that the implantation rate is significantly reduced in diabetic mice compared to controls, and the change of uterine environment is the main reason leading to the decreased implantation rate. Compared to control, the levels of LIF and p-STAT3 are significantly decreased in diabetic mice on day 4 of pregnancy, and serum estrogen level is significantly higher. Estrogen stimulates LIF expression under physiological level, but the excessive estrogen inhibits LIF expression. LIF, progesterone or insulin supplement can rescue embryo implantation in diabetic mice. Our data indicated that the dysregulated LIF-STAT3 pathway caused by the high level of estrogen results in the impaired implantation in diabetic mice, which can be rescued by LIF, progesterone or insulin supplement.

  16. Antihyperglycemic Effect of Ganoderma Lucidum Polysaccharides on Streptozotocin-Induced Diabetic Mice

    Science.gov (United States)

    Li, Fenglin; Zhang, Yiming; Zhong, Zhijian

    2011-01-01

    The current study evaluated the glucose-lowering effect of ganoderma lucidum polysaccharides (Gl-PS) in streptozotocin (STZ)-induced diabetic mice. The diabetic mice were randomly divided into four groups (8 mice per group): diabetic control group, low-dose Gl-PS treated group (50 mg/kg, Gl-PS), high-dose Gl-PS treated group (150 mg/kg, Gl-PS) and positive drug control treated group (glibenclamide, 4 mg/kg), with normal mice used as the control group. Body weights, fasting blood glucose (FBG), serum insulin and blood lipid levels of mice were measured. After 28 days of treatment with Gl-PS, body weights and serum insulin levels of the Gl-PS treated groups was significantly higher than that of the diabetic control group, whereas FBG levels was significantly lower. Moreover, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels of the Gl-PS treated groups had dropped, whereas the high density lipoprotein cholesterol (HDL-C) levels had increased. In addition, according to acute toxicity studies, Gl-PS did not cause behavioral changes and any death of mice. These data suggest that Gl-PS has an antihyperglycemic effect. Furthermore, considering the Gl-PS effects on lipid profile, it may be a potential hypolipidaemic agent, which will be a great advantage in treating diabetic conditions associated with atherosclerosis or hyperlipidemia. PMID:22016649

  17. Statin Therapy Alters Lipid Storage in Diabetic Skeletal Muscle.

    Directory of Open Access Journals (Sweden)

    Irena A Rebalka

    2016-07-01

    Full Text Available While statins significantly reduce cholesterol levels and thereby reduce the risk of cardiovascular disease, the development of myopathy with statin use is a significant clinical side-effect. Recent guidelines recommend increasing inclusion criteria for statin treatment in diabetic individuals; however, the impact of statins on skeletal muscle health in those with diabetes (who already suffer from impairments in muscle health is ill-defined. Here we investigate the effects of Fluvastatin treatment on muscle health in wild-type and streptozotocin (STZ-induced diabetic mice. Wild-type and STZ-diabetic mice received diet enriched with 600 mg/kg Fluvastatin or control chow for 24 days. Muscle morphology, intra and extracellular lipid levels, and lipid transporter content was investigated. Our findings indicate that short-term Fluvastatin administration induced a myopathy that was not exacerbated by the presence of STZ-induced diabetes. Fluvastatin significantly increased ectopic lipid deposition within the muscle of STZ-diabetic animals, findings that were not seen with diabetes or statin treatment alone. Consistent with this observation, only Fluvastatin-treated diabetic mice downregulated protein expression of lipid transporters FAT/CD36 and FABPpm in their skeletal muscle. No differences in FAT/CD36 or FABPpm mRNA content were observed. Altered lipid compartmentalization resultant of a downregulation in lipid transporter content in STZ-induced diabetic skeletal muscle was apparent in the current investigation. Given the association between ectopic lipid deposition in skeletal muscle and the development of insulin-resistance, our findings highlight the necessity for more thorough investigations into the impact of statins in humans with diabetes.

  18. The use of Alloxan and Streptozotocin in Experimental Diabetes Models

    Directory of Open Access Journals (Sweden)

    Zehra Kurçer

    2012-06-01

    Full Text Available Diabetes is a chronic metabolic disease which leads to several acute and chronic complications, morbidity and mortality, and decreased lifespan and quality of life. Therefore, in research studies that aim to enlighten the pathogenesis of diabetes and investigate possible treatment strategies, experimental animal models of diabetes provide many advantages to the investigator. Models of diabetes obtained by chemical induction, diet, surgical manipulations or combination thereof and also new genetically modified animal models are some of the experimental models. Alloxan and streptozotocin (STZ, which are toxic glucose analogues that preferentially accumulate in pancreatic beta cells, are widely used toxic agents to induce experimental diabetes in animals. This review gives an overview on the use of alloxan and STZ to induce chemical diabetes models with reference to their mechanisms, utilizable doses, advantages and disadvantages in diabetes research. Turk Jem 2012; 16: 34-40

  19. Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model.

    Science.gov (United States)

    Bhatta, Anil; Sangani, Rajnikumar; Kolhe, Ravindra; Toque, Haroldo A; Cain, Michael; Wong, Abby; Howie, Nicole; Shinde, Rahul; Elsalanty, Mohammed; Yao, Lin; Chutkan, Norman; Hunter, Monty; Caldwell, Ruth B; Isales, Carlos; Caldwell, R William; Fulzele, Sadanand

    2016-02-15

    A balanced diet is crucial for healthy development and prevention of musculoskeletal related diseases. Diets high in fat content are known to cause obesity, diabetes and a number of other disease states. Our group and others have previously reported that activity of the urea cycle enzyme arginase is involved in diabetes-induced dysregulation of vascular function due to decreases in nitric oxide formation. We hypothesized that diabetes may also elevate arginase activity in bone and bone marrow, which could lead to bone-related complications. To test this we determined the effects of diabetes on expression and activity of arginase, in bone and bone marrow stromal cells (BMSCs). We demonstrated that arginase 1 is abundantly present in the bone and BMSCs. We also demonstrated that arginase activity and expression in bone and bone marrow is up-regulated in models of diabetes induced by HFHS diet and streptozotocin (STZ). HFHS diet down-regulated expression of healthy bone metabolism markers (BMP2, COL-1, ALP, and RUNX2) and reduced bone mineral density, bone volume and trabecular thickness. However, treatment with an arginase inhibitor (ABH) prevented these bone-related complications of diabetes. In-vitro study of BMSCs showed that high glucose treatment increased arginase activity and decreased nitric oxide production. These effects were reversed by treatment with an arginase inhibitor (ABH). Our study provides evidence that deregulation of l-arginine metabolism plays a vital role in HFHS diet-induced diabetic complications and that these complications can be prevented by treatment with arginase inhibitors. The modulation of l-arginine metabolism in disease could offer a novel therapeutic approach for osteoporosis and other musculoskeletal related diseases. Published by Elsevier Ireland Ltd.

