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Sample records for ii diabetic rats

  1. [Effect of melatonin on antioxidant state under type ii diabetes at rat].

    PubMed

    Agarkov, A A; Popova, T N; Matasova, L V

    2013-01-01

    The effect of melatonin on the intensity of free radical processes and activities of superoxide dismutase (SOD, EC 1.15.1.1.) and catalase (EC 1.11.1.6) has been investigated in liver and blood serum of rats with diabetes mellitus type II. The development of diabetes was accompanied by the increase in biochemiluminescence parameters and the enzyme activities studied. Melatonin administration changed the parameters studied towards control values.

  2. 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.

  3. Angiotensin II receptor blocker telmisartan attenuates aortic stiffening and remodelling in STZ-diabetic rats

    PubMed Central

    2014-01-01

    Background Prevention or attenuation of diabetic vascular complications includes anti-hypertensive treatment with renin-angiotensin system inhibitors on account of their protective effects beyond blood pressure reduction. The present study aimed to investigate the effects of telmisartan, an angiotensin II type 1 receptor blocker (ARB), on blood pressure, aortic stiffening, and aortic remodelling in experimental type 1 diabetes in rats. Methods Diabetes was induced by streptozotocin (STZ) (65 mg/kg) in male Wistar rats. One diabetic group was treated for 10 weeks with telmisartan (10 mg/kg/day p/o). Pressure-independent aortic pulse wave velocity (PWV) was measured under anaesthesia after intravenous infusion of phenylephrine and nitroglycerine. Aortic wall samples were collected for histomorphometrical analysis. Results Untreated diabetes imposed differential effects on aortic stiffening, as demonstrated by increased isobaric PWV over a range of high blood pressures, but not at lower blood pressures. This was associated with loss and disruption of elastin fibres and an increase in collagen fibres in the aortic media. Treatment with telmisartan decreased resting blood pressure, reduced aortic stiffness, and partially prevented the degradation of elastin network within the aortic wall. Conclusions Telmisartan improved the structural and functional indices of aortic stiffening induced by untreated STZ-diabetes, demonstrating the importance of ARBs in the therapeutic approach to diabetic vascular complications. PMID:24920962

  4. Adipose Tissue-Derived Stem Cells Ameliorate Diabetic Bladder Dysfunction in a Type II Diabetic Rat Model

    PubMed Central

    Zhang, Haiyang; Qiu, Xuefeng; Shindel, Alan W.; Ning, Hongxiu; Ferretti, Ludovic; Jin, Xunbo; Lin, Guiting; Lin, Ching-Shwun

    2012-01-01

    Diabetes mellitus is associated with a broad constellation of voiding complaints that are often multifactorial and resistant to currently available therapies. The leading causes of diabetic bladder dysfunction (DBD) include alterations in the bladder smooth muscle, neuronal degeneration, and urothelial dysfunction. Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stromal cells, have shown promise as a novel tissue regenerative technique that may have utility in DBD. The aim of this study is to determine the efficacy and mechanism by which ADSCs may ameliorate DBD in rats fed a high-fat diet and treated with low-dose streptozotocin to induce type II diabetes. Improved voiding function was noted in ADSCs-treated rats as compared with phosphate-buffered saline-treated rats. Though some ADSCs differentiated into smooth muscle cells, paracrine pathway seems to play a main role in this process, thus resulting in reduction of apoptosis and preservation of “suburothelial capillaries network.” PMID:22008016

  5. Centrally Mediated Erectile Dysfunction in Rats with Type 1 Diabetes: Role of Angiotensin II and Superoxide

    PubMed Central

    Zheng, Hong; Liu, Xuefei; Patel, Kaushik P.

    2015-01-01

    Introduction Erectile dysfunction is a serious complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for penile erection. Aim To determine the contribution of angiotensin (ANG) II in the dysfunction of central N-methyl-D-aspartic acid (NMDA)-nitric oxide (NO)-induced erectile responses in streptozotocin-induced type 1 diabetic (T1D) rats. Methods Three weeks after streptozotocin injections, rats were randomly treated with the angiotensin-converting enzyme inhibitor-enalapril, or the ANG II type 1 receptor blocker, losartan, or the superoxide dismutase mimetic, tempol or vehicle via chronic intracerebroventricular infusion by osmotic mini-pump for 2 weeks. Main Outcome Measure Central NMDA receptor stimulation or the administration of the NO donor, sodium nitroprusside (SNP)-induced penile erectile responses and concurrent behavioral responses were monitored in conscious rats. Results Two weeks of enalapril, losartan or tempol treatment significantly improved the erectile responses to central microinjection of both NMDA and SNP in the paraventricular nucleus (PVN) of conscious T1D rats (NMDA responses – T1D+enalapril: 1.7 ± 0.6, T1D+losartan: 2.0 ± 0.3, T1D+tempol: 2.0 ± 0.6 vs. T1D+vehicle: 0.6 ± 0.3 penile erections/rat in the first 20 min, P < 0.05; SNP responses – T1D+enalapril: 0.9 ± 0.3, T1D+losartan: 1.3 ± 0.3, T1D+tempol: 1.4 ± 0.4 vs. T1D+vehicle: 0.4 ± 0.2 penile erections/rat in the first 20 min, P < 0.05). Concurrent behavioral responses including yawning and stretching, induced by central NMDA and SNP microinjections were also significantly increased in T1D rats after enalapril, losartan or tempol treatments. Neuronal NO synthase expression within the PVN was also significantly increased and superoxide production was reduced in T1D rats after these treatments. Conclusions These data strongly support the contention that enhanced ANG II mechanism/s within the PVN of T1D rats contributes

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

    PubMed

    Baynes, John; Murray, David B

    2009-01-01

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

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

    PubMed

    Ahmed, Aisha S; Li, Jian; Abdul, Alim M D; Ahmed, Mahmood; Östenson, Claes-Göran; Salo, Paul T; Hewitt, Carolyn; Hart, David A; Ackermann, Paul W

    2017-01-01

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

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

    PubMed Central

    Ahmed, Aisha S.; Li, Jian; Abdul, Alim M. D.; Ahmed, Mahmood; Östenson, Claes-Göran; Salo, Paul T.; Hewitt, Carolyn; Hart, David A.; Ackermann, Paul W.

    2017-01-01

    Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering painful connective tissue disorders and tendon ruptures. The pathomechanisms, however, by which diabetes adversely affects connective tissue matrix metabolism and regeneration, still need better definition. Our aim was to study the effect of DM-II on expressional changes of neuro- and angiotrophic mediators and receptors in intact and healing Achilles tendon. The right Achilles tendon was transected in 5 male DM-II Goto-Kakizaki (GK) and 4 age-matched Wistar control rats. The left Achilles tendons were left intact. At week 2 post-injury, NGF, BDNF, TSP, and receptors TrkA, TrkB and Nk1 gene expression was studied by quantitative RT-PCR (qRT-PCR) and their protein distribution by immunohistochemistry in intact and injured tendons. The expression of tendon-related markers, Scleraxis (SCX) and Tenomodulin (TNMD), was evaluated by qRT-PCR in intact and injured tendons. Injured tendons of diabetic GK rats exhibited significantly down-regulated Ngf and Tsp1 mRNA and corresponding protein levels, and down-regulated Trka gene expression compared to injured Wistar controls. Intact tendons of DM-II GK rats displayed reduced mRNA levels for Ngf, Tsp1 and Trkb compared to corresponding intact non-diabetic tendons. Up-regulated Scx and Tnmd gene expression was observed in injured tendons of normal and diabetic GK rats compared to intact Wistar controls. However, these molecules were not up-regulated in injured DM-II GK rats compared to their corresponding controls. Our results suggest that DM-II has detrimental effects on neuro- and angiotrophic pathways, and such effects may reflect the compromised repair seen in diabetic Achilles tendon. Thus, novel approaches for regeneration of injured, including tendinopathic, and surgically repaired diabetic tendons may include therapeutic molecular modulation of neurotrophic pathways such as NGF and its receptors. PMID:28122008

  9. In vivo creatine kinase reaction kinetics at rest and stress in type II diabetic rat heart

    PubMed Central

    Bashir, Adil; Coggan, Andrew R.; Gropler, Robert J.

    2015-01-01

    Abstract The effects of type II diabetes on cardiac creatine kinase (CK) enzyme activity and/or flux are unknown. We therefore measured steady‐state phosphocreatine (PCr) and adenosine triphosphate (ATP) content and forward CK reaction kinetic parameters in Zucker Diabetic Fatty (ZDF) rat hearts, a type II diabetes research model. At baseline the PCr to ATP ratio (PCr/ATP) was significantly lower in diabetic heart when compared with matched controls (1.71 ± 0.21 vs. 2.26 ± 0.24, P < 0.01). Furthermore, the forward CK reaction rate constant (kf) was higher in diabetic animals (0.52 ± 0.09 s−1 vs. 0.35 ± 0.06 s−1, P < 0.01) and CK flux calculated as a product of PCr concentration ([PCr]) and kf was similar between two groups (4.32 ± 1.05 μmol/g/s vs. 4.94 ± 1.23 μmol/g/s, P = 0.20). Dobutamine administration resulted in similar increases in heart rate (~38%) and kf (~0.12 s−1) in both groups. No significant change in PCr and ATP content was observed with dobutamine. In summary, our data showed reduced PCr/ATP in diabetic myocardium as an indicator of cardiac energy deficit. The forward CK reaction rate constant is elevated at baseline which might reflect a compensatory mechanics to support energy flux through the CK shuttle and maintain constant ATP supply. When hearts were stimulated similar increase in kf was observed in both groups thus it seems that CK shuttle does not limit ATP supply for the range of workload studied. PMID:25626865

  10. Cross-talk related to insulin and angiotensin II binding on myocardial remodelling in diabetic rat hearts.

    PubMed

    Maharsy, Wael M; Kadi, Lina N; Issa, Nahla G; Bitar, Khalil M; Der-Boghossian, Asdghig H; Abrahamian, Roy; Bikhazi, Anwar B

    2007-06-01

    This study focused on the regulation and affinity modulation of angiotensin II (Ang II) binding to its receptor subtypes (AT(1)- and AT(2)-receptor) in the coronary endothelium (CE) and cardiomyocytes (CM) of Sprague-Dawley male rats in normal (N), normal treated with losartan (NL), streptozotocin-induced diabetic (D), insulin-treated diabetic (DI), losartan-treated diabetic (DL), and diabetic co-treated with insulin and losartan (DIL). Heart perfusion was used to estimate Ang II binding affinity (tau=1/k-(n)) to its receptor subtypes on CE and CM. Diabetes decreased tau value on CE and increased it on CM as compared to normal. In DL group, the tau value decreased on CE but was normalised on CM. Insulin treatment alone (DI) or with losartan (DIL) restored t to normal on both CE and CM. Western blot results for AT(1)-receptor density showed an increase in diabetics compared to normal with no normalising effect with insulin treatment. The AT(1)-receptor density was normalised in the diabetic groups treated with losartan +/- insulin. Results for AT(2)-receptor regulation revealed a significant difference between untreated (D) and losartan-treated (DL, DIL) diabetic groups. All of these data show the interrelated pathway and cross-talk between insulin and Ang II system indicating potentially negative effects on the diabetic heart.

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

    PubMed

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

    2010-11-01

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

  12. Synthesis, characterization, and efficacy evaluation of a new anti-diabetic vanadyl(II) thiamine hydrochloride complex in streptozotocin-induced diabetic rats.

    PubMed

    Ahmed El-Shazly, Samir; Ahmed, Mohamed Mohamed; Ibrahim, Zein Shaban; Refat, Moamen S

    2015-06-01

    Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to abnormalities in either insulin secretion or action. A range of vanadium complexes have been synthesized and demonstrated to be effective in lowering hyperglycemia. Thiamine administration was also reported to prevent deterioration in fasting glucose and insulin levels, and to improve glucose tolerance in hyperglycemic patients. This study has been conducted to evaluate the ionic vanadyl(II) thiamine hydrochloride complex (VC) as a new anti-diabetic candidate. The new complex was characterized by infrared spectroscopy (FT-IR), electronic spectra, magnetic susceptibility, electron spin resonance (ESR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The anti-diabetic effect of VC was investigated in comparison to vanadium sulfate in streptozotocin (STZ)-induced diabetic rats. Treatment of diabetic rats with VC versus vanadyl sulfate showed a more potent effect on reducing serum glucose and cholesterol close to normal levels. VC suppressed the diabetes-induced upregulation of hepatic glucose transporter (GLUT)-2, Phosphoenol pyruvate carboxykinase (PEPCK), and hormone-sensitive lipase (HSL) more significantly than vanadyl sulfate. Either vanadyl sulfate or VC restored hepatic sterol regulatory element-binding protein transcription factor-1c (SREBP-1c) and muscle hexokinase (HK) mRNA expression that was downregulated in diabetic group. Pyruvate kinase (PK) mRNA expression was restored more significantly in VC-treated than vanadyl sulfate-treated diabetic rats. These results indicate that the newly synthesized VC could be an effective anti-diabetic candidate as the anti-diabetic activity of the ionic vanadium was enhanced after being modified with the organic ligand, thiamin. The results also suggest that VC achieves its effect most likely through modulating the transcription of energy metabolizing enzymes.

  13. Curcumin Inhibits Neuronal Loss in the Retina and Elevates Ca2+/Calmodulin-Dependent Protein Kinase II Activity in Diabetic Rats

    PubMed Central

    Wang, Peipei; Zhu, Yanxia; Chen, Zhen; Shi, Tianyan; Lei, Wensheng

    2015-01-01

    Abstract Purpose: To determine whether curcumin offers neuroprotection to minimize the apoptosis of neural cells in the retina of diabetic rats. Methods: Streptozotocin (STZ)-induced diabetic rats and control rats were used in this study. A subgroup of STZ-induced diabetic rats were treated with curcumin for 12 weeks. Retinal histology, apoptosis of neural cells in the retina, electroretinograms, and retinal glutamate content were evaluated after 12 weeks. Retinal levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII), phospho-CaMKII (p-CaMKII), and cleaved caspase-3 were determined by Western blot analysis. Results: The amplitudes a-wave, b-wave, and oscillatory potential were reduced by diabetes, but curcumin treatment suppressed this reduction of amplitudes. Curcumin also prevented cell loss from the outer nuclear, inner nuclear, and ganglion cell layers. Apoptosis of retinal neurons was detected in diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats, but was significantly reduced in the curcumin-treated group. Furthermore, p-CaMKII and cleaved caspase-3 expression were upregulated in the diabetic retina, but reduced in curcumin-treated rats. Conclusions: Curcumin attenuated diabetes-induced apoptosis in retinal neurons by reducing the glutamate level and downregulating CaMKII. Thus, curcumin might be used to prevent neuronal damage in the retina of patients with diabetes mellitus. PMID:26207889

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

    EPA Science Inventory

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

  15. Changes in protein and gene expression of angiotensin II receptors (AT1 and AT2) in aorta of diabetic and hypertensive rats.

    PubMed

    Romero-Nava, R; Rodriguez, J E; Reséndiz-Albor, A A; Sánchez-Muñoz, F; Ruiz-Hernandéz, A; Huang, F; Hong, E; Villafaña, S

    2016-01-01

    Diabetes and hypertension have been associated with cardiovascular diseases and stroke. Some reports have related the coexistence of hypertension and diabetes with increase in the risk of developing vascular complications. Recently some studies have shown results suggesting that in the early stages of diabetes and hypertension exist a reduced functional response to vasopressor agents like angiotensin II (Ang II), which plays an important role in blood pressure regulation mechanism through the activation of its AT1 and AT2 receptors. For that reason, the aim of this work was to study the gene and protein expression of AT1 and AT2 receptors in aorta of diabetic SHR and WKY rats. Diabetes was induced by the administration of streptozotocin (60 mg/kg i.p.). After 4 weeks of the onset of diabetes, the protein expression was obtained by western blot and the mRNA expression by RT-PCR. Our results showed that the hypertensive rats have a higher mRNA and protein expression of AT1 receptors than normotensive rats while the AT2 expression remained unchanged. On the other hand, the combination of diabetes and hypertension increased the mRNA and protein expression of AT1 and AT2 receptors significantly. In conclusion, our results suggest that diabetes with hypertension modifies the mRNA and protein expression of AT1 and AT2 receptors. However, the overexpression of AT2 could be associated with the reduction in the response to Ang II in the early stage of diabetes.

  16. Diabetes-induced alterations in tissue collagen and carboxymethyllysine in rat kidneys: Association with increased collagen-degrading proteinases and amelioration by Cu(II)-selective chelation.

    PubMed

    Brings, Sebastian; Zhang, Shaoping; Choong, Yee S; Hogl, Sebastian; Middleditch, Martin; Kamalov, Meder; Brimble, Margaret A; Gong, Deming; Cooper, Garth J S

    2015-08-01

    Advanced glycation end-products (AGEs) comprise a group of non-enzymatic post-translational modifications of proteins and are elevated in diabetic tissues. AGE-modification impairs the digestibility of collagen in vitro but little is known about its relation to collagen-degrading proteinases in vivo. N(ε)-carboxymethyllysine (CML) is a stable AGE that forms on lysyl side-chains in the presence of glucose, probably via a transition metal-catalysed mechanism. Here, rats with streptozotocin-induced diabetes and non-diabetic controls were treated for 8weeks with placebo or the Cu(II)-selective chelator, triethylenetetramine (TETA), commencing 8weeks after disease induction. Actions of diabetes and drug treatment were measured on collagen and collagen-degrading proteinases in kidney tissue. The digestibility and CML content of collagen, and corresponding levels of mRNAs and collagen, were related to changes in collagen-degrading-proteinases. Collagen-degrading proteinases, cathepsin L (CTSL) and matrix metalloproteinase-2 (MMP-2) were increased in diabetic rats. CTSL-levels correlated strongly and positively with increased collagen-CML levels and inversely with decreased collagen digestibility in diabetes. The collagen-rich mesangium displayed a strong increase of CTSL in diabetes. TETA treatment normalised kidney collagen content and partially normalised levels of CML and CTSL. These data provide evidence for an adaptive proteinase response in diabetic kidneys, affected by excessive collagen-CML formation and decreased collagen digestibility. The normalisation of collagen and partial normalisation of CML- and CTSL-levels by TETA treatment supports the involvement of Cu(II) in CML formation and altered collagen metabolism in diabetic kidneys. Cu(II)-chelation by TETA may represent a treatment option to rectify collagen metabolism in diabetes independent of alterations in blood glucose levels.

  17. The calcium channel antagonist benidipine reduces plasma and cardiac endothelin-1 levels in type II diabetic rat model.

    PubMed

    Jesmin, Subrina; Sakuma, Ichiro; Hattori, Yuichi; Kitabatake, Akira; Miyauchi, Takashi

    2004-11-01

    Cardiovascular complications are the central feature of type 2 diabetes mellitus, and insulin resistance is an early clinical manifestation of type 2 diabetes mellitus. Calcium channel blockers are widely used to treat cardiovascular diseases in diabetic patients; however, it remains unknown how endothelin-1 (ET-1) is altered and associated with cardiac lesions at the insulin-resistant early stage of type 2 diabetes mellitus, and, if so, whether calcium channel blockers can reverse such alterations. We examined plasma and cardiac expression of ET-1 in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a spontaneous model of human type 2 diabetes mellitus. At 8 weeks of age, OLETF rats were treated for 12 weeks with a long acting calcium channel blocker, benidipine (3 mg/kg per day p.o.) (BEN, n = 15), or with vehicle (OLETF, n = 15), and age-matched genetic control, male Long-Evans Tokushima Otsuka (LETO) rats were also used (n = 15). Blood pressure was significantly higher in OLETF than LETO rats, and benidipine treatment of OLETF rats for 12 weeks did not reduce their blood pressure significantly. Plasma and cardiac levels of ET-1 were significantly higher in OLETF compared with LETO rats (both P < 0.01), and were reversed after benidipine treatment. Our results suggest that ET-1 plays a pivotal role in the pathogenesis of cardiac complications at the insulin-resistant stage of diabetes mellitus, and that benidipine treatment may have a beneficial effect on these complications.

  18. Effect of des-aspartate-angiotensin I on the actions of angiotensin II in the isolated renal and mesenteric vasculature of hypertensive and STZ-induced diabetic rats.

    PubMed

    Dharmani, M; Mustafa, M R; Achike, F I; Sim, M K

    2005-07-15

    The present study investigated the action of des-aspartate-angiotensin I (DAA-I) on the pressor action of angiotensin II in the renal and mesenteric vasculature of WKY, SHR and streptozotocin (STZ)-induced diabetic rats. Angiotensin II-induced a dose-dependent pressor response in the renal vasculature. Compared to the WKY, the pressor response was enhanced in the SHR and reduced in the STZ-induced diabetic rat. DAA-I attenuated the angiotensin II pressor action in renal vasculature of WKY and SHR. The attenuation was observed for DAA-I concentration as low as 10(-18) M and was more prominent in SHR. However, the ability of DAA-I to reduce angiotensin II response was lost in the STZ-induced diabetic kidney. Instead, enhancement of angiotensin II pressor response was seen at the lower doses of the octapeptide. The effect of DAA-I was not inhibited by PD123319, an AT2 receptor antagonist, and indomethacin, a cyclo-oxygenase inhibitor in both WKY and SHR, indicating that its action was not mediated by angiotensin AT2 receptor and prostaglandins. The pressor responses to angiotensin II in mesenteric vascular bed were also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses were significantly smaller in SHR but no significant difference was observed between STZ-induced diabetic and WKY rat. Similarly, PD123319 and indomethacin had no effect on the action of DAA-I. The findings reiterate a regulatory role for DAA-I in vascular bed of the kidney and mesentery. By being active at circulating level, DAA-I subserves a physiological role. This function appears to be present in animals with diseased state of hypertension and diabetes. It is likely that DAA-I functions are modified to accommodate the ongoing vascular remodeling.

  19. Identification of T cell subsets and class I and class II antigen expression in islet grafts and pancreatic islets of diabetic BioBreeding/Worcester rats.

    PubMed Central

    Weringer, E. J.; Like, A. A.

    1988-01-01

    The BioBreeding/Worcester (BB/Wor) rat develops a spontaneous disorder that closely resembles human insulin-dependent (Type I) diabetes mellitus. The syndrome is preceded by lymphocytic insulitis that destroys pancreatic beta cells. The morphologic features of the spontaneous insulitis lesions are also observed within islets transplanted beneath the renal capsule of diabetes-prone and diabetic animals. This study reports the results of experiments in which immunohistochemical techniques were used to characterize the phenotype of the infiltrating mononuclear cells and detect the expression of class I and class II MHC antigens in native islets and islet transplants in diabetic and diabetes-prone BB/Wor rats. The infiltrates within native pancreatic islets and islet grafts were comprised predominantly of Ia+ cells (dendritic cells and macrophages) CD4+ cells (helper/inducer lymphocytes and macrophages), CD5+ (pan-T) cells and smaller numbers of CD8+ (cytotoxic/suppressor and NK) cells. Pancreatic and graft insulitis were accompanied by markedly enhanced class I antigen expression on islet and exocrine cells. Class II (Ia) antigens were not detected on normal islet cells, islets undergoing insulitis or on islet transplants subjected to immune attack. In islet grafts stained with polymorphic MAbs that distinguish Ia antigens of donor and host origin, Ia antigen expression was limited to infiltrating dendritic cells and macrophages of host origin. It is concluded that the phenotypes of infiltrating mononuclear cells that comprise the insulitis lesion in spontaneous BB/Wor diabetes, and the inflammatory attack on islets transplanted into diabetic BB/Wor rats are the same, that pancreatic islet and graft insulitis occur in the presence of enhanced class I antigen expression but in the absence of class II antigen expression, and that infiltrating Ia+ cells within islet grafts are exclusively of recipient (BB/Wor) origin and may explain the initiation of immune insulitis

  20. Quantitative proteomic profiling identifies new renal targets of copper(II)-selective chelation in the reversal of diabetic nephropathy in rats.

    PubMed

    Gong, Deming; Chen, Xiuyin; Middleditch, Martin; Huang, Liangdong; Vazhoor Amarsingh, Greeshma; Reddy, Shiva; Lu, Jun; Zhang, Shaoping; Ruggiero, Katya; Phillips, Anthony R J; Cooper, Garth J S

    2009-09-01

    This study aimed to identify new diabetic nephropathy (DN)-related proteins and renal targets of the copper(II)-selective chelator, triethylenetetramine (TETA) in streptozotocin-diabetic rats. We used the recently developed iTRAQ technology to compare renal protein profiles among non-diabetic, diabetic, and TETA-treated diabetic rats. In diabetic kidneys, tubulointerstitial nephritis antigen (TINag), voltage-dependent anion-selective channel (VDAC) 1, and VDAC2 were up-regulated in parallel with alterations in expression of proteins with functions in oxidative stress and oxidative phosphorylation (OxPhos) pathways. By contrast, mitochondrial HSP 60, Cu/Zn-superoxide dismutase, glutathione S-transferase alpha3 and aquaporin-1 were down-regulated in diabetic kidneys. Following TETA treatment, levels of D-amino acid oxidase-1, epoxide hydrolase-1, aquaporin-1, and a number of mitochondrial proteins were normalized, with concomitant amelioration of albuminuria. Changes in levels of TINag, collagen VIalpha1, actinin 4alpha, apoptosis-inducing factor 1, cytochrome C, histone H3, VDAC1, and aquaporin-1 were confirmed by Western blotting or immunohistochemistry. Changes in expression of proteins related to tubulointerstitial function, podocyte structure, and mitochondrial apoptosis are implicated in the mechanism of DN and their reversal by TETA. These findings are consistent with the hypothesis that this new experimental therapy may be useful for treatment of DN.

  1. Heart failure progression is accelerated following myocardial infarction in type II diabetic rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients and following an infarction, diabetes is associated with an increased risk for the development of left ventricular dysfunction and heart failure. The goal of this study was to determine if the progression o...

  2. Garlic Attenuates Plasma and Kidney ACE-1 and AngII Modulations in Early Streptozotocin-Induced Diabetic Rats: Renal Clearance and Blood Pressure Implications

    PubMed Central

    Al-Qattan, Khaled K.; Jayasree, Divya; Ali, Muslim

    2016-01-01

    Raw garlic aqueous extract (GE) has ameliorative actions on the renin-angiotensin system in type-1 diabetes mellitus (DM); however its effects on plasma and kidney angiotensin I converting enzyme type-1 (ACE-1) and angiotensin II (AngII) require further elucidation. This study investigated the effect of GE on plasma and kidney ACE-1 and AngII concentrations and in relation to systemic and renal clearance indicators significant to blood pressure (BP) homeostasis in early streptozotocin- (STZ-) induced type-1 DM. Normal rats (n = 10) received 0.5 mL normal saline (NR/NS), diabetic rats (n = 10) received 0.5 mL NS (DR/NS), and treated diabetic rats (n = 10) received 50 mg/0.1 mL/100 g body weight GE (DR/GE) as daily intraperitoneal injections for 8 weeks. Compared to NR/NS, DR/NS showed a significant increase in plasma ACE-1 and AngII and conversely a decrease in kidney ACE-1 and AngII. These changes were associated with an increase in BP and clearance functions. Alternatively and compared to DR/NS, DR/GE showed normalization or attenuation in plasma and kidney ACE-1 and AngII. These GE induced rectifications were associated with moderation in BP elevation and renal clearance functions. Garlic attenuates modulations in plasma and kidney ACE-1 and AngII, in addition to BP and renal clearance function in type-1 DM. PMID:27293465

  3. Pancreas transplantation using type I and type II spontaneously diabetic rats--our experimental experience.

    PubMed

    Ito, Toshinori; Shimada, Kazunori; Gang, Miao; Uchikoshi, Fumihiro; Tori, Masayuki; Komoda, Hiroshi; Fumimoto, Yuichi; Ohmori, Ken; Kawamoto, Koichi; Tanemura, Masahiro; Nozawa, Masumi

    2007-01-01

    Pancreas transplantation (PTx) is the only therapy that can cure type 1 diabetes mellitus. With the recent advance of surgical procedures and immunosuppression, the outcome of PTx has become better than it used to be before, but some problems still remain. It is rather difficult to induce tolerance and to reverse rejection once it occurred because pancreas graft itself has a strong immunogenicity. Another important issue is regarding the recurrence of autoimmune disease in the pancreatic graft, therefore, some animal models are necessary to delineate and regulate those immune responses specific for PTx. Recently, PTx is also clinically applicable for type 2 diabetic patients with end-stage renal disease. It has been shown that insulin resistance was improved by PTx in type 2 diabetic recipients. In the current study, we have introduced some useful type 1 and type 2 diabetic models mainly based on our experimental experiences.

  4. Untargeted serum metabolomics reveals Fu-Zhu-Jiang-Tang tablet and its optimal combination improve an impaired glucose and lipid metabolism in type II diabetic rats.

