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Sample records for stz-induced diabetic rats

  1. Attenuated Effects of Deep-Sea Water on Hepatic Apoptosis in STZ-Induced Diabetic Rats.

    PubMed

    Hsu, Tsai-Ching; Chiu, Chun-Ching; Lin, Hsou-Lin; Kao, Tseng-Wei; Chen, Li-Jeng; Wu, Li-Yi; Huang, Chih-Yang; Tzang, Bor-Show

    2015-06-30

    Diabetes mellitus (DM) is a metabolic disorder and increasing evidences have indicated a connection between DM and hepatic abnormality. Deep-sea water (DSW) has been applied in many fields, especially in medicine; herein, we investigated the influence of DSW on hepatic apoptosis in streptozocin (STZ)-induced diabetes rats. Our experimental results firstly demonstrated the beneficial effects of 1×DSW, 2×DSW and 3×DSW in alleviating hepatic apoptosis in STZ-induced diabetic rats. We demonstrated that 1×DSW, 2×DSW and 3×DSW significantly suppressed the caspase-3 activity and TUNEL-positive cells in livers of STZ-induced diabetic rats. Significant reductions of both Fas-dependent and mitochondrial-dependent apoptotic molecules were also detected in livers of STZ-induced diabetic rats receiving DSW. Additionally, apoptotic signaling molecules such as phosphorylated I?B-? and NF-?B were significantly reduced in livers of DSW-treated STZ-induced diabetic rats. These findings indicate hepatic protective effects of DSW on DM and suggest DSW as a possible ingredient for health food. PMID:26014125

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

    PubMed Central

    2013-01-01

    Background The available drugs for diabetes, Insulin or Oral hypoglycemic agents have one or more side effects. Search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic and antihyperlipidemic effects of Piper longum root aqueous extract (PlrAqe) in streptozotocin (STZ) induced diabetic rats. Methods Diabetes was induced in male Wister albino rats by intraperitoneal administration of STZ (50 mg/kg.b.w). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The activities of liver and kidney functional markers were measured. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by DMRT. Results During the short term study the aqueous extract at a dosage of 200 mg/kg.b.w was found to possess significant antidiabetic activity after 6 h of the treatment. The administration of aqueous extract at the same dose for 30 days in STZ induced diabetic rats resulted in a significant decrease in FBG levels with the corrections of diabetic dyslipidemia compared to untreated diabetic rats. There was a significant decrease in the activities of liver and renal functional markers in diabetic treated rats compared to untreated diabetic rats indicating the protective role of the aqueous extract against liver and kidney damage and its non-toxic property. Conclusions From the above results it is concluded that the plant extract is capable of managing hyperglycemia and complications of diabetes in STZ induced diabetic rats. Hence this plant may be considered as one of the potential sources for the isolation of new oral anti hypoglycemic agent(s). PMID:23414307

  3. The inhibitory effect of Isoflavones isolated from Caesalpinia pulcherrima on aldose reductase in STZ induced diabetic rats.

    PubMed

    Kumar, Munipally Praveen; Sankeshi, Venu; Naik, R Ravindar; Thirupathi, P; Das, Biswanath; Raju, T N

    2015-07-25

    Increased aldose reductase activity has been implicated in the development of retinopathy due to accumulation of intracellular sugar alcohol, i.e., sorbitol. In this study, the compounds isolated from the Caesalpinia pulcherrima, have been examined for its inhibitory effects on aldose reductase (AR), which plays a major role in diabetic retinopathy. 3,6,7,4',5'-Pentamethoxy-5,3'-dihydroxyflavone (Compound 2) has shown significant inhibition of rat retina AR with an IC50 value of 16.24±0.046?M in a non-competitive manner. Molecular docking study results are steady with the pattern of AR inhibition by Compound 2 and its specificity. The supplementation of Compound 2 suppresses sorbitol accumulation in retina by decreased AR activity in STZ induced diabetic rat in dose dependent manner. Besides this, rats fed with Compound 2 have shown improved levels of antioxidant enzymes. This study revealed that Compound 2 has pharmacologically active component with a potential to inhibit rat retina AR and affecting the delaying process of diabetic retinopathy in STZ induced diabetic rats. PMID:25986969

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

    PubMed Central

    Abbasnezhad, Abbasali; Hayatdavoudi, Parichehr; Niazmand, Saeed; Mahmoudabady, Maryam

    2015-01-01

    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 thiol levels were determined by calorimetric assay. Results: Serum glucose level in the diabetic rats treated with 200 mg/kg Nigella sativa extract at the days 24 and 45 decreased in comparison to untreated diabetic group (p<0.05, p<0.01, respectively). Weight loss was significantly different between metformin and Nigella sativa extract at the dose of 200 and 400 mg/kg (p<0.05). Thiol content of hippocampus increased by 200 mg/kg Nigella sativa extract in comparison to untreated diabetic group (p<0.05). Malondialdehyde content of hippocampus reduced by Nigella sativa extract, 200 mg/kg (p<0.001), 400 mg/kg (p<0.05), and metformin (p<0.05) in comparison to the untreated diabetic group. Conclusion: The results of the present study showed that hydroalcoholic extract of the Nigella sativa decreased oxidative stress in hippocampus of the STZ-induced diabetic rats. Nigella sativa at the dose of 200 mg/kg was more effective to reduce oxidative stress in hippocampus of rats. PMID:26445713

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

    PubMed

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

    2013-09-01

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

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

    PubMed

    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 ?-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. PMID:24689449

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

    PubMed

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

    2013-09-01

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

  8. Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats.

    PubMed

    Sato, K; Fujita, S; Iemitsu, M

    2014-09-01

    Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30 min for 150 min after injection of diosgenin or dioscorea (3mg/kg). On another day, muscle was resected 150 min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120 min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ?/?, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5?-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150 min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats. PMID:24607838

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

    PubMed Central

    Koellisch, Ulrich; Laustsen, Christoffer; Nørlinger, Thomas S; Østergaard, Jakob Appel; Flyvbjerg, Allan; Gringeri, Concetta V; Menzel, Marion I; Schulte, Rolf F; Haase, Axel; Stødkilde-Jørgensen, Hans

    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 [1-13C]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 that the hyperpolarized acetylcarnitine to acetate ratio was independent of blood glucose levels and prolonged hyperglycemia following diabetes induction in a type-1 diabetes model. PMID:26272734

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

    Qian, Xiaoqian; Li, Xuechen; Ilori, Titilayo O.; Klein, Janet D.; Hughey, Rebecca P.; Li, Cong-jun; Alli, Abdel A.; Guo, Zhengyu; Yu, Peng; Song, Xiang; Chen, Guangping

    2015-01-01

    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, ?-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 with 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, fucosylated and branched. Consistently, a number of crucial glycosylation related genes are changed under diabetic conditions. The alteration of these genes may contribute to changes in the UT-A1 glycan structure and therefore modulate kidney urea transport activity and alleviate osmotic diuresis caused by glucosuria in diabetes. PMID:26483702

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The UT-A1 urea transporter is crucial to the kidney’s ability to generate the 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, protein abundance, particularly the 117 kD isoform, is si...

  13. Modulation of liver function, antioxidant responses, insulin resistance and glucose transport by Oroxylum indicum stem bark in STZ induced diabetic rats.

    PubMed

    Singh, Jyotsna; Kakkar, Poonam

    2013-12-01

    A decoction of stem bark of Oroxylum indicum Vent. (OI) is taken (2-3 times/day) by the tribal people of Sikkim, India to treat diabetes but scientific validation of its overall potential is lacking. Present study was aimed to assess in vitro antihyperglycemic activity of standardized OI extract using inhibition of ?-glucosidase, BSA glycation and enhancement of insulin sensitivity. Antidiabetic and antioxidant modulatory effects of OI extract along with the blood biomarkers of toxic response were studied in streptozotocin (STZ) induced diabetic rats. In vitro analysis showed strong antioxidant capacity of OI -and potential to inhibit BSA glycation and ?-glucosidase activity which was comparable to standard counterparts. Extract also improved insulin sensitivity in mature 3T3-L1 adipocytes. In vivo effects of OI extract (oral 250 mg/kg b.wt.) on STZ induced type II diabetic rats normalized the antioxidant status (p?0.01). Analysis of blood biomarkers of toxic response indicated its safety. Lowering of total cholesterol and HDL levels (p?0.05) and restoration of glycated Hb (p?0.01) were also found in OI treated diabetic rats. HOMA-IR, QUICKI analysis along with area under the curve analysis showed the capacity of OI extract to enhance the insulin sensitivity significantly (p?0.01) which was confirmed by increased GLUT-4 translocation in skeletal muscles. PMID:24140466

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

    PubMed Central

    Moraes, Izabela Barbosa; Manzan-Martins, Camilla; de Gouveia, Neire Moura; Calábria, Luciana Karen; Hiraki, Karen Renata Nakamura; Moraes, Alberto da Silva; Espindola, Foued Salmen

    2015-01-01

    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. PMID:25763088

  15. The effect of swimming exercise and powdered-Salicornia herbacea L. ingestion on glucose metabolism in STZ-induced diabetic rats

    PubMed Central

    Lee, Se Sil; Seo, Hyobin; Ryu, Sungpil; Kwon, Tae-Dong

    2015-01-01

    Purpose The purpose of this study is to observe the effects of Salicornia herbacea L. powder ingestion on carbohydrate metabolism in STZ-induced diabetic rats. Methods To achieve this objective, 35 Sprague-Dawley male rats were raised with feed mixed with Salicornia herbacia L. powder and given specific periods to swim for 5 weeks. There was no significant difference in the insulin increase rate while ingesting Salicornia herbacea L. powder and simultaneously exercising. Results Compared to the diabetes mellitus group, HOMA-IR was significantly decreased in the diabetes mellitus + exercise group, diabetes mellitus + Salicornia herbacea group, and the diabetes mellitus + Salicornia herbacea + exercise group. However, changes in blood glucose were significant in each group. Thus, for the result of GLUT-4 and GLUT-2, which are the glycose transporters of the liver and muscle, diabetes mellitus + exercise group, diabetes mellitus + Salicornia herbacea group, and diabetes mellitus + Salicornia herbacea + exercise group showed significantly higher expressions. The glycogen concentration of the liver and muscle was significantly increased in the diabetes mellitus + exercise group, diabetes mellitus + Salicornia herbacea group, and diabetes mellitus + Salicornia herbacea + exercise group. Conclusion With the results above, it seems that taking Salicornia herbacea L. powder and exercise will help prevent various diabetic complications. Therefore, the findings of this study could justify Salicornia herbacea L. powder with its basal data of physiological activities and pharmacological components as a type of health functional food. PMID:26525167

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

    PubMed Central

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

    2013-01-01

    To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ? 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of ?-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment. PMID:23698784

  17. Methoxy VO-salen stimulates pancreatic ? cell survival by upregulation of eNOS and downregulation of apoptosis in STZ-induced diabetic rats.

    PubMed

    Roy, Souvik; Mondru, Anil Kumar; Dontamalla, Sudheer Kumar; Vaddepalli, Ram Prasad; Sannigrahi, Santanu; Veerareddy, Prabhakar Reddy

    2011-12-01

    The present study was designed to investigate the effect of MetVO-salen in ameliorating diabetes and oxidative stress in the pancreas of diabetic rats. Streptozotocin (STZ)-induced diabetic rats were treated with MetVO-salen complex intraperitonially (0.3 and 0.6 mg/kg) thrice a week and continued for 8 weeks. Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides in serum, and blood glucose were estimated. Furthermore, oxidative stress in rats was also investigated in terms of superoxide dismutase (SOD), catalase, lipid peroxidation, and glutathione (GSH). In addition, the anti-diabetic activity of MetVO-salen was also investigated by assessing histopathological, immunohistochemical in terms of endothelial nitric oxide synthase expression, and apoptotic events in pancreas. Treatment with MetVO-salen complex reduced the blood glucose level and significantly altered the serum biochemical parameters of diabetic rats. Treatment with above complex decreased the lipid peroxidation and the antioxidant enzymes such as SOD, CAT, and GSH to near-control levels. Histopathological, immunohistochemical, and apoptotic studies also revealed that MetVO-salen-induced amelioration of the diabetic state appears to be significant to the preservation of a functional portion of the pancreatic ? cells which initially prevent STZ toxicity. This study provides new direction for the management of diabetes but needs further clinical evaluation. PMID:21748304

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

    PubMed Central

    Ishak, Nur Akmal; Ismail, Maznah; Hamid, Muhajir; Ahmad, Zalinah; Abd Ghafar, Siti Aisyah

    2013-01-01

    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, PPAR?, PPAR?, 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. PMID:23762147

  19. Effects of vanadium (III, IV, V)-chlorodipicolinate on glycolysis and antioxidant status in the liver of STZ-induced diabetic rats.

    PubMed

    Xie, Mingxia; Chen, Deliang; Zhang, Fang; Willsky, Gail R; Crans, Debbie C; Ding, Wenjun

    2014-07-01

    Vanadium compounds exert various insulin-mimetic and anti-diabetic effects both in vitro and in vivo. Vanadium(III, IV, V)-chlorodipicolinate (Vdipic-Cl) compounds, including H[V(III)(dipic-Cl)2]·5H2O (V3dipic-Cl), V(IV)O(dipic-Cl)(H2O)2 (V4dipic-Cl) and K[V(V)O2(dipic-Cl)] (V5dipic-Cl), were synthesized with the indicated oxidation states. The present study was conducted to investigate if chemical valence and anti-oxidation effects of vanadium compounds are involved in the anti-diabetic effects observed in streptozotocin (STZ)-induced diabetic rats treated with these vanadium compounds. V3dipic-Cl, V4dipic-Cl, V5dipic-Cl, inorganic vanadium salts vanadyl sulfate (VOSO4) or sodium metavanadate (NaVO3) were orally administered in drinking water (50 ?gV/ml) to STZ-induced diabetic rats for 28 days. The results showed that Vdipic-Cl treatment significantly improved hyperglycemia and glucose intolerance, as well as increased hepatic glycogen synthesis in diabetic rats. The mRNA levels of key glycolytic enzymes in liver, phosphoenolpyruvate carboxykinase (PEPCK), glucokinase (GK), and L-pyruvate kinase (L-PK) altered in diabetic animals were significantly restored towards normal values by treatment with some of the vanadium compounds. Moreover, the diabetes elevated activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in serum were significantly decreased after treatment with Vdipic-Cl complexes. Furthermore, treatment of diabetic rats with V4dipic-Cl and V5dipic-Cl compounds significantly reduced malondialdehyde (MDA) production and increased glutathione peroxidase (GSH-Px) and catalase (CAT) activities. These data suggest that vanadium compounds with the indicated chemical valence promote glycogen synthesis and recover suppressed glycolysis in the liver of diabetic rats due to their capacity to reduce oxidative stress by stimulating antioxidant enzymes. PMID:24747360

  20. Effect of VIVO(dipic-Cl)(H2O)2 on Lipid Metabolism Disorders in the Liver of STZ-Induced Diabetic Rats

    PubMed Central

    Xie, Mingxia; Chen, Deliang; Li, Jian; Ding, Wenjun

    2013-01-01

    Vanadium complexes are potent antidiabetic agents for therapeutical treatment of diabetes. In the present study, we investigated the hypolipidemic effect of VIVO(dipic-Cl)(H2O)2 (V4dipic-Cl) in liver of streptozotocin- (STZ-)-induced diabetic rats. We found that diabetic animals exhibited hepatic inflammatory infiltration and impaired liver function along with triglyceride (TG) accumulation in the liver. V4dipic-Cl treatment not only ameliorated liver pathological state but also reduced hepatic TG level. Moreover, the upregulation of fatty acid translocase (FAT/CD36) mRNA (4.0-fold) and protein (8.2-fold) levels in the liver of diabetic rats were significantly reversed after V4dipic-Cl treatment. However, no significant effects of V4dipic-Cl on the mRNA expression of fatty acid metabolism-related fatty acid bounding protein 1 (FABP1) and fatty acid transporter 5 (FATP5) were observed. These results suggest that the modification of lipid metabolism-related FAT/CD36 in the liver of diabetic rats is likely involved in the hypolipidemic effects of V4dipic-Cl. PMID:23691525

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

    PubMed

    Chaudagar, Kiranj K; Mehta, Anita A

    2014-04-01

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

  2. Telmisartan ameliorates germ cell toxicity in the STZ-induced diabetic rat: studies on possible molecular mechanisms.

    PubMed

    Kushwaha, S; Jena, G B

    2013-07-01

    Testicular damage is a common clinical problem in diabetic individuals that severely affects the quality of life. The present study investigates the possible protective mechanisms of telmisartan, an angiotensin II-receptor antagonist in the germ cell of diabetic rat. Male SD rats were used and randomized into six groups: control, telmisartan control, diabetic control and diabetic group treated with telmisartan at the doses of 3, 6 and 12mg/kg/day, per oral for 4 weeks. Diabetes was induced by injecting a single dose of streptozotocin (STZ), (55mg/kg) dissolved in ice-cold 10mM citrate buffer; pH 4.4 and administered i.p. immediately after preparation to the SD rats. At the end of the study, rats were sacrificed and the levels of nitrite, superoxide, malondialdehyde (MDA), glutathione (reduced and peroxidase) and superoxide dismutase (SOD) were measured. Germ cell toxicity was evaluated by using sperm count, sperm comet assay, histology of testes and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Further to confirm the oxidative and nitrosative damage, immunohistological quantification of 8-oxo-dG (8-oxo-7,8-dihydro-2'-deoxyguanosine) and 3-nitrotyrosine were evaluated respectively. Results showed that telmisartan significantly restored the levels of nitrite, superoxide, malondialdehyde, and glutathione and superoxide dismutase in diabetic testes. Further, telmisartan significantly increased the sperm counts, reduced apoptotic cell death, sperm DNA damage, oxidative and nitrosative damage in diabetic rat. Western blot analysis showed that telmisartan reduced the testicular inflammation and cell death by down-regulating the expression of NF-?B, IL-6, TNF-?, p-ERK1/2, iNOS, caspase-3 and increasing the PPAR-? expression. Results clearly indicate that telmisartan significantly reduced the both oxidative and nitrosative stress, inflammation and cell death in diabetic testes. The present results confirmed that telmisartan exhibited beneficial role in the germ cell of diabetic rat. PMID:23648321

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

    PubMed

    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 ?-amylase and ?-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 ?-amylase and ?-glucosidase activities, with IC50 values of 4.0 and 3.5 ?g/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. PMID:26604360

  4. Toll-like receptor 2 mediates vascular contraction and activates RhoA signaling in vascular smooth muscle cells from STZ-induced type 1 diabetic rats.

    PubMed

    Schmidt, Luke; Carrillo-Sepulveda, Maria Alicia

    2015-11-01

    Increased vascular smooth muscle cell (VSMC) contraction is an early and critical contributor to the pathogenesis of vascular dysfunction in diabetes; however, knowledge regarding the underlying mechanisms is scarce. Toll-like receptor 2 (TLR2), a well-known component of the innate immunity, is expressed in VSMC and recently has been identified to be systemically activated in diabetes. Whether TLR2 is locally activated in the diabetic blood vessels and have effect on contraction is not known. In the current study, we examined the role of TLR2 in increased vascular contraction in diabetes. Utilizing rat model of type 1 diabetes (induced by streptozotocin (STZ)), we demonstrated that aortas from STZ-diabetic rats exhibit increased expression of TLR2 and its adaptor protein, myeloid differentiation primary response 88 (MyD88), as well as enhanced protein-protein interaction between TLR2 and MyD88, suggesting a TLR2 signaling activation. Blockade of TLR2 in intact aortas using anti-TLR2 antibody attenuated increased vascular contraction in STZ-diabetic rat as assessed by wire myograph. Activation of TLR2 by specific ligand in primary aortic VSMC cultures triggered activation of RhoA which was exacerbated in cells from STZ-diabetic rats than control rats. Activation of RhoA was accompanied by phosphorylation and therefore activation of its downstream targets myosin phosphatase target subunit I and myosin light chain (markers of VSMC contraction). Taken together, these results provide evidence for the role of TLR2 in increased contraction in diabetic blood vessels that involves RhoA signaling. Thus, targeting vascular TLR2 offers a promising drug target to treat vascular dysfunction in diabetes. PMID:25600901

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

    PubMed Central

    Sánchez-González, Cristina; López-Chaves, Carlos; Trenzado, Cristina E.; Aranda, Pilar; López-Jurado, María; Gómez-Aracena, Jorge; Montes-Bayón, María; Sanz-Medel, Alfredo; Llopis, Juan

    2014-01-01

    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(P)H: 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. PMID:24511298

  6. Virus-Mediated Knockdown of Nav1.3 in Dorsal Root Ganglia of STZ-Induced Diabetic Rats Alleviates Tactile Allodynia

    PubMed Central

    Tan, Andrew M; Samad, Omar A; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2015-01-01

    Diabetic neuropathic pain affects a substantial number of people and represents a major public health problem. Available clinical treatments for diabetic neuropathic pain remain only partially effective and many of these treatments carry the burden of side effects or the risk of dependence. The misexpression of sodium channels within nociceptive neurons contributes to abnormal electrical activity associated with neuropathic pain. Voltage-gated sodium channel Nav1.3 produces tetrodotoxin-sensitive sodium currents with rapid repriming kinetics and has been shown to contribute to neuronal hyperexcitability and ectopic firing in injured neurons. Suppression of Nav1.3 activity can attenuate neuropathic pain induced by peripheral nerve injury. Previous studies have shown that expression of Nav1.3 is upregulated in dorsal root ganglion (DRG) neurons of diabetic rats that exhibit neuropathic pain. Here, we hypothesized that viral-mediated knockdown of Nav1.3 in painful diabetic neuropathy would reduce neuropathic pain. We used a validated recombinant adeno-associated virus (AAV)-shRNA-Nav1.3 vector to knockdown expression of Nav1.3, via a clinically applicable intrathecal injection method. Three weeks following vector administration, we observed a significant rate of transduction in DRGs of diabetic rats that concomitantly reduced neuronal excitability of dorsal horn neurons and reduced behavioral evidence of tactile allodynia. Taken together, these findings offer a novel gene therapy approach for addressing chronic diabetic neuropathic pain. PMID:26101954

  7. Effects of L-3-n-butylphthalide on cognitive dysfunction and NR2B expression in hippocampus of streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Li, Jie; Zhang, Songyun; Zhang, Lihui; Wang, Ruiying; Wang, Mian

    2015-01-01

    Diabetes mellitus is associated with rapid cognitive decline. Currently, there is no effective treatment for cognitive dysfunction induced by diabetes. L-3-n-Butylphthalide (L-NBP) is a nerve protective drug extracted from seeds of celery, which has been proved to improve learning and memory in vascular dementia animal models by improving microcirculation, protecting mitochondria and increasing long-term potentiation (LTP). NR2B, one of the subunits of N-methyl-D-aspartate receptor, has been proved to be an important factor for the formation of LTP. The study aimed to investigate the role of NR2B in cognitive dysfunction in the rats with type 1 diabetes and define the protective effects of L-NBP on cognition. A rat model of type 1 diabetes was established by a single intraperitoneal injection of streptozotocin at 60 mg/kg. Animals were randomly allocated to four groups: normal control (NC); diabetic control (DC); diabetic + low L-NBP (DL, administered L-NBP 60 mg/kg per day for 12 weeks); and diabetic + high L-NBP (DH, administered L-NBP 120 mg/kg per day, for 12 weeks). After 12 weeks, cognitive and memory changes were investigated in the Morris water maze. The expression of NR2B was assessed by real-time polymerase chain reaction, Western blotting, and immunohistochemistry. Our results indicated that the escape latency was significantly increased and the number of crossing platform was significantly decreased in DC group compared to NC group. Also, the expression of NR2B was significantly declined in DC group. However, compared to DC group, the expression of NR2B of the L-NBP-treated groups was significantly increased and the escape latency was shortened with the DH group being the most obvious. Therefore, L-NBP can improve the cognitive function by up-regulating the expression of NR2B in STZ-diabetic rats, which may provide the direction for future diabetic encephalopathy therapy. PMID:25149651

  8. Insulin secreting and alpha-glucosidase inhibitory activity of hexane extract of Annona squamosa Linn. in streptozotocin (STZ) induced diabetic rats.

    PubMed

    Ranjana; Tripathi, Yamini B

    2014-06-01

    The hexane extract of A. squamosa (ASHE) in 100 and 400 mg/kg body weight dose raised the insulin level when compared with Glimepiride (1 mg/kg) and also inhibited alpha-glucosidase activity when compared with Acarbose (10 mg/kg) in streptozotocin induced diabetic rats. The ASHE significantly reduced peak blood glucose (Gp30) and area under curve (AUC) in diabetic rats in oral glucose (OGTT) and oral sucrose (OSTT) tolerance test, but there was more reduction of Gp30 value than AUC in OSTT. Thus, it can be suggested that the ASHE, has hypoglycemic role at 2 levels, i.e. it acts as secretagogue and also inhibits the intestinal enzymes, responsible for glucose metabolism. PMID:24956893

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

    PubMed

    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-? were measured, and also the levels of lipid peroxidation and antioxidant enzymes were observed. SA significantly (p < .05) reduced and normalized blood glucose levels and also decreased the levels of HbA1c as compared with that of HFD STZ control group. SA treatment also significantly (p < .05) increased the levels of antioxidant enzymes while decreasing the levels of lipid peroxidation. The potential antihyperglycemic action and antioxidant role might be due to the presence of flavonoids in the drug. PMID:22432800

  10. A novel insulin mimetic vanadium-flavonol complex: synthesis, characterization and in vivo evaluation in STZ-induced rats.

    PubMed

    Pillai, Subramanian Iyyam; Subramanian, Sorimuthu Pillai; Kandaswamy, Muthusamy

    2013-05-01

    Since 1985, when Heyliger et al., first demonstrated a serendipitous discovery that oral administration of 0.8 mg/ml of sodium orthovanadate in drinking water to streptozotocin-induced diabetic rats resulted in normoglycemia, numerous extensive studies have been pursued on the anti-diabetic and insulinomimetic actions of vanadium. The acceptance of vanadium compounds as promising therapeutic antidiabetic agents has been slowed due to the concern for chronic toxicity associated with vanadium accumulation. In order to circumvent the toxic effects of vanadium, we have taken up a combinational approach wherein a novel vanadium-flavonol complex was synthesized, characterized and its toxic as well as insulin mimetic potential was evaluated in STZ-induced experimental diabetes in rats. The results indicate that the complex is non-toxic and possess anti-diabetic activity. PMID:23466606

  11. A Novel Role for SIRT-1 in L-Arginine Protection against STZ Induced Myocardial Fibrosis in Rats

    PubMed Central

    Rizk, Sherine M.; El-Maraghy, Shohda A.; Nassar, Noha N.

    2014-01-01

    Background L-arginine (L-ARG) effectively protects against diabetic impediments. In addition, silent information regulator (SIRT-1) activators are emerging as a new clinical concept in treating diabetic complications. Accordingly, this study aimed at delineating a role for SIRT-1 in mediating L-ARG protection against streptozotocin (STZ) induced myocardial fibrosis. Methods Male Wistar rats were allocated into five groups; (i) normal control rats received 0.1 M sodium citrate buffer (pH 4.5); (ii) STZ at the dose of 60 mg/kg dissolved in 0.1 M sodium citrate buffer (pH 4.5); (iii) STZ + sirtinol (Stnl; specific inhibitor of SIRT-1; 2 mg/Kg, i.p.); (iv) STZ + L-ARG given in drinking water (2.25%) or (v) STZ + L-ARG + Stnl. Results L-ARG increased myocardial SIRT-1 expression as well as its protein content. The former finding was paralleled by L-ARG induced reduction in myocardial fibrotic area compared to STZ animals evidenced histopathologically. The reduction in the fibrotic area was accompanied by a decline in fibrotic markers as evident by a decrease in expression of collagen-1 along with reductions in myocardial TGF-?, fibronectin, CTGF and BNP expression together with a decrease in TGF-? and hydroxyproline contents. Moreover, L-ARG increased MMP-2 expression in addition to its protein content while decreasing expression of PAI-1. Finally, L-ARG protected against myocardial cellular death by reduction in NF?-B mRNA as well as TNF-? level in association with decline in Casp-3 and FAS expressions andCasp-3protein content in addition to reduction of FAS positive cells. However, co-administration of L-ARG and Stnl diminished the protective effect of L-ARG against STZ induced myocardial fibrosis. Conclusion Collectively, these findings associate a role for SIRT-1 in L-ARG defense against diabetic cardiac fibrosis via equilibrating the balance between profibrotic and antifibrotic mediators. PMID:25501750

  12. Anti-diabetic activity of Vaccinium bracteatum Thunb. leaves' polysaccharide in STZ-induced diabetic mice.

    PubMed

    Wang, Li; Zhang, Ying; Xu, Maochao; Wang, Yingyao; Cheng, Sujiao; Liebrecht, Alex; Qian, Haifeng; Zhang, Hui; Qi, Xiguang

    2013-10-01

    Vaccinium bracteatum Thunb. (VBT) is a traditional Chinese herbal medicine. The anti-diabetic activity of VBT leaves' polysaccharide (VBTLP) is studied in this paper. The results indicated VBTLP had a dose-dependent decrease on the blood glucose (BG) level, and the time effect of VBTLP on BG level was also significant. The insulin level of high dose group (HDG) was significantly higher (p<0.05) than that of model control (MC) group. Compared to MC, HDG and lose dose group (LDG) had significantly lower (p<0.05) TC and LDL-C levels, however, TG and HDL-C levels are similar. Compared to non-diabetic control (NC), HDG and LDG had similar plasma lipid levels except for higher LDL-C level. Although body weights of LDG and HDG were significant lower (p<0.05) than that of NC from week 2 to week 6, they were similar to that of PC. The results indicate VBTLP possesses a potential hypoglycemic effect in streptozotocin-induced diabetic mice. PMID:23916645

  13. Mast cells control insulitis and increase Treg cells to confer protection against STZ-induced type 1 diabetes in mice.

    PubMed

    Carlos, Daniela; Yaochite, Juliana N U; Rocha, Fernanda A; Toso, Vanina D; Malmegrim, Kelen C R; Ramos, Simone G; Jamur, Maria C; Oliver, Constance; Camara, Niels O; Andrade, Marcus V M; Cunha, Fernando Q; Silva, João S

    2015-10-01

    Quantitative alterations in mast cell numbers in pancreatic lymph nodes (PLNs) have been reported to be associated with type 1 diabetes (T1D) progression, but their potential role during T1D remains unclear. In this study, we evaluated the role of mast cells in T1D induced by multiple low-dose streptozotocin (MLD-STZ) treatments, using two strains of mast cell-deficient mice (W/W(v) or Wsh/Wsh) and the adoptive transfer of mast cells. Mast cell deficient mice developed severe insulitis and accelerated hyperglycemia, with 100% of mice becoming diabetic compared to their littermates. In parallel, these diabetic mice had decreased numbers of T regulatory (Treg) cells in the PLNs. Additionally, mast cell deficiency caused a significant reduction in IL-10, TGF-?, and IL-6 expression in the pancreatic tissue. Interestingly, IL-6-deficient mice are more susceptible to T1D associated with reduced Treg-cell numbers in the PLNs, but mast cell transfer from wild-type mice induced protection to T1D in these mice. Finally, mast cell adoptive transfer prior to MLD-STZ administration conferred resistance to T1D, promoted increased Treg cells, and decreased IL-17-producing T cells in the PLNs. Taken together, our results indicate that mast cells are implicated in resistance to STZ-induced T1D via an immunological tolerance mechanism mediated by Treg cells. PMID:26234742

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

    PubMed

    Ishizaka, Masanori; Gohda, Tomohito; Takagi, Miyuki; Omote, Keisuke; Sonoda, Yuji; Oliva Trejo, Juan Alejandro; Asao, Rin; Hidaka, Teruo; Asanuma, Katsuhiko; Horikoshi, Satoshi; Tomino, Yasuhiko

    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. PMID:26435502

  15. Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses.

    PubMed

    Chu, Shenghui; Gu, Junfei; Feng, Liang; Liu, Jiping; Zhang, Minghua; Jia, Xiaobin; Liu, Min; Yao, Danian

    2014-04-01

    Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD. In the present study, we demonstrated that Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-? and IL-1? (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). In addition, Congo red and immunohistochemistry staining results showed that Rg5 alleviated A? deposition but enhanced the expressions of insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) in the hippocampus and cerebral cortex (P<0.05). Western blot analysis also demonstrated that Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly A? deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Rg5, which was associated with attenuating neuroinflammatory responses. Our findings suggested that Rg5 could be a beneficial agent for the treatment of AD. PMID:24503167

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

    PubMed

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

    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 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. PMID:26703560

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

    PubMed Central

    Liu, Hua-Yu; Fang, Meng; Zhang, Yu-Qing

    2014-01-01

    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 ?-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. PMID:25177729

  18. Cavernous antioxidant effect of green tea, epigallocatechin-3-gallate with/without sildenafil citrate intake in aged diabetic rats.

    PubMed

    Mostafa, T; Sabry, D; Abdelaal, A M; Mostafa, I; Taymour, M

    2013-08-01

    This study aimed to assess the cavernous antioxidant effect of green tea (GT), epigallocatechin-3-gallate (EGCG) with/without sildenafil citrate intake in aged diabetic rats. One hundred and four aged male white albino rat were divided into controls that received ordinary chow, streptozotocin (STZ)-induced aged diabetic rats, STZ-induced diabetic rats on infused green tea, induced diabetic rats on epigallocatechin-3-gallate and STZ-induced diabetic rats on sildenafil citrate added to EGCG. After 8 weeks, dissected cavernous tissues were assessed for gene expression of eNOS, cavernous malondialdehyde (MDA), glutathione peroxidase (GPx), cyclic guanosine monophosphate (cGMP), and serum testosterone (T). STZ-induced diabetic rats on GT demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats. Diabetic rats on EGCG demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats or diabetic rats on GT. Diabetic rats on EGCG added to sildenafil showed significant increase in cavernous eNOS, cGMP and significant decrease in cavernous MDA compared with other groups. Serum T demonstrated nonsignificant difference between the investigated groups. It is concluded that GT and EGCG have significant cavernous antioxidant effects that are increased if sildenafil is added. PMID:22928786

  19. Characteristics of dendroaspis natriuretic peptide and its receptor in streptozotocin-induced diabetic rats.

    PubMed

    Park, Byoung Hyun; Kim, Sun Young; Kim, Soo Mi; Noh, Hye Jung; Cho, Chong Gu; Kim, Sung Zoo

    2015-08-01

    Dendroaspis natriuretic peptide (DNP) shares a functionally important sequence homology with other natriuretic peptides. However, the characteristics of DNP and its receptor in the context of diabetes remafin to be fully elucidated. In the present study, alterations in the plasma levels and tissue contents of DNP and the properties of its receptor in diabetic rats, induced by streptozotocin (STZ) injection, were investigated. The plasma levels of DNP were 90.01 ± 4.12 and 196.68 ± 5.60 pg/ml in the control and STZ-induced diabetic rats, respectively. The tissue contents of DNP in the cardiac atrium, ventricle, renal cortex and inner medulla of the STZ-induced diabetic rats were also significantly increased compared with the control rats. Specific (125)I-DNP-binding sites were located predominantly in the glomeruli and inner medulla of the rat kidney. In the glomeruli of the kidney, the apparent dissociation constants (Kd) of (125)I-DNP in the control and STZ-induced diabetic rats were 0.41 ± 0.03 and 0.56 ± 0.06 nM, respectively. The maximum binding capacities (Bmax) of (125)I-DNP in control and STZ-induced diabetic rats were 2.98 ± 0.21 and 6.22 ± 1.06 fmol/mg protein, respectively. However, no differences were observed in the apparent Kd and Bmax of (125)I-DNP in the inner medulla of the kidney between the control and STZ-induced diabetic rats. In the glomerular and inner medullary kidney membranes, DNP stimulated the production of cyclic guanosine monophosphate (cGMP) in a dose-dependent manner. The magnitude of cGMP production in glomerular membranes was greater in the STZ-induced diabetic rats, whereas the magnitude of cGMP production in the inner medullary membranes was lower in the STZ-induced diabetic rats compared with the control rats. These results indicated that STZ-induced diabetes modulate DNP and its receptor, and also suggested that modulation of the DNP system is involved in the renal function of diabetic animals via the intracellular domain of the kidney NP receptor. PMID:25937111

  20. Protective effect of polysaccharides from Opuntia dillenii Haw. fruits on streptozotocin-induced diabetic rats.

    PubMed

    Gao, Jie; Han, Yu-Lu; Jin, Zheng-Yu; Xu, Xue-Ming; Zha, Xue-Qiang; Chen, Han-Qing; Yin, Yan-Yan

    2015-06-25

    In this study, a novel water-soluble polysaccharide fraction with molecular weight of 6479.1kDa was isolated from the fruits of Opuntia dillenii Haw., which consisted of rhamnose, xylose, mannose and glucose in the molar ratio of 14.99:1.14:1.00:6.47. The protective effect of O. dillenii Haw. fruits polysaccharide (ODFP) against oxidative damage in streptozotocin (STZ)-induced diabetic rats was investigated. The results showed that oral administration of ODFP significantly decreased food intake, water intake, urine production, organ weights and blood glucose level, and increased body weight in STZ-induced diabetic rats. ODFP also significantly increased the activities of SOD, GPx and CAT, and decreased malondialdehyde level in serum, liver, kidney, and pancreas in STZ-induced diabetic rats. Moreover, histopathological examination showed that ODFP could markedly improve the structure integrity of pancreatic islet tissue in STZ-induced diabetic rats. These results suggest that ODFP have hypoglycemic and antioxidant properties and can protect rats from STZ-induced oxidative damage. PMID:25839790

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

    PubMed Central

    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. PMID:22593683

  2. Attenuation of erythrocyte membrane oxidative stress by Sesbania grandiflora in streptozotocin-induced diabetic rats.

    PubMed

    Sureka, Chandrabose; Ramesh, Thiyagarajan; Begum, Vavamohaideen Hazeena

    2015-08-01

    The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190-220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications. PMID:26176361

  3. Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA)

    PubMed Central

    2012-01-01

    Background The prevalence, and associated healthcare burden, of diabetes mellitus is increasing worldwide. Mortality and morbidity are associated with diabetic complications in multiple organs and tissues, including the eye, kidney and cardiovascular system, and new therapeutics to treat these complications are required urgently. Triethylenetetramine (TETA) is one such experimental therapeutic that acts to chelate excess copper (II) in diabetic tissues and reduce oxidative stress and cellular damage. Methods Here we have performed two independent metabolomic studies of serum to assess the suitability of the streptozotocin (STZ)-induced rat model for studying diabetes and to define metabolite-related changes associated with TETA treatment. Ultraperformance liquid chromatography-mass spectrometry studies of serum from non-diabetic/untreated, non-diabetic/TETA-treated, STZ-induced diabetic/untreated and STZ-induced diabetic/TETA-treated rats were performed followed by univariate and multivariate analysis of data. Results Multiple metabolic changes related to STZ-induced diabetes, some of which have been reported previously in other animal and human studies, were observed, including changes in amino acid, fatty acid, glycerophospholipid and bile acid metabolism. Correlation analysis suggested that treatment with TETA led to a reversal of diabetes-associated changes in bile acid, fatty acid, steroid, sphingolipid and glycerophospholipid metabolism and proteolysis. Conclusions Metabolomic studies have shown that the STZ-induced rat model of diabetes is an appropriate model system to undertake research into diabetes and potential therapies as several metabolic changes observed in humans and other animal models were also observed in this study. Metabolomics has also identified several biological processes and metabolic pathways implicated in diabetic complications and reversed following treatment with the experimental therapeutic TETA. PMID:22546713

  4. Effects of chronic administration of the novel endothelin antagonist J-104132 on endothelial dysfunction in streptozotocin-induced diabetic rat

    PubMed Central

    Kanie, Noriyasu; Kamata, Katsuo

    2002-01-01

    The biosynthesis of endothelin-1 is increased in the diabetic state. So this peptide may cause diabetic vascular complications. We tested this possibility by chronically administering J-104132, a potent orally active mixed antagonist of endothelin A and B (ETA/ETB) receptors to streptozotocin (STZ)-induced diabetic rats and focusing on changes in endothelial function. The acetylcholine (ACh)-induced endothelium-dependent relaxation was impaired in diabetic rats and this impairment was significantly attenuated following chronic administration of J-104132 (10?mg?kg?1, p.o., daily for 4 weeks). In an in vitro experiment using aortae from diabetic rats, the ACh-induced relaxation was not changed by the presence of J-104132 (3×10?9?M). The expression levels of the mRNA for endothelial nitric oxide synthase was comparable among aortae from the three groups (control, diabetic and chronically J-104132-treated diabetic). The amount of superoxide anion was significantly greater in aortae from diabetic rats than in controls. Chronic J-104132 treatment significantly decreased the level of superoxide anion in diabetic rats. The expression of the p22phox mRNA for the NADH/NADPH oxidase subunit was significantly increased in STZ-induced diabetic rats and this increase was completely prevented by chronic administration of J-104132. These results suggest that in STZ-induced diabetic rats, ET-1 may be directly involved in impairing endothelium-dependent relaxation via increased superoxide-anion production. PMID:11959796

  5. Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin-induced diabetic rats and its active compound emodin inhibits methylglyoxal-mediated glycation of proteins

    PubMed Central

    SOHN, EUNJIN; KIM, JUNGHYUN; KIM, CHAN SIK; JO, KYUHYUNG; KIM, JIN SOOK

    2015-01-01

    Podocyte injury contributes to renal damage and, eventually, to the occurrence of proteinuria in diabetic nephropathy. The aim of the present study was to investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying mechanism for streptozotocin (STZ)-induced diabetic nephropathy. The protective effects of P. cuspidatum extract (PCE) on renal podocytes in STZ-induced diabetic rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ-induced diabetic rats for 16 weeks, and blood glucose levels, body weight and proteinuria were measured. A double labeling technique with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed and synaptopodin expression was observed. In addition, cleaved caspase-3, methylglyoxal (MGO) and 8-hydroxydeoxyguanosine (8-OHdG) expression levels were measured. STZ-induced diabetic rats developed hyperglycemia and proteinuria. Increased apoptosis of the podocytes and increased cleaved caspase-3, MGO and 8-OHdG expression levels, as well as decreased synaptopodin expression were detected in the glomeruli of STZ-induced diabetic rats. However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis. Levels of caspase-3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment. In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO-derived advanced glycation end-product formation. These findings indicate that PCE may be administered to prevent proteinuria and podocyte loss in STZ-induced diabetic rats partly by inhibiting podocyte apoptosis and cleaved caspase-3 expression, and by restoring the balance of oxidative stress and MGO expression. PMID:26299942

  6. Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin?induced diabetic rats and its active compound emodin inhibits methylglyoxal?mediated glycation of proteins.

    PubMed

    Sohn, Eunjin; Kim, Junghyun; Kim, Chan Sik; Jo, Kyuhyung; Kim, Jin Sook

    2015-10-01

    Podocyte injury contributes to renal damage and, eventually, to the occurrence of proteinuria in diabetic nephropathy. The aim of the present study was to investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying mechanism for streptozotocin (STZ)?induced diabetic nephropathy. The protective effects of P. cuspidatum extract (PCE) on renal podocytes in STZ?induced diabetic rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ?induced diabetic rats for 16 weeks, and blood glucose levels, body weight and proteinuria were measured. A double labeling technique with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed and synaptopodin expression was observed. In addition, cleaved caspase?3, methylglyoxal (MGO) and 8?hydroxydeoxyguanosine (8?OHdG) expression levels were measured. STZ?induced diabetic rats developed hyperglycemia and proteinuria. Increased apoptosis of the podocytes and increased cleaved caspase?3, MGO and 8?OHdG expression levels, as well as decreased synaptopodin expression were detected in the glomeruli of STZ?induced diabetic rats. However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis. Levels of caspase?3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment. In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO?derived advanced glycation end?product formation. These findings indicate that PCE may be administered to prevent proteinuria and podocyte loss in STZ?induced diabetic rats partly by inhibiting podocyte apoptosis and cleaved caspase?3 expression, and by restoring the balance of oxidative stress and MGO expression. PMID:26299942

  7. Antidepressant-like and anxiolytic-like effects of hydrogen sulfide in streptozotocin-induced diabetic rats through inhibition of hippocampal oxidative stress.

    PubMed

    Tang, Zhuo-Jun; Zou, Wei; Yuan, Juan; Zhang, Ping; Tian, Ying; Xiao, Zhi-Fang; Li, Mang-Hong; Wei, Hai-Jun; Tang, Xiao-Qing

    2015-08-01

    Depression is highly prevalent in individuals with diabetes, and depressive symptoms are less responsive to current antidepressant therapies. Oxidative stress plays a major role both in the pathogenesis of diabetes and in major depression and anxiety disorders. Hydrogen sulfide (H2S), the third gaseous mediator, is a novel signaling molecule in the brain that has both antioxidative activity and antidepressant-like and anxiolytic-like effects. We hypothesized that H2S could produce antidepressant-like and anxiolytic-like effects in diabetic patients through its antioxidative effect. To test this hypothesis, we generated streptozotocin (STZ)-induced diabetic rats. We found that H2S alleviated depressive-like behaviors of STZ-induced diabetic rats in the forced swimming and tail suspension tests and reduced their anxiety-like behaviors in the elevated plus maze test. We also found that H2S significantly reduced levels of malondialdehyde and 4-hydroxynonenal and elevated levels of superoxide dismutase and reduced glutathione in the hippocampus of STZ-induced diabetic rats. The results provide evidence for antidepressant-like and anxiolytic-like effects of H2S in STZ-induced diabetic rats and suggest that the therapeutic effects may result from inhibition of hippocampal oxidative stress. These findings suggest that elevating H2S signaling is a potential target for treatment of depressive and anxiety disorders related to diabetes. PMID:25932716

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

    PubMed

    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. PMID:15964674

  9. Hypoglycemic effect of the water extract of Smallantus sonchifolius (yacon) leaves in normal and diabetic rats.

    PubMed

    Aybar, M J; Sánchez Riera, A N; Grau, A; Sánchez, S S

    2001-02-01

    The hypoglycemic effect of the water extract of the leaves of Smallantus sonchifolius (yacon) was examined in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Ten-percent yacon decoction produced a significant decrease in plasma glucose levels in normal rats when administered by intraperitoneal injection or gastric tube. In a glucose tolerance test, a single administration of 10% yacon decoction lowered the plasma glucose levels in normal rats. In contrast, a single oral or intraperitoneal administration of yacon decoction produced no effect on the plasma glucose levels of STZ-induced diabetic rats. However, the administration of 2% yacon tea ad libitum instead of water for 30 days produced a significant hypoglycemic effect on STZ-induced diabetic rats. After 30 days of tea administration, diabetic rats showed improved body (plasma glucose, plasma insulin levels, body weight) and renal parameters (kidney weight, kidney to body weight ratio, creatinine clearance, urinary albumin excretion) in comparison with the diabetic controls. Our results suggest that yacon water extract produces an increase in plasma insulin concentration. PMID:11167030

  10. Anti-depressant effect of hesperidin in diabetic rats.

    PubMed

    El-Marasy, Salma A; Abdallah, Heba M I; El-Shenawy, Siham M; El-Khatib, Aiman S; El-Shabrawy, Osama A; Kenawy, Sanaa A

    2014-11-01

    This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain. PMID:25358020

  11. Effects of pentoxifylline administration on histomorphological parameters of streptozotocin-induced diabetic rat testes

    PubMed Central

    Piryaei, Abbas; Najar, Azam

    2015-01-01

    The effect of pentoxifylline (PTX) administration on histomorphological parameters of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) in male rat testes were evaluated. We randomly divided 40 male rats into the following four groups: group 1: control or normal glycemic (NG) rats; group 2 or NG rats that received only normal saline (NS), (NG+NS); group 3 or diabetic rats which were not treated by PTX (DM+vehicle solution (NS)); and group 4 which comprised diabetic rats treated with 50 mg/kg of PTX (DM+PTX). Type 1 DM was induced by intraperitoneal injection of STZ (55 mg/kg). Rats were held for 30 days after which the experimental group received PTX twice daily (25 mg/kg) or NS. After 14 days of treatment by PTX or NS, the left testes from all rats were extracted and prpared for histological study. Apoptotic cells, blood vessel density, and spermatogenesis were evaluated. Data were analyzed by ANOVA test. PTX-treated-diabetic rats showed a significant decrease in number of apoptotic cells and decrease in blood vessel density compared to the DM+NS rats. A significant increase in spermatogenesis was observed in the PTX-treated diabetic group, compared to the DM+NS groups. It was concluded that PTX administration to STZ-induced type 1 DM rats affected apoptotic cell number positively. Moreover, blood vessel density significantly decreased and improvements were observed in spermatogenesis. PMID:26472963

  12. Comparative effects of Citrullus colocynthis, sunflower and olive oil-enriched diet in streptozotocin-induced diabetes in rats.

    PubMed

    Sebbagh, N; Cruciani-Guglielmacci, C; Ouali, F; Berthault, M-F; Rouch, C; Sari, D Chabane; Magnan, C

    2009-06-01

    Citrullus colocynthis (colocynth) seeds are traditionally used as antidiabetic medication in Mediterranean countries. The present study evaluated the differential effects of diets enriched with C. colocynthis, sunflower or olive oils on the pancreatic beta-cell mass in streptozotocin (STZ)-induced diabetes in rats. STZ injection induced rapid hyperglycaemia in all animals. However, 2 months later, hyperglycaemia was significantly less pronounced in the rats fed a C. colocynthis oil-enriched diet compared with other rat groups (7.9mM versus 12mM and 16mM with colocynth versus olive and sunflower oils, respectively). Assessment of insulin sensitivity using the homoeostasis model assessment (HOMA) method also indicated less insulin resistance in the rats fed a C. colocynthis oil-enriched diet versus the other rats. Finally, 2 months after STZ injection, the pancreatic beta-cell mass was similar in both the STZ-treated rats fed the colocynth oil-enriched diet and their controls fed the same diet. In contrast, the pancreatic beta-cell mass remained lower in the STZ-induced diabetic rats fed with olive oil- and sunflower oil-enriched diets compared with the C. colocynthis group. We conclude that C. colocynthis oil supplementation may have a beneficial effect by partly preserving or restoring pancreatic beta-cell mass in the STZ-induced diabetes rat model. PMID:19264524

  13. An Early Diagnostic Tool for Diabetic Peripheral Neuropathy in Rats

    PubMed Central

    Kambiz, Shoista; van Neck, Johan W.; Cosgun, Saniye G.; van Velzen, Marit H. N.; Janssen, Joop A. M. J. L.; Avazverdi, Naim; Hovius, Steven E. R.; Walbeehm, Erik T.

    2015-01-01

    The skin’s rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats’ hind paws. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats. PMID:25984949

  14. Effects of curcumin on antioxidation in diabetic rats.

    PubMed

    Miao, Mingsan; Guo, Lin; Tian, Shuo; Wang, Tan

    2015-01-01

    To investigate the effects of curcumin on antioxidation and its mechanism in diabetic rat model.After streptozotocin (STZ) induced diabetic rat model, large, medium and small doses of curcumin group were partly given curcumin solution 200,100,50mg•kg-1, administered once a day, continuously 30 days. In 30th day, determine blood glucose (BG) value, after the last injection, determine the serum superoxide dismutase (SOD), malondialdehyde (MDA), glycosylated serum protein (GSP) and free fatty acid (FFA) levels. Compared with the model group rats, In the 10th, 30th administrate, each dose of curcumin group rats' BG, MDA, GSP, FFA levels were significantly reduced, SOD levels was increased significantly.curcumin can significantly improve the antioxidant capacity of diabetic model, improve the metabolic disorder. PMID:25631515

  15. Polyphenols-rich Cyamopsis tetragonoloba (L.) Taub. beans show hypoglycemic and ?-cells protective effects in type 2 diabetic rats.

    PubMed

    Gandhi, Gopalsamy Rajiv; Vanlalhruaia, Pautu; Stalin, Antony; Irudayaraj, Santiagu Stephen; Ignacimuthu, Savarimuthu; Paulraj, Michael Gabriel

    2014-04-01

    The aim of this study was to evaluate the antidiabetic activity of Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans in high-fat diet (HFD) fed-streptozotocin (STZ)-induced type 2 diabetic rats. Dose dependent response of oral treatment of C. tetragonoloba beans' methanol extract (CTme) (200 and 400mg/kg b wt.) was assessed by measuring fasting blood glucose, changes in body weight, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, oral glucose tolerance, intraperitoneal insulin tolerance, hepatic glycogen, marker enzymes of carbohydrate metabolism in HFD fed-STZ-induced type 2 diabetic rats. Histology and immunohistochemical analysis of pancreatic islets were also performed. High-performance liquid chromatography (HPLC) analysis of CTme showed the presence of polyphenols such as gallic acid and caffeic acid in the concentrations of 2.46% (W/W) and 0.32% (W/W). CTme significantly reverted the altered biochemical parameters to near normal levels in diabetic rats. Furthermore CTme showed the protective effect on the ?-cells of pancreatic tissues in diabetic rats. These findings indicate that C. tetragonoloba beans have therapeutic potential in HFD fed-STZ-induced hyperglycemia; therefore this can be used in the management of type 2 diabetes. PMID:24525096

  16. Anti-diabetic activity of methanolic extract of Alpinia galanga Linn. aerial parts in streptozotocin induced diabetic rats

    PubMed Central

    Verma, Ramesh Kumar; Mishra, Garima; Singh, Pradeep; Jha, Keshri K.; Khosa, Ratan L.

    2015-01-01

    Introduction: Alpinia galanga Linn. belongs to the family Zingiberaceae has been used as a traditional medicine in China for relieving stomach ache, treating cold, invigorating the circulatory systems, diabetes, and reducing swelling. Aim: To evaluate the antidiabetic activity of methanolic extract of A. galanga aerial parts on streptozotocin (STZ) induced diabetic rats. Materials and Methods: Diabetes was induced by single intraperitoneal injection of STZ at a dose of 60 mg/kg bodyweight. Test drug methanolic extract of A. galanga (200 and 400 mg/kg b.w.) and glibenclamide (10 mg/kg b.w.) as standard drug was administered orally for 21 consecutive days in STZ-induced diabetic rats. Fasting blood glucose level, serum lipid profiles, as well as initial and final changes in body weight were assessed along with histopathology. All the parameters were statistically analyzed by using one-way ANOVA followed by Bonferroni t-test. Results: Experimental findings showed significant dose dependent antidiabetic potential of methanolic extract in terms of reduction of fasting blood glucose level and various biochemical parameters in diabetic rats when compared with that of the diabetic control group, which might be due to the stimulatory effect of methanolic extracts on the regenerating ?-cells and also on the surviving ?-cells. Conclusion: Methanolic extract of aerial parts of A. galanga was effective in controlling blood glucose level and improve lipid profile in euglycemic as well as diabetic rats.

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

    PubMed Central

    Tian, Wenjie; Lei, Hongen; Guan, Ruili; Xu, Yongde; Li, Huixi; Wang, Lin; Yang, Bicheng; Gao, Zhezhu; Xin, Zhongcheng

    2015-01-01

    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-?/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-?/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-?/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney. Conclusion ICA II treatment could ameliorate diabetic nephropathy in STZ-induced diabetic rats by increasing endothelial cell contents, downregulating TGF-?/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation both in kidney cortex and medulla. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU+ progenitor cells into the kidney tissue. PMID:26379427

  18. Diabetes alters the blood glucose response to ketamine in streptozotocin-diabetic rats

    PubMed Central

    Chen, Huayong; Li, Li; Xia, Hui

    2015-01-01

    Ketamine is a commonly used short-acting anesthetic and recently attempted to treat pain which is a complication of diabetes. In this study we investigated the effect of ketamine on glucose levels of normal rats and diabetic rats. The results showed that no significance between the glucose levels in ketamine treatment group and saline treatment group at all time points was observed in normal rats. Ketamine did not produce hyperglycemia in normal fasted rats. However, ketamine dose dependently elevated glucose in diabetic rats from 80 mg/kg to 120 mg/kg at 1 hour after injection. The glucose did not return to the levels before treatment in streptozotocin (STZ) induced diabetic rats. Insulin revealed a powerful potency in decreasing glucose levels in diabetic rats. Ketamine did not induce acute hyperglycemia any more after diabetic rats pretreated with insulin. Serum corticosterone was significantly increased in all treatment groups including saline group after 1 hour treatment compared with baseline values. Then the corticosterone declined in both saline treatment groups. However, ketamine induced a more significant increase in corticosterone at 1 hour after injection compared with that of saline control group of diabetic rats. And no decline trend of corticosterone was observed after ketamine treatment 2 hours. Insulin did not reduce the elevated corticosterone level induced by ketamine either. The results suggested that the diabetic rats had a risk of hyperglycaemia when they were treated with ketamine. Pretreatment with insulin is a good symptomatic treatment for hyperglycaemia induced by ketamine. PMID:26379948

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

    PubMed Central

    Duan, Huihui; Huang, Jianmei; Li, Wei; Tang, Minke

    2013-01-01

    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 in rats. PMID:24204392

  20. Relationship between peroxisome proliferator-activated receptors (PPAR? and PPAR?) and endothelium-dependent relaxation in streptozotocin-induced diabetic rats

    PubMed Central

    Kanie, Noriyasu; Matsumoto, Takayuki; Kobayashi, Tsuneo; Kamata, Katsuo

    2003-01-01

    The aim of the present study was to investigate the causal relationship between peroxisome proliferator-activated receptor (PPAR) and endothelium-dependent relaxation in streptozotocin (STZ)-induced diabetic rats. Acetylcholine (ACh)-induced endothelium-dependent relaxation was significantly weaker in diabetic rats than in age-matched controls. The decreased relaxation in diabetes was improved by the chronic administration of bezafibrate (30 mg kg?1, p.o., 4 weeks). The expressions of the mRNAs for PPAR? and PPAR? were significantly decreased in STZ-induced diabetic rats (compared with the controls) and this decrease was restored partially, but not completely, by the chronic administration of bezafibrate. Superoxide dismutase activity in the aorta was not significantly different between diabetic rats and bezafibrate-treated diabetic rats. The expression of the mRNA for the p22phox subunit of NAD(P)H oxidase was significantly higher in diabetics than in controls, but it was lower in bezafibrate-treated diabetic rats than in nontreated diabetic rats. Although the expression of the mRNA for prepro ET-1 (ppET-1) was markedly increased in diabetic rats (compared with controls), this increase was prevented to a significant extent by the chronic administration of bezafibrate. These results suggest that downregulations of PPAR? and PPAR? may lead to an increased expression of ppET-1 mRNA in diabetic states and this increment may trigger endothelial dysfunction. PMID:12967931

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

    PubMed

    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-? (TNF-?), in addition to brain-derived neurotrophic factor (BDNF) and relative expression of nuclear factor kappa B (NF-?B)/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-?, serum DPP-IV activities and NF-?B/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-?B/p65 over expression. PMID:26607467

  2. Branched-chain amino acids attenuate early kidney injury in diabetic rats.

    PubMed

    Mi, Na; Zhang, Xiu Juan; Ding, Yan; Li, Guo Hua; Wang, Wei Dong; Xian, Hui Xia; Xu, Jin

    2015-10-16

    Diabetic nephropathy (DN) is the most severe diabetic microvascular complication. The pathogenesis of diabetic nephropathy is complex, and oxidative stress plays an important role in the development of diabetic nephropathy. Elevated reactive oxygen species (ROS) levels activate various signaling pathways and influence the activities of transforming growth factor-? (TGF-?) and matrix metalloproteinase-9 (MMP-9), which contributes to glomerular hypertrophy. Branched-chain amino acids (BCAAs) are widely used in clinical treatment, and BCAAs can reduce the oxidative stress associated with the diabetic pancreas and some liver diseases. Thus, the aim of the present study was to determine whether BCAAs could attenuate oxidative stress in the kidneys of streptozotocin (STZ)-induced diabetic rats to prevent early diabetic kidney injury. Male Wistar rats were fed for two weeks with a normal chow diet or a high-fat diet in which 40% of calories were derived from fat. After this two-week period, the mice fed normal chow were injected with vehicle, while the high-fat diet group was injected intraperitoneally (i.p.) with 40 mg/kg STZ. The STZ-treated group was randomly divided into four subgroups that were treated with different doses of BCAAs or vehicle for two months by oral gavage. Plasma glucose, plasma creatinine, urinary protein and JNK, TGF-?, and MMP-9 mRNA and protein expression levels were measured in the rats. The ROS levels and proteinuria in the STZ-induced diabetic rats were significantly higher than those in the control groups. Moreover, early kidney injury occurred in the STZ-induced diabetic rats. However, BCAAs treatment decreased ROS levels, proteinuria and kidney injury. Moreover, JNK, TGF-? and MMP-9 mRNA and protein levels were significantly increased in the diabetic rats when compared with the control rats, and BCAAs treatment reversed these changes. Our results suggest that BCAAs counter oxidative stress in the kidneys of diabetic rats and alleviate diabetic kidney injury via the JNK/TGF-?/MMP-9 pathway. PMID:26362188

  3. Hemodynamic alterations in chronically conscious unrestrained diabetic rats

    SciTech Connect

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

    1987-05-01

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

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

    PubMed

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

    2013-01-01

    Diabetic retinopathy is one of the most important microvascular complications in diabetes, and it is the major cause of visual loss. Physical exercise is known to ameliorate the symptoms of metabolic syndromes such as diabetic mellitus. In the present study, we investigated the effects of treadmill exercise on vascular endothelial growth factor (VEGF) expression and apoptotic cell death in the retinas of streptozotocin (STZ)-induced diabetic rats. The male Sprague-Dawley rats were randomly divided into three groups (n = 10 in each group): control group, STZ-induce diabetes group, STZ-induced diabetes and treadmill exercise group. To induce diabetes in the experimental animals, a single intraperitioneal injection of STZ (50 mg/kg) was given to each animal. The rats in the exercise group were forced to run on a motorized treadmill for 30 min once a day during 1 week starting 6 weeks after STZ injection. In the present results, VEGF expression in the retinas was increased by induction of diabetes. The numbers of caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the retinas were also enhanced by induction of diabetes. Treadmill exercise significantly decreased VEGF expression and suppressed the number of TUNEL-positive and caspase-3-positive cells in the retinas of diabetic rats. In the present study, we have shown that treadmill exercise might alleviate the progression of diabetic retinopathy through suppressing VEGF expression and apoptotic cell death in the retinas of the diabetic rats. PMID:24278883

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

    PubMed Central

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

    2013-01-01

    Diabetic retinopathy is one of the most important microvascular complications in diabetes, and it is the major cause of visual loss. Physical exercise is known to ameliorate the symptoms of metabolic syndromes such as diabetic mellitus. In the present study, we investigated the effects of treadmill exercise on vascular endothelial growth factor (VEGF) expression and apoptotic cell death in the retinas of streptozotocin (STZ)-induced diabetic rats. The male Sprague-Dawley rats were randomly divided into three groups (n = 10 in each group): control group, STZ-induce diabetes group, STZ-induced diabetes and treadmill exercise group. To induce diabetes in the experimental animals, a single intraperitioneal injection of STZ (50 mg/kg) was given to each animal. The rats in the exercise group were forced to run on a motorized treadmill for 30 min once a day during 1 week starting 6 weeks after STZ injection. In the present results, VEGF expression in the retinas was increased by induction of diabetes. The numbers of caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the retinas were also enhanced by induction of diabetes. Treadmill exercise significantly decreased VEGF expression and suppressed the number of TUNEL-positive and caspase-3-positive cells in the retinas of diabetic rats. In the present study, we have shown that treadmill exercise might alleviate the progression of diabetic retinopathy through suppressing VEGF expression and apoptotic cell death in the retinas of the diabetic rats. PMID:24278883

  6. Enriched Environment Protects the Optic Nerve from Early Diabetes-Induced Damage in Adult Rats

    PubMed Central

    Dorfman, Damián; Aranda, Marcos L.; Rosenstein, Ruth E.