  20. Experimental periodontitis induced by Porphyromonas gingivalis does not alter the onset or severity of diabetes in mice.

    Science.gov (United States)

    Li, H; Yang, H; Ding, Y; Aprecio, R; Zhang, W; Wang, Q; Li, Y

    2013-10-01

    Diabetes mellitus is believed to increase the risk and severity of periodontitis. However, less evidence is available on the converse effects of periodontitis on diabetes. The objective of the study was to investigate to what degree experimental periodontitis induced by Porphyromonas gingivalis might influence the onset and severity of diabetes in different mouse models. Twenty-eight male Tallyho/JngJ mice (type 2 diabetes), 20 male streptozotocin-induced diabetes C57BL/6J mice (type 1 diabetes) and 20 male C57BL/6J mice at 4 wks of age were evenly divided into two groups: periodontal infection and sham infection. Periodontitis was induced by Porphyromonas gingivalis W50 (P. gingivalis) oral inoculation before the development of diabetes. Sham-infected mice received vehicle as control. P. gingivalis in the oral cavity were identified by quantitative polymerase chain reaction. Fasting glucose, body weight and food intake levels were monitored and glucose tolerance tests were performed to assess glucose homeostasis for the onset and progression of diabetes. The level of alveolar bone loss and tumor necrosis factor-alpha were determined in week 20 when mice were killed. Mice in the infection groups developed more alveolar bone loss than those in sham-infection groups (Tallyho p = 0.021; C57-STZ p = 0.014; C57 p = 0.035). Hyperglycemic mice exhibited significantly more bone loss compared to those normal glucose mice (Tallyho vs. C57 p = 0.029; C57-STZ vs. C57 p = 0.024). The level of tumor necrosis factor-alpha was consistent with that of periodontal bone loss and hyperglycemia. There was no significant effect of mouse species on the amount of bone loss at the same level of blood glucose. No statistically significant difference or trend in glucose metabolism was found between the infection and sham-infection group. Diabetes enhanced the risk for periodontal disease induced by P. gingivalis. However, no converse impact was found between this periodontal

  1. The Effectiveness of Various Salacca Vinegars as Therapeutic Agent for Management of Hyperglycemia and Dyslipidemia on Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Elok Zubaidah

    2017-01-01

    Full Text Available The aim of this study was to explore the potency of salacca vinegar made from various Indonesian salacca fruit extracts as therapeutic agent for hyperglycemia and dyslipidemia for STZ-induced diabetic rats. The rats were grouped into untreated rats, STZ-induced diabetic rats without treatment, and STZ-induced diabetic rats treated with Pondoh salacca vinegar, Swaru salacca vinegar, Gula Pasir salacca vinegar, Madu salacca vinegar, or Madura salacca vinegar. Parameter observed included blood glucose, total cholesterol (TC, high density lipoprotein (HDL, low density lipoprotein (LDL, triglyceride (TG, malondialdehyde (MDA, superoxide dismutase (SOD, and pancreas histopathology of the samples. The results demonstrated that all salacca vinegars were capable of reducing blood sugar (from 25.1 to 62% and reducing LDL (from 9.5 to 14.8 mg/dL, TG (from 58.3 to 69.5 mg/dL, MDA (from 1.1 to 2.2 mg/dL, and TC (from 56.3 to 70.5 mg/dL as well as increasing HDL blood sugar of STZ-induced diabetic Wistar rats (from 52.3 to 60 mg/dL. Various salacca vinegars were also capable of regenerating pancreatic cells. Nevertheless, the ability of Swaru salacca vinegar to manage hyperglycemia and dyslipidemia appeared to be superior to other salacca vinegars. Swaru salacca vinegar is a potential therapeutic agent to manage hyperglycemia and dyslipidemia of STZ-induced diabetic rats.

  2. Effects of diabetes on oxidative and nitrosative stress in kidney mitochondria from aged rats.

    Science.gov (United States)

    Pérez-Gallardo, Rocío V; Noriega-Cisneros, Ruth; Esquivel-Gutiérrez, Edgar; Calderón-Cortés, Elizabeth; Cortés-Rojo, Christian; Manzo-Avalos, Salvador; Campos-García, Jesús; Salgado-Garciglia, Rafael; Montoya-Pérez, Rocío; Boldogh, Istvan; Saavedra-Molina, Alfredo

    2014-12-01

    Diabetes mellitus (DM) is characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. Diabetic nephropathy (DN) develops in diabetic patients and is characterized by a progressive deterioration of renal function. The mitochondrial electron transport chain (ETC) produces most of the reactive oxygen species (ROS) that are involved in diabetic nephropathy. Due to the high incidence of DM in the elderly, the aim of this study was to evaluate oxidative and nitrosative stress in kidney mitochondria from aged rats. We evaluated lipid peroxidation (LPO), nitric oxide (NO(•)) production, S-nitrosylation profiles, glutathione levels, and glutathione reductase and aconitase activities under streptozotocin (STZ)-induced experimental diabetes in kidney mitochondria from aged rats. The results showed an increase in LPO, NO(•) production, and S-nitrosylated proteins in rats with STZ-induced diabetes. A decrease in glutathione (GSH) levels and glutathione reductase (GR) and aconitase activities in the rats that received the STZ-induced diabetes treatment was also observed, when compared with the age-related controls. The data suggest that oxidative and nitrosative stresses promote mitochondrial oxidative dysfunction in the more advanced age rat kidney in STZ-induced diabetes.