    PubMed

    Tao, Yi; Chen, Xi; Cai, Hao; Li, Weidong; Cai, Baochang; Chai, Chuan; Di, Liuqing; Shi, Liyun; Hu, Lihong

    2017-01-01

    Fu-Zhu-Jiang-Tang tablet, a six-herb preparation, was proved to show beneficial effects on type II diabetes patients in clinical. This study aims to optimize the component proportion of the six-herb preparation and explore the serum metabolic signatures of type II diabetes rats after treatment with Fu-Zhu-Jiang-Tang tablet and its optimal combination. The component proportion of the preparation was optimized using uniform experimental design and machine learning techniques. Untargeted GC-MS metabolomic experiments were carried out with serum samples from model group and treatment groups. Data were normalized, multivariate and univariate statistical analysis performed and metabolites of interest putatively identified. 23 metabolites were significantly changed by Fu-Zhu-Jiang-Tang tablet treatment and the majority of these were decreased, including various carbohydrates (glucose, mannose, fructose, allose and gluconic acid), unsaturated fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid, arachidonic acid), alanine, valine, propanoic acid, 3-hydroxybutyrate, along with pyrimidine and cholesterol. Increased concentrations of oxalic acid, leucine, glycine, serine, threonine, proline, lysine and citrate were observed. In the optimal combination-fed group, 21 metabolites were significantly affected and strikingly, the magnitudes of changes here were generally much greater than that of Fu-Zhu-Jiang-Tang tablet treated rats. 18 metabolites affected in both groups included various carbohydrates (mannose, glucose, allose, fructose and gluconic acid), unsaturated fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid and arachidonic acid), short-chain fatty acids (oxalic acid, 3-hydroxybutyrate), and amino acids (alanine, valine, leucine, glycine, proline and lysine), as well as pyrimidine. Metabolites exclusively affected in optimal combination treated rat included succinic acid, cysteine and phenylalanine, whilst four metabolites (propanoic acid, citrate

  5. The bioflavonoid quercetin synergises with PPAR-γ agonist pioglitazone in reducing angiotensin-II contractile effect in fructose-streptozotocin induced diabetic rats.

    PubMed

    Kunasegaran, Thubasni; Mustafa, Mohd Rais; Murugan, Dharmani Devi; Achike, Francis I

    2016-06-01

    This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 μM), pioglitazone (P, 0.1 μM) or their combination (P + Q; 0.1 μM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects.

  6. Leptin and Its Relation to Obesity and Insulin in the SHR/N-corpulent Rat, A Model of Type II Diabetes Mellitus

    PubMed Central

    Bhathena, Sam J.; Hansen, Carl T.

    2001-01-01

    The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic animal model that exhibits obesity, metabolic features of hyperinsulinemia, hyperglycemia, and hyperlipidemia, which are characteristic of type II diabetes and mild hypertension. To determine the role of leptin, the protein product of the ob gene, in the development of obesity and diabetes in this model, we measured steady-state circulating levels of leptin in obese and lean SHR/N-cp rats and examined the relation between plasma leptin levels and metabolic variables at the stage of established obesity in these animals. Mean fasting plasma leptin concentration was 8-fold higher in obese than in lean rats (p<0.01). This was associated with a 6-fold elevation in plasma insulin in the obese group. Fasting levels of plasma glucose, cholesterol, and triglyceride were all significantly higher in obese rats than in lean controls. Spearman correlation analysis showed a significant positive correlation between plasma leptin concentration and body weight among the animals (r=0.73, p<0.01). Similarly, plasma insulin concentration was significantly correlated with BW in all animals (r=0.54, p<0.05). There was also a significant positive.correlation between plasma leptin and plasma insulin in the entire group (r=0.70, p<0.01). However, this relationship was significant only for lean rats but not for obese rats (r=0.59, p<0.05 for lean rats, and r=0.23, p=NS, for obese rats). Plasma leptin also correlated positively with fasting plasma glucose (r=0.75, p<0.05), total cholesterol (r=0.63, p<0.05), and triglyceride (r=0.67, p <0.05). The marked elevation of plasma leptin in obese SHR/N-cp rats suggests that obesity in this animal model is related to up-regulation of the ob gene. Circulating leptin appears to be one of the best biological markers of obesity and that hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in the diabesity syndrome. PMID:12369710

  7. Metallothionein metabolism in the streptozotocin-diabetic rat

    SciTech Connect

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

    1986-03-05

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

  8. An Extended Minimal Physiologically Based Pharmacokinetic Model: Evaluation of Type II Diabetes Mellitus and Diabetic Nephropathy on Human IgG Pharmacokinetics in Rats.

    PubMed

    Chadha, Gurkishan S; Morris, Marilyn E

    2015-11-01

    Although many studies have evaluated the effects of type 2 diabetes mellitus (T2DM) on the pharmacokinetics (PK) of low molecular weight molecules, there is limited information regarding effects on monoclonal antibodies. Our previous studies have reported significant increases in total (2-4 fold) and renal (100-300 fold) clearance of human IgG, an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Pioglitazone treatment incompletely reversed the disease-related PK changes. The objective of this study was to construct a mechanistic model for simultaneous fitting plasma and urine data, to yield physiologically relevant PK parameters. We propose an extended minimal physiologically based PK (mPBPK) model specifically for IgG by classifying organs as either leaky or tight vascular tissues, and adding a kidney compartment. The model incorporates convection as the primary mechanism of IgG movement from plasma into tissues, interstitial fluid (ISF) in extravascular distribution space, and glomerular filtration rate (GFR), sieving coefficient and fraction reabsorbed in the kidney. The model captured the plasma and urine PK profiles well, and simulated concentrations in ISF. The model estimated a 2-4 fold increase in nonrenal clearance from plasma and 30-120 fold increase in renal clearance with T2DM, consistent with the experimental findings, and these differences in renal clearance were related to changes in GFR, sieving coefficient, and proximal tubular reabsorption. In conclusion, the mPBPK model offers a more relevant approach for analyzing plasma and urine IgG concentration-time data than conventional models and provides insight regarding alterations in distributional and elimination parameters occurring with T2DM.

  9. Quercetin-Rich Guava (Psidium guajava) Juice in Combination with Trehalose Reduces Autophagy, Apoptosis and Pyroptosis Formation in the Kidney and Pancreas of Type II Diabetic Rats.

    PubMed

    Lin, Chia-Fa; Kuo, Yen-Ting; Chen, Tsung-Ying; Chien, Chiang-Ting

    2016-03-10

    We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was induced in Wistar rats by intraperitoneal administration of nicotinamide and streptozotocin and combination with high fructose diets for 8 weeks. The rats fed with different dosages of guava juice in combination with or without trehalose for 4 weeks were evaluated the parameters including OGTT, plasma insulin, HbA1c, HOMA-IR (insulin resistance) and HOMA-β (β cell function and insulin secretion). We measured oxidative and inflammatory degrees by immunohistochemistry stain, fluorescent stain, and western blot and serum and kidney reactive oxygen species (ROS) by a chemiluminescence analyzer. High content of quercetin in the guava juice scavenged H2O2 and HOCl, whereas trehalose selectively reduced H2O2, not HOCl. T2DM affected the levels in OGTT, plasma insulin, HbA1c, HOMA-IR and HOMA-β, whereas these T2DM-altered parameters, except HbA1c, were significantly improved by guava and trehalose treatment. The levels of T2DM-enhanced renal ROS, 4-hydroxynonenal, caspase-3/apoptosis, LC3-B/autophagy and IL-1β/pyroptosis were significantly decreased by guava juice and trehalose. The combination with trehalose and guava juice protects the pancreas and kidney against T2DM-induced injury.

  10. Expression and localization of the AT1 and AT2 angiotensin II receptors and α1A and α1D adrenergic receptors in aorta of hypertensive and diabetic rats.

    PubMed

    Rodríguez, Jessica Edith; Romero-Nava, Rodrigo; Reséndiz-Albor, Aldo Arturo; Rosales-Cruz, Erika; Hong, Enrique; Huang, Fengyang; Villafaña, Santiago

    2017-01-01

    Hypertension and diabetes are multifactorial diseases that frequently coexist and exacerbate each another. During the development of diabetes, the impairment of noradrenergic and renin-angiotensin systems has been reported in the response mediated by α1-AR and AT1 receptors. Although their participation in the development of cardiovascular complications is still controversial, some studies have found increased or diminished response to the vasoconstrictive effect of noradrenaline or angiotensin II in a time-dependent manner of diabetes. Thus, the aim of this work was to investigate the possible changes in the expression or localization of α1-AR (α1A and α1D) and angiotensin II receptors (AT1 and AT2) in aorta of rats after 4 weeks of the onset of diabetes. In order to be able to examine the expression of these receptors, immunofluorescence procedure was performed in tunica intima and tunica media of histological sections of aorta. Fluorescence was detected by a confocal microscopy. Our results showed that the receptors are expressed in both tunics, where adrenergic receptors have a higher density in tunica intima and tunica media of SHR compared with WKY; meanwhile, the expression of angiotensin II receptors is not modified in both groups of rats. On the other hand, the results showed that diabetes produced an increase or a decrease in the expression of receptors that is not associated to a specific type of receptor, vascular region, or strain of rat. In conclusion, diabetes and hypertension modify the expression of the receptors in tunica intima and tunica media of aorta in a different way.

  11. 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-α 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-α, 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-α, 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

  12. Renal Ischemia/Reperfusion Injury in Diabetic Rats: The Role of Local Ischemic Preconditioning

    PubMed Central

    Ozbilgin, Sule; Ozkardesler, Sevda; Akan, Mert; Boztas, Nilay; Ozbilgin, Mucahit; Ergur, Bekir Ugur; Derici, Serhan; Guneli, Mehmet Ensari; Meseri, Reci

    2016-01-01

    Background. The aim of this study was to evaluate the effects of local ischemic preconditioning using biochemical markers and histopathologically in the diabetic rat renal IR injury model. Methods. DM was induced using streptozotocin. Rats were divided into four groups: Group I, nondiabetic sham group (n = 7), Group II, diabetic sham group (n = 6), Group III, diabetic IR group (diabetic IR group, n = 6), and Group IV, diabetic IR + local ischemic preconditioning group (diabetic IR + LIPC group, n = 6). Ischemic renal injury was induced by clamping the bilateral renal artery for 45 min. 4 h following ischemia, clearance protocols were applied to assess biochemical markers and histopathologically in rat kidneys. Results. The histomorphologic total cell injury scores of the nondiabetic sham group were significantly lower than diabetic sham, diabetic IR, and diabetic IR + LIPC groups. Diabetic IR group scores were not significantly different than the diabetic sham group. But diabetic IR + LIPC group scores were significantly higher than the diabetic sham and diabetic IR groups. Conclusion. Local ischemic preconditioning does not reduce the risk of renal injury induced by ischemia/reperfusion in diabetic rat model. PMID:26925416

  13. Diabetic rat testes: morphological and functional alterations.

    PubMed

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

    2009-12-01

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

  14. Antidepressant effect of taurine in diabetic rats.

    PubMed

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

    2012-10-01

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

  15. 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.

  16. 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

  17. Anti diabetic effect of cherries in alloxan induced diabetic rats.

    PubMed

    Lachin, Tahsini; Reza, Heydari

    2012-01-01

    Diabetes mellitus (DM) is a metabolic disorder in the endocrine system resulting from a defect in insulin secretion, insulin action or both of them. Adverse side effects of chemical drugs for treatment of diabetes persuaded the using of medical plants. Cherry as a traditionally used plant for treatment of diabetes, is packed with powerful plant pigments called anthocyanins. They give cherries their dark red color and are one of the richest antioxidant sources which lower the blood sugar and bear other beneficial health effects. The purpose of this study is to evaluate the effect of ethanolic extract of cherry fruit on alloxan induced diabetic rats. In this study 36 Male Wistar rats, body weight of 150-200gr were divided into 6 groups. Diabetes was induced by intra peritoneal injection of 120 mg/kg Alloxan. The duration of the cherries treatment was 30 days in which single dose of extracts (200mg/kg) were oral administered to diabetic rats. Blood glucose levels were estimated with glucometer before treatment, 2h and 1- 4 weeks after administration of extracts. Treatment with extracts of the cherries resulted in a significant reduction in blood glucose and urinary microalbumin and an increase in the creatinine secretion level in urea. Extract of this plant is useful in controlling the blood glucose level. Cherries appear to aid in diabetes control and diminution of the complications of the disease. Some relevant patents are also outlined in this article.

  18. Testicular lesions of streptozotocin diabetic rats.

    PubMed

    Oksanen, A

    1975-01-01

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

  19. 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

  20. Comparison of the effects of levocetirizine and losartan on diabetic nephropathy and vascular dysfunction in streptozotocin-induced diabetic rats.

    PubMed

    Anbar, Hanan S; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M

    2016-06-05

    This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress, nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated. Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to body weight ratio, serum albumin, urinary proteins and creatinine clearance). Moreover, levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by losartan. Moreover, levocetirizine, similar to losartan, reduced the enhanced responsiveness of diabetic aorta to phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of levocetirizine on diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular hypertrophy by levocetirizine than by losartan. In conclusion, levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than, losartan in streptozotocin-diabetic rats.

  1. Hypoglycemic Activity of Fumaria parviflora in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Fathiazad, Fatemeh; Hamedeyazdan, Sanaz; Khosropanah, Mohamad Karim; Khaki, Arash

    2013-01-01

    Purpose: Fumaria parviflora Lam (Fumariaceae) has been used in traditional medicine in the treatment of several diseases such as diabetes. The present work was designed to evaluate the hypoglycaemic effects of methanolic extract (ME) of F. parviflora in normal and streptozotocin-induced diabetic rats. Methods: The rats used were allocated in six (I, II, III, IV, V and VI) experimental groups (n=5). Group I rats served as ‘normal control’ animals received distilled water and group II rats served as ‘diabetic control’ animals. Diabetes mellitus was induced in groups II, V and VI rats by intraperitoneal single injection of streptozotocin (STZ, 55 mg kg-1). Group V and VI rats were addi-tionally treated with ME (150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively) 24 hour post STZ injection, for seven consecutive days. Groups III and IV rats received only ME 150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively for seven days. The levels of blood glucose were determined using a Glucometer. Results: Administra-tion of F. parviflora extract showed a potent glucose lowering effect only on streptozo-tocin (STZ) induced diabetic rats below 100 mg/dl (P<0.001). However, no significant differences in the blood glucose levels were recorded between diabetic rats received 125 or 250 mg/kg of plant extracts. Conclusion: The findings of the study indicated that F. parviflora has significant hypoglycemic effect on STZ-induced diabetic rats with no effects on blood glucose levels of normal rats. PMID:24312837

  2. Expression of oxytocin receptor in diabetic rat penis.

    PubMed

    Li, M; Wang, T; Guo, S; Rao, K; Liu, J; Ye, Z

    2012-05-01

    Oxytocin receptor (OTR) expressed in the rat penis and mediated the contractility of the corpus cavernosum smooth muscle both in vitro and in vivo, and OTR could maintain penile detumescence; however, the expression of OTR in diabetic rat penis remains unknown. In the present study, we investigated the expression of OTR in diabetic rat penis. The experimental rats were randomly divided into control group and STZ-diabetic rats group. The expressions of mRNA and protein were examined by real-time quantitative PCR, Western blotting and immunohistochemistry respectively. Erectile function was evaluated by measuring intracavernous pressure following electrostimulation of the cavernous nerves. mRNA and protein expression of OTR significantly increased in diabetic rats group compared with the control group. Erectile function of diabetic rats group significantly decreased compared with the control group. Our data showed that the expression of OTR significantly increased in diabetic rats group and OTR may involve in the development of diabetic erectile dysfunction.

  3. Ozone partially prevents diabetic neuropathy in rats.

    PubMed

    Erken, H A; Genç, O; Erken, G; Ayada, C; Gündoğdu, G; Doğan, H

    2015-02-01

    Neuropathy is one of the most common complications of diabetes mellitus. Although the beneficial effects of good blood glucose control on diabetic neuropathy are known, this control cannot completely prevent the occurrence and progression of diabetic neuropathy. The aim of this study was to investigate whether ozone prevents diabetic neuropathy. 36 adult female Sprague-Dawley rats were randomly divided into 6 groups (n=6): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). Diabetes was induced by a single injection of streptozotocin (60 mg/kg, intraperitoneal [i.p.]), after which insulin was administered (3 IU, i.p.) to the DI and DOI groups for 28 days, and 1.1 mg/kg (50 µg/ml) ozone was given to the O, DO, and DOI groups for 15 days. 4 weeks after the induction of diabetes, the nerve conduction velocity (NCV), amplitude of the compound action potential (CAP), total oxidant status (TOS), and total antioxidant status (TAS) were measured, and the oxidative stress index (OSI) was calculated. The NCV, amplitude of CAP, and TAS of the DI and DOI groups were higher than those of the D group; the amplitudes of CAP and TAS of the DO group were higher than those of the D group; and the TOS and OSI of the DO, DI, and DOI groups were lower than those of the D group. These findings indicate that ozone partially prevents diabetic neuropathy in rats. It appears that the preventive effects of ozone are mediated through oxidant/antioxidant mechanisms.

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

    PubMed

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

    2016-10-01

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

  5. Wound healing activity of Malva sylvestris and Punica granatum in alloxan-induced diabetic rats.

    PubMed

    Pirbalouti, Abdollah Ghasemi; Azizi, Shahrzad; Koohpayeh, Abed; Hamedi, Behzad

    2010-01-01

    The flowers of Malva sylvestris Linn. (Malvaceae) and Punica granatum Linn. (Punicaceae) are important medicinal plants in Iranian traditional medicine (Unani) whose have been used as remedy against edema, bum, wound and for their carminative, antimicrobial and anti-inflammatory activities. The diethyl ether extract of M. sylvestris and P. granatum flowers were used to evaluate the wound healing activity at 200 mg/kg/day dose in alloxan-induced diabetic rats. Wounds were induced in Wister rats divided into six groups as following; Group I, normal rats were treated with simple ointment base. Group II, diabetic rats were treated with simple ointment base (control). Groups III and IV, diabetic rats were treated with simple ointment base containing of extracts (diabetic animals), Groups V, diabetic rats were treated with simple ointment base containing of mixed extracts (1:1), Group VI, diabetic rats received the standard drug (nitrofurazone). The efficacy of treatment was evaluated based on wound area relative and histopathological characteristics. The extract-treated diabetic animals showed significant reduction in the wound area when compared with control. Also, histological studies of the tissue obtained on days 9th and 18th from the extract-treated by extract of M. sylvestris showed increased well organized bands of collagen, more fibroblasts and few inflammatory cells. These findings demonstrate that extract of M. sylvestis effectively stimulates wound contraction as compared to control group and other groups. M. sylvestris accelerated wound healing in rats and thus supports its traditional use.

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

    PubMed

    Takeda, Yuji; Shimomura, Tomoko; Asao, Hironobu; Wakabayashi, Ichiro

    2017-01-01

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

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

    PubMed Central

    Shimomura, Tomoko; Asao, Hironobu; Wakabayashi, Ichiro

    2017-01-01

    A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models. In this review, we introduce rat models of diabetes and summarize the immune reactions in diabetic rat models. Finally, we speculate on the relationship between immune reactions and diabetic episodes. For example, diabetes-prone Biobreeding rats, type 1 diabetes model rats, exhibit increased autoreactive cellular and inflammatory immune reactions, while Goto-Kakizaki rats, type 2 diabetes model rats, exhibit increased Th2 reactions and attenuation of phagocytic activity. Investigation of immunological abnormalities in various diabetic rat models is useful for elucidating complicated mechanisms in the pathophysiology of diabetes. Studying immunological alterations, such as predominance of Th1/17 or Th2 cells, humoral immunity, and innate immune reactions, may improve understanding the structure of amplification circuits for diabetes in future studies. PMID:28299342

  8. Obestatin and insulin in pancreas of newborn diabetic rats treated with exogenous ghrelin.

    PubMed

    Turk, Neslihan; Dağistanli, Fatma Kaya; Sacan, Ozlem; Yanardag, Refiye; Bolkent, Sema

    2012-07-01

    The aim of the study was to evaluate the effect of ghrelin treatment on obestatin, insulin gene expression and biochemical parameters in the pancreas of newborn-streptozocin (STZ) diabetic rats. Rats were divided into 4 groups. Group I: control rats treated with physiological saline; group II: control rats treated with 100 μg/kg/day ghrelin; group III: two days after birth rats that received 100mg/kg STZ injected as a single dose to induce neonatal diabetes; group IV: neonatal-STZ-diabetic rats treated with ghrelin for four weeks. Sections of the pancreas were examined with immunohistochemistry for the expression of obestatin and insulin and in situ hybridization for the expression of insulin mRNA. The blood glucose levels were measured. Tissue homogenates were used for protein, glutathione, lipid peroxidation and non-enzymatic glycosylation levels and antioxidant enzyme analysis. There was a significant difference in blood glucose levels in newborn-STZ-diabetic rats compared to ghrelin treated diabetic rats at weeks 1, 2 and 4. In group IV, pancreatic non-enzymatic glycosylation and lipid peroxidation levels were decreased, however, glutathione levels and enzymatic activities were increased. Insulin peptide and mRNA (+) signals in islets of Langerhans and obestatin immunopositive cell numbers showed an increase in group IV compared to group III. These results suggest that administration of ghrelin to newborn rats may prevent effects of diabetes.

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

    PubMed Central

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

    2016-01-01

    Diabetic ulcers are one of the most serious and costly chronic complications for diabetic patients. Hyperglycemia-induced oxidative stress may play an important role in diabetes and its complications. The aim of the study was to explore the effect of heme oxygenase-1 on wound closure in diabetic rats. Diabetic wound model was prepared by making an incision with full thickness in STZ-induced diabetic rats. Wounds from diabetic rats were treated with 10% hemin ointment for 21 days. Increase of HO-1 protein expression enhanced anti-inflammation and antioxidant in diabetic rats. Furthermore, HO-1 increased the levels of VEGF and ICAM-1 and expressions of CBS and CSE protein. In summary, HO-1 promoted the wound closure by augmenting anti-inflammation, antioxidant, and angiogenesis in diabetic rats. PMID:26798657

  10. Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats

    PubMed Central

    Bujak-Giżycka, B.; Jawień, J.; Olszanecki, R.; Madej, J.; Rutowski, J.; Korbut, R.

    2016-01-01

    Purpose. Products of angiotensin (ANG) I metabolism may predispose to vascular complications of diabetes mellitus. Methods. Diabetes was induced with streptozotocin (75 mg/kg i.p.). Rat aorta fragments, isolated 4 weeks later, were pretreated with perindoprilat (3 μM), thiorphan (3 μM), or vehicle and incubated for 15 minutes with ANG I (1 μM). Products of ANG I metabolism through classical (ANG II, ANG III, and ANG IV) and alternative (ANG (1–9), ANG (1–7), and ANG (1–5)) pathways were measured in the buffer, using liquid chromatography-mass spectrometry. Results. Incubation with ANG I resulted in higher concentration of ANG II (P = 0.02, vehicle pretreatment) and lower of ANG (1–9) (P = 0.048, perindoprilat pretreatment) in diabetes. Preference for the classical pathway is suggested by higher ANG III/ANG (1–7) ratios in vehicle (P = 0.03), perindoprilat (P = 0.02), and thiorphan pretreated (P = 0.02) diabetic rat. Within the classical pathway, ratios of ANG IV/ANG II (P = 0.01) and of ANG IV/ANG III (P = 0.049), but not of ANG III/ANG II are lower in diabetes. Conclusions. Diabetes in rats led to preference toward deleterious (ANG II, ANG III) over protective (ANG IV, ANG (1–9), and ANG (1–7)) ANG I metabolites. PMID:27803936

  11. Carvedilol protected diabetic rat hearts via reducing oxidative stress

    PubMed Central

    Huang, He; Shan, Jiang; Pan, Xiao-hong; Wang, Hui-ping; Qian, Ling-bo

    2006-01-01

    Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant properties. To study the effect of carvedilol on the antioxidant status in diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage carvedilol-administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde, activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac tissues were measured. The diabetic rats not only had cardiac disfunction, weaker activities of antioxidant enzymes, but also showed lower expression of Bcl-2. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that carvedilol partly improves cardiac function via its antioxidant properties in diabetic rats. PMID:16909474

  12. Major histocompatibility complex gene product expression on pancreatic beta cells in acutely diabetic BB rats.

    PubMed Central

    Issa-Chergui, B.; Yale, J. F.; Vigeant, C.; Seemayer, T. A.

    1988-01-01

    Type I diabetes mellitus was induced in young, diabetes-prone BB rats by the passive transfer of concanavalin A-activated T lymphocytes from the spleens of acutely diabetic BB rats. The pancreas of the recipients was examined 1-2 days after the onset of glycosuria by immunocytochemistry by means of monoclonal antibodies for determining whether 1) Class I and/or II major histocompatibility gene complex (MHC) products were expressed on beta cells and 2) the mononuclear cell infiltrates were represented by T cells. Marked expression of Class I MHC gene products was evident on beta cells. In contrast, Class II MHC gene products were not identified on normal-appearing beta cells. Dendritic cells dispersed throughout the acinar and interstitial pancreas were markedly increased in number. The mononuclear cell infiltrate contained few cells (1-15%) recognized by a pan-T cell marker. Although it is possible that this passive transfer model might differ considerably from the spontaneously occurring diabetic state in the rat, this study suggests that 1) Class I, rather than Class II, MHC gene expression may be pivotal to beta-cell injury in diabetic rats, and 2) non-T cells may constitute an effector cell population central to beta-cell necrosis in Type I diabetes mellitus. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3276208

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

    PubMed Central

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

    2016-01-01

    Introduction Diabetic neuropathy is one of the most common complications affecting 50% of diabetic patients. Neuropathic pain is the most difficult types of pain to treat. There is no specific treatment for neuropathy. Nishamalaki (NA), combination of Curcuma longa and Emblica officinalis used to treat Diabetes Mellitus (DM). So, efforts were made to test whether NA is useful in prevention of diabetic neuropathy. Aim To evaluate the effect of NA on diabetic neuropathy in type 2 diabetic wistar rats. Materials and Methods Group I (Control) vehicle treated consists of 6 rats. Diabetes induced in 36 wistar rats with Streptozotocin (STZ) (35mg/kg) intra-peritoneally followed by High Fat High Fructose diet. After confirmation of development of diabetes; rats divided into six groups (n=6). Group II – VII Diabetic Control, NA low dose, NA High dose, Glibenclamide, Pioglitazone and Epalrestat. Animals received drug treatment for next 12 weeks. Monitoring of Blood Sugar Level (BSL) done every 15 days and lipid profile at the end. Eddy’s hot plate and tail immersion test performed to assess thermal hyperalgesia and cold allodynia. Walking function test performed to assess motor function. Results Diabetic rats exhibited significant (p<0.001) hyperalgesia and increased BSL compared to control rats. Dose-dependent improvement was observed in thermal hyperalgesia & cold allodynia in NA groups. Activity of NA was more than Glibenclamide, Epalrestat and Pioglitazone in high dose and comparable in low dose. Nishamalaki improved lipid profile. Conclusion Apart from controlling hyperglycaemia and reducing lipid levels, NA effectively prevented the development of diabetic neuropathy. PMID:27891351

  14. Effect of hydroalcoholic Allium ampeloprasum extract on oxidative stress, diabetes mellitus and dyslipidemia in alloxan-induced diabetic rats.

    PubMed

    Rahimi-Madiseh, Mohammad; Heidarian, Esfandiar; Kheiri, Soleiman; Rafieian-Kopaei, Mahmoud

    2017-02-01

    Allium ampeloprasum (AA) is a medicinal plant which is used in Iranian traditional medicine to treat or prevent different diseases. The aim of this study is to investigate the effect of AA extract on oxidative stress and dyslipidemia in diabetic rats induced by alloxan. In this experimental study, 60 male Wistar rats weighing 200-250gr were randomly divided to five groups of 12 each including healthy control (group I), diabetic control (group II), metformin-treated diabetic positive control (group III) and two groups treated with doses 400 (group IV) and 800 (groupV) mg/kg/BW of AA extracts. Diabetes mellitus was experimentally induced by injection of two doses of alloxan-120 and 65mg/kg-within two consecutive days. Alloxan-induced diabetes caused significant increase in serum glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and high density lipoprotein (HDL) levels in group II (p<0.05). Furthermore, serum malondialdehyde (MDA) levels increased significantly and liver catalase activity decreased significantly in the 2nd group compared to 1st control; respectively p=0.0001 and p=0.009. In the group IV has seen a significant decrease in serum TG (p=0.01), TC (p=0.0001), VLDL (p=0.01), and MDA (p=0.0001) levels and significant increase in the liver and kidney catalase activities of the rats compared to the group II; respectively p=0.0001 and p=0.0001. In Conclusion our results highlight potentially relevant health beneficial effects of AA extract which exerts hypoglycemic, hypolipidemic, and anti-oxidative stress effects in rats with alloxan-induced diabetes. Therefore, it may be considered as useful dietary supplements in diabetic patients.