    2015-01-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Axoglial alterations of the distal (close to the chiasm) optic nerve (ON) could be the first structural change of the visual pathway in streptozotocin (STZ)-induced diabetes in rats. We analyzed the effect of environmental enrichment on axoglial alterations of the ON provoked by experimental diabetes. For this purpose, three days after vehicle or STZ injection, animals were housed in enriched environment (EE) or remained in a standard environment (SE) for 6 weeks. Anterograde transport, retinal morphology, optic nerve axons (toluidine blue staining and phosphorylated neurofilament heavy immunoreactivity), microglia/macrophages (ionized calcium binding adaptor molecule 1 (Iba-1) immunoreactivity), astrocyte reactivity (glial fibrillary acid protein-immunostaining), myelin (myelin basic protein immunoreactivity), ultrastructure, and brain derived neurotrophic factor (BDNF) levels were assessed in non-diabetic and diabetic animals housed in SE or EE. No differences in retinal morphology or retinal ganglion cell number were observed among groups. EE housing which did not affect the STZ-induced weight loss and hyperglycemia, prevented a decrease in the anterograde transport from the retina to the superior colliculus, ON axon number, and phosphorylated neurofilament heavy immunoreactivity. Moreover, EE housing prevented an increase in Iba-1 immunoreactivity, and astrocyte reactivity, as well as ultrastructural myelin alterations in the ON distal portion at early stages of diabetes. In addition, EE housing avoided a decrease in BDNF levels induced by experimental diabetes. These results suggest that EE induced neuroprotection in the diabetic visual pathway. PMID:26312758

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

    PubMed Central

    Qin, Yali; Luo, Dan; Yang, Shufei; Kou, Xinyun; Zi, Yingxin; Deng, Tingting; Jin, Ming

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:26176548

  8. Streptozocin diabetes alters immunoreactive beta-endorphin levels and pain perception after 8 wk in female rats.

    PubMed

    Forman, L J; Estilow, S; Lewis, M; Vasilenko, P

    1986-12-01

    Plasma, pituitary, and hypothalamic levels of the endogenous opioid peptide beta-endorphin were measured by radioimmunoassay and column chromatography in female rats 8 wk after the induction of diabetes with streptozocin (STZ) and in control female rats. In addition, pain perception was determined by measuring the latency to paw lick or jump after being placed on a hot plate. Plasma levels of immunoreactive beta-endorphin (IR-BE) were significantly reduced in STZ-induced diabetic female rats, as were the content and concentration of IR-BE in the neurointermediate lobe of the pituitary (NIL) and the content of IR-BE in the hypothalamus. The concentration but not the content of IR-BE in the anterior pituitary (AP) of the STZ-induced diabetic rats was increased significantly. Streptozocin-induced diabetes also resulted in a significant reduction in the total protein content of the AP, NIL, and hypothalamus. Column chromatography indicated that the decrease in IR-BE in the plasma, NIL, and hypothalamus represented a decrease in beta-endorphin, whereas the increase in IR-BE in the AP represented an increase in both beta-endorphin and beta-lipotropin. Diabetic animals consistently showed decreased latencies to paw lick or jump when subjected to hot-plate testing after 7 wk. These findings suggest that in female rats, central and peripheral endogenous opiate levels and tolerance to nociceptive thermal stimulation were diminished by 8 wk of chemically induced diabetes. PMID:2945745

  9. Hypoglycemic and ?-cells regenerative effects of Aegle marmelos (L.) Corr. bark extract in streptozotocin-induced diabetic rats.

    PubMed

    Gandhi, Gopalsamy Rajiv; Ignacimuthu, Savarimuthu; Paulraj, Michael Gabriel

    2012-05-01

    The aim of this study was to examine the antidiabetic potential of Aegle marmelos (L.) Corr. (Rutaceae) bark in a diabetic rat model. Dose dependent effects of methanol extract of Aegle marmelos bark (AM) (200 and 400 mg/kg) on blood glucose, plasma insulin, glycated haemoglobin (HbA1c), total protein, hepatic glycogen, marker enzymes of hepatic function and carbohydrate metabolism were evaluated in (streptozotocin) STZ-induced diabetic rats by oral administration for 30 days. Structural integrity of pancreatic islets was assessed by routine histology while, their functional status was assessed by immunolocalization for insulin. High-performance liquid chromatography (HPLC) study established that AM contained antihyperglycemic constituents, aegelin (1.27% w/w) and lupeol (0.29% w/w). AM at 200 and 400 mg/kg showed significant reduction in blood glucose level by 19.14% and 47.32%, respectively in diabetic rats. AM treatment significantly increased insulin level, and produced similar effects on other biochemical parameters. Histological studies showed the regenerative effect of AM on the ?-cells of diabetic rats. Immunohistochemical observations in the extract treated diabetic rats showed increased insulin-immunoreactive ?-cells. These findings suggest that A. marmelos bark extract has the therapeutic potential in STZ-induced hyperglycemia; hence it can be used in the treatment of diabetes mellitus. PMID:22310238

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

    PubMed Central

    Erejuwa, Omotayo Owomofoyon; Sulaiman, Siti Amrah; Wahab, Mohd Suhaimi Abdul; Salam, Sirajudeen Kuttulebbai Nainamohammed; Salleh, Md Salzihan Md; Gurtu, Sunil

    2010-01-01

    Hyperglycemia exerts toxic effects on the pancreatic ?-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage. PMID:20559501

  11. Antidiabetic effect of aqueous extract of seed of Tamarindus indica in streptozotocin-induced diabetic rats.

    PubMed

    Maiti, R; Jana, D; Das, U K; Ghosh, D

    2004-05-01

    In Indian traditional system of medicine, herbal remedies are prescribed for the treatment of diseases including diabetes mellitus. In recent years, plants are being effectively tried in a variety of pathophysiological states. Tamarindus indica Linn. is one of them. In the present study, aqueous extract of seed of Tamarindus indica Linn. was found to have potent antidiabetogenic activity that reduces blood sugar level in streptozotocin (STZ)-induced diabetic male rat. Supplementation of this aqueous extract by gavage at the dose of 80 mg/0.5 ml distilled water/100 g body weight per day in STZ-induced diabetic rat resulted a significant diminution of fasting blood sugar level after 7 days. Continuous supplementation of this extract for 14 days resulted no significant difference in this parameter from control level. Moreover, this supplementation produced a significant elevation in liver and skeletal muscle glycogen content, activity of liver glucose-6-phosphate dehydrogenase in respect to diabetic group. Activities of liver glucose-6-phosphatase, liver and kidney glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities were decreased significantly in the aqueous extract supplemented group in respect to diabetic group. All these parameters were not resettled to the controlled level after 7 days of this extract supplementation but after 14 days of this supplementation, all the above mentioned parameters were restored to the control level. PMID:15099853

  12. Decreased cholinergic receptor expression in the striatum: motor function deficit in hypoglycemic and diabetic rats.

    PubMed

    Sherin, A; Peeyush, K T; Jayanarayanan, S; Amee, K K; Paulose, C S

    2012-01-01

    Hypoglycemic brain injury is a common and serious complication of insulin therapy associated with diabetes. This study evaluated the effect of insulin-induced hypoglycemia and STZ-induced diabetes on striatal cholinergic receptors and enzyme expression and on motor function. Cholinergic enzymes: AChE and ChAT gene expression, radioreceptor binding assay and immunohistochemistry of muscarinic M1, M3 receptors and ?7nAChR were carried out. Motor performance on grid walk test was analysed. AChE and ChAT expression significantly downregulated in hypoglycemic and diabetic rats. Total muscarinic and Muscarinic M3 receptor binding decreased in hypoglycemic rats compared to diabetic rats whereas muscarinic M1 receptor binding increased in hypoglycemic rats compared to diabetic rats. Real-time PCR analysis and confocal imaging of muscarinic M1, M3 receptors confirmed the changes in muscarinic receptor binding in hypoglycemic and diabetic rats. In hypoglycemic rats, ?7nAChR expression significantly up regulated compared to diabetic rats. Grid walk test demonstrated the impairment in motor function and coordination in hypoglycemic and hyperglycemic rats. Neurochemical changes along with the behavioral data implicate a role for impaired striatal cholinergic receptor function inducing motor function deficit induced by hypo and hyperglycemia. Hypoglycemia exacerbated the neurobehavioral deficit in diabetes which has clinical significance in the treatment of diabetes. PMID:21796364

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

    PubMed Central

    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-?; interleukin, IL-6; and interleukin, IL-1?) 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

  14. Comparison of antinociceptive and antidiabetic effects of sertraline and amitriptyline on streptozotocin-induced diabetic rats.

    PubMed

    Mahmood, Danish; Akhtar, M; Vohora, Divya; Khanam, Razia

    2010-10-01

    Antidepressants (ADs) are frequently used for the treatment of persistent pain associated with diabetic neuropathy. The aim of this study is to investigate the antinociceptive effects of sertraline (Ser) and amitriptyline (Ami) in diabetic rats, and additionally monitoring their effects on grip strength, blood glucose and percentage glycosylated hemoglobin (GHb%) levels. Streptozotocin (STZ; 55 mg/kg, intraperitoneal [ip]) was injected in rats to induce diabetes. After 7 days, Ser (30 mg/kg) or Ami (15 mg/kg) was administered in diabetic rats orally. After 28 days drug treatment, the antinociceptive effects were evaluated using hot plate test both in diabetic and non-diabetic rats. The effects of these drugs on grip strength, blood glucose and GHb% were also measured. Ser and Ami showed antinociceptive effects in diabetic and non-diabetic rats. Both the drugs increased the grip strength reduction in STZ-induced diabetic rats. Ser reduces and Ami increases the serum glucose levels in diabetic and normal rats. Administration of Ami per se increased GHb% levels, while Ser per se has no effects. The effects of Ser (30 mg/kg, per os [po]) on glucose, GHb% and antinociceptive action on hot plate test showed an association between improved blood glucose levels and analgesia. However, the results of Ami treatment are controversial and needs further studies. PMID:20194573

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

    PubMed Central

    Singh, Rambir; Bhardwaj, Priyanka; Sharma, Poonam

    2013-01-01

    Background: Multiple-organ failure is the main cause of death in diabetes mellitus (DM). Hyperglycemia-induced oxidative stress is responsible for major diabetic complications, including multiple-organ failure. Medicinal plants possessing antioxidant activity may reduce oxidative stress and improve the functions of various organs affected by hyperglycemia. Objectives: This study was designed to evaluate the antioxidant effect of Aqueous Extract of Cassia sophera (AECS) in streptozotocin (STZ)-induced diabetic Wistar rats. Materials and Methods: AECS (200 mg/kg body weight (bw)) and the standard antidiabetic drug glibenclamide (10 mg/kgbw) were administered orally by gavaging for 28 days. Results: Oral administration of AECS inhibited STZ-induced increase in lipid peroxidation (LPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, creatinine and urea in liver of diabetic rats. Significant increase in activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and a reduced level of glutathione (GSH), were observed in the liver, kidney, pancreas and testis on AECS treatment. Conclusion: The results demonstrate that AECS is not only useful in controlling blood glucose, but also has antioxidant potential to protect the liver, kidney, pancreas and testis against damage caused by hyperglycemia-induced oxidative stress. PMID:24174814

  16. Canavanine activates imidazoline I-2 receptors to reduce hyperglycemia in type 1-like diabetic rats.

    PubMed

    Chang, Chin-Hong; Chao, Pin-Chun; Niu, Ho-Shan; Huang, Gin-Chi; Chen, Li-Jen; Cheng, Juei-Tang

    2015-10-01

    Canavanine is a guanidinium derivative that has the basic structure of a ligand for the imidazoline receptor (I-R). Furthermore, canavanine is found in an herb that has been shown to improve diabetic disorders. Thus, the present study was designed to investigate the anti-hyperglycemic action of canavanine in rats with streptozotocin (STZ)-induced type 1-like diabetes. Canavanine decreased hyperglycemia in the STZ-induced diabetic rats, and this action was blocked by the antagonist specific to imidazoline I-2 receptors (I-2R), BU224, in a dose-dependent manner. Additionally, canavanine increased the plasma ?-endorphin level, as measured using enzyme-linked immunosorbent assay (ELISA), and this increase was also blocked by BU224 in the same manner. Moreover, amiloride at a dose sufficient to block I-2AR attenuated the actions of canavanine, including the increased ?-endorphin level and the antihyperglycemic effect. Otherwise, canavanine increased the radioactive glucose uptake into skeletal muscles isolated from the diabetic rats. Furthermore, canavanine increased the phosphorylation of AMPK measured using Western blot analysis in these isolated skeletal muscles in a dose-dependent manner. Additionally, the insulin sensitivity of the diabetic rats was markedly increased by canavanine, and this action was also blocked by BU224. Overall, canavanine is capable of activating imidazoline I-2R; I-2AR is linked to an increase in the plasma level of ?-endorphin, and I-2BR is related to effects on the glucose uptake by skeletal muscle that reduces hyperglycemia in type 1-like diabetic rats. Therefore, canavanine can be developed as effective agent to treat the diabetic disorders in the future. PMID:26362499

  17. Antiarrhythmic effects and ionic mechanisms of allicin on myocardial injury of diabetic rats induced by streptozotocin.

    PubMed

    Huang, Wei; Wang, Ye; Cao, Yong-Gang; Qi, Han-Ping; Li, Lei; Bai, Bing; Liu, Yang; Sun, Hong-Li

    2013-08-01

    The aim of this study was to evaluate the antiarrhythmic effect of allicin (AL) on streptozotocin (STZ)-induced diabetic rats and explore the possible mechanisms. Hyperglycemia was induced in rats by single intraperitoneal injection of STZ (40 mg/kg). Three days after STZ treatment, the hyperglycemic rats (plasma glucose levels?16.7 mM) were administered with AL (4, 8, and 16 mg/kg) by intraperitoneal injection daily for 28 days. The fasting blood glucose levels were measured on every seventh day during the 28 days of treatment. The body weight and blood glucose levels were detected after 28 days. Antiarrhythmic effect of AL was observed in the diabetic rats induced by BaCl2. To determine the ionic mechanism in rat ventricular myocytes of AL, action potential duration (APD), L-type calcium current (ICa-L), and inward rectifier potassium current (IK1) were recorded by the whole cell-patch clamp technique. The expressions of L-type calcium channel protein ?1C mRNA and cell potassium channels protein Kir2.1 mRNA were studied by RT-PCR. AL normalized the RR interval and QT interval in diabetic rats. AL obviously delayed the onset of ventricular arrhythmia and reduced the score of arrhythmia induced by BaCl2. Electrophysiological experiment revealed that AL could shorten APD through inhibition of ICa-L and enhancement of IK1. RT-PCR analysis indicated that long-term treatment with AL could decrease the expression of ?1C mRNA and increase the expression of Kir2.1 mRNA. AL has antiarrhythmic effect in STZ-induced diabetic rats. It is tempting for the application of AL to be a useful therapeutic approach in diabetes with ventricular arrhythmia. PMID:23604291

  18. Lespedeza davurica (Lax.) Schindl. Extract Protects against Cytokine-Induced ?-Cell Damage and Streptozotocin-Induced Diabetes

    PubMed Central

    2015-01-01

    Lespedeza has been used for the management of diabetes in folklore medicine. The purpose of this study is to investigate the protective effects of the methanol extract of Lespedeza davurica (LD) on cytokine-induced ?-cell damage and streptozotocin- (STZ-) induced diabetes. RINm5F cells were treated with interleukin- (IL-) 1? and interferon- (IFN-) ? to induce pancreatic ?-cell damage. The exposure of LD extract significantly decreased cell death, nitric oxide (NO) production, nitric oxide synthase (iNOS) expression, and nucleus factor-kappa B (NF-?B) p65 activation. Antidiabetic effects of LD extract were observed by oral glucose tolerance test (OGTT) in normal rats and by checking the biochemical, physiological, and histopathological parameters in STZ-induced diabetic rats. In OGTT, glucose clearance levels improved by oral treatment of LD extract. The water intake, urine volume, blood glucose, and serum TG, TC, TBARS, and DPP-IV levels were significantly decreased, and liver glycogen content was significantly increased by treatment of LD extract (250?mg/kg BW) in STZ-induced diabetic rats. Also, insulin immunoreactivity of the pancreases was increased in LD extract administrated rats compared with diabetic control rats. These results indicate that LD extract may protect pancreatic ?-cell damage and regulate the blood glucose in STZ-induced diabetic rats. PMID:25793188

  19. Effect of Diashis, a polyherbal formulation, in streptozotocin-induced diabetic male albino rats

    PubMed Central

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

    2010-01-01

    This study focuses on the effect of ‘Diashis’, a polyherbal formulation composed of eight medicinal plants for the management of streptozotocin (STZ)-induced diabetes in rats. As oxidative stress is one of the consequences of diabetes, the activities of hepatic antioxidant enzymes and metabolic enzymes were evaluated. Treatment with ‘Diashis’ in STZ-induced diabetic rats resulted in a significant (P < 0.01) recovery in the activities of hepatic hexokinase, glucose-6-phosphate dehydrogenase, and glucose-6-phosphatase along with correction in the levels of fasting blood glucose, glycated hemoglobin, and liver and skeletal muscle glycogen. The oxidative stress status in the liver was corrected by ‘Diashis’ which was highlighted by the recovery in the activities of catalase, peroxidase, and glutathione-S-transferase along with the correction in the quantity of thiobarbituric acid-reactive substances and conjugated diene. ‘Diashis’ was not found to have any metabolic toxicity. The antidiabetic effects of ‘Diashis’ were compared with those of the antidiabetic drug, ‘Glibenclamide’. PMID:20532093

  20. Ultrastructural Analysis of In Vivo Hypoglycemiant Effect of Two Polyoxometalates in Rats with Streptozotocin-Induced Diabetes.

    PubMed

    Bâlici, ?tefana; Wankeu-Nya, Modeste; Rusu, Dan; Nicula, Gheorghe Z; Rusu, Mariana; Florea, Adrian; Matei, Horea

    2015-10-01

    Two polyoxometalates (POMs), synthesized through a self-assembling method, were used in the treatment of streptozotocin (STZ)-induced diabetic rats. One of these nanocompounds [tris(vanadyl)-substituted tungsto-antimonate(III)-anions-POM1] was previously described in the literature, whereas the second [tris-butyltin-21-tungsto-9-antimonate(III)-anions-POM2], was prepared by us based on our original formula. In rats with STZ-induced diabetes treated with POMs (up to a cumulative dose of 4 mg/kg bodyweight at the end of the treatments), statistically significant reduced levels of blood glucose were measured after 3 weeks, as compared with the diabetic control groups (DCGs). Ultrastructural analysis of pancreatic ?-cells (including the mean diameter of secretory vesicles and of their insulin granules) in the treated diabetic rats proved the POMs contribute to limitation of cellular degeneration triggered by STZ, as well as to the presence of increased amounts of insulin-containing vesicles as compared with the DCG. The two POMs also showed hepatoprotective properties when ultrastructural aspects of hepatocytes in the experimental groups of rats were studied. Based on our in vivo studies, we concluded that the two POMs tested achieved hypoglycemiant effects by preventing STZ-triggered apoptosis of pancreatic ?-cells and stimulation of insulin synthesis. PMID:26343528

  1. Antidiabetic and antihyperlipidemic activities of a novel polyherbal formulation in high fat diet/streptozotocin induced diabetic rat model

    PubMed Central

    Subhasree, N.; Kamella, Ananthkumar; Kaliappan, Ilango; Agrawal, Aruna; Dubey, Govind Prasad

    2015-01-01

    Objective: To investigate the antidiabetic and antihyperlipidemic activities of polyherbal formulation (PHF) containing hydroalcoholic extracts of four plants namely Salacia oblonga, Salacia roxbhurgii, Garcinia indica and Lagerstroemia parviflora in streptozotocin (STZ)-induced diabetic rats by administering oral doses (200 and 400 mg/kg body weight). Materials and Methods: Animals were divided into diabetic and nondiabetic groups. Rats were fed with a high-fat diet (HFD) and induced with a single low dose of STZ (35 mg/kg) i.p. Diabetic rats were treated with formulation (200 and 400 mg/kg) and metformin 250 mg/kg. Blood glucose levels were measured using blood glucose test strips with ACCU CHEK glucometer. Lipid profile and gluconeogenic enzymes were determined in normal and STZ-induced diabetic rats after oral administration of the PHF for 28 days. Histopathological changes in diabetic rat organs (pancreas, liver, and kidney) were also observed after PHF treatment. Results: Treatment of diabetic rats with PHF and metformin decreased plasma glucose and lipid profile levels. Blood glucose level showed significant reduction after 28 days of treatment with formulation at 200 and 400 mg/kg and in metformin. Formulation treated rats showed significant (P < 0.001) decrease in the activities of gluconeogenic enzymes. Histological examination of various organ tissues of normal control, diabetic control, and drug-treated rats revealed significant results. Treatment with PHF reverses the most blood and tissue changes toward the normal level. Conclusion: These findings suggested the antihyperglycemic and antihyperlipidemic properties of the PHF and thus help in preventing future complications of diabetes. PMID:26600639

  2. Effects of 20-hydroxyecdysone on improving memory deficits in streptozotocin-induced type 1 diabetes mellitus in rat.

    PubMed

    Xia, Xichao; Zhang, Qingyuan; Liu, Rongzhi; Wang, Zhongxiao; Tang, Nianya; Liu, Fei; Huang, Guosheng; Jiang, Xiao; Gui, Gaixia; Wang, Lijuan; Sun, Xiuli

    2014-10-01

    We investigate the effects of 20-hydroxyecdysone (20E) on improving memory deficits in the current study by using an animal model of type 1 diabetes mellitus in rats. Animals in control group went on a normal diet. Rats that developed diabetes were divided into 4 groups, including STZ-induced diabetic group which was treated with saline and three 20E groups received different 20E concentrations for 12 weeks. Spatial memory performance was measured in rats by the Morris water maze. The level of nuclear factor-?B (NF-?B) in the brain was determined by real-time quantitative PCR. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were analyzed by real-time quantitative PCR and spectrophotometry. The concentrations of brain-derived neurotrophic factor (BDNF) in the brain were detected by ELISA. Compared with the control group, rats in the STZ-induced diabetic group that developed type 1 diabetes exhibited significant memory loss. In addition to the hippocampus CA1 area that displayed severe damage, significantly higher expression levels of NF-?B were observed in these rats. Furthermore, the expression levels of SOD, catalase, GSH-Px GR and BDNF were significantly decreased in rats with diabetes. By contrast, the treatment with 20E, especially at higher concentrations, reversed the above-mentioned conditions caused by diabetes. The results suggest that the 20E has a protective role in counteracting memory deficits in rats with diabetes of rat, possibly through enhancing the antioxidative ability in the brain. PMID:24997424

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

    PubMed Central

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

    2013-01-01

    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 < 0.001) fall in fasting blood glucose level, TBARS, bilirubin, AST, ALT, and SALP, while elevating the GSH levels, and SOD and CAT activities in diabetic rats. Histopathologic studies also revealed the protective effect of 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. PMID:24716175

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

    PubMed Central

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

    2009-01-01

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

  5. Evaluation of the hypoglycemic and hypolipidemic effects of an ethylacetate fraction of Artocarpus heterophyllus (jak) leaves in streptozotocin-induced diabetic rats

    PubMed Central

    Chackrewarthy, S.; Thabrew, M. I.; Weerasuriya, M. K. B.; Jayasekera, S.

    2010-01-01

    Aqueous extracts of mature leaves of Artocarpus heterophyllus (jak) are used by traditional medical practitioners in Sri Lanka and India for the treatment of diabetes. This study was conducted to investigate the hypoglycemic and hypolipidemic effects of an ethylacetate (EA) fraction of the mature leaves of A. heterophyllus in a streptozotocin (STZ) induced diabetic rat model. In normoglycemic rats, administration of a single dose (20 mg/kg) of the EA fraction resulted in a significant (P < 0.05) reduction in the fasting blood glucose concentration and a significant improvement in glucose tolerance (P < 0.05), compared to the controls. In STZ-induced diabetic rats, chronic administration of the EA fraction of A. heterophyllus leaves daily for 5 weeks resulted in a significant lowering of serum glucose, cholesterol and triglyceride (TG) levels. Compared to control diabetic rats, the extract-treated rats had 39% less serum glucose, 23% lower serum total cholesterol and 40% lower serum TG levels and 11% higher body weight at the end of the fifth week. The percentage reductions in the serum parameters mediated by the test fraction were comparable with those produced by glibenclamide (0.6 mg/kg), the reference drug used in this study. It can be concluded that the EA fraction of A. heterophyllus leaves contains one or more hypoglycemic and hypolipidemic principles which have the potential to be developed further for the treatment of diabetes specifically associated with a hyperlipidemic state. PMID:20931077

  6. Does bosentan protect diabetic brain alterations in rats? The role of endothelin-1 in the diabetic brain.

    PubMed

    Demir, Recep; Cadirci, Elif; Akpinar, Erol; Cayir, Yasemin; Atmaca, Hasan Tarik; Un, Harun; Kunak, Celalettin Semih; Yayla, Muhammed; Bayraktutan, Zafer; Demir, Ilknur

    2015-03-01

    Diabetes mellitus (DM) is a major problem all over the world, affecting more people in recent years. Individuals with diabetes are more prone to disease than non-diabetics, especially vascular complications. The aim of this study was to examine the roles of the endothelin (ET)-1 in brain damage formed in a streptozocin (STZ)-induced diabetes model, and the effect of bosentan, which is the non-specific ET1 receptor blocker in the prevention of the diabetes-induced brain damage. To examine the effects of bosentan (50 mg/kg and 100 mg/kg) in this study, the rats were given the drug for 3 months. The rats were divided into four groups: the sham group (n = 10), the diabetic control group (n = 10), the group of diabetic rats given bosentan 50 mg/kg (n = 10) and the group of diabetic rats given bosentan 100 mg/kg (n = 10). Diabetes was induced in the rats by STZ (60 mg/kg i.p.). On day 91, all rats were killed. Brain tissues of the rats were measured by molecular, biochemical and histopathological methods. Antioxidant levels in the therapy groups were observed as quite near to the values in the healthy group. In this study, while the brain eNOS levels in the diabetic groups decreased, the ET1 and iNOS levels were found to be increased. However, in the diabetes group, hippocampus and cerebellum, pericellular oedema and a number of neuronal cytoretraction were increased in neuropiles, whereas these results were decreased in the therapy group. Based on all of these results, ET1 will not be ignored in diabetes-induced cerebral complications. PMID:25200216

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

    PubMed Central

    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/EBP?) and its targets (TNF?, 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 TNF? 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

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

    PubMed

    Badole, Sachin L; Chaudhari, Swapnil M; Jangam, Ganesh B; Kandhare, Amit D; Bodhankar, Subhash L

    2015-01-01

    Pongamia pinnata (L.) Pierre has been used in traditional medicine for the treatment for diabetes and metabolic disorder. The aim of this study was to investigate the effect of petroleum ether extract of the stem bark of P. pinnata (known as PPSB-PEE) on cardiomyopathy in diabetic rats. Diabetes was induced in overnight fasted Sprague-Dawley rats by using injection of streptozotocin (55 mg/kg, i.p.). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Rats were divided into group I: nondiabetic, group II: diabetic control (tween 80, 2%; 10 mL/kg, p.o.) as vehicle, and group III: PPSB-PEE (100 mg/kg, p.o.). The blood glucose level, ECG, hemodynamic parameters, cardiotoxic and antioxidant biomarkers, and histology of heart were carried out after 4 months after STZ with nicotinamide injection. PPSB-PEE treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters; and histological changes in STZ induced diabetic rats. PPSB-PEE (100 mg/kg, p.o.) decreased blood glucose level, improved electrocardiographic parameters (QRS, QT, and QTc intervals) and hemodynamic parameters (SBP, DBP, EDP, max dP/dt, contractility index, and heart rate), controlled levels of cardiac biomarkers (CK-MB, LDH, and AST), and improved oxidative stress (SOD, MDA, and GSH) in diabetic rats. PPSB-PEE is a promising remedy against cardiomyopathy in diabetic rats. PMID:25954749

  9. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats

    PubMed Central

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

    2013-01-01

    Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-? and decreased insulin growth factor (IGF)-1? in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-? and IGF-1?, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and antiapototic effects. PMID:23840309

  10. Acute and subchronic antihyperglycemic activities of Bowdichia virgilioides roots in non-diabetic and diabetic rats

    PubMed Central

    Silva, Ana Carolina Mazei; dos Santos, Maísa Pavani; de França, Suélem Aparecida; da Silva, Virginia Claudia; da Silva, Luiz Everson; de Figueiredo, Uir Santana; Dall’Oglio, Evandro Luiz; Júnior, Paulo Teixeira de Sousa; Lopes, Carbene França; Baviera, Amanda Martins; Kawashita, Nair Honda

    2015-01-01

    Aim: The present study was undertaken to evaluate the acute and subchronic antihyperglycemic effects of methanolic extract of Bowdichia virgilioides root bark of B. virgilioides in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: The extract (100, 250 or 500 mg/kg) was orally administered to male Wistar diabetic (STZ, 42 mg/kg i.v.) and non-diabetic rats into two main protocols: (i) subchronic experiments, where animals were treated for 21 days with B. virgilioides extract and the following parameters were evaluated: Body weight, fluid and food intake (determined daily), urinary glucose and urea (every 3 days) and glycemia (every 5 days). At the end of the experimental period, skeletal muscles (extensor digitorum longus [EDL] and soleus), retroperitoneal and epididymal white adipose tissues were collected and weighed; liver samples were used for the determination of the lipid and glycogen contents; (ii) acute experiments, which evaluated the alterations on fasting and post-prandial glycemia and on glucose tolerance using the oral glucose tolerance test (OGTT). Results: In subchronic experiments, the treatment with B. virgilioides extract did not change any parameter evaluated in diabetic and non-diabetic animals. On fasting and post-prandial glycemia, the extract treatment did not promote changes in the glycemia values in diabetic or non-diabetic animals. In OGTT, the treatment with 500 mg/kg B. virgilioides extract reduced the hyperglycemia peak after a glucose overload, when compared with non-treated diabetic animals, resulting in a lower area under curve. Conclusion: The results of our work indicate that B. virgilioides root extract promotes an acute antihyperglycemic effect in STZ-diabetic rats; this effect probably occurs through an inhibition of the intestinal glucose absorption. The continuity of the research is necessary to elucidate these possibilities. PMID:26401386

  11. Effect of dragon fruit extract on oxidative stress and aortic stiffness in streptozotocin-induced diabetes in rats

    PubMed Central

    Anand Swarup, Kolla R. L.; Sattar, Munavvar A.; Abdullah, Nor A.; Abdulla, Mohammed H.; Salman, Ibrahim M.; Rathore, Hassaan A.; Johns, Edward J.

    2010-01-01

    Cardiovascular complications are consistently observed in diabetic patients across all age groups. The objective of the present study was to investigate the effect of aqueous extract of the fruit pulp of Hylocereus undatus (DFE) on aortic stiffness and oxidative stress in streptozotocin (STZ)-induced diabetes in rats. Twenty-four male, Sprague-Dawley rats were randomized into four groups: I (control), II (diabetic), III (DFE, 250 mg/kg) and IV (DFE 500 mg/kg). Diabetes was induced in groups II, III and IV by intraperitoneal (i.p.) injection of STZ (40 mg/kg). After confirmation of diabetes, group III and IV received DFE for 5 weeks. Pulse wave velocity (PWV) was used as a marker of aortic stiffness and was determined at the end of 5 weeks. DFE significantly decreased (P < 0.05) the fasting blood glucose levels in diabetic rats, but not to normal levels. Systolic blood pressure, pulse pressure and PWV were significantly increased (P < 0.05) in diabetic rats at the end of 5 weeks in comparison with control group. DFE treatment significantly decreased (P < 0.05) these elevations. Oxidative damage was observed in group II after 5 weeks. Plasma malondialdehyde levels significantly decreased (P < 0.05), while superoxide dismutase and total antioxidant capacity significantly increased (P < 0.05) with DFE treatment in comparison with group II. These data demonstrate that DFE treatment was effective in controlling oxidative damage and decreasing the aortic stiffness measured by PWV in STZ-induced diabetes in rats. PMID:21808536

  12. Antihyperglycemic Effect of Methanol Extract of Syzygium polyanthum (Wight.) Leaf in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Widyawati, Tri; Yusoff, Nor Adlin; Asmawi, Mohd Zaini; Ahmad, Mariam

    2015-09-01

    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. PMID:26389944

  13. Antihyperglycemic Effect of Methanol Extract of Syzygium polyanthum (Wight.) Leaf in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Widyawati, Tri; Adlin Yusoff, Nor; Asmawi, Mohd Zaini; Ahmad, Mariam

    2015-01-01

    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. PMID:26389944

  14. Curcumin restores diabetes induced neurochemical changes in the brain stem of Wistar rats.

    PubMed

    Kumar, Peeyush T; George, Naijil; Antony, Sherin; Paulose, Cheramadathikudiyil Skaria

    2013-02-28

    Diabetes mellitus, when poorly controlled, leads to debilitating central nervous system (CNS) complications including cognitive deficits, somatosensory and motor dysfunction. The present study investigated curcumin's potential in modulating diabetes induced neurochemical changes in brainstem. Expression analysis of cholinergic, insulin receptor and GLUT-3 in the brainstem of streptozotocin (STZ) induced diabetic rats were studied. Radioreceptor binding assays, gene expression studies and immunohistochemical analysis were done in the brainstem of male Wistar rats. Our result showed that Bmax of total muscarinic and muscarinic M3 receptors were increased and muscarinic M1 receptor was decreased in diabetic rats compared to control. mRNA level of muscarinic M3, ?7-nicotinic acetylcholine, insulin receptors, acetylcholine esterase, choline acetyltransferase and GLUT-3 significantly increased and M1 receptor decreased in the brainstem of diabetic rats. Curcumin and insulin treatment restored the alterations and maintained all parameters to near control. The results show that diabetes is associated with significant reduction in brainstem function coupled with altered cholinergic, insulin receptor and GLUT-3 gene expression. The present study indicates beneficial effect of curcumin in diabetic rats by regulating the cholinergic, insulin receptor and GLUT-3 in the brainstem similar to the responses obtained with insulin therapy. PMID:23380686

  15. 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.

    PubMed

    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. PMID:25210695

  16. 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

    PubMed Central

    Kim, Young Hoon; Sung, Yun-Hee; Lee, Hee-Hyuk; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Kim, Bo-Kyun

    2014-01-01

    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. PMID:25210695

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

    PubMed Central

    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 ?-amylase and ?-glucosidase and glucose transporters SGLT1 and GLUT2 in the small intestine intestines isolated from diabetic rats treated with OA/MA for 5 weeks. In vitro assays were used to assess the inhibitory activities of OA and MA against ?-amylase, ?-glucosidase and sucrase. Results OA and MA ameliorated postprandial hyperglycemia in carbohydrate loaded diabetic rats as indicated by the significantly small glucose area under the curve (AUC) in treated diabetic animals compared with that in untreated diabetic rats. Western blotting showed that OA and MA treatment not only down-regulated the increase of SGLT1 and GLUT2 expressions in the small intestine of STZ-induced diabetic rats, but also inhibited small intestine ?-amylase, sucrase and ?-glucosidase activity. IC50 values of OA against ?-amylase (3.60 ± 0.18 mmol/L), ?-glucosidase (12.40 ± 0.11 mmol/L) and sucrase (11.50 ± 0.13 mmol/L) did not significantly differ from those of OA and acarbose. Conclusions The results of suggest that OA and MA may be used as potential supplements for treating postprandial hyperglycemia. Novelty of the Work The present observations indicate that besides improving glucose homeostasis in diabetes, OA and MA suppress postprandial hyperglycaemia mediated in part via inhibition of carbohydrate hydrolysis and reduction of glucose transporters in the gastrointestinal tract. Inhibition of ?-glucosidase and ?-amylase can significantly decrease the postprandial hyperglycaemia after a mixed carbohydrate diet and therefore can be an important strategy in the management of postprandial blood glucose levels in NIDDM patients. PMID:24278452

  18. Magnetic resonance imaging of the pancreas in streptozotocin-induced diabetic rats: Gadofluorine P and Gd-DOTA

    PubMed Central

    Cho, Hye Rim; Lee, Youkyung; Doble, Philip; Bishop, David; Hare, Dominic; Kim, Young-Jae; Kim, Kwang Gi; Jung, Hye Seung; Park, Kyong Soo; Choi, Seung Hong; Moon, Woo Kyung

    2015-01-01

    AIM: To investigate the performance of Gadofluorine P-enhanced magnetic resonance imaging (MRI) on the diagnosis of diabetes in a streptozotocin (STZ) -induced diabetic rat model. METHODS: Fischer 344 rats were treated with STZ. Rats not treated with STZ served as controls. T1-weighted MRI was performed using a 3T scanner before and after the injection of Gd-DOTA or Gadofluorine P (6 diabetic rats, 5 controls). The normalized signal intensity (SI) and the enhancement ratio (ER) of the pancreas were measured at each time point, and the values were compared between the normal and diabetic rats using the Mann-Whitney test. In addition, the values were correlated with the mean islet number. Optimal cut-off values were calculated using a positive test based on receiver operating characteristics. Intrapancreatic Gd concentration after the injection of each contrast media was measured using laser ablation-inductively coupled plasma-mass spectrometry in a separate set of rats (4 diabetic rats, 4 controls for Gadofluorine P; 2, 2 for Gd-DOTA). RESULTS: The normalized SI and ER of the pancreas using Gd-DOTA were not significantly different between diabetic rats and controls. With Gadofluorine P, the values were significantly higher in the diabetic rats than in the control rats 30 min after injection (P < 0.05). The area under the receiver operating characteristic curve that differentiated diabetic rats from the control group was greater for Gadofluorine P than for Gd-DOTA (0.967 vs 0.667, P = 0.085). An increase in normalized SI 30 min after Gadofluorine P was correlated with a decrease in the mean number of islets (r2 = 0.510, P = 0.014). Intra-pancreatic Gd was higher in rats with Gadofluorine P injection than Gd-DOTA injection (Gadofluorine P vs Gd-DOTA, 7.37 vs 0.00, P < 0.01). A significant difference in the concentration of intrapancreatic Gd was observed between the control and diabetic animals that were sacrificed 30 min after Gadofluorine P injection (control vs diabetic, 3.25 ng/g vs 10.55 ng/g, P < 0.05) CONCLUSION: In this STZ-induced diabetes rat model, Gadofluorine P-enhanced MRI of the pancreas showed high accuracy in the diagnosis of diabetes. PMID:26019447

  19. A stereological study of effects of aqueous extract of Tamarindus indica seeds on pancreatic islets in streptozotocin-induced diabetic rats.

    PubMed

    Hamidreza, Hamidreza; Heidari, Zahra; Shahraki, Mohammadreza; Moudi, Bita

    2010-10-01

    Tamarindus indica Linn was used as a traditional medicine for the management of diabetes mellitus in human and experimental animals. This study investigated effects of aqueous extract of Tamarindus indica seeds (AETIS) against STZ-induced damages in pancreatic islands by means of stereological methods. sixty matured normoglycemic male Wistar rats, weighing 200-250 gr, were selected and randomly divided into 6 groups (n=10). Control, STZ-induced diabetic; by intraperitoneal injection of 55 mg/Kg streptozotocin, Treated control group (TC); received AETIS at a dose of 200mg/kg/day, and AETIS treated diabetic groups (TD1-3); received respectively AETIS at the dose of 50, 100,and 200 mg/kg/day by gavage from one week after induction of diabetes by STZ. After 8 weeks of experiment, stereological estimation of volume density and total volume of islets and beta cells, volume weighted mean islets volume, mass of beta cells, islets, and pancreas and total number of islets were done. Volume density and total volume of islets, volume weighted mean islets volume, volume density islets/pancreas, volume density beta cells/islet, mass of islets and pancreas of treated diabetic groups (TD1-3) were significantly higher than untreated diabetic group (P<0.001), and in TD3 group these values were comparable to controls. Although total volume and mass of beta cells in TD1-3 were significantly higher than D group but they were significantly lower than control group (P>0.05). Total number of islets, pancreas wet weight and volume did not show any significant changes between control and experimental groups (P>0.05). Results suggested that AETIS partially restores pancreatic beta cells and repairs STZ-induced damages in rats. PMID:20884458

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

    PubMed Central

    Asri-Rezaei, Siamak; Tamaddonfard, Esmaeal; Ghasemsoltani-Momtaz, Behnaz; Erfanparast, Amir; Gholamalipour, Sima

    2015-01-01

    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.? Conclusion: 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. PMID:26468459

  1. Blocking VEGF/Caveolin-1 signaling contributes to renal protection of fasudil in streptozotocin-induced diabetic rats

    PubMed Central

    Jin, Jing; Peng, Chao; Wu, Su-zhen; Chen, Hong-min; Zhang, Bai-fang

    2015-01-01

    Aim: RhoA/ROCK signaling plays an important role in diabetic nephropathy, and ROCK inhibitor fasudil exerts nephroprotection in experimental diabetic nephropathy. In this study we investigated the molecular mechanisms underlying the protective actions of fasudil in a rat model of diabetic nephropathy. Methods: Streptozotocin (STZ)-induced diabetic rats, to which fasudil or a positive control drug enalapril were orally administered for 8 months. Metabolic parameters and blood pressure were assessed during the treatments. After the rats were euthanized, kidney samples were collected for histological and molecular biological studies. VEGF, VEGFR1, VEGFR2 and fibronectin expression, and Src and caveolin-1 phosphorylation in the kidneys were assessed using RT-PCR, Western blot and immunohistochemistry assays. The association between VEGFR2 and caveolin-1 was analyzed with immunoprecipitation. Results: Chronic administration of fasudil (30 and 100 mg·kg?1·d?1) or enalapril (10 mg/kg, bid) significantly attenuated the glomerular sclerosis and albuminuria in the diabetic rats. Furthermore, fasudil treatment prevented the upregulation of VEGF, VEGFR1, VEGFR2 and fibronectin, and the increased association between VEGFR2 and caveolin-1 in the renal cortices, and partially blocked Src activation and caveolin-1 phosphorylation on tyrosine 14 in the kidneys, whereas enalapril treatment had no effects on the VEGFR2/Src/caveolin-1 signaling pathway. Conclusion: Fasudil exerts protective actions in STZ-induced diabetic nephropathy by blocking the VEGFR2/Src/caveolin-1 signaling pathway and fibronectin upregulation. Thus, VEGFR2 may be a potential therapeutic target for the treatment of diabetic nephropathy. PMID:25937636

  2. Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment

    PubMed Central

    Chowdhury, Subir K. Roy; Zherebitskaya, Elena; Smith, Darrell R.; Akude, Eli; Chattopadhyay, Sharmila; Jolivalt, Corinne G.; Calcutt, Nigel A.; Fernyhough, Paul

    2010-01-01

    OBJECTIVE Impairments in mitochondrial physiology may play a role in diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in sensory neurons is due to abnormal mitochondrial respiratory function. RESEARCH DESIGN AND METHODS Rates of oxygen consumption were measured in mitochondria from dorsal root ganglia (DRG) of 12- to- 22-week streptozotocin (STZ)-induced diabetic rats, diabetic rats treated with insulin, and age-matched controls. Activities and expression of components of mitochondrial complexes and reactive oxygen species (ROS) were analyzed. RESULTS Rates of coupled respiration with pyruvate + malate (P + M) and with ascorbate + TMPD (Asc + TMPD) in DRG were unchanged after 12 weeks of diabetes. By 22 weeks of diabetes, respiration with P + M was significantly decreased by 31–44% and with Asc + TMPD by 29–39% compared with control. Attenuated mitochondrial respiratory activity of STZ-diabetic rats was significantly improved by insulin that did not correct other indices of diabetes. Activities of mitochondrial complexes I and IV and the Krebs cycle enzyme, citrate synthase, were decreased in mitochondria from DRG of 22-week STZ-diabetic rats compared with control. ROS levels in perikarya of DRG neurons were not altered by diabetes, but ROS generation from mitochondria treated with antimycin A was diminished compared with control. Reduced mitochondrial respiratory function was associated with downregulation of expression of mitochondrial proteins. CONCLUSIONS Mitochondrial dysfunction in sensory neurons from type 1 diabetic rats is associated with impaired rates of respiratory activity and occurs without a significant rise in perikaryal ROS. PMID:20103706

  3. Achillea Millefolium L. Hydro- Alcoholic Extract Protects Pancreatic Cells by Down Regulating IL- 1? and iNOS Gene Expression in Diabetic Rats

    PubMed Central

    Zolghadri, Yalda; Fazeli, Mehdi; Kooshki, Marzieh; Shomali, Tahoora; Karimaghayee, Negar; Dehghani, Maryam

    2014-01-01

    Interleukin-1? (IL-1?) has a role in ?- cell destruction in autoimmune diabetes by stimulating the expression of inducible nitric oxide synthase (iNOS) that generates the free radical nitric oxide. We aimed to investigate the effect of Achillea millefolium L, as a traditional hypoglycemic agent, on IL-1? and iNOS gene expression of pancreatic tissue in the STZ- induced diabetic rats. Forty adult male Wistar rats were randomly divided into four groups: 1. diabetic control; 2. diabetic rats treated with Achillea millefolium L. extract; 3. normal rats received only extract and 4. negative control (n= 10 each). Diabetes was induced by single i.p. injection of 45 mg/ kg streptozotocin (STZ). Rats in groups 2 and 3 were treated with i.p. injection of Achillea millefolium L. extract (100 mg/ kg/ day) for 14 days. Body weight, serum glucose and insulin levels were assayed at baseline and on days 3, 7, 10 and 14 of the experiment. Finally, the quantity of pancreatic IL-1? and iNOS mRNA was determined by real- time PCR. The mRNA expression level of IL-1? and iNOS genes, was significantly (p<0.001) increased in diabetic rats of group 1. Treatment with Achillea millefolium L. caused a significant (p<0.01) reduction in both IL-1? and iNOS genes expression. Moreover, rats in group 2 had higher insulin level associated with lower glucose level and higher body weight compared to control diabetic group. It seems that beneficial effect of Achillea millefolium L. on STZ- induced diabetes is at least partly due to amelioration of IL-1? and iNOS gene over expression which can have a ?-cell protective effect. PMID:25635252

  4. Investigation of hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats

    PubMed Central

    Ramachandran, Subramaniam; Rajasekaran, Aiyalu; Manisenthilkumar, KT

    2012-01-01

    Objective To investigate the hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark (AETPB) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity was studied in rats after the oral administration of AETPB to determine the dose to assess hypoglycemic activity. In rats, diabetes was induced by injection of STZ (60 mg/kg, i.p.) and diabetes was confirmed 72 h after induction, and then allowed for 14 days to stabilize blood glucose level. In diabetic rats, AETPB was orally given for 28 days and its effect on blood glucose and body weight was determined on a weekly basis. At the end of the experimental day, fasting blood sample was collected to estimate the haemoglobin (Hb), glycosylated haemoglobin (HbA1c), serum creatinine, urea, serum glutamate-pyruvate transaminase (SGPT), serum glutamate-oxaloacetate transaminase (SGOT) and insulin levels. The liver and kidney were collected to determine antioxidants levels in diabetic rats. Results Oral administration of AETPB did not exhibit toxicity and death at a dose of 2?000 mg/kg. AETPB treated diabetic rats significantly (P<0.001, P<0.01 and P<0.05) reduced elevated blood glucose, HbA1c, creatinine, urea, SGPT and SGOT levels when compared with diabetic control rats. The body weight, Hb, insulin and total protein levels were significantly (P<0.001, P<0.01 and P<0.05) increased in diabetic rats treated with AETPB compared to diabetic control rats. In diabetic rats, AETPB treatment significantly reversed abnormal status of antioxidants and lipid profile levels towards near normal levels compared to diabetic control rats. Conclusions Present study results confirm that AETPB possesses significant hypoglycemic, hypolipidemic and antioxidant activities in diabetic condition. PMID:23569911

  5. Study on The Effect of Royal Jelly on Reproductive Parameters in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ghanbari, Elham; Nejati, Vahid; Najafi, Gholamreza; Khazaei, Mozafar; Babaei, Mohammad

    2015-01-01

    Background Diabetes mellitus has a variety of structural and functional effects on the male reproductive system. Diabetes results in reduced sperm parameters and libido. The present study aims to investigate the effects of royal jelly (RJ) on reproductive parameters of testosterone and malondialdehyde (MDA) production in diabetic rats. Materials and Methods This experimental study was conducted on adult male Wistar rats. The animals were divided into four groups (n=8 per group): control, RJ, diabetic and diabetic treated with RJ. Diabetes was induced by intraperitoneal injection of 60 mg/kg body weight (BW) of streptozotocin (STZ). RJ, at a dose of 100 mg/kg BW was given by gavage. The duration of treatment was six weeks. After the treatment period the rats were sacrificed. The testes were weighed and changes in sperm count, motility, viability, deformity, DNA integrity and chromatin quality were analyzed. Serum testosterone and MDA concentrations of testicular tissue were determined. Data were analyzed by oneway ANOVA with p<0.05 as the significant level. Results STZ-induced diabetes decreased numerous reproductive parameters in rats. Testicular weight, sperm count, motility, viability and serum testosterone levels increased in the diabetic group treated with RJ. There was a significant decrease observed in sperm deformity, DNA integrity, chromatin quality, and tissue MDA levels in diabetic rats treated with RJ compared to the diabetic group (p<0.05). Conclusion RJ improved reproductive parameters such as testicular weight, sperm count, viability, motility, deformity, DNA integrity, chromatin quality, serum testosterone and testicular tissue MDA levels in diabetic rats. PMID:25918599

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

    PubMed Central

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

    2011-01-01

    Objective To evaluate antidiabetic and antioxidant potential of Hybanthus enneaspermus in different models. Methods The oral glucose tolerance test (OGTT) and normoglycemic effect of alcoholic extract of Hybanthus enneaspermus (AHE) were evaluated at a dose of 125, 250 and 500 mg/kg p.o. while hypoglycemic activity and effect on body weight were tested at 250 and 500 mg/kg p.o. per day for 21 days in Streptozotocin (STZ) induced diabetic rats. Further, glucose uptake by hemidiaphram was also evaluated. The total polyphenolic and flavonoid were determined and their correlation with various antioxidant assays was also determined. Results The results showed high level of phenolic content in AHE. AHE also exhibited higher total antioxidant capacity, good reducing power and a significant scavenger of reactive oxygen species like DPPH radical, nitric oxide, hydrogen peroxide and deoxyribose. Furthermore there was a significant increase in the body weight and decrease in the blood glucose level on treatment with the AHE. AHE increased glucose uptake on isolated rat hemi-diaphragm compared to control group. Conclusions AHE reduce blood glucose level in STZ-induced diabetic model. It does not show significant effect in normoglycemic study but showes significant effect in OGT. AHE has significant antioxidant activity, which may be attributed to high phenolic content. PMID:23569783

  7. Modulatory effects of l-arginine and soy enriched diet on bone homeostasis abnormalities in streptozotocin-induced diabetic rats.

    PubMed

    El-Maraghy, Shohda A; Mehana, Noha Ali

    2015-03-01

    Diabetes mellitus is a complex syndrome which is responsible for numerous complications affecting the whole body. Osteoporosis is regarded as one of the chronic complications of diabetes mellitus that results from reduced bone formation and increased resorption. In this context, we searched for dietary supplements that preserve diabetic bone loss. Parathyroid hormone (PTH) has been suggested as a possible mechanism affecting bone homeostasis in streptozotocin (STZ)-induced diabetic rats. The osteoprotective effects of l-arginine and soy enriched diet were also investigated. Male Wistar rats were allocated into four groups; normal control, untreated STZ-diabetic rats and STZ-diabetic rats treated with either l-arginine (10mg/kg/day) or fed soy enriched diet (200 g/kg diet) for 12 weeks. l-Arginine and soy enriched diet normalized serum PTH level and increased serum osteocalcin level; bone osteocalcin, osteoprotegerin and runt-related transcription factor2 mRNA levels compared to diabetic rats. A decrease in serum pyridinoline, C-terminal telopeptides of type I collagen, cathepsin k levels and bone cathepsin k mRNA level was observed in both treated groups. Both treatments increased serum insulin and insulin like growth factor-1 levels and decreased urinary calcium excretion. In conclusion, l-arginine and soy enriched diet are effective in prevention of osteoporosis associated with diabetes mellitus. PMID:25617479

  8. The effect of glutathione treatment on the biochemical and immunohistochemical profile in streptozotocin-induced diabetic rats.

    PubMed

    Yur, Fatmagül; Dede, Semiha; Karaca, Turan; Ciftçi Yegin, Sevim; De?er, Yeter; Ozdemir, Hülya

    2013-06-01

    This study investigated the possible role of glutathione (GSH) in diabetic complications and its biochemical safety in experimental diabetic rats. Serum biochemical parameters and the histology of the pancreas were investigated. Seven rats were separated as controls. To create the diabetes in rats, 45 mg/kg single-dose streptozotocin (STZ) was administered i.p. The treatment was continued for 1 month. STZ was administered to the diabetes + GSH group, then reduced GSH, dissolved in isotonic salt solution (200 mg/kg), was applied i.p. two times a week. The GSH group received i.p. GSH. Serum biochemical parameters were determined by autoanalyzer. Immunohistochemical procedures were used to determine the percentage of the insulin-immunoreactive ?-cell area in the islets of Langerhans. The biochemical parameters changed to different degrees or did not change. Pancreatic cells of the control and GSH groups were healthy, but in the diabetic and GSH-treated diabetic groups we found damage in different numbers. The results from these analyses show that GSH supplementation can exert beneficial effects on pancreatic cells in STZ-induced diabetic rats and can safely be used for therapy in and protection from diabetes and complications of diabetes. PMID:23681352

  9. Protective effects of Salvia miltiorrhiza injection against learning and memory impairments in streptozotocin-induced diabetic rats.

    PubMed

    Cai, Huabo; Lian, Luya; Wang, Yu; Yu, Yuanyuan; Liu, Wei

    2014-10-01

    The aim of this study was to explore the protective effects of Salvia miltiorrhiza injection against learning and memory impairment in streptozotocin (STZ)-induced diabetic rats and the possible mechanism involved. Sprague Dawley male rats (n=30) were randomized into three groups: Diabetes, diabetes treated with S. miltiorrhiza injection and normal control. Diabetes was induced by an intraperitoneal injection of STZ (65 mg/kg). The S. miltiorrhiza injection-treated rats received an intraperitoneal injection of S. miltiorrhiza (5 ml/kg/day) while the rats of the other two groups were administered an intraperitoneal injection of the same volume of 0.9% saline for four weeks. After four weeks of treatment, the escape latency and search strategies in the rats were assessed by the Morris water maze test. The protein levels of mitogen-activated protein kinase phosphatase-1 (MKP-1) were also assessed by immunohistochemistry. Four weeks after the induction of diabetes, the body weight of the diabetic rats was significantly lower and the blood glucose concentration was significantly higher than that of the control rats. S. miltiorrhiza injection was observed to improve the blood glucose and learning ability (P<0.05). Compared with the control group, the expression of MKP-1 was significantly decreased in the hippocampal area of the diabetes group; S. miltiorrhiza injection-treated rats showed an increased expression compared with the diabetic rats, but the expression remained lower than that of the normal control group (P<0.05). In conclusion, S. miltiorrhiza injection can improve the learning and memory decline of diabetic rats. The changes in expression of MKP-1 under hyperglycemia may play a role in the protective effects of S. miltiorrhiza against dementia in diabetic rats. PMID:25187809

  10. Protective effects of Salvia miltiorrhiza injection against learning and memory impairments in streptozotocin-induced diabetic rats

    PubMed Central

    CAI, HUABO; LIAN, LUYA; WANG, YU; YU, YUANYUAN; LIU, WEI

    2014-01-01

    The aim of this study was to explore the protective effects of Salvia miltiorrhiza injection against learning and memory impairment in streptozotocin (STZ)-induced diabetic rats and the possible mechanism involved. Sprague Dawley male rats (n=30) were randomized into three groups: Diabetes, diabetes treated with S. miltiorrhiza injection and normal control. Diabetes was induced by an intraperitoneal injection of STZ (65 mg/kg). The S. miltiorrhiza injection-treated rats received an intraperitoneal injection of S. miltiorrhiza (5 ml/kg/day) while the rats of the other two groups were administered an intraperitoneal injection of the same volume of 0.9% saline for four weeks. After four weeks of treatment, the escape latency and search strategies in the rats were assessed by the Morris water maze test. The protein levels of mitogen-activated protein kinase phosphatase-1 (MKP-1) were also assessed by immunohistochemistry. Four weeks after the induction of diabetes, the body weight of the diabetic rats was significantly lower and the blood glucose concentration was significantly higher than that of the control rats. S. miltiorrhiza injection was observed to improve the blood glucose and learning ability (P<0.05). Compared with the control group, the expression of MKP-1 was significantly decreased in the hippocampal area of the diabetes group; S. miltiorrhiza injection-treated rats showed an increased expression compared with the diabetic rats, but the expression remained lower than that of the normal control group (P<0.05). In conclusion, S. miltiorrhiza injection can improve the learning and memory decline of diabetic rats. The changes in expression of MKP-1 under hyperglycemia may play a role in the protective effects of S. miltiorrhiza against dementia in diabetic rats. PMID:25187809

  11. Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats.