  3. Anti-diabetic and spermatogenic activity of Cocculus hirsutus (L) Diels

    African Journals Online (AJOL)

    blood glucose levels. After STZ-induced diabetes, it was observed that both standard drug (glibenclamide) and methanolic extract of C. hirsutus were significantly superior to control in reducing blood sugar on long treatment (15 days). The data suggested that C. hirsutus could be of benefit in diabetes mellitus in controlling ...

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

    Directory of Open Access Journals (Sweden)

    Lin-Yu Wang

    2013-01-01

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

  5. Decrease of PPARδ in Type-1-Like Diabetic Rat for Higher Mortality after Spinal Cord Injury

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    Cheng-Chia Tsai

    2014-01-01

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

  6. Lutein dietary supplementation attenuates streptozotocin-induced testicular damage and oxidative stress in diabetic rats.

    Science.gov (United States)

    Fatani, Amal J; Al-Rejaie, Salim S; Abuohashish, Hatem M; Al-Assaf, Abdullah; Parmar, Mihir Y; Ahmed, Mohammed M

    2015-06-30

    Diabetes mellitus with the successive generation of reactive oxygen species signifies a major risk factor for testicular dysfunction. Antioxidant supplements are one of the best options to prevent such disorder. In the present study, lutein as dietary supplement has been used to explore its potential protective effects against diabetes-induced oxidative stress in testicular cells. Diabetes was induced using a single i.p. injection of streptozotocin (STZ). Lutein was mixed with rat chow powder and supplemented to diabetic rats for 5 weeks. Serum testosterone levels were estimated. In testicular cells, thiobarbituric acid reactive substances (TBARS), total sulfhydryl groups (T-GSH), non-protein sulfhydryl groups (NP-SH), superoxide dismutase (SOD) and catalase (CAT) activities were measured. Pro-inflammatory mediators like tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were measured in the testis. Nucleic acids and total protein (TP) levels were also estimated in testicular cells. Histopathological changes were evaluated in testis. Serum testosterone level was significantly decreased in diabetic animals compared to controls. Diabetes markedly reduced T-GSH, NP-SH, CAT and SOD, while TBARS, TNF-α and IL-1β levels were increased in the diabetic testis compared to non-diabetic controls. Lutein supplementation, significantly and dose dependently increased the serum testosterone level. The elevated TBARS levels were significantly decreased compared to diabetic group, while the decreased levels of T-GSH and NP-SH and activities of CAT and SOD were found increased by lutein treatments in dose dependent manner. Lutein pretreatment also inhibited the TNF-α and IL-1β levels compared to diabetic group. The decreased values of nucleic acids and total protein in diabetic group were also significantly increased in lutein supplemented groups. The histopathological evaluation revealed protection the damaged testicular cells in the diabetic rats by lutein

  7. Synthesis, characterization, and efficacy evaluation of a new anti-diabetic vanadyl(II) thiamine hydrochloride complex in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Ahmed El-Shazly, Samir; Ahmed, Mohamed Mohamed; Ibrahim, Zein Shaban; Refat, Moamen S

    2015-06-01

    Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to abnormalities in either insulin secretion or action. A range of vanadium complexes have been synthesized and demonstrated to be effective in lowering hyperglycemia. Thiamine administration was also reported to prevent deterioration in fasting glucose and insulin levels, and to improve glucose tolerance in hyperglycemic patients. This study has been conducted to evaluate the ionic vanadyl(II) thiamine hydrochloride complex (VC) as a new anti-diabetic candidate. The new complex was characterized by infrared spectroscopy (FT-IR), electronic spectra, magnetic susceptibility, electron spin resonance (ESR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The anti-diabetic effect of VC was investigated in comparison to vanadium sulfate in streptozotocin (STZ)-induced diabetic rats. Treatment of diabetic rats with VC versus vanadyl sulfate showed a more potent effect on reducing serum glucose and cholesterol close to normal levels. VC suppressed the diabetes-induced upregulation of hepatic glucose transporter (GLUT)-2, Phosphoenol pyruvate carboxykinase (PEPCK), and hormone-sensitive lipase (HSL) more significantly than vanadyl sulfate. Either vanadyl sulfate or VC restored hepatic sterol regulatory element-binding protein transcription factor-1c (SREBP-1c) and muscle hexokinase (HK) mRNA expression that was downregulated in diabetic group. Pyruvate kinase (PK) mRNA expression was restored more significantly in VC-treated than vanadyl sulfate-treated diabetic rats. These results indicate that the newly synthesized VC could be an effective anti-diabetic candidate as the anti-diabetic activity of the ionic vanadium was enhanced after being modified with the organic ligand, thiamin. The results also suggest that VC achieves its effect most likely through modulating the transcription of energy metabolizing enzymes. © The Author(s) 2015.

  8. New 1,4-Dihydropyridines Down-regulate Nitric Oxide in Animals with Streptozotocin-induced Diabetes Mellitus and Protect Deoxyribonucleic Acid against Peroxynitrite Action.

    Science.gov (United States)

    Leonova, Elina; Sokolovska, Jelizaveta; Boucher, Jean-Luc; Isajevs, Sergejs; Rostoka, Evita; Baumane, Larisa; Sjakste, Tatjana; Sjakste, Nikolajs

    2016-07-01

    Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic actions of nitric oxide (NO) are responsible to a large extent for development of complications of DM. Search for compounds regulating NO production in patients with DM is thus important for the development of pharmacological drugs. Dihydropyridines (1,4-DHPs) are prospective compounds from this point of view. The goals of this study were to study the in vivo effects of new DHPs on NO and reactive nitrogen and oxygen species production in a streptozotocin (STZ)-induced model of DM in rats and to study their ability to protect DNA against nocive action of peroxynitrite. STZ-induced diabetes caused an increase in NO production in the liver, kidneys, blood and muscles, but a decrease in NO in adipose tissue of STZ-treated animals. Cerebrocrast treatment was followed by normalization of NO production in the liver, kidneys and blood. Two other DHPs, etaftorone and fenoftorone, were effective in decreasing NO production in kidneys, blood and muscles of diabetic animals. Furthermore, inhibitors of nitric oxide synthase (NOS) and an inhibitor of xanthine oxidoreductase (XOR) decreased NO production in kidneys of diabetic animals. Treatment with etaftorone decreased expression of inducible NOS and XOR in kidneys, whereas it increased the expression of endothelial NOS. In vitro, the studied DHPs did not significantly inhibit the activities of NOS and XOR but affected the reactivity of peroxynitrite with DNA. These new DHPs thus appear of strong interest for treatment of DM complications. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  9. Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