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

    PubMed

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

    2015-03-01

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

  16. 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

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

    SciTech Connect

    Lohr, J.; Mazurchuk, R.J.; Acara, M.A.; Nickerson, P.A.; Fiel, R.J. )

    1991-01-01

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

  18. 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

  19. [Effect of sulodexide on aortic vasodilation capacity and associated morphological changes in rats with streptozotocin-induced diabetes].

    PubMed

    Vásquez, José; Mathison, Yaira; Romero-Vecchione, Eduardo; Suárez, Claudia

    2010-12-01

    Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans (GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, i.v. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.

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

    SciTech Connect

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

    1987-05-01

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

  1. Ulcer healing potential of ethanolic extract of Caralluma attenuata on experimental diabetic rats

    PubMed Central

    Garg, Sunil; Srivastava, Sajal; Singh, Kisanpal; Sharma, Alok; Garg, Kavita

    2016-01-01

    Introduction: Available data indicated that diabetes mellitus (DM) increases the vulnerability of the gastric ulcers and the need of the hour is to develop effective agents to treat ulcer with diabetes for better patient compliance and cost effectiveness. The ulcer-healing properties of ethanolic extract of Caralluma attenuata (CAEt) against both chemically- and physically induced gastric ulcers in experimental rats are recently studied. Aim: To assess the ulcer healing potential of Ethanolic Extract of Caralluma attenuata on Experimental Diabetic Rats. Material and Methods: The current study aimed to evaluate ulcer healing properties of CAEt on the aspirin induced gastric ulcer in rats with streptozotocin induced DM. The hypothesis is based on the fact that DM results in compromising the mucosal defensive factors associated with delay in gastric ulcer healing, and if these changes can be corrected by using agents known for their antidiabetic and antiulcer properties. Experimental albino rats were divided into six groups. Except for Group I, other groups contained streptozotocin-induced diabetic rats. Group I (normal control) and Group II (diabetic control) were administered vehicle, Groups III and IV (diabetic experimental) were administered CAEt in dose of 100 mg/kg and 250 mg/kg, respectively, and Groups V and VI (positive controls) were respectively administered oral standard drugs omeprazole, 20 mg/kg, and tolbutamide 10 mg/kg. Result: The results confirmed that the CAEt significantly decreases the ulcer index (P < 0.05) in the aspirin-induced gastric ulcers and also significantly exhibit antioxidant and glucose lowering activity in the diabetic ulcer rats. The study showed that C. attenuata has the potential to be used as an antiulcer agent in experimental diabetic rats. PMID:27621520

  2. Aberrant Activation of the Intrarenal Renin-Angiotensin System in the Developing Kidneys of Type 2 Diabetic Rats

    PubMed Central

    Fan, Y.-Y.; Kobori, H.; Nakano, D.; Hitomi, H.; Mori, H.; Masaki, T.; Sun, Y.-X.; Zhi, N.; Zhang, L.; Huang, W.; Zhu, B.; Li, P.; Nishiyama, A.

    2013-01-01

    We have previously reported that intrarenal angiotensin II (Ang II) levels are increased long before diabetes becomes apparent in obese Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of type 2 diabetes. In this study, we examined the changes in intrarenal renin-angiotensin system (RAS) activity in the developing kidneys of OLETF rats. Ang II contents and mRNA levels of RAS components were measured in male OLETF and control Long-Evans Tokushima (LETO) rats at postnatal days (PND) 1, 5, and 15, and at 4–30 weeks of age. In both LETO and OLETF rats, kidney Ang II levels peaked at PND 1, then decreased during the pre- and post-weaning periods. However, Ang II levels and gene expression of RAS components, including angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE), were not significantly different between LETO and OLETF rats. Intrarenal Ang II contents further decreased during puberty (from 7 to 11 weeks of age) in LETO rats, bur not in OLETF rats. At 11 weeks of age, kidney Ang II levels, urinary AGT excretion, and mRNA levels of AGT and renin were higher in OLETF rats than in LETO rats, while blood glucose levels were not significantly different between these groups of rats. These data indicate that continued intrarenal expression of Ang II during pubescence contributes to the increases in intrarenal Ang II levels in prediabetic OLETF rats, and is associated with increased intrarenal AGT and renin expression. Inappropriate activation of the intrarenal RAS in the prediabetic stage may facilitate the onset and development of diabetic nephropathy in later life. PMID:23322513

  3. Dual Effect of Curcumin-Zinc Complex in Controlling Diabetes Mellitus in Experimentally Induced Diabetic Rats.

    PubMed

    Al-Ali, Khalil; Abdel Fatah, Hala Salah; El-Badry, Yaser Abdel-Moemen

    2016-01-01

    Ultrasound-assisted extraction of curcumin from Curcuma longa was performed in an ultrasonic bath at 30°C using ethanol for 40 min. A successful attempt has been made to prepare curcumin-zinc (Zn) complex using a simple chemical procedure. The complex formation and its stoichiometry were characterized using elemental analysis, Fourier transform (FT)-IR and UV spectroscopy which revealed the interaction of Zn(II) ion (M) with curcumin (ligand, L) to proceed via (ML) complex type formation. Oral administration of curcumin-Zn complex at a concentration of 150 mg/kg body weight/rat/d for 45 d in streptozotocin-induced diabetic rats in comparison to curcumin and/or Zn administration exerted a hypoglycemic effect. A significant reduction in blood glucose, glycosylated hemoglobin (Hb)A1c, and lipid profile parameters with an excellent improvement in plasma insulin levels have been attained. Also, the reduced activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine in the diabetic rats treated with the complex exhibited the non-toxic nature of the curcumin-Zn complex. Finally, the larger extent of the complex in hyperglycemic improvement in comparison to curcumin and/or Zn supplementation was interpreted by its dual action on glucose and insulin maintenance.

  4. Diabetes mitigates the recovery following intracranial hemorrhage in rats.

    PubMed

    Fan, Zhenzeng; Yuan, Yunchao; Wang, Feng; Qi, Yuepeng; Han, Haie; Wu, Jianliang; Zhang, Gengshen; Yang, Lijun

    2017-03-01

    Intracranial hemorrhage (ICH) is a common subtype of stroke with high morbidity and mortality. However, few studies have examined the effects of diabetes on the recovery from ICH-induced brain injury. Therefore, we examined the effects of diabetes on protein levels of aquaporins, neuronal loss, angiogenesis, blood brain barrier (BBB) integrity, and neurological deficits following intra-DH collagenase-induced ICH in the hippocampus. We found that diabetic rats exhibited enhanced AQP9 expression in the hippocampus relative to non-diabetic rats, which was associated with increased behavioral deficits. Additionally, ICH induced neovascularization, proliferation of brain microvascular endothelial cells, and hippocampal neuronal loss. However, ICH-induced neovascularization and proliferation of brain microvascular endothelial cells was severely impaired in diabetic rats. Furthermore, ICH-induced hippocampal neuronal loss was exaggerated in diabetic rats. Finally, ICH impaired BBB integrity in the ipsilateral hemisphere, which was increased in diabetic rats. Taken together, the attenuated brain angiogenesis, increased hippocampal neuronal loss, and impaired BBB integrity in diabetic rats after ICH were associated with enhanced AQP9 expression. This may suggest that AQP9 is one of the underlying mechanisms that can mitigate the recovery from ICH in diabetic populations.

  5. Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats.

    PubMed

    Makni, Mohamed; Sefi, Mediha; Fetoui, Hamadi; Garoui, El Mouldi; Gargouri, Nabil K; Boudawara, Tahia; Zeghal, Najiba

    2010-01-01

    This study investigated the hypoglycemic and antioxidant effects of Flax and Pumpkin seeds mixture on the kidney of alloxan-induced diabetic rats. Animals were allocated into three groups of six rats each: a control group (CD), a diabetic group (DD) and diabetic rats fed with Flax and Pumpkin seeds mixture (DMS) group. The DD rats showed a significant increase of glycemia and lipid parameters such as total lipid, total cholesterol and triglycerides levels compared to those of the control group (CD). In addition, plasma and kidney malonaldialdehyde levels (MDA) were significantly increased compared to (CD) group. Antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD) and non-enzymatic levels of reduced glutathione (GSH) significantly decreased in the plasma and kidney of diabetic rats compared to those of controls. Diet supplemented with Flax and Pumpkin seeds mixture ameliorated the antioxidant enzymes activities observed in diabetic rats and significantly decreased MDA levels. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In DMS rats, these histopathological changes were less prominent. Our results suggest that Flax and Pumpkin seeds mixture supplemented in diet of diabetic rats may be helpful to prevent diabetes and its complications.

  6. Depression among patients with type-II diabetes mellitus.

    PubMed

    Khan, Mohammad Akmal; Sultan, Sayed Mohammad; Nazli, Rubina; Akhtar, Tasleem; Khan, Mudasar Ahmad; Sher, Nabila; Aslam, Hina

    2014-10-01

    This study aimed to determine the frequency of depression among patients with type-II diabetes mellitus in Peshawar at Khyber Teaching Hospital, Peshawar, from March to September 2010. Depression was assessed by using Beck Depressive Inventory-II (BDI-II). Out of 140 patients with type-II diabetes, 85 (61%) were women and 55 (39%) were men. Mean age was 45±7.45 years. Eighty four (60%) patients presented with severe depression. Depression was higher in females than males and widows. Depression was high in diabetic patients, especially in females and widows. It is of essence that psychiatric attention may be necessary to be incorporated in diabetes care both for prevention and treatment.

  7. Type II (noninsulin-dependent) diabetes: new treatment options.

    PubMed

    Bodzin, B J

    1997-01-01

    Type II diabetes (noninsulin-dependent diabetes mellitus [NIDDM]) is a common primary and secondary diagnosis in home care patients. This article describes the pathophysiology of NIDDM, the new drugs that have been released for treatment, and the nursing implications inherent in using these new medications.

  8. Knowledge Is Power: Teaching Children about Type II Diabetes

    ERIC Educational Resources Information Center

    Feild-Berner, Natalie; Balgopal, Meena

    2011-01-01

    World Diabetes Day (November 14) offers a wonderful opportunity to educate elementary children about the power they have to control their health. First lady Michelle Obama has urged Americans to educate themselves about childhood obesity, which is often associated with the onset of type II diabetes (Rabin 2010). The authors developed activities to…

  9. Antidiabetic activity of Bauhinia forficata extracts in alloxan-diabetic rats.

    PubMed

    Lino, Cleide de Sousa; Diógenes, João Paulo Luz; Pereira, Bruno Azevedo; Faria, Rozilaine Aparecida Pelegrine Gomes; Andrade Neto, Manoel; Alves, Renata Sousa; de Queiroz, Maria Goreti Rodrigues; de Sousa, Francisca Cléa Florenço; Viana, Glauce Socorro Barros

    2004-01-01

    The antidiabetic activity of aqueous, ethanolic and hexanic extracts of Bauhinia forficata was investigated in a model of alloxan-induced diabetes in rats. The biochemical parameters studied were: plasma glucose, serum triglycerides, cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL). Extracts were administered daily for 7 d at doses of 200 and 400 mg/kg, p.o., 48 h after alloxan injection (60 mg/kg, i.v.). The alloxan-diabetic rats showed significant reductions in plasma glucose, triglycerides, total cholesterol and HDL-cholesterol after treatment with the extracts and glibenclamide (used as standard) as compared to the diabetic controls. Levels of LDL were not altered. In conclusion, our results showed that the plant extracts when administered by gavage may reduce glucose, triglycerides, total cholesterol and HDL-cholesterol levels. These results suggest the validity of the clinical use of B. forficata in the treatment of diabetes mellitus type II.

  10. Protein expression in salivary glands of rats with streptozotocin diabetes

    PubMed Central

    Mednieks, Maija I; Szczepanski, Andrew; Clark, Brett; Hand, Arthur R

    2009-01-01

    Diabetes mellitus (DM) is a widespread disease with high morbidity and health care costs. An experimental animal model was employed, using morphological and biochemical methods, to investigate the effects of DM on the expression and compartmentation of salivary gland proteins. The distribution of proline-rich proteins (PRP), submandibular mucin (Muc10) and the regulatory (RI and RII) subunits of cyclic AMP-dependent protein kinase type I and type II was determined in the parotid and submandibular (SMG) glands of rats treated with streptozotocin. Quantitative immunocytochemistry of secretory granules in diabetic glands revealed decreases of 30% for PRP in both the parotid and SMG, and a 40% decrease in Muc10 in the SMG. Immunogold labelling showed that RII decreased in nuclei and the cytoplasm in diabetic acinar cells while labelling of secretory granules was similar in control and diabetic parotid. Electrophoresis and Western blotting of tissue extracts of two secretory proteins showed that the response to DM and insulin treatment was gland specific: PRP showed little change in the SMG, but decreased in the parotid in DM and was partially restored after insulin treatment. Photoaffinity labelling showed only RI present in the SMG and mainly RII in the parotid. The results of this and previous studies demonstrating highly specific changes in salivary protein expression indicate that the oral environment is significantly altered by DM, and that oral tissues and their function can be compromised. These findings may provide a basis for future studies to develop tests using saliva for diabetic status or progression in humans. PMID:19659899

  11. Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes.

    PubMed

    Kulkarni, Yogesh A; Garud, Mayuresh S

    2016-10-01

    Among various metabolic disorders, diabetes mellitus is one of the most common disorder. Present study was designed to evaluate the effectiveness of aqueous extract of Bauhinia variegata leaves (AE) in animal models of type I and type II diabetes. Type I diabetes was induced by streptozotocin at the dose of 55mg/kg (i.p.) in male Sprague Dawley rats while type II diabetes was induced by high fat diet and streptozotocin at the dose of 35mg/kg (i.p.). Diabetic animals were treated with AE at the dose of 250, 500 and 1000mg/kg. Glipizide (5mg/kg) was used as standard treatment drug. Treatment was given for 28days. Parameters evaluated were body weight, plasma glucose, cholesterol, triglyceride, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total proteins, albumin, creatinine and bun urea nitrogen. In type II diabetes, high density lipoprotein levels in plasma and plasma insulin level were also evaluated. Histopathological study of pancreases were carried out in type I study. AE showed significant decrease in plasma glucose significantly. AE was also found to decrease cholesterol, triglyceride, creatinine and blood urea nitrogen level in both types of diabetes. AE did not show any significant effect on plasma levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase. AE was found to increase the albumin and total protein levels. Histopathological study showed that AE decreases the necrotic changes in the pancreatic tissue. Aqueous extract of B. variegata leaves was found effective in treatment of both type I and type II diabetes.

  12. Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.

    PubMed

    Refaat, Rowaida; Sakr, Ahmed; Salama, Mona; El Sarha, Ashgan

    2016-09-01

    Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.

  13. 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

  14. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats.

    PubMed

    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.

  15. The Diabetic Nephropathy and the Development of Hypertension in Rats

    PubMed Central

    Zuccollo, Adriana; Navarro, Monica

    2001-01-01

    The present study was designed to examine the development of hypertension in diabetic rats treated with streptozotocin (STZ, 1mg/g bw). The rats were studied at 3, 6, 9, 12 and 15 weeks. From the third week the rats were divided in diabetic rats according their glycemias and controls, along 15 weeks. After the third week a group, of rats showed increased urinary protein excretion (93, 134, 155 and 191%) compared to controls. In this group of rats the urinary kallikrein excretion was lower than control and the systolic blood pressure became significantly elevated between 3 and 6 weeks and persisted up to 15 weeks. On the other hand a group of diabetic rats were normotensive with urinary protein excretion similar to controls and urinary kallikrein lower compared to control but significantly higher compared diabetic hypertensive rats. These data suggest that the association of progressive diabetic nephropathy with abnormal endothelium-dependent vasodilation may produce a high prevalence of hypertensive diabetes. PMID:12369707

  16. Role of Nitric Oxide in the Pathogenesis of Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Choi, Ki Chul; Lee, Seong Cheol; Kim, Soo Wan; Kim, Nam Ho; Lee, Jong-Un; Kang, Young Joon

    1999-01-01

    Objectives Several reports suggest that enhanced generation or actions of nitric oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration and hyperperfusion that occurs in early diabetes. However, the precise role of altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The present study was aimed at investigating the role of nitric oxide in the pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin-induced diabetic rats. Methods To evaluate the role of NO in diabetic hyperfiltration, we measured plasma and urine concentrations of NO2−/NO3−, stable metabolic products of NO and protein expressions of three isoforms of nitric oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also investigated renal hemodynamic changes, such as glomerular filtration rate (GFR) and renal plasma flow (RPF), in responses to acute and chronic administration of NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and control rats. Results Diabetic rats exhibited significantly elevated plasma and urinary NO2−/NO3− levels at 28 days after streptozotocin injection, and total excretion of NO2−/NO3− was approximately five-fold higher in diabetic rats than controls. Insulin and L-NAME treatment prevented the increases in plasma and urinary NO2−/NO3− concentrations in diabetic rats, respectively. The three isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex, whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were significantly elevated in diabetic rats, and acute and chronic inhibition of NO synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR and RPF) in diabetic rats, respectively. Conclusions NO synthesis was increased due to enhanced NOS expression in diabetic rats, and chronic NO blockade attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In addition, diabetic rats

  17. Hydrogen sulfide accelerates wound healing in diabetic rats

    PubMed Central

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

    2015-01-01

    Aim: The aim of this study was to explore the role of hydrogen sulfide on wound healing in diabetic rats. Methods: Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (STZ) (in 0.1 mol/L citrate buffer, Ph 4.5) at dose of 70 mg/kg. Diabetic and age-matched non-diabetic rats were randomly assigned to three groups: untreated diabetic controls (UDC), treated diabetic administrations (TDA), and non-diabetic controls (NDC). Wound Healing Model was prepared by making a round incision (2.0 cm in diameter) in full thickness. Rats from TDA receive 2% sodium bisulfide ointment on wound, and animals from UDC and NDC receive control cream. After treatment of 21 days with sodium bisulfide, blood samples were collected for determination of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), antioxidant effects. Granulation tissues from the wound were processed for histological examination and analysis of western blot. Results: The study indicated a significant increase in levels of VEGF and ICAM-1 and a decline in activity of coagulation in diabetic rats treated with sodium bisulfide. Sodium bisulfide treatment raised the activity of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein expression, and decreased tumor necrosis factor α (TNF-α) protein expression in diabetic rats. Conclusions: The findings in present study suggested that hydrogen sulfide accelerates the wound healing in rats with diabetes. The beneficial effect of H2S may be associated with formation of granulation, anti-inflammation, antioxidant, and the increased level of vascular endothelial growth factor (VEGF). PMID:26191204

  18. Steps of glucocorticoid action in normal and diabetic rat placenta.

    PubMed

    Heller, C L; Weisenberg, L S; Ortí, E; De Nicola, A F

    1988-07-01

    This investigation examined the effects of Streptozotocin diabetes in pregnancy on several parameters of glucocorticoid action in the rat placenta. Pregnant diabetic rats showed reduced body weight, increased adrenal weight and serum corticosterone concentrations. Glucocorticoid receptors in placental cytosol of labyrinthine zone, measured in the absence of MoO4Na2 were similar in control and diabetic rats, but after addition of MoO4Na2 receptor number were moderately, but significantly reduced in diabetic placentas (P less than 0.01). No changes in affinity were detected in saturation analysis. Furthermore, transformation of the receptor assessed by its capacity for binding to DNA-cellulose, was enhanced in diabetic animals, suggesting increased efficiency of the receptor-bound hormone. Since the function of the glucocorticoid receptor of rat placenta may be the inhibition of local progesterone production (Heller and De Nicola, J. steroid Biochem. 19 (1983) 1339-1343), we determined progesterone synthesis in vitro and found that diabetic placentas synthesized significantly less progesterone than control tissue (P less than 0.05). Lastly, we found that the metabolism of corticosterone to 11-dehydrocorticosterone, while declining in control placentas as pregnancy advanced, it was sustained in diabetic pregnancy. It is suggested that diabetic rat placentas showed increased activity towards the glucocorticoid receptor, resulting in reduction in progesterone synthesis and sustained catabolism of corticosterone. The latter may possibly constitute a compensatory mechanism to protect the fetal compartment from high levels of maternal glucocorticoids.

  19. Chronic cobalt treatment decreases hyperglycemia in streptozotocin-diabetic rats.

    PubMed

    Vasudevan, Harish; McNeill, John H

    2007-04-01

    Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 +/- 2 gm) compared to controls (482 +/- 3 gm). Body weight was further reduced by cobalt treatment (290 +/- 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 +/- 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 +/- 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose.

  20. Chromium yeast supplementation improves fasting plasma glucose and LDL-cholesterol in streptozotocin-induced diabetic rats.

    PubMed

    Lai, Ming-Hoang; Chen, Ya-Yen; Cheng, Hsing-Hsien

    2006-11-01

    Chromium yeast supplementation has been studied for its ability to improve carbohydrate and lipid abnormalities. There have been some earlier literature-reported studies involving chromium supplementation amongst patients suffering diabetes, but the results would appear to be somewhat varied. Forty male Wistar rats (ten weeks old, 300 g in average body mass) were divided into one of four groups, namely (i) controls; (ii) controls treated with chromium yeast; (iii) diabetic controls; and (iv) diabetic rats treated with chromium yeast. In the present investigation, the effect of a four-week oral administration of chromium yeast (600 microg of Cr/kg body mass/day, by gavage) upon the glucose and lipid metabolism in streptozotocin (STZ)-induced diabetic rats was assessed. Supplemental Cr yeast decreased the fasting blood glucose amongst the STZ-diabetic rats. No significant difference was observed in plasma fructosamine levels of rats treated with chromium yeast compared to control rats. Supplemental Cr yeast did decrease the plasma low-density lipoprotein (LDL)-cholesterol level for the STZ-diabetic rats as compared to controls. We noted no significant effect of chromium supplementation upon plasma high-density lipoprotein (HDL)-cholesterol or triglycerides compared to controls. Treatment with chromium yeast significantly increased the blood and urine chromium levels for both the diabetic and normal rats compared to respective control groups. The results of these studies suggest that Cr yeast decreased the fasting blood glucose and LDL-cholesterol levels in STZ-induced diabetic rats. This raises the possibility that Cr yeast supplementation can be considered to improve carbohydrate and lipid metabolism amongst human patients featuring type 2 diabetes mellitus.

  1. Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)

    SciTech Connect

    Hsiao,Y.; Jogl, G.; Esser, V.; Tong, L.

    2006-01-01

    Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the {beta}-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Angstroms resolution. The overall structure shares strong similarity to those of short- and medium-chain carnitine acyltransferases, although detailed structural differences in the active site region have a significant impact on the substrate selectivity of CPT-II. Three aliphatic chains, possibly from a detergent that is used for the crystallization, were found in the structure. Two of them are located in the carnitine and CoA binding sites, respectively. The third aliphatic chain may mimic the long-chain acyl group in the substrate of CPT-II. The binding site for this aliphatic chain does not exist in the short- and medium-chain carnitine acyltransferases, due to conformational differences among the enzymes. A unique insert in CPT-II is positioned on the surface of the enzyme, with a highly hydrophobic surface. It is likely that this surface patch mediates the association of CPT-II with the inner membrane of the mitochondria.

  2. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats

    PubMed Central

    Yu, Tianyi; Chang, Qingxuan; Wang, Di; Gao, Min; Zhang, Xiong; Liu, Yan

    2016-01-01

    Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds. PMID:27028201

  3. Remodeling Intestinal Flora with Sleeve Gastrectomy in Diabetic Rats

    PubMed Central

    Huang, Xiaofei; Weng, Pan; Zhang, Huixin; Lu, Yingli

    2014-01-01

    Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals' weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism. PMID:25165722

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

    PubMed

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

    2012-01-01

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

  5. Insulin modulates inflammatory and repair responses to elastase-induced emphysema in diabetic rats.

    PubMed

    Di Petta, Antonio; Greco, Karin V; Castro, Eveline O; Lopes, Fernanda D T Q S; Martins, Milton A; Capelozzi, Vera L; Moreira, Luiz F P; Sannomiya, Paulina

    2011-12-01

    As pulmonary emphysema and diabetes mellitus are common diseases, concomitance of both is correspondingly expected to occur frequently. To examine whether insulin influences the development of inflammation in the alveolar septa, diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., n = 37) and matching controls (n = 31) were used. Ten days after alloxan injection, diabetic and control rats were instilled with physiologic saline solution containing porcine pancreatic elastase (PPE, 0.25 IU/0.2 ml, right lung) or saline only (left lung). The following analyses were performed: (i) number of leucocytes in the bronchoalveolar lavage (BAL) fluid of the animals, 6 h after PPE/saline instillation (early time point); and (ii) mean alveolar diameter (μm) and quantification of elastic and collagen fibres (%) 50 days after PPE/saline instillation (late time point). Relative to controls, alloxan-induced diabetic rats showed a 42% reduction in the number of neutrophils in BAL fluid, a 20% increase in the mean alveolar diameter and a 33% decrease in elastic fibre density in the alveolar septa. Treatment of diabetic rats with 4 IU neutral protamine Hagedorn (NPH) insulin, 2 h before elastase instillation, restored the number of neutrophils in the BAL fluid. The mean alveolar diameter and elastic fibre content in alveolar septa matched the values observed in control rats if diabetic rats were treated with 4 IU NPH insulin 2 h before instillation followed by 2 IU/day for the next 50 days. Density of collagen fibres did not differ between the various groups. Thus, the data presented suggest that insulin modulates the inflammatory and repair responses in elastase-induced emphysema, and assures normal repair and tissue remodelling.

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

    PubMed

    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.

  7. 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

  8. Hepcidin and iron metabolism in non-diabetic obese and type 2 diabetic rats.

    PubMed

    Chen, Yue; Yin, Hui-qing; Liu, Hao-ling; Xiu, Lei; Peng, Xiao-yu

    2015-12-01

    The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups: control group, non-diabetic obese group and type 2 diabetic group (n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin (HE) staining. The mRNA expression patterns of hepcidin, interleukin-6 (IL-6), hypoxia-inducible factor (HIF) and ferroportin (Fpn) in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further analyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly (P<0.001). However, there was no significant difference in soluble transferring receptor (sTfR):ferritin ratio among the three groups (P>0.05). The real-time RT-PCR, immunohistochemistry and Western blotting results all revealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group (P<0.001). The expression levels of hepcidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant difference (P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group (P<0.05). Compared to control group, the expression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn mRNA decreased (P<0.05). However, the expression levels of HIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is

  9. Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis.

    PubMed

    Khodeer, Dina M; Zaitone, Sawsan A; Farag, Noha E; Moustafa, Yasser M

    2016-05-01

    Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.

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

    PubMed

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

    2004-12-01

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

  11. Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin.

    PubMed

    Wu, Duo; Wen, Wei; Qi, Chun-Li; Zhao, Ru-Xia; Lü, Jun-Hua; Zhong, Chun-Yan; Chen, Yi-Yu

    2012-06-15

    Berberine (BBR) is one of the main constituents in Rhizoma coptidis and it has widely been used for the treatment of diabetic nephropathy. The aims of the study were to investigate the effects and mechanism of action of berberine on renal damage in diabetic rats. Diabetes and hyperglycaemia were induced in rats by a high-fat diet and intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Rats were randomly divided into 5 groups, such as i) control rats, ii) untreated diabetic rats iii) 250 mg/kg metformin-treated, iv and v) 100 and 200 mg/kg berberine-treated diabetic rats and treated separately for 8 weeks. The fasting blood glucose, insulin, total cholesterol, triglyceride, glycosylated hemoglobin were measured in rats. Kidneys were isolated at the end of the treatment for histology, Western blot analysis and estimation of malonaldehyde (MDA), superoxide dismutase (SOD) and renal advanced glycation endproducts (AGEs). The results revealed that berberine significantly decreased fasting blood glucose, insulin levels, total cholesterol, triglyceride levels, urinary protein excretion, serum creatinine (Scr) and blood urea nitrogen (BUN) in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with berberine. In addition, the protein expressions of nephrin and podocin were significantly increased. It seems likely that in rats berberine exerts an ameliorative effect on renal damage in diabetes induced by high-fat diet and streptozotocin. The possible mechanisms for the renoprotective effects of berberine may be related to inhibition of glycosylation and improvement of antioxidation that in turn upregulate the expressions of renal nephrin and podocin.

  12. Topical embryonic stem cells enhance wound healing in diabetic rats.

    PubMed

    Lee, Keun-Bae; Choi, Jin; Cho, Seong-Beom; Chung, Jae-Yoon; Moon, Eun-Sun; Kim, Nack-Sung; Han, Ho-Jae

    2011-10-01

    The effects of embryonic stem cells (ESCs) on diabetic wound healing were investigated using an excisional skin wound model in 110 diabetes-induced rats. We transplanted a clonal population of ESCs (5 × 10(6)) by topical injection into full thickness skin wounds. Four study groups were used; nondiabetic rats as a control, non-insulin controlled diabetic rats not treated with ESCs, insulin controlled diabetic rats not treated with ESCs, and insulin controlled diabetic rats treated with ESCs. Five rats in each experimental group were sacrificed on days 1, 5, 10, 15, and 20 after wounding. Wounds images were acquired daily and wound sizes were calculated. We measured the mRNA levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and fibronectin levels in extracellular matrix, and assessed wound healing by assessing histological parameters of epidermal regeneration, granulation tissue thickness, and angiogenesis. In the ESC-treated group, wound sizes were significantly smaller than in the insulin controlled diabetic group not treated with ESCs on days 5 and 10 (p < 0.05), and EGF and VEGF levels were markedly higher on days 5 and 10, fibronectin levels on day 5 after injection. All histological scores in the ESC-treated group were significantly higher than those of the insulin controlled diabetic group on day 5 (p < 0.05). Our results shows that topical ESCs enhance diabetic wound healing during the early stage, and suggest that ESCs transplantation offers a novel therapeutic modality for the treatment of diabetic wounds.