    PubMed

    Erejuwa, O O; Sulaiman, S A; Wahab, M S; Sirajudeen, K N S; Salleh, M S Md; Gurtu, S

    2010-09-01

    Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas. PMID:20398890

  12. Attenuation of hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats by aqueous extract of seed of Tamarindus indica.

    PubMed

    Maiti, Rajkumar; Das, Uttam Kumar; Ghosh, Debidas

    2005-07-01

    Streptozotocin (STZ)-induced diabetic rats were divided into mild diabetic (MD) and severe diabetic (SD) on the basis of fasting blood glucose (FBG) levels. Diabetes was confirmed here by intravenous glucose tolerance test (GTT), biochemical assay of glycogen content in liver and skeletal muscle, glucose-6-phosphatase activity in liver, and serum insulin levels. Hyperlipidemia developed in these experimental diabetic rats was assessed by quantification of total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) and triglyceride (TG) in serum. Aqueous extract of seed of Tamarindus indica was given to MD and SD rats at the dose of 80 mg and 120 mg/0.5 ml distilled water/100 g body weight/d respectively for 14 d. Significant attenuation of hyperglycemia was indicated by measuring FBG, glycogen level and glucose-6-phosphatase activity along with monitoring of intravenous GTT and serum insulin level. Similarly, correction of hyperlipidemia in diabetic rats after this extract supplementation was confirmed by significant reduction in the levels of above-mentioned hyperlipidemic indicators. Intravenous GTT was performed that highlights the antidiabetic action of this extract is not due to its effect on the intestinal rate of glucose absorption but may be due to modulation of intracellular glucose utilization in target organs. This study focus the efficacy of this extract for the management of experimental diabetes in rat model which may shed some light on the scientific basis of ancient herbal therapy in this line using this seed. PMID:15997092

  13. A new Agkistrodon halys venom-purified protein C activator prevents myocardial fibrosis in diabetic rats

    PubMed Central

    Li, Shu; Hong, Yun; Jin, Xin; Zhang, Genbao; Hu, Zaichang; Nie, Liuwang

    2015-01-01

    Aim To assess the effects of protein C activator (PCA) from Agkistrodon halys snake venom on cardiac fibrosis in streptozotocin (STZ) induced diabetic rat model, and investigate the mechanisms of its action. Methods PCA was identified by one-dimensional reversed phase liquid chromatography – mass spectrometry/mass spectrometry. Male Sprague-Dawley rats (120-140 g) were randomly assigned to negative control (NC) and diabetic group. Diabetes was induced by STZ in high-fat diet fed rats. Diabetic group was subdivided into three groups: diabetic group (DM), diabetic group treated with PCA (0.5, 2, and 8 mg/kg), and diabetic group treated with metformin (5 mg/kg, positive control). NC and DM groups received the same volume of distilled water. Left ventricular mass index (LVWI) and collagen volume fraction were measured by hematoxylin and eosin and Masson staining. Transforming growth factor beta-1 (TGF-?1) and interleukin 1 beta (IL-1?) levels were determined by enzyme-linked immunosorbent assay. Results The diabetic rat model was successfully established by STZ induction and high-fat diet. Glucose level, LVWI, TGF-?1 and IL-1? level, and collagen volume fraction were significantly reduced in diabetic rats treated by PCA in a dose-dependent manner (P?diabetes group. The high dose PCA had the same effect as metformin positive control in reducing the level of fasting blood glucose. PCA decreased the expression of MMP-2 and reduced that of TIMP-2. Conclusion Our results indicate that PCA has anti-fibrotic effects and that it may be used to treat myocardial fibrosis. PMID:26526881

  14. Increased GABAergic Output in the Ventromedial Hypothalamus Contributes to Impaired Hypoglycemic Counterregulation in Diabetic Rats

    PubMed Central

    Chan, Owen; Paranjape, Sachin; Czyzyk, Daniel; Horblitt, Adam; Zhu, Wanling; Ding, Yuyan; Fan, Xiaoning; Seashore, Margretta; Sherwin, Robert

    2011-01-01

    OBJECTIVE Impaired glucose counterregulation during hypoglycemia is well documented in patients with type 1 diabetes; however, the molecular mechanisms underlying this defect remain uncertain. We reported that the inhibitory neurotransmitter ?-aminobutyric acid (GABA), in a crucial glucose-sensing region within the brain, the ventromedial hypothalamus (VMH), plays an important role in modulating the magnitude of the glucagon and epinephrine responses to hypoglycemia and investigated whether VMH GABAergic tone is altered in diabetes and therefore might contribute to defective counterregulatory responses. RESEARCH DESIGN AND METHODS We used immunoblots to measure GAD65 protein (a rate-limiting enzyme in GABA synthesis) and microdialysis to measure extracellular GABA levels in the VMH of two diabetic rat models, the diabetic BB rat and the streptozotocin (STZ)-induced diabetic rat, and compared them with nondiabetic controls. RESULTS Both diabetic rat models exhibited an ~50% increase in GAD65 protein as well as a twofold increase in VMH GABA levels compared with controls under baseline conditions. Moreover, during hypoglycemia, VMH GABA levels did not change in the diabetic animals, whereas they significantly declined in nondiabetic animals. As expected, glucagon responses were absent and epinephrine responses were attenuated in diabetic rats compared with their nondiabetic control counterparts. The defective counterregulatory response in STZ-diabetic animals was restored to normal with either local blockade of GABAA receptors or knockdown of GAD65 in the VMH. CONCLUSIONS These data suggest that increased VMH GABAergic inhibition is an important contributor to the absent glucagon response to hypoglycemia and the development of counterregulatory failure in type 1 diabetes. PMID:21411513

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

    PubMed Central

    Kamboj, Anil; Kumar, Sunil; Kumar, Vipin

    2013-01-01

    Objective. To investigate antidiabetic activity of hydroalcoholic extract of Cestrum nocturnum leaves in Wistar rats. Method. Cestrum nocturnum leaves extract in hydroalcoholic solution were prepared by Soxhletation method and stored in refrigerator at 4°C for two days before use. Wistar rats were made diabetic by a single dose of streptozotocin (150?mg/kg i.p.). Hydroalcoholic leaves extract of Cestrum nocturnum was screened for antidiabetic activity and given to the STZ-induced diabetic rats at a concentration of 200?mg/kg and 400?mg/kg of body weight in different groups of 6 diabetic rats each orally once a day for 15 days. Metformin is also given to another group to support the result at a dose of 10?mg/kg of body weight orally once a day for 15 days. Blood glucose levels and body weights of rats were measured on 0, 5, 7, and 15th days. Results. Oral administration of the extracts for 15 days caused a significant (P < 0.01) reduction in blood glucose levels in diabetic rats. The body weight of diabetic animals was also improved after daily administration of extracts. The extract also improved other altered biochemical parameters associated with diabetes. Also the changes in food intake, water intake, and weight of internal organs were also restored to normal by the prolonged effect of extract treatment. PMID:24151502

  16. Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats

    PubMed Central

    2014-01-01

    Background Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats. Methods Type 1 diabetes mellitus was induced in Sprague–Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (N?-nitro-l-arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats. Results Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (l-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals. Conclusions CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals. PMID:24923878

  17. Protective effect of chemically modified SOD on lipid peroxidation and antioxidant status in diabetic rats.

    PubMed

    Mansuro?lu, Banu; Derman, Serap; Yaba, Aylin; K?z?lbey, Kadriye

    2015-01-01

    Reactive oxygen species mediated oxidative stress play an important role on the injury of tissue damage and increased attention has been focused on the role of free radicals in diabetes mellitus (DM). In the present study firstly superoxide dismutase (SOD) enzyme was chemically modified with two different polymer and physicochemical properties of these conjugates clearly analyzed. Then, the stability of carboxymethylcellulose-SOD (CMC-SOD) and poly methyl vinyl ether-co-maleic anhydride-SOD (PMVE/MA-SOD) conjugates was investigated against temperature and externally added H2O2. Moreover, we investigated the effect of chemically modified SOD enzyme on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetic rats. PMVE/MA-SOD conjugate treatment significantly reduced MDA level compared with the control groups, native and CMC-SOD conjugate treated groups in brain, kidney and liver tissue. GSH and SOD enzyme activity in diabetic groups was significantly increased by treatment of CMC-SOD and PMVE/MA-SOD conjugates. The protective effects on degenerative changes in diabetic rats were also further confirmed by histopathological examination. This study provides the preventative activity of SOD-polymer conjugates against complication of oxidative stress in experimentally induced diabetic rats. These results suggest that chemically modified SOD is effective on the oxidative stress-associated disease and offer a therapeutic advantage in clinical use. PMID:25124383

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

    PubMed Central

    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 ?-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

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

    PubMed

    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 ?-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

  20. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats

    PubMed Central

    Zakaria, Mohamed Naguib; El-Bassossy, Hany M.; Barakat, Waleed

    2015-01-01

    Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS) complications in STZ-induced (50?mg/kg, IP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze), neuronal degeneration (Fluoro-Jade staining), AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications. PMID:26491434

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

    PubMed Central

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

    2013-01-01

    Objectives: 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. Methods: 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 15th 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. Results: The ethyl-acetate fraction at doses of 200 and 400 mg/kg significantly (P< 0.001) and dose-dependently reduced serum cholesterol, triglycerides and LDL, but increased HDL towards near normal levels as compared to diabetic control rats. The fraction also significantly (P< 0.001) lowered the atherogenic index (AI) and coronary risk index (CAI) in a dose-dependent manner. Conclusion: The present study demonstrated that the ethyl-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. PMID:25780672

  2. Anti-diabetic effects of ethanol extract of Bryonia laciniosa seeds and its saponins rich fraction in neonatally streptozotocin-induced diabetic rats

    PubMed Central

    Patel, Sandip B.; Santani, Devdas; Patel, Veena; Shah, Mamta

    2015-01-01

    Context: Bryonia laciniosa Linn. (Cucurbitaceae) seed is used in traditional medicine for a number of ailments including metabolic disorders. Aim: This study evaluated the anti-diabetic action of the ethanol extract of B. laciniosa seeds and saponin fraction of it through its effect on hyperglycemia, dyslipidaemia and oxidative stress in neonatally streptozotocin (n-STZ)-induced diabetic rats (n-STZ diabetic rats). Materials and Methods: Ethanol extract (250 and 500 mg/kg; p.o.), saponin fraction (100 and 200 mg/kg; p.o.) and standard drug glibenclamide (3 mg/kg; p.o.) were administered to diabetic rats when the rats were 6 weeks old and continued for 10 consecutive weeks. Effects of ethanol extract and saponin fraction on various biochemical parameters were studied in diabetic rats. Results: The treatment with ethanol extract and saponin fraction for 10 weeks decrease in the levels of glucose, triglycerides, cholesterol, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, serum urea, serum creatinine and diminished activities of aspartate transaminase, and alanine transaminase. The anti-hyperglycemic nature of B. laciniosa is probably brought about by the extra- the pancreatic mechanism as evidenced from unchanged levels of plasma insulin. B. laciniosa modulated effect of diabetes on the liver malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity. Administration of ethanol extract and saponin fraction to diabetic rats showed a significant reversal of disturbed antioxidant status. Significant increase in SOD, CAT, and levels of GSH was observed in treated n-STZ diabetic rats. Conclusion: The present study reveals the efficacy of B. laciniosa seed extract and its saponin fraction in the amelioration of n-STZ diabetic rats. PMID:25598641

  3. Amelioration of pancreatic and renal derangements in streptozotocin-induced diabetic rats by polyphenol extracts of Ginger (Zingiber officinale) rhizome.

    PubMed

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin

    2015-12-01

    Free and bound polyphenol extracts of Zingiber officinale rhizome were investigated for their antidiabetic potential in the pancreatic and renal tissues of diabetic rats at a dose of 500mg/kg body weight. Forty Wistar rats were completely randomized into five groups: A-E consisting of eight animals each. Group A (control) comprises normal healthy animals and were orally administered 1.0mL distilled water on a daily basis for 42 days while group B-E were made up of 50mg/kg streptozotocin (STZ)-induced diabetic rats. Group C and D received 1.0mL 500mg/kg body weight free and bound polyphenol extracts respectively while group E received 1.0mL 0.6mg/kg of glibenclamide. Administration of the extracts to the diabetic rats significantly reduced (p<0.05) serum glucose and urea concentrations, increased (p<0.05) serum insulin and Homeostatic Model Assessment for ?-cell dysfunction (HOMA-?) while the level of creatinine and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were not affected. Histological examination of the pancreas and kidney revealed restoration of the structural derangements caused by streptozotocin in the polyphenol extracts treated diabetic rats compared to the control groups. Therefore, polyphenols from Zingiber officinale could ameliorate diabetes-induced pancreatic and renal derangements in rats. PMID:26349770

  4. Dietary fish oil inhibits mechanical allodynia and thermal hyperalgesia in diabetic rats by blocking nuclear factor-?B-mediated inflammatory pathways.

    PubMed

    Li, Meng-Ying; Wang, Ya-Yun; Cao, Rui; Hou, Xiang-Hong; Zhang, Lei; Yang, Rui-Hua; Wang, Feng

    2015-11-01

    One of the most common complications of early-onset diabetes mellitus is peripheral diabetic neuropathy, which is manifested either by loss of nociception or by allodynia and hyperalgesia. Diabetes mellitus is a common metabolic disease in human beings with characteristic symptoms of hyperglycemia, chronic inflammation and insulin resistance. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown anti-inflammatory role in various experimental conditions. The present study investigated the effects of fish oil supplementation on the inflammation in the dorsal root ganglion (DRG) of streptozotocin (STZ)-induced diabetes rats. The effects of diabetes and fish oil treatment on the allodynia and hyperalgesia were also evaluated. Dietary fish oil effectively attenuated both allodynia and hyperalgesia induce by STZ injection. Along with the behavioral findings, DRG from fish oil-treated diabetic rats displayed a decrease in inflammatory cytokines and the expression of nuclear factor-?B (NF-?B) compared with untreated diabetic rats. Fish oil supplementation also increased the phosphorylation of AKT in DRG of diabetic rats. These results suggested that dietary fish oil-inhibited allodynia and hyperalgesia in diabetic rats may stem from its anti-inflammatory potential by regulating NF-?B and AKT. Fish oil might be useful as an adjuvant therapy for the prevention and treatment of diabetic complications. PMID:26118694

  5. Anti-diabetic effect of a preparation of vitamins, minerals and trace elements in diabetic rats: a gender difference

    PubMed Central

    2014-01-01

    Background Although multivitamin products are widely used as dietary supplements to maintain health or as special medical food in certain diseases, the effects of these products were not investigated in diabetes mellitus, a major cardiovascular risk factor. Therefore, here we investigated if a preparation of different minerals, vitamins, and trace elements (MVT) for human use affects the severity of experimental diabetes. Methods Two days old neonatal Wistar rats from both genders were injected with 100 mg/kg of streptozotocin or its vehicle to induce diabetes. At week 4, rats were fed with an MVT preparation or vehicle for 8 weeks. Well established diagnostic parameters of diabetes, i.e. fasting blood glucose and oral glucose tolerance test were performed at week 4, 8 and 12. Moreover, serum insulin and blood HbA1c were measured at week 12. Results An impaired glucose tolerance has been found in streptozotocin-treated rats in both genders at week 4. In males, fasting blood glucose and HbA1c were significantly increased and glucose tolerance and serum insulin was decreased at week 12 in the vehicle-treated diabetic group as compared to the vehicle-treated non-diabetic group. All of the diagnostic parameters of diabetes were significantly improved by MVT treatment in male rats. In females, streptozotocin treatment resulted in a less severe prediabetic-like phenotype as only glucose tolerance and HbA1c were altered by the end of the study in the vehicle-treated diabetic group as compared to the vehicle-treated non-diabetic group. MVT treatment failed to improve the diagnostic parameters of diabetes in female streptozotocin-treated rats. Conclusion This is the first demonstration that MVT significantly attenuates the progression of diabetes in male rats with chronic experimental diabetes. Moreover, we have confirmed that females are less sensitive to STZ-induced diabetes and MVT preparation did not show protection against prediabetic state. This may suggest a gender difference in the pathogenesis of diabetes. PMID:25160946

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

    PubMed Central

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

    2013-01-01

    Curcumin, the active principle present in the yellow spice turmeric, has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Previously we have reported that dietary curcumin delays diabetes-induced cataract in rats. However, low peroral bioavailability is a major limiting factor for the success of clinical utilization of curcumin. In this study, we have administered curcumin encapsulated nanoparticles in streptozotocin (STZ) induced diabetic cataract model. Oral administration of 2 mg/day nanocurcumin was significantly more effective than curcumin in delaying diabetic cataracts in rats. The significant delay in progression of diabetic cataract by nanocurcumin is attributed to its ability to intervene the biochemical pathways of disease progression such as protein insolubilization, polyol pathway, protein glycation, crystallin distribution and oxidative stress. The enhanced performance of nanocurcumin can be attributed probably to its improved oral bioavailability. Together, the results of the present study demonstrate the potential of nanocurcumin in managing diabetic cataract. PMID:24155984

  7. Aqueous extract of tamarind seeds selectively increases glucose transporter-2, glucose transporter-4, and islets' intracellular calcium levels and stimulates ?-cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes mellitus.

    PubMed

    Sole, Sushant Shivdas; Srinivasan, B P

    2012-08-01

    Tamarindus indica Linn. has been in use for a long time in Asian food and traditional medicine for different diseases including diabetes and obesity. However, the molecular mechanisms of these effects have not been fully understood. In view of the multidimensional activity of tamarind seeds due to their having high levels of polyphenols and flavonoids, we hypothesized that the insulin mimetic effect of aqueous tamarind seed extract (TSE) might increase glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family and sterol regulatory element-binding proteins (SREBP) 1c messenger RNA (mRNA) in the liver. Daily oral administration of TSE to streptozotocin (STZ)-induced (90 mg/kg intraperitoneally) type 2 diabetic male Wistar rats at different doses (120 and 240 mg/kg body weight) for 4 weeks showed positive correlation with intracellular calcium and insulin release in isolated islets of Langerhans. Tamarind seed extract supplementation significantly improved the GLUT-2 protein and SREBP-1c mRNA expression in the liver and GLUT-4 protein and mRNA expression in the skeletal muscles of diabetic rats. The elevated levels of serum nitric oxide (NO), glycosylated hemoglobin level (hemoglobin (A1c)) and tumor necrosis factor ? (TNF-?) decreased after TSE administration. Immunohistochemical findings revealed that TSE abrogated STZ-induced apoptosis and increased ?-cell neogenesis, indicating its effect on islets and ?-cell mass. In conclusion, it was found that the antidiabetic effect of TSE on STZ-induced diabetes resulted from complex mechanisms of ?-cell neogenesis, calcium handling, GLUT-2, GLUT-4, and SREBP-1c. These findings show the scope for formulating a new herbal drug for diabetes therapy. PMID:22935346

  8. Effect of insulin deficiency on the rewarding properties of methamphetamine in streptozotocin-induced diabetic rats.

    PubMed

    Bayat, Amir-Hossein; Haghparast, Abbas

    2015-01-01

    The reward is a positive behavioural response to the pleasant stimuli that can be induced by drugs, such as psychostimulants. Furthermore, diabetes mellitus is a chronic disease that many people throughout the world suffer from. Methamphetamine (METH), as a psychostimulant, engages the dopaminergic system in the reward circuitry and the synapses of dopaminergic terminals can be modified by insulin. In this study, in order to assess the effect of insulin deficiency on reward, streptozotocin (STZ)-induced diabetic animals were used as an appropriate model. One hundred and thirty-two adult male rats were divided into nine groups (three non-diabetic and six diabetic groups) to determine the most effective dose of METH (0.25, 0.5, 1 and 2mg/kg ip), and insulin replacement (10U/kg; ip) during the acquisition period in a conditioned place preference (CPP) paradigm. The diabetes model was induced by a single injection of STZ (60mg/kg; ip). The conditioning score was considered to be the difference in time spent in drug- and saline-paired compartments. The results demonstrated that the most effective doses of METH were 1 and 2mg/kg in non-diabetic animals. Although the place preference was not shown in non-diabetic animals at the dose of 0.5mg/kg, this dose significantly induced place preference to METH in STZ-diabetic rats. Additionally, insulin replacement could reverse the METH-induced CPP in diabetic animals. Our findings suggest that the positive effect of insulin deficiency on METH rewarding properties is dependent on insulin level in part, and the replacement of the insulin in diabetic rats as a treatment can improve the rewarding properties of METH. PMID:25444864

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

    PubMed Central

    2012-01-01

    Aim of the study This study was made to investigate the antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala, (Buch.-Ham.) Nees & Eberm (Tejpat) oil (CTO) in streptozotocin (STZ) induced diabetes in rats along with evaluation of chemical constituents. Materials and methods The GC-MS (Gas chromatography–mass spectrometry) analysis of the oil showed 31 constituents of which cinnamaldehyde was found the major component (44.898%). CTO and cinnamaldehyde was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic models. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. Results CTO (100?mg/kg and 200?mg/kg), cinnamaldehyde (20?mg/kg) and glibenclamide (0.6?mg/kg) in respective groups of diabetic animals administered for 28?days reduced the blood glucose level in streptozotocin induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in the blood glucose, glycosylated hemoglobin and total plasma cholesterol in test groups as compared to control group. The results of CTO and cinnamaldehyde were found comparable with standard drug glibenclamide. In vitro antioxidant studies on CTO using various models showed significant antioxidant activity. In vivo antioxidant studies on STZ induced diabetic rats revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH). Conclusion Thus the investigation results that CTO has significant antidiabetic, antioxidant and hypolipidemic activity. PMID:22882757

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

    PubMed Central

    2014-01-01

    Background Diabetes mellitus is a heterogeneous metabolic disorders characterized by abnormally high levels of blood glucose The main objective of the present work is to study the effect of Alpinia calcarata on glucose uptake in streptozotocin (STZ) induced diabetic rats. Methods The diabetes was induced by single dose of STZ (45 mg/kg) in citrate buffer, while the normal control group was given the vehicle (citrate buffer) only. After induction of diabetes, the diabetic animals were treated with ethanolic extract of Alpinia calcarata (200 mg/kg) and glibenclamide (2 mg/kg) for 30 days. Blood glucose estimation was performed every week of the study. At the end of study period, animals were sacrificed for biochemical studies. Results Streptozotocin induced diabetic rats shows the altered levels of various biochemical profiles. Those levels were brought back to near normal upon treatment with ethanolic extract of Alpinia calcarata and standard drug glibanclamide. No significant changes were observed on treatment with plant extract alone group indicated that there are no toxic substances present in Alpinia calcarata. The antidiabetic activity of plant extract was also further confirmed by histopathological studies. The ethanolic extract of Alpinia calcarata shows significant inhibition of alpha glucosidase activity and also enhancing the glucose uptake in rat hemidiaphragm. Conclusions In conclusion, the ethanolic extract of Alpinia calcarata ameliorates the condition associated with diabetes. PMID:24502532

  11. Quantitative-profiling of neurotransmitter abnormalities in the disease progression of experimental diabetic encephalopathy rat.

    PubMed

    Zhou, Xueyan; Zhu, Qiuxiang; Han, Xiaowen; Chen, Renguo; Liu, Yaowu; Fan, Hongbin; Yin, Xiaoxing

    2015-11-01

    Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters. Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF, hippocampus, and cortex were all significantly down-regulated as early as 6 weeks in the STZ treatment group. In contrast, the glutamate (Glu) levels were decreased in CSF and the hippocampus, but unaffected in the serum and cortex of STZ-treated rats. As for ?-aminobutyric acid (GABA), it was down-regulated in serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated group. The mRNA expressions of neurotransmitter-related rate limiting enzymes (including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL-1? and TNF-?) were all increased in the DE rats. Our data suggest that DM induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and that neuroinflammation may underlay the nervous system dysfunction observed in the progression of DE. PMID:26426748

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

    PubMed

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

    2007-01-01

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

  13. Development of Selective Axonopathy in Adult Sensory Neurons Isolated From Diabetic Rats

    PubMed Central

    Zherebitskaya, Elena; Akude, Eli; Smith, Darrell R.; Fernyhough, Paul

    2009-01-01

    OBJECTIVE Reactive oxygen species (ROS) are pro-oxidant factors in distal neurodegeneration in diabetes. We tested the hypothesis that sensory neurons exposed to type 1 diabetes would exhibit enhanced ROS and oxidative stress and determined whether this stress was associated with abnormal axon outgrowth. RESEARCH DESIGN AND METHODS Lumbar dorsal root ganglia sensory neurons from normal or 3- to 5-month streptozotocin (STZ)-diabetic rats were cultured with 10 or 25–50 mmol/l glucose. Cell survival and axon outgrowth were assessed. ROS were analyzed using confocal microscopy. Immunofluorescent staining detected expression of manganese superoxide dismutase (MnSOD) and adducts of 4-hydroxy-2-nonenal (4-HNE), and MitoFluor Green dye detected mitochondria. RESULTS Dorsal root ganglion neurons from normal rats exposed to 25–50 mmol/l glucose did not exhibit oxidative stress or cell death. Cultures from diabetic rats exhibited a twofold (P < 0.001) elevation of ROS in axons after 24 h in 25 mmol/l glucose compared with 10 mmol/l glucose or mannitol. Perikarya exhibited no change in ROS levels. Axonal outgrowth was reduced by approximately twofold (P < 0.001) in diabetic cultures compared with control, as was expression of MnSOD. The antioxidant N-acetyl-cysteine (1 mmol/l) lowered axonal ROS levels, normalized aberrant axonal structure, and prevented deficits in axonal outgrowth in diabetic neurons (P < 0.05). CONCLUSIONS Dorsal root ganglia neurons with a history of diabetes expressed low MnSOD and high ROS in axons. Oxidative stress was initiated by high glucose concentration in neurons with an STZ-induced diabetic phenotype. Induction of ROS was associated with impaired axonal outgrowth and aberrant dystrophic structures that may precede or predispose the axon to degeneration and dissolution in human diabetic neuropathy. PMID:19252136

  14. Bioactive fraction of Saraca indica prevents diabetes induced cataractogenesis: An aldose reductase inhibitory activity

    PubMed Central

    Somani, Gauresh; Sathaye, Sadhana

    2015-01-01

    Background: The present study was designed to investigate the effect of Saraca indica (SI) flowers extract and different bioactive fraction on in vitro aldose reductase (AR) inhibitory activity, high glucose-induced cataract in goat lens and in vivo streptozotocin (STZ; 45 mg/kg, i.p) induced cataract in rats. Methods: Extract of flowers of SI tested for inhibition against rat lens AR. Furthermore, bioactive fraction was investigated against high glucose-induced opacification of the lens in vitro lens culture and STZ induced diabetic cataract in rats. Identification of the bioactive component was attempted through high-performance thin-layer chromatography, high-performance liquid chromatography and liquid chromatography-mass spectrometry analysis. Results: Ethyl acetate fraction of S. indica (EASI) produced maximum inhibition that may be due to high phenolic content. Goat lenses in media containing glucose developed a distinctly opaque ring in 72 h and treatment with EASI fraction lowered lens opacity in 72 h. Prolonged treatment with EASI to STZ-induced diabetic rats inhibited the AR activity and delayed cataract progression in a dose dependent manner. Conclusion: Ethyl acetate fraction of S. indica fraction has potential to inhibit rat lens AR enzyme and prevent cataractogenesis not only in goat lens model (in vitro), but also in STZ induced diabetic rats (in vivo). This study is suggestive of the anticataract activity of EASI fraction that could be attributed to the phytoconstituents present in the same. PMID:25709218

  15. Herbal formulation, DIA-2 and Rosiglitazone ameliorates hyperglycemia and hepatic steatosis in type 2 diabetic rats.

    PubMed

    Kesavanarayanan, K S; Priya, R J; Selvakkumar, C; Kavimani, S; Prathiba, D

    2015-08-01

    DIA-2 is a herbal mixture containing standardized extract of Allium sativum and Lagerstroemia speciosa. Recently we have reported the anti-diabetic effect of DIA-2 in high fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic (T2D) rats. The purpose of this study was to investigate and compare the effects of DIA-2 with Rosiglitazone (RG) on plasma biomarkers of hepatocellular injury, liver carbohydrate metabolizing enzymes, glycogen content, oxidant/antioxidant status and histopathological changes in T2D rats. ALT and ALP levels were significantly decreased after DIA-2 and RG treatment compared to T2D rats. Total protein and albumin remained unaltered in all the groups. Significant decrease in AST levels were observed after DIA-2 (125 mg/kg) and RG treatment. Hepatic hexokinase activity was significantly increased after RG and DIA-2 treatment and fructose-1, 6-bisphosphatase activity were inversely correlated with hexokinase activity. Hepatic gucose-6-phosphatase activity was significantly (p < 0.05) reduced after DIA-2 (62.5 mg/kg) and RG treatment. Lipid peroxides levels was significantly decreased in the liver of DIA-2 (62.5; p < 0.01 & 125 mg/kg; p < 0.05) treated animals. Hepatic glycogen content (p < 0.05) and antioxidant enzymes [SOD (p < 0.01; 62.5 mg/kg); GPx and GSH (125 mg/kg; p < 0.01)] were significantly increased after DIA-2 treatment. RG treatment on hepatic glycogen, GPx (p < 0.01) and SOD, GSH (p < 0.05) levels were significant when compared to T2D rats. These biochemical parameters were also correlated with histopathological evaluation. The above findings revealed that administration of DIA-2 could ameliorate the biochemical and histopathological changes in liver of T2D rats indicating the protective role of DIA-2 against HFD/STZ induced diabetes. In addition, DIA-2 and RG treatment resulted in amelioration of hepatic steatosis in T2D rats. PMID:26367735

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

    PubMed Central

    2014-01-01

    Background 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-?B (NF-?B) activation in anti-inflammatory pathways. We hypothesized that ruscogenin protects against diabetic nephropathy (DN) by inhibiting NF-?B-mediated inflammatory pathway. To test this hypothesis, the present study was to examine the effects of ruscogenin in rats with streptozotocin (STZ)-induced DN. Methods 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. Results 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-?B 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-?1 and fibronectin in the diabetic kidneys. Conclusions Our data demonstrated that ruscogenin suppressed the inflammation and ameliorated the structural and functional abnormalities of the diabetic kidney in rats might be associated with inhibition of NF-?B mediated inflammatory genes expression. PMID:24666993

  17. Embelia ribes extract reduces high fat diet and low dose streptozotocin-induced diabetic nephrotoxicity in rats

    PubMed Central

    Chaudhari, Hemantkumar Somabhai; Bhandari, Uma; Khanna, Geetika

    2013-01-01

    Nephropathy associated with type 2 diabetes is the single most common cause of end-stage renal disease. The aim of the present study was to evaluate the preventive effect of ethanolic extract of Embelia ribes fruit (EER) against high fat diet (HFD) and low dose streptozotocin (STZ)-induced diabetic nephrotoxicity in Wistar rats. HFD-fed and low dose STZ (35 mg/kg, i.p)-induced diabetic rats were treated with EER (100 and 200 mg/kg/day) for 21 days while continuing on HFD. Preventive effects of EER were demonstrated by significant reduction (p< 0.01) in body weight gain, fasting blood glucose, blood pressure, serum lactate dehydrogenase (LDH), creatinine, alkaline phosphatase (ALP), total cholesterol and triglyceride levels, while elevation in serum albumin and total protein levels. Insulin sensitizing effects were seen during oral glucose tolerance testing. Further, EER treatment significantly (p< 0.01) decreased the kidney thiobarbituric acid-reactive substance (TBARS) levels, while increasing the superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels in diabetic rats. Histological studies of kidney also supported the experimental findings. Taken together, our data suggest that EER attenuates renal injury in type 2 diabetic rats, possibly by improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, blood pressure lowering, and inhibition of lipid peroxidation process.

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

    PubMed Central

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

    2012-01-01

    Although diabetic hepatopathy is potentially less common, it may be appropriate for addition to the list of target organ conditions related to diabetes. This study was designed to evaluate the hepatoprotective properties of green tea extract (GTE) in STZ-induced diabetes in rats. Wistar rats were made diabetic through single injection of STZ (75?mg/kg i.p.). The rats were randomly divided into four groups of 10 animals each: Group 1, healthy control; Group 2, nondiabetics treated with GTE administered orally (1.5%, w/v); Group 3, diabetics; Group 4, diabetics treated with GTE (1.5%, w/v) for 8 weeks. Serum biomarkers were assessed to determine hepatic injury. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were measured to assess free radical activity in the liver tissue. Hepatic antioxidant activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were also determined. The biochemical findings were matched with histopathological verifications. Liver MDA content and serum levels of ALT, AST, ALP, and bilirubin in Group 3 significantly increased compared to Group 1 (P < 0.05) and significantly decreased in Group 4 compared to Group 3 (P < 0.05). Serum albumin level and GSH, SOD, CAT, and GSH-Px contents of the liver in Group 3 were significantly decreased compared to Group 1 (P < 0.05) and were significantly increased in Group 4 compared to Group 3 (P < 0.05). Histopathologically, the changes were in the same direction with biochemical findings. This study proved the hepatoprotective activity of GTE in experimentally induced diabetic rats. PMID:22956978

  19. Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration.

    PubMed

    Soares, Ana F; Carvalho, Rui A; Veiga, Francisco J; Alves, Marco G; Martins, Fátima O; Viegas, Ivan; González, Juan D; Metón, Isidoro; Baanante, Isabel V; Jones, John G

    2012-10-01

    Type 1 diabetes subjects are characterized by impaired direct pathway synthesis of hepatic glycogen that is unresponsive to insulin therapy. Since it is not known whether this is an irreversible defect of insulin-dependent diabetes, direct and indirect pathway glycogen fluxes were quantified in streptozotocin (STZ)-induced diabetic rats and compared with STZ rats that received subcutaneous or intraperitoneal insulin (I-SC or I-IP). Three groups of STZ rats were studied at 18 days post-STZ treatment. One group was administered I-SC and another I-IP as two daily injections of short-acting insulin at the start of each light and dark period for days 9-18. A third group did not receive any insulin, and a fourth group of nondiabetic rats was used as control. Glycogen synthesis via direct and indirect pathways, de novo lipogenesis, and gluconeogenesis were determined over the nocturnal feeding period using deuterated water. Direct pathway was residual in STZ rats, and glucokinase activity was also reduced significantly from control levels. Insulin administration restored both net glycogen synthesis via the direct pathway and glucokinase activity to nondiabetic control levels and improved the lipogenic pathway despite an inefficient normalization of the gluconeogenic pathway. We conclude that the reduced direct pathway flux is not an irreversible defect of insulin-dependent diabetes. PMID:22850684

  20. Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats.

    PubMed

    Paterniti, Irene; Di Paola, Rosanna; Campolo, Michela; Siracusa, Rosalba; Cordaro, Marika; Bruschetta, Giuseppe; Tremolada, Gemma; Maestroni, Anna; Bandello, Francesco; Esposito, Emanuela; Zerbini, Gianpaolo; Cuzzocrea, Salvatore

    2015-12-15

    Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR. PMID:26607470

  1. Effect of Unripe Plantain (Musa paradisiaca) and Ginger (Zingiber officinale) on Blood Glucose, Body Weight and Feed Intake of Streptozotocin-induced Diabetic Rats

    PubMed Central

    M, Iroaganachi; C.O, Eleazu; P.N, Okafor; N, Nwaohu

    2015-01-01

    Objective: To determine the effect of unripe plantain (Musa paradisiaca) and ginger (Zingiber officinale) on blood glucose (BG), feed intake (FI) and weight of streptozotocin (STZ) induced diabetic rats. Methods: Twenty four male albino rats were used and were divided into 4 groups of 6 rats each. Group 1 (non-diabetic) and Group 2 (diabetic) received standard rat feed; Group 3 received unripe plantain incorporated feed (810 /kg body weight) and Group 4 received unripe plantain+ginger incorporated feed (710:100 g/kg body weight). The weights and FI of the rats were measured daily throughout the experimentation. Results: Groups 3 and 4 rats had 159.52% and 71.83% decreases in BG but 24.91% and 35.32% decreases in weights compared with groups 1 and 2 rats that had 2.09% and 22.94% increases in BG with 13.42% increase and 45.36% decrease in weights respectively. The FI of the experimental rats did not differ significantly from each other (P>0.05) at the end of experimentation. The standard rat feed contained higher amounts of Ca but lower amounts of Mg and Fe compared with the unripe plantain and unripe plantain+ginger incorporated feeds. Conclusion: Combination of unripe plantain and ginger at the dose used in the management of diabetes was not very effective compared with unripe plantain alone. PMID:25674161

  2. Protective effects of geraniol (a monoterpene) in a diabetic neuropathy rat model: attenuation of behavioral impairments and biochemical perturbations.

    PubMed

    Prasad, Sathya N; Muralidhara

    2014-09-01

    Involvement of oxidative stress, inflammatory response, and mitochondrial dysfunction in the development of diabetic neuropathy (DN) is well appreciated. The present study examines the potential of geraniol (GE), a well-known phytoconstituent commonly found in lemon, spices, rose oil, etc., to attenuate DN-associated oxidative/nitrosative stress by employing a streptozotocin (STZ) diabetic rat model. STZ-induced diabetic rats provided with oral supplements of GE (100 mg/kg bw/day, 8 weeks) exhibited significant improvement in tail-flick latency (sensory function) and the narrow beam test (motor function). Terminally, elevated levels of oxidative markers (reactive oxygen species, malondialdehyde, hydroperoxides) in cytosol of the sciatic nerve (SN) and in selected regions of the brain of diabetic rats were markedly reduced by GE supplements. Furthermore, GE significantly diminished the levels of protein carbonyls (a measure of protein oxidation) and nitrites in diabetic rats. In addition, in mitochondria, GE supplements restored the activities of enzymes, such as complexes I-III, succinate dehydrogenase, and citrate synthase, in brain regions of diabetic rats, with a concomitant reduction in the levels of oxidative markers. GE significantly lowered the enhanced cytosolic calcium levels and acetylcholinesterase activity in the SN and the brain regions of diabetic rats. Depleted dopamine levels evident in the SN and the cortex/striatum among diabetic rats were restored by GE. From our data, we hypothesize that GE may be a promising therapeutic candidate in the management of DN in humans. Further understanding of the molecular mechanisms of its neuromodulatory effects is essential in order to exploit its therapeutic efficacy. PMID:24752916

  3. Losartan reduces oxidative damage to renal DNA and conserves plasma antioxidant capacity in diabetic rats.

    PubMed

    Lodovici, Maura; Bigagli, Elisabetta; Tarantini, Francesca; Di Serio, Claudia; Raimondi, Laura

    2015-11-01

    Increased reactive oxygen species (ROS) levels produced by hyperglycemia and angiotensin-II (AT-II) are considered among the pathogenic factors in the malignant transformation of diabetic renal cells. We aimed to investigate the potential role of AT-II in the increased cancer risk seen in diabetes; measuring oxidative damage to renal DNA and protective antioxidant defenses, including adiponectin (Adp) and plasma antioxidant capacity by the Ferric Reducing Ability of Plasma (FRAP) method. In the kidney of streptozotocin (STZ)-induced (55?mg/kg) diabetic rats either treated or not treated for 3 weeks with losartan, an AT-II type 1 receptor antagonist (20?mg/kg/day); we measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels, as an index of oxidative DNA damage, circulating Adp and FRAP. Diabetic rats showed significantly higher 8-oxodGuo levels in renal DNA (8.48?±?0.98?×?10(-6) dG, mean?±?SEM n?=?11) than normoglycemic ones (1.18?±?0.04?×?10(-6) dG, mean?±?SEM, n=7) and lower plasma Adp and FRAP levels in comparison to normoglycemics. The treatment of diabetic rats with losartan significantly (P?diabetic rats. Losartan treatment preserves FRAP levels, reduces DNA oxidative injury and thus the carcinogenesis risk. Furthermore, our results indicate that Adp plasma levels are a further marker of oxidative injury to the kidney and confirm that it is an important part of the plasma antioxidant defense. PMID:25710927

  4. Ocular nerve growth factor administration counteracts the impairment of neural precursor cell viability and differentiation in the brain subventricular area of rats with streptozotocin-induced diabetes.

    PubMed

    Tirassa, Paola; Maccarone, Mattia; Carito, Valentina; De Nicolò, Sara; Fiore, Marco

    2015-05-01

    The ocular administration of nerve growth factor (NGF) as eye drops (oNGF) has been shown to exert protective effects in forebrain-injured animal models, including adult diabetes induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). This type 1 diabetes model was used in this study to investigate whether oNGF might extend its actions on neuronal precursors localised in the subventricular zone (SVZ). NGF or saline was administrated as eye drops twice daily for 2 weeks in rats with STZ-induced diabetes and healthy control rats. The expression of mature and precursor NGF and the NGF receptors, tropomyosin-related kinase A and neurotrophin receptor p75, and the levels of DNA fragmentation were analysed by ELISA and western blotting. Incorporation of bromodeoxyuridine was used to trace newly formed cells. Nestin, polysialylated neuronal cell adhesion molecule (PSA-NCAM), doublecortin (DCX) and glial fibrillary acidic protein antibodies were used to identify the SVZ cells by confocal microscopy. It was found that oNGF counteracts the STZ-induced cell death and the alteration of mature/pro-NGF expression in the SVZ. It also affects the survival and differentiation of SVZ progenitors. In particular, oNGF counteracts the reduction in the number of cells expressing PSA-NCAM/DCX (neuroblast type A cells) and the related reductions in the number and distribution of nestin/DCX-positive cells (C-type cells), or glia-committed cells (type B cells), observed in the SVZ of diabetic rats. These findings show that oNGF treatment counteracts the effect of type 1 diabetes on neuronal precursors in the SVZ, and further support the neuroprotective and reparative role of oNGF in the brain. PMID:25728260

  5. Effects of lichen extracts on haematological parameters of rats with experimental insulin-dependent diabetes mellitus.

    PubMed

    Colak, Suat; Geyiko?lu, Fatime; Aslan, Ali; Deniz, Gül?ah Y?ld?z

    2014-11-01

    The prevalence of diabetes mellitus in the world is steadily increasing. Oxidative stress contributes to the development of diabetic complications, including diabetic haematological changes. Lichens are used as food supplements and are also used as possible natural antioxidant, antimicrobial and anticancer agents. We hypothesized that antioxidant activity of lichens may decrease hyperglycaemia-induced oxidative stress and prevent the development of diabetic complications, including abnormality in haematological condition. Therefore, the effects of Cetraria islandica water extract (CIWE) and Pseudevernia furfuracea water extract (PFWE) on the haematological parameters of rats with type 1 DM were investigated for the first time in the present study. Control Sprague-Dawley or streptozotocin (STZ)-induced diabetic rats were either untreated or treated with water lichen extracts (5-500 mg/kg body weight (bw)/day) for 2 weeks, starting at 72 h after STZ injection. On day 14, animals were anaesthetized and haematological and metabolic parameters were determined between control and experimental groups. In addition, the total oxidative stress (TOS), a specific indicator of oxidative stress, and the total antioxidant capacity (TAC) were measured by biochemical studies. In diabetic rats, CIWE of 250-500 mg/kg bw dose showed more prominent results when compared with doses of PFWE for TAC. The results obtained in the present study suggested that the antioxidant activities of lichens might be the possible reason behind the observed antihaematological status. However, the protective effect of lichen extracts were inadequate on diabetes-induced microcytic hypochromic anaemia. In addition, the extracts have no effect on metabolic complications. Our experimental data showed that high doses of CIWE and PFWE alone have no detrimental effect on blood cells and TOS status of plasma. Hence, they are safe and suitable for different administration routes. PMID:23114377

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

    PubMed Central

    Gireesh, G; Kumar, T Peeyush; Mathew, Jobin; Paulose, CS

    2009-01-01

    Acetylcholine (ACh), the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR) have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). Previous reports from our laboratory on streptozotocin (STZ) induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE) enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax) of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax) and affinity (Kd) of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors. PMID:19344500

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

    PubMed Central

    Kumar, Manoj; Sharma, Sunil; Vasudeva, Neeru

    2013-01-01

    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. PMID:24312861

  8. Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model

    PubMed Central

    Lubbad, Loay; Öberg, Carl M; Dhanasekaran, Subramanian; Nemmar, Abderrahim; Hammad, Fayez; Pathan, Javed Y; Rippe, Bengt; Bakoush, Omran

    2015-01-01

    Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ?20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (?) for FITC-Ficoll (molecular radius 20–90 Å) using size exclusion HPLC. The values of ? for FITC-Ficoll of radius >50 Å were significantly increased in STZ-diabetic rats compared to age-matched controls (? for 50–69 Å = 0.001 vs. 0.0002, and ? for 70–90 Å = 0.0007 vs. 0.00006, P < 0.001), while ? for FITC-Ficoll <50 Å tended to be lower in diabetic rats than in controls (? for 36–49 Å = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes. PMID:26009635

  9. Improvement of biochemical parameters in type 1 diabetic rats after the roots aqueous extract of yacon [Smallanthus sonchifolius (Poepp.& Endl.)] treatment.

    PubMed

    Oliveira, Gilberto Ornelas; Braga, Camila Pereira; Fernandes, Ana Angélica Henrique

    2013-09-01

    The aim of this study was to evaluate the effect of yacon (Smallanthus sonchifolius) (Poepp.& Endl.) on clinical parameters under diabetic conditions. The aqueous extract of yacon tuberous roots (YRAE; 0.76 g fructan kg?¹ body weight) was prepared at the moment of each administration. Thirty-two male rats were divided into four groups (n=8): control group (C); group that received YRAE (Y); untreated diabetic group (DM1); and diabetic group treated with YRAE (Y-DM1). The diabetes mellitus was induced by streptozotocin (60 mg kg?¹ body weight). The animals from Y2 and Y-DM1 received YRAE by gavage, at 7-day intervals, for 30 days. The aqueous extract of yacon roots decreased (p<0.05) the water and food intake in diabetic rats (Y-DM1). YRAE treatment reduced (p<0.05) glycaemia, total cholesterol, VLDL-c, LDL-c and triacylglycerol levels in diabetic rats (YRAE). HDL, urea and creatinine levels did not differ (p>0.05) between the Y and Y-DM1 groups. YRAE normalised alanine aminotransferase (ALT) activity, when comparing DM1 and Y-DM1 rats, but had no effect on lactate dehydrogenase activity (LDH). In conclusion, YRAE was sufficient for controlling water and food consumption, hyperglycaemia and dyslipidaemia, and promote the reduction of the ALT, suggesting a hepatoprotective effect in rats with STZ-induced DM1. PMID:23770327

  10. In vitro toxicity and antidiabetic activity of a newly developed polyherbal formulation (MAC-ST/001) in streptozotocin-induced diabetic Wistar rats.

    PubMed

    Yadav, Deepak; Chaudhary, Anis Ahmad; Garg, Veena; Anwar, Mohammad Faiyaz; Rahman, Md Mahfooz-ur; Jamil, Sayed Sakir; Khan, Haider Ali; Asif, Mohd

    2013-06-01

    The present study was designed to investigate the hypoglycemic effect of an aqueous extract of MAC-ST/001 (a new polyherbal formulation) which was given once daily to rats at different doses. The animals were divided into diabetic and nondiabetic control groups. The duration of each experiment lasted from 1 week to 1 month, and the results were compared with that of the standard hypoglycemic drug glibenclamide (10 mg/kg), which was given once daily. In this study, biochemical and histopathological parameters were studied in streptozotacin (STZ) (single intraperitoneal injection of 55 mg/kg)-induced diabetic rats. The diabetic rats showed a significant (p?diabetes. Cytotoxicity of MAC-ST/001 formulation was also studied on C2C12, 3T3-L1, and HepG2 cells through MTT assay. Histological examination of the liver and pancreas of normal control, diabetic control, and drug-treated rats revealed significant results. Finally, it was concluded that administration of this MAC-ST/001 extract reversed most blood and tissue changes caused by STZ-induced diabetes in rats. PMID:23053765

  11. Downregulation of apoptosis and modulation of TGF-?1 by sodium selenate prevents streptozotocin-induced diabetic rat renal impairment.

    PubMed

    Roy, Souvik; Dontamalla, Sudheer Kumar; Mondru, Anil Kumar; Sannigrahi, Santanu; Veerareddy, Prabhakar Reddy

    2011-01-01

    To investigate whether sodium selenate treatment would impact on the onset of diabetic nephropathy, we examined blood glucose, serum biochemical components, and interrelationship between oxidative stress, TGF-?1, and apoptosis in streptozotocin (STZ) induced diabetic rats. Sixty male Wistar rats were divided into six groups. Group I (n?=?10), normal control; Group II (n?=?10), diabetic control; Group III (n?=?10), sodium selenate (16 ?moles/kg) + diabetic; Group IV (n?=?10), sodium selenate (32 ?moles/kg) + diabetic; Group V (n?=?10), sodium selenate (16 ?moles/kg) control; and Group VI (n?=?10), sodium selenate (32 ?moles/kg) control. Sodium selenate was administered via orogastric route for 10 weeks. In the diabetic group, diabetes was induced by single intraperitoneal injection of STZ (50 mg/kg). The levels of blood glucose were estimated and total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, creatinine, urea, and albumin were detected in serum. Antioxidant status was examined by measuring the superoxide dismutase (SOD), catalase, glutathione, and lipid peroxidation in kidney tissues. Histopathological studies were performed in the kidney tissue sections. The expression of TGF-?1 was estimated by the immunohistochemical analysis in kidneys. Apoptotic study in kidney was performed using the TdT-mediated dUTP nick end labeling technique. It was observed that blood glucose, serum, total cholesterol, HDL cholesterol, triglycerides, creatinine, urea, and albumin were significantly higher in diabetic control groups. Diabetic + sodium selenate (16 and 32 ?moles/kg) significantly reduced blood glucose, serum, total cholesterol, HDL cholesterol, triglycerides, creatinine, urea, and albumin levels. Selenium-treated groups significantly increased antioxidant enzyme activities (SOD, catalase, and glutathione) in kidneys of diabetic rats. All enzyme activities of selenium control groups did not differ compared with the normal control. Sodium selenate reduces significantly lipid peroxidation in diabetic rats. Cellular architecture of the diabetic rats was altered whereas sodium selenate administration rectifies the degenerative changes of the kidney. Profound immunopositivity of TGF-?1 was observed in the glomerular and tubulointerstitial cells of diabetic rat kidney. Immunopositivity of TGF-?1 was significantly reduced in both low and high dose of sodium-selenate-treated rats (P?diabetic rats whereas sodium selenate in both doses significantly reduces the incidence of apoptosis (P?diabetic rats. PMID:20174975

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

    PubMed Central

    Patil, Madhoosudan A.; Suryanarayana, Palla; Putcha, Uday Kumar; Srinivas, Myadara

    2014-01-01

    Type 2 diabetes (T2D) generally follows prediabetes (PD) conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ) induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70%) of nSTZ injected pups developed IGT (nSTZ-PD) by two months but not cataract even after seven months, remaining (30%) nSTZ rats developed hyperglycemia (nSTZ-D) by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities. PMID:25505935

  13. Therapeutic potential of some plant extracts used in Turkish traditional medicine on streptozocin-induced type 1 diabetes mellitus in rats.

    PubMed

    Ozkol, Halil; Tuluce, Yasin; Dilsiz, Nihat; Koyuncu, Ismail

    2013-01-01

    Diabetes mellitus (DM) is known to impair many physiological functions. Some reports claim that medicinal plants can reduce these alterations caused by DM. The aim of this study was to investigate the therapeutic potential of aqueous-methanol extracts of Urtica dioica, Thymus vulgaris (TV), Myrtus communis (MC), Scolymus hispanicus (SH) and Cinnamomun zeylanicum (CZ) on streptozotocin (STZ)-induced type 1 DM in rats. Diabetes was induced via a single i.p. injection of STZ (65 mg/kg body weight). After 1 week to allow for development of diabetes, each plant extract was administered to diabetic rats separately at a dose of 100 mg/kg body weight daily for 28 days. The results showed that only SH extract significantly (P < 0.05) amended fasting blood glucose level. The lipid profile was ameliorated especially by supplementations of TV, MC and CZ extracts. Almost all plant extract treatments markedly (P < 0.05) increased reduced glutathione content and decreased lipid peroxidation levels of erythrocyte, plasma, retina and lens tissues. They also significantly (P < 0.05) amended erythrocyte catalase activity, levels of marker serum enzymes (except amylase), urea and blood urea nitrogen when compared to diabetic rats treated with nothing. Furthermore, none of the plant extracts counteracted body weight loss of diabetic rats. Our data revealed that the aforementioned plant extracts have remarkable potential to counteract DM-caused alterations, probably through their antioxidant and free radical-defusing effects. PMID:23052826

  14. The Effect of the Medicinal Mushrooms Agaricus brasiliensis and Ganoderma lucidum (Higher Basidiomycetes) on the Erythron System in Normal and Streptozotocin-Induced Diabetic Rats.

    PubMed

    Vitak, Taras Y; Wasser, Solomon P; Nevo, Eviatar; Sybirna, Nataliya O

    2015-01-01

    Diabetes mellitus (DM) is accompanied by the development of hypoxia, which disturbs the physicochemical properties of the erythrocyte membrane and further leads to the occurrence of anemia and a reduction of the lifespan. In response, the body activates compensatory reactions directed at a renewal of the red blood cell pool and an increase in tissue oxygenation. In this study the influence of Agaricus brasiliensis and Ganoderma lucidum medicinal mushroom mycelia on the erythron system of control and streptozotocin (STZ)-induced diabetic rats were investigated. Wistar outbred white male rats were intraperitoneally injected with saline (control rats) or STZ (50 mg/kg, DM rats) and orally treated with placebo or submerged culture mycelium powder (1 g/kg/day) for 2 weeks. Peripheral blood erythrocytes were collected. Hypoglycemic effects of A. brasiliensis and G. lucidum occurred in the diabetic rats, as evidenced by decreased blood glucose and glycosylated hemoglobin concentrations. In STZ-diabetic animals treated with submerged culture mycelium powder, an increase in the number of erythrocytes in the bloodstream (an antianemic effect), erythrocyte resistance to acid hemolysis, and the normalization of fetal hemoglobin concentrations, along with the intensification of erythropoiesis were observed. In conclusion, our results suggest that in diabetic animals A. brasiliensis and G. lucidum have therapeutic effects that manifest in hypoglycemic and antianemic action. PMID:25954911

  15. Antioxidant effects of maslinic acid in livers, hearts and kidneys of streptozotocin-induced diabetic rats: effects on kidney function.

    PubMed

    Mkhwanazi, Blessing N; Serumula, Metse R; Myburg, Rene B; Van Heerden, Fanie R; Musabayane, Cephas T

    2014-04-01

    Studies indicate that hyperglycemia-induced oxidative stress triggers the development of microvascular and macrovascular complications in diabetes. Accordingly, we hypothesized that maslinic acid (MA) prevents these complications due to its antioxidant properties. We, therefore, investigated the effects of 5-week MA treatment of streptozotocin (STZ)-induced diabetic rats on anti-oxidative status of cardiac, hepatic and renal tissues as well as on kidney function. Proximal tubular effects of MA were studied in anesthetized rats challenged with hypotonic saline after a 3.5?h equilibration for 4 h of 1 h control, 1.5?h treatment and 1.5?h recovery periods using lithium clearance. MA was added to the infusate during the treatment period. Oral glucose tolerance responses to MA were monitored in rats given a glucose load after an 18?h fast. Compared with untreated diabetic rats, MA-treated diabetic animals exhibited significantly low malondialdehyde (MDA, a marker of lipid peroxidation) and increased the activity of antioxidant enzymes; superoxide dismutase and glutathione peroxidase in hepatic, cardiac and renal tissues. The expressions of gastrocnemius muscle GLUT4 and kidney GLUT1 and GLUT2 were assessed to elucidate the mechanism of the hypoglycemic effects of MA. MA-treatment diminished the expression of GLUT1 and GLUT2 in diabetic kidney and reduced glycemia values of diabetic rats. MA administration increased urinary Na+ outputs and additionally the FENa indicating that at least part of the overall reduction in Na+ reabsorption occurred in the proximal tubules. These results suggest antioxidant effects of MA can ameliorate oxidative stress and improve kidney function in diabetes mellitus. PMID:24344651

  16. Tripterygium Glycosides Tablet Ameliorates Renal Tubulointerstitial Fibrosis via the Toll-Like Receptor 4/Nuclear Factor Kappa B Signaling Pathway in High-Fat Diet Fed and Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ma, Ze-jun; Zhang, Xiao-na; Li, Li; Yang, Wei; Wang, Shan-shan; Guo, Xin; Sun, Pei; Chen, Li-ming

    2015-01-01

    Tripterygium glycosides tablet (TGT) is a Chinese traditional medicine that has been shown to protect podocytes from injury and reduce the proteinuria. The aim of this study was to assess the effect of TGT on renal tubulointerstitial fibrosis and its potential mechanism in high-fat diet fed and STZ-induced diabetic rats. Rats were randomly divided into normal control rats (NC group), diabetic rats without drug treatment (DM group), and diabetic rats treated with TGT (1, 3, or 6?mg/kg/day, respectively) for 8 weeks. The results showed that 24?h proteinuria and urinary N-acetyl-glucosaminidase (NAG) in diabetic rats were decreased by TGT treatment without affecting blood glucose. Masson's trichrome stains showed that apparent renal tubulointerstitial fibrosis was found in DM group, which was ameliorated by TGT treatment. The expression of ?-SMA was significantly decreased, accompanied by increased expression of E-cadherin in TGT-treated rats, but not in untreated DM rats. Further studies showed that TGT administration markedly reduced expression of TLR4, NF-?B, IL-1?, and MCP-1 in TGT-treated diabetic rats. These results showed that TGT could ameliorate renal tubulointerstitial fibrosis, the mechanism which may be at least partly associated with the amelioration of EMT through suppression of the TLR4/NF-?B pathway. PMID:26347890

  17. Characterization of L-type calcium channel activity in atrioventricular nodal myocytes from rats with streptozotocin-induced Diabetes mellitus

    PubMed Central

    Yuill, Kathryn H; Al Kury, Lina T; Howarth, Frank Christopher

    2015-01-01

    Cardiovascular complications are common in patients with Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. We have previously shown that spontaneous cellular electrical activity is altered in atrioventricular nodal (AVN) myocytes, isolated from the streptozotocin (STZ) rat model of type-1 DM. In this study, utilizing the same model, we have characterized the changes in L-type calcium channel activity in single AVN myocytes. Ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with STZ-induced diabetes. Patch-clamp recordings were used to assess the changes in cellular electrical activity in individual myocytes. Type-1 DM significantly altered the cellular characteristics of L-type calcium current. A reduction in peak ICaL density was observed, with no corresponding changes in the activation parameters of the current. L-type calcium channel current also exhibited faster time-dependent inactivation in AVN myocytes from diabetic rats. A negative shift in the voltage dependence of inactivation was also evident, and a slowing of restitution parameters. These findings demonstrate that experimentally induced type-1 DM significantly alters AVN L-type calcium channel cellular electrophysiology. These changes in ion channel activity may contribute to the abnormalities in cardiac electrical function that are associated with high mortality levels in patients with DM. PMID:26603460

  18. Gender-dimorphic regulation of DJ1 and its interactions with metabolic proteins in streptozotocin-induced diabetic rats

    PubMed Central

    Chaudhari, Harmesh N; Kim, Sang Woo; Yun, Jong Won

    2015-01-01

    Regulation of DJ1 is associated with a number of human diseases. To determine the involvement of DJ1 in progression of diabetes in a gender-dependent manner, we investigated its tissue-specific expression in streptozotocin (STZ)-induced diabetic male and female rats in this study. In animal experiments, females showed greater susceptibility towards developing diabetes because of lower insulin secretion and higher blood glucose levels as compared to male diabetic rats upon exposure to STZ. Immunoblotting confirmed sexually dimorphic regulation of DJ1 in various metabolic tissues such as the liver, pancreas and skeletal muscle. Immunofluorescence analysis revealed the location as well as reinforced the gender-dependent expression of DJ1 in hepatic tissue. Co-immunoprecipitation assay identified several interacting proteins with DJ1 whose functions were shown to be involved in various metabolic pathways viz. antioxidative and stress defence system, protein and methionine metabolism, nitrogen metabolism, urea metabolism, etc. Using GeneMANIA, a predictive web interface for gene functions, we showed for the first time that DJ1 may regulate T1DM via the JNK1 pathway, suggesting DJ1 interacts with other proteins from various metabolic pathways. We anticipate that the current data will provide insights into the aetiology of T1DM. PMID:25726699

  19. Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats

    PubMed Central

    Farshid, Amir Abbas; Tamaddonfard, Esmaeal

    2015-01-01

    Objectives: Crocin and safranal, the major constituents of saffron, exert neuroprotective effects. In the present study, we investigated the effects of crocin and safranal (alone or in combination with insulin) on peripheral neuropathy in diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (i.p.) injection of 60 mg/kg of streptozotocin (STZ) and confirmed by blood glucose level higher than 250 mg/dl. After confirmation of diabetes, crocin (30 mg/kg, i.p.), safranal (1 mg/kg, i.p.) (alone or in combination with insulin) and insulin (5 IU/kg, s.c.) were administered for eight weeks. Neuropathic pain was evaluated using acetone drop test. Histopathological changes of sciatic nerve were evaluated using light microscope. Blood glucose levels and sciatic nerve malondialdehyde (MDA) contents were also measured. Results: STZ caused cold allodynia, edema and degenerative changes of sciatic nerve, hyperglycemia and an elevation of sciatic nerve MDA levels. Crocin, safranal and insulin improved STZ-induced behavioral, histopathological and biochemical changes. Combined treatments produced more documented improving effects. Conclusion: The results of the present study showed neuroprotective effects of crocin, safranal and insulin in a rat model of diabetic neuropathy. In addition, crocin and safranal enhanced the neuroprotective effect of insulin. The neuroprotective effects of theses chemical compounds could be associated with their anti-hyperglycemic and antioxidant properties. PMID:26468467

  20. Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic Sprague-Dawley rats.