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    Minglong Shao

    Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

  10. Catalase therapy corrects oxidative stress-induced pathophysiology in incipient diabetic retinopathy.

    Science.gov (United States)

    Giordano, Courtney R; Roberts, Robin; Krentz, Kendra A; Bissig, David; Talreja, Deepa; Kumar, Ashok; Terlecky, Stanley R; Berkowitz, Bruce A

    2015-05-01

    Preclinical studies have highlighted retinal oxidative stress in the pathogenesis of diabetic retinopathy. We evaluated whether a treatment designed to enhance cellular catalase reduces oxidative stress in retinal cells cultured in high glucose and in diabetic mice corrects an imaging biomarker responsive to antioxidant therapy (manganese-enhanced magnetic resonance imaging [MEMRI]). Human retinal Müller and pigment epithelial cells were chronically exposed to normal or high glucose levels and treated with a cell-penetrating derivative of the peroxisomal enzyme catalase (called CAT-SKL). Hydrogen peroxide (H2O2) levels were measured using a quantitative fluorescence-based assay. For in vivo studies, streptozotocin (STZ)-induced diabetic C57Bl/6 mice were treated subcutaneously once a week for 3 to 4 months with CAT-SKL; untreated age-matched nondiabetic controls and untreated diabetic mice also were studied. MEMRI was used to analytically assess the efficacy of CAT-SKL treatment on diabetes-evoked oxidative stress-related pathophysiology in vivo. Similar analyses were performed with difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. After catalase transduction, high glucose-induced peroxide production was significantly lowered in both human retinal cell lines. In diabetic mice in vivo, subnormal intraretinal uptake of manganese was significantly improved by catalase supplementation. In addition, in the peroxisome-rich liver of treated mice catalase enzyme activity increased and oxidative damage (as measured by lipid peroxidation) declined. On the other hand, DFMO was largely without effect in these in vitro or in vivo assays. This proof-of-concept study raises the possibility that augmentation of catalase is a therapy for treating the retinal oxidative stress associated with diabetic retinopathy.

  11. Effect of Urtica Dioica Decoction on Serum Glucose and Lipid Profile in Stereptozotocin Induced Diabetic Male Rats

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    Mohammad Reza Sahraki

    Full Text Available Background: Since Urtica dioica is a traditional treatment plant and is used for antihypertensive, antilipidemic and antidiabetic agents, this survey was carried out to evaluate the effect of Urtica dioica decoction on serum glucose and lipid profile in diabetic male rats induced by stereptozotocin (STZ. Materials and Methods: This experiment was performed on 30 Wistar-Albino male rats, weighing 200-250 g, which were divided in sham control (A, diabetic control (B and diabetic test groups (C randomly (N=10. Type I diabetes was induced by single intraperitoneal injection of STZ (65 mg/kg. Test group received 0.40-0.60 ml of Urtica dioica decoction for a month by gavages, control group (B received the same volume of distill water. Group (A did not receive any agent during the experiment period. Finally, animals were anesthetized, sacrificed and blood samples were collected from the cervical vein. Then, serum glucose and lipid profiles were measured by ordinary methods. Data were analyzed by SPSS-11, using ANOVA and post hoc Tukey tests. Results were expressed as mean±SD, and statistical difference was considered significant by p<0.05.Results: Results in the present study showed that fasting blood glucose (FBS, total cholesterol (TCho, triglyceride (TG, LDL, food and water intake were significantly decreased in group C compared with those of group B, but body weight gain was significantly increased compared with that of control group (B.Conclusion: These results indicated that Urtica dioica decoction caused decreased FBS and improved serum lipids in diabetic male rats. Some more studies have shown the same mechanism.

  12. Cardioprotective effects of magnesium valproate in type 2 diabetes mellitus.

    Science.gov (United States)

    Patel, Bhoomika M; Raghunathan, Suchi; Porwal, Urvashi

    2014-04-05

    We have evaluated the effect of magnesium valproate (210 mg/kg/day, p.o.) in type 2 diabetes induced cardiovascular complications induced by streptozotocin (STZ, 90 mg/kg, i.p.) in neonatal wistar rats. Various biochemical, cardiovascular and hemodynamic parameters were measured at the end of 8 weeks of treatment. STZ produced significant hyperglycaemia, hypoinsulinemia and dyslipidemia, which was prevented by magnesium valproate treatment. STZ produced increase in Creatinine Kinase, C-reactive protein and lactate dehydrogenase levels and treatment with magnesium valproate produced reduction in these levels. STZ produced increase in cardiac and LV hypertrophy index, LV/RV ratio, LV collagen deposition and LV cardiomyocyte diameter which were decreased by magnesium valproate treatment. Magnesium valproate also prevented STZ induced hemodynamic alterations and oxidative stress. These results were further supported by histopathological studies in which magnesium valproate showed marked reduction in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that magnesium valproate is beneficial as an anti-diabetic agent in type-2 diabetes mellitus and also prevents its cardiac complications. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Diabetes Mellitus Induces Bone Marrow Microangiopathy

    NARCIS (Netherlands)

    Oikawa, Atsuhiko; Siragusa, Mauro; Quaini, Federico; Mangialardi, Giuseppe; Katare, Rajesh G.; Caporali, Andrea; van Buul, Jaap D.; van Alphen, Floris P. J.; Graiani, Gallia; Spinetti, Gaia; Kraenkel, Nicolle; Prezioso, Lucia; Emanueli, Costanza; Madeddu, Paolo

    2010-01-01

    Objective-The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and Results-We found profound structural alterations in BM from mice with

  14. Quantitative assessment of early experimental diabetes in rats using dynamic contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Murase, Kenya [Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871 (Japan)], E-mail: murase@sahs.med.osaka-u.ac.jp; Kitamura, Akihiro; Tachibana, Atsushi; Kusakabe, Yoshinori; Matsuura, Risa; Miyazaki, Shohei [Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2010-04-15