  13. Glucose Intolerance and Hyperlipidemia Prior to Diabetes Onset in Female Spontaneously Diabetic Torii (SDT) Rats

    PubMed Central

    Oikawa, Toshihiro; Sato, Kahei; Kanazawa, Yasunori

    2004-01-01

    The Spontaneously Diabetic Torii (SDT) rat, a newly established animal model for diabetes mellitus, presents nonobese type 2 diabetes with ocular complications. In the present study, oral glucose tolerance tests and biochemical and histopathological examinations were performed in female SDT rats at 16 and/or 25 weeks of age, before the onset of diabetes. At 25 weeks of age, glucose tolerance was significantly impaired, and plasma immunoreactive insulin levels at 120 min after glucose loading were significantly higher (P < 0.05). Body weight and fasting levels of plasma triglycerides and nonesterified fatty acids were significantly higher than those in control animals. Histopathologically, inflammatory cell infiltration and fibrosis were observed in and around the pancreatic islets. These results strongly suggest that female SDT rats are useful as a model to investigate impairment of glucose tolerance and hyperlipidemia prior to the onset of diabetes. PMID:15763939

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

    PubMed

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

    2017-02-26

    The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (p<0.001). Electrophysiologically, compound muscle action potential (CMAP) amplitudes of the saline treated DM group were significantly reduced than those of controls (p<0.0001). Also, distal latency and CMAP durations were significantly prolonged in saline treated DM group (p<0.05) compared to control. However, treatment of diabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (p<0.05). Histomorphometric assessment of the sciatic nerve demonstrated a significant reduction in perineural thickness in OCT treated group compared to saline group. In conclusion, OCT possesses beneficial effects against STZ-induced diabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

  15. The protective effect of vanadium against diabetic cataracts in diabetic rat model.

    PubMed

    Sun, Lei; Shi, De-Jing; Gao, Xiang-Chun; Mi, Shu-Yong; Yu, Ying; Han, Qing

    2014-05-01

    The present study was designed to investigate the effect of vanadium in alloxan-induced diabetes and cataract in rats. Different doses of vanadium was administered once daily for 8 weeks to alloxan-induced diabetic rats. To know the mechanism of action of vanadium, lens malondialdehyde (MDA), protein carbonyl content, activity of superoxide dismutase (SOD), activities of aldose reductase (AR), and sorbitol levels were assayed, respectively. Supplementation of vanadium to alloxan-induced diabetic rats decreased the blood glucose levels due to hyperglycemia, inhibited the AR activity, and delayed cataract progression in a dose-dependent manner. The observed beneficial effects may be attributed to polyol pathway activation but not decreased oxidative stress. Overall, the results of this study demonstrate that vanadium could effectively reduce the alloxan-induced hyperglycemia and diabetic cataracts in rats.

  16. Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase.

    PubMed

    Winiarska, Katarzyna; Dzik, Jolanta M; Labudda, Mateusz; Focht, Dorota; Sierakowski, Bartosz; Owczarek, Aleksandra; Komorowski, Lukasz; Bielecki, Wojciech

    2016-01-01

    Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47(phox) subunits, elevated level of p47(phox) phosphorylation, and enlarged phospho-p47(phox) and p67(phox) content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho-p47(phox) and p67(phox) . Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.

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

    PubMed

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

    2000-01-01

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

  18. Effects of Atorvastatin on Nitrate Tolerance in Diabetic Rats

    PubMed Central

    Imenshahidi, Mohsen; Karimi, Gholamreza; Kazemzadeh, Ehsan

    2010-01-01

    Statins have been reported to show preventive effect on nitrate tolerance in normal rats, but there are no reports on their effect in diabetic animals. In this study, diabetes was induced in male wistar rats by a single intraperitoneal injection of streptozotocin (45 mg/kg). Five groups of diabetic and five groups of normal rats were treated; groups 1 (of normal and diabetic rats) received atorvastatin (10 mg/kg/d p.o. for 8 weeks) and groups 2 received atorvastatin (10 mg/kg/d p.o. for last 3 days). Groups 3 and groups 4 were similar to groups 1 and 2 respectively, except that they received nitroglycerin (50 mg/kg/d, b.i.d. for last 3 days of the study). Groups 5 received neither atorvastatin nor nitroglycerin. After 8 weeks, relaxations to nitroglycerin (0.01 to 10 nM) and nitroprusside (0.01 to 10 nM) were determined on phenylephrine-preconstricted aortic rings. The relaxation response to nitroglycerin in diabetic and normal aorta were not significantly different. The results showed that 8 weeks treatment with atorvastatin prevents nitrate tolerance in diabetic and normal rats, but in nitrate tolerant animals, 3 days treatment with atorvastatin was not effective on protection against nitrate tolerance. PMID:24363707

  19. Elevated glutamine metabolism in splenocytes from spontaneously diabetic BB rats.

    PubMed

    Wu, G Y; Field, C J; Marliss, E B

    1991-02-15

    To investigate the metabolic fates of glutamine in splenocytes from the BB rat with spontaneous immunologically mediated insulin-dependent diabetes, freshly isolated cells were incubated in Krebs-Ringer Hepes buffer with 1.0 mM-[U-14C]glutamine and 0, 4 mM- or 15 mM-glucose. (1) The major products of glutamine metabolism in splenocytes from normal and diabetic rats were ammonia, glutamate, aspartate and CO2. (2) The addition of glucose increased (P less than 0.01) glutamate production, but decreased (P less than 0.01) aspartate and CO2 production from glutamine, as compared with the values obtained in the absence of glucose. However, there were no differences in these metabolites of glutamine at 4 mM- and 15 mM-glucose. (3) At all glucose concentrations used, the productions of ammonia, glutamate, aspartate and CO2 from glutamine were all markedly increased (P less than 0.01) in splenocytes from diabetic rats. (4) Potential ATP production from glutamine in the splenocytes was similar to that from glucose, and was increased in cells from the diabetic rat. (5) ATP concentrations were increased (P less than 0.01) in diabetic-rat splenocytes in the presence of glutamine with or without glucose. (6) Our results demonstrate that glutamine is an important energy substrate for splenocytes and suggest that the increased glutamine metabolism may be associated with the activation of certain subsets of splenocytes in the immunologically mediated diabetic syndrome.

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

    PubMed

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

    2008-07-01

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

  1. Hemodynamic alterations in chronically conscious unrestrained diabetic rats.

    PubMed

    Carbonell, L F; Salom, M G; Garcia-Estañ, 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. 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/dtmax and dP/dtmin 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 state, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.

  2. Timing behavior in streptozotocin-induced diabetic rats.

    PubMed

    Orduña, Vladimir; Hong, Enrique; Bouzas, Arturo

    2011-10-10

    There is evidence of deterioration of spatial cognition in streptozotocin (STZ)-induced diabetic rats. Here, we evaluate a possible dissociation in the cognitive deficits due to diabetes by examining another crucial aspect of animal cognition: temporal perception. Timing behavior and temporal memory were evaluated in STZ-induced diabetic rats employing two timing tasks: the peak-interval procedure, with its Gap variant, and the interval bisection task. A spatial memory task, rewarded alternation in the T-maze, was also evaluated to explore spatial cognition. The two timing tasks employed coincide in the finding of a normal timing performance in STZ-induced diabetic rats. The peak-interval procedure provided results that suggest that the timing behavior is equally accurate and precise than in control subjects; in the Gap procedure, an equal change in peak time in both groups indicates that temporal working memory is also intact. In the interval bisection task, we analyzed the acquisition of a temporal discrimination and the sensitivity to changes in the duration of the stimulus; no differences were found in either the acquisition process or the sensitivity index. In contrast, in the rewarded alternation task, STZ-induced diabetic rats exhibited a significant deficit in spatial cognition. The cognitive processes involved in timing behavior and temporal memory are not deteriorated as a consequence of diabetes; the cognitive deficits associated to diabetes thus seem to be restricted to the spatial domain.

  3. Diabetic foot ulcers: Part II. Management.

    PubMed

    Alavi, Afsaneh; Sibbald, R Gary; Mayer, Dieter; Goodman, Laurie; Botros, Mariam; Armstrong, David G; Woo, Kevin; Boeni, Thomas; Ayello, Elizabeth A; Kirsner, Robert S

    2014-01-01

    The management of diabetic foot ulcers can be optimized by using an interdisciplinary team approach addressing the correctable risk factors (ie, poor vascular supply, infection control and treatment, and plantar pressure redistribution) along with optimizing local wound care. Dermatologists can initiate diabetic foot care. The first step is recognizing that a loss of skin integrity (ie, a callus, blister, or ulcer) considerably increases the risk of preventable amputations. A holistic approach to wound assessment is required. Early detection and effective management of these ulcers can reduce complications, including preventable amputations and possible mortality.

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

    PubMed Central

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

    2016-01-01

    Diabetes mellitus (DM) is a metabolic syndrome caused by multiple genetic and environmental factors. Traditional Chinese medicine preparations have shown a comprehensive and function-regulating characteristic. Purslane (Portulaca oleracea L.) is an annual succulent herb. Currently, there have been some related reports on the treatment of diabetes with purslane. The current study was designed to separate and purify the polysaccharide, a systematic study of its physical and chemical properties, antioxidant activity, and anti-diabetic mechanism, in order to provide a theoretical basis for the development of drugs of purslane. A crude water soluble polysaccharide extracted from purslane was named CPOP (crude Portulaca oleracea L. polysaccharide). Effects of CPOP on bodyweight, glucose tolerance test (GTT), fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity index (ISI), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), methane dicarboxylic aldehyde (MDA), and superoxygen dehydrogenises (SOD) were investigated. The results indicate that the oral administration of CPOP could significantly increase the body weight and significantly improve the glucose tolerance in diabetic rats. Meanwhile, CPOP could significantly reduce the FBG level, and elevate the FINS level and ISI value in diabetic rats. In addition, CPOP could significantly reduce TNF-α and IL-6 levels in diabetic rats; CPOP could also reduce MDA and SOD activities in the liver tissue of diabetic rats. These results suggest that the anti-diabetic effect of CPOP may be associated with its antioxidant and anti-inflammatory effects. PMID:27463713

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

    PubMed

    Abo El Gheit, R; Emam, M N

    2016-12-01

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

  6. Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria.

    PubMed

    Ortiz-Avila, Omar; Sámano-García, Carlos Alberto; Calderón-Cortés, Elizabeth; Pérez-Hernández, Ismael H; Mejía-Zepeda, Ricardo; Rodríguez-Orozco, Alain R; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2013-06-01

    Impaired complex III activity and reactive oxygen species (ROS) generation in mitochondria have been identified as key events leading to renal damage during diabetes. Due to its high content of oleic acid and antioxidants, we aimed to test whether avocado oil may attenuate the alterations in electron transfer at complex III induced by diabetes by a mechanism related with increased resistance to lipid peroxidation. 90 days of avocado oil administration prevented the impairment in succinate-cytochrome c oxidoreductase activity caused by streptozotocin-induced diabetes in kidney mitochondria. This was associated with a protection against decreased electron transfer through high potential chain in complex III related to cytochromes c + c1 loss. During Fe(2+)-induced oxidative stress, avocado oil improved the activities of complexes II and III and enhanced the protection conferred by a lipophilic antioxidant against damage by Fe(2+). Avocado oil also decreased ROS generation in Fe(2+)-damaged mitochondria. Alterations in the ratio of C20:4/C18:2 fatty acids were observed in mitochondria from diabetic animals that not were corrected by avocado oil treatment, which yielded lower peroxidizability indexes only in diabetic mitochondria although avocado oil caused an augment in the total content of monounsaturated fatty acids. Moreover, a protective effect of avocado oil against lipid peroxidation was observed consistently only in control mitochondria. Since the beneficial effects of avocado oil in diabetic mitochondria were not related to increased resistance to lipid peroxidation, these effects were discussed in terms of the antioxidant activity of both C18:1 and the carotenoids reported to be contained in avocado oil.

  7. Macrovascular complications in Mexican Americans with type II diabetes.

    PubMed

    Haffner, S M; Mitchell, B D; Stern, M P; Hazuda, H P

    1991-07-01

    Mexican Americans have a threefold greater prevalence of non-insulin-dependent (type II) diabetes mellitus than non-Hispanic whites in the San Antonio Heart Study, a population-based study of diabetes. In addition, Mexican-American diabetic subjects (n = 365) have greater fasting glycemia than non-Hispanic white diabetic subjects (P less than 0.001). Despite these findings, and despite a higher prevalence of microvascular complications among Mexican Americans, there does not appear to be a marked difference in prevalence of macrovascular complications between Mexican-American and non-Hispanic white diabetic subjects. Mexican-American diabetic subjects have only a moderate excess of peripheral vascular disease (as judged by ankle-arm blood pressure ratios) relative to non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 1.84, 95% confidence interval 0.75-4.49). Mexican-American diabetic subjects actually reported fewer myocardial infarctions than non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 0.73, 95% confidence interval 0.31-1.71). Duration was not associated with either peripheral vascular disease or myocardial infarction. Severity of glycemia was only mildly associated with presence of peripheral vascular disease and negatively associated with self-reported myocardial infarction. This latter finding may represent a survival bias in that more severe diabetic subjects have already died and are not ascertained in a prevalence study. The absence of an ethnic difference in the prevalence of macrovascular disease contrasts with our previous reports from the San Antonio Heart Study, in which the prevalence of both retinopathy and proteinuria was observed to be higher in Mexican-American diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Prevention of diabetes in rats by bone marrow transplantation.

    PubMed

    Alinaji; Silvers, W K; Bellgrau, D; Anderson, A O; Plotkin, S; Barker, C F

    1981-09-01

    Hyperglycemia, hypoinsulinemia and ketonemia often develop abruptly in previously normal young "BB" rats. The syndrome mimics human juvenile diabetes closely and is, thus, appropriate for assessing pancreatic transplantation. Transplantation of islet cells from closely histocompatible Wistar Furth (WF) donor resulted in permanent normoglycemia when immunosuppression with ALS was given. However, when islet cells from nondiabetic "BB" donors were transplanted to nonimmunosuppressed diabetic "BB" recipients, only transient normoglycemia followed. Transplantation of WF islets cells also failed in diabetic "BB" rats which were tolerant of WF antigens, again suggesting destruction of transplanted islet cells by the original disease process-possibly autoimmunity. Evidence for autoimmunity was strengthened by the finding that newly diabetic "BB" rats could be rendered normoglycemic by immunosuppression. Since genetic susceptibility to spontaneous autoimmune diabetes is unique to some members of the "BB" stock, an attempt was made to alter their vulnerability by modifying their cellular immune system. Accordingly, 50 million bone marrow cells from WF donors were inoculated into half the newborn members of "BB" litters, leaving the littermates as unmodified controls. Most bone marrow recipients were protected, only four of 37 (10.8%) ever becoming diabetic, while the incidence of diabetes in noninoculated littermates was 22 of 39 (56.4%). The ultimate goal in human diabetes, which also seems very likely to be an autoimmune disease, may not be replacement of destroyed islet cells but identification of potentially susceptible children and prevention of islet destruction by immunologic manipulation.

  9. Cardioprotective Effect of Sodium Ferulate in Diabetic Rats

    PubMed Central

    Xu, Xiaohong; Xiao, Haijuan; Zhao, Jiangpei; Zhao, Tongfeng

    2012-01-01

    Reactive oxygen species (ROS) play important roles in the occurrence and development in diabetic cardiomyopathy (DC). Ferulic acid is one of the ubiquitous compounds in diet. Sodium ferulate (SF) is its sodium salt. SF has potent free radical scavenging activity and can effectively scavenge ROS. The study investigated the effect of SF on cardioprotection in diabetic rats. The diabetic rats induced by streptozotocin (STZ) were treated with SF (110mg/kg) by gavage per day for 12 weeks. Results showed that the levels of nitric oxide (NO) and superoxide dismutase (SOD) activity in plasma and myocardium in SF-treated group were significantly higher than those in diabetic control group. The levels of malondialdehyde (MDA) in plasma and myocardium in SF-treated group were significantly lower than those in diabetic control group. Expression of connective tissue growth factor (CTGF) in myocardium in SF-treated group was apparently lower than that in diabetic control group. Compared with normal control group, electron micrographs of myocardium in diabetic control group showed apparently abnormality, while that was significantly ameliorated in SF-treated group. The study demonstrated that SF has a cardioprotective effect via increasing SOD activity and NO levels in plasma and myocardium, inhibiting oxidative stress in plasma and myocardium, and inhibiting the expression of CTGF in myocardium in diabetes rats. PMID:22701336

  10. Aminoguanidine prevents impaired healing and deficient angiogenesis in diabetic rats.

    PubMed

    Teixeira, A S; Caliari, M V; Rocha, O A; Machado, R D; Andrade, S P

    1999-12-01

    The diabetic organism is unable to produce normal amount of granulation tissue which results in delayed wound healing, a significant clinical problem. In the present study, the effect of oral administration of aminoguanidine (AG), in the diabetes-induced inhibition of angiogenesis and granulation tissue formation was tested. Subcutaneous implantation of sponge discs in nondiabetic rats induced a wound repair response as determined by the amount of hemoglobin (vascular index) and granulation tissue formation (morphometric analysis) of the implants. In the streptozotocin-induced diabetic rats the predominant response indicative of healing was inhibitory. Aminoguanidine was effective in preventing in 50% the diabetes-induced inhibition of fibrovascular tissue growth in the implants, as indicated by the values of hemoglobin content and vascular growth areas of the implants. These results indicate that AG holds potential therapeutic value in the management of healing impairment of the diabetic condition.

  11. Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats.

    PubMed

    Kurtz, M; Capobianco, E; Careaga, V; Martinez, N; Mazzucco, M B; Maier, M; Jawerbaum, A

    2014-03-01

    Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

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

    PubMed

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

    2005-04-01

    Endomorphins, the endogenous, potent and selective mu-opioid receptor agonists, have been shown to decrease systemic arterial pressure (SAP) in rats. In the present study, responses to endomorphins were investigated in systemic vascular bed of alloxan-induced diabetic rats and in non-diabetic rats. Diabetes was induced by alloxan (220 mg/kg, i.p.) in male Wistar rats. At 4-5 weeks after the onset of diabetes, intravenous injections of endomorphins (1-30 nmol/kg) led to an increase of SAP and heart rate (HR) consistently and dosed-dependently. SAP increased 7.68+/-3.73, 11.19+/-4.55, 21.19+/-2.94 and 27.48+/-6.21% from the baseline at the 1, 3, 10 and 30 nmol/kg dose, respectively, of endomorphin 1 (n=4; p<0.05), and similar changes were observed in response to endomorphin 2. The hypertension could be antagonized markedly by i.p. 2 mg/kg of naloxone. On the other hand, bilateral vagotomy would attenuate the effects of hypertension and diminished the changes of HR in response to endomorphins. With diabetic rats, 6-10 weeks after the induction of diabetes, intravenous injections of endomorphins produced non-dose-related various changes in SAP, such as a single decrease, or a single increase, or biphasic changes characterized by an initial decrease followed by a secondary increase, or no change at all. These results suggest that diabetes may lead to the dysfunction of the cardiovascular system in response to endomorphins. Furthermore, the diabetic rats of 4-5 weeks after alloxan-treatment, the increase in SAP and HR caused by i.v. endomorphins might be explained by a changed effect of vagus and by a naloxone-sensitive mechanism.

  13. Serum markers for type II diabetes mellitus

    DOEpatents

    Metz, Thomas O; Qian, Wei-Jun; Jacobs, Jon M; Polpitiya, Ashoka D; Camp, II, David G; Smith, Richard D

    2014-03-18

    A method for identifying persons with increased risk of developing type 2 diabetes mellitus utilizing selected biomarkers described hereafter either alone or in combination. The present invention allows for broad based, reliable, screening of large population bases and provides other advantages, including the formulation of effective strategies for characterizing, archiving, and contrasting data from multiple sample types under varying conditions.

  14. The synergistic effect of antiglycating agents (MB-92) on inhibition of protein glycation, misfolding and diabetic complications in diabetic-atherosclerotic rat.

    PubMed

    Mahdavifard, S; Bathaie, S Z; Nakhjavani, M; Taghikhani, M

    2016-10-04

    Protein glycation due to hyperglycemia resulting in misfolding and aggregation, which is known as one of the most important reasons of diabetes complications. We previously showed the beneficial effects of some antiglycating agents in diabetic rats. Here, the effect of MB-92, a combination of some amino acids and crocetin (Crt, a saffron carotenoid), was studied in the prevention of diabetic complications in diabetic-atherosclerotic rats. In addition, the inhibitory effect of these treatments on glycation intermediates, aggregation and misfolding of proteins was investigated both in vivo and in vitro. Thus, the streptozotocin-induced diabetic rats that underwent an atherogenic diet were treated with Crt, N-acetylcyctein and MB-92. Then, glycated products and markers of oxidation and inflammation, in addition to other markers of diabetes complications were studied. The results of the in vivo study indicated that the mentioned treatments prevented the atheromatos formation, reduced the increased blood glucose; inhibited the formation of various glycation products, induced glyoxalase system (I and II), diminished oxidation and inflammatory markers, and improved lipid profile and atherosclerotic index in the diabetic-atherosclerotic rats; but MB-92 was the most effective treatment. In vitro results also confirmed that MB-92 was the most effective treatment to inhibit protein glycation and misfolding in comparison with the other treatments. In conclusion, MB-92 showed the greatest potential for inhibition of glycation and oxidation products, atheromatose plaque formation and inflammation in diabetic-atherosclerotic rats, and to control protein glycation, misfolding and aggregation in high glucose concentration; thus, it can be suggested as a new drug to prevent diabetic complications.

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

    PubMed

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

    2012-01-15

    We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy.

  16. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Kant, Vinay; Kumar, Dinesh; Kumar, Dhirendra; Prasad, Raju; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surender K

    2015-05-01

    Substance P (SP) is known to stimulate angiogenesis, fibroblasts proliferation and expressions of cytokines and growth factors involved in wound healing. However, SP level reduces in dermis in diabetics and, hence, it was hypothesized that exogenously applied SP could be helpful in improving wound healing in diabetic rats. Excision skin wound was created on the back of diabetic rats and rats were divided into three groups i.e. (i) saline-, (ii) gel- and (iii) SP-treated. Normal saline, pluronic gel and SP (10(-6)M) in gel were topically applied once daily for 19days. SP treatment significantly increased the wound closure, levels of interleukin-10, and expressions of vascular endothelial growth factor, transforming growth factor-beta1, heme oxygenase-1 and endothelial nitric oxide synthase, whereas it significantly decreased the expression of tumor necrosis factor-alpha, interleukin-1beta and matrix metalloproteinases-9 in the granulation/healing tissue. The inflammatory cells were present for long time in normal saline-treated group. Histological evaluation revealed better extracellular matrix formation with marked fibroblast proliferation and collagen deposition in SP-treated group. Early epithelial layer formation, increased microvessel density and greater growth associated protein-43 positive nerve fibers were also evidenced in SP-treated group. In conclusion, SP treatment markedly accelerated cutaneous wound healing in diabetic rats.

  17. Effects of acute diabetes on rat cutaneous wound healing.

    PubMed

    Komesu, Marilena Chinali; Tanga, Marcelo Benetti; Buttros, Kemli Raquel; Nakao, Cristiano

    2004-10-01

    INTRODUCTION:: Diabetes mellitus is a chronic hyperglycaemic disorder. Complicated metabolic mechanisms and increased incidence of infections are clinical hallmarks, mostly associated with its chronicity. There is little information about the early pathological processes in diabetes. The objective of our study was to evaluate the healing process during early phases of experimental diabetes on rat skin. METHODS:: Alloxan induced diabetic rats were used. Non-injected animals were used as control. Punch byopsies on dorsal skin had histopathological evaluation of the healing areas made on days 1, 3 and 7 post-surgery. RESULTS:: The results showed that: (1) in diabetics, the inflammation, the initial healing phase, has a slow beginning and tends to last longer; and (2) diabetic animals showed lower density of neutrophils in healing areas up to 3 days after surgery, and in addition, after day 3, when the neutrophils should leave the healing area, and be replaced by macrophages, compared to controls, diabetic animals showed higher numbers of neutrophils. PRINCIPAL CONCLUSION:: Although diabetes is a chronic progressive disease, acute diabetes can be associated to subclinical alterations, and responsible for deficiencies in defense cells and in repair tissue failures.

  18. 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.

  19. Sweet taste and diet in type II diabetes.

    PubMed

    Tepper, B J; Hartfiel, L M; Schneider, S H

    1996-07-01

    The relationship between sweet taste function and dietary intake was studied in 21 patients with type II diabetes mellitus and 16 age-, weight-, and sex-matched controls. Subjects rated the sweetness intensity and pleasantness of a series of beverage samples sweetened with sucrose: 1.5-24%, fructose: 1-18%, or aspartame: 0.25-4%. They also kept 7-day food records. No group differences were found in sweet taste perception, pleasantness ratings, daily energy intakes, or macronutrient composition of the diets. However, subjects with diabetes consumed less sucrose but 3.5 times more alternative sweeteners than did controls. Peak pleasantness ratings for the beverage samples were positively correlated with dietary sweetness content in the subjects with diabetes but not the controls. These findings suggest that in diabetes, hedonic ratings for a sweetened beverage were related to dietary sweetness intake rather than changes in sweet taste perception.

  20. 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.

  1. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Li; Deng, Yuanxiong; Yu, Sen; Lu, Shousi; Xie, Lin; Liu, Xiaodong

    2008-05-01

    Previous studies demonstrated anti-diabetic effects of berberine. However, the facts that berberine had low bioavailability and poor absorption through the gut wall indicated that berberine might exert its antihyperglycaemic effect in the intestinal tract before absorption. The purpose of this study was to investigate whether berberine attenuates disaccharidase activities and beta-glucuronidase activity in the small intestine of streptozotocin (STZ)-induced diabetic rats. Two groups of STZ-induced diabetic rats were treated with protamine zinc insulin (10 U/Kg) subcutaneously twice daily and berberine (100 mg/Kg) orally once daily for 4 weeks, respectively. Both age-matched normal rats and diabetic control rats received physiological saline only. Fasting blood glucose levels, body weight, intestinal disaccharidase and beta-glucuronidase activities in duodenum, jejunum and ileum were assessed for changes. Our findings suggested that berberine treatment significantly decreases the activities of intestinal disaccharidases and beta-glucuronidase in STZ-induced diabetic rats. The results demonstrated that the inhibitory effect on intestinal disaccharidases and beta-glucuronidase of berberine might be one of the mechanisms for berberine as an antihyperglycaemic agent.

  2. 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

  3. 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

  4. Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats.

    PubMed

    Moreira, Josimar D; Pernomian, Larissa; Gomes, Mayara S; Moreira, Rafael P; do Prado, Alejandro F; da Silva, Carlos H T P; de Oliveira, Ana M

    2016-07-15

    Diabetes mellitus is associated with reactive oxygen and nitrogen species accumulation. Behavioral stress increases nitric oxide production, which may trigger a massive impact on vascular cells and accelerate cardiovascular complications under oxidative stress conditions such as Diabetes. For this study, type-1 Diabetes mellitus was induced in Wistar rats by intraperitoneal injection of streptozotocin. After 28 days, cumulative concentration-response curves for angiotensin II were obtained in endothelium-intact carotid rings from diabetic rats that underwent to acute restraint stress for 3h. The contractile response evoked by angiotensin II was increased in carotid arteries from diabetic rats. Acute restraint stress did not alter angiotensin II-induced contraction in carotid arteries from normoglycaemic rats. However acute stress combined with Diabetes increased angiotensin II-induced contraction in carotid rings. Western blot experiments and the inhibition of nitric oxide synthases in functional assays showed that neuronal, endothelial and inducible nitric oxide synthase isoforms contribute to the increased formation of peroxynitrite and contractile hyperreactivity to angiotensin II in carotid rings from stressed diabetic rats. In summary, these findings suggest that the increased superoxide anion generation in carotid arteries from diabetic rats associated to the increased local nitric oxide synthases expression and activity induced by acute restrain stress were responsible for exacerbating the local formation of peroxynitrite and the contraction induced by angiotensin II.