    PubMed

    Sani, Nur Fathiah Abdul; Belani, Levin Kesu; Sin, Chong Pui; Rahman, Siti Nor Amilah Abdul; Das, Srijit; Chi, Thent Zar; Makpol, Suzana; Yusof, Yasmin Anum Mohd

    2014-01-01

    Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P < 0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P < 0.05) in STZ-induced diabetic rats compared to diabetic control rats. PMID:24822178

  1. Effect of hypothalamic-pituitary-adrenal axis alterations on glucose and lipid metabolism in diabetic rats.

    PubMed

    Si, M W; Yang, M K; Fu, X D

    2015-01-01

    This study investigated the relationship between alterations in the hypothalamic-pituitary-adrenal (HPA) axis function and glucose and lipid metabolism in diabetic rats. To accomplish this a diabetes model was established by jointly administering a long-term high-fat diet plus Streptozotocin (STZ; 50 mg/kg ip). The rats were randomly divided into four groups: 1) a normal control group, 2) a model group, 3) astragalus polysaccharide (APS) group, and 4) a metformin group. APS and metformin hydrochloride were administered intragastrically (100 mg?kg(-1)d(-1)). Rat blood glucose and body weight were measured once per week, and urine was collected for 24 h after 30 days of administration of APS. The levels of blood lipids, insulin, and corticosterone (CORT), as well as hypothalamic CRH, pituitary ACTH, urine sugar and CORT were measured. Compared with the normal control group, the levels of blood sugar, urine sugar, TC, and TG significantly increased in the model group, and the levels of hepatic glycogen and HDL-C decreased. Administration of APS was shown to reverse these changes. Furthermore, as compared with the normal control group, the levels of insulin and hypothalamic CRH in the model group decreased significantly, while the levels of plasma ACTH and CORT, pituitary ACTH, and urine CORT were elevated. Again, APS administration improves these outcomes and returns their levels to normal. Thus, the glucose and lipid metabolic disorder in the high-fat diet and STZ-induced diabetes model may be related to increased HPA axis activity. The hypoglycemic effect of the traditional Chinese medicine, ASP, may improve HPA axis functioning and aid in the treatment of diabetes. PMID:26345889

  2. Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

    PubMed

    da Silva, Márcia F; Natali, Antônio J; da Silva, Edson; Gomes, Gilton J; Teodoro, Bruno G; Cunha, Daise N Q; Drummond, Lucas R; Drummond, Filipe R; Moura, Anselmo G; Belfort, Felipe G; de Oliveira, Alessandro; Maldonado, Izabel R S C; Alberici, Luciane C

    2015-07-15

    We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts. PMID:25997948

  3. The effects of Cetraria islandica and Pseudevernia furfuracea extracts in normal and diabetic rats.

    PubMed

    Bak?r, Tülay Özhan; Geyikoglu, Fatime; Çolak, Suat; Türkez, Hasan; Aslan, Ali; Bak?r, Murat

    2015-12-01

    Lichens are symbiotic organisms composed of a fungus joined to a photosynthesizing partner that can be either an alga or a cyanobacterium. They can be used as a novel bioresource for natural antioxidants. However, there is also a need for further studies to validate the lichens used in medicinal remedies. This study covers a previously unrecognized effects of Cetraria islandica (CIAE) and Pseudevernia furfuracea (PFAE) in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250-500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anesthetized, metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), Masson trichrome and Congo red. Our experimental data showed that increasing doses of CIAE and PFAE did not have any detrimental effects on the studied parameters and the malondialdehyde level of kidney. CIAE extract showed prominent results compared to doses of PFAE extract for antioxidant capacity. However, the protective effect of CIAE extract was inadequate on diabetes-induced disorders and kidney damages. Moreover, animals subjected to diabetes mellitus (DM) therapy did not benefit unfortunately from the usage of increasing lichen doses due to their unchanged antioxidant activity to tissue. The results obtained in present study suggested that CIAE and PFAE are safe but the power of these is limited because of the intensive oxidative stress in kidney of type 1 diabetic rats. It is also implied that CIAE extract is especially suitable for different administration routes in DM. PMID:23833245

  4. Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of methanol/dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats

    PubMed Central

    2014-01-01

    Background Hypoglycemic and/or anti-hyperglycemic activities have been recorded with numerous plants, many of which are used as traditional herbal treatments of diabetes. Albizzia Lebbeck Benth. stem bark have been used in traditional medicine along with some preliminary reports on its hypoglycemic action. The aim of present investigation was to evaluate the antidiabetic and antioxidant activities of methanolic extract of stem bark of Albizzia Lebbeck Benth. in streptozotocin induced diabetic rats. Methods The powdered stem bark of Albizzia Lebbeck Benth.. was extracted with methanol (MeOH) using soxhlation method and subjected to phytochemical analysis. The methanol/dichloromethane extract of Albizzia Lebbeck Benth. (ALEx) was concentrated to dryness using Rotary Evaporator. Diabetes was experimentally induced in the rats by single intraperitoneal administration of Streptozotocin (60 mg/kg). They glycemic control was measured by the blood glucose, glycated heamoglobin and plasma insulin. The oxidative stress was evaluated in the liver and kidney by level of antioxidant markers and various biochemical parameters were assessed in diabetic control and extract treated rats. Results Streptozotocin induced diabetic rats depicted the increased blood glucose levels, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), diminished level of high density lipoprotein cholesterol (HDL-c) level and perturb level of antioxidant markers. Oral administration of MeAL at a concentration of 100, 200, 300 and 400 mg/kg b.w daily for 30 days results a momentous decrease in fasting blood glucose, glycated heamoglobin and enhancement of plasma insulin level as compared with STZ induced diabetic rats. Furthermore, it significantly (p?STZ induced diabetic rats. Histopathological studies suggest the diminution in the pancreatic, liver and cardiac muscle damage. Conclusion Our research exertion clearly indicates the considerable antihyperglycemic, antihyperlipidemic, antioxidant & pancreas/renal/hepatic/cardiac protective action of ALEx. PMID:25026962

  5. Preventive effect of danhong huayu koufuye on diabetic retinopathy in rats

    PubMed Central

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

    2011-01-01

    AIM To study the effects of danhong huayu koufuye (DHK) on fasting blood glucose (FBG) and diabetic retinopathy (DR) in streptozotocin (STZ)-induced type 1 diabetic rats to facilitate the rational usage of this drug. METHODS Diabetic rats were induced by injection of a single dose of STZ intraperitoneally at 50mg/kg. Flash electroretinogram (FERG) and oscillatory potentials (OPs) were used to measure retinal function. The microvascular perfusion of ears was performed to study the microcirculation in rats. FBG, body-weight, and 24-h urine volume, water intake and diet intake were also assessed. RESULTS DHK had no effect on FBG in normal rats. However, STZ + DHK group were significantly different from those of Model and moved toward those of normal control. It reversed the increase in diet intake (P?0.05 vs model control) and the loss in body-weight (P?0.05 vs model control) in diabetic rats. DHK decreased the FBG of diabetic rats by 25.6% (P?0.05) and 37.9% (P?0.01) after 14 and 21 days administration as compared with the model control, respectively. Moreover, DHK significantly increased the FERG b-wave amplitude by 80% (P?0.05 vs model control) and decreased the FERG b-wave latency by 15.3% (P?0.01 vs model control) after 24 days administration. The OP1 and OP2 amplitudes in DHK group were 2.6 (P?0.01) and 2.0 (P?0.01) times of model group after 24 days of DHK treatment, respectively. At the same time, OP1 and OP2 latencies in DHK group reduced by 16.0% (P?0.001) and 14.7% (P?0.001) as compared with the model control, respectively. Furthermore, the microvascular perfusion of DHK group was 2.4 times of model group (P?0.001) after 21 days administration. CONCLUSION DHK had no effect on normal FBG. But it had antihyperglycemic activity, and had a preventive and therapeutic effect on DR in diabetic rats. PMID:22553728

  6. Protective Effects of the Mushroom Lactarius deterrimus Extract on Systemic Oxidative Stress and Pancreatic Islets in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Mihailovi?, Mirjana; Arambaši? ?ovanovi?, Jelena; Uskokovi?, Aleksandra; Grdovi?, Nevena; Dini?, Svetlana; Vidovi?, Senka; Poznanovi?, Goran; Muji?, Ibrahim; Vidakovi?, Melita

    2015-01-01

    The aim of this study was to assess the in vivo effects of the extract of the medicinal mushroom, Lactarius deterrimus, when administered (60?mg/kg, i.p.) daily for four weeks to streptozotocin- (STZ-) induced diabetic rats. Diabetic rats treated with the L. deterrimus extract displayed several improved biochemical parameters in the circulation: reduced hyperglycemia, lower triglyceride concentration and reduced glycated hemoglobin, glycated serum protein, and advanced glycation end product (AGE) levels. This treatment also adjusted the diabetes-induced redox imbalance. Thus, higher activities of the antioxidative enzymes, superoxide dismutase, and catalase in the circulation were accompanied by increased levels of free intracellular thiols and glutathionylated proteins after treatment with the L. deterrimus extract. In addition to a systemic antioxidant effect, the administration of the extract to diabetic rats also had a positive localized effect on pancreatic islets where it decreased AGE formation, and increased the expression of chemokine CXCL12 protein that mediates the restoration of ?-cell population through the activation of the serine/threonine-specific Akt protein kinase prosurvival pathway. As a result, the numbers of proliferating cell nuclear antigen- (PCNA-) and insulin-positive ?-cells were increased. These results show that the ability of the L. deterrimus extract to alleviate oxidative stress and increase ?-cell mass represents a therapeutic potential for diabetes management. PMID:26221612

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

    PubMed Central

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

    2014-01-01

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

  8. Upregulation of PPAR? by Aegle marmelos ameliorates insulin resistance and ?-cell dysfunction in high fat diet fed-streptozotocin induced type 2 diabetic rats.

    PubMed

    Sharma, Ashok Kumar; Bharti, Saurabh; Goyal, Sameer; Arora, Sachin; Nepal, Saroj; Kishore, Kamal; Joshi, Sujata; Kumari, Santosh; Arya, Dharamvir Singh

    2011-10-01

    The global epidemic of type 2 diabetes demands the rapid evaluation of new and accessible interventions. This study investigated whether Aegle marmelos fruit aqueous extract (AMF; 250, 500 and 1000?mg/kg) improves insulin resistance, dyslipidemia and ?-cell dysfunction in high fat diet fed-streptozotocin (HFD-STZ)-induced diabetic rats by modulating peroxisome proliferator-activated receptor-? (PPAR?) expression. The serum levels of glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of ?-cell function (HOMA-B), lipid profile, TNF-? and IL-6 were evaluated. Further, the TBARS level and SOD activity in pancreatic tissue and PPAR? protein expression in liver were assessed. In addition, histopathological and ultrastructural studies were performed to validate the effect of AMF on ?-cells. The HFD-STZ treated rats showed a significant increase in the serum levels of glucose, insulin, HOMA-IR, TNF-?, IL-6, dyslipidemia with a concomitant decrease in HOMA-B and PPAR? expression. Treatment with AMF for 21?days in diabetic rats positively modulated the altered parameters in a dose-dependent manner. Furthermore, AMF prevented inflammatory changes and ?-cell damage along with a reduction in mitochondrial and endoplasmic reticulum swelling. These findings suggest that the protective effect of AMF in type 2 diabetic rats is due to the preservation of ?-cell function and insulin-sensitivity through increased PPAR? expression. PMID:21351301

  9. Allicin protects against myocardial apoptosis and fibrosis in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Yang; Qi, Hanping; Wang, Ye; Wu, Mingli; Cao, Yonggang; Huang, Wei; Li, Lei; Ji, Zhong; Sun, Hongli

    2012-06-15

    To evaluate the cardioprotective effect of allicin (AL) on myocardial injury of streptozotocin (STZ)-induced diabetic rats and to further explore its underlying mechanisms. Hyperglycemia was induced in rats by single intraperitoneal injection of STZ (40 mg/kg). Three days after STZ induction, the hyperglycemic rats (plasma glucose levels ? 16.7 mmol/l) were treated with AL by intraperitoneal injection at the doses of 4 mg/kg, 8 mg/kg, and 16 mg/kg daily for 28 days. The fasting blood glucose levels were measured on every 7th day during the 28 days of treatment. The body weight, blood glucose, and parameter of cardiac function were detected after 4 weeks to study the cardioprotective effects of AL on diabetic rats in vivo. The apoptotic index of cardiomyocytes was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The expressions of Fas, Bcl-2, CTGF, and TGF-?(1) protein were studied by immunohistochemistry. Laser scanning confocal microscopy technique was utilized to observe the effects of AL on intracellular calcium concentration ([Ca(2+)](i)) in rat ventricular cardiomyocytes. AL at the doses of 4 mg/kg, 8 mg/kg, and 16 mg/kg significantly reduced blood glucose levels in a dose-dependent manner and increased body weight as well compared with the model group. Hemodynamic parameters including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximum rate of left ventricular pressure rise and fall (+dp/dtmax and -dp/dtmax) were significantly restored back to normal levels in AL-treated (8 mg/kg and 16 mg/kg) rats compared with diabetic model rats. AL markedly inhibited cardiomyocyte apoptosis induced by diabetic cardiac injury. Further investigation revealed that this inhibitory effect on cell apoptosis was mediated by increasing anti-apoptotic protein Bcl-2 and decreasing pro-apoptotic protein Fas. Additional experiments demonstrated AL abrogated myocardial fibrosis by blocking the expressions of CTGF and TGF-?(1) protein. AL shows protective action on myocardial injury in diabetic rats. The possible mechanisms were involved in reducing blood glucose, correcting hemodynamic impairment, reducing Fas expression, activating Bcl-2 expression, decreasing intracellular calcium overload, inhibiting the expressions of TGF-?(1) and CTGF, and further improving cardiac function. PMID:22633288

  10. Alleviation of hyperglycemia and hyperlipidemia by Phyllanthus virgatus forst extract and its partially purified fraction in streptozotocin induced diabetic rats

    PubMed Central

    Hashim, Arshya; Khan, M. Salman; Ahmad, Saheem

    2014-01-01

    Since, we previously demonstrated that sequentially extracted methanolic fraction showed marked antioxidant and antidiabetic property in vitro, the present study was design to evaluate the beneficial effects of Phyllanthus virgatus methanolic extract and its partially purified fraction on hyperglycemia and hyperlipidemia in streptozotocin (STZ) induced diabetic rats. The plant extract was subjected to repeated thin layer chromatographic fractionation followed by GC-MS analysis of active fraction. TLC data illustrated the presence of six prominent bands and the prelimnary screening of these bands against ?-amylase inhibitory activity showed that the band with Rf value 0.514 has marked inhibitory property (IC50, 48 µg/ml). The diabetic rats were treated for four weeks with methanolic extract of P. virgatus (50 and 10 mg/rat/day), partially isolated active fraction (0.5 and 0.1 mg/rat/day) and glibenclamide (0.1 mg/rat/day). The level of fasting blood glucose (FBG), hemoglobin, glycated hemoglobin (HbA1c) and insulin were significantly alleviated in plant extract and partially purified fraction treated group after 28 days of administration. Moreover, total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein cholesterol (HDL-C) were also markedly ameliorated in the entire treatment group, with a maximum restoration observed in group treated with partially purified fraction (0.5 mg/rat/day). The results demonstrate a strong antidiabetic and hypolipidemic impact of plant extract and its partially purified fraction coupled with their potent antioxidative property, which can provide additional benefits in the inhibition of oxidative stress and hence in the prevention and treatment of diabetes as well as diabetes linked hyperlipidemia. PMID:26417304

  11. Curcumin modulates dopaminergic receptor, CREB and phospholipase c gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats

    PubMed Central

    2010-01-01

    Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, Bmax showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes. PMID:20513244

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

    PubMed

    Rashid, Kahkashan; Sil, Parames C

    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-?, IL1-? and IFN-?), 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. PMID:25541178

  13. Antihyperglycemic effect of thymoquinone and oleuropein, on streptozotocin-induced diabetes mellitus in experimental animals

    PubMed Central

    Sangi, Sibghatullah Muhammad Ali; Sulaiman, Mansour Ibrahim; El-wahab, Mohammed Fawzy Abd; Ahmedani, Elsamoual Ibrahim; Ali, Soad Shaker

    2015-01-01

    Background: Diabetes mellitus is one of the most important diseases related with endocrines. Its main manifestation includes abnormal metabolism of carbohydrates and lipids and inappropriate hyperglycemia that is caused by absolute or relative insulin deficiency. It affects humankind worldwide. Objectives: Our research was aimed to observe antihyperglycemic activity of thymoquinone and oleuropein. Materials and Methods: In this study, rats were divided into six groups, 6 rats in each. Diabetes was inducted by streptozotocin (STZ). The level of fasting blood glucose was determined for each rats during the experiment, doses of thymoquinone and oleuropein (3 mg/kg and 5 mg/kg) for both, were injected intraperitoneal. Pancreatic tissues were investigated to compare ?-cells in diabetic and treated rats. Result and Conclusion: It was found that thymoquinone and oleuropein significantly decrease serum Glucose levels in STZ induced diabetic rats. PMID:26664013

  14. Betaine inhibits vascularization via suppression of Akt in the retinas of streptozotocin-induced hyperglycemic rats

    PubMed Central

    KIM, YOUNG-GIUN; LIM, HYUNG-HO; LEE, SUH-HA; SHIN, MAL-SOON; KIM, CHANG-JU; YANG, HYEON JEONG

    2015-01-01

    Diabetic retinopathy is a severe microvascular complication amongst patients with diabetes, and is the primary cause of visual loss through neovascularization. Betaine is one of the components of Fructus Lycii. In the present study, the effects of betaine on the expression levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1? in association with the Akt pathway were investigated in the retinas of streptozotocin (STZ)-induced diabetic rats using western blot and immunohistochemical analyses. The results of the present study revealed that the expression levels of VEGF, HIF-1?, and Akt were increased in the retinas of the STZ-induced diabetic rats. Betaine treatment attenuated this increase in VEGF and HIF-1? expression via suppression of diabetes-induced Akt activation in the retinas of the diabetic rats. The results suggested that betaine may potentially be used to delay the onset of complications associated with diabetic retinopathy via inhibition of retinal neovascularization in patients with diabetes. PMID:25891515

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

    PubMed Central

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

    2013-01-01

    Background Cisplatin (CP) therapy as the most common potent chemotherapeutic process is accompanied by nephrotoxicity. The diabetic state may protect rat kidney against this toxicity, and magnesium (Mg) on the other hand may reduce the glucose level in diabetic animals. Objectives Current study was planned to investigate the effect of oral administration of magnesium supplementation on CP-induced nephrotoxicity in normal and Streptozocin (STZ)-induced diabetic rats. Materials and Methods Male Wistar rats were divided into seven groups and underwent two experiment protocols. As protocol 1, group 1 was considered as the sham group. Group 2 (CP group) received CP (2 mg/kg/d) for five consecutive days. Group 3 (CP + Mg group) received magnesium sulphate (MgSO4, 10 g/L added to the drinking water) for 10 days and then treated with CP from sixth day. As protocol 2, animals received a single dose of STZ (65 mg/kg i.p.). Three days after diabetes induction, animals were divided into four groups; Groups 4 (D group), 5 (D + CP group), and 7 (D + Mg + CP group) followed the same manner as groups 1 to 3, respectively; and group 6 (D + Mg group) was treated with MgSO4 alone for 10 days. Finally, blood samples were obtained, and all animals were killed for kidney tissue investigation. Results CP administration in normoglycemic rats significantly elevated the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) (P < 0.05). However, coadministration of CP and Mg statistically increased the serum levels of BUN and Cr in both normoglycemic and diabetic animals when compared to the rats treated with CP alone (P < 0.05), while the serum level of Mg was significantly increased in nondiabetic groups (P < 0.05). No significant changes were observed in serum and kidney levels of nitrite; as well as the testis weight between all normoglycemic groups, whereas Mg decreased kidney levels of nitrite in diabetic groups when accompanied by CP (P < 0.05). The kidney and serum levels of malondialdehyde (MDA) enhanced significantly in nondiabetic rats treated with Mg and CP (P < 0.05). Kidney tissue damage score (KTDS), kidney weight, and body weight loss were significantly different among normoglycemic groups (P < 0.05), and Mg promoted the KTDS in diabetic animals treated with CP. Conclusions Oral Mg supplementation did not protect the CP induced nephrotoxicity in diabetic rats. PMID:24350087

  16. Uncoupling protein-2 in diabetic kidneys: increased protein expression correlates to increased non-transport related oxygen consumption.

    PubMed

    Friederich, Malou; Olerud, Johan; Fasching, Angelica; Liss, Per; Hansell, Peter; Palm, Fredrik

    2008-01-01

    Diabetic patients have an elevated risk to develop renal dysfunction and it has been postulated that altered energy metabolism is involved. We have previously shown that diabetic rats have markedly decreased oxygen availability in the kidney, resulting from increased oxygen consumption. A substantial part of the increased oxygen consumption is unrelated to tubular transport, suggesting decreased mitochondrial efficiency. In this study, we investigated the protein expression of mitochondrial uncoupling protein (UCP)-2 in kidney tissue from control and streptozotocin (STZ)-induced diabetic rats. Protein levels of UCP-2 were measured in adult male control and STZ-diabetic Wistar Furth as well as Sprague Dawley rats in both the kidney cortex and medulla by Western blot technique. Two weeks of hyperglycemia resulted in increased protein levels of UCP-2 in kidneys from both Wistar Furth and Sprague Dawley rats. Both cortical and medullary UCP-2 levels were elevated 2-3 fold above control levels. We conclude that sustained STZ-induced hyperglycemia increases the kidney levels of mitochondrial UCP-2, which could explain the previously reported increase in non-transport related oxygen consumption in diabetic kidneys. The elevated UCP-2 levels may represent an effort to reduce the increased production of superoxide radicals which is evident during diabetes. PMID:18290312

  17. The cardioprotective effect of an aqueous extract of fermented rooibos (Aspalathus linearis) on cultured cardiomyocytes derived from diabetic rats.

    PubMed

    Dludla, P V; Muller, C J F; Louw, J; Joubert, E; Salie, R; Opoku, A R; Johnson, R

    2014-04-15

    Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle that contributes to cardiovascular deaths in the diabetic population. Excessive generation of free radicals has been directly implicated in the pathogenesis of DCM. The use of antioxidants, through dietary supplementation, to combat increased cellular oxidative stress has gained popularity worldwide. Aspalathus linearis (rooibos) is a popular herbal tea that contains a novel antioxidant, aspalathin. Literature has reported on the antidiabetic, anti-inflammatory and free radical scavenging effects of rooibos. However, its protective effect against DCM has not been established. Therefore, this study investigated whether chronic exposure to an aqueous extract of fermented rooibos (FRE) has an ex vivo cardioprotective effect on hearts obtained from streptozotocin (STZ) induced diabetic rats. Adult Wistar rats were injected with 40 mg/kg of STZ. Two weeks after STZ injection, cardiomyocytes were isolated and cultured. Cultured cardiomyocytes were treated with FRE (1 and 10 ?g/ml), vitamin E (50 ?g/ml), and n-acetyl cysteine (1mM) for 6h, before exposure to either hydrogen peroxide (H2O2) or an ischemic solution. Cardiomyocytes exposed to H2O2 or an ischemic solution showed a decrease in metabolic activity and glutathione content with a concomitant increase in apoptosis and intracellular reactive oxygen species. Pretreatment with FRE was able to combat these effects and the observed amelioration was better than the known antioxidant vitamin E. This study provides evidence that an aqueous extract of fermented rooibos protects cardiomyocytes, derived from diabetic rats, against experimentally induced oxidative stress and ischemia. PMID:24268738

  18. Diabetes decreases limbic extracellular dopamine in rats.

    PubMed

    Murzi, E; Contreras, Q; Teneud, L; Valecillos, B; Parada, M A; De Parada, M P; Hernandez, L

    1996-01-01

    Mesolimbic dopamine (DA) was measured by ventral striatum (including nucleus accumbens) microdialysis in freely moving streptozotocin (STZ)-diabetic male rats. DA and dihydroxyphenylacetic acid (DOPAC) basal levels and amphetamine-induced DA increase were lower in diabetic than in normal rats. These results are discussed in terms of decreased DA neuron activity and DA receptor hypersensitivity in the mesolimbic system of STZ-diabetic rats. PMID:8848251

  19. Roles of the co-culture of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells with rat pancreatic cells in the treatment of rats with diabetes mellitus

    PubMed Central

    WANG, GUANGYU; LI, YONG; WANG, YU; DONG, YU; WANG, FU-SHENG; DING, YI; KANG, YUDONG; XU, XUYING

    2014-01-01

    The aim of the present study was to investigate the roles of the co-culture of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hUC-MSCs) with rat pancreatic cells in the treatment of rats with diabetes mellitus. hUC-MSCs were isolated and passaged, followed by Transwell co-culture with rat pancreatic cells. The induced islet-like cell clusters were transplanted into the renal capsule in rats with streptozotocin (STZ)-induced diabetes mellitus. The effects of co-culture on blood glucose levels in rats were observed. The isolated hUC-MSCs expressed the specific surface markers, including cluster of differentiation 44 (CD44) (91.4%), CD29 (91.3%) and CD105 (99.2%). Following co-culture with hUC-MSCs for 7 and 10 days, the rat pancreatic cells were strongly stained by pancreatic and duodenal homeobox-1 and human insulin. The insulin and C-peptide concentrations were increased significantly compared to the pure culture group. One week following the transplantation of induced islet-like cells into the renal capsule, the blood glucose level of rats in the STZ experimental group was significantly lower than that of the STZ control group. There were notable 5-bromo-2?-deoxyuridine-positive nuclei and insulin-positive cytoplasm in the renal capsule following cell transplantation. Therefore, co-culture of hUC-MSCs with rat pancreatic cells can lower the blood glucose levels in rats with diabetes mellitus. PMID:25289028

  20. Modulation of Adipocytokines Production and Serum NEFA Level by Metformin, Glimepiride, and Sitagliptin in HFD/STZ Diabetic Rats

    PubMed Central

    Saad, Mohamed I.; Kamel, Maher A.; Hanafi, Mervat Y.

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a group of metabolic disorders characterized by hyperglycemia owing to insulin resistance and/or insulin deficiency. Current theories of T2DM pathophysiology include a decline in ?-cells function, a defect in insulin signaling pathways, and a dysregulation of secretory function of adipocytes. This study aimed to investigate the effect of different antidiabetic drugs on serum levels of certain adipocytokines and nonesterified fatty acids (NEFA) in high-fat diet (HFD)/streptozotocin- (STZ-) induced diabetic rats. All treatments significantly decreased serum NEFA level. Metformin and sitagliptin increased serum adiponectin level, whereas they decreased serum leptin level. Glimepiride showed significant decline in serum levels of both adiponectin and leptin. All treatments remarkably ameliorated insulin resistance, suggested by an improvement of glycemic control, a significant reduction in homeostasis model assessment of insulin resistance (HOMA-IR), and a correction in lipid profile. Modulation of adipocytokines production (i.e., increased serum adiponectin and decreased serum leptin) may also underlie the improvement of insulin resistance and could be a possible mechanism for the beneficial cardiovascular effects of metformin and sitagliptin. PMID:25838947

  1. ?-cell regenerative efficacy of a polysaccharide isolated from methanolic extract of Tinospora cordifolia stem on streptozotocin -induced diabetic Wistar rats.

    PubMed

    Rajalakshmi, Manikkam; Anita, Roy

    2016-01-01

    The use of herbal supplements either as extracts or plant-derived individual molecules has significantly increased in the process of drug discovery and development for their potential efficacy or reduced risk in treating human disorders. Tinospora cordifolia (T. cordifolia) is a widely used herbal source to treat various human ailments, including diabetes mellitus. The present study was aimed on evaluating the antidiabetic property of a novel polysaccharide isolated from the methanolic extract of T. cordifolia stem. Bioassay guided fractionation was followed to isolate a compound from the methanol extract. The compound was administered orally at a dose of 20 mg/kg.b.wt for 60 days to control and STZ-induced diabetic male Wistar rats. It was found that plasma glucose was significantly (p < 0.05) reduced compared to normal. Oral administration of the compound significantly decreased HBA1c, triglycerides and total cholesterol and at the same time markedly increased hemoglobin, tissue glycogen and HDL cholesterol. Also the compounds restored the altered carbohydrate metabolizing enzymes, insulin, C-peptide, (14)C-glucose oxidation levels to near normal. In addition, the histological studies revealed that there was regeneration of ?-cells in the pancreatic sections. The expression of Glut-4 mRNA and protein in the gasrtocnemius muscle were significantly enhanced after the compound treatment. These results confirm that the novel polysaccharide possesses hypoglycemic, glucose oxidizing, hypolipidemic and ?-cell regenerative properties and hence it could be developed into potential oral hypoglycemic drug with lesser side effects. PMID:26616445

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

    PubMed

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

    2005-04-29

    The present study was designed to investigate the hypoglycemic and hypolipidemic activities of the semi-purified fractions of an ethanolic leaf extract of Averrhoa bilimbi (ABe) in high fat diet (HFD)-streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats aged 10 weeks (200-250 g) were fed with a high fat diet obtained from Glen Forrest stock feeders (Western Australia) for 2 weeks prior to intraperitoneal injection with streptozotocin (STZ, 50 mg/kg). The leaves of A.bilimbi were exhaustively extracted with 80% ethanol, concentrated at 40 degrees C using a rotavapor and partitioned successively with butanol, ethylacetate and hexane to get aqueous (AF), butanol (BuF), ethylacetate (EF), and hexane fractions (HF). The fractions were freeze-dried to obtain powders of each. To investigate the effect of long term administration of the hypoglycemic fractions, diabetic animals were treated with vehicle (distilled water), AF (125 mg/kg), or BuF (125 mg/kg), twice a day for 14 days. The long term administration of AF and BuF at a dose of 125 mg/kg significantly (P < 0.05) lowered blood glucose and triglyceride concentrations when compared to the vehicle. The hepatic glycogen content was significantly higher (P < 0.05) in AF-treated rats when compared to diabetic control, however no change was found in the BuF-treated rats. Moreover, AF as well as BuF did not cause any significant change in the total cholesterol and HDL-cholesterol. There was also no difference in liver thiobarbituric acid reactive substances (TBARS) and cytochrome P450 values between AF, BuF and vehicle-treated control rats. In conclusion, the results indicate that AF is more potent than BuF in the amelioration of hyperglycemia and hyperlipidemia in HFD fed-STZ diabetic rats. Hence, AF is a potential source for the isolation of active principle(s) for oral anti-diabetic therapy. PMID:15808883

  3. Investigation into the cardiac effects of spironolactone in the experimental model of type 1 diabetes.

    PubMed

    Goyal, Bhoomika R; Solanki, Nilay; Goyal, Ramesh K; Mehta, Anita A

    2009-12-01

    We have studied the effect of 8-week treatment with spironolactone (20 mg*kg(-1)*day(-1)) on cardiovascular complications associated with streptozotocin (STZ)-diabetic rats. Wistar rats were made diabetic with STZ (45 mg/kg, intravenously). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzyme, and C-reactive protein levels; reduction in heart rate; and cardiac hypertrophy. Chronic treatment with spironolactone significantly prevented STZ-induced bradycardia, hypertension, and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly reduced the elevated cholesterol, very-low-density lipoprotein, and triglyceride levels and increased the lower high-density lipoprotein-cholesterol levels in diabetic rats. Furthermore, spironolactone also produced a significant reduction in the elevated creatinine levels, C-reactive protein, and levels of lactate dehydrogenase and creatinine kinase. It also produced beneficial effect in diabetic rats by preventing cardiac hypertrophy as evident from decrease in left ventricular collagen levels, cardiac hypertrophy index, and left ventricular hypertrophy index. Our data suggest that spironolactone prevents not only the STZ-induced metabolic abnormalities but also cardiovascular complications. PMID:19738487

  4. Beneficial effect of 17{beta}-estradiol on hyperglycemia and islet {beta}-cell functions in a streptozotocin-induced diabetic rat model

    SciTech Connect

    Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting

    2010-11-15

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

  5. Preventive Effect of Garlic (Allium sativum L.) on Serum Biochemical Factors and Histopathology of Pancreas and Liver in Streptozotocin- Induced Diabetic Rats

    PubMed Central

    Masjedi, Fatemeh; Gol, Ali; Dabiri, Shahriar

    2013-01-01

    Antidiabetic action of garlic is established in animal studies. Since all of the pervious studies have focused on the therapeutic role of garlic, this study investigated the preventive effect of garlic juice on biochemical factors and histological features in Streptozotocin (STZ)- induced diabetic rats. Forty male rats were divided into five groups (n = 8): 1-Normal group (N), 2-Normal+Garlic group (N+G) received garlic juice (1 mL/100g BW) for 6 weeks, 3-Diabetic group (D) was injected with STZ (60 mg/kg, IP), 4-Diabetic+Garlic-before group (D+Gb) received garlic juice for 3 weeks before STZ injection and continued for another 3 weeks, 5-Diabetic+Garlic-after group (D+Ga), three days after STZ injection, they received garlic juice for 3 weeks. Serum biochemical factors were measured by the enzymatic methods and H&E stained sections of pancreas and liver were prepared for light microscopy. In diabetic rats, elevated levels of glucose, cholesterol and triglycerides, the increment of the activities of ALT and AST, increased food and water consumption were observed. The abnormal increases were significantly (p < 0.05) decreased in D+Gb groups compared to D group. In D group, scattered degeneration of the hepatocytes with lymphocytic infiltration in the portal areas, decrease of pancreatic islets numbers and diameter, atrophy of pancreatic islets were observed. These abnormal histological signs were dramatically ameliorated in D+Gb group compared to D group. In D+Ga group compared to D+Gb group slighter effects of garlic juice on histopathological and biochemical changes were seen. These results indicate that garlic juice may help in the prevention of the complications of diabetes. PMID:24250639

  6. Effect of the hydroalcoholic extract and juice of Prunus divaricata fruit on blood glucose and serum lipids of normal and streptozotocin-induced diabetic rats

    PubMed Central

    Minaiyan, M.; Ghannadi, A.; Movahedian, A.; Ramezanlou, P.; Osooli, F.S.

    2014-01-01

    Prunus divaricata (Alloocheh) is a small tree cultivating in Iran, Middle East and central Asia. Prunus genus has many species with anti-oxidant, anti-hyperlipidemia and anti-hyperglycemia effects. In the present study the anti-diabetic and anti-hyperlipidemic effects of P. divaricata fruits were examined in normal and streptozotocin (STZ)-induced diabetic rats. Both groups, control and reference rats received normal saline and glibenclamide respectively. Test groups were treated with Prunus freeze dried juice (PFDJ, 200, 400, 800 mg/kg) and Prunus freeze dried extract (PFDE, 100, 200, 400 mg/kg) started at the 3rd day of the experiment and continued for 27 days thereafter. Weight changes of animals were checked periodically. Fasting blood glucose (FBG) level as well as serum triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were determined. Different treatments had no significant effect on body weight increments of normal rats, while in diabetic rats, PFDJ (800 mg/kg) and PFDE (400 mg/kg) opposed with weight loss. In acute phase of experiment (0-8 h of 3rd day), none of tested fractions were effective in reducing FBG and serum lipids of normal rats. During the sub-acute phase (13th and 30th days) however, the greatest test doses of PFDJ (800 mg/kg) and PFDE (400 mg/kg) induced hypoglycema. In diabetic groups, PFDJ and PFDE, at all test doses, could diminish FBG during sub-acute phase of the experiment. In addition, PFDJ and PFDE at most examined doses could diminish TG significantly and they were also effective on cholesterol derivatives in different magnitude. PMID:26339257

  7. Upregulation of podocyte-secreted angiopoietin-like-4 in diabetic nephropathy.

    PubMed

    Ma, Jing; Chen, Xiao; Li, Jian-Si; Peng, Lei; Wei, Shi-Yao; Zhao, Shi-Lei; Li, Tong; Zhu, Dan; He, Yi-Xin; Wei, Qiu-Ju; Li, Bing

    2015-06-01

    Podocyte injury plays a key role in the development of diabetic nephropathy (DN). Understanding the changes in podocyte structure and function in diabetes mellitus may lead to novel diagnostic tools and treatment strategies for DN. Albuminuria, histological alterations, and podocyte injury were detected at different time points in streptozotocin (STZ)-induced diabetic rats. Increased urinary albumin-to-creatinine ratios (ACR) and podocyte injury were significantly observed 4 weeks post-STZ injection. We determined the glomerular expression and distribution of angiopoietin-like 4 (Angptl4) by immunofluorescence and real-time PCR. Glomerular Angptl4 expression was mostly colocalized with synaptopodin, a podocyte marker, with substantial additional overlap with the glomerular basement membrane (GBM). This finding indicated that Angptl4 might be primarily secreted by podocytes and moved toward the GBM. Moreover, we observed by Western blot analysis and ELISA that the urinary Angptl4 level was gradually upregulated in both STZ-induced rats and diabetic patients with microalbuminuria and macroalbuminuria. We further found that the increased glomerular Angptl4 expression was closely related to the urinary ACR level and podocyte injury. In addition, the urinary Angptl4 expression was closely associated with albuminuria in the rats and patients with DN. This study is the first to show that podocyte-secreted Angptl4 is upregulated in DN and can be detected in urine. Angptl4 might function as a podocyte injury marker and could be a potential and novel diagnostic and therapeutic biomarker for DN. PMID:25424436

  8. The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Preserves Endothelial Function in Mesenteric Arteries from Type 1 Diabetic Rats without Decreasing Plasma Glucose

    PubMed Central

    Salheen, Salheen M.; Panchapakesan, Usha; Pollock, Carol A.; Woodman, Owen L.

    2015-01-01

    The aim of the study was to investigate the effect of the DPP-4 inhibitor linagliptin on the mechanism(s) of endothelium-dependent relaxation in mesenteric arteries from STZ-induced diabetic rats. Both normal and diabetic animals received linagliptin (2 mg/kg) daily by oral gavage for a period of 4 weeks. To measure superoxide generation in mesenteric arteries, lucigenin-enhanced chemiluminescence was used. ACh-induced relaxation of mesenteric arteries was assessed using organ bath techniques and Western blotting was used to investigate protein expression. Pharmacological tools (1?M TRAM-34, 1?M apamin, 100 nM Ibtx, 100 ?M L-NNA, 10 ?M ODQ) were used to distinguish between NO and EDH-mediated relaxation. Linagliptin did not affect plasma glucose, but did decrease vascular superoxide levels. Diabetes reduced responses to ACh but did not affect endothelium-independent responses to SNP. Linagliptin improved endothelial function indicated by a significant increase in responses to ACh. Diabetes impaired the contribution of both nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) to endothelium-dependent relaxation and linagliptin treatment significantly enhanced the contribution of both relaxing factors. Western blotting demonstrated that diabetes also increased expression of Nox2 and decreased expression and dimerization of endothelial NO synthase, effects that were reversed by linagliptin. These findings demonstrate treatment of type 1 diabetic rats with linagliptin significantly reduced vascular superoxide levels and preserved both NO and EDH-mediated relaxation indicating that linagliptin can improve endothelial function in diabetes independently of any glucose lowering activity. PMID:26618855

  9. Effects of 4-phenylbutyric acid on the process and development of diabetic nephropathy induced in rats by streptozotocin: Regulation of endoplasmic reticulum stress-oxidative activation

    SciTech Connect

    Luo Zhifeng; Feng Bing; Mu Jiao; Qi Wei; Zeng Wei; Guo Yanhong; Pang Qi; Ye Zilin; Liu Li; Yuan Fahuan

    2010-07-15

    Oxidative stress may contribute to the pathogenesis of diabetic nephropathy (DN), although the precise regulatory mechanism is still unclear. Recent reports have shown that chemical molecular chaperone 4-phenylbutyric acid (4-PBA) can suppress oxidative stress by attenuating endoplasmic reticulum (ER) stress. We therefore hypothesized that 4-PBA could provide renoprotection through the suppression of oxidative stress in DN rats. Male Sprague-Dawley (SD) rats were randomly divided into three groups: a normal control (NC) group, a streptozotocin (STZ)-induced DN model group, and a DN plus 4-PBA (1 g/kg) treatment group. At the end of 4, 8, and 12 weeks, hydroxyproline content, NADPH oxidase activity and the expression of phosphorylation of inositol-requiring enzyme-1{alpha} (p-IRE1{alpha}), p47phox, nitrotyrosine (NT) and NF-E2-related factor 2 (Nrf2) in the kidneys of all rats were determined; malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in serum and urine were also detected; renal nuclear factor {kappa}B (NF-{kappa}B) activity in all of the rats was examined at the end of 12 weeks. Compared with the NC group, the DN rats showed a significant increase in hydroxyproline content, NADPH oxidase activity, NF-{kappa}B activity, the expression of p-IRE1{alpha}, p47phox, NT and Nrf2 in renal tissue; markedly, MDA levels were higher and SOD activity was lower in serum and urine of DN rats than in NC rats for the indicated time. These alterations were inhibited by the administration of 4-PBA. These findings first demonstrated that treatment with 4-PBA significantly inhibits the process and development of diabetic nephropathy in rats through the regulation of ER stress-oxidative activation.

  10. Antihyperglycemic Potential of Grewia asiatica Fruit Extract against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms

    PubMed Central

    Khattab, Hala A. H.; El-Shitany, Nagla A.; Abdallah, Inas Z. A.; Yousef, Fatimah M.; Alkreathy, Huda M.

    2015-01-01

    Diabetes mellitus is regarded as a serious chronic disease that carries a high risk for considerable complications. In folk medicine, the edible Grewia asiatica fruit is used in a number of pathological conditions. This study aimed to investigate the possible curative effect of G. asiatica fruit ethanolic extract against streptozotocin- (STZ-) induced hyperglycemia in rats. Furthermore, mechanism of antihyperglycemic action is investigated. Hyperglycemic rats are either treated with 100 or 200?mg/kg/day G. asiatica fruits extract. Serum glucose, liver glycogen, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin- (IL-) 1?, and tumor necrosis factor- (TNF-) ? are measured. G. asiatica fruits extract reduces blood glucose and pancreatic MDA levels. It increases liver glycogen and pancreatic GSH contents and SOD enzyme activity. Furthermore, Grewia asiatica fruits extract decreases serum IL-1? and TNF-?. The treatment also protects against STZ-induced pathological changes in the pancreas. The results of this study indicated that G. asiatica fruit extract exerts antihyperglycemic activity against STZ-induced hyperglycemia. The improvement in the pancreatic ?-cells and antioxidant and anti-inflammatory effects of G. asiatica fruit extract may explain the antihyperglycemic effect. PMID:26347423

  11. Antidiabetic effect of Korean traditional Baechu (Chinese cabbage) kimchi in a type 2 diabetes model of rats.

    PubMed

    Islam, Md Shahidul; Choi, Haymie

    2009-04-01

    The present study was conducted to examine the antidiabetic effects of two dietary dosages (0.5% and 2.0%) of freeze-dried Korean traditional Baechu (Chinese cabbage) kimchi in a high-fat (HF) diet-fed, streptozotocin (STZ)-induced type 2 diabetes (T2D) rat model. Five-week-old male Sprague-Dawley rats were fed HF diet for 2 weeks and then randomly divided into four groups of eight animals: normal control (NC), diabetic control (DBC), kimchi low (KML) (0.5%), and kimchi high (KMH) (2.0%) groups. Diabetes was induced by an intraperitoneal injection of STZ (40 mg/kg of body weight) in all groups except the NC group. After 4 weeks of feeding of experimental diets, serum insulin concentrations and Homeostatic Model Assessment pancreatic beta-cell function were increased and blood glycated hemoglobin was decreased in the kimchi-fed groups compared to the DBC group, while a significant (P < .05) difference was observed only in the KMH group for serum insulin concentration. Lower fasting blood glucose and better glucose tolerance were observed in the KMH group compared to the DBC and KML groups; however, differences were not significant. Food intake, body weight gain, Homeostatic Model Assessment insulin resistance index, and serum lipid profiles were not significantly influenced by kimchi-containing diets. Data of this study suggest that dietary Baechu kimchi has some antidiabetic effects even when fed with a HF-containing diet. Better results are possible if it is consumed with normal or low-fat rather than HF-containing diet. PMID:19459728

  12. Protective action of Citrullus colocynthis seed extracts against the deleterious effect of streptozotocin on both in vitro glucose-stimulated insulin release from rat pancreatic islets and in vivo glucose homeostasis.

    PubMed

    Benariba, Nabila; Bellakdhar, Wafaa; Djaziri, Rabeh; Hupkens, Emeline; Louchami, Karim; Malaisse, Willy J

    2013-01-01

    Citrullus colocynthis extracts improve glucose homeostasis in alloxan- or streptozotocin (STZ)-induced diabetic rats. Little is known, however, regarding the protective effect of these extracts against the ?-cytotoxic action of STZ. In the present study, an H2O-methanol extract was found to suppress the inhibition of glucose-stimulated insulin secretion by STZ in rat-isolated pancreatic islets. Similarly, when an aqueous extract from Citrullus colocynthis seeds was injected daily for 21 days prior to STZ administration, the perturbation of glucose homeostasis otherwise generated by the ?-cytotoxic agent was minimized in rats. PMID:24648906

  13. Nutraceutical potential of Aerva lanata (L.) Juss. ex Schult ameliorates secondary complications in streptozotocin-induced diabetic rats.

    PubMed

    Riya, M P; Antu, K A; Pal, S; Srivastava, A K; Sharma, S; Raghu, K G

    2014-09-01

    Nutraceuticals provide health benefits beyond their basic nutrition by modulating a number of biochemical pathways. They are derived from natural products and have gained recognition worldwide as an adjuvant or therapy in the treatment of metabolic disorders such as diabetes. Although the regulation of blood glucose with drugs and insulin greatly reduces the incidence of secondary complications, the need for long-term treatment raises issues of tolerance and affordability. Therefore, the aim of the present study is to explore the nutraceutical potential of Aerva lanata, a herb widely used for its culinary and therapeutic potential in streptozotocin (STZ)-induced diabetic rats. Treatment with 70% ethanolic extract (ALE) at 500 mg per kg b.w per day for 21 days significantly improved the fasting blood glucose (120.33 ± 1.99 mg dL(-1)), insulin level (9.81 ± 0.38 mU L(-1)), HbA1c (7.3 ± 0.36%) and glycogen content in the liver (35.33 ± 1.38 mg g(-1) protein) and muscle (7.67 ± 0.11 mg g(-1) protein) compared to diabetic controls. The extract also showed a significant decrease in blood glucose by 47.29% towards the end of 2 h in oral glucose tolerance test on Day 21. Its therapeutic potential could be partly attributable to the presence of flavonoids, tannins and terpenes (alpha amyrin, betulin and beta sitosterol) along with micronutrients such as potassium, magnesium, calcium and zinc. Hence, we suggest the suitability of Aerva lanata as a nutraceutical for diabetic patients. PMID:24993661

  14. Dysregulated miR-103 and miR-143 expression in peripheral blood mononuclear cells from induced prediabetes and type 2 diabetes rats.

    PubMed

    Vatandoost, Nasimeh; Amini, Masoud; Iraj, Bijan; Momenzadeh, Sedigheh; Salehi, Rasoul

    2015-11-01

    The progression from normal glucose tolerance (NGT) to type 2 diabetes (T2D) occurs through an intermediate state of glucose intolerance known as pre-diabetes. This transition is usually a gradual phenomenon that occurs over 5-10 years. Among the routinely practiced T2D screening criteria, like, FPG, IFG, IGT or HbA1c, still the issue of a preferable one is debated. The newly emerged microRNAs are created much hope to act as a class of suitable diabetes gene signature detectable at an early stage of the disease development. Although T2D related miRNA fluctuations are reported from the main insulin target organs, sampling of these organs for the sake of screening due to its invasive nature is not practicable. Peripheral blood mononuclear cells (PBMCs) are in constant touch with all body organs hence may exhibit the trace of miRNA changes which take place in insulin target organs. In this study we have evaluated miR-103 and miR-143 expression in three groups of rats namely; normal control, high fat diet (HFD) which is corresponding to prediabetes state, and high fat diet/streptozotocin (STZ) induced T2D. Quantitative real time PCR was used for profiling the selected miRNA expression at various time intervals of the three defined groups of rats. In prediabetes and overt diabetes stages, miR-103 showed significantly elevated expression in PBMC specimens compared to the normal healthy control group. Overexpression pattern of mir-143 was statistically significant in T2D compared to non-diabetic controls. However in HFD (prediabetic) rats also we observed an increasing pattern of miR-143 compared to the normal controls but it was not statistically significant. PMID:26164754

  15. Profiling of cardiac ?-adrenoceptor subtypes in the cardiac left ventricle of rats with metabolic syndrome: Comparison with streptozotocin-induced diabetic rats.

    PubMed

    Okatan, Esma N; Tuncay, Erkan; Hafez, Gaye; Turan, Belma

    2015-07-01

    Little is known about metabolic syndrome (MetS)-associated cardiomyopathy, especially in relation to the role and contribution of beta-adrenoceptor (?-AR) subtypes. Therefore, we examined the roles of ?-AR subtypes in the cardiac function of rats with MetS (MetS group) and compared it with that of rats with streptozotocin (STZ)-induced diabetes (STZ group). Compared with the normal control rats, the protein levels of cardiac ?1- and ?2-AR in the MetS group were significantly decreased and with no changes in their mRNA levels, whereas the protein levels of ?3-AR were similar to those of the controls. However, as shown previously, the protein levels of cardiac ?1- and ?2-AR in the STZ group were decreased, whereas the ?3-AR levels were significantly increased by comparison with the controls. Additionally, the mRNA levels of ?2- and ?3-AR were increased, but ?1-AR mRNA was decreased in the STZ group. Furthermore, left ventricular developed pressure responses to ?3-AR agonist BRL37344 were increased in the STZ group but not in the MetS group, whereas for both groups, the responses to noradrenaline were not different from those of the controls. However, the response to stimulation with high concentrations of fenoterol was depressed in the MetS group, compared with the controls, but not in the STZ group. Consequently, our data suggest that the contribution of the ?-AR system to cardiac dysfunction in the rats with MetS is not the same as that in the STZ group, although they have similar cardiac dysfunction with similar ultrastructural changes to the myocardium. PMID:25994289

  16. Isolation and structural characterization of 2R, 3R taxifolin 3-O-rhamnoside from ethyl acetate extract of Hydnocarpus alpina and its hypoglycemic effect by attenuating hepatic key enzymes of glucose metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Balamurugan, Rangachari; Vendan, Subramanian Ezhil; Aravinthan, Adithan; Kim, Jong-Hoon

    2015-04-01

    Hydnocarpus alpina Wt. (Flacourtiaceae) (H. alpina) is a large tree traditionally used to treat leprosy; it also posses antidiabetic property. The present study was undertaken to isolate, characterize and to evaluate the antidiabetic effect of 2R, 3R taxifolin 3-O-rhamnoside. (rhamnoside) and its impact on carbohydrate metabolic key enzymes in control and streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ) (40 mg/kg). Oral administration of rhamnoside for 21 days significantly reduced food intake, calorie intake, blood glucose and glycosylated hemoglobin levels, and improved plasma insulin levels. Administration of rhamnoside showed significant increase in the body weight, body composition (Lean body weight (LBW) and retro body fat), glycolytic hexokinase, glucose-6-phophate dehydrogenase and pyruvate kinase levels where as significant decrease was observed in the levels of glucose-6-phosphatase fructose-1, 6-bisphosphatase and lactate dehydrogenase in diabetic treated rats. Further, administration of rhamnoside significantly improved the glycogen content, glycogen synthase and glycogen phosphorylase, suggesting the antihyperglycemic potential of rhamnoside in diabetic rats. The results obtained were compared with glibenclamide a standard hypoglycaemic drug. Immunohistopathological study of pancreas revealed increased number of ?-cells and insulin granules in diabetes-induced rats after treatment with rhamnoside for 21 days. Furthermore, Co-administration of rhamnoside (50 mg/kg) with nifedipine (13.6 mg/kg), a Ca(2+)ion channel blocker, or nicorandil (6.8 mg/kg), an ATP-sensitive K(+) ion channel opener, reveals the insulin secretion property of rhamnoside via a K(+)-ATP channels dependent pathway in diabetic rats. In conclusion, rhamnoside normalized blood glucose, glycosylated hemoglobin, key hepatic enzymes and glycogen content by increasing insulin secretion via K(+)-ATP channels dependent signaling pathway. The results suggest that the rhamnoside from H. alpina could be used as a therapeutic agent to treat diabetes mellitus. PMID:25698613

  17. Total parenteral nutrition in diabetic rats

    SciTech Connect

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

    1986-03-01

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

  18. Soybeans Ameliolate Diabetic Nephropathy in Rats

    PubMed Central

    Choi, Young Eun; Ahn, Soo Kyung; Lee, Won Taek; Lee, Jong Eun; Park, Seung Hwa; Yoon, Bang Bu

    2010-01-01

    Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. Soybeans have been shown to reduce urinary albumin excretion and total cholesterol in non-diabetic patients with nephrotic syndrome. However, reports focusing specifically on diabetic nephropathy are scarce and the available results are inconsistent. It was reported that soybean consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas it was found to elicit an increase in urinary protein excretion when soybeans were consumed by type 2 diabetic patients. This study aims to investigate the effects of soybean in diabetic nephropathy, particularly the effects of consuming soybeans on the histopathology of diabetic nephropathy, using aquaporin (AQP) and osteopontin (OPN) expression as diagnostic markers. Male Sprague-Dawley rats were assigned to one of three groups: control, diabetic with red chow diet and diabetic with soybean diet. For histological examination, the expression of OPN and AQP, renal function and hemoglobin A1c were evaluated at the end of the study. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group given a soybean diet. OPN and AQP expression were suppressed in the kidney specimens of diabetic rats with the soybean diet. In conclusion, soybeans may prevent the weight loss and morphological disruption of the kidney associated with diabetes mellitus. Soybeans also may improve glycemic control. It seems likely that long-term control of blood glucose levels using a soybean diet could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented. PMID:18955330

  19. Arginine metabolism in enterocytes of diabetic rats 

    E-print Network

    Morrow, Natalie Anne

    2002-01-01

    Diabetic rats and patients exhibit decreased plasma arginine concentrations. Arginine is important in numerous cellular pathways, including the synthesis of nitric oxide and the release of insulin from pancreatic ? cells. At present, little...

  20. Chinese cabbage (Brassica campestris L.) does not improve glucose tolerance, serum insulin, or blood lipid profiles in a rat model of type-2 diabetes.

    PubMed

    Islam, M S; Choi, H

    2008-11-01

    The present study was conducted to investigate the effects of a low (0.5%) and a high (2.0%) dietary dose of freeze-dried Chinese cabbage (CC) (Brassica campestris L.) powder in a type-2 diabetes (T2D) model of rats. Five-week-old male Sprague-Dawley rats were fed a high fat (HF)-containing diet for 2 wk then randomly divided into 4 groups of 8 animals, namely: normal control (NC), diabetic control (DBC), Chinese cabbage low (CCL, 0.5%), and Chinese cabbage high (CCH, 2.0%) groups. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 40 mg/kg body weight) in all groups except the NC group. After 4 wk feeding of experimental diets, although food intake was not different among the DBC, CCL, and CCH groups, body weight gain was significantly (P < 0.05) higher in the CCH group compared to the DBC group. Relatively higher serum insulin concentrations and better glucose tolerance were observed in the CC-fed groups compared to the DBC group; however, the results were not significantly different. Fasting blood glucose, blood glycated hemoglobin (HbA1c), liver weight, and liver glycogen levels were not influenced by the CC-containing diets. Additionally, hypertriglyceridemic tendencies were observed in the CC-fed groups compared to the NC and DBC groups, while difference observed for total-, HDL-, and LDL-cholesterols between the groups were negligible. Results of this study suggest that up to 2% dietary dose of freeze-dried CC is not significantly effective to reduce diabetes-related symptoms in an HF diet-fed STZ-induced T2D model of rats. PMID:19021803

  1. Chlorophytum borivilianum Root Extract Maintains near Normal Blood Glucose, Insulin and Lipid Profile Levels and Prevents Oxidative Stress in the Pancreas of Streptozotocin-Induced Adult Male Diabetic Rats

    PubMed Central

    Giribabu, Nelli; Kumar, Kilari Eswar; Rekha, Somesula Swapna; Muniandy, Sekaran; Salleh, Naguib

    2014-01-01

    The effect of C. borivilianum root on blood glucose, glycated hemoglobin (HbAIc), insulin and lipid profile levels in diabetes mellitus are not fully understood. This study therefore investigated the effect of C. borivilianum root on the above parameters and oxidative stress of the pancreas in diabetes. Methods: C. borivilianum root aqueous extract (250 and 500 mg/kg/day) was administered to streptozotocin (STZ)-induced male diabetic rats for 28 days. Body weight, blood glucose, HbA1c, insulin, lipid profile levels and glucose homeostasis indices were determined. Histopathological changes and oxidative stress parameters i.e. lipid peroxidation (LPO) and antioxidant enzymes activity levels of the pancreas were investigated. Results: C. borivilianum root extract treatment to diabetic rats maintained near normal body weight, blood glucose, HbA1c, lipid profile and insulin levels with higher HOMA-? cell functioning index, number of Islets/pancreas, number of ?-cells/Islets however with lower HOMA-insulin resistance (IR) index as compared to non-treated diabetic rats. Negative correlations between serum insulin and blood glucose, HbA1c, triglyceride (TG) and total cholesterol (TC) levels were observed. C. borivilianum root extract administration prevented the increase in lipid peroxidation and the decrease in activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) with mild histopathological changes in the pancreas of diabetic rats. Conclusions: C. borivilianum root maintains near normal levels of these metabolites and prevented oxidative stress-induced damage to the pancreas in diabetes. PMID:25249786

  2. The Soybean Peptide Vglycin Preserves the Diabetic ?-cells through Improvement of Proliferation and Inhibition of Apoptosis.