    Purpose: To quantitatively assess the time course of changes of the renal volume and function in the early phase of streptozotocin (STZ)-induced diabetes in rats using dynamic contrast-enhanced computed tomography (DCE-CT). Methods: The DCE-CT studies were performed in 24 male Sprague-Dawley rats (n = 6 for control and n = 18 for STZ-treated group) on days 0, 4, 7, 11, and 14 using a multi-detector row CT. The rats of an STZ-treated group were given intraperitoneally 65 mg/kg body weight of STZ on day 0, and were divided into two groups based on the blood glucose concentration on day 4 being less than 300 mg/dL [STZ-treated group (L), n = 8] or greater than 300 mg/dL [STZ-treated group (G), n = 10]. The contrast clearance per unit renal volume (K{sub 1}) was estimated from the DCE-CT data using the Patlak model. The renal volume (V{sub CT}) was calculated by manually delineating the kidney on the contrast-enhanced CT image. The contrast clearance of the entire kidney (K) was obtained by K{sub 1} x V{sub CT}. Results: V{sub CT} in the STZ-treated group was significantly enlarged on day 4 compared to that on day 0 and continued until day 14. Although there were no significant changes in the time course of K{sub 1} in all groups, K in the STZ-treated groups (L) and (G) significantly increased on days 7 and 4, respectively, and continued until day 14, suggesting that hyperfiltration occurs in parallel with renal volume enlargement. Conclusion: The present method appears useful for quantitatively evaluating the time course of STZ-induced diabetes in rats, because it allows repeated and simultaneous evaluation of renal morphology and function.

  15. Ameliorative Potential of Morin in Streptozotocin-Induced ...

    African Journals Online (AJOL)

    Methods: Diabetes was induced by a single injection (65 mg/kg, ip) of streptozotocin (STZ). Morin (15 and 30 mg/kg/day) oral treatment was started 3 weeks after diabetes induction and continued for 5 consecutive weeks. Pain threshold behavior tests were performed at the end of the treatment. In sciatic nerve, inflammatory ...

  16. Urinary metabolomics study on the protective role of Orthosiphon stamineus in Streptozotocin induced diabetes mellitus in rats via (1)H NMR spectroscopy.

    Science.gov (United States)

    Azam, Amalina Ahmad; Pariyani, Raghunath; Ismail, Intan Safinar; Ismail, Amin; Khatib, Alfi; Abas, Faridah; Shaari, Khozirah

    2017-05-25

    Orthosiphon stamineus (OS) is a herb known in ethnomedicine for treating diabetes mellitus (DM). In this study, a (1)H NMR based urine metabolomics tool has been used for the first time to identify the metabolic protective mechanism of OS in DM using Streptozotocin (STZ) induced experimental model in rats. Four different solvent extracts of OS, namely aqueous, ethanolic, 50% aqueous ethanolic and methanolic, at a dose of 500 mg/kg body weight (bw) were orally administered for 14 days to diabetic rats induced via intraperitoneal injection of 60 mg/kg bw STZ. NMR metabolomics approach using pattern recognition combined with multivariate statistical analysis was applied in the rat urine to study the resulted metabolic perturbations. OS aqueous extract (OSAE) caused a reversal of DM comparable to that of 10 mg/kg bw glibenclamide. A total of 15 urinary metabolites, which levels changed significantly upon treatment were identified as the biomarkers of OSAE in diabetes. A systematic metabolic pathways analysis identified that OSAE contributed to the antidiabetic activity mainly through regulating the tricarboxylic acid cycle, glycolysis/gluconeogenesis, lipid and amino acid metabolism. The results of this study validated the ethnopharmacological use of OS in diabetes and unveiled the biochemical and metabolic mechanisms involved.

  17. Eugenosedin-A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide-induced diabetic rats

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    Kuo-Ping Shen

    2018-03-01

    Full Text Available This study examined the effects of eugenosedin-A (Eu-A in a streptozotocin (STZ/nicotinamide-induced rat model of type II diabetes mellitus (T2DM. Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1 RD group, normal rats fed a regular diet (RD, (2 DM group, T2DM rats fed a high-fat diet, and (3 Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day. After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK in liver and skeletal muscle and decreased protein expression of insulin receptor (IR, insulin receptor substrate-1 (IRS-1, IRS-2, AMP-activated protein kinase (AMPK, glucose transporter-4 (GLUT-4, glucokinase (GCK, and peroxisome proliferator-activated receptor γ (PPAR-γ. STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

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

    Science.gov (United States)

    Menard, Chantalle E; Durston, Melanie; Zherebitskaya, Elena; Smith, Darrell R; Freed, Darren; Glazner, Gordon W; Tian, Ganghong; Fernyhough, Paul; Arora, Rakesh C

    2014-06-04

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

  19. Berberine protects against metformin-associated lactic acidosis in induced diabetes mellitus.

    Science.gov (United States)

    Almani, Suhail Ahmed; Memon, Iqbal Ahmed; Shaikh, Tariq Zaffar; Khoharo, Haji Khan; Ujjan, Ikramuddin

    2017-05-01

    Causality of occurrence of metformin-associated lactic acidosis (MALA) is a clinical problem. Currently, there is no drug available to prevent MALA. The present study was conducted to evaluate the protective effect of Berberine (BBR) against MALA in induced diabetic rat model. A sample of 75 healthy male Wistar rats was randomly selected according to inclusion and exclusion criteria. 75 male Wistar rats were randomly divided into a control and 4 experimental groups. Streptozotocin (STZ) in citrate buffer (pH 4.5) at a dose of 45 mg/kg was injected for induction of diabetes mellitus and rats achieving fasting blood glucose >250 mg/dl were included. Blood samples were collected 18 hr after the last dose of metformin and berberine. Ethical approval was taken before the study was conducted. Staistix 10.0 (USA) software was used for data analysis. Berberine decreased MALA. Metformin, metformin + BBR 50 mg/kg bwt, and metformin + BBR 100 mg/kg bwt showed serum lactate as 1.87±0.4 mmol/lL, 1.62 ± 0.44 mmol/l and 1.47± 0.45 mmol/l, respectively (P=0.0001). Insulin resistance and liver enzymes were improved in BBR treated rats. The present study reports berberine protects against MALA in streptozocin-induced diabetes mellitus.