  5. Berberine chloride improved synaptic plasticity in STZ induced diabetic rats.

    PubMed

    Moghaddam, Hamid Kalalian; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Goshadrou, Fatemeh; Ronaghi, Abdolaziz

    2013-09-01

    Previous studies indicated that diabetes affects synaptic transmission in the hippocampus, leading to impairments of synaptic plasticity and defects in learning and memory. Although berberine treatment ameliorates memory impairment and improves synaptic plasticity in streptozotocin (STZ) induced diabetic rats, it is not clear if the effects are pre- or post-synaptic or both. The aim of this study was to evaluate the effects of berberine chloride on short-term plasticity in inhibitory interneurons in the dentate gyrus of STZ-induced diabetic rats. Experimental groups included: The control, control berberine treated (100 mg/kg), diabetic and diabetic berberine treated (50,100 mg/kg/day for 12 weeks) groups. The paired pulse paradigm was used to stimulate the perforant pathway and field excitatory post-synaptic potentials (fEPSP) were recorded in dentate gyrus (DG). In comparison with control, paired pulse facilitation in the diabetic group was significantly increased (P < 0.01) and this effect prevented by chronic berberine treatment (50,100 mg/kg). However, there were no differences between responses of the control berberine 100 mg/kg treated and diabetes berberine treated (50 and 100 mg/kg) groups as compared to the control group. The present results suggest that the pre-synaptic component of synaptic plasticity in the dentate gyrus is affected under diabetic conditions and that berberine prevents this effect.

  6. Role of AT1 receptors in permeability of the blood-brain barrier in diabetic hypertensive rats.

    PubMed

    Awad, Azza S

    2006-09-01

    The precise mechanisms of vascular diseases in patients with diabetic hypertensive are not clearly understood. There are evidences of alteration in permeability of blood-brain barrier (BBB) in diabetic hypertensive rats. This study sought to examine the effect of candesartan on the systolic blood pressure and the brain endothelial barrier function and antioxidant enzymes in rat brain. Five groups of eight male Sprague-Dawley rats include: control group (gpI), diabetic hypertensive group (gpII), diabetic hypertensive group treated with candesartan (gpIII), diabetic hypertensive rats with epinephrine (gpIV) and diabetic hypertensive rats with epinephrine treated with candesartan (gpV). Diabetes was induced by single injection of 55 mg kg(-1) streptozotocin (STZ) i.p. Blood glucose was measured, rats with blood glucose higher than 300 mg/dl were identified as diabetic. After induction of diabetes, rats received L-NAME (0.5 mg/ml in drinking water for 1 week) starting on the day 4 after STZ injection. Systolic blood pressure (SBP) was recorded two times, at day 0 (before starting L-NAME) and at day 7 (after L-NAME treatment). Also, body weight was measured two times, at initial time (before STZ injection) and terminal (at the last day in the experiment). On the day of acute experiment, rats were anesthetized with sodium pentobarbital (35 mg/kg, i.p.). The integrity of the BBB was investigated using Evans blue (EB) dye (4 ml/kg, 2%). Epinephrine was used (40 micro g/kg) to increase the permeability of the brain. After decapitation, first the brain was removed, next homogenized and then the content of EB dye in the brain was measured. Another five groups of rats manipulated with the same manner except EB dye injection. These second group to evaluate antioxidant enzymes, reduced glutathione (GSH), lipid peroxides and superoxide dismutase (SOD) in brain homogenate. This study indicates that, in diabetic hypertensive rats, epinephrine administration leads to increase in

  7. 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.

  8. Combination therapy with losartan and L-carnitine protects against endothelial dysfunction of streptozotocin-induced diabetic rats.

    PubMed

    Sleem, Mostafa; Taye, Ashraf; El-Moselhy, Mohamed A; Mangoura, Safwat A

    2014-12-05

    Endothelial dysfunction is a critical factor during the initiation of diabetic cardiovascular complications and angiotensin II appears to play a pivotal role in this setting. The present study aimed to investigate whether the combination therapy with losartan and the nutritional supplement, L-carnitine can provide an additional protection against diabetes-associated endothelial dysfunction and elucidate the possible mechanism(s) underlying this effect. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) in rat. Effects of losartan (20 mg/kg, orally, 3 months) and L-carnitine (200 mg/kg, orally, 3 months) on tumor necrosis factor (TNF)-α, oxidative stress parameters, endothelial nitric oxide synthase expression (eNOS), and vascular function were evaluated. Our results showed a marked increase in aortic superoxide anion (O2(-)) production and serum malondialdehyde (MDA) level alongside attenuating antioxidant enzyme capacities in diabetic rats. This was associated with a significant increase in anigiotensin II type 1 receptor gene expression and TNF-α serum level of diabetic rats alongside reducing aortic eNOS gene expression and nitric oxide (NO) bioavailability. The single or combined administration of losartan and L-carnitine significantly inhibited these changes. Additionally, the vascular endothelium-dependent relaxation with acetylcholine (ACh) in aortic diabetic rat was significantly ameliorated by the single and combined administration of losartan or L-carnitine. Noteworthy, the combination therapy exhibited a more profound response over the monotherapy. Collectively, our results demonstrate that the combined therapy of losartan and L-carnitine affords additive beneficial effects against diabetes-associated endothelial dysfunction, possibly via normalizing the dysregulated eNOS and reducing the inflammation and oxidative stress in diabetic rats.

  9. Angiotensin II induces differential insulin action in rat skeletal muscle.

    PubMed

    Surapongchai, Juthamard; Prasannarong, Mujalin; Bupha-Intr, Tepmanas; Saengsirisuwan, Vitoon

    2017-03-01

    Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague-Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia. At the cellular level, insulin-stimulated glucose uptake in the soleus muscle of the ANGII-100 group was 33% lower (P < 0.05) than that in the SHAM group and was associated with increased insulin-stimulated IRS-1 Ser(307) and decreased Akt Ser(473) and AS160 Thr(642) phosphorylation and GLUT-4 expression. However, ANGII-500 infusion did not induce skeletal muscle insulin resistance or impair insulin signaling elements as initially anticipated. Moreover, we found that insulin-stimulated glucose uptake in the ANGII-500 group was accompanied by the enhanced expression of ACE2 and MasR proteins, which are the key elements in the non-classical pathway of the renin-angiotensin system. Collectively, this study demonstrates for the first time that chronic infusion with these two pressor doses of ANGII induced differential metabolic responses at both the systemic and skeletal muscle levels.

  10. Advanced glycation end products and diabetic nephropathy: a comparative study using diabetic and normal rats with methylglyoxal-induced glycation.

    PubMed

    Rodrigues, Lisa; Matafome, Paulo; Crisóstomo, Joana; Santos-Silva, Daniela; Sena, Cristina; Pereira, Paulo; Seiça, Raquel

    2014-03-01

    Hyperglycemia-related advanced glycation end product (AGE) formation is a key mechanism in diabetic nephropathy. Since methylglyoxal (MG) is a potent AGE precursor, we aimed to assess the role of MG-related AGE formation in the progression of renal damages. A comparative study between Wistar (W, normal) and Goto-Kakizaki (GK, nonobese type 2 diabetic) rats was performed at 6 and 14 months old and after 14 weeks of MG administration to 6-month-old rats. Diabetic rats showed progressive structural, biochemical, and functional alterations, including AGE, albuminuria, and tissue hypoxia, which were partially mimicked by MG administration to young GK rats. Aged Wistar rats had an impairment of some parameters, whereas MG administration caused a phenotype similar to young GK rats, including oxidative stress, impaired apoptotic and angiogenic markers, and structural lesions. MG accumulation specifically impaired several of the renal disease markers progressively observed in diabetic rats, and thus, it contributes to the progression of diabetic nephropathy.

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

    PubMed

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

    2016-10-01

    We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (P<0·05). Compared with C in the liver, REP prevented lipid accumulation (total lipid, TAG and total cholesterol, P<0·01). Liver metabolome analysis indicated that levels of metabolites associated with glycolysis, the pentose phosphate pathway and carnitine metabolism were significantly greater in the REP group than in the C group (P<0·05), suggesting activation of both glucose catabolism and fatty acid oxidation. The metabolite increases promoted by REP may contribute to suppression of liver lipid accumulation. Urinary excretion of albumin and N-acetyl-β-d-glucosaminidase was significantly reduced in rats fed REP for 8 weeks (P<0·01). In addition, there was a distinct suppression of mesangial matrix expansion and glomerular hypertrophy in response to REP (P<0·01). Thus, REP had preventive effects on obese diabetes, fatty liver and diabetic nephropathy.

  12. 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-α; interleukin, IL-6; and interleukin, IL-1β) and oxidative stress (lipid peroxidation product: LPO, superoxide dismutase: SOD, catalase: CAT, and glutathione peroxidase: GPx) were determined. The hippocampal sections were visualized for histopathological changes. Results. Administration of C. asiatica leaf aqueous extract to diabetic rats maintained near normal ATPases activity levels and prevents the increase in the levels of inflammatory and oxidative stress markers in the hippocampus. Lesser signs of histopathological changes were observed in the hippocampus of C. asiatica leaf aqueous extract treated diabetic rats. Conclusions. C. asiatica leaf protects the hippocampus against diabetes-induced dysfunction which could help to preserve memory in this condition. PMID:25161691

  13. Antihyperalgesic Activity of Rhodiola rosea in a Diabetic Rat Model.

    PubMed

    Déciga-Campos, Myrna; González-Trujano, Maria Eva; Ventura-Martínez, Rosa; Montiel-Ruiz, Rosa Mariana; Ángeles-López, Guadalupe Esther; Brindis, Fernando

    2016-02-01

    Preclinical Research Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated that R. rosea had anti-inflammatory activity in animal models, for example, carrageenan- and nystatin-induced edema in rats, possibly by inhibiting phospholipase A2 and cyclooxygenases-1 and -2. In addition, R. rosea had antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract of Rhodiola rosea (R. rosea) in a diabetic rat model. Rats were administered a single dose of streptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin-evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1-100 mg/kg, i.p.) and local (0.1-10 mg/paw into the dorsal surface of the right hind paw) administration of R. rosea ethanol extract dose-dependently reduced formalin-induced hyperalgesia in diabetic rats. The antihyperalgesic effect of R. rosea was compared with gabapentin. These results suggest that R. rosea ethanol extract may have potential as a treatment for diabetic hyperalgesia.

  14. 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 < 0.01) reduced 8-oxodGuo levels (5.4 ± 0.58 × 10(-6) dG, mean ± SEM n=9) in renal DNA and conserved FRAP values. Moreover, an inverse correlation was found between 8-oxodGuo in kidney DNA and circulating Adp levels in normoglycemic and 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.

  15. Streptozotocin-Induced Diabetic Models in Mice and Rats.

    PubMed

    Furman, Brian L

    2015-09-01

    Streptozotocin (STZ) is an antibiotic that produces pancreatic islet β-cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this unit are protocols for producing STZ-induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition.

  16. 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 α-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 β-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.

  17. Effects of enalapril, losartan, and verapamil on blood pressure and glucose metabolism in the Cohen-Rosenthal diabetic hypertensive rat.

    PubMed

    Rosenthal, T; Erlich, Y; Rosenmann, E; Cohen, A

    1997-06-01

    We undertook the present study to examine the effect of the angiotensin-converting enzyme inhibitor enalapril, the angiotensin II antagonist losartan, and calcium antagonist verapamil on systolic pressure and spontaneous blood glucose levels in rats from the Cohen-Rosenthal diabetic hypertensive strain. Genetic hypertension and diabetes developed in this strain after crossbreeding of Cohen diabetic and spontaneously hypertensive rats. The new rat strain was fed their usual copper-poor sucrose diet, which is essential for the development of this model, and for 4 weeks received either enalapril, losartan, or verapamil. Systolic pressure was reduced significantly compared with controls in all treated groups. Chronic treatment with enalapril or verapamil, but not with losartan, succeeded in lowering spontaneous blood glucose, indicating improved diabetic control. Data suggest that angiotensin-converting enzyme inhibition by enalapril, but not angiotensin II antagonism by losartan, can improve glucose metabolism in addition to its hypotensive effect in a genetic diabetic hypertensive rat strain. This confirms that the drop in glucose with converting enzyme inhibition is highly dependent on bradykinin accumulation. Data further suggest that calcium channel blockade by verapamil can also improve glucose metabolism. The question remains whether the reduction in glucose by verapamil was a result of inhibition of glucogenesis.

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

    PubMed Central

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

    2016-01-01

    Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p < 0.05). Mitochondrial superoxide increased with high glucose in Wistar SMCs (p < 0.05) with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets. PMID:27034743

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

    PubMed

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

    2016-01-01

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

  20. 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.

  1. Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat.

    PubMed

    Howarth, Frank C; Jacobson, Michael; Shafiullah, Mohamed; Adeghate, Ernest

    2008-03-01

    In vivo biotelemetry studies have demonstrated a variety of heart rhythm disturbances in type 1 diabetes mellitus. In the streptozotocin (STZ)-induced diabetic rat, these disturbances have included reductions in heart rate (HR) and heart rate variability (HRV) and an electrocardiogram that displays prolonged QRS duration and Q-T interval. The aim of this study was to investigate the chronic effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki (GK) rat. Transmitter devices were surgically implanted in the peritoneal cavity of young male GK and age-matched Wistar control rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded in rats from age 2 to 15 months. Data were acquired for 2 weeks each month. Non-fasting blood glucose, glucose tolerance and body weight were measured periodically. In GK rats, growth rate and maximal attained body weight were significantly reduced and non-fasting blood glucose was progressively increased compared with age-matched Wistar control animals. Heart rate was significantly lower in GK compared with control rats at 2, 7 and 15 months of age. At 2 months of age, HR was 316 +/- 6 beats min(-1) in GK rats compared with 370 +/- 7 beats min(-1) in Wistar control animals. There was a progressive age-dependent decline in HRV in Wistar control rats; however, HRV in GK rats did not alter significantly with age. Heart rate variability was significantly reduced in GK compared with Wistar control rats at 2 and 7 months. At 2 months of age, HRV was 28 +/- 2 beats min(-1) in GK rats compared with 38 +/- 3 beats min(-1) in Wistar control rats. Reduced HR in GK rats may be an inherited characteristic. The absence of age-dependent reductions in HRV in GK rats may be a consequence of an underlying impairment of autonomic control which manifests at early age.

  2. Type II Diabetes Mellitus in Arabic-Speaking Countries

    PubMed Central

    Badran, Mohammad; Laher, Ismail

    2012-01-01

    The global epidemic of diabetes has not spared the Arabic-speaking countries, which have some of the highest prevalence of type II diabetes. This is particularly true of the Arab Gulf, a conglomerate of high income, oil-producing countries where prevalence rates are the highest. The prevalence rates among adults of the Arabic speaking countries as a whole range between 4%–21%, with the lowest being in Somalia and the highest in Kuwait. As economic growth has accelerated, so has the movement of the populations to urban centers where people are more likely to adopt lifestyles that embrace increased high-calorie food consumption and sedentary lifestyles. These factors likely contribute to the increased prevalence of obesity and diabetes in the Arabic speaking countries. PMID:22851968

  3. [Diabetes insipidus in infancy. II. Study of eleven cases (author's transl)].

    PubMed

    de Yturriaga, R; Barrio, R; Nieto, J A; Rabadán, B; Lledó, G; Gracia, R

    1977-01-01

    Eleven cases of diabetes insipidus are revised and distributed in the following four groups: I. Idiopathic diabetes insipidus, three. II. Secondary diabetes insipidus, four. III. Nephrogenic diabetes insipidus, two. IV. Psychogenic diabetes insipidus, two. In all these cases, clinical parameters, general analysis, hydric metabolism (static and dinamic), are studied. The precocious beginning of psychogenic diabetes insipidus, and some conclusions, on a difficult case of hard diagnosis are emphasized.

  4. Antinociceptive Effect of Mirtazapine in Rats with Diabetic Neuropathy

    PubMed Central

    İNAL, Ahmet; BÜYÜKŞEKERCİ, Murat; ULUSOY, Hasan Basri

    2016-01-01

    Introduction To evaluate the antinociceptive effect of mirtazapine and the mechanisms mediating this effect in neuropathic pain in rats with diabetes. Methods The experiments were performed in Sprague Dawley rats using a hot-plate device. Streptozotocin (STZ) was administered to the rats after taking control measurements. Rats with a blood glucose level of 240 mg/dL or above in the blood specimen obtained from the tail vein 3 days after STZ administration were considered as being diabetic. Three weeks after STZ administration, the hot-plate test was performed. Compared with the control measurements, rats that exhibited >20% decrease in the second hot-plate test measurements were considered to have developed neuropathy. Drugs [mirtazapine, naloxone (opioidergic antagonist), metergoline (serotonergic antagonist), and BRL44408 (adrenergic antagonist)] and drug combinations were administered to those rats that developed neuropathy. After administrating the drugs or drug combinations, the third hot-plate test was performed. Results Mirtazapine at doses of 10 and 15 mg/kg exhibited a significant antinociceptive effect. Naloxone, metergoline, or BRL44408 alone did not cause an antinociceptive effect. However, combinations of these drugs with mirtazapine (15 mg/kg) significantly decreased the antinociceptive effect of mirtazapine. Conclusion It is suggested that mirtazapine has a significant antinociceptive effect in diabetic neuropathy and that opioidergic, serotonergic, and adrenergic systems have roles to play in this effect. PMID:28360759

  5. [Ameliorative effects on retinal disorder in diabetic SHRSP (stroke-prone spontaneously hypertensive rat)].

    PubMed

    Nagisa, Yasutaka; Shintani, Asae; Nakagawa, Shizue

    2002-10-01

    The results of the EUCLID highlighted the importance of the renin-angiotensin system in the pathogenesis of diabetic retinopathy. We aimed to evaluate the effectiveness of candesartan cilexetil(TCV-116), a potent angiotensin II receptor antagonist, in ameliorating retinal disorders in stroke-prone spontaneously hypertensive rats(SHRSP) with storeptozotocin(STZ)-induced diabetes. Retinal VEGF mRNA expression was significantly higher and the latencies of oscillatory potentials were significantly elongated in STZ-treated SHRSP compared with a non-treated SHRSP group matched for age. Treatment with TCV-116(3 mg/kg) significantly diminished retinal VEGF mRNA expression and the latencies of oscillatory potentials, but had no effect on plasma glucose concentrations. These results suggest that TCV-116 is effective in preventing the development of diabetic retinopathy already in the early stages.

  6. Ibuprofen attenuates nephropathy in streptozotocin‑induced diabetic rats.

    PubMed

    Liu, Yao-Wu; Zhu, Xia; Cheng, Ya-Qin; Lu, Qian; Zhang, Fan; Guo, Hao; Yin, Xiao-Xing

    2016-06-01

    Ibuprofen, a commonly administered nonsteroidal anti‑inflammatory therapeutic agent, is also a partial agonist of peroxisome proliferator‑activated receptor γ (PPARγ). The present study investigated the effects of ibuprofen on type 1 diabetic nephropathy (DN) in rats, and the potential mechanisms associated with the activation of PPARγ. Diabetic rats were induced through a single intraperitoneal injection of streptozotocin before oral treatment with ibuprofen or pioglitazone for 8 weeks. The 24‑h urine collection was performed for measurement of total protein content. The kidney was fixed in 10% formalin for periodic acid‑Schiff and Masson's trichrome staining. Blood and residual kidney tissue samples were collected to measure the associated biochemical parameters. Chronic ibuprofen treatment decreased urinary protein excretion, blood urea nitrogen, glomerular basement membrane thickening and renal fibrosis, which were accompanied by increases in PPARγ protein expression, glutathione (GSH) level, and superoxide dismutase (SOD) activity, decreases in cyclooxygenase 2 and inducible nitric oxide synthase protein expressions, as well as a decreased interleukin 1β (IL‑1β) level in the renal cortex of DN rats. Furthermore, the reduced IL‑1β level, increased GSH quantities and stronger SOD activity in the rat serum were evaluated in ibuprofen‑treated diabetic rats and were compared with untreated diabetic rats. Regarding GSH and IL‑1β levels, ibuprofen was identified to be superior to the positive control, pioglitazone, while levels of the other indices were identified to be similar. Thus, ibuprofen was observed to prevent the development of DN, caused by type 1 diabetes, by anti‑inflammatory and anti‑oxidative action, potentially via PPARγ activation.

  7. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Kant, Vinay; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surendra K; Kumar, Dinesh

    2014-06-01

    Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics.

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

    PubMed

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

    2014-10-01

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

  9. 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-α, 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

  10. The protective effects of DA-9801 (Dioscorea extract) on the peripheral nerves in streptozotocin-induced diabetic rats.

    PubMed

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

    2013-01-01

    It has been reported that DA-9801, an extract mixture of Dioscorea japonica Thunb and Dioscorea nipponica Makino, produces a neurotrophic activity. Therefore, this study was conducted to examine the neuroprotective effects of DA-9801 in streptozotocin-induced diabetic rats. The experimental rats were divided into six groups: the control group, Group I (non-diabetic rats treated with DA-9801), Group II (diabetic, non-treated rats) and Groups III, IV, and V (diabetic rats treated with DA-9801 at doses of 10, 50 or 100 mg/kg/d). Following a 16-wk course of oral treatment with DA-9801, functional parameters (von Frey filament test, hot plate test), biochemical parameters (nerve growth factor (NGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6) were measured. An immunohistochemical staining was done to assess the neuroprotective effects of DA-9081 in the skin, sciatic nerve, gastric mucosa and renal cortex. In Week 8, pain was evoked by either tactile or thermal stimuli, whose threshold was significantly higher in Group III, IV and V than Group II. Western blot analysis showed a more significant increase in NGF and decrease in TNF-α and IL-6 in Group III, IV and V than in Group II (p<0.05). Moreover, following the treatment with DA-9801, a loss of intraepidermal nerve fibers (IENFs) was inhibited to a significant level in the skin, myelinated axonal fibers of the sciatic nerve and small nerve fibers innervating the gastric mucosa or renal cortex (p<0.05). Our results demonstrated that DA-9801 is a beneficial agent that protects the peripheral nerves in diabetic rats.

  11. Histological changes and antidiabetic activities of Icacina trichantha tuber extract in beta-cells of alloxan induced diabetic rats

    PubMed Central

    Monday, Onakpa Michael; Uzoma, Asuzu Isaac

    2013-01-01

    Objective To investigate the antidiabetic, hypolipidaemic activities and histopathological changes of Icacina trichantha (I. trichantha) tuber extract in alloxan induced diabetic rats. Methods In the present study, 80% methanol extract of I. trichantha tuber was tested on alloxan induced diabetic rats. They were randomly grouped into control (distilled water and glibenclamide) and experimental (200, 400 and 600 mg/kg body weight). Diabetes was induced by a single intraperitoneal injection of 160 mg/kg body weight of alloxan. Blood glucose levels were measured using blood glucose test strips with AccuCheck Advantage II glucometer at 1, 3, 6, and 24 h on the first day and 1 h after treatment on Day 7, 14 and 21. Blood samples were collected and centrifuged to separate serum for estimation of lipid profile and other biochemical parameters. Histopathological changes in diabetic rats pancreas were also studied after extract treatment. Results Daily oral administration of I. trichantha tuber extract (200, 400, and 600 mg/kg body weight) and glibenclamide (2 mg/kg) showed beneficial effects on blood glucose level (P<0.01) as well as improving liver, kidney functions and hyperlipidaemia due to diabetes. The extract had a favourable effect on the histopathological changes of the pancreas in alloxan induced diabetes. Conclusions I. trichantha tuber extracts posses antidiabetic activities as well as improve liver and renal profile and total lipids levels. I. trichantha tuber extracts also have favourable effects to inhibit the histopathological changes of the pancreas in alloxan induced diabetes. PMID:23905020

  12. Effect of Urtica dioica Leaf Alcoholic and Aqueous Extracts on the Number and the Diameter of the Islets in Diabetic Rats.

    PubMed

    Qujeq, Durdi; Tatar, Mohsen; Feizi, Farideh; Parsian, Hadi; Sohan Faraji, Alieh; Halalkhor, Sohrab

    2013-01-01

    Urtica dioica has been known as a plant that decreases blood glucose. Despite the importance of this plant in herbal medicine, relatively little research has been down on effects of this plant on islets yet. The objective of the current study was to evaluate the effect of dried Urtica dioica leaf alcoholic and aqueous extracts on the number and the diameter of the islets and histological parameters in streptozocin-induced diabetic rats. Six rats were used in each group. Group I: Normal rats were administered saline daily for 8 weeks. Group II: Diabetic rats were administered streptozotocin, 50 mg/kg of body weight; Group III: Diabetic rats were administered dried Urtica dioica leaf aqueous extracts for 8 weeks; Group IV: Diabetic rats were administered dried Urtica dioica leaf alcoholic extracts for 8 weeks. The animals, groups of diabetic and normal, were sacrificed by ether anaesthesia. Whole pancreas was dissected. The tissue samples were formalin fixed and paraffin embedded for microscopic examination. Histologic examination and grading were carried out on hematoxylin-eosin stained sections. The effects of administration of dried Urtica dioica leaf alcoholic and aqueous extracts to diabetic rats were determined by histopathologic examination. The pancreas from control rats showed normal pancreatic islets histoarchitecture. Our results also, indicate that the pancreas from diabetic rats show injury of pancreas tissue while the pancreas from diabetic rats treated with dried Urtica dioica leaf alcoholic and aqueous extracts show slight to moderate rearrangement of islets. According to our findings, dried Urtica dioica leaf alcoholic and aqueous extracts can cause a suitable repair of pancreatic tissue in streptozocin-induced diabetic experimental model.

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

    PubMed

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

    2016-03-01

    Mallotus roxburghianus has long been used by Mizo tribal people for the treatment of diabetes. Scientific validation at known doses may provide information about its safety and efficacy. Methanolic leaf extract of M. roxburghianus (MRME 100 and 400mg/kg) was tested in comparison with normal and alloxan diabetic rats for 28 days p.o. in terms of body and pancreatic weight, blood glucose level, antioxidant enzymes, expression of visfatin and PCNA, histopathology and histomorphometric measurements of pancreas. The results were evaluated statistically using ANOVA, correlation and regression and Principal component analysis (PCO). MRME (100 and 400mg/kg) treatment significantly (p<0.0001) decreased the body weight, blood glucose level, improved the mass and size of pancreas, elevated the levels of antioxidant enzymes and up regulate the expression of visfatin and PCNA. PCO analysis was good to fitness and prediction distinguishes the therapeutic effects of M. roxburghianus from the alloxan induced diabetic rats. MRME has significant role in protecting animals from alloxan-induced diabetic oxidative stress in pancreas and exhibited promising antihyperglycaemic and antioxidant activities along with significant reversal of disturbed antioxidant status and lipid peroxidative damage. Pancreatic architecture and physiology under diabetic oxidative stress have been significantly modulated by MRME and validated as a drug candidate for antidiabetic treatment. M. roxburghianus treatment restores the antioxidant enzyme system and rejuvenates the islets mass in alloxanized rat by accelerating visfatin and PCNA expression in pancreatic tissue.

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

    PubMed Central

    Rosenthal, Talma; Younis, Firas; Alter, Ariela

    2010-01-01

    Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD), and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH) rats. The use of various drugs, such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs), various angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment. PMID:27713282

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

    PubMed Central

    A. Bakheet, Saleh; M. Attia, Sabry

    2011-01-01

    We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients. PMID:21941606

  16. Effect of All-Trans Retinoic Acid on the Pancreas of Streptozotocin-Induced Diabetic Rat.

    PubMed

    Eltony, Sohair A; Elmottaleb, Nashwa A; Gomaa, Asmaa M; Anwar, Mamdouh M; El-Metwally, Tarek H

    2016-03-01

    All-trans Retinoic acid (atRA) is instructive for the development of endocrine pancreas and is an integral component of β-cell induction protocols. We showed that atRA induces glucose-responsive endocrine transdifferentiation of pleomorphic pancreatic ductal adenocarcinoma cells in vitro. This study aimed to detect the role of atRA in improving the histological changes of the pancreas in diabetic rats. Forty young male Wistar rats were used and divided into three groups. Group I: normal vehicle control (N = 5). Group II: streptozotocin-induced diabetic rats (N = 20) were followed up at 0.0, 1, 2, and 4 weeks. Group III: streptozotocin-induced diabetic rats (N = 15) treated with atRA (2.5 mg/kg/day), were followed up at 1, 2, and 4 weeks. Specimens from the pancreas were processed for light, electron microscopy and pancreatic insulin mRNA expression. Blood samples were assayed for the levels of glucose, insulin, and total peroxides. In the atRA-treated group, the number of the islets and the islet area significantly increased. Strong insulin-immunoreactive endocrine-like cells were observed nearby the pancreatic acini and the interlobular ducts. Interestingly, insulin-positive cells seemed to arise from pancreatic acinar and ductal epithelium. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. Pancreatic insulin mRNA and blood indices were almost normalized. AtRA improved the histological changes of the pancreas and the blood indices in diabetic rats.