    PubMed

    Jiang, Hua; Tong, Yuxing; Yan, Dongjing; Jia, Shaohui; Ostenson, Claes-Goran; Chen, Zhengwang

    2015-01-01

    Replenishment of insulin-producing pancreatic ?-cells would be beneficial in diabetes. The number of ?-cells is maintained primarily by self-neogenesis to compensate for ?-cell failure, loss or dedifferentiation. We present here a polypeptide vglycin, which was isolated and purified from germinating pea seeds. Vglycin exhibited positive effects in our diabetic models by promoting the proliferation and suppressing the apoptosis and dedifferentiation of ?-cells. Vglycin promoted the restoration of ?-cells in both young streptozotocin (STZ)-induced type 1 diabetic SD rats and in aged high-fat diet with (or without) STZ-induced type 2 diabetic C57BL/6 mice. We demonstrated that vglycin triggers this positive signaling by activating the insulin receptor and corresponding transcription factors. Impaired insulin sensitivity and glucose tolerance in aged T2DM mice were dramatically improved after long-term vglycin treatment, consistent with the altered level of inflammatory factor IL-1?/6. In addition, energy expenditure and body weights were significantly decreased in the mouse models after vglycin therapy. These results provide insight into the protective effects of vglycin on ameliorating ?-cell function in standing glucolipotoxicity. Thus, vglycin may represent a new therapeutic agent for preventing and treating diabetes by replenishing endogenous insulin-positive cells. PMID:26510947

  3. The Soybean Peptide Vglycin Preserves the Diabetic ?-cells through Improvement of Proliferation and Inhibition of Apoptosis

    PubMed Central

    Jiang, Hua; Tong, Yuxing; Yan, Dongjing; Jia, Shaohui; Ostenson, Claes-Goran; Chen, Zhengwang

    2015-01-01

    Replenishment of insulin-producing pancreatic ?-cells would be beneficial in diabetes. The number of ?-cells is maintained primarily by self-neogenesis to compensate for ?-cell failure, loss or dedifferentiation. We present here a polypeptide vglycin, which was isolated and purified from germinating pea seeds. Vglycin exhibited positive effects in our diabetic models by promoting the proliferation and suppressing the apoptosis and dedifferentiation of ?-cells. Vglycin promoted the restoration of ?-cells in both young streptozotocin (STZ)-induced type 1 diabetic SD rats and in aged high-fat diet with (or without) STZ-induced type 2 diabetic C57BL/6 mice. We demonstrated that vglycin triggers this positive signaling by activating the insulin receptor and corresponding transcription factors. Impaired insulin sensitivity and glucose tolerance in aged T2DM mice were dramatically improved after long-term vglycin treatment, consistent with the altered level of inflammatory factor IL-1?/6. In addition, energy expenditure and body weights were significantly decreased in the mouse models after vglycin therapy. These results provide insight into the protective effects of vglycin on ameliorating ?-cell function in standing glucolipotoxicity. Thus, vglycin may represent a new therapeutic agent for preventing and treating diabetes by replenishing endogenous insulin-positive cells. PMID:26510947

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

    PubMed

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

    2014-01-01

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

  5. Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration.

    PubMed

    Hulse, Richard P; Beazley-Long, Nicholas; Ved, Nikita; Bestall, Samuel M; Riaz, Hamza; Singhal, Priya; Ballmer Hofer, Kurt; Harper, Steve J; Bates, David O; Donaldson, Lucy F

    2015-10-01

    Diabetic peripheral neuropathy affects up to half of diabetic patients. This neuronal damage leads to sensory disturbances, including allodynia and hyperalgesia. Many growth factors have been suggested as useful treatments for prevention of neurodegeneration, including the vascular endothelial growth factor (VEGF) family. VEGF-A is generated as two alternative splice variant families. The most widely studied isoform, VEGF-A165a is both pro-angiogenic and neuroprotective, but pro-nociceptive and increases vascular permeability in animal models. Streptozotocin (STZ)-induced diabetic rats develop both hyperglycaemia and many of the resulting diabetic complications seen in patients, including peripheral neuropathy. In the present study, we show that the anti-angiogenic VEGF-A splice variant, VEGF-A165b, is also a potential therapeutic for diabetic neuropathy. Seven weeks of VEGF-A165b treatment in diabetic rats reversed enhanced pain behaviour in multiple behavioural paradigms and was neuroprotective, reducing hyperglycaemia-induced activated caspase 3 (AC3) levels in sensory neuronal subsets, epidermal sensory nerve fibre loss and aberrant sciatic nerve morphology. Furthermore, VEGF-A165b inhibited a STZ-induced increase in Evans Blue extravasation in dorsal root ganglia (DRG), saphenous nerve and plantar skin of the hind paw. Increased transient receptor potential ankyrin 1 (TRPA1) channel activity is associated with the onset of diabetic neuropathy. VEGF-A165b also prevented hyperglycaemia-enhanced TRPA1 activity in an in vitro sensory neuronal cell line indicating a novel direct neuronal mechanism that could underlie the anti-nociceptive effect observed in vivo. These results demonstrate that in a model of Type I diabetes VEGF-A165b attenuates altered pain behaviour and prevents neuronal stress, possibly through an effect on TRPA1 activity. PMID:26201024

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

    PubMed

    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. PMID:24682898

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

    PubMed Central

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

    2013-01-01

    Background: Psoralea corylifolia (Somraji) and Trigonella foenum-graecum L. (Methi), important medicinal plants widely used in India as folk medicine. Local people of West Bengal traditionally used the seeds of these plants to cure diabetes. Objective: Present study was designed to investigate the antidiabetic efficacy of aqueous extract of seeds of these plants in separate or in composite manner in streptozotocin (STZ)-induced diabetic rat. Materials and Methods: Diabetes was induced by intramuscular injection of STZ at the dose of 40 mg/ml of citrate buffer/kg body weight. Fasting blood glucose (FBG), glyclated hemoglobin (HbA1C) and activities of hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase of liver in experimental animals were assessed. Hyperlipidemic state developed in the experimental diabetic rat was assessed by measuring the levels of total cholesterol, triglyceride, and lipoproteins in serum. Results: There was significant increased in the levels of FBG, HbA1C and lipid profiles along with diminution (P < 0.001) in the activities of hepatic hexokinase, glucose-6-phosphate dehydrogenase and elevation in glucose-6-phosphatase in diabetic control animals in respect to the untreated control. Significant recovery (P < 0.05) in the activities of above mentioned enzymes along with the correction in the levels of FBG, HbA1C and serum lipid profiles were noted towards the control level after the treatment of composite extract (i.e. 100 mg of Somraji: 100 mg of Methi, total 200 mg/kg body weight) than the individual extract (i.e. 200 mg of Somraji or 200 mg of Methi, per kg body weight) treatment. Conclusion: Results suggest that composite extract of above plant parts has more potent antidiabetic efficacy than the individual extract. PMID:24174822

  8. Tumor necrosis factor-? elevates neurite outgrowth through an NF-?B-dependent pathway in cultured adult sensory neurons: Diminished expression in diabetes may contribute to sensory neuropathy.

    PubMed

    Saleh, Ali; Smith, Darrell R; Balakrishnan, Savitha; Dunn, Lori; Martens, Corina; Tweed, Christopher W; Fernyhough, Paul

    2011-11-14

    The presence of a proinflammatory environment in the sensory neuron axis in diabetes was tested by measuring levels of proinflammatory cytokines in lumbar dorsal root ganglia (DRG) and peripheral nerve from age matched control and streptozotocin (STZ)-induced diabetic rats. The levels of tumor necrosis factor-? (TNF?) and other cytokines were diminished in lumbar DRG from diabetic animals. Consequently, we tested the hypothesis that TNF? modulated axonal plasticity in adult sensory neurons and posited that impairments in this signal transduction pathway may underlie degeneration in diabetic sensory neuropathy. Cultured adult rat sensory neurons were grown under defined conditions and TNF? caused a dose-dependent 2-fold (P<0.05) elevation in neurite outgrowth. Neurons derived from 3 to 5month STZ-induced diabetic rats exhibited significantly reduced levels of neurite outgrowth in response to TNF?. TNF? enhanced NF-?B activity as assessed using Western blotting and plasmid reporter technology. Blockade of TNF?-induction of NF-?B activation caused inhibition of neurite outgrowth in cultured neurons. Immunofluorescent staining for NF-?B subunit p50 within neuronal nuclei revealed that medium to large diameter neurons were most susceptible to NF-?B inhibition and was associated with decreased neurite outgrowth. The results demonstrating reduced cytokine expression in DRG confirm that diabetic sensory neuropathy does not involve a neuroinflammatory component at this stage of the disease in experimental animal models. In addition, it is hypothesized that reduced TNF? expression in the DRG and possibly associated deficits in anterograde transport may contribute to impaired collatoral sprouting and regeneration in target tissue in type 1 diabetes. PMID:21985959

  9. Ciliary neurotrophic factor activates NF-?B to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents

    PubMed Central

    Saleh, Ali; Roy Chowdhury, Subir K.; Smith, Darrel R.; Balakrishnan, Savitha; Tessler, Lori; Martens, Corina; Morrow, Dwane; Schartner, Emily; Frizzi, Katie E.; Calcutt, Nigel A.; Fernyhough, Paul

    2012-01-01

    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-?B 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-?B, as assessed by Western blotting for the NF-?B p50 subunit and reporter assays for NF-?B promoter activity. Conversely, blockade of NF-?B signaling using SN50 peptide inhibited CNTF-mediated neurite outgrowth. Studies in mice with STZ-induced diabetes demonstrated that systemic therapy with CNTF prevented functional and structural indices of peripheral neuropathy along with deficiencies in dorsal root ganglion (DRG) NF-?B 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-?B-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-?B activation, and improvement of cellular bioenergetics. PMID:23022047

  10. Ciliary neurotrophic factor activates NF-?B to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents.

    PubMed

    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-?B 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-?B, as assessed by Western blotting for the NF-?B p50 subunit and reporter assays for NF-?B promoter activity. Conversely, blockade of NF-?B 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-?B 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-?B-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-?B activation, and improvement of cellular bioenergetics. PMID:23022047

  11. Effect of Imipramine, Paroxetine, and Lithium Carbonate on Neurobehavioral Changes of Streptozotocin in Rats: Impact on Glycogen Synthase Kinase-3 and Blood Glucose Level.

    PubMed

    Nadeem, Rania I; Ahmed, Hebatalla I; El-Denshary, Ezz-El-Din S

    2015-09-01

    Recent studies have demonstrated a scrutinized association of diabetes mellitus with depressive symptoms and major depression. Glycogen synthase kinase-3 (GSK-3) is a protein kinase enzyme constitutively active in non-stimulated cells and in multiple signalings. Independent lines of research provide a converging evidence for an involvement of GSK-3 in the regulation of behavior and hyperglycemia. The present study revealed that streptozotocin (STZ)-induced diabetic rats were found to show lengthened duration of immobility in the forced-swimming test (FST) and reduced locomotor and exploratory activities in the open-field test (OFT). Imipramine (15 mg/kg), Paroxetine (10 mg/kg) and lithium carbonate (36.94 mg/kg) for 14 days reduced immobility behavior in FST. Paroxetine and lithium carbonate increased the locomotor and exploratory activities, while imipramine decreased the locomotor activity in the OFT. Imipramine and lithium carbonate reduced the blood glucose level while paroxetine didn't alter it. STZ-induced diabetes increased GSK-3 gene expression which was determined using the reverse transcription-quantitative polymerase chain reaction test, while the three drugs decreased its expression. It can be concluded that lithium carbonate and imipramine can control both hyperglycemia and the associated symptoms of depression at the same time by inhibiting GSK-3 activity. On the other hand, paroxetine may only manage the depressive-like symptoms associated with diabetes through modulating the enzyme GSK-3, without changing blood glucose levels. PMID:26216050

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

    PubMed

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

    2015-01-01

    The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of ?-cells maintaining normal insulin and glucose levels. PMID:26501316

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

    PubMed Central

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

    2015-01-01

    The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of ?-cells maintaining normal insulin and glucose levels. PMID:26501316

  14. Boldine Prevents Renal Alterations in Diabetic Rats

    PubMed Central

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

    2013-01-01

    Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50?mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100?µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects. PMID:24416726

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

    PubMed Central

    Szkudelska, Katarzyna; Nogowski, Leszek; Szkudelski, Tomasz

    2014-01-01

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

  16. Naringin Alleviates Diabetic Kidney Disease through Inhibiting Oxidative Stress and Inflammatory Reaction

    PubMed Central

    Chen, Fenqin; Zhang, Ning; Ma, Xiaoyu; Huang, Ting; Shao, Ying; Wu, Can; Wang, Qiuyue

    2015-01-01

    Naringin, a flavanone glycoside extracted from Citrus grandis Osbeck, has a wide range of pharmacological effects. In the present study we aimed at demonstrating the protective effect of naringin against diabetic kidney disease (DKD) and elucidating its possible molecular mechanism underlying. The beneficial effect of naringin was assessed in rats with streptozotocin (STZ)-induced diabetes and high glucose-induced HBZY-1 cells. According to our results, first we found that naringin relieved kidney injury, improved renal function and inhibited collagen formation and renal interstitial fibrosis. Second, we confirmed that naringin restrained oxidative stress by activating Nrf2 antioxidant pathway. Moreover, the results suggested that naringin significantly resisted inflammatory reaction by inhibiting NF- ? B signaling pathway. Taken together, our results demonstrate that naringin effectively alleviates DKD, which provide theoretical basis for naringin clinically used to treatment of DKD. PMID:26619044

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

    PubMed Central

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

    2014-01-01

    Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy. PMID:25371906

  18. Influence of fluoride on streptozotocin induced diabetic nephrotoxicity in mice: Protective role of Asian ginseng (Panax ginseng) & banaba (Lagerstroemia speciosa) on mitochondrial oxidative stress

    PubMed Central

    Basha, Mahaboob P.; Saumya, S.M.

    2013-01-01

    Background & objectives: Chronic fluoride intoxication through drinking water is a serious health problem. Patients with diabetes are known to have impaired renal function and elimination of fluoride from the body is mainly done through kidney. Fluoride toxicity in diabetes patients may aggravate complications. In this study, the influence of fluoride was assessed on streptozotocin (STZ) induced diabetes in mice as also the efficacy/protective effective of oral supplementation of ginseng (GE) and banaba leaf extracts (BLE). Methods: The efficacy of plant extracts, GE and BLE at doses of 50, 150, 250 mg/kg b.w./day alone and in combination, was tested for a period of 15 days on fluoride treated STZ induced diabetic animals. Results: Fluoride exposure to mice with STZ-induced diabetes produced significant changes in OSI (organo-somatic index), fluoride content, blood glucose, urea, serum creatinine and oxidative stress indices in kidney tissues with evident histological alterations. Among the antioxidant treatments, combination therapy of GE and BLE at 150 mg/kg b.w. significantly normalized the impaired biochemical variables in kidney tissues of fluoride toxicated diabetic mice. Interpretations & conclusions: High fluoride uptake was found to be diabetogenic and further aggravated the renal oxidative damage and thereby the toxicity in mice with STZ induced diabetes mice. GE and BLE exposure individually or in combination at a dose of 150 mg/kg b.w./day for 15 days exhibited protective effects on fluoride toxicated STZ induced nephrotoxicity in mice. PMID:23563382

  19. Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats.

    PubMed

    Barzegar-Fallah, Anita; Alimoradi, Houman; Asadi, Firouzeh; Dehpour, Ahmad Reza; Asgari, Mojgan; Shafiei, Massoumeh

    2015-04-01

    It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti-inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin-induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor-? were also determined. Streptozotocin-treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor-?, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor-?, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti-oxidative and anti-inflammatory mechanisms that appear to be independent of the 5-HT3 receptor. PMID:25676798

  20. Antihyperglycemic, antihyperlipidemic and antioxidant activity of phenolic rich extract of Brassica oleraceae var gongylodes on streptozotocin induced Wistar rats.

    PubMed

    Sharma, Indumati; Aaradhya, Mallikarjun; Kodikonda, Madhuri; Naik, Prakash Ramchandra

    2015-01-01

    Cruciferous vegetables, in particular those included into the Brassica genus, are good sources of a variety of nutrients and health-promoting phytochemicals. Phenolic compounds are the major antioxidants of Brassica; hence the contribution of Brassica vegetables to health improvement has largely been associated to their antioxidant capacity. This study aimed to assess anti-diabetic, antilipidemic, and antioxidant activity of phenolic rich extract of Brassica oleraceae var gongylodes (BOvG) in Wistar rats. The findings revealed that the administration of BOvG extract to diabetic rats significantly reduced fasting blood glucose by 64% within 7 days of treatment. Additionally, BOvG extract was also observed to normalize the diabetic rats' lipid profile and HbA1c (Glycated hemoglobin). BOvG extract also showed protection of liver- kidney functions, which was evidenced by the significant decrease in Blood Urea Nitrogen (BUN), Serum glutamic oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT). The treatment also improved the antioxidant status of the diabetic rats where the enzymatic activities of Catalase (CAT) and Super Oxide Dismutase (SOD) were significantly increased. Furthermore, RP-HPLC analysis detected chlorogenic acid, rutin, and sinapic acid against known standards in BOvG extract. Hence, the present investigation suggests that BOvG phenolic rich extract (as a multi-component therapy) exhibited anti-diabetic, antilipidemic and antioxidant properties in STZ-induced diabetic rats. PMID:26020019

  1. Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences.

    PubMed

    Kuhad, Anurag; Chopra, Kanwaljit

    2007-12-01

    Emerging epidemiological data indicates that diabetes is a potential predisposing factor for neuropsychiatric deficits as stroke, cerebrovascular diseases, diabetic encephalopathy, depression and anxiety. Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involves direct neuronal damage caused by intracellular glucose. Curcumin, a well-established phenolic antioxidant and anti-inflammatory molecule, is capable of playing an important role against amyloid and dendritic pathology and thus has neuroprotective properties. The aim of the present study was to explore the effect of curcumin (60 mg/kg; p.o.) on cognitive functions, oxidative stress and inflammation in diabetic rats. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 80% in the cerebral cortex of diabetic rats. There was 107% and 121% rise in thiobarbituric acid reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Reduced glutathione level and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in cerebral cortex and hippocampus were increased by 112% and 94% respectively. Serum TNF-alpha, a marker for inflammation, was found to increase by 1100% in diabetic rats. Chronic treatment with curcumin (60 mg/kg; p.o.) significantly attenuated cognitive deficit, cholinergic dysfunction, oxidative stress and inflammation in diabetic rats. The results emphasize the involvement of cholinergic dysfunction, oxidative stress and inflammation in the development of cognitive impairment in diabetic animals and point towards the potential of curcumin as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy. PMID:17822693

  2. Oxymatrine attenuates diabetes-associated cognitive deficits in rats

    PubMed Central

    Wang, Suo-bin; Jia, Jian-ping

    2014-01-01

    Aim: Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait (the Chinese herb Kushen) and exhibits diverse pharmacological actions. In this work we investigated the effects of OMT on diabetes-associated cognitive decline (DACD) in a rat model of diabetes and explored the mechanisms of action. Methods: Male Wistar rats were injected with streptozotocin (65 mg/kg, ip) once to induce diabetes. The rats were then treated with vehicle or OMT (60 or 120 mg/kg per day, ip) for 7 weeks. Memory function was assessed using Morris water maze test. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), NF-?B p65 unit, TNF-?, IL-1? and caspase-3 in the cerebral cortex and hippocampus were quantified. Results: The diabetic rats exhibited markedly reduced body weight and increased plasma glucose level. The memory function of the rats assessed using Morris water maze test showed significant reduction in the percentage of time spent in the target quadrant and the number of times crossing the platform, coupled with markedly prolongation of escape latency and mean path length. Moreover, the rats showed oxidative stress (significantly increased MDA, decreased SOD and reduced GSH levels), as well as significant increases of NF-?B p65 unit, TNF-?, IL-1? and caspase-3 levels in the cerebral cortex and hippocampus. Chronic treatment with OMT dose-dependently reversed these behavioral, biochemical and molecular changes in the diabetic rats. However, the swimming speed had no significant difference among the control, diabetic and OMT-treated diabetic rats. Conclusion: Chronic treatment with OMT alleviates diabetes-associated cognitive decline in rats, which is associated with oxidative stress, inflammation and apoptotic cascades. PMID:24442148

  3. Antidepressant-like effect of simvastatin in diabetic rats.

    PubMed

    ElBatsh, Maha Mohamed

    2015-08-01

    Diabetes mellitus is accompanied by hormonal and neurochemical changes that can be associated with anxiety and depression. I investigated the antidepressant effect of simvastatin (SMV) on diabetic rats. Rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were orally administered 0, 5, or 10 mg/kg of SMV daily for 14 days, then exposed to the forced swimming test (FST). Our results showed that diabetic rats had higher immobility duration than the CTR rats, and SMV decreased this depressive-like behavior in the diabetic rats. However, clomipramine lowered the immobility time in the CTR and STZ rats. STZ decreased serotonin concentration in the hippocampus, which was reversed by SMV and clomipramine. The dopamine concentration in the hippocampus decreased in the STZ groups compared with the CTR groups. However, SMV and clomipramine had no significant effect on the dopamine levels in either the CTR or STZ groups. Corticosterone levels were increased in the untreated STZ group; SMV and clomipramine significantly decreased corticosterone levels in the STZ groups, but had no effect on the CTR groups. In conclusion, SMV exerts an antidepressant-like effect on diabetic rats that are submitted to the FST. The antidepressant-like effect of SMV in the FST appears to be mediated, at least in part, by the biochemical changes to the blood levels of corticosterone and of serotonin concentration in the hippocampus. PMID:26120891

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

    PubMed Central

    Ohta, Takeshi; Masuyama, Taku; Yokoi, Norihide; Kakehashi, Akihiro; Shinohara, Masami

    2013-01-01

    The Spontaneously Diabetic Torii (SDT) rat is an inbred strain of Sprague-Dawley rat and recently is established as a nonobese model of type 2 diabetes (T2D). Male SDT rats show high plasma glucose levels (over 700?mg/dL) by 20 weeks. Male SDT rats show pancreatic islet histopathology, including hemorrhage in pancreatic islets and inflammatory cell infiltration with fibroblasts. Prior to the onset of diabetes, glucose intolerance with hypoinsulinemia is also observed. As a result of chronic severe hyperglycemia, the SDT rats develop profound complications. In eyes, retinopathy, cataract, and neovascular glaucoma are observed. Proliferative retinopathy, especially, resulting from retinal neovascular vessels is a unique characteristic of this model. In kidney, mesangial proliferation and nodular lesion are observed. Both peripheral neuropathy such as decreased nerve conduction velocity and thermal hypoalgesia and autonomic neuropathy such as diabetic diarrhea and voiding dysfunction have been reported. Osteoporosis is another complication characterized in SDT rat. Decreased bone density and low-turnover bone lesions are observed. Taking advantage of these features, SDT rat has been used for evaluating antidiabetic drugs and drugs/gene therapy for diabetic complications. In conclusion, the SDT rat is potentially a useful T2D model for studies on pathogenesis and treatment of diabetic complications in humans. PMID:23691526

  5. Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

    PubMed Central

    Naderi, Roya; Mohaddes, Gisou; Mohammadi, Mustafa; Ghaznavi, Rana; Ghyasi, Rafigheh; Vatankhah, Amir Mansour

    2015-01-01

    Purpose: Oxidative stress plays a key role in the onset and development of diabetes complications. In this study, we evaluated whether voluntary exercise could alleviate oxidative stress in the heart and blood of streptozotocin - induced diabetic rats. Methods: 28 male Wistar rats were randomly divided into four groups (n=7): control, exercise, diabetes and exercise + diabetes. Diabetes was induced by injection of streptozotocin in male rats. Rats in the trained groups were subjected to voluntary running wheel exercise for 6 weeks. At the end of six weeks blood and heart tissue samples were collected and used for determination of antioxidant enzymes (including SOD, GPX and CAT activities) and MDA level. Results: Exercise significantly reduced MDA levels both in the heart tissue (p<0.01) and blood samples (p<0.05). In addition, exercise significantly increased SOD (p<0.05), GPX (p<0.001) and CAT (p<0.05) in the heart tissue. Voluntary exercise also significantly increased SOD (p<0.01), GPX (p<0.05) and CAT (p<0.001) in the blood. Conclusion: Voluntary exercise diminishes the MDA level in blood and heart tissue of diabetic rats. It also accentuates activities of SOD, GPX and CAT. Therefore, it may be considered a useful tool for the reduction of oxidative stress in diabetes. PMID:26236662

  6. Regulation of Coronary Arterial BK Channels by Caveolae-Mediated Angiotensin II Signaling in Diabetes Mellitus

    PubMed Central

    Lu, Tong; Zhang, Dai-Min; Wang, Xiao-Li; He, Tongrong; Wang, Ru-Xing; Chai, Qiang; Katusic, Zvonimir S.; Lee, Hon-Chi

    2010-01-01

    Rationale The large conductance Ca2+-activated K+ (BK) channel, a key determinant of vascular tone, is regulated by angiotensin II (Ang II) type 1 receptor (AT1R) signaling. Upregulation of Ang II functions and downregulation of BK channel activities have been reported in diabetic vessels. However, the molecular mechanisms underlying Ang II-mediated BK channel modulation, especially in diabetes mellitus, have not been thoroughly examined. Objectives The aim in this study was to determine whether caveolae-targeting facilitates BK channel dysfunction in diabetic vessels. Results We found that BK channels, AT1R, G?q/11, non-phagocytic NAD(P)H oxidases (NOX-1) and c-Src kinases (c-Src) were co-localized in the caveolae of rat arterial smooth muscle cells (SMC) and the integrity of caveolae in SMC was critical for Ang II-mediated BK channel regulation. Most importantly, membrane microdomain targeting of these proteins was upregulated in the caveolae of streptozotocin (STZ)-induced rat diabetic vessels, leading to enhanced Ang II-induced redox-mediated BK channel modification and causing BK channel and coronary dysfunction. The absence of caveolae abolished the effects of Ang II on vascular BK channel activity and preserved BK channel function in diabetes. Conclusion These results identified a molecular scheme of receptor-enzyme-channel-caveolae microdomain complex, which facilitates the development of vascular BK channel dysfunction in diabetes. PMID:20167931

  7. Extracellular HSP70 levels in diabetic environment in rats.

    PubMed

    Santos, T M M; Sinzato, Y K; Gallego, F Q; Iessi, I L; Volpato, G T; Dallaqua, B; Damasceno, D C

    2015-07-01

    The expression of HSP70 in embryonic cells of mammals and its role for their normal development and protection is an important aspect to be investigated in pregnancy and/or mild diabetes. In this sense, the present study evaluated the effects of mild diabetes on maternal reproductive parameters and HSP70 levels in Wistar rats at different stages of life and in their offspring. Mild diabetes was induced by a beta-cytotoxic drug (streptozotocin) at birth. Four experimental groups were evaluated: at 90 days of age: nonpregnant nondiabetic (ND90) and nonpregnant mild diabetic (D90) female rats, and at term pregnancy: pregnant female rats of both glycemic status were examined (NDP and DP, respectively). The rats were submitted to oral glucose tolerance test, and blood samples were collected for determination of HSP70 levels. In addition, the reproductive performance of pregnant rats was assessed and HSP70 levels determined in their offspring blood samples. The HSP70 levels and maternal reproductive performance presented no difference between ND and D rats, regardless of the life stage. The HSP70 levels were increased in D90 rats and lower in offspring from D rats. Maternal HSP70 levels were positively correlated to the number of dead embryos. In conclusion, mild diabetes did not affect maternal reproductive performance, but high maternal HSP70 levels compromised embryo development. In addition, offspring from D rats exhibited lower HSP70 levels, showing that this protein can be used as an indicator of metabolic consequences of diabetes and predictor of related disorders in adulthood. PMID:25813004

  8. Forced-exercise delays neuropathic pain in experimental diabetes: effects on voltage-activated calcium channels.

    PubMed

    Shankarappa, Sahadev A; Piedras-Rentería, Erika S; Stubbs, Evan B

    2011-07-01

    Physical exercise produces a variety of psychophysical effects, including altered pain perception. Elevated levels of centrally produced endorphins or endocannabinoids are implicated as mediators of exercise-induced analgesia. The effect of exercise on the development and persistence of disease-associated acute/chronic pain remains unclear. In this study, we quantified the physiological consequence of forced-exercise on the development of diabetes-associated neuropathic pain. Euglycemic control or streptozotocin (STZ)-induced diabetic adult male rats were subdivided into sedentary or forced-exercised (2-10 weeks, treadmill) subgroups and assessed for changes in tactile responsiveness. Two weeks following STZ-treatment, sedentary rats developed a marked and sustained hypersensitivity to von Frey tactile stimulation. By comparison, STZ-treated diabetic rats undergoing forced-exercise exhibited a 4-week delay in the onset of tactile hypersensitivity that was independent of glucose control. Exercise-facilitated analgesia in diabetic rats was reversed, in a dose-dependent manner, by naloxone. Small-diameter (< 30 ?m) DRG neurons harvested from STZ-treated tactile hypersensitive diabetic rats exhibited an enhanced (2.5-fold) rightward (depolarizing) shift in peak high-voltage activated (HVA) Ca(2+) current density with a concomitant appearance of a low-voltage activated (LVA) Ca(2+) current component. LVA Ca(2+) currents present in DRG neurons from hypersensitive diabetic rats exhibited a marked depolarizing shift in steady-state inactivation. Forced-exercise attenuated diabetes-associated changes in HVA Ca(2+) current density while preventing the depolarizing shift in steady-state inactivation of LVA Ca(2+) currents. Forced-exercise markedly delays the onset of diabetes-associated neuropathic pain, in part, by attenuating associated changes in HVA and LVA Ca(2+) channel function within small-diameter DRG neurons possibly by altering opioidergic tone. PMID:21554321

  9. Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats

    PubMed Central

    Silva, Viviane A. O.; Polesskaya, Anna; Sousa, Thaís A.; Corrêa, Vani M. A.; André, Nayara Delgado; Reis, Rosana I.; Kettelhut, Isis C.; Harel-Bellan, Annick

    2011-01-01

    Purpose The apoptosis of retinal neurons plays a critical role in the pathogenesis of diabetic retinopathy (DR), but the molecular mechanisms underlying this phenomenon remain unclear. The purpose of this study was to investigate the cellular localization and the expression of microRNA-29b (miR-29b) and its potential target PKR associated protein X (RAX), an activator of the pro-apoptotic RNA-dependent protein kinase (PKR) signaling pathway, in the retina of normal and diabetic rats. Methods Retinas were obtained from normal and diabetic rats within 35 days after streptozotocin (STZ) injection. In silico analysis indicated that RAX is a potential target of miR-29b. The cellular localization of miR-29b and RAX was assessed by in situ hybridization and immunofluorescence, respectively. The expression levels of miR-29b and RAX mRNA were evaluated by quantitative reverse transcription PCR (qRT–PCR), and the expression of RAX protein was evaluated by western blot. A luciferase reporter assay and inhibition of endogenous RAX were performed to confirm whether RAX is a direct target of miR-29b as predicted by the in silico analysis. Results We found that miR-29b and RAX are localized in the retinal ganglion cells (RGCs) and the cells of the inner nuclear layer (INL) of the retinas from normal and diabetic rats. Thus, the expression of miR-29b and RAX, as assessed in the retina by quantitative RT–PCR, reflects their expression in the RGCs and the cells of the INL. We also revealed that RAX protein is upregulated (more than twofold) at 3, 6, 16, and 22 days and downregulated (70%) at 35 days, whereas miR-29b is upregulated (more than threefold) at 28 and 35 days after STZ injection. We did not confirm the computational prediction that RAX is a direct target of miR-29b. Conclusions Our results suggest that RAX expression may be indirectly regulated by miR-29b, and the upregulation of this miRNA at the early stage of STZ-induced diabetes may have a protective effect against the apoptosis of RGCs and cells of the INL by the pro-apoptotic RNA-dependent protein kinase (PKR) signaling pathway. PMID:21897745

  10. Effects of Etanercept against Transient Cerebral Ischemia in Diabetic Rats

    PubMed Central

    Iwata, Naohiro; Takayama, Hiroko; Xuan, Meiyan; Kamiuchi, Shinya; Matsuzaki, Hirokazu; Okazaki, Mari; Hibino, Yasuhide

    2015-01-01

    Diabetes mellitus is known to exacerbate acute cerebral ischemic injury. Previous studies have demonstrated that infarction volumes caused by transient cerebral ischemia were greater in diabetic rats than in nondiabetic rats. Tumor necrosis factor-? (TNF-?) is a proinflammatory protein produced in the brain in response to cerebral ischemia that promotes apoptosis. Etanercept (ETN), a recombinant TNF receptor (p75)-Fc fusion protein, competitively inhibits TNF-?. Therefore, we evaluated the neuroprotective effects of chronic or acute treatment with ETN on cerebral injury caused by middle cerebral artery occlusion/reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. Furthermore, we evaluated the effects of ETN against the apoptosis and myeloperoxidase activity. Single administration of ETN before MCAO significantly suppressed exacerbation of cerebral damage in nondiabetic rats, as assessed by infarct volume. In contrast, the diabetic state markedly aggravated MCAO/Re-induced cerebral damage despite ETN treatment within 24?h before MCAO. However, the damage was improved by repeated administration of ETN at 900??g/kg/daily in rats in an induced diabetic state. These results suggested that repeated administration of ETN can prevent exacerbation of cerebral ischemic injury in the diabetic state and is mainly attributed to anti-inflammatory effects.

  11. Standardized Aqueous Tribulus terristris (nerunjil) extract attenuates hyperalgesia in experimentally induced diabetic neuropathic pain model: role of oxidative stress and inflammatory mediators.

    PubMed

    Ranjithkumar, Ravichandran; Prathab Balaji, S; Balaji, Bhaskar; Ramesh, R V; Ramanathan, Muthiah

    2013-11-01

    The present study aimed to evaluate standardized aqueous Tribulus terristris (nerunjil) extract on the pain threshold response in streptozotocin (STZ)-induced diabetic neuropathic pain model in rats. After a single injection of STZ (40?mg/kg; i.p.), Wistar male rats were tested by the thermal and chemical-induced pain models. Diabetic rats exhibited significant hyperalgesia, and these rats were left untreated for the first four weeks. Thereafter, treatment was initiated and continued up to week-8. All the rats except the vehicle-treated group received insulin 5?IU/kg/day to maintain plasma glucose levels. Treatment with nerunjil (100 and 300?mg/kg; p.o.) for 4?weeks significantly attenuated the nociception in behavioural models. Nerunjil also inhibited the tumour necrosis factor-? and interleukin-1 beta levels. The effect of nerunjil (300?mg/kg) is comparable to the standard drug Pregabalin (100?mg/kg). Nerunjil increased the superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and decreased the lipid peroxide levels in dose-dependent manner. Insulin alone-treated rats failed to attenuate hyperalgesic response. In comparison to insulin alone-treated rats, nerunjil exhibited significant increase in the pain threshold response. It could be concluded that in controlled diabetic states, nerunjil attenuated the neuropathic pain through modulation of oxidative stress and inflammatory cytokine release. PMID:23280817

  12. Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity

    SciTech Connect

    Sawant, Sharmilee P.; Dnyanmote, Ankur V.; Warbritton, Alan; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-03-15

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

  13. Topical erythropoietin promotes wound repair in diabetic rats.

    PubMed

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

    2010-01-01

    Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds. PMID:19626038

  14. Astragaloside IV ameliorates diabetic nephropathy involving protection of podocytes in streptozotocin induced diabetic rats.

    PubMed

    Chen, Jianguo; Chen, Yifang; Luo, Yunling; Gui, Dingkun; Huang, Jianhua; He, Dongyuan

    2014-08-01

    Podocyte loss and dysfunction play key role during the development of diabetic nephropathy (DN). The aim of this study was to observe the protective effects of astragaloside IV on podocyte in diabetic rats and explore its mechanisms preliminary. Healthy male Sprague-Dawley (SD) rats were randomized into normal control group, diabetic nephropathy group and diabetic nephropathy with AS-IV treatment group. DN was induced by intraperitoneal injection of streptozotocin (STZ). AS-IV treatment started 2 weeks before STZ injection and lasted 14 weeks. 24h Urinary proteins were measured 4, 8 and 12 weeks after STZ injection. Body weight, blood glucose, blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured 12 weeks after STZ injection. Renal pathology, podocyte morphological changes, podocyte density, protein and mRNA expression of integrin ?3, integrin ?1 and integrin-linked kinase (ILK) were detected by histopathology, electron microscopy, immunohistochemistry, western blot and real-time PCR, respectively. Hyperglycemia, proteinuria, mesangial expansion and podocyte loss, increased protein expression of ILK and decreased protein expression of integrin ?3 and integrin ?1 were detected in diabetic rats. AS-IV treatment ameliorated podocyte loss, renal histopathology and podocyte foot process effacement, decreased proteinuria, partially restored protein expression of integrin ?3, integrin ?1 and ILK. These findings suggested that AS-IV may protect podocyte and ameliorate diabetic nephropathy by inhibiting the expression of ILK and restoring the expression of integrin ?3?1 in diabetic rats. PMID:24809932

  15. Beneficial Antioxidative and Antiperoxidative Effect of Cinnamaldehyde Protect Streptozotocin-Induced Pancreatic ?-Cells Damage in Wistar Rats

    PubMed Central

    Subash-Babu, P.; Alshatwi, Ali A.; Ignacimuthu, S.

    2014-01-01

    The present study was aimed to evaluate the antioxidant defense system of cinnamaldehyde in normal, diabetic rats and its possible protection of pancreatic ?-cells against its gradual loss under diabetic conditions. In vitro free radical scavenging effect of cinnamaldehyde was determined using DPPH (1,1-diphenyl-2-dipicrylhydrazyl), superoxide radical, and nitric oxide radical. Streptozotocin (STZ) diabetic rats were orally administered with cinnamaldehyde at concentrations of 5, 10 and 20 mg/kg body weight for 45 days. At the end of the experiment, the levels of plasma lipid peroxides and antioxidants such as vitamin C, vitamin E, ceruloplasmin, catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase were determined. A significant increase in the levels of plasma glucose, vitamin E, ceruloplasmin, and lipid peroxides and significant decrease in the levels of plasma insulin and reduced glutathione were observed in the diabetic rats. Also the activities of pancreatic antioxidant enzymes were altered in the STZ-induced diabetic rats. The altered enzyme activities were reverted to near-normal levels after treatment with cinnamaldehyde and glibenclamide. Histopathological studies also revealed a protective effect of cinnamaldehyde on pancreatic ?-cells. Cinnamaldehyde enhances the antioxidant defense against reactive oxygen species produced under hyperglycemic conditions and thus protects pancreatic ?-cells against their loss and exhibits antidiabetic properties. PMID:24596621

  16. Acetylsalicylic acid protects erectile function in diabetic rats.

    PubMed

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

    2014-01-01

    We aimed to evaluate the effect of acetylsalicylic acid (ASA) treatment on diabetes-induced erectile dysfunction. Adult male Sprague-Dawley rats were divided into four groups as follows: (i) control (C), (ii) diabetic (D), (iii) ASA-treated control (C+ASA) and (iv) ASA-treated diabetic (D+ASA) groups. In groups 2 and 4, diabetes was induced by injection of 35 mg kg(-1) streptozotocin. ASA (100 mg kg(-1) day(-1) , orally) was administrated to rats in groups 3 and 4 for 8 weeks. Both intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) were measured in in vivo studies. In organ bath, the relaxation responses to acetylcholine (ACh), electrical field stimulation (EFS) and sodium nitroprusside were tested in corpus cavernosum (CC) strips. The mRNA expression for neuronal nitric oxide synthase (nNOS) was calculated using reverse transcription polymerase chain reaction technique. In in vivo experiments, diabetic rats displayed reduced ICP/MAP values, which were normalised with ASA treatment. The relaxant response to high-dose ACh and EFS at low frequencies (1-8 Hz) in CC strips from the D+ASA group were significantly higher when compared to the D group. Treatment with ASA normalised the raised mRNA expressions of nNOS in diabetic penile tissues. ASA may be involved in mRNA of protein synthesis of NO released from nonadrenergic and noncholinergic cavernosal nerve in diabetes. PMID:24428436

  17. Electrophysiological changes in optic neuropathy of streptozotocin induced diabetic rats

    PubMed Central

    Ghita, AM; Parvu, D; Sava, R; Georgescu, L; Zagrean, L

    2013-01-01

    The visually evoked potentials are electrical signals generated by the occipital cortex due to electrical stimulus. The clinical importance of VEP is to diagnose the functional changes of the optic nerve in different diseases such as diabetic mellitus. Our study sought latency of VEP changes depending on glycemic value and duration of diabetes in Wistar rats. Methods: this study evaluated the VEP of 25 rats in three groups: control group, diabetic group 1 with glycemic values between 200-400mg/dl and diabetic group 2 with glycemic values between 400 and 600mg/dl. These rats from diabetic group 2 were followed for 4 months and the ones in control group and diabetic group 1 for 5 months. Results: the latency of VEP shows slight changes without any statistical significance in the control group. In diabetic group 1 and 2 similar changes occurred, with statistical significance and the amplitude of the changes was proportional with the glycemic value. The rats had a rapid increase of VEP latency after the induction of diabetes and returned to a normal range in the first month. After a time, when the latencies of VEP were in normal range, a new growth appeared faster and larger as the glycemic values were higher. Conclusion: diabetes brings changes to the visual signal transmission and to the central processing, this being revealed by the examination of the visually evoked potential. Increased VEP latency is statistically correlated with the changes that occur at the level of the values of glucose in blood. A rapid growth in blood sugar lowers the visual signal transmission. This change is temporary despite the persistence of elevated blood glucose values, probably by adjusting to the new condition. However, maintaining high glycemic values remotely produces a progressive increase of the delay of the visual signal. This progressive increase is faster as blood glucose levels are higher. PMID:24155786

  18. Ghrelin reverses experimental diabetic neuropathy in mice

    SciTech Connect

    Kyoraku, Itaru; Shiomi, Kazutaka; Kangawa, Kenji; Nakazato, Masamitsu

    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.

  19. Effect of curcumin on diabetic rat model of cerebral ischemia.

    PubMed

    Miao, Mingsan; Cheng, Bolin; Li, Min

    2015-01-01

    To investigate the effect of curcumin on cerebral ischemia in diabetic rats the effects and features. intravenous injection alloxan diabetes model, to give alloxan first seven days the tail measured blood glucose value, the election successful model rats were fed with large, medium and small doses of curcumin suspension, Shenqijiangtang suspension and the same volume of saline, administered once daily. The first 10 days after administration 2h (fasting 12h) rat tail vein blood glucose values measured in the first 20 days after administration of 2h (fasting 12h), do cerebral ischemia surgery; rapid carotid artery blood after 30min rats were decapitated, blood serum, blood glucose and glycated serum protein levels; take part of the brain homogenates plus nine times the amount of normal saline, made 10 percent of brain homogenates. Another part of the brain tissue, in the light microscope observation of pathological tissue. Compared with model group, large, medium and small doses of curcumin can significantly lower blood sugar and glycated serum protein levels, significantly reduced brain homogenates lactic acid content and lactate dehydrogenase activity; large, medium-dose curcumin can significantly increase brain homogenates Na(+)-K(+)-ATP activity, dose curcumin can significantly improve brain homogenates Ca(+)-Mg(+)- ATP activity. Curcumin can reduce blood sugar in diabetic rat model of cerebral ischemia and improve brain energy metabolism, improve their brain tissue resistance to ischemia and hypoxia, cerebral ischemia in diabetic rats have a good drop the role of sugar and protect brain tissue. PMID:25631517

  20. Dietary supplementation with fermented legumes modulate hyperglycemia and acetylcholinesterase activities in Streptozotocin-induced diabetes.

    PubMed

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Boligon, Aline A; Athayde, Margareth L

    2015-12-01

    The study investigated the hypoglycemic and anticholinesterase activities of some fermented legumes (bambara groundnut and locust bean) in Streptozotocin (STZ)-induced diabetic rats. The rats were made diabetic by intraperitoneal administration of STZ (35mg/kg b.w.) and were fed diets containing fermented legumes (10% inclusion) for 14 days. The effect of the diets on blood glucose, pancreatic glutathione peroxidase (GPx) activity, reduced glutathione (GSH) and malondialdehyde (MDA) contents, ?-amylase, intestinal ?-glucosidase and acetylcholinesterase activities were studied. Significant (P<0.05) increase in blood glucose, pancreatic MDA, ?-amylase, intestinal ?-glucosidase and acetylcholinesterase activities with concomitant decrease in pancreatic GPx and GSH contents were observed in diabetic rats. However, this trend was reversed in rats fed fermented legumes supplemented diets for 14 days. The HPLC-DAD finger printing revealed the presence of gallic acid, catechin, caffeic acid, epicatechin, rutin, isoquercitrin, quercitrin, quercetin and kaempferol as the dominant phenolic compounds of the fermented legumes. However, possible contributing role of some bioactive peptides could not be ruled out. Hence, the hypoglycemic and antiacetylcholinesterase activities of the fermented legume condiments could be attributed to their constituent phytochemicals. PMID:26349771

  1. Purification, characterization and anti-diabetic activity of a polysaccharide from mulberry leaf.

    PubMed

    Zhang, Yao; Ren, Chunjiu; Lu, Guobing; Cui, Weizheng; Mu, Zhimei; Gao, Huiju; Wang, Yanwen

    2014-12-01

    In the present study, a high-purity polysaccharide from mulberry leaf (MLP) was purified and characterized, and its anti-diabetic effects were investigated in streptozotocin (STZ)-induced diabetic rats. Our results showed that the obtained MLP (purity 99.8%) was determined to be composed of d-arabinose, d-xylose, d-glucose, d-rhamnose and d-mannose with molar ratio of 1:2.13:6.53:1.04:8.73. Oral administration of MLP at 50-200mg/kgbodyweight daily for 5weeks significantly reduced the levels of fasting blood glucose (FBG), glycosylated serum protein (GSP), serum total cholesterol (TC), and serum triglyceride (TG), and increased the body weight, fasting insulin (FINS), C-peptide (C-P), liver glycogen, liver glucokinase, and serum high-density lipoprotein cholesterol (HDL-C). Moreover, MLP promoted marked pancreatic ?-cell regeneration and insulin secretion, and reduced liver fat accumulation in diabetic rats. The treatment effect of MLP on diabetes was similar to the effect of antidiabetic drug glibenclamide. These results clearly indicated that MLP may have a potential for the treatment of hyperglycemia and hyperlipidemia in diabetes. PMID:25455227

  2. Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats

    PubMed Central

    Chen, Wen-Pei; Wang, Yan-Dong; Ma, Yan; Zhang, Zi-Yang; Hu, Lu-Yun; Lin, Jun-Li; Lin, Bao-Qin

    2015-01-01

    AIM To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type-2 diabetes, and then to investigate the mechanisms. METHODS ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism. PMID:26682154

  3. An evaluation of the protective role of Ficus racemosa Linn. in streptozotocin-induced diabetic neuropathy with neurodegeneration

    PubMed Central

    Solanki, Nilay D.; Bhavsar, Shailesh K.

    2015-01-01

    Objective: Ficus racemosa (FR) is one of the herbs mentioned in the scriptures of the Ayurveda as Udumbara with high medicinal value. The objective of this study was to estimate the protective effect of FR against streptozotocin (STZ) induced diabetic neuropathy with neurodegeneration (DNN). Materials and Methods: Diabetes was induced in Wistar rats with STZ and were divided into six groups namely diabetic vehicle control, FR (four) and glibenclamide (one) treated rats; while one group was of normal control rats. After the 4th week of diabetes, induction treatment was started for further 28 days (5th to 8th week) with FR aqueous extract (250 mg/kg and 500 mg/kg) and ethanolic extract (200 mg/kg and 400 mg/kg). Investigation of DNN was carried out through biochemical and behavioral parameter assessment in rats. Results: Study showed a significant fall in glycosylated hemoglobin (HbA1c) and blood glucose level by the treatment of FR in diabetic rats. Antioxidant potential of FR showed a great rise in superoxide dismutase, catalase content and reduction observed in serum nitrite level; while significant fall in lipid peroxidation level and of C-reactive protein was observed in FR treated diabetic rats. Further FR treated diabetic rats also showed marked improvement in tail flick latency, pain threshold, the rise in locomotion and fall latency period. Conclusion: Treatment with FR shows protection in the multiple pathways of DNN by improving blood glucose, HbA1c, biochemical, and behavioral parameters, which suggest the protective role of FR in the reversal of DNN.

  4. Albumin permeation of new vessels is increased in diabetic rats

    SciTech Connect

    Kilzer, P.; Chang, K.; Marvel, J.; Rowold, E.; Jaudes, P.; Ullensvang, S.; Kilo, C.; Williamson, J.R.

    1985-04-01

    /sup 125/I-bovine serum albumin (BSA) permeation of the vasculature of 3-wk-old granulation tissue (induced by subcutaneous implantation of polyester fabric) formed in the diabetic milieu was assessed in female BB/W, spontaneously diabetic rats and in male, Sprague-Dawley rats with streptozocin-induced diabetes as well as in corresponding nondiabetic controls. Albumin permeation of new granulation tissue vessels was markedly increased in both groups of diabetic animals relative to that of nondiabetic controls, while albumin permeation of vessels in most other tissues did not differ for controls and diabetics. These observations indicate that the functional integrity of new vessels formed in the diabetic milieu is impaired: (1) to a greater extent than that of older vessels formed before induction of diabetes and (2) relative to new vessels in nondiabetics. The implication of these observations is that molecular constituents of vessels synthesized in the diabetic milieu are quantitatively and/or qualitatively abnormal and/or their incorporation into vessels is defective.

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

  6. Xiaokening stimulates endothelial nitric oxide release in diabetic rats

    PubMed Central

    Liu, Hong; Liu, Lei; Wei, Qunli; Cui, Jie; Yan, Changdong; Wang, Xin; Wu, Yongping

    2015-01-01

    INTRODUCTION Diabetes mellitus induces microangiopathic changes that lead to endothelial dysfunction. This study investigated the effect of Xiaokening, a type of Chinese compound medicine, on the mesenteric arteriolar endothelial cell function of diabetic rats and its underlying mechanism. METHODS Diabetes mellitus was induced in rat models via intraperitoneal injection of 60 mg/kg streptozotocin and observed over three weeks. Mesenteric arterioles, which were isolated in a cannulated and pressurised state, were incubated with intravascular injections of 1, 3 or 5 g/L Xiaokening for 24, 48 or 72 hours. The effects of Xiaokening on the release of nitric oxide (NO) on the mesenteric arterioles were detected under shear stress of 1, 10 and 20 dyn/cm2. Biochemical methods were used to determine the activities of superoxide dismutase (SOD) and xanthine oxidase (XO). The expressions of endothelial NO synthase (eNOS), SOD and XO in the mesenteric arterioles were assessed using Western blot. RESULTS Compared to normal rat arterioles, less NO was released in the mesenteric arterioles of diabetic rats. Xiaokening was found to have a concentration- and time-dependent effect on NO release; when the shear stress was increased, there was a gradual increase in the release of NO. Compared to normal arterioles, the expression of eNOS in the mesenteric arterioles of diabetic rats was lower. Incubation with Xiaokening increased SOD activity and expression, and decreased XO activity and expression in the mesenteric arterioles of the diabetic rats. CONCLUSION Xiaokening was able to significantly increase NO release and improve the endothelial function of mesenteric arterioles through antioxidative mechanisms. PMID:26243977

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

    PubMed Central

    Kazemian, Mostafa; Abad, Mansur; Haeri, Mohammad reza; Ebrahimi, Mansoor; Heidari, Reza

    2015-01-01

    Objective: Diabetes mellitus is the most common metabolic disorders with severe impact on quality of life. Reducing serum glucose levels and normalization of serum lipid is of great clinical importance for treating diabetes. To our knowledge, there are not any evidences about the anti-diabetic action of capparis spinosa root. In the present study the effects of the C. spinosa root extract on diabetic metabolic disorders have been studied in experimental diabetes. Materials and Methods: Rats were divided into six groups: normal control (NC), diabetic control (DC), diabetic rats receiving 0.2, 0.4 g/kg of plant extract or 0.6 mg/kg glibenclamide (groups D0.2, D0.4 or DG respectively). A normal group of rats was also designed to receive 0.2 g/kg of plant extract (N0.2). Rats were rendered diabetic (streptozotocin 60 mg/kg, i.p.) and treated with 0.2, 0.4 g/ kg of plant extract or glibenclamide for four weeks. At the end of the experiment, blood was drawn through heart puncture under deep anesthesia. Weight was measured weekly, glucose levels were measured at the first and fourth week and lipid profiles, insulin and liver enzymes at the end of the study. Results: Glucose levels significantly decreased after treating with plant extract (p=0.003). However, insulin levels did not increase in any treating groups. Plant extract could significantly raise HDL and reduce levels of LDL and liver enzymes (ALT and ALP). Conclusion: These results showed that C. spinosa root extract could improve diabetic related metabolic derangement such as hyperglycemia, dyslipidemia, and elevated liver markers in an insulin-independent manner. PMID:26445712

  8. Microarray analysis of thioacetamide-treated type 1 diabetic rats

    SciTech Connect

    Devi, Sachin S.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-04-01

    It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats.

  9. Diabetes mellitus effect on rat corneal dielectric properties.

    PubMed

    Olszewski, J; Marzec, E; Florek, E; Kulza, M

    2012-03-01

    In the course of the study, we carried out a dielectric examination to determine the effect of diabetes mellitus on the rat corneal function. Measurements were performed over the frequency range of 500 Hz-100 kHz in air and at the temperatures from 25 to 150°C. The frequency dependencies of the loss tangent for the healthy and the diabetic cornea exhibit two peaks at 2 kHz and 16 kHz in the ?-dispersion region. The amplitude of these both peaks is smaller for the diabetic cornea than that for the healthy one. The temperature dependencies of the loss tangent for the healthy and the diabetic cornea reveal ?-relaxation in the range of 30-70°C and 50-90°C, respectively. The present study exhibits that the dielectric spectroscopy is useful in detection of the effect of diabetes mellitus on the corneal molecular behavior. PMID:22136803

  10. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

    PubMed Central

    Nagayach, Aarti; Patro, Nisha; Patro, Ishan

    2014-01-01

    Behavioral impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45 mg/kg body weight; intraperitoneally). Motor function alterations were studied using Rotarod test (motor coordination) and grip strength (muscle activity) at 2nd, 4th, 6th, 8th, 10th, and 12th week post-diabetic confirmation. Scenario of glial (astroglia and microglia) activation, cell death and glutamate transportation was gaged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labeling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioral alterations following STZ-induced diabetes. PMID:25400546

  11. Beta-cell regeneration from vimentin+/MafB+ cells after STZ-induced extreme beta-cell ablation

    PubMed Central

    Cheng, Yu; Kang, Hongjun; Shen, Jing; Hao, Haojie; Liu, Jiejie; Guo, Yelei; Mu, Yiming; Han, Weidong

    2015-01-01

    Loss of functional beta-cells is fundamental in both type 1 and type 2 diabetes. In situ beta-cell regeneration therefore has garnered great interest as an approach to diabetes therapy. Here, after elimination of pre-existing beta cells by a single high-dose of streptozotocin (STZ), we demonstrated that a considerable amount of beta-like-cells was generated within 48?hrs. But the newly formed insulin producing cells failed to respond to glucose challenge at this time and diminished afterwards. Insulin treatment to normalize the glucose level protected the neogenic beta-like cells and the islet function was also gradually matured. Strikingly, intermediate cells lacking epithelial marker E-cadherin but expressing mesenchymal cell-specific marker vimentin appeared within 16?hrs following STZ exposure, which served as the major source of insulin-producing cells observed at 24 hrs. Moreover, these intermediate cells strongly expressed alpha-cell-specific marker MafB. In summary, the data presented here identified a novel intermediate cell type as beta-cell progenitors, showing mesenchymal cell feature as well as alpha-cell marker MafB. Our results might have important implications for efforts to stimulate beta-cell regeneration. PMID:26129776

  12. Sensitized peripheral nociception in experimental diabetes of the rat.

    PubMed

    Fuchs, D; Birklein, F; Reeh, P W; Sauer, S K

    2010-11-01

    Painful neuropathy is a common complication of diabetes. Particularly in the early stage of diabetic neuropathy, patients are characterized by burning feet, hyperalgesia to heat, and mechanical stimuli, as if residual nociceptors were sensitized. Such symptoms are barely explained by common pathophysiological concepts of diabetic neuropathy. Diabetes was induced in Wistar rats by streptozotocin (STZ). After 4 weeks behavioral testing (Plantar test, Randall-Selitto) was conducted. Basal and stimulated release of calcitonin gene-related peptide (CGRP), Substance P (SP) and prostaglandin E(2) (PGE(2)) from isolated skin and sciatic nerve were assessed by enzyme immunoassays. Electrophysiological properties of identified nociceptors under hyperglycemic, hypoxic, and acidotic conditions were investigated using the skin-nerve preparation. The diabetic rats showed hyperalgesia to heat and pressure stimulation. The basal CGRP/SP release was reduced, but chemical stimulation with bradykinin induced greater release of SP, CGRP and PGE(2) than in control animals. In contrast, capsaicin-stimulated CGRP release was reduced in sciatic nerves. Hypoxia per se lowered von Frey thresholds of most C-nociceptors to half. Hyperglycemic hypoxia induced ongoing discharge in all diabetic but not control C-fibers which was further enhanced under acidosis. Sensory and neurosecretory nociceptor functions are sensitized in diabetes. Diabetic C-fibers show exaggerated sensitivity to hyperglycemic hypoxia with and without additional acidosis, conditions that are thought to mimic ischemic episodes in diabetic nerves. Ongoing C-fiber discharge is known to induce spinal sensitization. Together with altered receptor and ion channel expressions this may contribute to painful episodes in diabetic neuropathy. PMID:20832942

  13. Intervention of D-glucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat

    SciTech Connect

    Vikram, A.; Tripathi, D.N.; Ramarao, P.; Jena, G.B.

    2008-01-01

    Streptozotocin (STZ) is a naturally occurring compound isolated from Streptomyces achromogens. It is used extensively for inducing diabetes in experimental animals. Diabetes mellitus is known to have proven adverse effects on male sexual organs and their reproductive functions. The atrophy of prostate gland and other organs of the genitourinary tract were observed in experimental diabetic animals. STZ exhibits a structural resemblance to D-glucose due to the presence of sugar moiety in its structure. Pancreatic {beta}-cells mainly contain GLUT1 and GLUT2 glucose transporters. Possibly due to structural resemblance, STZ and D-glucose, share a common recognition site for entry into the {beta}-cells. The objective of the present study is to evaluate the effect of D-glucose on STZ-induced toxicity in accessory sex organs of male rats. Animals were kept on overnight fasting. One group received vehicle and served as negative control, while all other groups were given STZ (45 mg/kg). Animals that received only STZ served as positive control. The effect of D-glucose was studied on STZ treated animals with different dosage of D-glucose (250, 500, 1000 and 2000 mg/kg). Restoration of body weight, plasma glucose and plasma insulin was evident only at 1000 and 2000 mg/kg of D-glucose. The protective effect of D-glucose is evident only when it is administered simultaneously with STZ. In the present investigation, we report that simultaneous administration of D-glucose along with STZ ameliorates STZ-induced toxicity. This is evident from the restoration of accessory sex organ's weight, cellular morphology as well as insulin level.

  14. Carvedilol Ameliorates Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Morsy, Mohamed A.; Ibrahim, Salwa A.; Amin, Entesar F.; Kamel, Maha Y.; Abdelwahab, Soha A.; Hassan, Magdy K.

    2014-01-01

    Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65?mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10?mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor-?, and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury. PMID:24991534

  15. Inhibition of calcineurin/NFAT pathway plays an essential role in renoprotective effect of tropisetron in early stage of diabetic nephropathy.