  20. Berberine protects against metformin-associated lactic acidosis in induced diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Suhail Ahmed Almani

    2017-05-01

    Full Text Available Objective(s: Causality of occurrence of metformin-associated lactic acidosis (MALA is a clinical problem. Currently, there is no drug available to prevent MALA. The present study was conducted to evaluate the protective effect of Berberine (BBR against MALA in induced diabetic rat model. Materials and Methods: A sample of 75 healthy male Wistar rats was randomly selected according to inclusion and exclusion criteria. 75 male Wistar rats were randomly divided into a control and 4 experimental groups. Streptozotocin (STZ in citrate buffer (pH 4.5 at a dose of 45 mg/kg was injected for induction of diabetes mellitus and rats achieving fasting blood glucose >250 mg/dl were included. Blood samples were collected 18 hr after the last dose of metformin and berberine. Ethical approval was taken before the study was conducted. Staistix 10.0 (USA software was used for data analysis. Results: Berberine decreased MALA. Metformin, metformin + BBR 50 mg/kg bwt, and metformin + BBR 100 mg/kg bwt showed serum lactate as 1.87±0.4 mmol/lL, 1.62 ± 0.44 mmol/l and 1.47± 0.45 mmol/l, respectively (P=0.0001.  Insulin resistance and liver enzymes were improved in BBR treated rats. Conclusion: The present study reports berberine protects against MALA in streptozocin-induced diabetes mellitus.

  1. Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes.

    Science.gov (United States)

    Zakula, Zorica; Koricanac, Goran; Putnikovic, Biljana; Markovic, Ljiljana; Isenovic, Esma R

    2007-01-01

    Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. Data from literature indicate that iNOS is expressed in vascular smooth muscle cells (VSMC) and that IGF-1-induced release of NO is both rapid and delayed. We hypothesize that impaired IGF-1-induced sodium pump activity/expression in rats with type 1 diabetes is related to activation of phosphatidylinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin-treated rat heart (STZ). Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. Future investigations should now focus on mechanisms of action of IGF-1 and its clinical applicability.

  2. Low-Magnitude High-Frequency Vibration Accelerated the Foot Wound Healing of n5-streptozotocin-induced Diabetic Rats by Enhancing Glucose Transporter 4 and Blood Microcirculation.

    Science.gov (United States)

    Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Jiang, Jonney Lei; Wang, Tina Bai-Yan; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

    2017-09-14

    Delayed wound healing is a Type 2 diabetes mellitus (DM) complication caused by hyperglycemia, systemic inflammation, and decreased blood microcirculation. Skeletal muscles are also affected by hyperglycemia, resulting in reduced blood flow and glucose uptake. Low Magnitude High Frequency Vibration (LMHFV) has been proven to be beneficial to muscle contractility and blood microcirculation. We hypothesized that LMHFV could accelerate the wound healing of n5-streptozotocin (n5-STZ)-induced DM rats by enhancing muscle activity and blood microcirculation. This study investigated the effects of LMHFV in an open foot wound created on the footpad of n5-STZ-induced DM rats (DM_V), compared with no-treatment DM (DM), non-DM vibration (Ctrl_V) and non-DM control rats (Ctrl) on Days 1, 4, 8 and 13. Results showed that the foot wounds of DM_V and Ctrl_V rats were significantly reduced in size compared to DM and Ctrl rats, respectively, at Day 13. The blood glucose level of DM_V rats was significantly reduced, while the glucose transporter 4 (GLUT4) expression and blood microcirculation of DM_V rats were significantly enhanced in comparison to those of DM rats. In conclusion, LMHFV can accelerate the foot wound healing process of n5-STZ rats.

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

    Directory of Open Access Journals (Sweden)

    Minghua Zhang

    2014-01-01

    Full Text Available Oxidative stress (OS has been regarded as one of the major pathogeneses of diabetic nephropathy (DN through damaging kidney which is associated with renal cells dysfunction. The aim of this study was to investigate whether Moutan Cortex (MC could protect kidney function against oxidative stress in vitro or in vivo. The compounds in MC extract were analyzed by HPLC-ESI-MS. High-glucose-fat diet and STZ (30 mg kg−1 were used to induce DN rats model, while 200 μg mL−1 AGEs were for HBZY-1 mesangial cell damage. The treatment with MC could significantly increase the activity of SOD, glutathione peroxidase (GSH-PX, and catalase (CAT. However, lipid peroxidation malondialdehyde (MDA was reduced markedly in vitro or in vivo. Furthermore, MC decreased markedly the levels of blood glucose, serum creatinine, and urine protein in DN rats. Immunohistochemical assay showed that MC downregulated significantly transforming growth factor beta 2 (TGF-β2 protein expression in renal tissue. Our data provided evidence to support this fact that MC attenuated OS in AGEs-induced mesangial cell dysfunction and also in high-glucose-fat diet and STZ-induced DN rats.

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

    Science.gov (United States)

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

    2014-08-01

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

  5. MSC attenuate diabetes-induced functional impairment in adipocytes via secretion of insulin-like growth factor-1.

    Science.gov (United States)

    Gao, Dongyun; Xie, Jiangfan; Zhang, Junhua; Feng, Changjiang; Yao, Bin; Ma, Kui; Li, Jiwei; Wu, Xu; Huang, Sha; Fu, Xiaobing

    2014-09-12

    The function of subcutaneous adipocytes in promoting wound healing is significantly suppressed in diabetic wounds. Recent studies have demonstrated the ability of mesenchymal stem cell (MSC) to ameliorate impaired diabetic wound healing. We hypothesized that MSC function may involve subcutaneous adipocytes. The abnormal function of subcutaneous adipocytes from STZ induced diabetic mice including glucose uptake and free fatty acid (FFA) secretion level were assessed. Then these cells were co-cultured with MSC via a transwell system to observe the changes of metabolic index and glucose transporter four (GLUT4) as well as phosphoinositide 3-kinase/protein kinase (PI3K/AKT) signaling pathway expression. The results of metabolic index suggest that MSC obviously attenuated the diabetes-induced functional impairment. Both mRNA and protein expression analyses showed that PI3K/AKT insulin signaling pathway and GLUT4 expression were up-regulated. These changes were substantially associated with a increased level of insulin-like growth factor-1 (IGF-1) secretion from MSC. These findings suggest that MSC could attenuate abnormal function of diabetic adipocytes by IGF-1secretion, which was more or less associated with the beneficial effects of MSC on improving diabetic wound healing. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Protective role of Nigella sativa against experimentally induced type-II diabetic nuclear damage in Wistar rats