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

    SciTech Connect

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

    2009-11-15

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

  18. Increase of cardiac M2-muscarinic receptor gene expression in type-1 but not in type-2 diabetic rats.

    PubMed

    Lee, Liang-Ming; Chang, Cheng Kuei; Cheng, Kai-Chun; Kou, Dai-Huang; Liu, I-Min; Cheng, Juei-Tang

    2008-08-22

    Changes of cardiac M2-muscarinic receptor (M2-mAChR) gene expression was investigated in type-1 like diabetic rats induced by intravenous injection of streptozotocin (STZ) and type-2 like diabetic rats induced by fed with fructose-rich chow. Systolic blood pressure (SBP) in STZ-diabetic rats was significantly lower than that in age-matched non-diabetic rats, while the SBP in type-2 like diabetic rats was higher than in non-diabetic rats. Also, the mRNA or protein level of cardiac M2-mAChR in STZ-diabetic rats was markedly higher than non-diabetic rats, but it was not observed in type-2 like diabetic rats as compared to age-matched non-diabetic rats. Arecaidine propargyl ester (APE), the agonist of M2-mAChR, produced a marked reduction of heart rate in STZ-diabetic rats but made less influence on heart rate in fructose-fed rats or non-diabetic rats. The results suggest that cardiac M2-mAChR gene expression is raised in type-1 like diabetic rats but not in type-2 like diabetic rats, this difference mainly due to hyperglycemia, for the production of hypotension in diabetic disorders.

  19. Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats

    PubMed Central

    Yeom, Eunseop; Byeon, Hyeokjun; Lee, Sang Joon

    2016-01-01

    Diabetes mellitus with abnormal glucose concentration is associated with changes in hemorheological properties, endothelial function, and platelets hyperactivity. Disturbances may significantly be responsible for diabetes-related vascular complications. In this study, hemorheological and hemodynamic properties were measured according to diabetic duration after streptozotocin treatment in rats. For ex vivo measurements, an extracorporeal model was adopted. Flow rate and blood viscosity were measured using a microfluidic device. Erythrocyte aggregation and morphological parameters of erythrocytes were measured by modified erythrocyte sedimentation rate and the phase-contrast holography under in vitro conditions. The platelet aggregation and mean pressure in the femoral artery were estimated under ex vivo conditions. Hemorheological properties including blood viscosity, erythrocyte aggregation and shape parameters for the control group are significantly different with those for diabetic groups. The changes with respect to diabetic duration were relatively unnoticeable. However, the platelet aggregation is strongly dependent on the diabetic duration. Based on these results, hyperglycemia exposure may induce hemorheological variations in early stages of diabetes mellitus. High platelet aggregation may become more pronounced according to the diabetic duration caused by variations in hemorheological properties resulting in endothelial dysfunction. This study would be helpful in understanding the effects of diabetic duration on biophysical properties. PMID:26898237

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

    PubMed

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

    2011-08-01

    Mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species in response to hyperglycemia during diabetes lead to pathological consequences of hyperglycemia. The aim of the present work was to investigate the role of a specific functional damage in rat liver mitochondria during diabetes as well as to evaluate the possibility of metabolic and antioxidative correction of mitochondrial disorders by pharmacological doses of succinate and melatonin. In rat liver mitochondria, streptozotocin-induced diabetes was accompanied by marked impairments of metabolism: we observed a significant activation of α-ketoglutarate dehydrogenase (by 60%, p<0.05) and a damage of the respiratory function. In diabetic animals, melatonin (10 mg/kg b.w., 30 days) or succinate (50 mg/kg b.w., 30 days) reversed the oxygen consumption rate V(3) and the acceptor control ratio to those in nondiabetic animals. Melatonin enhanced the inhibited activity of catalase in the cytoplasm of liver cells and prevented mitochondrial glutathione-S-transferase inhibition while succinate administration prevented α-ketoglutarate dehydrogenase activation. The mitochondria dysfunction associated with diabetes was partially remedied by succinate or melatonin administration. Thus, these molecules may have benefits for the treatment of diabetes. The protective mechanism may be related to improvements in mitochondrial physiology and the antioxidative status of cells.

  1. Hepatoprotetive, Cardioprotective and Nephroprotective Actions of Essential Oil Extract of Artemisia sieberi in Alloxan Induced Diabetic Rats

    PubMed Central

    Irshaid, Fawzi; Mansi, Kamal; Bani-Khaled, Ahmad; Aburjia, Talal

    2012-01-01

    The aim of the current study is to evaluate the potential mechanism of antidiabetic action of the essential oil of Artemisia sieberi and its effects on some hematological and biochemical parameters in alloxan induced diabetic rats. Extraction of the essential oil from aerial parts of A. sieberi was preformed by hydrodistillation. Fifty rats were divided into five groups. Groups I and II normal rats given 1 mL/day of dimethyl sulfoxide and 80 mg/kg BW of this oil extract, respectively. Groups III, IV and V diabetic rats given 1 mL/day of dimethyl sulfoxide, oil extract (80 mg/kg BW) and metformin (14.2 mg/kg BW), respectively. Several hematological and biochemical parameters were assessed. Oral administration of the extract resulted in a significant reduction in the mean values of blood glucose, glucagon, cholesterol, triglyceride, LDL-C, ESR, urea, uric acid, creatinine accompanied by an increase in the mean values of the total protein, albumin, insulin, HDL-C, neutrophile count and PCV in diabetic rats. No significant changes in these parameters were found in the control group. The effects produced by this extract were closely similar to a standard antidiabetic drug, metformin. In conclusion, the present study indicates that the essential oil extract of A. sieberi appears to exhibit cardioprotective, nephroprotective and hepatoprotective activities in alloxan induced diabetic rats. PMID:24250557

  2. Sulfur amino acid metabolism in Zucker diabetic fatty rats.

    PubMed

    Kwak, Hui Chan; Kim, Young-Mi; Oh, Soo Jin; Kim, Sang Kyum

    2015-08-01

    The present study was aimed to investigate the metabolomics of sulfur amino acids in Zucker diabetic fatty (ZDF) rats, an obese type 2 diabetic animal model. Plasma levels of total cysteine, homocysteine and methionine, but not glutathione (GSH) were markedly decreased in ZDF rats. Hepatic methionine, homocysteine, cysteine, betaine, taurine, spermidine and spermine were also decreased. There are no significant difference in hepatic S-adenosylmethionine, S-adenosylhomocysteine, GSH, GSH disulfide, hypotaurine and putrescine between control and ZDF rats. Hepatic SAH hydrolase, betaine-homocysteine methyltransferase and methylene tetrahydrofolate reductase were up-regulated while activities of gamma-glutamylcysteine ligase and methionine synthase were decreased. The area under the curve (AUC) of methionine and methionine-d4 was not significantly different in control and ZDF rats treated with a mixture of methionine (60mg/kg) and methionine-d4 (20mg/kg). Moreover, the AUC of the increase in plasma total homocysteine was comparable between two groups, although the homocysteine concentration curve was shifted leftward in ZDF rats, suggesting that the plasma total homocysteine after the methionine loading was rapidly increased and normalized in ZDF rats. These results show that the AUC of plasma homocysteine is not responsive to the up-regulation of hepatic BHMT in ZDF rats. The present study suggests that the decrease in hepatic methionine may be responsible for the decreases in its metabolites, such as homocysteine, cysteine, and taurine in liver and consequently decreased plasma homocysteine levels.

  3. Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes

    PubMed Central

    Matsumoto, Yasuhiko; Ishii, Masaki; Hayashi, Yohei; Miyazaki, Shinya; Sugita, Takuya; Sumiya, Eriko; Sekimizu, Kazuhisa

    2015-01-01

    We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1 h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18 h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes. PMID:26024298

  4. Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes.

    PubMed

    Matsumoto, Yasuhiko; Ishii, Masaki; Hayashi, Yohei; Miyazaki, Shinya; Sugita, Takuya; Sumiya, Eriko; Sekimizu, Kazuhisa

    2015-05-29

    We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1 h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18 h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes.

  5. Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats.

    PubMed

    Jatobá, Carlos André Nunes; de Rezende, Adriana Augusto; de Paiva Rodrigues, Sarah Jane; de Almeida Câmara, Maria Margareth; das Graças Almeida, Maria; Freire-Neto, Francisco; da Rocha, Luiz Reginaldo Menezes; da Medeiros, Aldo Cunha; Brandão-Neto, José; de Carvalho Formiga, Maria Célia; de Azevedo, Italo Medeiros; de Oliveira Ramos, Ana Maria

    2008-04-01

    Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.

  6. 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

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

    PubMed

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

    2015-09-01

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

  8. Molecular changes evoked by triethylenetetramine treatment in the extracellular matrix of the heart and aorta in diabetic rats.

    PubMed

    Gong, Deming; Lu, Jun; Chen, Xiuyin; Choong, Soon Y; Zhang, Shaoping; Chan, Yih-Kai; Glyn-Jones, Sarah; Gamble, Gregory D; Phillips, Anthony R J; Cooper, Garth J S

    2006-12-01

    Most patients with diabetes die from cardiac or arterial disease, for which there are limited therapeutic options. Free Cu(2+) ions are strongly pro-oxidant, and chelatable-Cu(II) is increased in the diabetic heart. We reported previously that treatment by Cu(II)-selective chelation with triethylenetetramine (TETA) evokes elevated urinary Cu(II) in diabetic rats and humans in whom it also improved hallmarks of established left ventricular (LV) disease. Here, we treated diabetic rats with TETA and evaluated its ability to ameliorate Cu(2+)-mediated LV and arterial damage by modifying the expression of molecular targets that included transforming growth factor (TGF)-beta1, Smad4, extracellular matrix (ECM) proteins, extracellular superoxide dismutase (EC-SOD), and heparan sulfate (HS). Eight-weeks of TETA treatment significantly improved cardiac diastolic function but not [glucose](plasma) in diabetic animals. LV and aortic mRNAs corresponding to TGF-beta1, Smad4, collagen types I, III, and IV, and fibronectin-1, and plasminogen activator inhibitor-1, were elevated in untreated diabetic animals and normalized after TETA treatment. EC-SOD mRNA and protein, and [HS](tissue) were significantly decreased in diabetes and restored by drug treatment. Candidate molecular mechanisms by which TETA could ameliorate diabetic cardiac and arteriovascular disease include the suppression of an activated TGF-beta/Smad signaling pathway that mediates increased ECM gene expression and restoration of normal EC-SOD and HS regulation. These findings are relevant to the restoration toward normal by TETA treatment of cardiac and arterial structure and function in diabetes.

  9. Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography–tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Lee, Jong Cheol; Kim, Il Yong; Son, Yeri; Byeon, Seul Kee; Yoon, Dong Hyun; Son, Jun Seok; Song, Han Sol; Song, Wook; Seong, Je Kyung; Moon, Myeong Hee

    2016-07-01

    We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography–tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of

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

    PubMed Central

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

    2017-01-01

    Background Obesity is associated with a decrease in mortality in the intensive care unit (ICU) (the "obesity paradox"). We hypothesized that obesity may paradoxically improve diaphragmatic function. Methods Diaphragm contractility was prospectively recorded in vitro in adult male Zucker lean (control), fatty, and diabetic fatty rats, at rest, after 12h mechanical ventilation and after fatigue. We analyzed diaphragm morphology, cytokines, and protein expression of the protein kinase signaling pathways. Results Diaphragm active-force (AF) was higher in fatty (96±7mN.mm-2,P = 0.02) but not in diabetic fatty rats (90±17mN.mm-2) when compared with controls (84±8mN.mm-2). Recovery from fatigue was improved in fatty and diabetic fatty groups compared with controls. Ventilator-induced diaphragmatic dysfunction was observed in each group, but AF remained higher in fatty (82±8mN.mm-2,P = 0.03) compared with controls (70±8mN.mm-2). There was neutral lipid droplet accumulation in fatty and diabetic fatty. There were shifts towards a higher cross-sectional-area (CSA) of myosin heavy chain isoforms (MyHC)-2A fibers in fatty and diabetic fatty compared with control rats (P = 0.002 and P<0.001, respectively) and a smaller CSA of MyHC-2X in fatty compared with diabetic fatty and control rats (P<0.001 and P<0.001, respectively). The phosphorylated total-protein-kinase-B (pAKT)/AKT ratio was higher in fatty (182±58%,P = 0.03), but not in diabetic fatty when compared with controls and monocarboxylate-transporter-1 was higher in diabetic fatty (147±36%,P = 0.04), but not in fatty. Conclusions Diaphragmatic force is increased in Zucker obese rats before and after mechanical ventilation, and is associated with activation of AKT pathway signaling and complex changes in morphology. PMID:28328996

  11. Hypoglycemic effect of syringin from Eleutherococcus senticosus in streptozotocin-induced diabetic rats.

    PubMed

    Niu, Ho-Shan; Liu, I-Min; Cheng, Juei-Tang; Lin, Che-Ling; Hsu, Feng-Lin

    2008-02-01

    Eleutherococcus senticosus (Araliaceae ) is a very powerful adaptogenic agent. In the present study, the effects of syringin, an active principle of this herb, on plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats) were investigated. Thirty minutes after syringin was intravenously injected into fasting STZ-diabetic rats, plasma glucose levels dose-dependently decreased. In normal rats, syringin at the effective dose (1.0 mg/kg) significantly attenuated the increase in plasma glucose caused by an intravenous glucose challenge. Syringin dose-dependently (0.01 to 10.0 micromol/L) stimulated glucose uptake in soleus muscle isolated from STZ-diabetic rats. Syringin treatment of hepatocytes isolated from STZ-diabetic rats enhanced glycogen synthesis . The ability of syringin to enhance glucose utilization and lower plasma glucose level in rats suffering from insulin deficiency suggest that this chemical may be useful in the treatment of human diabetes.

  12. Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic fatty rats

    PubMed Central

    SARIKAPHUTI, ARIYA; NARARATWANCHAI, THAMTHIWAT; HASHIGUCHI, TERUTO; ITO, TAKASHI; THAWORANUNTA, SITA; KIKUCHI, KIYOSHI; OYAMA, YOKO; MARUYAMA, IKURO; TANCHAROEN, SALUNYA

    2013-01-01

    The mulberry plant (Morus alba L.) contains abundant anthocyanins (ANCs), which are natural antioxidants. The aim of this study was to determine the ANC composition of Thai Morus alba L. fruits and to assess the effect of an ANC extract on blood glucose and insulin levels in male leptin receptor-deficient Zucker diabetic fatty (ZDF) rats. The major components of the ANC extract were identified by high-performance liquid chromatography-electrospray ionization-mass spectrometry. ZDF and lean rats were treated with 125 or 250 mg ANCs/kg body weight, or 1% carboxymethylcellulose (CMC) twice daily for 5 weeks. Neither ANC dose had an effect on body weight. Following 5 weeks of treatment, glucose levels were observed to increase from 105.5±8.7 to 396.25±21 mg/dl (P<0.0001) in the CMC-treated ZDF rats; however, the glucose levels were significantly lower in the rats treated with 125 or 250 mg/kg ANCs (228.25±45 and 131.75±10 mg/dl, respectively; P<0.001 versus CMC). The administration of 250 mg/kg ANCs normalized glucose levels in the ZDF rats towards those of the lean littermates. Insulin levels were decreased significantly in the ZDF rats treated with CMC or 125 mg/kg ANCs (P<0.0001), but not in the rats treated with 250 mg/kg ANCs. Histologically, 250 mg/kg ANCs was observed to prevent islet degeneration compared with the islets in CMC-treated rats. This study, demonstrated that ANCs extracted from Morus alba L. were well tolerated and exhibited effective anti-diabetic properties in ZDF rats. ANCs represent a promising class of therapeutic compounds that may be useful in the prevention of type 2 diabetes. PMID:24137248

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

    PubMed

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

    2014-10-17

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

  14. Pharmacological Evaluation of Chrozophora tinctoria as Wound Healing Potential in Diabetic Rat's Model

    PubMed Central

    Semwal, Monika; Dubey, Susheel Kumar

    2016-01-01

    Objective. The study was designed to evaluate pharmacological potential of hydroalcoholic leaves extract of Chrozophora tinctoria intended for wound healing in diabetic rats' model. Methods. The method used to evaluate the pharmacological potential of hydroalcoholic leave extract was physical incision rat model. In this model, cutting of the skin and/or other tissues with a sharp blade has been made and the rapid disruption of tissue integrity with minimal collateral damage was observed shortly. Animals used in the study were divided into four groups that consist of six animals in each group. Group I serves as normal control, Group II serves as disease control, Group III was used as standard treatment (Povidone iodine 50 mg/kg b.w.), and Group IV was used for test drug (C. tinctoria 50 mg/kg b.w.). Result. The hydroalcoholic leave extract of Chrozophora tinctoria has been significantly observed to heal the wound (98%) in diabetic rats within 21 days, while standard drug (Povidone iodine) healed the wound about 95% in the same condition. The oral dose (50 mg/kg b.w.) of Chrozophora tinctoria was also found to improve the elevated blood glucose level in comparison to disease control group, which increased after the oral administration of Streptozotocin. Conclusion. The Chrozophora tinctoria has significant wound healing potential in the animal having physically damaged tissue in diabetic condition. PMID:28097147

  15. Metformin restores endothelial function in aorta of diabetic rats

    PubMed Central

    Sena, Cristina M; Matafome, Paulo; Louro, Teresa; Nunes, Elsa; Fernandes, Rosa; Seiça, Raquel M

    2011-01-01

    BACKGROUND AND PURPOSE The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus. EXPERIMENTAL APPROACH Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high-fat diet during 4 months were treated with metformin for 4 weeks before evaluation. Systemic oxidative stress, endothelial function, insulin resistance, nitric oxide (NO) bioavailability, glycation and vascular oxidative stress were determined in the aortic rings of the different groups. A pro-inflammatory biomarker the chemokine CCL2 (monocyte chemoattractant protein-1) was also evaluated. KEY RESULTS High-fat fed GK rats with hyperlipidaemia showed increased vascular and systemic oxidative stress and impaired endothelial-dependent vasodilatation. Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta. CONCLUSION AND IMPLICATIONS Metformin restores endothelial function and significantly improves NO bioavailability, glycation and oxidative stress in normal and high-fat fed GK rats. This supports the concept of the central role of metformin as a first-line therapeutic to treat diabetic patients in order to protect against endothelial dysfunction associated with type 2 diabetes mellitus. PMID:21250975

  16. Effects of decompression on behavioral, electrophysiologic, and histomorphologic recovery in a chronic sciatic nerve compression model of streptozotocin-induced diabetic rats

    PubMed Central

    Wang, Ping-Hui; Yang, Cheng-Chang; Su, Wei-Ren; Wu, Po-Ting; Cheng, Shun-Chien; Jou, I-Ming

    2017-01-01

    Purpose To determine susceptibility to decompression surgery in diabetic and nondiabetic peripheral neuropathy using a chronic compression neuropathy model. Materials and methods Twenty-four streptozotocin-induced diabetic rats were randomly divided into three groups: group I, chronic compression of the left sciatic nerve for 4 weeks with decompression; group II, similar without decompression; and group III, sham exposing the sciatic nerve only. The other 24 nondiabetic rats were assigned to groups IV–VI, which received compression–decompression, compression, and the sham operation, respectively. Mixed-nerve-elicited somatosensory evoked potentials (M-SSEPs) and compound muscle action potentials (CMAPs) were measured to verify the compression neuropathy in the posttreatment follow-up. Behavioral observations in thermal hyperalgesia tests were quantified before electrophysiologic examinations. Treated and contralateral nerves were harvested for histomorphologic analysis. Results Chronic compression of sciatic nerve induced significant reduction of amplitude and increment of latency of M-SSEP and CMAP in both diabetic and nondiabetic rats. Diabetic group changes were more susceptible. Decompression surgery significantly improved both sensory and motor conduction, thermal hyperalgesia, and the mean myelin diameter of the rat sciatic nerve in both diabetic and nondiabetic groups. Near full recovery of motor and sensory function occurred in the nondiabetic rats, but not in the diabetic rats 8 weeks postdecompression. Conclusion Behavioral, electrophysiologic, and histomorphologic findings indicate that decompression surgery is effective in both diabetic and nondiabetic peripheral neuropathy. PMID:28360533

  17. Pharmacological Evaluation of “Sugar Remedy,” A Polyherbal Formulation, on Streptozotocin-Induced Diabetic Mellitus in Rats

    PubMed Central

    Singhal, Sandeep; Rathore, Arvind Singh; Lohar, Vikram; Dave, Rakesh; Dave, Jeetesh

    2014-01-01

    In the present study, Sugar Remedy, a polyherbal formulation (manufactured by Umalaxmi Organics Pvt Ltd, Jodhpur, Rajasthan, India) was evaluated for its antihyperglycemic, antihyperlipidemic, and antioxidant effects against normal and streptozotocin (STZ)-induced diabetic rats. Type II diabetes was induced in male Wistar rats by administration of a single intraperitoneal (IP) injection of STZ at a dose of 60 mg/kg. Effects of three different doses of Sugar Remedy suspension (185, 370, and 740 mg/kg/day, orally) and Metformin (500 mg/kg/day, orally) administered for 21 days were studied on parameters such as blood glucose, lipid profile, and antioxidant levels. Results were analyzed using one-way analysis of variance (ANOVA) followed by Dunnett's test. No significant changes were noticed in blood glucose, serum lipid levels, and kidney parameters in normal rats treated with Sugar Remedy suspension alone. The efficacy of Sugar Remedy as an antihyperglycemic, antihyperlipidemic, and antioxidant agent in STZ-induced diabetes was comparable to that of the standard, 500 mg/kg of Metformin. Present findings provide experimental evidence that Sugar Remedy has significant antihyperglycemic, antihyperlipidemic, and antioxidative effects in diabetic experimental rats. Hence, Sugar Remedy may be regarded as a promising natural and safe remedy for the prevention or delay of diabetic complications. PMID:25161924

  18. In Vivo Evaluation of Anti Diabetic, Hypolipidemic, Antioxidative Activities of Saudi Date Seed Extract on Streptozotocin Induced Diabetic Rats

    PubMed Central

    Mohieldein, Abdelmarouf

    2016-01-01

    Introduction Phoenix dactylifera (date palm) is major fruit of gulf region. In folk medicine; dates have been traditionally use. The date seed is used as hypoglycaemic, expectorant, tonic, aphrodisiac, antidiarrheic and mouth hygiene. Aim This study intended to evaluate the anti-diabetic, hypolipidaemic and antioxidative activities of date seed extract in diabetes-induced rats. Materials and Methods Total of seven groups of rats, consisting of control rats and streptozotocin induced diabetic rats treated with aqueous seed extract in concentration of 100g/L in dosage of 10ml/day/rat. To evaluate the anti-diabetic property, glucose and weight was analysed weekly and at the end of eight week all rats were sacrificed. To evaluate the hypolipidaemic and antioxidative activities, serum cholesterol, triglyceride, malondialdehyde, superoxide dismutase, 8-hydroxy-2’-deoxyguanosine were estimated. Liver enzymes and kidney function tests were performed. Moreover to verify the glycaemic effect; glycated haemoglobin and serum insulin was performed. Results Aqueous seed extract in concentration of 100 gm/L in dosage of 10ml/day/rat brings a significant reduction of blood glucose levels in diabetic rats in comparison of control rats. There were significant differences in the investigated clinical chemistry and oxidative stress parameters between control and diabetic rats with both seed extract of Ajwa and Sukkari dates. Conclusion Present study verifies the antidiabetic property, of aqueous seed extracts of two different varieties of dates namely Ajwa and Sukkari of Kingdom of Saudi on streptozotocin induced Diabetic rats. Prolong treatments with the extract restores the function of liver and kidney and balance the oxidative stress condition in diabetic treated rats. PMID:27134893

  19. Anti-diabetic Effect of Fermented Milk Containing Conjugated Linoleic Acid on Type II Diabetes Mellitus

    PubMed Central

    Yang, Hee-Sun; Lee, Sang-Cheon; Huh, Chang-Ki

    2016-01-01

    Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has been reported to be able to reduce body fat. In this study, we investigated the antidiabetic effect of fermented milk (FM) containing CLA on type II diabetes db/db mice. Mice were treated with 0.2% low FM, 0.6% high FM, or Glimepiride (GLM) for 6 wk. Our results revealed that the body weight and the levels of fasting blood glucose, serum insulin, and leptin were significantly decreased in FM fed mice compared to db/db mice. Oral glucose tolerance and insulin tolerance were significantly ameliorated in FM fed mice compared to db/db mice. Consistent with these results, the concentrations of serum total cholesterol, triglycerides, and LDL cholesterol were also significantly decreased in FM fed mice compared to db/db mice. However, the concentration of HDL cholesterol was significantly higher in FM fed mice compared to db/db mice. These results were similar to those of GLM, a commercial anti-diabetic drug. Therefore, our results suggest that FM has anti-diabetic effect as a functional food to treat type II diabetes mellitus. PMID:27194924

  20. Catechin Treatment Ameliorates Diabetes and Its Complications in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh

    2017-01-01

    Context: Diabetes mellitus causes atherosclerosis and lipid abnormalities. Hypolipidemic and antioxidative properties of catechin (CTN) have been reported in several studies. Objective: This study assesses the possible protective effects of CTN against oxidative damage in the diabetic rats. Materials and Methods: The rats were divided into the control, untreated diabetic, and 3 CTN-treated diabetic groups (20, 40, and 80 mg/kg/d, intraperitoneal). The diabetic rats were induced by streptozotocin. Catechin was injected for 4 weeks. At the end of the experimental period, glucose, lipid profile, apoprotein A-I (apo A-I), apoprotein B (apo B), malondialdehyde (MDA) levels, and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in serum. Statistical analyses were performed using the InStat 3.0 program. Results: Streptozotocin caused an elevation of glucose, MDA, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apo B with reduction in high-density lipoprotein cholesterol (HDL-C), apo A-I, SOD, CAT, and GST in the serum (P < .05). The findings showed that the significant elevation in the body weight, glucose, MDA, TG, TC, LDL-C, and apo B and reduction in HDL-C, apo A-I, SOD, CAT, and GST were ameliorated in the CTN-treated diabetic groups versus the untreated group, in a dose-dependent manner (P < .05). Conclusion: The present investigation proposes that CTN may ameliorate diabetes and its complications by modification of oxidative stress. PMID:28228702

  1. 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.

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

    SciTech Connect

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

    1985-05-01

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

  3. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats

    PubMed Central

    2011-01-01

    Background Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD). Aim of the study The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Methods Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised. Results The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Conclusion Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats. PMID:21569626

  4. Elevation of circulating LOX-1 ligand levels in Zucker obese and diabetic rats.

    PubMed

    Wakabayashi, Ichiro; Shimomura, Tomoko; Nakanishi, Mamoru; Uchida, Kagehiro

    2015-01-01

    LOX-1 ligands containing apolipoprotein B (LAB) reflect ligand activity of LOX-1, which is a key molecule for initiation of atherosclerosis. The Zucker rat is a well-known model used for research on obesity and diabetes. Blood levels of LAB were compared among Zucker fatty (ZF), Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. Log-transformed LAB was significantly higher in ZF and ZDF rats than in control ZL rats, while no significant difference was found in log-transformed LAB of ZF and ZDF rats. This study for the first time demonstrated that circulating LOX-1 ligands were elevated in obesity and diabetes model rats.

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

    PubMed Central

    Tufiño, Cecilia; Villanueva-López, Cleva; Ibarra-Barajas, Maximiliano; Bracho-Valdés, Ismael; Bobadilla-Lugo, Rosa Amalia

    2014-01-01

    Diabetic conditions increase vascular reactivity to angiotensin II in several studies but there are scarce reports on cardiovascular effects of hypercaloric diet (HD) induced gestational diabetes mellitus (GDM), so the objective of this work was to determine the effects of HD induced GDM on vascular responses. Angiotensin II as well as phenylephrine induced vascular contraction was tested in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4 before and 3 weeks during pregnancy) with standard (SD) or hypercaloric (HD) diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired vasoconstrictor response (P < 0.05 versus SD) in intact (e+) but not in endothelium-free (e−) vessels. Losartan reduced GDM but not SD e− vasoconstriction (P < 0.01 versus SD). AT1R, AT2R, and COX-1 and COX-2 protein expression were significantly increased in GDM vessels (P < 0.05 versus SD). Results suggest an increased participation of endothelium vasodilator mediators, probably prostaglandins, as well as of AT2 vasodilator receptors as a compensatory mechanism for vasoconstrictor changes generated by experimental GDM. Considering the short term of rat pregnancy findings can reflect early stage GDM adaptations. PMID:25610861

  6. Tissue-specific up-regulation of arginase I and II induced by p38 MAPK mediates endothelial dysfunction in type 1 diabetes mellitus

    PubMed Central

    Pernow, J; Kiss, A; Tratsiakovich, Y; Climent, B

    2015-01-01

    Background and Purpose Emerging evidence suggests a selective up-regulation of arginase I in diabetes causing coronary artery disease; however, the mechanisms behind this up-regulation are still unknown. Activated p38 MAPK has been reported to increase arginase II in various cardiovascular diseases. We therefore tested the role of p38 MAPK in the regulation of arginase I and II expression and its effect on endothelial dysfunction in diabetes mellitus. Experimental Approach Endothelial function was determined in septal coronary (SCA), left anterior descending coronary (LAD) and mesenteric (MA) arteries from healthy and streptozotocin-induced diabetic Wistar rats by wire myographs. Arginase activity and protein levels of arginase I, II, phospho-p38 MAPK and phospho-endothelial NOS (eNOS) (Ser1177) were determined in these arteries from diabetic and healthy rats treated with a p38 MAPK inhibitor in vivo. Key Results Diabetic SCA and MA displayed impaired endothelium-dependent relaxation, which was prevented by arginase and p38 MAPK inhibition while LAD relaxation was not affected. Arginase I, phospho-p38 MAPK and eNOS protein expression was increased in diabetic coronary arteries. In diabetic MA, however, increased expression of arginase II and phospho-p38 MAPK, increased arginase activity and decreased expression of eNOS were observed. All these effects were reversed by p38 MAPK inhibition. Conclusions and Implications Diabetes-induced activation of p38 MAPK causes endothelial dysfunction via selective up-regulation of arginase I expression in coronary arteries and arginase II expression in MA. Therefore, regional differences appear to exist in the arginase isoforms contributing to endothelial dysfunction in type 1 diabetes mellitus. PMID:26140333

  7. 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.