    PubMed

    Barzegar-Fallah, Anita; Alimoradi, Houman; Razmi, Ali; Dehpour, Ahmad Reza; Asgari, Mojgan; Shafiei, Massoumeh

    2015-11-15

    Recent studies have shown that calcineurin plays a central role in hypertrophy and extracellular matrix (ECM) accumulation in glomeruli at the early stages of diabetic nephropathy. Tropisetron is an effective antiemetic drug which also can potently inhibit calcineurin. The aim of this study was to investigate whether tropisetron can prevent glomerular hypertrophy and ECM expansion in early diabetic nephropathy. Streptozotocin (STZ)-induced diabetic rats were treated with tropisetron and cyclosporine A, a pharmacological calcineurin inhibitor, and the renal function and the expression of calcineurin and fibronectin were then assessed as well as nuclear localization of nuclear factor of activated T-cell c1 (NFATc1). 2 weeks after diabetes induction, all STZ-treated rats showed hyperglycemia, polyuria, body weight loss and renal dysfunction, as evidenced by increased glomerular filtration rate (GFR), along with a marked pathological changes in kidney. Calcineurin expression was increased in association with increased nuclear localization of the calcineurin substrate NFATc1 and fibronectin expression in glomeruli of diabetic rats. In parallel, the diabetic glomeruli became hypertrophic with an increase in kidney weight. Tropisetron, as potent as cyclosporine A, significantly ameliorated the early nephropathy symptoms, potentially through suppression of calcineurin expression, nuclear localization of NFATc1 and accumulation of fibronectin, and thereby reduced hypertrophy in glomeruli of diabetic rats. In conclusion, our results showed that tropisetron could ameliorate kidney injury in the early stage of diabetic nephropathy in rats. The renoprotective effects of tropisetron can be attributed, at least in part, to the suppression of diabetes-induced increases in calcineurin expression in kidney tissue. PMID:26481166

  16. Lead exposure causes thyroid abnormalities in diabetic rats

    PubMed Central

    Zadjali, Salah Al; Nemmar, Abderrahim; Fahim, Mohamed Abdelmonem AY; Azimullah, Sheikh; Subramanian, Dhanasekaran; Yasin, Javed; Amir, Naheed; Hasan, Mohammed Yousif; Adem, Abdu

    2015-01-01

    Lead is a widely-spread environmental pollutant and a commonly-used industrial chemical that can cause multisystemic adverse health effects. However, the effects of lead exposure on diabetic animals have not been reported so far. The aim of this study is to evaluate the effects of lead exposure on thyroid, renal and oxidative stress markers in diabetic Wistar rats. Diabetes was induced with an intraperitoneal (i.p.) injection of streptozocin (STZ). Six weeks later, rats were exposed i.p. to either distilled water (control group) or 25, 50 and 100 mg/kg of lead acetate (treatment groups). We found a positive relationship between the administered doses of lead acetate and its measured levels in blood samples (P < 0.01). Treatment of diabetic animals with lead acetate resulted in significant weight loss (P < 0.001). It also caused an increase in thyroid stimulating hormone levels (P < 0.05) and reductions in thyroxine (P < 0.05) and triiodothyronine levels (P < 0.01), a clinical picture consistent with hypothyroidism. Lead acetate exposure increased urea levels (P < 0.05) and caused a significant decrease in creatinine (P < 0.05). Besides, while the concentrations of malondialdehyde were not affected, glutathione stores were depleted (P < 0.01); in response to lead exposure. In conclusion, exposure of diabetic rats to lead acetate resulted in weight loss, clinical hypothyroidism, renal damage and oxidative stress. PMID:26221254

  17. Persistence of inflammatory response to intense exercise in diabetic rats.

    PubMed

    Bortolon, José Ricardo; Silva Junior, Antonio José de Almeida; Murata, Gilson Masahiro; Newsholme, Philip; Curi, Rui; Pithon-Curi, Tania Cristina; Hatanaka, Elaine

    2012-01-01

    In this study we evaluated the onset and resolution of inflammation in control and streptozotocin-induced diabetic rats subjected to a single session of intense exercise. The following measurements were carried out prior to, immediately after, and 2 and 24 hours after exercise: plasma levels of proinflammatory cytokines (TNF-?, IL-1?, IL-6, CINC-2?/?, MIP-3?, and IL-6), immunoglobulins (IgA and IgM), acute phase proteins (CRP and C3), and creatine kinase (CK) activity. We also examined the occurrence of macrophage death by measurements of macrophages necrosis (loss of membrane integrity) and DNA fragmentation. An increase was observed in the concentration of IL-1? (3.3-fold) and TNF-? (2.0-fold) and in the proportion of necrotic macrophages (4.5-fold) in diabetic rats 24 hours after exercise, while the control group showed basal measurements. Twenty-four hours after the exercise, serum CK activity was elevated in diabetic rats but not in control animals. We concluded that lesion and inflammations resulting from intense exercise were greater and lasted longer in diabetic animals than in nondiabetic control rats. PMID:22927832

  18. Genetic Control of Differential Acetylation in Diabetic Rats

    PubMed Central

    Kaisaki, Pamela J.; Otto, Georg W.; McGouran, Joanna F.; Toubal, Amine; Argoud, Karène; Waller-Evans, Helen; Finlay, Clare; Caldérari, Sophie; Bihoreau, Marie-Thérèse; Kessler, Benedikt M.; Gauguier, Dominique; Mott, Richard

    2014-01-01

    Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK) rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rats compared to normoglycemic Brown Norway (BN) rats. We show first that a promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then use mass-spectrometry to identify proteome-wide differential lysine acetylation of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include many proteins in pathways connected to diabetes and metabolic syndrome. We finally sequence GK and BN liver transcriptomes and find that mRNA expression of these targets does not differ significantly between GK and BN rats, in contrast to other components of the same pathways. We conclude that physiological differences between GK and BN rats are mediated by a combination of differential protein acetylation and gene transcription and that genetic variation can modulate acetylation independently of expression. PMID:24743600

  19. Carnosine treatment in combination with ACE inhibition in diabetic rats.

    PubMed

    Peters, V; Riedl, E; Braunagel, M; Höger, S; Hauske, S; Pfister, F; Zschocke, J; Lanthaler, B; Benck, U; Hammes, H-P; Krämer, B K; Schmitt, C P; Yard, B A; Köppel, H

    2014-11-01

    In humans, we reported an association of a certain allele of carnosinase gene with reduced carnosinase activity and absence of nephropathy in diabetic patients. CN1 degrades histidine dipeptides such as carnosine and anserine. Further, we and others showed that treatment with carnosine improves renal function and wound healing in diabetic mice and rats. We now investigated the effects of carnosine treatment alone and in combination with ACE inhibition, a clinically established nephroprotective drug in diabetic nephropathy. Male Sprague-Dawley rats were injected i.v. with streptozotocin (STZ) to induce diabetes. After 4 weeks, rats were unilaterally nephrectomized and randomized for 24 weeks of treatment with carnosine, lisinopril or both. Renal CN1 protein concentrations were increased under diabetic conditions which correlated with decreased anserine levels. Carnosine treatment normalized CN1 abundance and reduced glucosuria, blood concentrations of glycosylated hemoglobin (HbA1c), carboxyl-methyl lysine (CML), N-acetylglucosamine (GlcNac; all p<0.05 vs. non-treated STZ rats), reduced cataract formation (p<0.05) and urinary albumin excretion (p<0.05), preserved podocyte number (p<0.05) and normalized the increased renal tissue CN1 protein concentration. Treatment with lisinopril had no effect on HbA1C, glucosuria, cataract formation and CN1 concentration, but reduced albumin excretion rate more effectively than carnosine treatment (p<0.05). Treatment with both carnosine and lisinopril combined the effects of single treatment, albeit without additive effect on podocyte number or albuminuria. Increased CN1 amount resulted in decreased anserine levels in the kidney. Both carnosine and lisinopril exert distinct beneficial effects in a standard model of diabetic nephropathy. Both drugs administered together combine the respective effects of single treatment, albeit without exerting additive nephroprotection. PMID:25234296

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

    PubMed

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

    2014-10-01

    The present study aims to investigate anti-hyperglycaemic, anti-hyperlipidaemic and toxic effects of long-term consumption of selected green leafy porridges in a streptozotocin-induced diabetic Wistar rat model. Porridges made with Asparagus racemosus Willd. (AR), Hemidesmus indicus (L) R. Br. W. T. Aiton (HI), Scoparia dulcis L. (SD) and coconut milk porridge (CM) were incorporated into diets of diabetic Wistar rats. Diabetic control (DM) and normal control groups (NC) were provided with standard rat diet. Fasting blood glucose (FBG), HbA1c , C reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), liver enzymes and creatinine were measured. Feed and water intake among diabetic groups were significantly high when compared with those of NC (p?rats in SD (mean?=?39?±?19?g) and NC (mean?=?114?±?7?g) groups gained weight, whereas most rats in other diabetic groups lost weight. Among the diabetic groups, SD group had the lowest mean FBG, FBG increment percentage (45%) and HbA1c (5.8?±?2.1). FBG increment percentage and HbA1c of SD group were not significantly different to those of NC (38%; 4.7?±?0.7) (p?>?0.05). Among the diabetic groups, lowest TC (119?±?20.6?mg/dL) and highest HDL-C (33?±?6.3?mg/dL) were also detected in SD group. Alanine transaminase and creatinine were not significantly different (p?>?0.05) among diabetic groups but significant when compared with those of NC. When compared with those of NC, aspartate transaminase levels were significantly (p?diabetes-induced Wistar rats. PMID:24840113

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

    PubMed Central

    Haley, James M.; Thackeray, James T.; Thorn, Stephanie L.; DaSilva, Jean N.

    2015-01-01

    Objectives Reduced cardiac ?-adrenoceptor (?-AR) expression and cardiovascular dysfunction occur in models of hyperglycemia and hypoinsulinemia. Cardiac ?-AR expression in type-2 diabetes models of hyperglycemia and hyperinsulinemia, remain less clear. This study investigates cardiac ?-AR expression in type-2 diabetic Zucker diabetic fatty (ZDF) rats. Methods Ex vivo biodistribution experiments with [3H]CGP12177 were performed in Zucker lean (ZL) and ZDF rats at 10 and 16 weeks of age as diabetes develops. Blood glucose, body mass, and diet consumption were measured. Western blotting of ?-AR subtypes was completed in parallel. Echocardiography was performed at 10 and 16 weeks to assess systolic and diastolic function. Fasted plasma insulin, free fatty acids (FFA), leptin and fed-state insulin were also measured. Results At 10 weeks, myocardial [3H]CGP12177 was normal in hyperglycemic ZDF (17±4.1mM) compared to ZL, but reduced 16-25% at 16 weeks of age as diabetes and hyperglycemia (22±2.4mM) progressed. Reduced ?-AR expression not apparent at 10 weeks also developed by 16 weeks of age in ZDF brown adipose tissue. In the heart, Western blotting at 10 weeks indicated normal ?1-AR (98±9%), reduced ?2-AR (76±10%), and elevated ?3-AR (108±6). At 16 weeks, ?1-AR expression became reduced (69±16%), ?2-AR expression decreased further (68±14%), and ?3-AR remained elevated, similar to 10 weeks (112±9%). While HR was reduced at 10 and 16 weeks in ZDF rats, no significant changes were observed in diastolic or systolic function. Conclusions Cardiac ?-AR are reduced over 6 weeks of sustained hyperglycemia in type-2 diabetic ZDF rats. This indicates cardiac [3H]CGP12177 retention and ?1- and ?2-AR expression are inversely correlated with the progression of type-2 diabetes. PMID:25996498

  2. P2X and P2Y purinoceptor expression in pancreas from streptozotocin-diabetic rats

    E-print Network

    Burnstock, Geoffrey

    P2X and P2Y purinoceptor expression in pancreas from streptozotocin-diabetic rats Robson Coutinho and P2Y4, in the pancreas of the streptozotocin- induced diabetic rat was investigated using Elsevier Science Ireland Ltd. All rights reserved. Keywords: Diabetes; Purinoceptors; Pancreas; Adenosine

  3. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus

    PubMed Central

    Liu, J-Y; Yao, J; Li, X-M; Song, Y-C; Wang, X-Q; Li, Y-J; Yan, B; Jiang, Q

    2014-01-01

    Long noncoding RNAs (lncRNAs) have important roles in diverse biological processes. Our previous study has revealed that lncRNA-MALAT1 deregulation is implicated in the pathogenesis of diabetes-related microvascular disease, diabetic retinopathy (DR). However, the role of MALAT1 in retinal vasculature remodeling still remains elusive. Here we show that MALAT1 expression is significantly upregulated in the retinas of STZ-induced diabetic rats and db/db mice. MALAT1 knockdown could obviously ameliorate DR in vivo, as shown by pericyte loss, capillary degeneration, microvascular leakage, and retinal inflammation. Moreover, MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. The crosstalk between MALAT1 and p38 MAPK signaling pathway is involved in the regulation of endothelial cell function. MALAT1 upregulation represents a critical pathogenic mechanism for diabetes-induced microvascular dysfunction. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for diabetes-related microvascular complications. PMID:25356875

  4. IGF-1 Induction by Acylated Steryl ?-Glucosides Found in a Pre-Germinated Brown Rice Diet Reduces Oxidative Stress in Streptozotocin-Induced Diabetes

    PubMed Central

    Usuki, Seigo; Tsai, Ying-Ying; Morikawa, Keiko; Nonaka, Shota; Okuhara, Yasuhide; Kise, Mitsuo; Yu, Robert K.

    2011-01-01

    Background The pathology of diabetic neuropathy involves oxidative stress on pancreatic ?-cells, and is related to decreased levels of Insulin-like growth factor 1 (IGF-1). Acylated steryl ?-glucoside (PR-ASG) found in pre-germiated brown rice is a bioactive substance exhibiting properties that enhance activity of homocysteine-thiolactonase (HTase), reducing oxidative stress in diabetic neuropathy. The biological importance of PR-ASG in pancreatic ?-cells remains unknown. Here we examined the effects of PR-ASG on IGF-1 and glucose metabolism in ?-cells exposed to oxidative stress. Methodology/Principal Findings In the present study, a pre-germinated brown rice (PR)-diet was tested in streptozotocin (STZ)-induced diabetic rats. Compared with diabetic rats fed control diets, the PR-diet fed rats showed an improvement of serum metabolic and neurophysiological parameters. In addition, IGF-1 levels were found to be increased in the serum, liver, and pancreas of diabetic rats fed the PR-diet. The increased IGF-1 level in the pancreas led us to hypothesize that PR-ASG is protective for islet ?-cells against the extensive injury of advanced or severe diabetes. Thus we examined PR-ASG to determine whether it showed anti-apoptotic, pro-proliferative effects on the insulin-secreting ?-cells line, INS-1; and additionally, whether PR-ASG stimulated IGF-1 autocrine secretion/IGF-1-dependent glucose metabolism. We have demonstrated for the first time that PR-ASG increases IGF-1 production and secretion from pancreatic ?-cells. Conclusion/Significance These findings suggest that PR-ASG may affect pancreatic ?-cells through the activation of an IGF-1-dependent mechanism in the diabetic condition. Thus, intake of pre-germinated brown rice may have a beneficial effect in the treatment of diabetes, in particular diabetic neuropathy. PMID:22194889

  5. Effect of Polyherbal Mixtures on the Treatment of Diabetes

    PubMed Central

    Panda, Aparajeya; Jena, Somanatha; Sahu, Pramod Kumar; Nayak, Sanghamitra; Padhi, Payodhar

    2013-01-01

    The study focuses on polyherbal antidiabetic formulations of different plants used in the treatment of diabetes mixed in different concentrations. In the present study eleven medicinal plants with proven antidiabetic and related beneficial effects were selected for the preparation of five mixtures. The efficacy of prepared mixtures has been tested on streptozotocin- (STZ-) induced diabetic rats and compared with a commercially available drug glibenclamide. The mixtures at the dose levels of 400?mg/kg b.w. produced a significant decrease in blood glucose level by 69.6%, 70.97%, 64.45%, 71.82%, and 64.44% after 21?days of treatment. The elevated level of SGPT, SGOT, and ALP in the diabetic controlled group reflected the significant alteration of liver function by STZ induction and was found to be equipotent to glibenclamide in restoration of the elevated enzyme levels to normal. The elevated lipid levels (triglyceride and total cholesterol) were restored to near normal by these mixtures for all the estimated parameters. The results of the mixtures on treated group were found to restore the glycemic level to the near normal level thereby indicating antihyperglycemic activity of the formulated mixtures. PMID:23691349

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

    PubMed

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

    2015-08-01

    Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic-induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity. PMID:25904243

  7. Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with ?-catenin accumulation.

    PubMed

    Dorfman, Tatiana; Pollak, Yulia; Sohotnik, Rima; Coran, Arnold G; Bejar, Jacob; Sukhotnik, Igor

    2015-09-01

    The Wnt/?-catenin signaling cascade is implicated in the control of stem cell activity, cell proliferation, and cell survival of the gastrointestinal epithelium. Recent evidence indicates that the Wnt/?-catenin pathway is activated under diabetic conditions. The purpose of this study was to evaluate the role of Wnt/?-catenin signaling during diabetes-induced enteropathy in a rat model. Male rats were divided into three groups: control rats received injections of vehicle; diabetic rats received injections of one dose of streptozotocin (STZ); and diabetic-insulin rats received injections of STZ and were treated with insulin given subcutaneously at a dose of 1?U/kg twice daily. Rats were killed on day 7. Wnt/?-catenin-related genes and expression of proteins was determined using real-time PCR, western blotting, and immunohistochemistry. Among 13 genes identified by real-time PCR, seven genes were upregulated in diabetic rats compared with control animals including the target genes c-Myc and Tcf4. Diabetic rats also showed a significant increase in ?-catenin protein compared with control animals. Treatment of diabetic rats attenuated the stimulating effect of diabetes on intestinal cell proliferation and Wnt/?-catenin signaling. In conclusion, enhanced intestinal epithelial cell proliferation in diabetic rats correlates with ?-catenin accumulation. PMID:26297291

  8. The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats

    PubMed Central

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

    2014-01-01

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

  9. Efficiency of noopept in streptozotocin-induced diabetes in rats.

    PubMed

    Ostrovskaya, R U; Ozerova, I V; Gudascheva, T A; Kapitsa, I G; Ivanova, E A; Voronina, T A; Seredenin, S B

    2013-01-01

    We studied the effects of new nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) in various dosage regimens on the dynamics of glycemia, body weight, and pain sensitivity in rats receiving diabetogenic toxin streptozotocin. In experimental diabetic rats, Noopept alleviated glycemia and weight loss and normalized enhanced pain sensitivity. The normalizing effect of Noopept was most pronounced when it was administered as a preventive agent prior to injection of the toxin. Both preventive and therapeutic administration of Noopept (delayed injections included) significantly weakened the examined metabolic effects of diabetogenic toxin. Possible mechanisms of the antidiabetic action of Noopept are analyzed. PMID:23484194

  10. Systemic Perturbations of Key Metabolites in Diabetic Rats During the Evolution of Diabetes Studied by Urine Metabonomics

    PubMed Central

    Guan, Mimi; Xie, Liyun; Diao, Chengfeng; Wang, Na; Hu, Wenyi; Zheng, Yongquan; Jin, Litai; Yan, Zhihan; Gao, Hongchang

    2013-01-01

    Background Elucidation of metabolic profiles during diabetes progression helps understand the pathogenesis of diabetes mellitus. In this study, urine metabonomics was used to identify time-related metabolic changes that occur during the development of diabetes mellitus and characterize the biochemical process of diabetes on a systemic, metabolic level. Methodology/Principal Findings Urine samples were collected from diabetic rats and age-matched controls at different time points: 1, 5, 10, and 15 weeks after diabetes modeling. 1H nuclear magnetic resonance (1H NMR) spectra of the urine samples were obtained and analyzed by multivariate data analysis and quantitative statistical analysis. The metabolic patterns of diabetic groups are separated from the controls at each time point, suggesting that the metabolic profiles of diabetic rats were markedly different from the controls. Moreover, the samples from the diabetic 1-wk group are closely associated, whereas those of the diabetic 15-wk group are scattered, suggesting that the presence of various of complications contributes significantly to the pathogenesis of diabetes. Quantitative analysis indicated that urinary metabolites related to energy metabolism, tricarboxylic acid (TCA) cycle, and methylamine metabolism are involved in the evolution of diabetes. Conclusions/Significance The results highlighted that the numbers of metabolic changes were related to diabetes progression, and the perturbed metabolites represent potential metabolic biomarkers and provide clues that can elucidate the mechanisms underlying the generation and development of diabetes as well as its complication. PMID:23573250

  11. Islet remodeling in female mice with spontaneous autoimmune and streptozotocin-induced diabetes.

    PubMed

    Plesner, Annette; Ten Holder, Joris T; Verchere, C Bruce

    2014-01-01

    Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core. We determined how islet remodeling in autoimmune diabetes compares to streptozotocin (STZ)-induced diabetes. Islet cell mass, proliferation, and immune cell infiltration in pancreas sections from diabetic NOD mice and mice with STZ-induced diabetes was assessed using quantitative image analysis. Serial sections were stained for various beta-cell markers and Ngn3, typically restricted to embryonic tissue, was only upregulated in diabetic NOD mouse islets. Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state. Total pancreatic alpha-cell mass did not change as autoimmune diabetes developed in NOD mice despite the proportion of islet area comprised of alpha- and delta-cells increased. By contrast, alpha- and delta-cell mass was increased in mice with STZ-induced diabetes. Serum levels of glucagon reflected these changes in alpha-cell mass: glucagon levels remained constant in NOD mice over time but increased significantly in STZ-induced diabetes. Increased serum GLP-1 levels were found in both models of diabetes, likely due to alpha-cell expression of prohormone convertase 1/3. Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation. Hence, the inflammatory milieu in NOD mouse islets may restrict alpha-cell expansion highlighting important differences between these two diabetes models and raising the possibility that increased alpha-cell mass might contribute to the hyperglycemia observed in the STZ model. PMID:25101835

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  14. Therapeutic efficacy of Stephania tetrandra S. Moore for treatment of neovascularization of retinal capillary (retinopathy) in diabetes--in vitro study.

    PubMed

    Liang, Xiao-chun; Hagino, Nobuyoshi; Guo, Sai-shan; Tsutsumi, Taiki; Kobayashi, Shinjiro

    2002-07-01

    The present study was designed to examine therapeutic efficacy of the root extract of Stephania Tetrandra S. Moore (STMS) (traditional Chinese medicine; Han Fang Ji) for treatment of neovascularization of the retinal capillary (retinopathy) in streptozotocin (STZ)-induced diabetic rats (STZ diabetic rats) in culture. Recently we have established the culture system in which fetal bovine serum (FBS) in Dulbecco modified Eagle medium (DMEM) induced neovascularization of the retinal capillary and choroidal capillary in normal rats in culture. STZ diabetic rats showed more neovascularization of the retinal capillary and choroidal capillary than did normal rats in culture. In this study, the retinal tissue was removed for the posterior ocular region and cultured in DMEM containing FBS. The choroidal tissue of the posterior ocular region was also removed and cultured as an internal reference. Administration of STSM (0.91, 9.1 and 91 microg/ml) significantly suppressed neovascularization of the retinal capillary in both STZ diabetic rats and normal rats in a dose-dependent manner. Similar results were obtained with the choroidal capillary; administration of STSM suppressed neovascularization of the choroidal capillary in both STZ diabetic rats and normal rats. In order to determine the component of STSM inhibiting neovascularization of the retinal capillary, tetrandrine (a major chemical constituent of STSM) was administered and neovascularization of the retinal capillary was examined in culture. The effect of tetrandrine on the choroidal capillary was also examined as an internal reference. Administration of tetrandrine (0.1, 1.0 and 10 microM) suppressed neovascularization of the retinal capillary in both STZ diabetic rats and normal rats in a dose-dependent manner. Similar results were obtained with the choroidal capillary of both STZ diabetic rats and normal rats. We infer, therefore, that STSM has a direct effect on the retinal capillary of posterior ocular region and suppresses neovascularization of retinal capillary in STZ diabetic rats through the activation of tetrandrine. These results suggest that STSM may prevent for delay the progression of retinopathy in diabetic patients. PMID:12222655

  15. Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes

    PubMed Central

    WANG, YONG-BIN; GE, ZHI-MING; KANG, WEI-QIANG; LIAN, ZHE-XUN; YAO, JIAN; ZHOU, CHANG-YONG

    2015-01-01

    Diabetic cardiomyopathy (DCM), an independent coronary heart disease that develops in diabetic individuals, is characterized by changes in the myocardial structure and function. The aim of the present study was to investigate the protective effect of rutin on DCM in a streptozotocin-induced diabetic rat model. Rutin was orally administrated at a dose of 8 mg/kg body weight. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. The expression levels of cellular proteins associated with apoptosis were measured by western blot analysis, while the levels of inflammatory factors were assessed by immunohistochemical analyses. Rats with DCM exhibited an abnormal metabolic profile, aberrant myocardial enzymes, elevation of oxidative stress markers, increased levels of inflammatory factors and enhanced apoptotic cell death. Notably, rutin was shown to protect and improve myocardial dysfunction, oxidative stress, apoptosis and inflammation in the hearts of the diabetic rats. In conclusion, these results indicated that rutin may have great therapeutic potential in the treatment of DCM, and possibly other cardiovascular disorders, by preventing oxidative stress, inflammation and cell death. However, further detailed studies are required to reveal the exact mechanisms underlying the protective effect of rutin. PMID:25574214

  16. Glycemic and urinary volume responses in diabetic mellitus rats treated with Solanum lycocarpum.

    PubMed

    Farina, Fabiane; Piassi, Flávia Grillo; Moysés, Margareth Ribeiro; Bazzolli, Denise Mara Soares; Bissoli, Nazaré de Souza

    2010-02-01

    Dietary fiber performs important functions in diabetes mellitus control and treatment. In this study, we evaluate the reduction in plasma glucose after the treatment of diabetic rats with high-fiber Solanum lycocarpum flour. We found that serum glucose, water and food intake, urine excretion, and urine sodium concentration were reduced in S. lycocarpum flour-treated diabetic rats (TDRs), compared with diabetic control rats (DCRs). In addition, TDRs did not show signs of kidney hypertrophy, unlike those in the DCR group. These results suggest that the use of S. lycocarpum flour can be an effective support in diabetes mellitus treatment. PMID:20130665

  17. Chick embryo pancreatic transplants reverse experimental diabetes of rats.

    PubMed Central

    Eloy, R; Haffen, K; Kedinger, M; Grenier, J F

    1979-01-01

    The effectiveness of xenogeneic embryonic tissue in the treatment of experimental diabetes has been investigated in rats. The splenic lobes (80) of 15- to 18-d-old chick embryos, composed almost exclusively of endocrine tissue, were implanted directly into the hepatic parenchyma of the rat recipient. The biochemical and metabolic changes in the recipients suggest that embryonic transplants of 15-d-old chick pancreases were able to significantly improve, for a prolonged period of time (18 mo), the diabetic state of nonimmunosuppressed rats. None of the recipients of 18-d-old embryos splenic lobes exhibited a long-term improvement of the diabetic state after transplantation. The complete destruction of the pancreatic B cells of the recipients was assessed by: (a) immunocytochemical investigations of the recipient's pancreas, (b) measurement of insulin in the liver and pancreas of the recipients and (c) in situ vascular perfusion of their pancreas submitted to high glucose challenge. The results suggest that pancreatic tissue of the 15-d-old embryos is immunologically immature lacking one or several lymphocyte subsets implicated in the afferent lood of "non-self" recognition. Images PMID:156734

  18. Role of NADPH Oxidase and Stat3 in Statin-Mediated Protection against Diabetic Retinopathy

    PubMed Central

    Al-Shabrawey, Mohamed; Bartoli, Manuela; El-Remessy, Azza B.; Ma, Guochuan; Matragoon, Suraporn; Lemtalsi, Tahira; Caldwell, R. William; Caldwell, Ruth B.

    2010-01-01

    PURPOSE Inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (statins) reduce signs of diabetic retinopathy in diabetic patients and animals. Indirect clinical evidence supports the actions of statins in improving cardiovascular function, but the mechanisms of their protective actions in the retina are not understood. Prior studies have implicated oxidative stress and NADPH oxidase–mediated activation of signal transducer and activator of transcription 3 (STAT3) in diabetes-induced increases in expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM)-1 and breakdown of the blood–retinal barrier (BRB). Because statins are known to be potent antioxidants, the hypothesis for the current study was that the protective effects of statins in preventing diabetic retinopathy involve blockade of diabetes-induced activation of NADPH oxidase and STAT3. METHODS The hypothesis was tested by experiments in which rats with streptozotocin (STZ)-induced diabetes and retinal endothelial cells maintained in high-glucose medium were treated with simvastatin. Blood–retinal barrier (BRB) function was assayed by determining extravasation of albumin. Oxidative stress was assayed by measuring lipid peroxidation, protein nitration of tyrosine, dihydroethidine oxidation, and chemiluminescence. Immunoprobe techniques were used to determine the levels of NADPH oxidase subunit expression and STAT3 activation. RESULTS These studies showed that simvastatin blocks diabetes or high-glucose–induced increases in VEGF and ICAM-1 and preserves the BRB by a process involving blockade of diabetes/high-glucose–induced activation of STAT3 and NADPH oxidase. Statin treatment also prevents diabetes-induced increases in expression of the NADPH oxidase catalytic and subunit NOX2. CONCLUSIONS These results suggest that simvastatin protects against the early signs of diabetic retinopathy by preventing NADPH oxidase-mediated activation of STAT3. PMID:18378570

  19. Nitric oxide differentially affects ERK and Akt in type 1 and type 2 diabetic rats

    PubMed Central

    Varu, Vinit N.; Ahanchi, Sadaf S.; Martinez, Janet; Kibbe, Melina R.

    2014-01-01

    Background We have shown that nitric oxide (NO) is more effective at inhibiting neointimal hyperplasia in type 2 diabetic rats than in nondiabetic rats, but is not effective in type 1 diabetic rats. Insulin signaling is mediated by the ERK and Akt pathways, and thus we hypothesized that NO differentially affects ERK and Akt activity in type 1 versus type 2 diabetic rats. Materials and methods To investigate this hypothesis, we induced type 2 diabetes in Zucker diabetic fatty (ZDF) rats by feeding them Purina 5008 chow. To induce type 1 diabetes, lean Zucker (LZ) rats were injected with streptozotocin (STZ; 60 mg/kg). The carotid artery injury model was performed. Groups included injury and injury + PROLI/NO (20 mg/kg) (n = 6/group). Results Three days following injury, all animal models exhibited an increase in pERK levels. Whereas NO reduced pERK levels in LZ and STZ rats, NO had no effect on pERK levels in ZDF rats. Following a similar pattern, NO reduced pAkt levels in LZ and STZ rats but increased pAkt levels in ZDF rats. Fourteen days following injury, NO increased total pERK levels throughout the arterial wall in both the STZ and ZDF rats. These changes were greatest in the adventitia. Interestingly, whereas NO decreased total pAkt levels in LZ and STZ rats, NO increased pAkt levels in ZDF rats. Evaluation of the pERK:pAkt ratio revealed that NO increased this ratio in LZ and STZ rats but decreased the ratio in ZDF rats. Conclusions We report that NO differentially affects the expression of pERK and pAkt in type 1 versus type 2 diabetic rats. Given that NO is more effective at inhibiting neointimal hyperplasia in type 2 diabetic animals, the pERK:pAkt ratio may be the best surrogate to predict efficacy. PMID:23608617

  20. Oxidative stress status and placental implications in diabetic rats undergoing swimming exercise after embryonic implantation.

    PubMed

    Volpato, Gustavo Tadeu; Damasceno, Débora Cristina; Sinzato, Yuri Karen; Ribeiro, Viviane Maria; Rudge, Marilza Vieira Cunha; Calderon, Iracema Mattos Paranhos

    2015-05-01

    The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control-nondiabetic sedentary rats, control exercised-nondiabetic exercised rats, diabetic-diabetic sedentary rats, and diabetic exercised-diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR. PMID:25361551

  1. Plasma glucose-lowering action of Hon-Chi in streptozotocin-induced diabetic rats.

    PubMed

    Chang, J-C; Wu, M C; Liu, I-M; Cheng, J-T

    2006-02-01

    Hon-Chi was used for anti-hyperglycemic activity screening in streptozotocin-induced diabetic rats (STZ-diabetic rats) in an attempt to develop new substances for handling diabetes. Mandarin Hon-Chi is red yeast rice fermented with Monascus pilous and Monascus purpureus. Single oral administration of Hon-Chi decreased plasma glucose in STZ-diabetic rats in a dose-dependent manner from 50 mg/kg to 350 mg/kg. Similar treatment with Hon-Chi also lowered the plasma glucose in normal rats as effectively as that produced in STZ-diabetic rats. In addition, oral administration of Hon-Chi at the highest dose (350 mg/kg) attenuated the elevation of plasma glucose induced by an intravenous glucose challenge test in normal rats. Moreover, mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) in liver from STZ-diabetic rats were reversed in a dose-dependent manner by the repeated oral treatment of Hon-Chi three times daily for two weeks. Otherwise, hyperphagia in STZ-diabetic rats was markedly reversed by similar repeated treatment of Hon-Chi. The obtained results suggest that oral administration of Hon-Chi could decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin. PMID:16523406

  2. Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats

    PubMed Central

    Guo, Yong; Zhang, Jie; Ding, Zhenghua; Ha, Wenjing; Harding, J.J.

    2008-01-01

    Purpose To investigate the effect of carnosine (CA), aminoguanidine (AG), and aspirin (ASA) drops, all inhibitors of glycation, on the development of diabetic cataract in rat. Methods Rats were made diabetic with streptozotocin, and based on the level of plasma glucose, they were assigned as non-diabetic rats (<14 mmol/l plasma glucose) and diabetic rats (>14 mmol/l plasma glucose). Animals in the treated groups received CA, AG, and ASA as drops to the left eyes starting from the day of streptozotocin injection. Progression of lens opacification was recorded using the slit lamp at regular time intervals. All the rats were killed after the week 13, and the levels of advanced glycation end products (AGE), glutathione reductase (GR), catalase (CAT), and glutathione (GSH) were determined. Results Lens opacification progressed in a biphasic manner in the diabetic rats, an initial slow increase during the first eight weeks of diabetes followed by a steep increase in the next five weeks. Carnosine treatment delayed the progression of cataracts in diabetic rats, and the delay was statistically significant on the fourth week of diabetes (p<0.05, when compared with untreated moderately diabetic rats). A decrease in the antioxidant enzymes of CAT and the level of GSH was found in the lens of the untreated diabetic rats at 13 weeks after injection. Some protection was provided in the treated eyes. The level of glycation in the untreated diabetic rats was significantly higher than that in the normal rats (p<0.001). After treatment with CA, AG, and ASA, those diabetic rats had a lower level of glycated lens protein compared to the untreated diabetic rats (p<0.001). Conclusions These results thus suggest that the effect of CA, AG, and ASA is indeed inhibition of the formation of AGEs. However, the effect of CA, AG, and ASA is overwhelmed by the excessive accumulation of AGEs in the severely diabetic rats. CA compared with AG and ASA treatment can delay the progression of lens opacification in the diabetic rats only during the earlier stages. It also protects against the inactivation of enzymes. PMID:19081783

  3. Pentamethylquercetin protects against diabetes-related cognitive deficits in diabetic Goto-Kakizaki rats.

    PubMed

    Li, Xian-Hui; Xin, Xin; Wang, Yan; Wu, Jian-zhao; Jin, Zhen-dong; Ma, Li-na; Nie, Chun-jie; Xiao, Xiao; Hu, Yan; Jin, Man-wen

    2013-01-01

    Diabetic patients have a signifiantly higher risk of developing all forms of dementia. Pentamethylquercetin (PMQ) has been proven to have potential as an anti-diabetic agent. Nevertheless, whether PMQ can improve diabetes-induced cognitive dysfunction has not been investigated. To address this, we evaluated the effectiveness and underlying mechanisms of PMQ for ameliorating diabetes-related cognitive dysfunction in vivo and in vitro. Our results showed that Goto-Kakizaki (GK) rats displayed impairment in their learning abilities and memory capabilities. Furthermore, GK rats reflected cognitive dysfunction in proportion to the intensity of insulin resistance index. In addition, dendritic spine density and the % cell viability significantly decreased in hippocampus neurons. High glucose conditions induced hippocampal neurons damage, inflicted dendritic spine dysontogenesis, and reduced Akt/cAMP response element-binding protein activation. Treatment with PMQ in GK rats significantly ameliorated cognitive deficits and neuronal damage and increased dendritic spine density, at least in part, by improving insulin resistance and metabolic disorders. Furthermore, PMQ significantly activated the Akt/cAMP response element-binding protein pathway and increased the expression of memory-related proteins in the downstream part of the Akt/cAMP response element-binding protein pathway, such as synaptophysin and glutamate receptor 1. In addition, PMQ inhibited high glucose-induced cellular toxicity. LY294002 appeared to partly inhibit PMQ-mediated protective effects in hippocampal neurons. The results suggest that insulin resistance could predominantly reduce Akt/cAMP response element-binding protein activation in the brain, which is associated with a higher risk of cognitive dysfunction. PMQ could provide a new potential option for the prevention of cognitive dysfunction in diabetes. PMID:23271319

  4. Respiratory muscle weakness in the Zucker diabetic fatty rat.

    PubMed

    Allwood, Melissa A; Foster, Andrew J; Arkell, Alicia M; Beaudoin, Marie-Soleil; Snook, Laelie A; Romanova, Nadya; Murrant, Coral L; Holloway, Graham P; Wright, David C; Simpson, Jeremy A

    2015-10-01

    The obesity epidemic is considered one of the most serious public health problems of the modern world. Physical therapy is the most accessible form of treatment; however, compliance is a major obstacle due to exercise intolerance and dyspnea. Respiratory muscle atrophy is a cause of dyspnea, yet little is known of obesity-induced respiratory muscle dysfunction. Our objective was to investigate whether obesity-induced skeletal muscle wasting occurs in the diaphragm, the main skeletal muscle involved in inspiration, using the Zucker diabetic fatty (ZDF) rat. After 14 wk, ZDF rats developed obesity, hyperglycemia, and insulin resistance, compared with lean controls. Hemodynamic analysis revealed ZDF rats have impaired cardiac relaxation (P = 0.001) with elevated end-diastolic pressure (P = 0.006), indicative of diastolic dysfunction. Assessment of diaphragm function revealed weakness (P = 0.0296) in the absence of intrinsic muscle impairment in ZDF rats. Diaphragm morphology revealed increased fibrosis (P < 0.0001), atrophy (P < 0.0001), and reduced myosin heavy-chain content (P < 0.001), compared with lean controls. These changes are accompanied by activation of the myostatin signaling pathway with increased serum myostatin (P = 0.017), increased gene expression (P = 0.030) in the diaphragm and retroperitoneal adipose (P = 0.033), and increased SMAD2 phosphorylation in the diaphragm (P = 0.048). Here, we have confirmed the presence of respiratory muscle atrophy and weakness in an obese, diabetic model. We have also identified a pathological role for myostatin signaling in obesity, with systemic contributions from the adipose tissue, a nonskeletal muscle source. These findings have significant implications for future treatment strategies of exercise intolerance in an obese, diabetic population. PMID:26246509

  5. Serotonin enhances beta-endorphin secretion to lower plasma glucose in streptozotocin-induced diabetic rats.

    PubMed

    Chi, Tzong-Cherng; Ho, Yi-Jin; Chen, Win-Pin; Chi, Tsung-Li; Lee, Shoei-Sheng; Cheng, Juei-Tang; Su, Ming-Jai

    2007-04-24

    Although serotonin, serotonin uptake inhibitors and serotonin precursors (including tryptophan or 5-hydroxytryptophan) are known to have hypoglycemic action in rodents or human, it is not clear whether serotonin has hypoglycemic effect in streptozotocin-induced diabetic rats (STZ-diabetic rats). The aim of this study was to investigate the action of serotonin in regulating the plasma glucose STZ-diabetic rats. Plasma glucose, insulin, beta-endorphin and adrenaline were assessed after intraperitoneal administration of serotonin. Serotonin produced hypoglycemic effects without altering plasma insulin and adrenaline levels but increasing beta-endorphin level in STZ-diabetic rats. The glycogen content in soleus muscle was increased at 90 min after application of serotonin (0.3 mg/kg) in STZ-diabetic rats. Dihydroergotamine (non-selective 5-HT receptor blocker) and pimozide (5-HT(7) receptor blocker) abolished the hypoglycemic effect of serotonin in STZ-diabetic rats. Serotonin-induced hypoglycemic effect in association with the increase of beta-endorphin release was abolished in bilaterally adrenalectomized STZ-diabetic rats. In isolated adrenal gland of STZ-diabetic rats, the increase of beta-endorphin secretion in response to serotonin was reduced by either dihydroergotamine or pimozide. Pretreatment with naloxone (1.0 mg/kg, i.p.) prevented serotonin-induced plasma glucose lowering effect in STZ-diabetic rats. The results demonstrated that serotonin may activate 5-HT(7) receptor on rat adrenal gland to enhance of beta-endorphin secretion, which then stimulates the opioid receptor to increase peripheral glucose utilization, resulting in decreased plasma glucose levels in STZ-diabetic rats. PMID:17397876

  6. Insulin resistance-induced hyperglycemia decreased the activation of Akt/CREB in hippocampus neurons: Molecular evidence for mechanism of diabetes-induced cognitive dysfunction.

    PubMed

    Xiang, Qiong; Zhang, Jie; Li, Chun-Yan; Wang, Yan; Zeng, Mao-Jun; Cai, Zhi-Xin; Tian, Rong-Bo; Jia, Wei; Li, Xian-Hui

    2015-12-01

    Several previous studies have indicated that diabetic have higher risk of suffering from Alzheimer's disease, which severely induced cognitive dysfunction. However, the underlying molecular mechanism and more details on the cognitive deficits induced by hyperglycemia have not been elucidated. Here in our present study, on the basis of Goto-Kakizaki (GK) rats and streptozotocin (STZ)-induced diabetic model, we detected the variation of dendritic spine density in hippocampus as well as the differential expression of some important signal transduction molecules that were of relevance in learning and memory function. We found that the magnitude of escape latency time was significantly increased in such diabetic animals; the phosphorylated Akt/CREB; SYP and BDNF as well as other downstream molecules in hippocampus neurons were also downregulated in both diabetic groups compared to the normal groups. Thus, all of these data indicate the obstacle of neuronal pathology and the Akt/CREB signaling pathway caused by hyperglycemia that may suppress cognitive behavior, which may provide a novel way for the prevention of diabetic encephalopathy and the cognitive deficits of Alzheimer's disease. PMID:26344332

  7. Polysaccharides of Trametes versicolor Improve Bone Properties in Diabetic Rats.

    PubMed

    Chen, Chung-Hwan; Kang, Lin; Lo, Hui-Chen; Hsu, Tai-Hao; Lin, Fang-Yi; Lin, Yi-Shan; Wang, Zai-Jie; Chen, Shih-Tse; Shen, Chwan-Li

    2015-10-28

    This study investigates the effects of Trametes versicolor (L.:Fr.) Pilát (TVP, also known as Yunzhi) on bone properties in diabetic rats. Forty-five male Wistar rats (8 weeks old) were fed either a chow diet (control) or a high-fat diet throughout the study period of 28 days. Animals in the high-fat-diet group were injected with nicotinamide and streptozotocin to induce diabetes mellitus (DM). The DM rats were divided into a group receiving distilled water (vehicle) and another group receiving TVP at 0.1 g/kg weight by gavage. Relative to the vehicle group, TVP gavage lowered postprandial blood sugar (225 ± 18 mg/dL for TVP vs 292 ± 15 mg/dL for vehicle, p < 0.001) on day 26. Compared to the vehicle group, TVP mitigated DM-induced bone deterioration as determined by increasing bone volume of proximal tibia (22.8 ± 1.4% for TVP vs 16.8 ± 1.3% for vehicle, p = 0.003), trabecular number (p = 0.011), and femoral bone strength (11% in maximal load, 22% in stiffness, 14% in modulus, p < 0.001), and by reducing loss of femoral cortical porosity by 25% (p < 0.001). Our study demonstrates the protective effect of TVP on bone properties was mediated through, in part, the improvement of hyperglycemic control in DM animals. PMID:26308886

  8. Evidence for increased peroxidative activity in muscles from streptozotocin-diabetic rats

    SciTech Connect

    Lammi-Keefe, C.J.; Swan, P.B.; Hegarty, P.V.J.

    1984-05-01

    The ability of cardiac and skeletal muscles from diabetic rats to metabolize superoxide and hydrogen peroxide was determined by the activities of superoxide dismutase (SOD) and catalase, respectively. Male and female Sprague-Dawley rats, 43 days old, were made diabetic with a single intravenous injection of streptozotocin (70 mg/kg body weight). On the 80th day after injection the blood glucose concentration of these rats was increased fourfold, and the plasma insulin concentration was decreased four- to fivefold compared to controls. Body weights of male diabetic rats were 61% and those of female diabetic rats were 66% of their ad libitum-fed controls. The seven different skeletal muscles examined weighed less in the diabetic rats than in controls of the same age and body weight. Comparison to the body weight controls allowed the distinction of specific effects due to lack of insulin from effects due to retardation in muscle growth. Increased catalase activity in all muscles examined from diabetic rats (plantaris, gastrocnemius, and heart) suggested a response in catalase activity similar to that of starved rats. SOD activity was not altered in the diabetic rat skeletal muscles and erythrocytes, but was somewhat decreased in the heart.

  9. New insights into mechanisms of opioid inhibitory effects on capsaicin-induced TRPV1 activity during painful diabetic neuropathy.

    PubMed

    Shaqura, Mohammed; Khalefa, Baled I; Shakibaei, Mehdi; Zöllner, Christian; Al-Khrasani, Mahmoud; Fürst, Susanna; Schäfer, Michael; Mousa, Shaaban A

    2014-10-01

    Painful diabetic neuropathy is a disease of the peripheral sensory neuron with impaired opioid responsiveness. Since ?-opioid receptor (MOR) activation can inhibit the transient receptor potential vanilloid 1 (TRPV1) activity in peripherally sensory neurons, this study investigated the mechanisms of impaired opioid inhibitory effects on capsaicin-induced TRPV1 activity in painful diabetic neuropathy. Intravenous injection of streptozotocin (STZ, 45 mg/kg) in Wistar rats led to a degeneration of insulin producing pancreatic ?-cells, elevated blood glucose, and mechanical hypersensitivity (allodynia). In these animals, local morphine's inhibitory effects on capsaicin-induced nocifensive behavior as well as on capsaicin-induced TRPV1 current in dorsal root ganglion cells were significantly impaired. These changes were associated with a loss in MOR but not TRPV1 in peripheral sensory neurons. Intrathecal delivery of nerve growth factor in diabetic animals normalized sensory neuron MOR and subsequently rescued morphine's inhibitory effects on capsaicin-induced TRPV1 activity in vivo and in vitro. These findings identify a loss in functional MOR on sensory neurons as a contributing factor for the impaired opioid inhibitory effects on capsaicin-induced TRPV1 activity during advanced STZ-induced diabetes. Moreover, they support growing evidence of a distinct regulation of opioid responsiveness during various painful states of disease (e.g. arthritis, cancer, neuropathy) and may give novel therapeutic incentives. PMID:24863039

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

    PubMed Central

    Qinna, Nidal A; Badwan, Adnan A

    2015-01-01

    Streptozotocin (STZ) is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL), noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents and insulin delivery systems. PMID:26005328

  11. SGLT2 inhibitor therapy improves blood glucose but does not prevent diabetic bone disease in diabetic DBA/2J male mice.

    PubMed

    Thrailkill, Kathryn M; Clay Bunn, R; Nyman, Jeffry S; Rettiganti, Mallikarjuna R; Cockrell, Gael E; Wahl, Elizabeth C; Uppuganti, Sasidhar; Lumpkin, Charles K; Fowlkes, John L

    2016-01-01

    Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10weeks of therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of cortical bone was assessed by ?CT analysis and a three-point bending test of the femur, and vertebral bone strength was determined by compression testing. In the femur metaphysis and L6 vertebra, long-term diabetes (DM) induced deficits in trabecular bone microarchitecture. In the femur diaphysis, a decrease in cortical bone area, cortical thickness and minimal moment of inertia occurred in DM (p<0.0001, for all) while cortical porosity was increased (p<0.0001). These DM changes were associated with reduced fracture resistance (decreased material strength and toughness; decreased structural strength and rigidity; p<0.001 for all). Significant increases in PTH (p<0.0001), RatLAPs (p=0.0002), and urine calcium concentration (p<0.0001) were also seen in DM. Canagliflozin treatment improved BG in DM mice by ~35%, but did not improve microarchitectural parameters. Instead, in canagliflozin-treated diabetic mice, a further increase in RatLAPs was evident, possibly suggesting a drug-related intensification of bone resorption. Additionally, detrimental metaphyseal changes were noted in canagliflozin-treated control mice. Hence, diabetic bone disease was not favorably affected by canagliflozin treatment, perhaps due to insufficient glycemic improvement. Instead, in control mice, long-term exposure to SGLT2 inhibition was associated with adverse effects on the trabecular compartment of bone. PMID:26211996

  12. Cardiovascular protective effect of polysaccharide from Ophiopogon japonicus in diabetic rats.

    PubMed

    Zhang, Junfeng; Fan, Sairong; Mao, Yingge; Ji, Yuan; Jin, Liqin; Lu, Jianxin; Chen, Xiaoming

    2016-01-01

    Ophiopogon japonicus (Thunb.) Ker-Gawl is a well known traditional Chinese medicine used to treat cardiovascular and chronic inflammatory diseases for thousands of years. The present study was set up to investigate the protective effects of O. japonicus polysaccharide (OJP1) on cardiovascular injuries in diabetic rats. Results showed that OJP1 significantly reduced the MDA concentration and increased the activities of GPx, CAT and SOD in heart of diabetic rats. The levels of AGE, hs-CRP, sICAM-1, NO and ET-1 in diabetic rats were significantly reversed by OJP1 treatment. In addition, the level of ET-1 mRNA was decreased significantly, whereas eNOS mRNA level was increased after administration of OJP1. Meanwhile, the histopathological analysis showed that OJP1 alleviates the heart injury in diabetic rats. Together, these results suggest that OJP1 maintains the antioxidant enzyme levels and improves cardiovascular performance in diabetic rats. PMID:26434529

  13. Hypoglycaemic effect of Calamintha officinalis Moench. in normal and streptozotocin-induced diabetic rats.

    PubMed

    Lemhadri, A; Zeggwagh, N-A; Maghrani, M; Jouad, H; Michel, J B; Eddouks, M

    2004-06-01

    The purpose of this study was to investigate the effects of a water extract from the aerial parts of Calamintha officinalis Moench., after either a single dose or daily oral administration for 15 days, on plasma blood glucose concentrations and basal insulin levels in normal and streptozotocin-induced diabetic rats (STZ diabetic rats). The results clearly demonstrated the hypoglycaemic effect of this plant extract in both normal and STZ diabetic rats. In addition, no changes were observed in basal plasma insulin concentrations after treatment with this plant in normal or STZ diabetic rats, indicating that the underlying mechanism of the plant's pharmacological action seems to be independent of insulin secretion. We conclude that the aqueous C. officinalis extract exhibits a significant hypoglycaemic effect in normal and STZ diabetic rats without affecting basal plasma insulin concentrations, and supports, therefore, its traditional use by the Moroccan population. PMID:15231045

  14. Hypoglycaemic effect of quinolizidine alkaloids--lupanine and 2-thionosparteine on non-diabetic and streptozotocin-induced diabetic rats.

    PubMed

    Bobkiewicz-Koz?owska, Teresa; Dworacka, Marzena; Kuczy?ski, Sebastian; Abramczyk, Ma?gorzata; Kolano?, Renata; Wysocka, Waleria; Garcia Lopez, Pedro M; Winiarska, Hanna

    2007-06-22

    The hypoglycaemic effects of two quinolizidine alkaloids: lupanine and 2-thionosparteine were examined in non-diabetic and in streptozotocin-induced diabetic rats. The model of experimental diabetes can be considered to be related to diabetes mellitus type 2 with regards to the impairment of beta-cells' secretory function. A single intraperitoneal injection of 2-thionosparteine at a dose of 8.6 mg/kg lowered the blood glucose levels in diabetic rats at 90 and 120 min after administration and showed similar hypoglycaemic effects to glibenclamide and sparteine, which were used as reference substances. In contrast to glibenclamide, 2-thionosparteine did not result in a significant increase in plasma insulin levels in diabetic rats; an increase was only observed in the non-diabetic group. It was found that lupanine did not exert hypoglycaemic potency in diabetic and in non-diabetic animals and did not significantly increase plasma insulin concentration independent of the group examined. From this study we can state that 2-thionosparteine, but not lupanine, is confirmed to be a possible plasma glucose lowering agent. It is possible that 2-thionosparteine-dependent decrease in blood glucose level is not the only result of this drug's related insulin secretion. PMID:17379208

  15. Diabetic hyperglycemia aggravates seizures and status epilepticus-induced hippocampal damage.

    PubMed

    Huang, Chin-Wei; Cheng, Juei-Tang; Tsai, Jing-Jane; Wu, Sheng-Nan; Huang, Chao-Ching

    2009-01-01

    Epileptic seizures in diabetic hyperglycemia (DH) are not uncommon. This study aimed to determine the acute behavioral, pathological, and electrophysiological effects of status epilepticus (SE) on diabetic animals. Adult male Sprague-Dawley rats were first divided into groups with and without streptozotocin (STZ)-induced diabetes, and then into treatment groups given a normal saline (NS) (STZ-only and NS-only) or a lithium-pilocarpine injection to induce status epilepticus (STZ + SE and NS + SE). Seizure susceptibility, severity, and mortality were evaluated. Serial Morris water maze test and hippocampal histopathology results were examined before and 24 h after SE. Tetanic stimulation-induced long-term potentiation (LTP) in a hippocampal slice was recorded in a multi-electrode dish system. We also used a simulation model to evaluate intracellular adenosine triphosphate (ATP) and neuroexcitability. The STZ + SE group had a significantly higher percentage of severe seizures and SE-related death and worse learning and memory performances than the other three groups 24 h after SE. The STZ + SE group, and then the NS + SE group, showed the most severe neuronal loss and mossy fiber sprouting in the hippocampal CA3 area. In addition, LTP was markedly attenuated in the STZ + SE group, and then the NS + SE group. In the simulation, increased intracellular ATP concentration promoted action potential firing. This finding that rats with DH had more brain damage after SE than rats without diabetes suggests the importance of intensively treating hyperglycemia and seizures in diabetic patients with epilepsy. PMID:19384590

  16. Hypoglycemic and antioxidant effects of Daraesoon (Actinidia arguta shoot) in animal models of diabetes mellitus

    PubMed Central

    Lee, Ah-Yeon; Kang, Min-Jung; Choe, Eunok

    2015-01-01

    BACKGROUND/OBJECTIVES The primary objective of the treatment of diabetes mellitus is the attainment of glycemic control. Hyperglycemia increases oxidative stress which contributes to the progression of diabetic complications. Thus, the purpose of this study was to investigate the hypoglycemic and antioxidant effects of Daraesoon (Actinidia arguta shoot) in animal models of diabetes mellitus. MATERIALS/METHODS Rats with streptozotocin-induced diabetes received an oral administration of a starch solution (1 g/kg) either with or without a 70% ethanol extract of Daraesoon (400 mg/kg) or acarbose (40 mg/kg) after an overnight fast and their postprandial blood glucose levels were measured. Five-week-old C57BL/6J mice were fed either a basal or high-fat/high-sucrose (HFHS) diet with or without Daraesoon extract (0.4%) or acarbose (0.04%) for 12 weeks after 1 week of adaptation to determine the effects of the chronic consumption of Daraesoon on fasting hyperglycemia and antioxidant status. RESULTS Compared to the control group, rats that received Daraesoon extract (400 mg/kg) or acarbose (40 mg/kg) exhibited a significant reduction in the area under the postprandial glucose response curve after the oral ingestion of starch. Additionally, the long-term consumption of Daraesoon extract or acarbose significantly decreased serum glucose and insulin levels as well as small intestinal maltase activity in HFHS-fed mice. Furthermore, the consumption of Daraesoon extract significantly reduced thiobarbituric acid reactive substances and increased glutathione levels in the livers of HFHS-fed mice compared to HFHS-fed mice that did not ingest Daraesoon. CONCLUSIONS Daraesoon effectively suppressed postprandial hyperglycemia via the inhibition of ?-glucosidase in STZ-induced diabetic rats. Chronic consumption of Daraesoon alleviated fasting hyperglycemia and oxidative stress in mice fed a HFHS diet. PMID:26060538

  17. Angiotensin-(1-7) attenuates diabetic nephropathy in Zucker diabetic fatty rats.

    PubMed

    Giani, Jorge F; Burghi, Valeria; Veiras, Luciana C; Tomat, Analía; Muñoz, Marina C; Cao, Gabriel; Turyn, Daniel; Toblli, Jorge E; Dominici, Fernando P

    2012-06-15

    Angiotensin (ANG)-(1-7) is known to attenuate diabetic nephropathy; however, its role in the modulation of renal inflammation and oxidative stress in type 2 diabetes is poorly understood. Thus in the present study we evaluated the renal effects of a chronic ANG-(1-7) treatment in Zucker diabetic fatty rats (ZDF), an animal model of type 2 diabetes and nephropathy. Sixteen-week-old male ZDF and their respective controls [lean Zucker rats (LZR)] were used for this study. The protocol involved three groups: 1) LZR + saline, 2) ZDF + saline, and 3) ZDF + ANG-(1-7). For 2 wk, animals were implanted with subcutaneous osmotic pumps that delivered either saline or ANG-(1-7) (100 ng·kg(-1)·min(-1)) (n = 4). Renal fibrosis and tissue parameters of oxidative stress were determined. Also, renal levels of interleukin-6 (IL-6), tumor necrosis factor-? (TNF-?), ED-1, hypoxia-inducible factor-1? (HIF-1?), and neutrophil gelatinase-associated lipocalin (NGAL) were determined by immunohistochemistry and immunoblotting. ANG-(1-7) induced a reduction in triglyceridemia, proteinuria, and systolic blood pressure (SBP) together with a restoration of creatinine clearance in ZDF. Additionally, ANG-(1-7) reduced renal fibrosis, decreased thiobarbituric acid-reactive substances, and restored the activity of both renal superoxide dismutase and catalase in ZDF. This attenuation of renal oxidative stress proceeded with decreased renal immunostaining of IL-6, TNF-?, ED-1, HIF-1?, and NGAL to values similar to those displayed by LZR. Angiotensin-converting enzyme type 2 (ACE2) and ANG II levels remained unchanged after treatment with ANG-(1-7). Chronic ANG-(1-7) treatment exerts a renoprotective effect in ZDF associated with a reduction of SBP, oxidative stress, and inflammatory markers. Thus ANG-(1-7) emerges as a novel target for treatment of diabetic nephropathy. PMID:22492942

  18. Protective effects of Piper nigrum and Vinca rosea in alloxan induced diabetic rats.

    PubMed

    Kaleem, M; Sheema; Sarmad, H; Bano, B

    2005-01-01

    In the present study aqueous extract of Piper nigrum seeds and Vinca rosea flowers were administered orally to alloxan induced diabetic rats once a day for 4 weeks. These treatments lead to significant lowering of blood sugar level and reduction in serum lipids. The levels of antioxidant enzymes, catalase and glutathione peroxidase decreased in alloxan induced diabetic rats however these levels returned to normal in insulin, P. nigrum and V. rosea treated rats. There was no significant difference in superoxide dismutase activity in all groups compared to controls. Lipid peroxidation levels were significantly higher in diabetic rats and it was slightly increased in insulin, P. nigrum and V. rosea treated rats as compared to control rat. These results suggest that oxidative stress plays a key role in diabetes, and treatment with P. nigrum and V. rosea are useful in controlling not only the glucose and lipid levels but these components may also be helpful in strengthening the antioxidants potential. PMID:15881860

  19. Use of unripe plantain (Musa paradisiaca) in the management of diabetes and hepatic dysfunction in streptozotocin induced diabetes in rats