    Directory of Open Access Journals (Sweden)

    T. J. Sheikh

    2013-07-01

    Full Text Available Aim: To identify the anti-mutagenic effect of Nigella sativa on the experimentally induced chronic diabetes (type – II in Wistar rats.Materials and Methods: The anti-mutagenic effect was evaluated in Nigella sativa treated diabetic rats against the streptozotocin - nicotinamide (STZ-NA (at a dose rate of 45-110 i.p mg/kg b.wt for 90 days induced type-II diabetes mellitus using bone marrow micronucleus tests. The antioxidant status was tested by estimating the serum levels of lipid peroxidation and superoxide dismutase.Results: Our results indicated that diabetic rats treated with Nigella sativa decreased the frequency of micronuclei in the erythrocytes of bone marrow (P < 0.05 and enhanced the antioxidant status (P < 0.05 in the treated diabetic rats as compared to controls.Conclusion: The observations indicated that the diabetic patients are more prone to cell mutations which are related to the level of cellular oxidative status and it could be reduced by Nigella sativa.

  7. Antidiabetic and antiacetylcholinesterase effects of ethyl acetate fraction of Chaenomeles sinensis (Thouin) Koehne fruits in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sancheti, Sandesh; Sancheti, Shruti; Seo, Sung-Yum

    2013-01-01

    The present study was intended to examine the effects of the supplementation of active α-glucosidase, α-amylase and lipase inhibitory ethyl acetate (CSE) fraction from the fruits of Chaenomeles sinensis (Thouin) Koehne on blood glucose (BG), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransaminase (AST), acetylcholinesterase (AChE) and antioxidant levels. The diabetic rats were treated orally with CSE at the doses of 50 and 100 mg/kg bw for 14 days. BG, TC, TG, HDL-C, ALT, AST and AChE levels were significantly reduced; on the other hand antioxidant levels were significantly increased in the treated groups. These observations suggest protective effects of CSE against STZ-induced diabetic dementia model. Copyright © 2011 Elsevier GmbH. All rights reserved.

  8. Type-1 diabetes induces depot-specific alterations in adipocyte diameter and mass of adipose tissues in the rat.

    Science.gov (United States)

    Ghorbani, A; Varedi, M; Hadjzadeh, M-Al-R; Omrani, G H

    2010-07-01

    Type-1 diabetes (T1D) is a metabolic disorder associated with massive reduction in mass of adipose tissue. Measuring cell diameter, an index of fat metabolism, we determined depot-specific alterations in weight of adipose tissue, fat cell diameter and size heterogeneity and distribution at 5 depots in streptozotocin (STZ)-induced diabetic rats. T1D was induced by a single injection of STZ. Seven days after the injection, fat depots were isolated, weighted, washed and maintained in tissue culture medium. Using a microscope equipped with calibrated micrometer, cell diameter as well as size distribution pattern and heterogeneity of adipocytes were determined in fresh tissue slices of subcutaneous (SC), proximal epididymal (PE), distal epididymal (DE), perirenal (PR) and retroperitoneal (RP) fat depots. The T1D induced marked reductions in fat mass and mean of fat cell diameter at all depots. The most affected depot was the SC. With the exception of PE, adipocytes at all depots showed significant increases in size heterogeneity. The effect of the diabetes on mean fat cell diameter and size heterogeneity was minimal at PE depot. Depots with similar cell size distribution pattern exhibited similar fat mass reduction. However, the DE depot with a unique cell size distribution pattern showed a fat mass reduction similar to that of PE and PR depots. These data indicate that T1D induces a massive fat mass reduction in a reasonably depot-specific manner and that the fat depots close to survival organs are less vulnerable to fat mobilization. Moreover, peculiar disagreement between cell size distribution and heterogeneity as well as the level of fat mass reduction at DE and PE depots suggests that not only cell size and heterogeneity but also local factors may play roles in depot-specific fat mobilization. J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart, New York.

  9. Amitriptyline and Sertraline in Diabetic Neuropathy: A Comparative ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of amitriptyline (Ami) and sertraline (Sert) in diabetes neuropathy. Methods: Diabetes was induced in 3 groups of rats (n=6) with streptozotocin (STZ, 55mg/kg, i.p.). Two of the groups of diabetic rats received amitriptyline (15 mg/kg, p.o) and sertraline (30 mg/kg, p.o.) while another 2 groups ...

  10. Quantitative Expression Analysis of APP Pathway and Tau Phosphorylation-Related Genes in the ICV STZ-Induced Non-Human Primate Model of Sporadic Alzheimer’s Disease

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    Sang-Je Park

    2015-01-01

    Full Text Available The accumulation and aggregation of misfolded proteins in the brain, such as amyloid-β (Aβ and hyperphosphorylated tau, is a neuropathological hallmark of Alzheimer’s disease (AD. Previously, we developed and validated a novel non-human primate model for sporadic AD (sAD research using intracerebroventricular administration of streptozotocin (icv STZ. To date, no characterization of AD-related genes in different brain regions has been performed. Therefore, in the current study, the expression of seven amyloid precursor protein (APP pathway-related and five tau phosphorylation-related genes was investigated by quantitative real-time PCR experiments, using two matched-pair brain samples from control and icv STZ-treated cynomolgus monkeys. The genes showed similar expression patterns within the control and icv STZ-treated groups; however, marked differences in gene expression patterns were observed between the control and icv STZ-treated groups. Remarkably, other than β-secretase (BACE1 and cyclin-dependent kinase 5 (CDK5, all the genes tested showed similar expression patterns in AD models compared to controls, with increased levels in the precuneus and occipital cortex. However, significant changes in gene expression patterns were not detected in the frontal cortex, hippocampus, or posterior cingulate. Based on these results, we conclude that APP may be cleaved via the general metabolic mechanisms of increased α- and γ-secretase levels, and that hyperphosphorylation of tau could be mediated by elevated levels of tau protein kinase, specifically in the precuneus and occipital cortex.

  11. The effects of helium-neon light therapy on healing of partial osteotomy of the tibia in streptozotocin induced diabetic rats.