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

    PubMed

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

    2012-03-01

    The aim of this study was to investigate the effects of melatonin on glucose homeostasis in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups, each composed of ten rats: naive (N), vehicle treated (V), and melatonin treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. ZDF rats developed DM (fasting hyperglycemia, 460±39.8mg/dL; HbA(1) c 8.3±0.5%) with both insulin resistance (HOMA-IR 9.28±0.9 versus 1.2±0.1 in ZL) and decreased β-cell function (HOMA1-%B) by 75%, compared with ZL rats. Melatonin reduced fasting hyperglycemia by 18.6% (P<0.05) and HbA(1) c by 11% (P<0.05) in ZDF rats. Also, melatonin lowered insulinemia by 15.9% (P<0.05) and HOMA-IR by 31% (P<0.01) and increased HOMA1-%B by 14.4% (P<0.05). In addition, melatonin decreased hyperleptinemia by 34% (P<0.001) and raised hypoadiponectinemia by 40% (P<0.001) in ZDF rats. Moreover, melatonin reduced serum free fatty acid levels by 13.5% (P<0.05). These data demonstrate that oral melatonin administration ameliorates glucose homeostasis in young ZDF rats by improving both insulin action and β-cell function. These observations have implications on melatonin's possible use as a new pharmacologic therapy for improving glucose homeostasis and of obesity-related T2DM, in young subjects.

  9. Intestinal transport of sugars and amino acids in diabetic rats

    PubMed Central

    Olsen, Ward A.; Rosenberg, Irwin H.

    1970-01-01

    The specificity and mechanism of altered intestinal transport of diabetic rats was studied with an everted ring technique. Increased intracellular accumulation of amino acids, as well as galactose and 3-O-methylglucose, was demonstrated in diabetes. The greater accumulation by diabetic intestine could not be attributed to a direct effect of the agent used to induce diabetes or to an alteration in food consumption. Although the changes were related to the severity of diabetes and could be reversed with treatment with insulin, they could not be modified by addition of insulin in vitro. The changes could not be induced in control intestine either with hyperglycemia from glucose infusion or preincubation with glucose in vitro. Although the higher concentration gradients of amino acids, galactose, and 3-O-methylglucose could result from increased energy utilization by diabetic intestine, an alteration of cell membrane function, as well, is suggested by the demonstration with kinetic studies of increased influx with an increase in Vmax. PMID:5409812

  10. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    PubMed Central

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID:27190533

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

    PubMed

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

    2016-08-09

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

  12. Histopathological changes in liver, kidney and muscles of pesticides exposed malnourished and diabetic rats.

    PubMed

    Benjamin, Nidhi; Kushwah, Ameeta; Sharma, R K; Katiyar, A K

    2006-03-01

    Histopathological changes were observed in liver, kidney and muscles of normal, protein-malnourished, diabetic as well as both protein-malnourished and diabetic albino rats when exposed to a mixture of monocrotophos, hexachlorocyclohexane and endosulfan at varying intervals. The examination revealed hepatotoxic, nephrotoxic and muscular necrotic effects in pesticides exposed rats. Toxicity was aggravated in protein-malnourished and diabetic animals and more so, if the animals were both diabetic and protein-malnourished.

  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 (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  14. 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 (ΔΨm), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress. PMID:26180820

  15. Proteoglycans in bones of streptozotocin-induced diabetic rats.

    PubMed

    Perez, C; Suarez, C; Kofoed, J

    1990-01-01

    Insulin seems to regulate the biosynthesis of proteoglycans in some tissues such as growth plate and glomeruli. The present investigation was undertaken to assess the ex vivo influence of insulin on proteoglycan metabolism in bones. Mandible and femur bones were used. Xiphoid cartilage was used as a control tissue of high glycosaminoglycan content. Diabetes was induced by 0.12 mg/g b.w. streptozotocin in male Sprague-Dawley rats, a number of which was treated with insulin (1 I.U./100 g b.w.) for 6 days. As compared with control animals, diabetic rats exhibited a decreased [35S]sulfate uptake as well as a shift to the right in Sephacryl S-500 chromatography. In addition, they showed lower density of proteoglycans in sucrose gradient and shorter glycosaminoglycan side chains in Sephadex G-200 chromatography. These changes were partly reversed by insulin.

  16. Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction.

    PubMed

    Elsner, Matthias; Terbish, Taivankhuu; Jörns, Anne; Naujok, Ortwin; Wedekind, Dirk; Hedrich, Hans-Jürgen; Lenzen, Sigurd

    2012-05-01

    Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5-7 days after the virus injection of 7 × 10(9) INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50-100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic β-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach.

  17. Decreased Neuronal Bursting and Phase Synchrony in the Hippocampus of Streptozotocin Diabetic Rats

    PubMed Central

    Xie, Kangning; Li, Guoliang

    2014-01-01

    Diabetic encephalopathy is one of the complications of diabetes. Cognitive dysfunction is the main consequence. Previous findings from neuroanatomical and in vitro electrophysiological studies showed that the structure and function of the hippocampus is impaired in diabetes, which may underlie the cognitive dysfunction induced by diabetes. However the study of electrophysiological abnormality of hippocampal neurons in intact networks is sparse. In the current study, we recorded the spontaneous firing of neurons in hippocampal CA1 area in anesthetized streptozotozin (STZ)-diabetic and age-matched control rats. Profound reduction in burst activity was found in diabetic rats. Compared to control rats, the intra-burst inter-spike intervals were prolonged significantly in diabetic rats, while the burst ratio and the mean number of spikes within a burst decreased significantly. Treatment with APP 17-mer peptide retarded the effects of diabetes on these parameters. In addition, the average PLV of diabetic rats was lower than that of control rats. These findings provide in vivo electrophysiological evidence for the impairment of hippocampal function in STZ-diabetic rats, and may have some implications in the mechanisms associated with cognitive deficits in diabetes. PMID:25093193

  18. Effect of L-carnitine treatment on lipid metabolism and cardiac performance in chronically diabetic rats.

    PubMed

    Rodrigues, B; Xiang, H; McNeill, J H

    1988-10-01

    The beneficial effects of L-carnitine administration were studied in vivo in isolated perfused working hearts from control and diabetic rats. Control and streptozocin-induced diabetic (STZ-D) rats were treated daily for 6 wk with high-dose L-carnitine (3 g.kg-1.day-1 i.p.). STZ-D results in loss of body weight and hypoinsulinemia. These effects were not altered by L-carnitine treatment. Myocardial free-carnitine levels were decreased in the untreated diabetic rats. L-Carnitine treatment of the diabetic rats increased myocardial free-carnitine levels, which were comparable with those of control rats. Six weeks after STZ administration, hearts from untreated diabetic animals exhibited depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with control animals. However, this depression was not seen in the L-carnitine-treated diabetic animals. L-Carnitine treatment of diabetic rats significantly reduced plasma glucose and lipid levels but had no effect on control rats. Furthermore, thyroid hormone levels were higher in the L-carnitine-treated diabetic rats than in the untreated diabetic group. The data suggest that high-dose L-carnitine treatment may reduce the severity of diabetes and result in improved cardiac performance.

  19. 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.

  20. Transgenic mice overexpressing insulin-like growth factor-II in β cells develop type 2 diabetes

    PubMed Central

    Devedjian, Jean-Christophe; George, Monica; Casellas, Alba; Pujol, Anna; Visa, Joana; Pelegrín, Mireia; Gros, Laurent; Bosch, Fatima

    2000-01-01

    During embryonic development, insulin-like growth factor-II (IGF-II) participates in the regulation of islet growth and differentiation. We generated transgenic mice (C57BL6/SJL) expressing IGF-II in β cells under control of the rat Insulin I promoter in order to study the role of islet hyperplasia and hyperinsulinemia in the development of type 2 diabetes. In contrast to islets from control mice, islets from transgenic mice displayed high levels of IGF-II mRNA and protein. Pancreases from transgenic mice showed an increase in β-cell mass (about 3-fold) and in insulin mRNA levels. However, the organization of cells within transgenic islets was disrupted, with glucagon-producing cells randomly distributed throughout the core. We also observed enhanced glucose-stimulated insulin secretion and glucose utilization in islets from transgenic mice. These mice displayed hyperinsulinemia, mild hyperglycemia, and altered glucose and insulin tolerance tests, and about 30% of these animals developed overt diabetes when fed a high-fat diet. Furthermore, transgenic mice obtained from the N1 backcross to C57KsJ mice showed high islet hyperplasia and insulin resistance, but they also developed fatty liver and obesity. These results indicate that local overexpression of IGF-II in islets might lead to type 2 diabetes and that islet hyperplasia and hypersecretion of insulin might occur early in the pathogenesis of this disease. PMID:10727441

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

    PubMed

    Coskun, Zeynep Mine; Bolkent, Sema

    2014-01-01

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

  2. The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats.

    PubMed

    Wang, Te; Cai, Leyi; Wang, Yangyang; Wang, Qingqing; Lu, Di; Chen, Hua; Ying, Xiaozhou

    2017-03-05

    Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkg(-1)day(-1) of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkg(-1)day(-1) of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkg(-1)day(-1) orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkg(-1)day(-1) orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes.

  3. The effect of endotoxin on heart rate dynamics in diabetic rats.

    PubMed

    Meamar, Morvarid; Dehpour, Tara; Mazloom, Roham; Sharifi, Fatemeh; Raoufy, Mohammad R; Dehpour, Ahmad R; Mani, Ali R

    2015-05-01

    The effect of endotoxin on heart rate variability (HRV) was assessed in diabetic and controls rats using a telemetric system. Endotoxin induced a reduction in sample entropy of cardiac rhythm in control animals. However, this effect was significantly blunted in streptozotocin-induced diabetic rats. Since uncoupling of cardiac pacemaker from cholinergic control is linked to reduced HRV in endotoxemia, chronotropic responsiveness to cholinergic stimulation was assessed in isolated atria. Endotoxemia was associated with impaired responsiveness to carbacholine in control rats. However, endotoxemia did not impair cholinergic responsiveness in diabetic atria. These findings corroborates with development of endotoxin tolerance in diabetic rats.

  4. Health perceptions among urban American Indians with type II diabetes.

    PubMed

    Patel, Sachin; Davila, Javier; Patel, Sonam; Norman, Dennis

    2014-01-01

    Since the 1940s, American Indians (AIs) have increasingly urbanized, moving off of reservations in large part due to federal policies of tribal termination and relocation. Though previous AI research has largely focused on reservation-associated challenges, many of these same challenges persist among urban AI populations. One mutual concern is the growing prevalence and incidence of type II diabetes mellitus (T2DM). While behavioral, genetic, and socioeconomic determinants of T2DM have been explored, much less is known about the influence of cultural and psychosocial factors. Recent studies suggest that the way AIs perceive diabetes may affect their health trajectory and explain their poor prognosis. Through the use of the Illness Perception Questionnaire, we explored this hypothesis in a pilot study of urban AI with T2DM living in Los Angeles County. We found that the majority of participants have a neutral perception about their diabetes: They view their condition to be long lasting yet treatable and indicate reasonable understanding of its symptoms and progression. We also identified "personal control," the level of perceived control one has over his or her disease, as a strong correlate of overall illness perception and, thus, a potentially useful psychological metric.

  5. Balneotherapy and platelet glutathione metabolism in type II diabetic patients

    NASA Astrophysics Data System (ADS)

    Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

    1996-09-01

    Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, P<0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG <150 mg/dl), the level increased ( P<0.01) and in poorly controlled patients (FPG >150 mg/dl), the value decreased ( P<0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG ( r=-0.430, P<0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

  6. Chromium and manganese interactions in streptozocin-diabetic rats

    SciTech Connect

    Davis, M.L.; Jarrett, C.R.; Adeleye, B.O.; Stoecker, B.J. )

    1991-03-15

    Weanling male rats were fed casein-based diets low in chromium and manganese ({minus}Cr-MN) or supplemented with 1 ppm chromium as chromium chloride (+Cr) and/or 55 ppm manganese as manganous carbonate in a factorial design. After 7 weeks on the experimental diets, half of the rats in each group were injected on 2 consecutive days with 55 mg/kg streptozocin (STZ) in citrate buffer pH 4. Four weeks after injection, serum glucose in the diabetic group supplement with both Cr and Mn was not different from non-diabetic animals; however, diabetic animals in {minus}Cr groups or in the +Cr-Mn group had significantly elevated serum glucose. Serum insulin was reduced by STZ. A significant interaction between Mn and diabetes affected serum cortisol concentrations. More new tissue was formed on a polyvinyl sponge inserted under the skin in +Mn animals. In this study, the STZ animals were more sensitive than the control animals to dietary Cr and Mn concentrations.

  7. A phytooxysterol, 28-homobrassinolide modulates rat testicular steroidogenesis in normal and diabetic rats.

    PubMed

    Premalatha, R; Jubendradass, Rajamanickam; Rani, S Judith Amala; Srikumar, K; Mathur, Premendu Prakash

    2013-05-01

    Steroidogenesis in testicular cells depends upon the availability of cholesterol within testicular mitochondria besides the activities of 3β-hydroxysteroid dehydrogenase (3β-HSD, 17β-hydroxysteroid dehydrogenase [17b-HSD]), and the tissue levels of steroidogenic acute regulatory protein (StAR), androgen-binding protein (ABP), and testosterone (T). Cellular cholesterol biosynthesis is regulated by endogenous oxycholesterols acting through nuclear hormone receptors. Plant oxysterols, such as 28-homobrassinolide (28-HB), available to human through diet, was shown to exhibit antihyperglycemic effect in diabetic male rat. Its role in rat testicular steroidogenesis and lipid peroxidation (LPO) was therefore assessed using normal and streptozotocin-induced diabetic male rats. Administration of 28-HB (333 µg/kg body weight) by oral gavage for 15 consecutive days to experimental rats diminished LPO, increased antioxidant enzyme, 3β-HSD and 17β-HSD activities, and elevated StAR and ABP expression and T level in rat testis. We report that 28-HB induced steroidogenesis in normal and diabetic rat testis.

  8. Zn(II) transport and distribution in rat spermatids.

    PubMed

    Reyes, J G; Arrate, M P; Santander, M; Guzman, L; Benos, D J

    1993-10-01

    Zn(II) is an essential trace element. In spermatozoa, Zn(II) modulates metabolism and chromatin condensation. The mechanisms of uptake and distribution of this ion in sperm cells have not been explored. In rat spermatids, our results indicate that 1) 65Zn(II) binds with fast kinetics to a labile, presumably extracellular, compartment. This binding is temperature insensitive and not modified by metabolic inhibitors. 2) Entry of 65Zn(II) in the absence of externally added proteins occurs through a mediated transport system that allows exchange to reach steady state in approximately 15 min at 34 degrees C. 3) Upon entering the cells, 65Zn(II) binds tightly to cellular organelles. 4) Exchangeable Zn(II) bound to cytoplasmic proteins plus free intracellular Zn(II) appears to be < 20% of total exchangeable Zn(II). 5) The intracellular exchangeable Zn(II) compartment is decreased by metabolic inhibitors, showing a direct or indirect link between energy metabolism and cellular Zn(II) levels. 6) 65Zn(II) efflux from rat spermatids is a process with a rate constant of 0.16 +/- 0.13 min-1 at 34 degrees C. This exit rate of Zn(II) is likely to be affected by Zn(II) release from cytoplasmic binding sites or organelles.

  9. Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats.

    PubMed

    Meena, Sunita; Rajput, Yudhishthir S; Pandey, Amit K; Sharma, Rajan; Singh, Raghvendar

    2016-08-01

    This study was designed to assess anti-diabetic potential of goat, camel, cow and buffalo milk in streptozotocin (STZ) induced type 1 diabetic albino wistar rats. A total of 48 rats were taken for the study where one group was kept as non-diabetic control group (8 rats) while others (40 rats) were made diabetic by STZ (50 mg/kg of body weight) injection. Among diabetic rats, a control group (8 rats) was kept and referred as diabetic control whereas other four groups (8 rats each) of diabetic rats were fed on 50 ml of goat or camel or cow or buffalo milk for 4 weeks. All the rats (non-diabetic and diabetic) were maintained on standard diet for four weeks. STZ administration resulted in enhancement of glucose, total cholesterol, triglyceride, low density lipoprotein, HbA1c and reduction in high density lipoprotein in plasma and lowering of antioxidative enzymes (catalase, glutathione peroxidase and superoxide dismutase) activities in pancreas, kidney, liver and RBCs, coupled with enhanced levels of TBARS and protein carbonyls in pancreas, kidney, liver and plasma. OGTT carried out at the end of 4 week milk feeding indicated that all milks helped in early maintenance of glucose level. All milks reduced atherogenic index. In camel milk fed diabetic group, insulin concentration enhanced to level noted for non-diabetic control while goat, cow and buffalo milk failed to restore insulin level. HbA1c level was also restored only in camel milk fed diabetic group. The level of antioxidative enzymes (catalase, GPx and SOD) in pancreas enhanced in all milk fed groups. Camel milk and to a reasonable extent goat milk reduced formation of TBARS and PCs in tissues and blood. It can be concluded that camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. Further, only camel milk completely ameliorated oxidative damage in pancreas and normalised insulin level.

  10. Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.

    PubMed

    Hill Gallant, Kathleen M; Gallant, Maxime A; Brown, Drew M; Sato, Amy Y; Williams, Justin N; Burr, David B

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.

  11. Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring.

    PubMed

    Eriksson, U J; Simán, C M

    1996-11-01

    The increased incidence of congenital malformations in diabetic pregnancy may be associated with an excess of free oxygen radicals in the embryo. We have previously blocked the dysmorphogenesis of rat embryos exposed to high glucose and beta-hydroxybutyrate concentrations in vitro by increasing the antioxidant capacity of the conceptus. In the present study, we attempted to diminish the teratogenic process in vivo in a rat model of diabetic pregnancy. Thus, pregnant diabetic and normal rats were fed either a standard diet or a diet enriched with 1% of the antioxidant butylated hydroxytoluene (BHT). The fetuses of the diabetic rats were smaller than the fetuses of the normal rats (body weight 2.70 g vs. 3.68 g) when the mothers were fed a standard diet. The BHT diet increased the fetal weight in the offspring of diabetic rats (3.17 g), with no change in fetuses of the normal rats (3.65 g). The placentas of diabetic rats were heavier than the placentas of normal rats; this difference was not present in the BHT-fed rats. The BHT treatment had no effect on the rate of resorptions, which was increased in the diabetic rats compared with the normal rats. In contrast, the increased rate of congenital malformations in the offspring of diabetic rats (19%), compared with that in the normal rats (0%), was markedly decreased by the BHT diet (2.3%). No malformations were found in the normal rats treated with BHT. These data support the notion that an excess of free oxygen radicals in the embryo contributes to the teratogenic process of diabetic pregnancy and, thus, suggest an area for future preventive therapeutic treatment.

  12. Interaction between Sex and Social Support in the Control of Type II Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Heitzmann, Carma A.; Kaplan, Robert M.

    1984-01-01

    Investigated the role of social support in the control of Type II diabetes mellitus. Participants (N=37) in a behavioral program in diabetes care completed questionnaires and provided blood samples. For women, satisfaction with supportive relationships was associated with control of diabetes. The opposite was true for men. (BH)

  13. [Effect of taurine and thioctacide on carbohydrate metabolism and the antioxydant system in rats with experimental diabetes].

    PubMed

    Gavrovskaia, L K; Ryzhova, O V; Safonova, A F; Aleksandrova, I Ia; Sapronov, N S

    2008-01-01

    Peroral administration of taurine and thioctacide in rats with alloxan-induced diabetes (i) decreased the levels of glucose, fructosamine and MDA, (ii) increased the levels of glycogen, insulin, and C-peptide in the liver, and (iii) increased the levels of enzymes of the antioxidant system of catalase and paraoxonase as compared to the control group of animals. These effects show that taurine and thioctacide possess hypoglycemic and antioxidant properties.

  14. Rad: A member of the Ras family overexpressed in muscle of type II diabetic humans

    SciTech Connect

    Reynet, C.; Kahn, C.R. )

    1993-11-26

    To identify the gene or genes associated with insulin resistance in Type II (non-insulin-dependent) diabetes mellitus, subtraction libraries were prepared from skeletal muscle of normal and diabetic humans and screened with subtracted probes. Only one clone out of 4000 was selectively overexpressed in Type II diabetic muscle as compared to muscle of non-diabetic or Type I diabetic individuals. This clone encoded a new 290 kilodalton member of the Ras-guanosine triphosphatase superfamily and was termed Rad (Ras associated with diabetes). Messenger ribonucleic acid of Rad was expressed primarily in skeletal and cardiac muscle and was increased an average of 8.6-fold in the muscle of Type II diabetics as compared to normal individuals.

  15. Effect of captopril and the bradykinin-PKC pathway on ROS production in type 1 diabetic rats.

    PubMed

    Rodrigues de Araujo, Glaucy; Granato de Faria, Karine; Lima, Wanderson Geraldo; Pádua, Bruno da Cruz; Rossoni, Joamyr Victor; Souza, Aline Arlindo; Chianca-Júnior, Deoclecio; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia; Chaves, Miriam Martins; Costa, Daniela Caldeira

    2011-12-01

    The aim of this study was to investigate the possible effects of captopril as a promoter in modulating the oxidant-antioxidant balance in rats with type 1 diabetes, and the influence of protein kinase C (PKC) pathways in the production of reactive oxygen species (ROS) induced by bradykinin in type 1 diabetic rats. This study evaluated the redox status in both the cardiac tissue and at the cellular level (neutrophils). Two concentrations of captopril were utilized: (i) 5 mg·(kg body mass)(-1), which was considered a therapeutic dose; and (ii) 10 mg·(kg body mass)(-1). Body mass, plasma glucose, and serum insulin were evaluated. To investigate the redox status of the cardiac tissue, we analyzed lipid peroxidation, concentration of carbonylated protein, catalase activity, and the concentration of glutathione. For a more accurate assessment of the possible antioxidant effect of captopril, we also analyzed ROS in neutrophils (in vivo), and ROS production induced by bradykinin and the influence of the PKC pathway in this production (in vitro). Our data show that the hearts of diabetic animals have increased oxidative damage, exemplified by the increased concentration of carbonylated protein and thiobarbituric acid reactive substances (TBARS). However, animals treated with captopril at both concentrations showed lower concentrations of carbonylated protein compared with untreated diabetic animals. We found an increase of catalase activity in the heart of diabetic rats, which was reversed by captopril treatment at both of the dosages tested. Our data showed that captopril was able to reduce ROS production in the neutrophils of diabetic rats at a dose of 10 mg captopril·(kg body mass)(-1). However, the antioxidant effect of captopril is independent of bradykinin. Diabetes induces oxidative stress, and these results suggest that captopril has an antioxidant effect and can modulate the production of ROS in circulating neutrophils.

  16. Antihyperlipidemic effect of fisetin, a bioflavonoid of strawberries, studied in streptozotocin-induced diabetic rats.

    PubMed

    Prasath, Gopalan Sriram; Subramanian, Sorimuthu Pillai

    2014-10-01

    Chronic hyperglycemia in diabetes is associated with profound changes in lipid and lipoprotein metabolism, with resultant alterations in particle distribution within lipoprotein classes. In the present study, an attempt has been made to explore the antihyperlipidemic effect of fisetin in streptozotocin-induced experimental diabetes in rats. Upon fisetin treatment to diabetic rats, the levels of blood glucose were significantly reduced with an improvement in plasma insulin. The increased levels of lipid contents in serum, hepatic, and renal tissues observed in diabetic rats were normalized upon fisetin administration. Also, the decreased levels of high-density lipoprotein cholesterol, and increased levels of low-density lipoprotein (LDL) and very LDL (VLDL) cholesterol in serum of diabetic rats were normalized. Oil Red O staining established a large number of intracellular lipid droplets accumulation in the diabetic rats. Fisetin treatment exacerbated the degree of lipid accumulation. The results of the present study exemplify the antihyperlipidemic property of the fisetin.

  17. Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats

    PubMed Central

    Niu, Ho-Shan; Liu, I-Min; Niu, Chiang-Shan; Ku, Po-Ming; Hsu, Chao-Tien; Cheng, Juei-Tang

    2016-01-01

    Background Eucommia bark, Eucommia ulmoides Oliver barks (Du-Zhong in Mandarin), is an herb used for renal dysfunction in Chinese traditional medicine. In an attempt to develop this herb as a treatment for diabetic nephropathy (DN), we investigated the effects of Du-Zhong on renal dysfunction in type 1-like diabetic rats. Methods Streptozotocin (STZ) was used to induce type 1-like diabetes in rats (STZ-diabetic rats). In addition to hyperglycemia, STZ-diabetic rats showed significant nephropathy, including higher plasma levels of blood urea nitrogen, creatinine, and renal fibrosis. Western blot analysis of renal cortical tissue was applied to characterize the changes in potential signals related to nephropathy. Results Oral administration of Du-Zhong (1 g/kg/day) to STZ-diabetic rats for 20 days not only decreased the plasma levels of blood urea nitrogen and creatinine but also improved renal fibrosis, whereas the plasma glucose level was not changed. The higher expressions of protein levels of transforming growth factor-beta (TGF-β) and connective tissue growth factor in diabetic rats were markedly attenuated by Du-Zhong. The increased phosphorylation of Smad2/3 in STZ-diabetic rats was also reduced by Du-Zhong. However, Du-Zhong cannot reverse the hyperglycemia-induced overproduction of signal transducers and activators of transcription 3 in the diabetic kidney. Conclusion Oral administration of Du-Zhong improves STZ-induced DN in rats by inhibiting TGF-β/Smad signaling and suppressing TGF-β/connective tissue growth factor expression. Therefore, active principle from Du-Zhong is suitable to develop as new agent for DN in the future. PMID:27041999

  18. Antidiabetic Effect of Sida cordata in Alloxan Induced Diabetic Rats

    PubMed Central

    Shah, Naseer Ali; Khan, Muhammad Rashid

    2014-01-01

    Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties. PMID:25114914

  19. Antidiabetic effect of Sida cordata in alloxan induced diabetic rats.

    PubMed

    Shah, Naseer Ali; Khan, Muhammad Rashid

    2014-01-01

    Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties.

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

    PubMed Central

    Newton, Victoria L.; Guck, Jonathan D.; Cotter, Mary A.

    2017-01-01

    Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ-) induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ). At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy. PMID:28293643

  1. Effects of long-acting somatostatin analogues on redox systems in rat lens in experimental diabetes

    PubMed Central

    Kunjara, Sirilaksana; Greenbaum, A Leslie; Sochor, Milena; Flyvbjerg, Allan; Grønbaek, Henning; McLean, Patricia

    2014-01-01

    The effects of long-acting somatostatin analogues, angiopeptin (AGP) and Sandostatin (SMS), on the early decline in the lens content of glutathione (GSH), ATP and NADPH and increase in sorbitol were studied in STZ diabetic rats, and comparison was made with the effect of insulin. Three factors prompted this study: (i) the known increase in IGF-1 in ocular tissue in diabetes and antagonistic effect of somatostatins, (ii) the known effect of IGF-1 in increasing lens aldose reductase and (iii) the lack of effect of somatostatins on diabetic hyperglycaemia, the latter enabling a differentiation to be made between effects of hyperglycaemia per se and site(s) of IGF-1/somatostatins. All four metabolites studied showed a significant restoration towards the normal control level after 7 days of treatment with AGP and SMS, and AGP was more effective on levels of GSH and ATP. A significant correlation was found between GSH and ATP across all groups at 7 days treatment. The redox state changes in diabetes include both NADP+/NADPH and NAD+/NADH in the conversion of glucose to sorbitol and via sorbitol dehydrogenase to fructose with a linked decrease in ATP formation via NAD+/NADH regulation of the glycolytic pathway. The interlinked network of change includes the requirement for ATP in the synthesis of GSH. The present study points to possible loci of action of somatostatins in improving metabolic parameters in the diabetic rat lens via effects on aldose reductase and/or glucose transport at GLUT 3. PMID:24602114

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

    PubMed

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

    2014-12-05

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

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

    PubMed

    Bardoux, P; Martin, H; Ahloulay, M; Schmitt, F; Bouby, N; Trinh-Trang-Tan, M M; Bankir, L

    1999-08-31

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P < 0.01) but failed to increase in DI-DM. Urinary albumin excretion more than doubled in LE-DM but rose by only 34% in DI-DM rats (P < 0.05). Kidney hypertrophy was also less intense in DI-DM than in LE-DM (P < 0.001). These results suggest that VP plays a critical role in diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.