    PubMed Central

    Okafor, Polycarp

    2015-01-01

    Aim This study aims to investigate the effect of unripe plantain (Musa paradisiaca) on markers of hepatic dysfunction in streptozotocin induced diabetic rats. Methods Blood glucose; relative liver weight (RLW); relative kidney weight (RKW); relative heart weight (RHW); relative pancreatic weight (RPW); serum and hepatic serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP); serum amylase, lipase, total, and conjugated bilirubin; and chemical analysis of the test feed were determined using standard techniques. Results The diabetic rats had significant alteration (P < 0.05) of blood glucose; RLW; RKW; RPW; serum and hepatic AST, ALT, and ALP; serum total and conjugated bilirubin; and serum lipase activities compared with nondiabetic while these parameters were significantly improved (P < 0.05) in the rats fed unripe plantain. There were no significant differences (P > 0.05) in the RHW of the rats in the three groups, as well as significant decreases (P < 0.05) in the amylase levels of the diabetic rats compared with the nondiabetic, but there was nonsignificant increase (P > 0.05) in the amylase levels of the rats fed unripe plantain compared with the nondiabetic rats. The test and standard rat feeds contained considerable amount of proteins, carbohydrates, fats, phenols, and crude fiber. Conclusion Amelioration of acute pancreatitis by unripe plantain could play a key role in its management of diabetes and related complications. PMID:25838921

  20. Visceral Hypersensitivity and Altered Colonic Motility in Type 2 Diabetic Rat

    PubMed Central

    Sung, Tae Sik; La, Jun-Ho; Kang, Tong Mook; Kim, Tae Wan; Yang, Il-Suk

    2015-01-01

    Background/Aims Abnormal visceral sensitivity and disordered motility are common in patients with diabetes mellitus. The purpose of the present study was to investigate whether visceral sensation and bowel motility were altered in a rat model of type 2 diabetes mellitus accompanied by weight loss. Methods A type 2 diabetic rat model in adulthood was developed by administrating streptozotocin (STZ; 90 mg/kg, i.p.) to neonatal rats. Eight weeks after STZ administration, rats with blood glucose level of 200 mg/dL or higher were selected and used as diabetic group (n = 35) in this study. Abdominal withdrawal reflex and arterial pulse rate were measured to examine visceral nociception induced by colorectal distension (0.1–1.0 mL). The amplitude, frequency, and area under the curve (AUC) of spontaneous phasic contractions of colonic circular muscles were recorded in vitro to examine colonic motility. Results STZ-treated diabetic rats gained significantly less weight for 8 weeks than control (P < 0.01). Forty-eight percent of the diabetic rats showed enhanced visceral nociceptive response to colorectal distension. Diabetic rats did not differ from control rats in colorectal compliance. However, the frequency and AUC, not the amplitude, of colonic spontaneous contraction in vitro was significantly decreased in diabetic rats compared to control rats (P < 0.01 in frequency and P < 0.05 in AUC). Conclusions These results demonstrate visceral hypersensitivity and colonic dysmotility in a rat model of type 2 diabetes mellitus accompanied by weight loss. PMID:26424043

  1. Eucalyptus globulus (Eucalyptus) Treatment of Candidiasis in Normal and Diabetic Rats

    PubMed Central

    Bokaeian, Mohammad; Nakhaee, Alireza; Moodi, Bita; Ali Khazaei, Hossein

    2010-01-01

    Background: The leaves of Eucalyptus globulus (eucalyptus) are used for treatment of diabetes mellitus in traditional medicine. The aim of this study was to evaluate the effects of eucalyptus in treatment of established systemic infection with Candida albicans in normal and streptozotocin-induced diabetic rats. Methods: Sixty normoglycemic male Wistar rats, weighing 200-250 g, were selected and randomly divided into six groups (n= 10): normal control, control + C. albicans, control + eucalyptus + C. albicans, diabetic control, diabetic + C. albicans, diabetic + eucalyptus + C. albicans. Diabetes was induced after a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and eucalyptus was added to the diet (62.5 g/kg) and drinking water (2.5 g/L) of treated animals for 4 weeks. The concerned groups were inoculated with C. albicans 15 days after diabetes induction. At the end of one month experiment, fasted rats were killed by cervical decapitation. Blood was collected from neck vein for estimation of glucose. C. albicans concentrations were estimated in liver and kidneys using serial dilution culture of tissue homogenates. Results: Eucalyptus administration significantly improved the hyperglycemia, polydipsia, polyphagia, and it also compensated weight loss of diabetic rats (P<0.05). Moreover, eucalyptus caused a significant reduction in C. albicans concentration in liver and kidney homogenates (P<0.01). Conclusion: The results revealed that eucalyptus improves Candidia infection in normal and diabetic rats that in some ways validates the traditional use of this plant in treatment of diabetic patients. PMID:21079663

  2. Native and oxidized low-density lipoproteins enhance superoxide production from diabetic rat glomeruli.

    PubMed

    Chen, H C; Tan, M S; Guh, J Y; Tsai, J H; Lai, Y L

    2000-01-01

    Oxygen free radicals have been implicated in mediating diabetic complications, and patients with diabetic nephropathy frequently show increased levels of circulating and oxidized low-density lipoproteins (LDL). In the present study, we measured the superoxide production of glomeruli isolated from poorly controlled diabetic (streptozotocin) rats sacrificed 1 week and 1, and 3 months after the induction of diabetes. The animals were stimulated with native and oxidized LDL isolated from normal humans with normolipidemia. The superoxide ion was measured by using a spectrophotometer. The results demonstrated that the poorly controlled diabetic rat glomeruli showed a significantly higher production of superoxide than normal glomeruli under basal conditions, and this production increased further with the progression of diabetes. Stimulation with either LDL or oxidized LDL enhanced superoxide production by diabetic glomeruli, with oxidized LDL being more potent than LDL. Our results suggest that oxidized LDL may play important roles in the pathogenesis of diabetic nephropathy through enhanced generation of oxygen free radicals. PMID:10765116

  3. Effect of tempol on the passive avoidance and novel object recognition task in diabetic rats.

    PubMed

    Jabbarpour, Zahra; Shahidi, Siamak; Saidijam, Massoud; Sarihi, Abdolrahman; Hassanzadeh, Taghi; Esmaeili, Rasoul

    2014-02-01

    Diabetes mellitus (DM) has several effects, including cognitive impairment. Oxidative stress is associated with complications from diabetes. It seems that antioxidants can reduce some complications of the diabetes induced by oxidative stress. The objective of this study was to evaluate the effect of synthetic antioxidant, tempol on the passive avoidance (PA) memory and novel object recognition (NOR) tests in the diabetic rats. Forty male Wistar rats randomly divided into the control, diabetic, diabetic receiving tempol and healthy receiving tempol groups. Diabetes was induced by injection of streptozotocin (STZ) (60 mg/kg, i.p.). Then, the rats received saline or tempol (30 mg/kg) orally by gavages for 60 days. After that, they were assessed using the PA memory and NOR tests. The results of NOR test showed that the discrimination index (DI) in the healthy receiving tempol group and diabetic control group was significantly lower than control group. Also the amount of this index in diabetic receiving tempol group was significantly higher than diabetic group. The results of PA test indicated that the number of trials to acquisition in the diabetic rats is significantly more than control and diabetic tempol treated groups. Also, the time spent in the dark compartment (TDC) in the control and diabetic receiving tempol groups was less than diabetic group. TDC in the healthy receiving tempol group was more than control group. It can be concluded that although use of tempol is restricted as a cognitive enhancer in non-diabetic subjects but long-term administration of synthetic antioxidant, tempol, is able to dramatically improve diabetes-induced learning and memory deficit in both PA and NOR tests. PMID:24412412

  4. Antidiabetic effect of hydroalcoholic extract of Carthamus tinctorius L. in alloxan-induced diabetic rats

    PubMed Central

    Asgary, Sedigheh; Rahimi, Parivash; Mahzouni, Parvin; Madani, Hossein

    2012-01-01

    Background: Carthamus tinctorius L. (Compositae) has been used in Iranian traditional medicine for treatment of diabetes. In this study, anti-diabetic effect of its hydroalcoholic extract was compared with that of glibenclamide. Methods: Male white Wistar rats were randomly allocated into four groups of six each: nondiabetic control; diabetic control; diabetic treated with hydroalcoholic extract of Carthamus tinctorius (200 mg kg-1 BW); diabetic rats treated with glibenclamide (0.6 mg kg-1 BW). Alloxan was administered (120 mg kg-1 BW), intraperitoneally to induce diabetes. Fasting blood samples were collected three times, before injection of alloxan, two weeks and six weeks after injection of alloxan and fasting blood sugar (FBS), Hb A1C, insulin, cholesterol, LDL-C, HDL-C, VLDL-C, triglyceride, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured each time. Results: FBS, triglyceride, cholesterol, LDL-C and VLDL-C had a meaningful decrease in diabetic rats treated with Carthamus tinctorius and diabetic rats treated with glibenclamide as compared with diabetic rats with no treatment. Insulin level increased significantly in diabetic groups received treatment (glibenclamide or Carthamus tinctorius L) in comparison with diabetic group with no treatment. The histological study revealed size of islets of Langerhans enlarged significantly consequentially as compared with diabetic rats with no treatment. The extract appeared non toxic as evidenced by normal levels of AST, ALP and ALT. Effects of administrating glibenclamide or extract of Carthamus tinctorius L on all biochemical parameters discussed above showed no difference and both tend to bring the values to near normal. Conclusion: These results suggested that the hydroalcoholic extract of Carthamus tinctorius possesses beneficial effect on treatment of diabetes. PMID:23267403

  5. Glucose cycling in islets from healthy and diabetic rats

    SciTech Connect

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

    1990-04-01

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

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

    PubMed Central

    Ohta, Takeshi; Katsuda, Yoshiaki; Miyajima, Katsuhiro; Kimura, Shuichi

    2014-01-01

    The Spontaneously Diabetic Torii Leprfa (SDT fatty) rat is a novel type 2 diabetic model wherein both male and female rats develop glucose and lipid abnormalities from a young age. In this study, we investigated gender differences in abnormalities and related complications in SDT fatty rats. Food intake was higher in males compared to female rats; however, body weight was not different between genders. Progression of diabetes, including increases in blood glucose and declines in blood insulin, was observed earlier in male rats than in females, and diabetic grade was more critical in male rats. Blood lipids tended to increase in female rats. Gonadal dysfunction was observed in both male and female rats with aging. Microangiopathies, such as nephropathy, retinopathy, neuropathy, and osteoporosis, were seen in both genders, and pathological grade and progression were more significant in males. Qualitative and quantitative changes were observed for metabolic disease gender differences in SDT fatty rats. The SDT fatty rat is a useful model for researching gender differences in metabolic disorders and related diseases in diabetes with obesity. PMID:24892034

  7. Perturbation in kidney lipid metabolic profiles in diabetic rats with reference to alcoholic oxidative stress

    PubMed Central

    Shanmugam, K. R.; Ramakrishna, C. H.; Mallikarjuna, K.; Reddy, K. Sathyavelu

    2009-01-01

    Diabetes is a major threat to global public health, and the number of diabetic patients is rapidly increasing worldwide. Evidence suggests that oxidative stress is involved in the pathophysiology of diabetic complications and alcoholic diseases. The aim of this study is to find out the impact of alcohol on lipid metabolic profiles in kidney tissue under streptozotocin induced diabetic condition. No study has been reported so far on the effect of alcohol on diabetic condition and also with reference to lipid metabolic profiles. Hence, the present study has been designed to elucidate the impact of alcoholism on diabetic condition. Male wistar strain albino rats were randomly divided into four groups: control (saline treated) NC, alcohol-treated (At), diabetic control (DC), and alcohol-treated diabetic rats (D+At). In alcohol-treated diabetic rats, we observed high levels of MDA, total cholesterol, triglycerides, phospholipids and also high levels of blood glucose than other groups. Moreover, degenerative changes of renal cells in alcohol-treated diabetic group were maximized by administration of alcohol as evinced by histopathological examination. This study suggests that alcohol consumption could be an aggravation factor which contributes for the formation of free radicals in diabetic condition. Therefore, consumption of alcohol during diabetic condition is harmful. PMID:20436729

  8. Antidiabetic Activity of Artemisia amygdalina Decne in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Ganai, Bashir A.; Akbar, Seema; Mubashir, Khan; Dar, Showkat Ahmad; Dar, Mohammad Younis; Tantry, Mudasir A.

    2014-01-01

    Artemisia species have been extensively used for the management of diabetes in folklore medicine. The current study was designed to investigate the antidiabetic and antihyperlipidemic effects of Artemisia amygdalina. Petroleum ether, ethyl acetate, methanol, and hydroethanolic extracts of Artemisia amygdalina were tested for their antidiabetic potentials in diabetic rats. The effect of extracts was observed by checking the biochemical, physiological, and histopathological parameters in diabetic rats. The hydroethanolic and methanolic extracts each at doses of 250 and 500?mg/kg b. w significantly reduced glucose levels in diabetic rats. The other biochemical parameters like cholesterol, triglycerides, low density lipoproteins (LDL), serum creatinine, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatise (ALP), were found to be reduced by the hydroethanolic and methanolic extracts. The extracts also showed reduction in the feed and water consumption of diabetic rats when compared with the diabetic control. The histopathological results of treated groups showed the regenerative/protective effect on ?-cells of pancreas in diabetic rats. The current study revealed the antidiabetic potential of Artemisia amygdalina being effective in hyperglycemia and that it can effectively protect against other metabolic aberrations caused by diabetes in rats, which seems to validate its therapeutic traditional use. PMID:24967338

  9. Pioglitazone reverses down-regulation of cardiac PPAR{gamma} expression in Zucker diabetic fatty rats

    SciTech Connect

    Pelzer, Theo . E-mail: pelzer_t@klinik.uni-wuerzburg.de; Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Segerer, Stephan; Lichtenwald, Margit; Law, Marilyn P.; Schaefers, Michael; Ertl, Georg; Neyses, Ludwig

    2005-04-08

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

  10. Cyproterone acetate and reversal of the impaired endometrial decidualization in streptozotocin-diabetic pseudopregnant rats.

    PubMed

    Zakaria, R; Ismail, Z; Chatterjee, A

    2000-08-01

    Reproductive dysfunction in the female diabetic rat is associated with impaired hypothalamic-hypophyseal system, anovulation, insufficiency of ovarian steroidogenesis and spontaneous failure of pregnancy. Formation of decidua, the highly modified endometrium of pregnancy and pseudopregnancy could only be achieved when the uterus was sensitized by a sequence of oestrogen and progesterone. In this study, we examined whether the impaired expression of endometrial decidualization in the pseudopregnant rat is linked with diabetes-associated hypersecretion of testosterone. Rats were made pseudopregnant by sterile mating. Diabetes was induced by streptozotocin on day 1 p.c. Deciduogenic stimulus was given on day 5 p.c. Treatment of cyproterone acetate (10 mg kg(-1)) was scheduled from day 5 through day 9 p.c. Animals were killed on day 10 p.c, and the degree of endometrial decidual growth, plasma levels of oestradiol, progesterone, ACTH and testosterone were determined. Results showed that compared to controls there was a concomitant drop in endometrial decidual growth concurrently with impaired levels of oestradiol and progesterone in diabetic pseudopregnant rats. ACTH and testosterone levels were, however, profoundly elevated. Cyproterone acetate treatment in the diabetic pseudopregnant rat resulted in a simultaneous elevation of oestradiol and progesterone, which eventually helped the endometrial differentiation to decidua in the diabetic pseudopregnant rat parallel to controls. Present experimental data suggest that diabetes-associated impaired endometrial decidualization in the pseudopregnant rat is possibly caused by testosterone-induced oestrogen deficiency. PMID:10887050

  11. Impact of Ellagic Acid in Bone Formation after Tooth Extraction: An Experimental Study on Diabetic Rats

    PubMed Central

    Al-Obaidi, Mazen M. Jamil; Al-Bayaty, Fouad Hussain; Hussaini, Jamal; Khor, Goot Heah

    2014-01-01

    Objectives. To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction. Methods. Twenty-four Sprague Dawley male rats weighing 250–300?g were selected for this study. All animals were intraperitoneally injected with 45?mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50?mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test. Results. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat. Conclusion. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction. PMID:25485304

  12. Polarized light improves cutaneous healing on diabetic rats

    NASA Astrophysics Data System (ADS)

    Ramalho, Luciana Maria Pedreira; Oliveira, Priscila Chagas; Marques, Aparecida Maria Cordeiro; Barbosa Pinheiro, Antonio L.

    2010-02-01

    The aim of this study was to evaluate the healing of 3rd degree burn on diabetic rats submitted or not to treatment with Polarized Light. Diabetes mellitus (Streptozotocin, 60mg/kg) was induced on 45 male Wistar albinus rats and a third degree burn (1.5× 1.5cm) was created in the dorsum of each animal under general anesthesia. After a regular quarantine period, the animals were randomly distributed into three groups as follows: G1: control (no treatment, n =15); G2: Polarized Light (?=400-2000nm, 20J/cm2) and G3: Polarized Light (?=400-2000nm, 40J/cm2). The phototherapy performed on group G2 was Polarized Light dose 20J/cm2 and G3 was Polarized Light dose 40J/cm2 (Bioptron®, ?400-2000 nm, 40mW; 2.4J/cm2 per minute; ? +/- 5.5 cm; Bioptron AG, Monchaltorf, Switzerland). The phototherapy started immediately post-burning and was repeated daily until the day before the animal death. The energy was applied transcutaneously respecting the focal distance of 10cm as recommended by the manufacturer. The dose was 20 or 40J/cm2 (4min 15s or 8min.and 30s). At each time point chosen (7, 14, and 21 days post-burning) and following macroscopic examination, each animal was killed by an overdose of general anesthesia. Slides were stained with HE, Sirius Red, and CK AE1/AE3 antibody. Qualitative and semi-quantitative analyses were performed under light microscopy. The animals submitted to phototherapy (20J/cm2) showed significant differences on regards revascularization and epithelialization. The use of 20J/cm2 was effective on improving the healing of third degree buns on diabetic animals at both early and late stages of the repair.

  13. Converting enzyme inhibition and the glomerular hemodynamic response to glycine in diabetic rats.

    PubMed

    Slomowitz, L A; Peterson, O W; Thomson, S C

    1999-07-01

    GFR normally increases during glycine infusion. This response is absent in humans and rats with established diabetes mellitus. In diabetic patients, angiotensin-converting enzyme inhibition (ACEI) restores the effect of glycine on GFR. To ascertain the glomerular hemodynamic basis for this effect of ACEI, micropuncture studies were performed in male Wistar-Froemter rats after 5 to 6 wk of insulin-treated streptozotocin diabetes. The determinants of single-nephron GFR (SNGFR) were assessed in each rat before and during glycine infusion. Studies were performed in diabetics, diabetics after 5 d of ACEI (enalapril in the drinking water), and weight-matched controls. Diabetic rats manifest renal hypertrophy and glomerular hyperfiltration but not glomerular capillary hypertension. ACEI reduced glomerular capillary pressure, increased glomerular ultrafiltration coefficient, and did not mitigate hyperfiltration. In controls, glycine increased SNGFR by 30% due to increased nephron plasma flow. In diabetics, glycine had no effect on any determinant of SNGFR. In ACEI-treated diabetics, the SNGFR response to glycine was indistinguishable from nondiabetics, but the effect of glycine was mediated by greater ultrafiltration pressure rather than by greater plasma flow. These findings demonstrate that: (1) The absent response to glycine in established diabetes does not indicate that renal functional reserve is exhausted by hyperfiltration; and (2) ACEI restores the GFR response to glycine in established diabetes, but this response is mediated by increased ultrafiltration pressure rather than by increased nephron plasma flow. PMID:10405200

  14. Anti-diabetic potentials of Momordica charantia and Andrographis paniculata and their effects on estrous cyclicity of alloxan-induced diabetic rats.

    PubMed

    Reyes, B A S; Bautista, N D; Tanquilut, N C; Anunciado, R V; Leung, A B; Sanchez, G C; Magtoto, R L; Castronuevo, P; Tsukamura, H; Maeda, K-I

    2006-04-21

    Momordica charantia and Andrographis paniculata are the commonly used herbs by the diabetic patients in Pampanga, Philippines. While the anti-diabetic potential of Momordica charantia is well established in streptozocin- or alloxan-induced diabetic animals, the anti-diabetic potential of Andrographis paniculata in alloxan-induced diabetic rat is not known. Neither the effects of these herbs on estrous cyclicity of alloxan-induced diabetic rats are elucidated. Thus, in these experiments, Momordica charantia fruit juice or Andrographis paniculata decoction was orally administered to alloxan-induced diabetic rats. Rats that were treated with Momordica charantia and Andrographis paniculata had higher body weight (BW) compared with diabetic positive control (P < 0.01) from day 22 to day 27 (D27) but exhibited lower BW than the non-diabetic control (P < 0.05). These rats had lower feed (P < 0.05) and liquid intakes (P < 0.01) compared with diabetic positive control from day 17 to D27, but similar with the non-diabetic control. The blood glucose levels in these groups were significantly reduced from day 12 to D27 compared with diabetic positive control (P < 0.01), however, comparable with non-diabetic control. The diabetic positive control had extended mean estrous cycles (8 days) compared to Momordica charantia and Andrographis paniculata-treated diabetic rats (5 days; P < 0.05). Our results suggest that the anti-diabetic potentials of Momordica charantia and Andrographis paniculata could restore impaired estrous cycle in alloxan-induced diabetic rats. PMID:16298503

  15. Diabetic Nephropathy Amelioration by a Low-Dose Sitagliptin in an Animal Model of Type 2 Diabetes (Zucker Diabetic Fatty Rat)

    PubMed Central

    Mega, Cristina; Teixeira de Lemos, Edite; Vala, Helena; Fernandes, Rosa; Oliveira, Jorge; Mascarenhas-Melo, Filipa; Teixeira, Frederico; Reis, Flávio

    2011-01-01

    This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl peptidase 4 inhibitor, on metabolic profile and on renal lesions aggravation in a rat model of type-2 diabetic nephropathy, the Zucker diabetic fatty (ZDF) rat. Diabetic and obese ZDF (fa/fa) rats and their controls ZDF (+/+) were treated for 6 weeks with vehicle (control) or sitagliptin (10?mg/kg/bw). Blood/serum glucose, HbA1c, insulin, Total-c, TGs, urea, and creatinine were assessed, as well as kidney glomerular and tubulointerstitial lesions (interstitial fibrosis/tubular atrophy), using a semiquantitative rating from 0 (absent/normal) to 3 (severe and extensive damage). Vascular lesions were scored from 0–2. Sitagliptin in the diabetic rats promoted an amelioration of glycemia, HbA1c, Total-c, and TGs, accompanied by a partial prevention of insulinopenia. Furthermore, together with urea increment prevention, renal lesions were ameliorated in the diabetic rats, including glomerular, tubulointerstitial, and vascular lesions, accompanied by reduced lipid peroxidation. In conclusion, chronic low-dose sitagliptin treatment was able to ameliorate diabetic nephropathy, which might represent a key step forward in the management of T2DM and this serious complication. PMID:22203828

  16. Polyopes lancifolia Extract, a Potent ?-Glucosidase Inhibitor, Alleviates Postprandial Hyperglycemia in Diabetic Mice

    PubMed Central

    Min, Seong Won; Han, Ji Sook

    2014-01-01

    This study was designed to investigate the inhibitory effects of Polyopes lancifolia extract (PLE) on ?-glucosidase activity, ?-amylase activitiy, and postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. The results of this study revealed a marked inhibitory effect of PLE on ?-glucosidase and ?-amylase activities. The IC50s of PLE against ?-glucosidase and ?-amylase were 0.20 mg/mL and 0.35 mg/mL, respectively. PLE was a more effective inhibitor of ?-glucosidase and ?-amylase activities than acarbose, the positive control. The postprandial blood glucose levels of STZ-induced diabetic mice were significantly lower in the PLE treated group than in the control group. Moreover, PLE administration was associated with a decreased area under the curve for the glucose response in diabetic mice. These results indicate that PLE may be a potent inhibitor of ?-glucosidase and ?-amylase activities and may suppress postprandial hyperglycemia. PMID:24772403

  17. Antidiabetic Activity of Vinca rosea Extracts in Alloxan-Induced Diabetic Rats

    PubMed Central

    Ahmed, Mohammed Fazil; Kazim, Syed Mohammed; Ghori, Syed Safiullah; Mehjabeen, Syeda Sughra; Ahmed, Shaik Rasheed; Ali, Shaik Mehboob; Ibrahim, Mohammed

    2010-01-01

    The present study was carried out to evaluate the antidiabetic activity of Vinca rosea methanolic whole plant extracts in alloxan induced diabetic rats for 14 days. The methanolic whole plant extract at high dose (500?mg/kg) exhibited significant anti-hyperglycemic activity than whole plant extract at low dose (300?mg/kg) in diabetic rats. The methanolic extracts also showed improvement in parameters like body weight and lipid profile as well as regeneration of ?-cells of pancreas in diabetic rats. Histopathological studies reinforce the healing of pancreas, by methanolic Vinca rosea extracts, as a possible mechanism of their antidiabetic activity. PMID:20652054

  18. Genistein Treatment Confers Protection against Gliopathy and Vasculopathy of the Diabetic Retina in Rats.

    PubMed

    Elgayar, Sanaa A M; Eltony, Sohair A; Sayed, Abdelrahman A; Abdel-Rouf, Maha M

    2015-12-01

    Retinopathy remains an important complication of diabetes. This work was carried out to evaluate the protective effects of genistein from diabetic retinopathy in rat. Fifteen adult male albino rats were divided into two groups; Group I: control (n?=?5) and Group II: streptozotocin induced diabetic group (n?=?10), which is equally divided into two subgroups; IIa (diabetic vehicle control) and IIb (diabetic genistein-treated). Specimens were taken from the retina 12 weeks post induction, processed and examined using light, immunohistochemical, ultrastructural techniques. Blood samples were assayed for the levels of glucose. In comparison with the diabetic non-treated group, the histological changes in macro and microglial glial cells reactivity and retinal blood capillaries were improved in genistein-treated groups. In addition, GFAP and iNOS expressions in the retina and the blood glucose level were reduced. Genistein ameliorates the histological changes of diabetic retinopathy reaching healing features, which resemble that of a normal retina. PMID:26548435

  19. Remission of diabetes by insulin gene therapy using a hepatocyte-specific and glucose-responsive synthetic promoter.

    PubMed

    Han, Jaeseok; McLane, Brienne; Kim, Eung-Hwi; Yoon, Ji-Won; Jun, Hee-Sook

    2011-03-01

    Efficient production of insulin in response to changes in glucose levels has been a major issue for insulin gene therapy to treat diabetes. To express target genes in response to glucose specifically in hepatocytes, we generated a synthetic promoter library containing hepatocyte nuclear factor-1, CAAT/enhancer-binding protein (C/EBP) response element, and glucose-response element. Combinations of these three cis-elements in 3-, 6-, or 9-element configurations were screened for transcriptional activity and then glucose responsiveness in vitro. The most effective promoter (SP23137) was selected for further study. Intravenous administration of a recombinant adenovirus expressing furin-cleavable rat insulin under control of the SP23137 promoter into streptozotocin (STZ)-induced diabetic mice resulted in normoglycemia, which was maintained for >30 days. Glucose tolerance tests showed that treated mice produced insulin in response to glucose and cleared exogenous glucose from the blood in a manner similar to nondiabetic control mice, although the clearance was somewhat delayed. Insulin expression was seen specifically in the liver and not in other organs. These observations indicate the potential of this synthetic, artificial promoter to regulate glucose-responsive insulin production and remit hyperglycemia, thus providing a new method of liver-directed insulin gene therapy for type 1 diabetes. PMID:21119621

  20. Diazoxide reduces status epilepticus neuron damage in diabetes.

    PubMed

    Huang, Chin-Wei; Wu, Sheng-Nan; Cheng, Juei-Tang; Tsai, Jing-Jane; Huang, Chao-Ching

    2010-05-01

    Diabetic hyperglycemia is associated with seizure severity and may aggravate brain damage after status epilepticus. Our earlier studies suggest the involvement of ATP-sensitive potassium channels (K(ATP)) in glucose-related neuroexcitability. We aimed to determine whether K(ATP) agonist protects against status epilepticus-induced brain damage. Adult male Sprague-Dawley rats were divided into two groups: the streptozotocin (STZ)-induced diabetes (STZ) group and the normal saline (NS) group. Both groups were treated with either diazoxide (15 mg/kg, i.v.) (STZ + DZX, NS + DZX) or vehicle (STZ + V, NS + V) before lithium-pilocarpine-induced status epilepticus. We evaluated seizure susceptibility, severity, and mortality. The rats underwent Morris water-maze tests and hippocampal histopathology analyses 24 h post-status epilepticus. A multi-electrode recording system was used to study field excitatory postsynaptic synaptic potentials (fEPSP). RNA interference (RNAi) to knockdown Kir 6.2 in a hippocampal cell line was used to evaluate the effect of diazoxide in the presence of high concentration of ATP. Seizures were less severe (P < 0.01), post-status epilepticus learning and memory were better (P < 0.05), and neuron loss in the hippocampal CA3 area was lower (P < 0.05) in the STZ + DZX than the STZ + V group. In contrast, seizure severity, post-status epilepticus learning and memory, and hippocampal CA3 neuron loss were comparable in the NS + DZX and NS + V groups. fEPSP was lower in the STZ + DZX but not in the NS + DZX group. The RNAi study confirmed that diazoxide, with its K(ATP)-opening effects, could counteract the K(ATP)-closing effect by high dose ATP. We conclude that, by opening K(ATP), diazoxide protects against status epilepticus-induced neuron damage during diabetic hyperglycemia. PMID:19728004

  1. Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in diabetic rats.

    PubMed

    Zhu, Xia; Cheng, Ya-Qin; Du, Lei; Li, Yu; Zhang, Fan; Guo, Hao; Liu, Yao-Wu; Yin, Xiao-Xing

    2015-02-01

    This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55?mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60?mg/kg/day, i.g.) for 9?weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and ?-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-?B p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1? in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-?B. PMID:25380391

  2. Effect of Transforming Growth Factor Beta 1 on Wound Healing in Induced Diabetic Rats

    PubMed Central

    El Gazaerly, Hanaa; Elbardisey, Dorria M.; Eltokhy, Heba M.; Teaama, Doaa

    2013-01-01

    Objective Delayed wound healing is one of the complications of diabetes mellitus, exhibited by profound inflammation and decreased granulation tissues. The current study was carried out to evaluate wound healing in both normal and diabetic rats. In addition, it evaluated the potential protective effect of transforming growth factor ?1 (TGF ?1), that has the broadest spectrum of actions, affecting all cell types that are involved in all stages of wound healing to accelerate wound healing in normal & diabetic rats. Methods : The present study was performed on 40 male albino rats. Each 10 rats were designed as a group. Group I saved as control. They received incisional wound in their tongues 1 cm length and 1/2 cm depth. Group II received 500 ng/kg of TGF ?1 5 minutes before wounding. Group III diabetes was induced then rats were treated as second group. At the 14th day post wounding, sections of tongues were taken for hematoxylin and eosin and Masson's trichome staining to examine the histological changes. The intracellular actions of TGF ?1 were studied by TEM. Results A higher cell proliferation rate and a denser and more organized new extracellular matrix and complete wound closure was detected at the 14th days in the TGF ?1 treated wound in comparison with the 14th days for the untreated, control groups. There were delayed wound healing in diabetic rats, decreased re-epithelialization, granulation tissue thickness, matrix density, number of infiltrated cells, and number of capillaries. In TGF ?1 treated diabetic rats, showed significant healing improvement was obvious as compared with diabetic rats. Conclusions A single intravenous injection of TGF ?1 was sufficient to enhance wound healing in rat's tongue. This approach represents a new strategy that may be applied to the treatment of incisional wounds in human diabetic patients. PMID:24421745

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

    SciTech Connect

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

    1990-05-01

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

  4. Biochemical and Neurotransmitters Changes Associated with Tramadol in Streptozotocin-Induced Diabetes in Rats

    PubMed Central

    Ezzeldin, Essam; Souror, Wafaa A. H.; El-Nahhas, Toqa; Soudi, Abdel Nasser M. M.; Shahat, Abdelaaty A.

    2014-01-01

    The incidence of diabetes is increasing worldwide. Chronic neuropathic pain occurs in approximately 25% of diabetic patients. Tramadol, an atypical analgesic with a unique dual mechanism of action, is used in the management of painful diabetic neuropathy. It acts on monoamine transporters to inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA). The purpose of this study was to evaluate the effects of diabetes on the brain neurotransmitter alterations induced by tramadol in rats, and to study the hepatic and renal toxicities of the drug. Eighty Sprague-Dawley rats were divided randomly into two sets: the normal set and the diabetic set. Diabetes was induced in rats. Tramadol was administered orally once daily for 28 days. The levels of DA, NE, and 5-HT in cerebral cortex, thalamus/hypothalamus, midbrain, and brainstem were evaluated in rats. In addition, the renal toxicity and histopathological effects of the drug were assessed. The induction of diabetes altered neurotransmitter levels. Oral administration of tramadol significantly decreased the neurotransmitter levels. Diabetes significantly altered the effects of tramadol in all brain regions. Tramadol affected function and histology of the liver and kidney. The clinical effects of tramadol in diabetic patients should be stressed. PMID:24971322

  5. Aminoguanidine partially prevents the reduction in liver pyruvate kinase activity in diabetic rats

    PubMed Central

    Majd, Alimohammad Amiri; Goodarzi, Mohammad Taghi; Hassanzadeh, Taghi; Tavilani, Heidar; Karimi, Jamshid

    2014-01-01

    Background: Low molecular weight aldehydes and carbonyl compounds which are derived from glucose metabolism are prevalent in diabetic plasma. These compounds react to amino groups of Lys and Arg and lead to the formation of advanced glycation end products (AGEs). This modification changes the function of the proteins. The present study aimed to survey the effect of diabetes on rat liver pyruvate kinase activity and to show the inhibitory effect of aminoguanidine (AG). Materials and Methods: Male Wistar rats (n = 18, 6 to 8 weeks old) were divided randomly in three groups: the first group as control; second and third groups were induced diabetes using streptozocin. Third group received AG orally for 8 weeks after diabetes induction. Liver cell homogenate was prepared from all studied groups and L-type pyruvate kinase was separated from the homogenate. Pyruvate kinase activity was determined in both liver cell homogenate and extracted L-type PK. The PK activity was compared in all samples between groups. Results: PK activity in isolated form and in liver cell homogenate was lower in diabetic rats as compared to control group. AG-treated group showed higher PK activity compared to untreated diabetic group; however, the difference was not significant. Non-significant difference in PK activity between AG-treated diabetic and non-diabetic (control) group indicated the inhibitory effect of AG in glycation of PK. Conclusion: The obtained results showed PK activity decreased in diabetic rats and AG can partially prevent the reduction in PK activity. PMID:25625099

  6. The Ethanol Extract of Zingiber zerumbet Attenuates Streptozotocin-Induced Diabetic Nephropathy in Rats

    PubMed Central

    Tzeng, Thing-Fong; Liou, Shorong-Shii; Chang, Chia Ju; Liu, I-Min

    2013-01-01

    The ethanol extract from the rhizome of Zingiber zerumbet (L.) Smith (EEZZR) has been indicated to possess an insulin-like property by ameliorating hyperglycemia in diabetes. We aimed to investigate whether EEZZR exerts an ameliorative effect on renal damage in diabetes induced by streptozotocin (STZ). Diabetic rats were treated orally with EEZZR (200 and 300?mg?kg?1 per day) or metformin (100?mg?kg?1 per day) for 8 weeks. The plasma glucose, creatinine, and blood urea nitrogen as well as urine protein levels and the ratio of kidney weight to body weight were significantly elevated in diabetic rats. EEZZR displayed similar characteristics to those of metformin in reducing hyperglycemia and renal dysfunction in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following the treatment with EEZZR. In addition, the protein expressions of renal nephrin and podocin in diabetic rats were significantly increased following the treatment with EEZZR. The AMP-activated protein kinase (AMPK) protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. EEZZR treatment significantly rescued the AMPK phosphorylation compared to nontreated diabetic group. This study suggested that the renoprotective effects of EEZZR may be similar, with the action of metformin, to the prevention of AMPK dephosphorylation and upregulate the expressions of renal nephrin and podocin. PMID:23476687

  7. Dysregulations of intestinal and colonic UDP-glucuronosyltransferases in rats with type 2 diabetes.

    PubMed

    Xie, Hao; Sun, Shiqing; Cheng, Xuefang; Yan, Tingting; Zheng, Xiao; Li, Feiyan; Qi, Qu; Wang, Guangji; Hao, Haiping

    2013-01-01

    Diabetes mellitus is a chronic disease of complex metabolic disorder associated with various types of complications. UDP-glucuronosyltransferases (UGTs), the major phase II conjugation enzymes, mediate the metabolism of both drugs and endogenous metabolites that may raise great concerns in the condition of diabetes. The aim of this study was to determine whether diabetes could affect UGTs in the intestinal and colonic tract. A high-fat diet combined with low-dose streptozotocin was used to induce a type 2 diabetic model in rats. The mRNA levels and enzymatic activities of UGT1A1, -1A6, and -1A7 in the diabetic intestine and colon were higher than those in nondiabetic rats. In contrast, both the activity and mRNA level of UGT2B1 in diabetic rats were lower than those in nondiabetic rats. Notably, the diabetic intestine and colon exhibited an inflammatory state with increased pro-inflammatory cytokines. Various transcriptional factors involved in UGT regulation were unanimously upregulated in the diabetic intestine and colon. These findings strongly suggest that the regulating pathways of the UGT1 family are adaptively upregulated in the diabetic gastrointestinal tract. Given the essential regulatory role of the gastrointestinal site in drug disposition, such changes in UGTs may have a dynamic and complex impact on therapeutic drugs and endogenous metabolomes. PMID:23545594

  8. Cardioprotection by Controlling Hyperamylinemia in a “Humanized” Diabetic Rat Model

    PubMed Central

    Despa, Sanda; Sharma, Savita; Harris, Todd R.; Dong, Hua; Li, Ning; Chiamvimonvat, Nipavan; Taegtmeyer, Heinrich; Margulies, Kenneth B.; Hammock, Bruce D.; Despa, Florin

    2014-01-01

    Background Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart. Methods and Results By Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP rats) and control myocytes incubated with human amylin, we show that amylin aggregation at the sarcolemma induces oxidative stress and Ca2+ dysregulation. In time, HIP rats developed cardiac hypertrophy and left?ventricular dilation. We then tested whether metabolites with antiaggregation properties, such as eicosanoid acids, limit myocardial amylin deposition. Rats were treated with an inhibitor of soluble epoxide hydrolase, the enzyme that degrades endogenous eicosanoids. Treatment doubled the blood concentration of eicosanoids, which drastically reduced incorporation of aggregated amylin in cardiac myocytes and blood cells, without affecting pancreatic amylin secretion. Animals in the treated group showed reduced cardiac hypertrophy and left?ventricular dilation. The cardioprotective mechanisms included the mitigation of amylin?induced cardiac oxidative stress and Ca2+ dysregulation. Conclusions The results suggest blood amylin as a novel therapeutic target in diabetic heart disease and elevating blood levels of antiaggregation metabolites as a pharmacological strategy to reduce amylin aggregation and amylin?mediated cardiotoxicity. PMID:25146704

  9. Effects of tungstate, a new potential oral antidiabetic agent, in Zucker diabetic fatty rats.

    PubMed

    Muñoz, M C; Barberà, A; Domínguez, J; Fernàndez-Alvarez, J; Gomis, R; Guinovart, J J

    2001-01-01

    Tungstate was orally administered to 7.5-week-old male Zucker diabetic fatty (ZDF) rats that already showed moderate hyperglycemia (180 +/- 16 mg/dl). The animals became normoglycemic for approximately 10 days. Then, glycemia started to rise again, although it did not reach the initial values until day 24, when levels stabilized at approximately 200 mg/dl for the duration of the experiment. Untreated ZDF rats showed steadily increased blood glucose levels between 7.5 and 10 weeks of age, when they reached a maximum value of 450 +/- 19 mg/dl, which was maintained throughout the experiment. In addition, tolerance to intraperitoneal glucose load improved in treated diabetic rats. Serum levels of triglycerides were elevated in untreated diabetic rats compared with their lean counterparts (ZLC). In the liver of diabetic animals, glucokinase (GK), glycogen phosphorylase a (GPa), liver-pyruvate kinase (L-PK), and fatty acid synthase (FAS) activities decreased by 81, 30, 54, and 35%, respectively, whereas phosphoenolpyruvate carboxykinase (PEPCK) levels increased by 240%. Intracellular glucose-6-phosphate (G6P) decreased by 40%, whereas glycogen levels remained unaffected. Tungstate treatment of these rats induced a 42% decrease in serum levels of triglycerides and normalized hepatic G6P concentrations, GPa activity, and PEPCK levels. GK activity in treated diabetic rats increased to 50% of the values of untreated ZLC rats. L-PK and FAS activity increased to higher values than those in untreated lean rats (1.7-fold L-PK and 2.4-fold FAS). Hepatic glycogen levels were 55% higher than those in untreated diabetic and healthy rats. Tungstate treatment did not significantly change the phosphotyrosine protein profile of primary cultured hepatocytes from diabetic animals. These data suggest that tungstate administration to ZDF rats causes a considerable reduction of glycemia, mainly through a partial restoration of hepatic glucose metabolism and a decrease in lipotoxicity. PMID:11147778

  10. Comparison of cardioprotective efficacy resulting from a combination of atorvastatin and ischaemic post-conditioning in diabetic and non-diabetic rats.

    PubMed

    Fan, Ying; Yang, Shusen; Zhang, Xiukun; Cao, Yang; Huang, Yonglin

    2012-11-01

    The aim of the present study was to investigate whether the combination of acute or chronic atorvastatin treatment with ischaemic post-conditioning (IPost) exerts differential effects within the hearts of diabetic and non-diabetic rats. Diabetic and non-diabetic rats were randomly assigned to one of six groups: (i) a non-conditioned group; (ii) a group subjected to IPost; (iii) acute statin treatment (50 ?mol/L atorvastatin during reperfusion) without IPost; (iv) acute statin treatment plus IPost; (v) chronic statin treatment (10 mg/kg atorvastatin per day for 2 weeks) without IPost; and (vi) chronic statin treatment plus IPost. The hearts from rats in each group were subjected to 30 min global ischaemia, followed by 120 min reperfusion. Infarct size, haemodynamics and Akt and endothelial nitric oxide synthase (eNOS) expression were examined. In hearts from diabetic rats, IPost did not limit infarct size or recover contractile dysfunction. Acute atorvastatin treatment with IPost limited infarct size and recovered contractile dysfunction in hearts from both diabetic and non-diabetic rats and further activated Akt and eNOS signalling pathways to enhance these protective effects in hearts from diabetic rats. Chronic statin treatment with IPost neither reduced infarct size nor increased recovery of myocardial dysfunction in hearts from both diabetic and non-diabetic rats; this may be associated with inhibition of Akt and eNOS phosphorylation. The combination of acute atorvastatin treatment with IPost had a greater protective effect within hearts from diabetic rats, but chronic statin treatment with IPost failed to protect against reperfusion injury in hearts from either diabetic or non-diabetic rats. These findings will be important for the design of future clinical investigations. PMID:23106693

  11. Cod liver oil supplementation improves cardiovascular and metabolic abnormalities in streptozotocin diabetic rats.

    PubMed

    Ceylan-Isik, Asli; Hünkar, Tu?ba; A?an, Esin; Kaymaz, Fugen; Ari, Nuray; Söylemezo?lu, Tülin; Renda, Nurten; Soncul, Halim; Bali, Musa; Karasu, Cimen

    2007-12-01

    Abnormalities in the metabolism of essential fatty acids and the results of increased oxidative stress have been implicated in cardiovascular disorders observed in diabetes mellitus. This study, therefore, aimed to investigate the effects of cod liver oil (CLO, Lysi Ltd, Iceland), which comprises mainly an antioxidant vitamin A, n:3 polyunsaturated fatty acids (n:3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular abnormalities in streptozotocin (STZ)-diabetic rats. Two days after single STZ (55 mg kg(-1), i.p.) or vehicle injection, diabetes was verified by increased blood glucose, and non-diabetic and diabetic rats were left untreated or treated with CLO (0.5 mL kg(-1) daily, by intragastric probing) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic rats; CLO provided better weight gain, entirely prevented the plasma lipid abnormalities, but partially controlled the glycaemia in diabetic rats. In isolated aorta rings, diabetes resulted in increased phenylephrine-induced vasoconstriction and isoprenaline-induced vasorelaxation, impaired endothelium-dependent vasodilatation and unchanged responsiveness to sodium nitroprusside. CLO treatment completely prevented endothelial deficiency, partly corrected the phenylephrine-induced vasoconstriction and did not affect the responses to isoprenaline and sodium nitroprusside in diabetic aorta. Diabetes also produced a marked decrease in the rate of spontaneously beating right atria and a significant increase in basal contractile force of left ventricular papillary muscle. The responsiveness of right atria to the positive chronotropic effect of isoprenaline was significantly decreased in diabetic rats, and was increased in CLO-treated diabetic rats. The positive chronotropic effect of noradrenaline was markedly increased in diabetic atria, but prevented by CLO treatment. Diabetes also resulted in an increased positive inotropic response of papillary muscle to both noradrenaline and isoprenaline, which were prevented by CLO treatment. CLO treatment also resulted in lower tissue sensitivity (pD(2)) to these agonists in diabetic papillary muscle. Ventricular hydroxyproline content was found to be unchanged among the experimental groups. The ultrastructure of diabetic myocardium displayed various degenerations (i.e. intracellular oedema, myofibrillar fragmentation, condensed pleomorphic mitochondria, thick capillary irregular basement membrane, swollen endothelial cells), which were partially prevented by CLO treatment. We conclude that the supplementation with CLO is effective in preventing cardiovascular disorders observed in experimental diabetes. PMID:18053324

  12. Evaluation of Buspirone on Streptozotocin Induced Type 1 Diabetes and Its Associated Complications

    PubMed Central

    Raghunathan, Suchi; Bhadada, Shraddha

    2014-01-01

    We have evaluated the effect of buspirone (1.5?mg/kg/day, p.o.) type 1 diabetes induced cardiovascular complications induced by streptozotocin (STZ, 45?mg/kg, i.v.) in 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 buspirone treatment. STZ produced increase in serum creatinine, urea, lactate dehydrogenase, creatinine kinase, and C-reactive protein levels and treatment with buspirone produced reduction in these levels. STZ produced increase in cardiac and LV hypertrophy index, LV/RV ratio, and LV collagen, which were decreased by buspirone treatment. Buspirone also prevented STZ induced hemodynamic alterations and oxidative stress. These results were further supported by histopathological studies in which buspirone showed marked reduction in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that buspirone is beneficial as an antidiabetic agent in type 1 diabetes mellitus and also prevents its cardiac complications. PMID:24563867

  13. Beneficial effects of dietary L-arginine supplementation to diabetic rats 

    E-print Network

    Kohli, Ripla

    2004-09-30

    Diabetic rats exhibit decrease in plasma arginine, NO synthesis and tetrahydrobiopterin in endothelial cells (EC). Treatment with L-arginine may be beneficial for enhancing NO synthesis in diseases associated with endothelial dysfunction. However...

  14. Effects of acetaldehyde on the isolated papillary muscle of diabetic rats.

    PubMed

    Savage, A O; Dunbar, J C; Brown, R A

    1995-08-01

    The effects of acetaldehyde (ACA) were examined in isolated electrically driven papillary muscle preparations from normal and streptozotocin-treated diabetic rats. Muscles from diabetic rats developed greater tension than those from normal rats. In muscles from both groups, ACA caused concentration-dependent negative inotropic effects that were independent of cholinergic or purinergic mechanisms and were not attributable to nitric oxide (NO) release. ACA was three to five times more potent with regard to its negative inotropic effect in diabetic than in normal rat muscles. A propranolol-sensitive, sympathetically mediated positive inotropic effect occurred at certain concentrations. Decreasing [Ca2+]o from 2.7 to 0.5 mM reduced basal developed force to a significantly greater extent in muscles from normal rats than in those from diabetic rats. In low [Ca2+]o, concentration-response curves to CaCl2 in diabetic muscles were displaced to the left of that in normal muscles, suggesting that diabetic muscles are more sensitive to the positive inotropic effect of added CaCl2 at low [Ca2+]o, whereas at higher [Ca2+]o (> 1 mM), normal muscles developed more force in response to added CaCl2. ACA 10 and 30 mM more readily inhibited CaCl2-induced positive inotropic effect in normal than in diabetic muscles. Force-frequency curves, (negative staircase response) were recorded in both normal and diabetic muscles. In diabetic muscles, the curve exhibited a positive component at the lowest frequencies applied and was displaced to the right of that in normal muscle. ACA concentration-dependently inhibited force development, and diabetic muscles were more susceptible to the negative inotropic effect of ACA, when the stimulation frequency was increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7475050

  15. Stimulation of autophagy promotes functional recovery in diabetic rats with spinal cord injury

    PubMed Central

    Zhou, Kai-liang; Zhou, Yi-fei; Wu, Kai; Tian, Nai-feng; Wu, Yao-sen; Wang, Yong-li; Chen, De-heng; Zhou, Bin; Wang, Xiang-yang; Xu, Hua-zi; Zhang, Xiao-lei

    2015-01-01

    In this study we examined the relationship between autophagy and apoptosis in diabetic rats after spinal cord injury (SCI), also we determined the role of autophagy in diabetes-aggravated neurological injury in vivo and in vitro. Our results showed that diabetes decreased the survival of neurons, promoted astrocytes proliferation, increased inflammatory cells infiltration and inhibited functional recovery after SCI. Diabetes was shown to confer increased activation of apoptotic pathways, along with an increase in autophagy; similar effects were also observed in vitro in neuronal PC12 cells. Treatment with rapamycin, an autophagy activator, partially abolished the adverse effect of diabetes, suggesting that diabetes may enhance neurological damage and suppress locomotor recovery after SCI, in addition to its effects on apoptosis and autophagy. In contrast, further stimulation of autophagy improved neurological function via inhibition of apoptosis. These results explained how diabetes exacerbates SCI in cellular level and suggested autophagy stimulation to be a new therapeutic strategy for diabetic SCI. PMID:26597839

  16. Hypoglycemia induced behavioural deficit and decreased GABA receptor, CREB expression in the cerebellum of streptozoticin induced diabetic rats.

    PubMed

    Sherin, A; Peeyush, K T; Naijil, G; Chinthu, R; Paulose, C S

    2010-11-20

    Intensive glycemic control during diabetes is associated with an increased incidence of hypoglycemia, which is the major barrier in blood glucose homeostasis during diabetes therapy. The CNS neurotransmitters play an important role in the regulation of glucose homeostasis. In the present study, we showed the effects of hypoglycemia in diabetic and non- diabetic rats on motor functions and alterations of GABA receptor and CREB expression in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. Scatchard analysis of [(3)H]GABA binding in the cerebellum of diabetic hypoglycemic and control hypoglycemic rats showed significant (P<0.01) decrease in B(max) and K(d) compared to diabetic and control rats. Real-time PCR amplification of GABA receptor subunit GABA(A?1) and GAD showed significant (P<0.001) down-regulation in the cerebellum of hypoglycemic rats compared to diabetic and control rats. Confocal imaging study confirmed the decreased GABA receptors in hypoglycemic rats. CREB mRNA expression was down-regulated during recurrent hypoglycemia. Both diabetic and non-diabetic hypoglycemic rats showed impaired performance in grid walk test compared to diabetic and control. Impaired GABA receptor and CREB expression along with motor function deficit were more prominent in hypoglycemic rats than hyperglycemic which showed that hypoglycemia is causing more neuronal damage at molecular level. These molecular changes observed during hypo/hyperglycemia contribute to motor and learning deficits which has clinical significance in diabetes treatment. PMID:20851745

  17. Myocardin restores erectile function in diabetic rats: phenotypic modulation of corpus cavernosum smooth muscle cells.

    PubMed

    He, S; Zhang, T; Liu, Y; Liu, L; Zhang, H; Chen, F; Wei, A

    2015-04-01

    This study aimed to investigate whether gene transfer of myocardin to the penis of diabetic rats can modulate corpus cavernosum smooth muscle (CCSM) cells phenotype and restore erectile function. Five normal control rats, and 22 diabetic rats were randomly divided into four groups: rats transfected with adCMV-myocardin (N = 6), treated with empty vector (N = 6), injected with medium (N = 5), and sham-operated rats (N = 5). The erectile response was measured 7 days after transfection. The percent of smooth muscle and the expressions of SM?-actin, smooth muscle myosin heavy chain (SMMHC), calponin were evaluated. The increases in intracorporal pressure(ICP)/mean arterial pressure and total ICP in response to nerve stimulation in the adCMV-myocardin treated rats were significantly greater than those in the empty vector (P < 0.001 and P < 0.001), medium only (P < 0.001 and P < 0.001), and sham-operated rats (P < 0.001 and P < 0.001). The suppressed expressions of SM?-actin, SMMHC and calponin were completely restored, and the amount of smooth muscle in diabetic rats were not restored after treatment. It is concluded that myocardin ameliorated erectile responses in diabetic rats mainly via promoting phenotypic modulation of CCSM cells from a proliferative to a contractile state. PMID:24620720

  18. Impaired mitochondrial metabolism and protein synthesis in streptozotocin diabetic rat hepatocytes

    SciTech Connect

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

    1990-02-26

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

  19. Blocking ?V?3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats

    PubMed Central

    Maile, Laura A.; Gollahon, Katherine; Wai, Christine; Busby, Walker; Clemmons, David

    2014-01-01

    This study determined if blocking ligand occupancy of the ?V?3 integrin could inhibit the pathophysiologic changes that occur in the early stages of diabetic nephropathy (DN). Diabetic rats were treated with either vehicle or a monoclonal antibody that binds the ?3 subunit of the ?V?3 integrin. After 4 weeks of diabetes the urinary albumin to creatinine ratio (UACR) increased in both diabetic animals that subsequently received vehicle and in the animals that subsequently received the anti-?3 antibody compared with control nondiabetic rats. After 8 weeks of treatment the UACR continued to rise in the vehicle-treated rats; however it returned to levels comparable to control nondiabetic rats in rats treated with the anti-?3 antibody. Treatment with the antibody prevented the increase of several profibrotic proteins that have been implicated in the development of DN. Diabetes was associated with an increase in phosphorylation of the ?3 subunit in kidney homogenates from diabetic animals, but this was prevented by the antibody treatment. This study demonstrates that, when administered after establishment of early pathophysiologic changes in renal function, the anti-?3 antibody reversed the effects of diabetes normalizing albuminuria and profibrotic proteins in the kidney to the levels observed in nondiabetic control animals. PMID:25389530

  20. Gum Arabic extracts protect against hepatic oxidative stress in alloxan induced diabetes in rats.

    PubMed

    Ahmed, Abdelkareem A; Fedail, Jaafar S; Musa, Hassan H; Kamboh, Asghar Ali; Sifaldin, Amal Z; Musa, Taha H

    2015-12-01

    Gum Arabic (GA) from Acacia seyal and Acacia senegal is a branched-chain polysaccharide which has strong antioxidant properties, and has been used to reduce the experimental toxicity. Yet, the effects of GA on oxidative stress in type I diabetic rats have not been reported. The aim of the study was to investigate the effects of GA on oxidative stress in Alloxan induced diabetes in rats. The rats were divided into 3 groups (n=20 of each): control group, diabetic group injected with allaoxan, and diabetic group given 15% GA in drinking water for 8 weeks. Oxidative damage to liver tissue was evaluated by measurement of key hepatic enzymes, lipid peroxidation, antioxidant enzymes and expression of oxidative stress genes. Activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were significantly (P<0.05) increased in GA group compared to diabetic and control groups. Treatment of GA decreased liver malondialdehyde (MDA), and increased glutathione (GSH). In addition, GA was significantly (P<0.05) reduced the activities of key liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST). SOD, GPx and heat shock protein 70 (HSP70) mRNA were significantly increased in GA group compared to control and diabetic groups. Liver of all diabetic rats showed marked degeneration whereas slight degeneration was observed in GA treated rats compared to control. The results suggest that GA may protect liver by modulating the expression of oxidative stress genes, and thus can improve antioxidant status. PMID:26321624

  1. Antidiabetic and antihyperlipidaemic activity of ethanol extract of Melastoma malabathricum Linn. leaf in alloxan induced diabetic rats

    PubMed Central

    Balamurugan, Karuppasamy; Nishanthini, Antony; Mohan, Veerabahu Ramasamy

    2014-01-01

    Objective To evaluate the antidiabetic and antihyperlipidaemic effect of ethanol extract of Melastoma malabathricum (M. malabathricum) Linn. leaf in alloxan induced diabetic rats. Methods Diabetes was induced in albino rats by administration of alloxan monohydrate (150 mg/kg i.p). the ethanol extracts of M. malabathricum at a dose of 150 and 300 mg/kg of body weight were administrated at a single dose per day to diabetes induced rats for a period of 14 d. The effect of ethanol extract of M. malabathricum leaf extract on blood glucose, plasma insulin, creatinine, glycosylated haemoglobin, urea serum lipid profile [total cholesterol, triglycerides, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and phospholipid, serum protein, albumin, globulin, serum enzymes (serum glutamate pyruvate transaminases), serum glutamate oxaloacetate transaminases, and alkaline phosphatase] were measured in the diabetic rats. Results In the acute toxicity study, ethanol extract of M. malabathricum leaf was non-toxic at 2?000 mg/kg in rats. The increased body weight, decreased blood glucose, glycosylated haemoglobin and other biochemical parameters level were observed in diabetic rats treated with both doses of ethanol extract of M. malabathricum leaf compared to diabetic control rats. In diabetic rats, ethanol extract of M. malabathricum leaf administration, altered lipid profiles were reversed to near normal than diabetic control rats. Conclusions Ethanol extract of M. malabathricum leaf possesses significant antidiabetic and antihyperlipidaemic activity in diabetic rats. PMID:25183126

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

    SciTech Connect

    Pitkaenen, O.M.; Akerblom, H.K.; Sariola, H.; Andersson, S.M. ); Martin, J.M. ); Hallman, M. )

    1991-01-01

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

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

    PubMed

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

    2015-04-01

    This study investigates the effect of insulin combined with idebenone on blood-brain barrier (BBB) permeability in experimental streptozotocin-induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ-associated proteins occludin, and zonula occludens (ZO)-1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end-products (RAGE) and nuclear factor-?B (NF-?B) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin-5, and ZO-1 and that the ROS/AGE/RAGE/NF-?B signal pathway might be involved in the process. PMID:25421718

  4. Antidiabetic effect of Merremia emarginata Burm. F. in streptozotocin induced diabetic rats

    PubMed Central

    Gandhi, G Rajiv; Sasikumar, P

    2012-01-01

    Objective To investigate the antidiabetic property of Merremia emarginata (M. emarginata) Burm. F. plant in streptozotocin induced diabetic rats. Methods The dose dependent effects of 28 days oral treatment with methanol extract (100, 200 and 400 mg/kg) from the plant of M. emarginata on blood glucose level, body weight, insulin, total hemoglobin, glycosylated haemoglobin (HbA1C), total protein, serum urea, serum creatinine and carbohydrate metabolizing enzymes were evaluated in streptozotocin induced diabetic rats. Histology of pancreas was also studied. Results A significant decrease in blood glucose, serum urea and serum creatinine and significant increase in body weight, insulin and protein level were observed in diabetic rats treated with M. emarginata. Treatment with M. emarginata resulted in a significant reduction of HbA1C and an increase in total hemoglobin level. The activities of carbohydrate metabolizing enzymes such as hexokinase were significantly increased whereas glucose-6-phosphatase, fructose-1, 6-bisphosphatase were significantly decreased by the administration of M. emarginata in diabetic rats. Histology of diabetic rats treated with M. emarginata showed the pancreatic ?-cells regeneration. Conclusions These findings suggest that M. emarginata has potent antidiabetic activity in streptozotocin induced diabetic rats. PMID:23569914

  5. Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Sundaram, Ramalingam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2014-05-15

    The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide - a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential. PMID:24629597

  6. Hypolipidemic, Hepatoprotective and Renoprotective Effects of Cydonia Oblonga Mill. Fruit in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Mirmohammadlu, Mansur; Hosseini, Seyed Hojjat; Kamalinejad, Mohammad; Esmaeili Gavgani, Majid; Noubarani, Maryam; Eskandari, Mohammad Reza

    2015-01-01

    Diabetes mellitus is associated with complications in several different systems of the body, and the incidence of diabetes is rapidly increasing worldwide. The objective of the present study was to evaluate the effect of aqueous extract of Cydonia oblonga Mill. Fruit on lipid profile and some biochemical parameters in streptozotocin-induced diabetic rats. The extract showed anti hyper lipidemic activity as evidenced by significant decreases in serum triglyceride, total cholesterol, and low density lipoprotein cholesterol (LDL-C) levels along with the elevation of high density lipoprotein cholesterol (HDL-C) in the diabetic rats. The biochemical liver functional tests were also analyzed and it was shown that serum biomarkers of liver dysfunction, including alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were significantly reduced in aqueous extract of Cydonia oblonga Mill. treated diabetic rats. In addition, our results showed that the oral administration of the extract prevented diabetes-induced increase in serum urea and creatinine levels as the markers of renal dysfunction. In conclusion, the present study indicates that aqueous extract of Cydonia oblonga Mill. Is able to improve some of the symptoms associated with diabetes and possesses hypolipidemic, hepatoprotective, and renoprotective effects in streptozotocin-induced diabetic rats.