    Science.gov (United States)

    Abdi, Shabnam; Bayat, Mohammad; Javadieh, Farshad; Mohsenifar, Zhaleh; Rezaie, Fatemesadat; Bayat, Maryam

    2009-12-01

    The effect of light therapy (LT) on surgically created partial osteotomy in streptozotocin (STZ)-induced diabetic rats was examined. LT has been shown to enhance bone repair in healthy human and animal models. Forty male rats were divided into groups 1 to 5. Diabetes was induced in rats of groups 1, 2, and 3 using an intraperitoneal injection of STZ. All diabetic rats were maintained for 30 days after STZ injection. Under general anesthesia and sterile conditions, a partial transversal standardized osteotomy was made in the mid-portion of the right tibia. The defects in groups 2, 3, and 5 were treated using a helium-neon (He-Ne) laser (632.8 nm, 10 mW, circular beam shape). Groups 1 and 4 were diabetic placebo and normal placebo groups, respectively. A dose of 369.4 J/cm2 for groups 2 and 5 and a dose of 66.8 J/cm2 for group 3 were applied three times a week. Six weeks after surgery, the right tibia was collected. The specimen was subjected to a three-point bending test. LT with 369.4 J/cm2 energy density resulted in significantly greater bending stiffness in group 5 (41.8+/-5.2) than in groups 1 (18.5+/-4.1), 2 (17.7+/-1.6), and 3 (11.5+/-4) (least significant difference (LSD) test, p<0.01, p<0.001, and p<0.001, respectively). LT with 369.4 J/cm2 energy density resulted in a significantly higher stress load in group 5 (10+/-0.4) than in groups 1 (4.9+/-1.5), 2 (5.7+/-0.52), and 3 (3.9+/-1.1) (LSD test, p<0.01, p<0.01, p<0.001, respectively). LT with a He-Ne laser in STZ-induced diabetic rats did not enhance bone repair of a partial transversal standardized osteotomy.

  12. Modulation of Diabetes and Dyslipidemia in Diabetic Insulin-Resistant Rats by Mangiferin: Role of Adiponectin and TNF-α

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    SAMIRA SALEH

    2014-12-01

    Full Text Available Mangiferin, present in Mangifera indica bark, was reported to produce hypoglycemic and antidiabetic activity in an animal model of genetic type 2 diabetes and in streptozotocin diabetic rats. Its effect on diabetic insulin-resistant animals has not been investigated. The current work aimed to explore the effect of mangiferin on diabetic insulin-resistant rat model. Diabetes was induced by high-fat/high fructose diet for eight weeks followed by a subdiabetogenic dose of streptozotocin (HFD-Fr-STZ. Rats were treated with mangiferin (20 mg/kg i.p. for 28 days starting one week after STZ and its effects were compared to the standard insulin sensitizer, rosiglitazone. HFD-Fr-STZ, induced obesity, hyperglycemia and insulin resistance accompanied by depletion in liver glycogen and dyslipidemia. Moreover, there was an elevation in serum TNF-α and a reduction in adiponectin. Mangiferin ameliorated the consequences of HFD-Fr-STZ and its actions were comparable to the effects of the standard insulin sensitizer, rosiglitazone. The results obtained in this study provide evidence that mangiferin is a possible beneficial natural compound for type 2 diabetes and metabolic disorders associated with the metabolic syndrome. This effect is mediated through improving insulin sensitivity, modulating lipid profile and reverting adipokine levels to normal.

  13. Ghrelin reverses experimental diabetic neuropathy in mice

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-11-20

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

  14. The effect of long term administration of ascorbic acid on the learning and memory deficits induced by diabetes in rat

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    Parisa Hasanein

    2010-04-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Ascorbic acid improves cognitive impairments in several experimental models. Diabetes causes learning and memory deficits. In this study we hypothesized that chronic treatment with ascorbic acid (100mg/kg, p.o would affect on the passive avoidance learning (PAL and memory in control and streptozocin-induced diabetic rats."n"nMethods: Diabetes was induced by a single i.p. injection of STZ (60mg/kg. The rats were considered diabetic if plasma glucose levels exceeded 250mg/dl on three days after STZ injection. Treatment was begun at the onset of hyperglycemia. PAL was assessed 30 days later. Retention test was done 24 h after training. At the end, animals were weighted and blood samples were drawn for plasma glucose measurement."n"nResults: Diabetes caused impairment in acquisition and retrieval processes of PAL and memory in rats. Ascorbic acid treatment improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. Ascorbic acid administration also improved the body weight loss and hyperglycemia of diabetics. Hypoglycemic and antioxidant properties of the vitamin may be involved in the memory improving effects of such treatment."n"nConclusion: These results show that

  15. DBiochemical effect of Ginko biloba extract on carbohydrate metabolism in (induced type two diabetic rats

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    Omayma A.R.

    2016-06-01

    Full Text Available Ginkgo biloba extract (EGb 761 has been used in traditional Chinese medicine for 5000 years that possesses various biological activities and has been shown to be useful in diabetes treatment. This study was carried out on 120, 12-14 weeks old male rats and weighted 150-200 gm. Rats were classified into two main large experiments. Experiment 1: Non-diabetic rats Included 40 of normal male rats were divided into two groups each one comprises 20 rats kept in separate metal cages and classified as follows: Group 1: Non-diabetic rats were administered with 0.2 ml of normal saline only (control group.Group 2:Non-diabetic rats were received (GBE (120 mg/kg, given orally by stomach tube and daily for 6 weeks.Experiment 2: Diabetic rats "STZ group" Included 80 male diabetic rats were divided into four groups each one comprises 20 rats kept in a separate metal cages and classified as follows: Group 1: Diabetic rats were administered with 0.2 ml of normal saline only (diabetic control group.Group 2: Diabetic rats were received (GBE (120 mg/kg, given orally by stomach tube and daily for 6 weeks. Group 3: Diabetic rats were received glimepiride (20mg/kg, given orally by stomach tube and daily for 6 weeks. Group 4: Diabetic rats received glimepiride in combination with (GBE, given orally by stomach tube and daily (1:1 for 6 weeks. Blood samples were collected from all animals groups after 3 and 6 weeks from treatment. Serum were separated and processed directly for (glucose, Lactate, total cholesterol, triacylglycerol, Minerals (Na+, K+, Ca++, L-MDA concentration-(insulin, Glucagon, Testosterone levels-