  7. Statistical Approaches to Analyzing Energy Expenditure Data Among Zucker Diabetic Fatty Rats

    E-print Network

    Kim, Hyunkyoung

    2014-01-07

    of energy expended frequently within a specified time period. For example, in studying obesity among Zucker diabetic fatty (ZDF) rats, an animal model often used for studying obesity and the onset of diabetes, energy expenditure can be assessed by the use...

  8. Polysaccharides from Enteromorpha prolifera Improve Glucose Metabolism in Diabetic Rats

    PubMed Central

    Lin, Wenting; Wang, Wenxiang; Liao, Dongdong; Chen, Damiao; Zhu, Pingping; Cai, Guoxi; Kiyoshi, Aoyagi

    2015-01-01

    This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600?mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of islet ?-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM. PMID:26347892

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

    PubMed

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

    2015-10-01

    Brain mitochondrial dysfunction has been demonstrated in diabetic animals with neurodegeneration. Protocatechuic acid (PCA), a major metabolite of anthocyanin, has been shown to exert glycemic control and oxidative stress reduction in the heart. However, its effects on oxidative stress and mitochondrial function in the brain under diabetic condition have never been investigated. We found that PCA exerted glycemic control, attenuates brain mitochondrial dysfunction, and contributes to the prevention of brain oxidative stress in diabetic rats. PMID:26316260

  10. Hypoglycemic and Hepatoprotective Activity of Fermented Fruit Juice of Morinda citrifolia (Noni) in Diabetic Rats

    PubMed Central

    Nayak, B. Shivananda; Marshall, Julien R.; Isitor, Godwin; Adogwa, Andrew

    2011-01-01

    Morinda citrifolia is a medicinal plant used to treat diabetes and liver diseases. The fermented fruit juice of the M. Citrifolia (optical density?=?1.25) was used to study the hypoglycemic and hepatoprotective properties in diabetes-induced rats. The rats were randomly distributed into 4 groups (control, diabetic experimental, diabetic standard, and diabetic untreated) of 6 each. Diabetes was induced by administering Streptozotocin (50?mg/kg body weight). Fasting blood glucose, body mass, liver tissue glycogen content, and the extent of liver degeneration were assessed. Diabetic experimental animals were treated with M. citrifolia juice (2?ml/kg, twice a day) and diabetic standard with reference hypoglycemic drug, glibenclamide orally for 20 days. Both the groups exhibited a significant reduction in blood glucose level of 150?mg/dl ±15.88 and 125?mg/dl ±3.89, respectively, as compared to diabetic untreated with FBS?=?360.0?mg/dl ±15.81, (P < .003). On 10th day of experiment, diabetic experimental animals exhibited a decrease in body mass (10.2?g, 5.11%) which increased significantly by the 20th day (6?g, 3.0%, P < .022). Histological study of liver tissue obtained from untreated diabetic animals revealed significant fatty degeneration as compared to other three groups. The data of this study proved the hypoglycemic and hepatoprotective activity of M. citrifolia. PMID:20981320

  11. Effects of Astragaloside IV on diabetic nephropathy in rats.

    PubMed

    Lu, W-S; Li, S; Guo, W-W; Chen, L-L; Li, Y-S

    2015-01-01

    The aims of this study were to explore the effects of Astragaloside IV on diabetic nephropathy (DN) rats. A total of 38 male Sprague-Dawley (SD) rats were divided into three groups: 10 in the normal (control) group, 14 in the DN model group, and 14 in the AS-IV group. Treatment began one week after the streptozotocin DN model was successfully established. Blood glucose and urine micro-albumin levels were measured every four weeks. After being treated for 12 weeks, all SD rats were sacrificed for blood and renal specimen collec-tion. Renal cortex specimens were observed after hematoxylin and eo-sin and Masson staining. Expression levels of protein ?1, ?1-integrin-linked protein kinase (ILK) and ?-actinin-4 were also measured. After eight weeks of intervention, blood glucose levels in the AS-IV group decreased significantly when compared with those of the model group (P < 0.01). By the end of the twelfth week, the urine micro-albumin levels showed significant differences (P < 0.01) between the AS-IV and model groups, and the expression levels of integrin ?1, ILK, and ?-actinin-4 also showed significant differences (P < 0.05, respectively). Concomitantly, expression levels of integrin ?1, ILK, and ?-actinin-4 in the model group were significantly different from those of normal group (P < 0.05). These results suggest that AS-IV can be quite effec-tive in decreasing blood glucose levels, reducing urine albumin excre-tion, and improving the adhesion function of potocytes, and can thus delay the development of DN. PMID:26125738

  12. Linkage study of embryopathy-polygenic inheritance of diabetes-induced skeletal malformations in the rat.

    PubMed

    Nordquist, Niklas; Luthman, Holger; Pettersson, Ulf; Eriksson, Ulf J

    2012-06-01

    We developed an inbred rat model of diabetic embryopathy, in which the offspring displays skeletal malformations (agnathia or micrognathia) when the mother is diabetic, and no malformations when she is not diabetic. Our aim was to find genes controlling the embryonic maldevelopment in a diabetic environment. We contrasted the fetal outcome in inbred Sprague-Dawley L rats (20% skeletal malformations in diabetic pregnancy) with that of inbred Wistar Furth rats (denotedW, no skeletal malformations in diabetic pregnancy). We used offspring from the backcross F(1)×L to probe for the genetic basis for malformation of the mandible in diabetic pregnancy. A set of 186 fetuses (93 affected, 93 unaffected) was subjected to a whole genome scan with 160 micro satellites. Analysis of genotype distribution indicated 7 loci on chromosome 4, 10 (3 loci), 14, 18, and 19 in the teratogenic process (and 14 other loci on 12 chromosomes with less strong association to the malformations), several of which contained genes implicated in other experimental studies of diabetic embryopathy. These candidate genes will be scrutinized in further experimentation. We conclude that the genetic involvement in rodent diabetic embryopathy is polygenic and predisposing for congenital malformations. PMID:22227068

  13. Protective effect of yacon leaves decoction against early nephropathy in experimental diabetic rats.

    PubMed

    Honoré, Stella M; Cabrera, Wilfredo M; Genta, Susana B; Sánchez, Sara S

    2012-05-01

    Nephropathy is the most common cause of morbidity and mortality in diabetic patients. Prevention of this complication has a major relevance. Smallanthus sonchifolius (yacon) leaves have been shown to ameliorate hyperglycemia in streptozotocin-induced diabetic rats. We examined the beneficial effects of yacon leaves decoction on diabetic nephropathy and explored the possible underlying action mechanism. Streptozotocin-diabetic rats were orally administered 10% yacon leaves water decoction (70mg dry extract/kg body weight) once a day for 4weeks. Biochemical parameters in blood and urine were analyzed and immunohistochemistry staining, western immunoblotting and qRT-PCR were assessed. Yacon decoction significantly decreased high blood glucose level in diabetic rats and improved insulin production. Diabetic-dependent alterations in urinary albumin excretion, creatinine clearance, kidney hypertrophy and basement membrane thickening were attenuated by yacon decoction. These findings were associated with a marked decrease in TGF-?1/Smad2/3 signaling. The expression of molecular markers of diabetic nephropathy such as collagen IV, laminin-1, fibronectin and collagen III were also diminished in the yacon-treated group compared to control diabetic group. These results suggest that yacon leaves decoction is a protective agent against renal damage in diabetic nephropathy, whose action can be mediated by TGF-?/Smads signals. PMID:22406203

  14. Changes of urinary angiotensinogen concentration and its association with urinary proteins in diabetic rats

    PubMed Central

    Zhuang, Zhen; Bai, Qiong; A, Lata; Liang, Yaoxian; Zheng, Danxia; Wang, Yue

    2015-01-01

    Objective: It had been reported that angiotensinogen might be a marker for activation of renin-angiotensin system, which was associated with the development of diabetic nephropathy. The purpose of this study was to investigate the functional roles of AGT in DN in vitro. Methods: Diabetic rat models were built by single intraperitoneal injection of streptozotocin. The diabetic rats were divided into three groups, two of the three groups were treated with different doses of losartan, the other diabetic group was as control and normal rats acted as healthy control. In a 12-week investigation, we detected the changes of AGT in all rats’ blood and urine and the association between AGT concentration and RAS activation and urinary proteins were analyzed in this study. Results: The serum AGT of rats had no significant differences (P>0.05 for all). The urinary AGT of the diabetic rats was significantly different from the control group, moreover, the urinary AGT of the diabetic rats under different treatments was also obviously different (P<0.05 for all). Besides, the results of immunohistochemical assay indicated that AGT expression level was correlated with renal tissues damage. The level of AGT was positively associated with urinary protein (r=0.493, P<0.01) and negatively correlated with CCr (r=-0.474, P=0.007) and the dose of ARB (r=-0.575, P=0.001). Moreover, the dose of ARB was independently associated with urinary AGT (B=-2.963, P=0.024) in diabetic rats. Conclusion: Urinary AGT may be a marker for the activation of local RAS in kidney and independently associated with ARB. PMID:26722381

  15. Augmented insulin effects on plasma glucose by cranberry procyanidins in streptozotocin-induced diabetic rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives of this study were to determine if cranberry proanthocyanidins (CPACs) had an antihyperglycemic effect in the presence or absence of insulin in male diabetic Sprague-Dawley rats. Rats (approximately 250 g)(n=6-10/ trt) were given a single intraperitoneal (ip) injection of freshly prepared...

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

    PubMed Central

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

    2015-01-01

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

  17. Effect of Biochanin A on Serum Visfatin Level of Streptozocin-Induced Diabetic Rats

    PubMed Central

    Azizi, Reza; Goodarzi, Mohamad Taghi; Salemi, Zahra

    2014-01-01

    Background: Bioflavonoids are well known for their multi directional biologic activity including antidiabetic effect. It has been demonstrated that flavonoids can act as insulin secretagogue or insulin mimetic agents. Objectives: This experimental study was designed in Arak University of Medical Sciences, Arak, Iran, to investigate the effects of biochanin A (a bioflavonoid) on fasting blood glucose (FBG), body weight, glycosylated hemoglobin (HbA1c), lipid profile, serum enzymes, and visfatin of streptozocin-induced diabetic rats. Patients and Methods: We used 24 male Wistar rats and randomly allocated them to four groups of six rats. One group was randomly assigned as control and diabetes was induced in three other groups by administration of streptozocin (35 mg/kg of body weight) intraperitoneally. The groups received the following treatments: group 1 (control), 5% DMSO; group 2 (diabetic control), 0.5% DMSO; and group 3 and 4, respectively 10 and 15 mg/kg biochanin A for 30 days. Body weight and biochemical parameters including FBG, HbA1c, lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and visfatin were measured in all rats. Results: FBG level was significantly reduced in treated diabetic rats (139.8 ± 9.3 and 206 ± 11 mg/dL in groups 3 and 4, respectively) in comparison to the diabetic control (295.1 ± 14 mg/dL) (P < 0.05). Administration of biochanin A significantly decreased HbA1c in group 3 (6.66 ± 0.33) and group 4 (7.11 ± 0.31) in comparison to the diabetic control group (8.26 ± 0.44) (P < 0.05). Levels of serum visfatin were improved to near normal levels in the treated rats (249 ± 35.5 and 161.33 ± 13.07 in groups 3 and 4, respectively) in comparison to the diabetic control (302.17 ± 19.4) (P < 0.05). Furthermore, biochanin A showed a protective effect against weight loss in diabetic rats (P < 0.05). In treated rats, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-c) were significantly decreased and high-density lipoprotein (HDL-c) was increased in comparison with the diabetic control group. In addition, biochanin A restored the altered plasma enzymes (AST, ALT, and ALP) activities to near normal. Histopathologic examination of the pancreas also indicated that biochanin A had protective effects on ?-cells in streptozocin-induced diabetic rats. Conclusions: This study demonstrated that biochanin A possessed hypoglycemic and antilipemic activities and could increase visfatin expression, which suggests its beneficial effect in the treatment of diabetes. PMID:25593725

  18. Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats

    PubMed Central

    Niwa, Atsuko; Tajiri, Takashi; Higashino, Hideaki

    2011-01-01

    Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg?1 d?1), Agaricus blazei (1 g kg?1 d?1) or Smallanthus sonchifolius (4 g kg?1 d?1) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-? production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic ?-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic ?-cells mass. PMID:21562638

  19. Mitochondrial inefficiencies and anoxic ATP hydrolysis capacities in diabetic rat heart.

    PubMed

    Pham, Toan; Loiselle, Denis; Power, Amelia; Hickey, Anthony J R

    2014-09-15

    As ~80% of diabetic patients die from heart failure, an understanding of diabetic cardiomyopathy is crucial. Mitochondria occupy 35-40% of the mammalian cardiomyocyte volume and supply 95% of the heart's ATP, and diabetic heart mitochondria show impaired structure, arrangement, and function. We predict that bioenergetic inefficiencies are present in diabetic heart mitochondria; therefore, we explored mitochondrial proton and electron handling by linking oxygen flux to steady-state ATP synthesis, reactive oxygen species (ROS) production, and mitochondrial membrane potential (??) within rat heart tissues. Sprague-Dawley rats were injected with streptozotocin (STZ, 55 mg/kg) to induce type 1 diabetes or an equivalent volume of saline (control, n = 12) and fed standard rat chow for 8 wk. By coupling high-resolution respirometers with purpose-built fluorometers, we followed Magnesium Green (ATP synthesis), Amplex UltraRed (ROS production), and safranin-O (??). Relative to control rats, the mass-specific respiration of STZ-diabetic hearts was depressed in oxidative phosphorylation (OXPHOS) states. Steady-state ATP synthesis capacity was almost one-third lower in STZ-diabetic heart, which, relative to oxygen flux, equates to an estimated 12% depression in OXPHOS efficiency. However, with anoxic transition, STZ-diabetic and control heart tissues showed similar ATP hydrolysis capacities through reversal of the F1F0-ATP synthase. STZ-diabetic cardiac mitochondria also produced more net ROS relative to oxygen flux (ROS/O) in OXPHOS. While ?? did not differ between groups, the time to develop ?? with the onset of OXPHOS was protracted in STZ-diabetic mitochondria. ROS/O is higher in lifelike OXPHOS states, and potential delays in the time to develop ?? may delay ATP synthesis with interbeat fluctuations in ADP concentrations. Whereas diabetic cardiac mitochondria produce less ATP in normoxia, they consume as much ATP in anoxic infarct-like states. PMID:24920675

  20. Metformin Ameliorates Podocyte Damage by Restoring Renal Tissue Podocalyxin Expression in Type 2 Diabetic Rats

    PubMed Central

    Zhai, Limin; Gu, Junfei; Yang, Di; Wang, Wei; Ye, Shandong

    2015-01-01

    Podocalyxin (PCX) is a signature molecule of the glomerular podocyte and of maintaining integrity of filtration function of glomerulus. The aim of this study was to observe the effect of different doses of metformin on renal tissue PCX expression in type 2 diabetic rats and clarify its protection on glomerular podocytes. Type 2 diabetic Sprague-Dawley (SD) rats in which diabetes was induced by high-fat diet/streptozotocin (HFD-STZ) were treated with different doses of metformin (150, 300, and 500?mg/kg per day, resp.) for 8 weeks. Various biochemical parameters, kidney histopathology, and renal tissue PCX expression levels were examined. In type 2 diabetic rats, severe hyperglycemia and hyperlipidemia were developed. Urinary albumin and PCX were markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, protein and mRNA expression of renal tissue PCX were highly decreased. However, treatment of rats with different doses of metformin restored all these changes to a varying degree. These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence. PMID:26075281

  1. Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abedi, Hassan Ali

    2014-01-01

    Objective(s): Diabetes plays an important role in the induction of the liver injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal properties against oxidative stress. In this study we evaluated antioxidant effects of GSP on liver in streptozotocin-induced diabetic rats. Materials and Methods: Thirty male Sprague–Dawley rats were divided into three groups: control, untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were administered via oral gavage (200 mg/kg) for 4 weeks. Results: GSP produced significant hepatoprotective effects by decreasing activities of serum aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde and bilirubin (P<0.05) levels. It increased liver superoxide dismutase, catalase and glutathione peroxidase activities and albumin level (P<0.05). Administration of GSP significantly ameliorated structural changes induced in liver of diabetic rats. Conclusion: GSP have protective effects against hepatic tissue injury due to antioxidant properties. PMID:25140209

  2. Antihyperlipidemic effect of a polyherbal mixture in streptozotocin-induced diabetic rats.

    PubMed

    Ghorbani, Ahmad; Shafiee-Nick, Reza; Rakhshandeh, Hassan; Borji, Abasalt

    2013-01-01

    The effects of a polyherbal mixture containing Allium sativum, Cinnamomum zeylanicum, Citrullus colocynthis, Juglans regia, Nigella sativa, Olea europaea, Punica granatum, Salvia officinalis, Teucrium polium, Trigonella foenum, Urtica dioica, and Vaccinium arctostaphylos were tested on biochemical parameters in diabetic rats. The animals were randomized into three groups: (1) normal control, (2) diabetic control, and (3) diabetic rats which received diet containing 15% (w/w) of this mixture for 4 weeks. Diabetes was induced by intraperitoneal injection of streptozotocin (55?mg/kg). At the end of experiment, the mixture had no significant effect on serum hepatic enzymes, aspartate aminotransferase, and alanine aminotransferase activities. However, the level of fasting blood glucose, water intake, and urine output in treated group was lower than that in diabetic control rats (P < 0.01). Also, the levels of triglyceride and total cholesterol in polyherbal mixture treated rats were significantly lower than those in diabetic control group (P < 0.05). Our results demonstrated that this polyherbal mixture has beneficial effects on blood glucose and lipid profile and it has the potential to be used as a dietary supplement for the management of diabetes. PMID:24383002

  3. Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.

    PubMed

    Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest

    2013-10-01

    There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes?+?POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes?+?POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. PMID:22886793

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

    SciTech Connect

    Georgiou, H.M.; Bellgrau, D.

    1989-05-15

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

  5. Coconut kernel-derived proteins enhance hypolipidemic and antioxidant activity in alloxan-induced diabetic rats.

    PubMed

    Salil, Gopalakrishnan; Nevin, Kottayath Govindan; Rajamohan, Thankappan

    2013-05-01

    Impaired lipid levels and oxidative stress are indicative of malfunction of endogenous antioxidant capacity. The aim of this study was to determine the effect of coconut kernel protein (CKP) on the lipid peroxides and antioxidant enzyme activities in diabetic rats. Diabetes was induced prior to feeding by injecting a single dose of alloxan (150 mg/kg body weight) intraperitoneally. CKP (8% w/w) was administered to these rats along with a semi-synthetic diet for 45 days. After the experimental period, peroxide products and antioxidant enzyme activities were determined. Results show that CKP maintained the antioxidant enzyme activities and levels of peroxides to the normal levels in treated group compared to diabetic rats. This study clearly show that CKP has potential effect in lowering oxidative stress associated with diabetes. This beneficial effect of CKP may be due to the high amount of biologically potent arginine present in it. PMID:23113582

  6. Vanadium-Enriched Cordyceps sinensis, a Contemporary Treatment Approach to Both Diabetes and Depression in Rats

    PubMed Central

    Guo, Jianyou; Li, ChangYu; Wang, Jie; Liu, Yongmei; Zhang, Jiahui

    2011-01-01

    This article studies a contemporary treatment approach toward both diabetes and depression management by vanadium-enriched Cordyceps sinensis (VECS). Streptozotocin-induced hyperglycemic rats were used in the study. After the rats were administered with VECS, a significant reduction in blood glucose levels was seen (P < .05) and the levels of serum insulin increased significantly (P < .05). At the same time, the study revealed a significant decrease in immobility with a corresponding increase in the swimming and climbing behavior in hyperglycemic rats following VECS treatment. The results described herein demonstrate that VECS is a contemporary treatment approach that advocates an aggressive stance toward both diabetes and depression management. PMID:21799679

  7. Antioxidant, Antihyperlipidaemic and Antidiabetic Activity of Eugenia Floccosa Bedd Leaves in Alloxan Induced Diabetic Rats

    PubMed Central

    Jelastin, Kala S Mary; Tresina, P.S.; Mohan, V.R.

    2011-01-01

    The ethanol extract of Eugenia floccosa Bedd (Family: Myrtaceae) leaf was investigated for its antioxidant, antihyperlipidaemic and antidiabetic effect in Wistar Albino rats. Diabetes was induced in Albino rats by administration of alloxan monohydrate (150mg/kg, i.p). The ethanol extracts of E. floccosa at a dose of 150 and 300mg/kg of body weight were administered at single dose per day to diabetes induced rats for a period of 14 days. The effect of ethanol extract of E. floccosa leaf extract on blood glucose, plasma insulin, creatinine, glycosylated haemoglobin, urea serum lipid profile [total cholesterol (TR), triglycerides (TG), low density lipoprotein – cholesterol (LDL-C), very low density lipoprotein – cholesterol (VLDL-C), high density lipoprotein – cholesterol (HDL-C) and phospholipid (PL)] serum protein, albumin, globulin, serum enzymes [serum glutamate pyruvate transaminases (SGPT) and serum glutamate oxaloacetate transaminases (SGOT), and alkaline phosphatase (ALP)], lipoprotein peroxidation (LPO) antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPx) were measured in the diabetic rats. The ethanol extract of Eugenia floccosa leaf elicited significant reductions of blood glucose (P<0.05), lipid parameters except HDL-C, serum enzymes and significantly increased HDL-C and antioxidant enzymes. The extracts also caused significant increase in plasma insulin (P<0.05) in the diabetic rats. From the above results, it is concluded that ethanol extract of Eugenia floccosa possesses significant antidiabetic, antihyperlipidaemic and antioxidant effects in alloxan induced diabetic rats. PMID:24826030

  8. Antidiabetic and antihyperlipidemic effects of Thespesia populnea fruit pulp extracts on alloxan-induced diabetic rats.

    PubMed

    Belhekar, S N; Chaudhari, P D; Saryawanshi, J S; Mali, K K; Pandhare, R B

    2013-03-01

    Present study was carried to find out the antihyperglycemic and antihyperlipidemic activity of ethanol and aqueous extract of Thespesia populnea fruit pulp on alloxan-induced diabetic rats. Diabetes was induced in rats by administration of alloxan (150 mg/kg, i.p.). After the successful induction of experimental diabetes, the rats were divided into five groups each comprising a minimum of six rats. Phytochemical analysis and acute toxicity study of extracts was also done. The effects of extracts and metformin on fasting blood glucose and plasma lipid were examined for 28 days. Statistical analysis was carried out by using analysis of variance followed by Dunnet's multiple comparison test and paired t-test were done as the test of significance using GraphPad Prism. P?0.05 was considered as the minimal level of statistical significance. Therapeutic dose of extract was found to be 200 mg/kg on the basis of acute toxicity study. Aqueous and alcoholic extract showed a significant reduction in blood glucose levels as well as a lipid profile of diabetic rats at the end of 28(th) day of treatment. However, in groups treated with plant extract the reduction in the blood glucose and improvement in lipid profile was slightly less than that achieved with the standard group (metformin). From this study, it can be concluded that ethanol and aqueous extract of Thespesia populnea exhibited significant antihyperglycemic and antihyperlipidemic effects on alloxan-induced diabetic rats. PMID:24019572

  9. Upregulation of TNF-alpha and Receptors Contribute to Endothelial Dysfunction in Zucker Diabetic Rats

    PubMed Central

    Gao, Xue; Picchi, Andrea; Zhang, Cuihua

    2010-01-01

    Diabetes mellitus is a major risk factor to impair endothelial function and induce cardiovascular diseases. TNF-alpha (TNF) is expressed during a variety of inflammatory conditions. We hypothesized that impairment in coronary endothelial function in type 2 diabetes is due to the overexpression of TNF and TNF receptors (TNFRs). Endothelium-dependent (acetylcholine, ACh) and –independent vasodilation (sodium nitroprusside, SNP) of isolated, pressurized (60 cmH2O) coronary arteries (50–100 ?m) from lean control and Zucker diabetic fatty (ZDF, the model of type 2 diabetes) rats were determined. In lean rats, SNP and ACh induced dose-dependent vasodilation, but dilation to only ACh was blocked by the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 ?M). In ZDF rats, dilation to ACh was blunted compared to lean rats, but SNP-induced dilation was comparable. Neutralizing antibodies to TNF, or blockade of NAD(P)H and xanthine oxidase, partially restored endothelium-dependent, NO-mediated vasodilation in isolated coronary arteries in ZDF rats, but anti-TNF did not alter endothelium-dependent vasodilation in lean rats. The mRNA expression of TNF receptor 1 (TNFR1, but not TNFR2) significantly increased in coronary arteries in ZDF rats. Protein expression of TNF and N-Tyr (ONOO?) were higher in coronary arteries in ZDF than those in lean rats. Production of H2O2, NAD(P)H oxidase and xanthine oxidase activity were all higher in ZDF rats than those in lean controls; anti-TNF reduces the production of H2O2, N-Tyr expression, NAD(P)H oxidase and xanthine oxidase activity in ZDF rats. These results demonstrate the endothelial dysfunction occurring in type 2 diabetes is the result of effects of the inflammatory cytokine TNF that activates NAD(P)H oxidase and xanthine oxidase; and perhaps acts mainly through the overexpression of TNFR1. PMID:20559450

  10. Resveratrol and diabetic cardiac function: focus on recent in vitro and in vivo studies.

    PubMed

    Turan, Belma; Tuncay, Erkan; Vassort, Guy

    2012-04-01

    Resveratrol, a natural phytoalexin found in wine has the potential to impact a variety of human diseases. Resveratrol like other polyphenols activates many of the same intracellular pathways as those activated by caloric restriction. It can quench reactive oxidative species, ROS and induce eNOS and iNOS expression. Resveratrol also can activate SIRT1, a NAD?-dependent deacetylase, that leads an improved in mitochondrial function, and then this procedure turns to activate the transcription factor Nrf2 that coordinates expression of key antioxidant mechanisms by binding to the antioxidant response elements. Resveratrol provides cardioprotection by triggering preconditioning and inducing autophagy. It also presents chemical similarities with estrogen and was reported to activate both nuclear and extranuclear estrogen receptors. Resveratrol treatment alleviated diabetes-induced cardiovascular system disorders via different endogeneous signaling pathways including oxidative stress/antioxidant defense system, glucose/insulin metabolism, overexpression of iNOS/nitrotyrosine, and preconditioning. Resveratrol treatment significantly reduced the blood glucose level in STZ-treated type 1 diabetic animals through insulin-dependent and insulin-independent pathways. Resveratrol triggers some of the similar intracellular insulin signalling components in myocardium such as eNOS, AKT through the AMPK pathway, and plays an essential role in Glut-4 translocation and glucose uptake in STZ-induced diabetic myocardium. However, resveratrol can exhibit hormetic action expressing health benefits at lower doses whereas being detrimental at higher doses. It might also exert antidiabetic effects by activating SIRT1 directly in the brain. This review includes a summary of the role of resveratrol and diabetic cardiac function including a brief discussion on in vitro and in vivo studies as well as our original observations in diabetic rats. PMID:22437738

  11. Tangzhining exhibits a protective effect against cognitive dysfunction in diabetic rats

    PubMed Central

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

    2015-01-01

    Previous studies have suggested that diabetes significantly impairs the cognitive function. Tangzhining (TZN), as a kind of Traditional Chinese Medicine (TCM), has been widely used to treat diabetes in China. However, the effect of TZN on treatment of diabetes-induced learning and memory deficits has not been well documented. The present study was to investigate the effect of TZN on diabetes-induced learning and memory deficits and delineate the underlying molecular mechanism. Diabetic rats were randomly grouped and treated with various doses of TZN (0.47, 0.94 and 1.4 g/kg) by intraperitoneal injection. Using the Morris water maze, TZN treatment (0.94 g/kg and 1.4 g/kg) reduced markedly the escape latency and path length of diabetic rats. The morphological changes of pyramidal cells in hippocampus of diabetic rats were apparently reversed and improved by TZN treatment, in comparison with that in diabetic rats without TZN treatment. Moreover, the results of Western blot analysis showed that TZN treatment significantly increased the protein expression of glutamic acid decarboxylase (GAD) and excitatory amino acid carrier 1 (EAAC1) in hippocampus of diabetic rats. Furthermore, TZN treatment increased the protein expression of N-methyl-D-aspartic acid (NMDA) receptor subunits including NR1 and NR2B. Taken together, our data suggest that TZN sustains the balance between glutamate (Glu) and GABA by regulating GAD and EAAC1, and maintains the NMDA receptors activity for learning and memory function through regulating the subunits NR1 and NR2B. PMID:26309554

  12. Decreased exposure of simvastatin and simvastatin acid in a rat model of type 2 diabetes

    PubMed Central

    Xu, Dan; Li, Feng; Zhang, Mian; Zhang, Ji; Liu, Can; Hu, Meng-yue; Zhong, Ze-yu; Jia, Ling-ling; Wang, Da-wei; Wu, Jie; Liu, Li; Liu, Xiao-dong

    2014-01-01

    Aim: Simvastatin is frequently administered to diabetic patients with hypercholesterolemia. The aim of the study was to investigate the pharmacokinetics of simvastatin and its hydrolysate simvastatin acid in a rat model of type 2 diabetes. Methods: Diabetes was induced in 4-week-old rats by a treatment of high-fat diet combined with streptozotocin. After the rats received a single dose of simvastatin (20 mg/kg, po, or 2 mg/kg, iv), the plasma concentrations of simvastatin and simvastatin acid were determined. Simvastatin metabolism and cytochrome P4503A (Cyp3a) activity were assessed in hepatic microsomes, and its uptake was studied in freshly isolated hepatocytes. The expression of Cyp3a1, organic anion transporting polypeptide 2 (Oatp2), multidrug resistance-associated protein 2 (Mrp2) and breast cancer resistance protein (Bcrp) in livers was measured using qRT-PCR. Results: After oral or intravenous administration, the plasma concentrations and areas under concentrations of simvastatin and simvastatin acid were markedly decreased in diabetic rats. Both simvastatin metabolism and Cyp3a activity were markedly increased in hepatocytes of diabetic rats, accompanied by increased expression of hepatic Cyp3a1 mRNA. Furthermore, the uptake of simvastatin by hepatocytes of diabetic rats was markedly increased, which was associated with increased expression of the influx transporter Oatp2, and decreased expression of the efflux transporters Mrp2 and Bcrp. Conclusion: Diabetes enhances the metabolism of simvastatin and simvastatin acid in rats via up-regulating hepatic Cyp3a activity and expression and increasing hepatic uptake. PMID:25152023

  13. Chronic Oral Epigallocatechin-gallate Alleviates Streptozotocin-induced Diabetic Neuropathic Hyperalgesia in Rat: Involvement of Oxidative Stress

    PubMed Central

    Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

    2012-01-01

    Due to the anti-diabetic and antioxidant activity of green tea epigallocatechin-gallate (EGCG), this research study was conducted to evaluate, for the first time, the efficacy of chronic treatment of EGCG on alleviation of hyperalgesia in streptozotocin-diabetic (STZ-diabetic) rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and diabetic and sodium salicylate (SS)-treated control and diabetic groups. For induction of diabetes, STZ was intraperitoneally injected (IP) at a single dose of 60 mg/Kg. EGCG was orally administered daily at doses of 20 and 40 mg/Kg for seven weeks; one week after diabetes induction. Finally, hyperalgesia was assessed using standard formalin, hot tail immersion and paw pressure tests. Meanwhile, markers of oxidative stress in brain were measured. Diabetic rats showed a marked chemical, thermal and paw pressure hyperalgesia, indicating that the development of diabetic neuropathy and EGCG treatment at a dose 40 mg/Kg significantly ameliorated the alteration in hyperalgesia (p < 0.05) in diabetic rats as compared with untreated diabetics. EGCG treatment (40 mg/Kg) also significantly decreased diabetes-induced thiobarbituric acid reactive substances formation (p < 0.05) and nitrite (p < 0.05) content and reversed the reduction of antioxidant defensive enzyme superoxide dismutase (p < 0.05). The results may suggest therapeutic potential of EGCG for the treatment of diabetic hyperalgesia through the attenuation of oxidative stress. PMID:24250559

  14. The Blocking on the Cathepsin B and Fibronectin Accumulation in Kidney Glomeruli of Diabetic Rats

    PubMed Central

    Wyczalkowska-Tomasik, Aleksandra; Bartlomiejczyk, Irena; Wirkowska, Agnieszka; Koperski, Lukasz; Gornicka, Barbara; Paczek, Leszek

    2015-01-01

    Hyperglycemia results in the activation of tissue angiotensin II. Angiotensin II stimulates the synthesis of ECM proteins and causes a decrease activity of proteolytic enzymes. The aim of this study was to assess the impact of multilevel blocking of the RAAS, cathepsin B activity, and fibronectin accumulation in the glomerular in the rats diabetes model. Sixty male Wistar rats were initially included. Diabetes was induced by intravenous administration of streptozotocin. The animals were randomized to six groups of ten rats in group. Rats in the four groups were treated with inhibitors of the RAAS: enalapril (EN), losartan (LOS), enalapril plus losartan (EN + LOS), and spironolactone (SPIR); another group received dihydralazine (DIH) and the diabetic rats (DM) did not receive any drug. After six weeks, we evaluated blood pressure, 24?h urine collection, and blood for biochemical parameters and kidneys. In this study, fluorometric, ELISA, and immunohistochemical methods were used. Administration of EN + LOS increased activity of cathepsin B in homogenates of glomeruli compared to DM. Losartan treatment resulted in reduction of the ratio kidney weight/body weight compared to untreated diabetic rats. SPIR resulted in the increase activity of cathepsin B in the homogenate of glomeruli. The values of cathepsin B in the plasma of rats in all studied groups were similar and showed no tendency. PMID:26089895

  15. Antidiabetic Activity of Differently Regioselective Chitosan Sulfates in Alloxan-Induced Diabetic Rats

    PubMed Central

    Xing, Ronge; He, Xiaofei; Liu, Song; Yu, Huahua; Qin, Yukun; Chen, Xiaolin; Li, Kecheng; Li, Rongfeng; Li, Pengcheng

    2015-01-01

    The present study investigated and compared the hypoglycemic activity of differently regioselective chitosan sulfates in alloxan-induced diabetic rats. Compared with the normal control rats, significantly higher blood glucose levels were observed in the alloxan-induced diabetic rats. The differently regioselective chitosan sulfates exhibited hypoglycemic activities at different doses and intervals, especially 3-O-sulfochitosan (3-S). The major results are as follows. First, 3,6-di-O-sulfochitosan and 3-O-sulfochitosan exhibited more significant hypoglycemic activities than 2-N-3, 6-di-O-sulfochitosan and 6-O-sulfochitosan. Moreover, 3-S-treated rats showed a more significant reduction of blood glucose levels than those treated by 3,6-di-O-sulfochitosan. These results indicated that –OSO3? at the C3-position of chitosan is a key active site. Second, 3-S significantly reduced the blood glucose levels and regulated the glucose tolerance effect in the experimental rats. Third, treatment with 3-S significantly increased the plasma insulin levels in the experimental diabetic rats. A noticeable hypoglycemic activity of 3-S in the alloxan-induced diabetic rats was shown. Clinical trials are required in the future to confirm the utility of 3-S. PMID:25988523

  16. TCM Formula Xiaoyaosan Decoction Improves Depressive-Like Behaviors in Rats with Type 2 Diabetes

    PubMed Central

    Li, Na; Liu, Qun; Li, Xiao-Juan; Bai, Xiao-Hui; Liu, Yue-Yun; Zhao, Hong-Bo; Jin, Zhong-Ye; Jing, Yu-Xia; Yan, Zhi-Yi; Chen, Jia-Xu

    2015-01-01

    The mechanism of depression with type 2 diabetes remains elusive, requiring further study. Objective. To evaluate the effect of TCM formula Xiaoyaosan on depressive-like behaviors in rats with type 2 diabetes. Methods. Rats were divided into 5 groups and drugs were administered during the model period of 21 days. The model of depressive-like behaviors in rats with type 2 diabetes was induced by a high fat diet, low doses of STZ injection, and chronic restraint stress for 21 days. The body weight, fasting blood glucose, ITT, OGTT, 5-HT, DA, depression behaviors, and morphological changes of formation were measured and observed. Results. After modeling, marked changes were found in model rats; behavioral analyses of rats indicated that this modeling method negatively impacts locomotor function. In the H&E staining, changes were found predominately in the CA1 and DG subregions of the hippocampus. After 21 days of treatment by fluoxetine and Xiaoyaosan, rats' body weights, behaviors and fasting blood glucose, and hippocampal formation were modified. Conclusions. A new model of depressive-like behaviors in rats with type 2 diabetes was successfully created. Xiaoyaosan and fluoxetine in this study independently contribute to exacerbate the disease progression. PMID:26508978

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  18. Inhibition of diabetic nephropathy in rats by an oral antidiabetic material extracted from yeast.

    PubMed

    Nakhoul, Farid; Abassi, Zaid; Morgan, Michal; Sussan, Sharbel; Mirsky, Nitza

    2006-04-01

    Diabetic nephropathy is one of the major complications of diabetes. The glucose tolerance factor (GTF) is a dietary agent extracted from several natural sources; the richest among them is brewer's yeast. Extraction and purification of an active and stable GTF preparation from brewer's yeast previously was successful, and a remarkable decrease in plasma glucose and lipids from administration of GTF to animals with type 1 diabetes was demonstrated. The purpose of the present study was to examine whether GTF affects nephropathy in diabetic rats. The average urinary volume and protein excretion throughout the collection period in diabetic rats was 56.95 +/- 2.2 ml/d and 5.42 +/- 0.95 mg/d, respectively. These values were significantly (P < 0.001 versus baseline values) higher compared with healthy controls (average urine volume 15.12 +/- 0.5 ml/d; average protein excretion 0.15 +/- 0.08 mg/d). Treatment with GTF reduced average urine volume and protein excretion to 29.1 +/- 1.94 ml/d (P < 0.01) and 1.55 +/- 1.17 mg/d (P < 0.05), respectively. Kidney weight, which was elevated in diabetic rats, slightly decreased in diabetic animals that were treated with GTF, in association with reduction of lipid peroxidation levels in the renal cortex and the heart. Endothelial nitric oxide immunoreactivity in the renal cortex of both healthy and diabetic rats that were treated with GTF was remarkably lower than that found in renal cortex of untreated diabetic animals. This study demonstrates that yeast-derived material, GTF, can inhibit the development of nephropathy that is induced by diabetes. PMID:16565236

  19. Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions

    PubMed Central

    Ishii, Yukihito; Motohashi, Yu; Muramatsu, Makoto; Katsuda, Yoshiaki; Miyajima, Katsuhiro; Sasase, Tomohiko; Yamada, Takahisa; Matsui, Tohru; Kume, Shinichi; Ohta, Takeshi

    2015-01-01

    AIM: To investigate the histological features of the liver in spontaneously diabetic Torii (SDT) fatty rats compared with age-matched Sprague-Dawley (SD) rats. METHODS: Female SDT Leprfa (SDT fatty) rats and age-matched SD rats were fed ad libitum. Body weight and biochemical parameters, such as serum glucose, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as well as fatty acid and TG accumulation in the liver were evaluated at 8 wk of age in the non-fasting state and at 8-wk intervals from 8 to 40 wk of age. Histopathological examinations of the liver were performed using hematoxylin and eosin and Sirius Red staining as well as double staining for ED-1 and toluidine blue. The expression of genes involved in TG synthesis, inflammation, and fibrosis was examined in the liver. RESULTS: SDT fatty rats showed significantly increased body weight compared with SD rats. Serum glucose, TG, and TC levels were significantly higher in SDT fatty rats compared with SD rats. The serum AST and ALT levels in SDT fatty rats were significantly elevated at 8 wk of age compared with the levels in SD rats. Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age. Histopathologically, severe hepatosteatosis accompanied by inflammation was observed at 8 wk of age, and fibrosis started to occur at 32 wk of age. Furthermore, Sirius Red and ED-1 staining were increased in the liver at 32 wk of age. Hepatic gene expression related to TG synthesis, inflammation and fibrosis tended to increase in SDT fatty rats compared with SD rats, and the gene expression related to TG secretion was decreased in SDT fatty rats compared with SD rats. CONCLUSION: Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity. PMID:26290633

  20. Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

    2016-01-01

    Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1?), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1?), transforming growth factor- beta1 (TGF-?1()), tumor necrosis factor-? (TNF-?) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1?) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1?, VEGF, SDF-1?, TGF-?1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-? and the mRNA of IL-1? and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. PMID:26679676

  1. Diabetes

    MedlinePLUS

    ... version of this page please turn Javascript on. Diabetes What is Diabetes? Too Much Glucose in the Blood Diabetes means ... high, causing pre-diabetes or diabetes. Types of Diabetes There are three main kinds of diabetes: type ...

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

    PubMed

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

    2015-06-01

    Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications. PMID:25514087

  3. Telmisartan, an angiotensin II type 1 receptor blocker, prevents the development of diabetes in male Spontaneously Diabetic Torii rats.

    PubMed

    Hasegawa, Goji; Fukui, Michiaki; Hosoda, Hiroko; Asano, Mai; Harusato, Ichiko; Tanaka, Muhei; Shiraishi, Emi; Senmaru, Takashi; Sakabe, Kazumi; Yamasaki, Masahiro; Kitawaki, Jo; Fujinami, Aya; Ohta, Mitsuhiro; Obayashi, Hiroshi; Nakamura, Naoto

    2009-03-01

    To assess the beneficial effects of the angiotensin II type 1 receptor blocker telmisartan on a non-obese animal model of reduced function and mass of islet beta-cells prior to the development of diabetes, Spontaneously Diabetic Torii (SDT) rats were treated with telmisartan at 8 weeks of age. At 24 weeks of age, the treatment with telmisartan dose-dependently ameliorated hyperglycemia and hypoinsulinemia, and high-dose (5 mg/kg/day) treated SDT rats did not developed diabetes. Real-time RT-PCR analysis revealed that treatment with high-dose telmisartan reduced mRNA expression of local renin-angiotensin system (RAS) components, components of NAD(P)H oxidase, transforming growth factor-beta1 and vascular endothelial growth factor in the pancreas of male SDT rats. Immunohistochemical and Western blot analyses revealed that treatment with telmisartan also reduced expression of p47(phox). These results suggest that treatment with telmisartan reduces oxidative stress by local RAS activation and protects against islet beta-cell damage and dysfunction. These findings provide at least a partial explanation for the reduced incidence of new-onset diabetes that has been observed in several clinical trials involving angiotensin II type 1 receptor blockers and ACE inhibitors. PMID:19171132

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

    PubMed Central

    Eleazu, Kate Chinedum; Ironkwe, Adanma; Iroaganachi, Mercy Amarachi

    2014-01-01

    Background The effect of livingstone potato (Plectranthus esculenthus N.E.Br) on diabetes and its complications in Streptozotocin induced diabetic rats was investigated. The duration of the experiment was 4 weeks. Methods The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The liver and kidney function parameters in the serum of the rats were determined using Biosystem Kits. Results The diabetic rats given livingstonepotato incorporated feeds, had 129.7% decrease in their hyperglycemia with corresponding amelioration of their elevated urinary protein, sugars, specific gravity, renal growth, liver growth as well as 15.64% decrease in body weights compared with the nondiabetic rats that had 5.54% decrease in blood glucose and 20.39% increase in body weight unlike the diabetic control rats that had 18.34% decrease in blood glucose and 52.68% decrease in body weight. There were significant differences (P<0.05) in the relative liver, pancreas, and kidney weights of the diabetic rats given livingstone potato feeds compared with the diabetic control while there were no significant differences (P>0.05) in the relative heart weights of all the rats in the three different groups. In terms of liver and kidney function parameters, values obtained for the diabetic rats given livingstone potato incorporated feeds were not significantly different from that of the nondiabetic rats except for total bilurubin, aspartate transaminase, and creatinine (P>0.05) while they were significantly different from the values obtained for the diabetic control rats (P<0.05). In addition, the serum amylase of the diabetic control rats were significantly higher (P<0.05) than that of the nondiabetic and diabetic rats treated with livingstone potato incorporated feeds. Conclusion Results show the antidiabetic actions of livingstone potato and its ability to ameliorate glomerular complication and liver hypertrophy in diabetics. PMID:25349824

  5. Depressed glucose utilization in lungs of BB wistar spontaneously diabetic rats

    SciTech Connect

    Uhal, B.D.; Moxley, M.A.; Longmore, W.J.

    1986-03-05

    Lungs of BB wistar spontaneously diabetic rats were perfused with (/sup 14/C(U))glucose in modified Krebs Ringer bicarbonate medium for 1.5 hours. Lungs from non-diabetic BB Wistar rats were perfused simultaneously and served as controls. The perfusions were terminated by rapid freezing of the tissue in liquid N/sub 2/ followed by separation of surfactant and residual lung fractions. The rates of glucose incorporation into surfactant DSPC, PG, and PE were decreased 4.7, 2.4 and 2.5-fold, respectively, in lungs of spontaneously diabetic rats when expressed as final product specific activities. The rate of glucose incorporation into residual PC was also reduced by 2.3-fold. Expressed as moles incorporated per gram wet weight of lung, incorporations into surfactant DSPC, PG and residual PC were also reduced by 4.1, 6.3 and 3.8-fold respectively. These data; (1) agree with previous studies of the lungs of streptozotocin and alloxan-diabetic rats; (2) show that the depressed glucose utilization for lipid synthesis observed previously is not due to streptozotocin or alloxan toxicity; (3) suggest that the BB Wistar rat will provide a useful model for the study of the effects of insulin-dependent diabetes on lung metabolism.

  6. Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats

    PubMed Central

    XIAO, XIAOYAN; WANG, JIE; CHANG, XIANGDI; ZHEN, JUNHUI; ZHOU, GENGYIN; HU, ZHAO

    2015-01-01

    Recent studies in animal models have revealed that mycophenolate mofetil (MMF) has certain protective effects against experimental diabetic nephropathy. The present study therefore aimed to investigate the hypothesis that diabetic nephropathy may be ameliorated by mycophenolate mofetil and benazepril treatment alone or in combination, and identify the potential underlying mechanisms in a rat model. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin. Rats were subsequently treated with benazepril, MMF or a combination of the two drugs, and blood glucose, normalized kidney weight, urine protein and serum creatinine were determined. The pathological changes in renal tissue were also observed. In addition, indices of epithelial mesenchymal transition, including ?-smooth muscle actin (?-SMA) and transforming growth factor (TGF)-?1 expression, were examined. Normalized kidney weight, urine protein and serum creatinine levels were significantly improved in the diabetic rats treated with benazepril or mycophenolate mofetil, compared with those of rats in the untreated diabetic group. Pathological changes in the kidney were detected concurrently with increasing kidney weight and urinary albumin excretion, with a similar trend in variation among groups. In addition, the expression of epithelial mesenchymal transition indices, including ?-SMA and TGF-?1, in the renal tubule interstitium were significantly decreased in the benazepril- and MMF-treated groups compared with those of the diabetic group. As expected, the aforementioned indices were markedly lower in the benazepril and MMF combined treatment group than those in the single medication groups. These data suggested that MMF may have a protective role in diabetic nephropathy, and that the underlying mechanism may be partially dependent upon the suppression of the epithelial mesenchymal transition. Furthermore, the combination of benazepril and MMF conferred enhanced efficacy over monotherapies in the treatment of diabetic nephropathy. PMID:26080907

  7. Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats.

    PubMed

    Xiao, Xiaoyan; Wang, Jie; Chang, Xiangdi; Zhen, Junhui; Zhou, Gengyin; Hu, Zhao

    2015-09-01

    Recent studies in animal models have revealed that mycophenolate mofetil (MMF) has certain protective effects against experimental diabetic nephropathy. The present study therefore aimed to investigate the hypothesis that diabetic nephropathy may be ameliorated by mycophenolate mofetil and benazepril treatment alone or in combination, and identify the potential underlying mechanisms in a rat model. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin. Rats were subsequently treated with benazepril, MMF or a combination of the two drugs, and blood glucose, normalized kidney weight, urine protein and serum creatinine were determined. The pathological changes in renal tissue were also observed. In addition, indices of epithelial mesenchymal transition, including ??smooth muscle actin (??SMA) and transforming growth factor (TGF)??1 expression, were examined. Normalized kidney weight, urine protein and serum creatinine levels were significantly improved in the diabetic rats treated with benazepril or mycophenolate mofetil, compared with those of rats in the untreated diabetic group. Pathological changes in the kidney were detected concurrently with increasing kidney weight and urinary albumin excretion, with a similar trend in variation among groups. In addition, the expression of epithelial mesenchymal transition indices, including ??SMA and TGF??1, in the renal tubule interstitium were significantly decreased in the benazepril? and MMF?treated groups compared with those of the diabetic group. As expected, the aforementioned indices were markedly lower in the benazepril and MMF combined treatment group than those in the single medication groups. These data suggested that MMF may have a protective role in diabetic nephropathy, and that the underlying mechanism may be partially dependent upon the suppression of the epithelial mesenchymal transition. Furthermore, the combination of benazepril and MMF conferred enhanced efficacy over monotherapies in the treatment of diabetic nephropathy. PMID:26080907

  8. Antihyperglycemic action of rhodiola-aqeous extract in type1-like diabetic rats

    PubMed Central

    2014-01-01

    Background Rhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world. It is mainly used in clinics as an adaptogen. Recently, it has been mentioned that Rhodiola increases plasma ?-endorphin to lower blood pressure. Thus, the present study aims to investigate the antidiabetic action of Rhodiola in relation to opioids in streptozotocin-induced diabetic rats (STZ-diabetic rats). Methods In the present study, the plasma glucose was analyzed with glucose oxidase method, and the determination of plasma ?-endorphin was carried out using a commercially available enzyme-linked immunosorbent assay. The adrenalectomy of STZ-diabetic rats was used to evaluate the role of ?-endorphin. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to investigate mRNA and protein expressions. Results Rhodiola-water extract dose-dependently lowered the plasma glucose in STZ-diabetic rats and this action was reversed by blockade of opioid ?-receptors using cyprodime. An increase of plasma ?-endorphin by rhodiola-water extract was also observed in same manner. The plasma glucose lowering action of rhodiola-water extract was attenuated in bilateral adrenalectomized rats. In addition, continuous administration of rhodiola-water extract for 3 days in STZ-diabetic rats resulted in an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle and a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These effects were also reversed by blockade of opioid ?-receptors. Conclusions Taken together, rhodiola-water extract improves hyperglycemia via an increase of ?-endorphin secretion from adrenal gland to activate opioid ?-receptors in STZ-diabetic rats. PMID:24417880

  9. Vanadium-enriched chickpea sprout ameliorated hyperglycemia and impaired memory in streptozotocin-induced diabetes rats.

    PubMed

    Mao, Xueqin; Zhang, Ling; Xia, Qing; Sun, Zhaofeng; Zhao, Xiaomin; Cai, Hongxin; Yang, Xiaoda; Xia, Zuoli; Tang, Yujing

    2008-10-01

    Vanadium compounds have been recognized for their hypoglycemic effects; however, potential short and long-term vanadium toxicity has slowed the acceptance for therapeutic use. In the present work, three batches of vanadium-enriched chickpea sprout (VCS) were prepared by incubating chickpea seeds in presence of 200, 100, and 50 microg/ml of sodium orthovanadate (SOV). The effects of oral administration of chickpea sprout (CS) and VCS food for 8 weeks on streptozotocin-induced (STZ) diabetic rats were investigated. Both CS and VCS food was found to ameliorate some hyperglycemic symptoms of the diabetic rats, i.e. improve lipid metabolism, decrease blood glucose level, prevent body weight loss, and reduce impairment of diabetic related spatial learning and memory. Serum insulin was substantially elevated in treated diabetic rats, which is probably one important reason for the hypoglycemic effect. Compared with CS alone, VCS100 food exhibited remarkably enhanced effectiveness in alleviating diabetes induced hyperglycemia and memory loss. Moreover, vanadium-enriched chickpeas appeared to abolish the vanadium induced toxicity associated with administration of this metal for diabetes during the 8-week study period. This study suggested further work of the vanadium speciation in CS and novel hypoglycemic mechanism for the antidiabetic activity of vanadium agents. Vanadium containing (VCS) food could be a dietary supplement for the diabetic status. PMID:18431678

  10. Renoprotective effect of berberine on type 2 diabetic nephropathy in rats.

    PubMed

    Sun, Si-Fan; Zhao, Ting-Ting; Zhang, Hao-Jun; Huang, Xiao-Ru; Zhang, Wei-Ku; Zhang, Lei; Yan, Mei-Hua; Dong, Xi; Wang, Hua; Wen, Yu-Min; Pan, Xin-Ping; Lan, Hui Yao; Li, Ping

    2015-06-01

    Inflammation, fibrosis, and lipid disorder are essential promoters in the pathogenesis of diabetic kidney injury in diabetes mellitus type 2. Berberine (BBR) has been reported to have beneficial effects on diabetic nephropathy, but its action mechanism is still unclear. The present study was designed to elucidate the therapeutic mechanism of BBR in a type 2 diabetic nephropathy rat model induced by a high-fat diet and low-dose streptozotocin injection. The diabetic rats were treated with or without BBR by gavage for 20 weeks and examined by serology, 24-h albuminuria, histology, immunohistochemistry, and molecular analyses. Results showed that treatment with BBR significantly reduced serum levels of blood glucose and lipids, inhibited urinary excretion of albumin, and attenuated renal histological injuries in diabetic rats. Berberine treatment also inhibited renal inflammation, which was associated with inactivation of nuclear factor kappa-light-chain-enhancer of activated B-cell signalling. As a result, the upregulation of pro-inflammatory cytokines (interleukin-1?, tumour necrosis factor-?) and chemokine (monocyte chemotactic protein-1) was blocked. In addition, BBR treatment also inactivated transforming growth factor-?/Smad3 signalling and suppressed renal fibrosis, including expression of fibronectin, collagen I, and collagen IV. The present study reveals that BBR is a therapeutic agent for attenuating type 2 diabetic nephropathy by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell-driven renal inflammation and transforming growth factor-?/Smad3 signalling pathway. PMID:25867602

  11. Hypoglycemic and hypolipidemic activities of Salvia hydrangea in streptozotocin-induced diabetes in rats

    PubMed Central

    Zarei, Ali; Vaezi, Gholamhasan; Malekirad, Ali Akbar; Abdollahi, Mohammad

    2015-01-01

    Objective(s): This study was to investigate the potential anti-diabetic effects of alcoholic extract of Salvia hydrangea in rats. Materials and Methods: Thirty five male Wistar rats were divided into five groups namely non-diabetic control, diabetic control, and three experimental diabetic that received either Salvia hydrangea extract for 21 days at the doses of 100 and 200 or glibenclamide at the dose of 10 mg/kg through gavage feeding. To induce diabetes, streptozotocin was injected intraperitoneally. Results: Insulin and HDL levels in the group receiving the high dose of the extract showed significant increase, whereas the amount of cholesterol in rats that received glibenclamide and the extract showed a significant decrease as compared to the diabetic control group (P<0.05). The blood glucose levels showed significant reduction in all experimental groups (P<0.05). Conclusion: Consumption of the extract of the aerial parts of S. hydrangea which reduces blood fat and increases insulin may have beneficial effects on the symptoms of diabetes and hyperlipidemia. PMID:26019807

  12. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg-1 body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes. PMID:26261706

  13. Intracerebroventricular insulin-like growth factor-1 decreases feeding in diabetic rats.

    PubMed

    Lu, H; Martinez-Nieves, B; Lapanowski, K; Dunbar, J

    2001-04-01

    Insulin-like growth factor-1 (IGF-1) is a hormone that is important in the regulation of growth processes and additionally has been demonstrated to modulate metabolic and autonomic responses. Some of its effects are mediated by the central nervous system (CNS), and there are IGF-1 receptors dispersed throughout the CNS. Both IGF-1 and insulin alter peripheral metabolic and autonomic nervous activity by a central mechanism, and the well-defined role of insulin in the regulation of feeding, especially in diabetes, led us to investigate the effect of chronic central administration of IGF-1 on metabolic and feeding parameters in normal and diabetic rats. Normal and diabetic rats with intracerebroventricular cannulas were given IGF-1, insulin (0.5 nmol/animal), or artificial cerebrospinal fluid via cannula twice daily for 4 d. Blood samples were collected on d 2 and 4, and the body weights and food intake were recorded daily. IGF-1 administered intracerebroventricularly did not alter plasma glucose, insulin, body weight, or food intake in normal rats. However, in diabetic animals, IGF-1 decreased food intake but did not alter blood glucose or plasma insulin. In correlated studies, intracerebroventricular insulin decreased food intake in both normal and diabetic animals. From these studies, we conclude that IGF-1 may act centrally to decrease food intake in the hyperphagic diabetic animals but not in normal animals. This suggests that diabetic animals have an increased sensitivity to CNS IGF-1. PMID:11444432

  14. Vulnerability of Gastric Mucosa in Diabetic Rats, Its Pathogenesis and Amelioration by Cuminum cyminum

    PubMed Central

    Vador, N.; Jagtap, Aarti G.; Damle, Archana

    2012-01-01

    Various studies have indicated that peptic ulcers occurring during the course of diabetic state are more severe and often associated with complications such as gastrointestinal bleeding. This study is the first attempt to understand the pathogenesis of gastric ulcers occurring during the diabetic state considering alternate biochemical pathways using suitable markers and its amelioration by Cuminum cyminum. In this study, diabetic rats showed a progressive increase in the stomach advanced glycated end products formation, gastric mucosal tumour necrosis factor-? and Thiobarbituric acid reactive substances levels as compared to normal control (nondiabetic) rats. There was decrease in gastric mucosal content, antioxidant enzymes and cellular ATPase enzyme levels of diabetic gastric mucosa when compared to the normal control group. mRNA expression of epidermal growth factor was found to be significantly higher as compared to normal control animals. Further methanol extract of Cuminum cyminum treatment to diabetic animals caused a reduction in blood glucose, and ulcer score when compared to diabetic control rats. It significantly increased gastric mucus content, antioxidant status and cellular ATPase enzyme levels as compared to diabetic control animals. Methanol extract of Cuminum cyminum inhibited advanced glycated end products formation in vitro as well as in vivo. PMID:23716866

  15. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats

    PubMed Central

    Yilmaz-Ozden, Tugba; Kurt-Sirin, Ozlem; Tunali, Sevim; Akev, Nuriye; Can, Ayse; Yanardag, Refiye

    2014-01-01

    Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes. PMID:24856383

  16. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats.

    PubMed

    Yilmaz-Ozden, Tugba; Kurt-Sirin, Ozlem; Tunali, Sevim; Akev, Nuriye; Can, Ayse; Yanardag, Refiye

    2014-05-01

    Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes. PMID:24856383

  17. Impairment of IKCa channels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy.

    PubMed

    Gokina, Natalia I; Bonev, Adrian D; Phillips, Julie; Gokin, Alexander P; Veilleux, Kelsey; Oppenheimer, Karen; Goloman, Gabriela

    2015-08-15

    Diabetes in rat pregnancy is associated with impaired vasodilation of the maternal uteroplacental vasculature. In the present study, we explored the role of endothelial cell (EC) Ca(2+)-activated K(+) channels of small conductance (SKCa channels) and intermediate conductance (IKCa channels) in diabetes-induced uterine vascular dysfunction. Diabetes was induced by injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with citrate buffer. Changes in smooth muscle cell intracellular Ca(2+) concentration, membrane potential, and vasodilation induced by SKCa/IKCa channel activators were studied in uteroplacental arteries of control and diabetic rats. The impact of diabetes on SKCa- and IKCa-mediated currents was explored in f