  4. Type II diabetes of early onset: a distinct clinical and genetic syndrome?

    PubMed Central

    O'Rahilly, S; Spivey, R S; Holman, R R; Nugent, Z; Clark, A; Turner, R C

    1987-01-01

    The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes. PMID:3107658

  5. Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats.

    PubMed

    Pugliese, G; Tilton, R G; Speedy, A; Chang, K; Santarelli, E; Province, M A; Eades, D; Sherman, W R; Williamson, J R

    1989-12-01

    Rats injected i.p. with a single dose of nicotinamide (250 mg/kg) 15 min prior to i.v. injection of streptozotocin (65 mg/kg) develop a very mild form of diabetes characterized by slight elevations of plasma glucose, increased levels of HbA1, and reduced insulin secretion in response to an i.v. glucose tolerance test. These rats gain weight normally and they are not hyperphagic, glycosuric, or polyuric. The effects of this very mild form of diabetes vs overt streptozotocin diabetes of three months duration on regional vascular 131I-albumin clearance, blood flow (assessed by 15 microns 85Sr-microspheres), and renal filtration function were examined in male Sprague-Dawley rats. Plasma glucose levels of rats with mild diabetes were 7.4 +/- 0.9 (mean +/- SD) (mmol/l) vs 6.5 +/- 0.6 for control rats and 31.3 +/- 6.0 for overtly diabetic rats. HbA1 levels were increased 1.4 fold in mildly diabetic and 2.3 fold in overtly diabetic rats. Vascular clearance of 131I-albumin was markedly increased in ocular tissues (anterior uvea, retina, and choroid), sciatic nerve, aorta, new (subcutaneous) granulation tissue, and kidney of both diabetic groups, although increases in overtly diabetic rats exceeded those in the mildly diabetic group (2.2-4.6 times control animals vs 1.6-3.3 times, respectively). Likewise, both overt and very mild diabetes markedly increased glomerular filtration rate (approximately 1.8 times and 1.2 times control animals, respectively), urinary excretion of endogenous albumin (approximately 9 times and 4 times) and IgG (approximately 15 times and 4 times), as well as regional blood flow in the anterior uvea, choroid, and sciatic nerve. Increases in tissue sorbitol levels were much larger in overtly diabetic rats (generally 10-20 times control animals) than in mildly diabetic rats (1.5-3 times controls). myo-Inositol levels were significantly decreased only in lens and sciatic nerve of overtly diabetic rats. These observations indicate that even very mild

  6. Effect of bis-1,4-dihydropyridine in the kidney of diabetic rats.

    PubMed

    Gómez-Pliego, Raquel; Gómez-Zamudio, Jaime; Velasco-Bejarano, Benjamín; Ibarra-Barajas, Maximiliano; Villalobos-Molina, Rafael

    2013-01-01

    The in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP, was induced by a single administration of STZ (55 mg·kg(-1), i.p.). In the drug-treated groups, treatment with bis-1,4-DHP (10 mg·kg(-1)·day(-1)) started one week before diabetes induction; bis-1,4-DHP was dissolved in DMSO (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). Parameters evaluated were body weight, blood glucose, albuminuria, proteinuria, creatinine, urea excretion, kidney's weight / body weight ratio, and kidney perfusion pressure in all rat groups at different times of diabetes (2, 4, 6, and 10 weeks). Kidney weight of diabetic rats significantly increased vs. control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats at different times of diabetes. The ratios % kidney weight / 100 g body weight were different between control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats vs. diabetic rats (P < 0.05). Kidney perfusion pressure was decreased by diabetes, while it was partially recovered by bis-1,4-DHP treatment in response to phenylephrine. Bis-1,4-DHP had a tendency to decrease hyperglycemia vs. diabetic rats, even though glycemia was too high as compared with controls, and it ameliorated albuminuria, creatinine, and urea excretion, suggesting a favorable effect on renal haemodynamics. Bis-1,4-DHP, by inhibiting Ca(2+) entrance, induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction, but does not have significant impact on hyperglycemia.

  7. Anti-diabetic properties of chromium citrate complex in alloxan-induced diabetic rats.

    PubMed

    Li, Fang; Wu, Xiangyang; Zhao, Ting; Zhang, Min; Zhao, Jiangli; Mao, Guanghua; Yang, Liuqing

    2011-12-01

    The chromium citrate complex [CrCIT] was synthesized and its structure was determined by infrared, UV-visible and atomic absorption spectroscopy, elemental and thermodynamic analysis. Anti-diabetic activity, oxidative DNA damage capacity and acute oral toxicity of [CrCIT] were investigated and compared with that of chromium trichloride hexahydrate. [CrCIT] was synthesized in a single step reaction by chelating chromium(III) with citric acid in aqueous solution. The molecular formula of [CrCIT] was inferred as CrC(6)H(5)O(7)·4H(2)O. The anti-diabetic activity of the complex [CrCIT] was assessed in alloxan-diabetic rats by daily oral gavage for 3 weeks. The biological activity results showed that the complex at the dose of 0.25-0.75 mg Cr/kg body weight could decrease the blood glucose level and increase liver glycogen level in alloxan-diabetic rats. [CrCIT] had more beneficial influences on the improvement of controlling blood glucose, serum lipid and liver glycogen levels compared with CrCl(3)·6H(2)O. Furthermore, [CrCIT] did not cause oxidative DNA damage under physiologically relevant conditions, and [CrCIT] did not produce any hazardous symptoms or deaths in acute oral toxicity test, showing the LD(50) value for female and male rats were higher than 15.1 g/kg body weight. The results suggested that [CrCIT] might represent a novel and proper chromium supplement with potential therapeutic value to control blood glucose in diabetes.

  8. 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

  9. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice.

    PubMed

    Sidhu, G S; Mani, H; Gaddipati, J P; Singh, A K; Seth, P; Banaudha, K K; Patnaik, G K; Maheshwari, R K

    1999-01-01

    Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re-epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor-beta1 in curcumin-treated wounds compared to controls. Enhanced transforming growth factor-beta1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.

  10. Chronic Oral Pelargonidin Alleviates Streptozotocin-Induced Diabetic Neuropathic Hyperalgesia in Rat: Involvement of Oxidative Stress

    PubMed Central

    Mirshekar, Mohammadali; Roghani, Mehrdad; Khalili, Mohsen; Baluchnejadmojarad, Tourandokht; Arab Moazzen, Saiedeh

    2010-01-01

    Background: Diabetes mellitus in some clinical cases is accompanied with hyperalgesia. In this study, we evaluated the possible beneficial effect of chronic pelargonidin (PG) treatment on hyperalgesia in streptozotocin (STZ)-diabetic neuropathic rat. Methods: Male Wistar rats (n = 56) were divided into seven groups, i.e. control, diabetic, PG-treated control, PG (single- and multiple-dose)-treated diabetic, and sodium salicylate-treated control and diabetics. For induction of diabetes, STZ was injected i.p. at a single dose of 60 mg/kg. PG was orally administered at a dose of 10 mg/kg once and/or on alternate days for 8 weeks; 1 week after diabetes induction. After two months, hyperalgesia was assessed using standard formalin and hot tail immersion tests. Meanwhile, markers of oxidative stress in brain were measured. One-way analysis of variance was used for statistical analysis of the data. Results: Diabetic rats showed a marked chemical and thermal hyperalgesia, indicating that development of diabetic neuropathy and PG treatment (especially multiple-doses) significantly ameliorated the alteration in hyperalgesia (P<0.05-0.01) in diabetic rats as compared to untreated diabetics. PG (multiple doses) also significantly decreased diabetes-induced thiobarbituric acid reactive substances formation and non-significantly reversed elevation of nitrite level and reduction of antioxidant defensive enzyme superoxide dismutase. Conclusion: These results clearly suggest that PG prevents diabetic neuropathic hyperalgesia through attenuation of oxidative stress. PMID:20683496

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

    PubMed

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

    2016-01-01

    Diabetic nephropathy is one of the most common chronic complications of diabetes with poor efficacy of clinical treatment. This study investigated the protective effects of leflunomide, a new immunosuppressant, on tubulointerstitial lesions in a rat model of diabetic nephropathy. Diabetes was induced with streptozotocin (STZ, 50 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 8 weeks with low (5 mg/kg) and high dose (10 mg/kg) of leflunomide, and benazepril hydrochloride (4 mg/kg) as a positive control. In diabetic rats, the 24-h urine volume, urine protein and microalbumin, blood creatinine and urea nitrogen significantly increased, which were attenuated by leflunomide treatment in a dose-dependent manner (all p < 0.05). The increase of kidney weight/body weight and the histopathological findings of tubulointerstitial lesion in diabetic rats were mitigated by leflunomide treatment. Immunohistochemistry study and real-time polymerase chain reaction results demonstrated that osteopontin (OPN), transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin and CD68 expression in the renal tubulointerstitial region were significantly increased in the diabetic rats, while these increases were inhibited by leflunomide treatment. These findings suggest that leflunomide protects the kidney injury of diabetic rats might through its inhibition of OPN/TGF-β1 mediated extracellular matrix deposition and tubulointerstitial fibrosis, as well as its inhibition on tubular epithelial-myofibroblast transdifferentiation.

  12. The neuroprotective effects of progesterone on experimental diabetic neuropathy in rats.

    PubMed

    Sameni, H R; Panahi, M; Sarkaki, A; Saki, G H; Makvandi, M

    2008-08-15

    This study was conducted to investigate the neuroprotective effects of progesterone (PROG) on electrophysiological and histomorphometrical alternation in STZ-induced diabetic neuropathy starting from 4 weeks after the diabetic induction. Thirty adult male Sprague-Dawley rats were randomly divided into 3 groups (with 10 rats in each), control (nondiabetic), untreated diabetic and diabetic PROG-treated. Diabetes was induced in adult male rats by a single dose injection of streptozotocin (STZ, 55 mg kg(-1), i.p.). In the PROG-treated group, 4 weeks after induce of diabetes; rats were treated with PROG (8 mg kg(-1), i.p., every two days) for 6 weeks. Diabetic rats showed a significant reduction in motor nerve conduction velocity (MNCV), mean myelinated fibers (MFs) diameter, axon diameter and myelin sheath thickness in the sciatic nerve after 6 weeks. In the untreated diabetic group endoneurial edema was observed in sciatic nerve and the numbers of MFs with infolding into the axoplasm, irregularity of fibers, myelin sheath with unclear boundaries and alteration in myelin compaction were also increased. Long-term treatment with PROG increased MNCV significantly and prevented all these abnormalities in treated diabetic rats. Our findings indicated that PROG as a therapeutic approach can protect neurophysiologic and histomorphologic alterations induced by peripheral diabetic neuropathy.

  13. Non-insulin-dependent (type II) diabetes mellitus.

    PubMed Central

    Rodger, W

    1991-01-01

    Non-insulin-dependent (type II) diabetes mellitus is an inherited metabolic disorder characterized by hyperglycemia with resistance to ketosis. The onset is usually after age 40 years. Patients are variably symptomatic and frequently obese, hyperlipidemic and hypertensive. Clinical, pathological and biochemical evidence suggests that the disease is caused by a combined defect of insulin secretion and insulin resistance. Goals in the treatment of hyperglycemia, dyslipidemia and hypertension should be appropriate to the patient's age, the status of diabetic complications and the safety of the regimen. Nonpharmacologic management includes meal planning to achieve a suitable weight, such that carbohydrates supply 50% to 60% of the daily energy intake, with limitation of saturated fats, cholesterol and salt when indicated, and physical activity appropriate to the patient's age and cardiovascular status. Follow-up should include regular visits with the physician, access to diabetes education, self-monitoring of the blood or urine glucose level and laboratory-based measurement of the plasma levels of glucose and glycated hemoglobin. If unacceptably high plasma glucose levels (e.g., 8 mmol/L or more before meals) persist the use of orally given hypoglycemic agents (a sulfonylurea agent or metformin or both) is indicated. Temporary insulin therapy may be needed during intercurrent illness, surgery or pregnancy. Long-term insulin therapy is recommended in patients with continuing symptoms or hyperglycemia despite treatment with diet modification and orally given hypoglycemic agents. The risk of pancreatitis may be reduced by treating severe hypertriglyceridemia (fasting serum level greater than 10 mmol/L) and atherosclerotic disease through dietary and, if necessary, pharmacologic management of dyslipidemia. Antihypertensive agents are available that have fewer adverse metabolic effects than thiazides and beta-adrenergic receptor blockers. New drugs are being developed that

  14. Complex modulation of the expression of PKC isoforms in the rat brain during chronic type 1 diabetes mellitus.

    PubMed

    Vetri, Francesco; Chavez, Rafael; Xu, Hao-Liang; Paisansathan, Chanannait; Pelligrino, Dale A

    2013-01-15

    We previously demonstrated that chronic hyperglycemia has a detrimental influence on neurovascular coupling in the brain-an effect linked to an alteration in the protein kinase C (PKC)-mediated phosphorylation pattern. Moreover, the activity of PKC was increased, in diabetic rat brain, in a tissue fraction composed primarily of the superficial glia limitans and pial vessels, but trended toward a decrease in cerebral cortical gray matter. However, that study did not examine the expression patterns of PKC isoforms in the rat brain. Thus, in a rat model of streptozotocin (STZ)-induced chronic type 1 diabetes mellitus (T1DM), and in non-diabetic (ND) controls, two hypotheses were addressed. First, chronic T1DM is accompanied by changes in the expression of PKC-α, βII, γ, δ, and ε Second, those changes differ when comparing cerebral cortex and glio-pial tissue. In addition, we analyzed the expression of a form of PKC-γ, phosphorylated on threonine 514 (pT514-PKC-γ), as well as the receptor for activated C kinase 1 (RACK1). The expression pattern of different PKC isoforms was altered in a complex and tissue-specific manner during chronic hyperglycemia. Notably, in the gray matter, PKC-α expression significantly decreased, while pT514-PKC-γ expression increased. However, PKC-βII, -γ, -δ, -ε, and RACK1 expressions did not change. Conversely, in glio-pial tissue, PKC-α and RACK1 were upregulated, whereas PKC-γ, pT514-PKC-γ, and PKC-ε were downregulated. PKC-βII, and PKC-δ, were unchanged. These findings suggest that the PKC activity increase previously seen in the glio-pial tissue of diabetic rats may be due to the selective upregulation of PKC-α, and ultimately lead to the impairment of neurovascular coupling.

  15. Antinociceptive effect of chlorogenic acid in rats with painful diabetic neuropathy.

    PubMed

    Bagdas, Deniz; Ozboluk, Hasret Yucel; Cinkilic, Nilufer; Gurun, Mine Sibel

    2014-06-01

    The present study aimed to evaluate possible antinociceptive effects of chlorogenic acid in streptozotocin-induced diabetic neuropathic pain in rats. Chlorogenic acid (100 mg/kg) was administered daily for 14 days. Our study showed for the first time that both single and chronic chlorogenic acid treatments produced significant antinociceptive effects in diabetic rats. In contrast, single dose of chlorogenic acid showed no signs of an antinociceptive effect, but chronic treatment exerted antinociceptive potential in nondiabetic rats. Additionally, chronic treatment effectively reduced hyperglycemia that induced by diabetes. In conclusion, chlorogenic acid has beneficial effects for the management of diabetic neuropathic pain.

  16. 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.

  17. 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.

  18. Antihyperglycemic and antihyperlipidemic effects of Tephrosia purpurea leaf extract in streptozotocin induced diabetic rats.

    PubMed

    Pavana, P; Manoharan, S; Renju, G L; Sethupathy, S

    2007-10-01

    Diabetes mellitus is a worldwide leading metabolic syndrome, associated with profound alterations in carbohydrate, lipids, lipoproteins and protein metabolisms. Worldwide, traditional practitioners for the treatment of diabetes and its complications use a wide variety of medicinal plants. In the present study the aqueous extract of Tephrosia purpurea leaves (TpALet) was evaluated for its antihyperglycemic and antihyperlipidemic effects in streptozotocin induced diabetic rats. Profound alterations in the concentrations of blood glucose, lipids and lipoproteins were observed in diabetic rats. Oral administration of TpALet to diabetic rats at a dose of 600 mg/kg body weight significantly reduced the level of blood glucose and increased the level of plasma insulin as well as normalized the lipids and lipoproteins profile. The present study thus demonstrated that TpALet has prominent antihyperglycemic and antihyperlipidemic effects in streptozotocin induced diabetic rats.

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

    PubMed

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

    2014-03-01

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

  20. Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ghasemi, Mohsen; Zendehbad, Bamdad; Zabihi, Hoda; Hosseini, Mahmoud; Hadjzadeh, Mousa Al Reza; Hayatdavoudi, Parichehr

    2016-01-01

    Background: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. Aims: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. Study Design: Animal experimentation. Methods: The rats were divided into three groups: 1-control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. Results: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. Conclusion: Leptin can exert positive effects on memory impairments in diabetic rats. PMID:26966625

  1. Protein synthesis in wound after tooth extraction in pancreatectomized diabetic rats.

    PubMed

    Grandini, S A; Brentegani, L G; Novaes, A B; Migliorini, R H

    1990-01-01

    The incorporation of alanine C14 in protein synthesis was analyzed in recently formed alveolar tissue after tooth extraction in partially-pancreatectomized diabetic rats. The incorporation of alanine C14 was higher in diabetic animals than in treated diabetic and control groups. The results can be explained by a delay in bone tissue repair.

  2. Discovery of a novel class of targeted kinase inhibitors that blocks protein kinase C signaling and ameliorates retinal vascular leakage in a diabetic rat model.

    PubMed

    Grant, Stephan; Tran, Phong; Zhang, Qin; Zou, Aihua; Dinh, Dac; Jensen, Jordan; Zhou, Sue; Kang, Xiaolin; Zachwieja, Joseph; Lippincott, John; Liu, Kevin; Johnson, Sarah Ludlum; Scales, Stephanie; Yin, Chunfeng; Nukui, Seiji; Stoner, Chad; Prasanna, Ganesh; Lafontaine, Jennifer; Wells, Peter; Li, Hui

    2010-02-10

    Protein kinase C (PKC) family members such as PKCbetaII may become activated in the hyperglycemic state associated with diabetes. Preclinical and clinical data implicate aberrant PKC activity in the development of diabetic microvasculature abnormalities. Based on this potential etiological role for PKC in diabetic complications, several therapeutic PKC inhibitors have been investigated in clinical trials for the treatment of diabetic patients. In this report, we present the discovery and preclinical evaluation of a novel class of 3-amino-pyrrolo[3,4-c]pyrazole derivatives as inhibitors of PKC that are structurally distinct from the prototypical indolocarbazole and bisindolylmaleimide PKC inhibitors. From this pyrrolo-pyrazole series, several compounds were identified from biochemical assays as potent, ATP-competitive inhibitors of PKC activity with high specificity for PKC over other protein kinases. These compounds were also found to block PKC signaling activity in multiple cellular functional assays. PF-04577806, a representative from this series, inhibited PKC activity in retinal lysates from diabetic rats stimulated with phorbol myristate acetate. When orally administered, PF-04577806 showed good exposure in the retina of diabetic Long-Evans rats and ameliorated retinal vascular leakage in a streptozotocin-induced diabetic rat model. These novel PKC inhibitors represent a promising new class of targeted protein kinase inhibitors with potential as therapeutic agents for the treatment of patients with diabetic microvascular complications.

  3. Increased Expression of Pyloric ERβ Is Associated With Diabetic Gastroparesis in Streptozotocin-Induced Male Diabetic Rats

    PubMed Central

    Crimmins, Stephen; Smiley, Rebecca; Preston, Kerry; Yau, Amy; Mccallum, Richard; Ali, Mohammed Showkat

    2016-01-01

    Background Gastroparesis is a significant co-morbidity affecting up to 50% of patients with diabetes and is disproportionately found in women. Prior studies have suggested that loss of interstitial cells of Cajal, hyperglycemia, and nitric oxide dysfunction are potential causes of gastroparesis. Since diabetic gastroparesis affects more women than men, we performed an exploratory study with a diabetic rat model to determine if sex hormone signaling is altered in those where gastroparesis develops. Methods We injected male rats with streptozotocin (STZ) to model type I diabetes, as confirmed by blood glucose levels. Gastroparesis was determined by acetaminophen gavage and serum acetaminophen levels. Rats were grouped based on acetaminophen and blood glucose data: diabetic (DM), diabetic and gastroparetic (DM + GP), and control (CM). Serum levels of testosterone, estrogen, and insulin were determined as well as aromatase expression in pyloric tissue and serum. Androgen receptor and estrogen receptor α (ERα) and β (ERβ) were also measured in the pylorus. Results Compared to CM, estrogen increased and testosterone decreased in both DM and DM + GP rats. Sex hormone levels were not different between DM and DM + GP. Serum aromatase was increased in DM and DM + GP rats; however, pyloric tissue levels were not significantly different from controls. ERα was unchanged and androgen receptor decreased in DM and DM + GP. ERβ was increased only in DM + GP animals. Conclusion Our study implicates increased pyloric ERβ in the development of gastroparesis in STZ-induced male diabetic rats. Increased serum aromatase is likely responsible for altered sex hormone levels. Our study supports the implication of sex hormone signaling in diabetic development and demonstrates a potential unique role for pyloric ERβ in male diabetic gastroparesis. PMID:27785323

  4. Spontaneous diabetes in rats: destruction of islets is prevented by immunological tolerance.

    PubMed

    Naji, A; Silvers, W K; Bellgrau, D; Barker, C F

    1981-09-18

    Spontaneous diabetes occurring in "BB" rats (derived from a colony of outbred Wistar rats) is the result of destruction of pancreatic islets by infiltrating mononuclear cells (insulitis) and may be a disease very similar to human juvenile onset diabetes. Both diseases probably have an autoimmune etiology. Evidence is presented that islets transplanted to diabetic BB rats are destroyed by the original disease process. Inoculation of bone marrow from normal (nondiabetes-susceptible) rat donors into neonatal BB recipients usually prevented the development of hyperglycemia.

  5. Impacts of the coexistence of diabetes and hypothyroidism on body weight gain, leptin and various metabolic aspects in albino rats.

    PubMed

    Ahmed, Osama M; Gabar, Mohamed Abdel; Ali, Tarek M

    2012-01-01

    The present study was conducted to assess the interrelationship and the influence of the coexistence of diabetes and hypothyroidism on thyroid hormone levels, insulin levels and biochemical variables related to carbohydrate, lipid and protein metabolism in addition to thyroid gland and Islets of Langerhans histological changes and antioxidant defense system. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin to fasting albino rats at dose level of 45 mg/kg b. w. Hypothyroidism in diabetic and normal rats was induced by adding methimazole in drinking water (0.02% w/v) for 4 weeks. The obtained results revealed that hypothyroidism interacts with diabetes in a way that prevents the progress of the hyperglycemic state. This may be due to the increase in the insulin secretory response in diabetic hypothyroid than diabetic rats. Serum T3 level decreased in order in diabetic (-26.63%), hypothyroid (-61.89%) and diabetic hypothyroid (-65.69%) rats while T4 level was increased in diabetic rats and decreased in hypothyroid ones. The decrease in T3 level in diabetic animals in spite of T4 increase may be attributed to the decrease in conversion of T4 to T3 as a result of hepatic 5'-DI decreased activity. Liver glycogen content was three-fold decreased in diabetic rats and was not significantly altered in both hypothyroid and diabetic hypothyroid rats. The serum leptin level and body weight gain were decreased in diabetic and diabetic hypothyroid rats; the leptin level was more deteriorated in diabetic hypothyroid rats while body weight gain was more affected in diabetic rats. Serum triglycerides level was more increased in diabetic rats than in diabetic hypothyroid ones on one hand, while total lipids, total cholesterol, LDL-cholesterol levels as well as cardiovascular indices were more deteriorated in diabetic hypothyroid rats than diabetic ones on the other hand. Serum total protein and globulin levels were decreased in diabetic rats and were

  6. Effects of Nitrate Intake on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

    PubMed Central

    Jeddi, Sajad; Khalifi, Saeedeh; Ghanbari, Mahboubeh; Bageripour, Fatemeh; Ghasemi, Asghar

    2016-01-01

    Background Coronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated. Objective We examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Method Rats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx). Results Recovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake. Conclusion Dietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart. PMID:27849257

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

    PubMed

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

    2015-09-01

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

  8. Responsiveness of renal glomeruli to adenosine in streptozotocin-induced diabetic rats dependent on hyperglycaemia level.

    PubMed

    Szczepańska-Konkel, M; Jankowski, M; Stiepanow-Trzeciak, A; Rudzik, A; Pawełczyk, T; Angielski, S

    2003-03-01

    Glomerular filtration rate (GFR) in response to adenosine precursor, NAD, and glomeruli contractility in response to adenosine were evaluated in streptozotocin-induced diabetic rats with severe (blood glucose 27.8 +/- 1.2 mmol/L) and moderate hyperglycaemia (18.2 +/- 0.9 mmol/L) compared with nondiabetic (ND)-rats. In anaesthetised rats, basal GFR was greater in moderately diabetic rats compared with severely diabetic rats (p < 0.05) and ND-rats (p < 0.02). Intravenous infusion of 5 nmol x min(-1) x kg(-1) NAD reduced GFR and renal plasma flow (RPF) in diabetic rats but had no effect on these parameters in ND-rats. Moreover, NAD-induced reduction of GFR and RPF was greater in rats with severe diabetes (41% and 30%, respectively) than in with moderate diabetes (25% and 26%, respectively). Theophylline (0.2 micromol x min(-1) x kg(-1) ) abolished renal response to NAD. Isolated glomeruli contraction in response to adenosine, assessed by glomerular 3H-inulin space reduction, was lowered in moderately diabetic-group and enhanced in severely diabetic-group. compared with ND-group (p < 0.05). Adenosine A1-receptor antagonist DPCPX inhibited adenosine-induced glomeruli contraction. This differential response of diabetic renal glomeruli to adenosine suggests that impaired glomerular contractility in response to adenosine could be responsible for hyperfiltration in moderate diabets, whereas, the increased adenosine-dependent contractility of glomeruli in severe diabetes may increase the risk of acute renal failure in this condition.

  9. 17β-Estradiol and vitamin E modulates oxidative stress-induced kidney toxicity in diabetic ovariectomized rat.

    PubMed

    Ulas, Mustafa; Cay, Mehmet

    2011-12-01

    The aim of this study was to investigate the effects of vitamin E (alpha-tocopherol) and 17β-estradiol (E(2)) supplementation on malondialdehyde (MDA), glutathione (GSH), vitamin A, beta carotene, selenium-dependent glutathione peroxidase (GSH-Px), zinc-dependent superoxide dismutase (SOD), and copper/zinc-dependent catalase (CAT) values in the kidney of ovariectomized (OVX) diabetic rats. Forty-two female rats were randomly divided into seven equal groups as follows: group I, control; group II, OVX; group III, OVX+E(2); group IV, OVX+E(2)+alpha-tocopherol; group V, OVX+diabetic; group VI, OVX+diabetic+E(2); and group VII, OVX+diabetic+E(2)+alpha-tocopherol. E(2) (40 μg kg(-1)/day) and alpha-tocopherol (100 μg kg(-1)/day) were given. Bilateral ovariectomy was performed in all groups except group I. After 4 weeks, antioxidant and MDA levels in the kidney for all groups were analyzed. GSH-Px, CAT, SOD, GSH levels, vitamin A, and beta carotene levels were decreased in OVX group compared to those in the control group but MDA level was elevated via ovariectomy. However, E(2) and E(2)+alpha-tocopherol supplementations in OVX group was associated with an increase in the GSH-Px, GSH, CAT and Zn-SOD values, vitamin A, and beta carotene levels but a decrease in MDA levels in kidney. The MDA levels in the kidney of diabetic OVX rats were found higher than those in the control and OVX groups. However, GSH, GSH-Px, CAT, SOD, vitamin A, and beta carotene levels in kidney were lower in OVX diabetic rats. On the other hand, E(2) and E(2)+alpha-tocopherol supplementations to OVX diabetic rats have caused an increase in GSH-Px, CAT and SOD, GSH, vitamin A, and beta carotene levels but a decrease in MDA levels. In conclusion, the E(2) and E(2)+alpha-tocopherol supplementations to diabetic OVX and OVX rats may strengthen the antioxidant defense system by reducing lipid peroxidation, and therefore they may play a role in preventing renal disorders.

  10. Poly I:C induces development of diabetes mellitus in BB rat.

    PubMed

    Sobel, D O; Newsome, J; Ewel, C H; Bellanti, J A; Abbassi, V; Creswell, K; Blair, O

    1992-04-01

    Polyinosinic polycytidilic acid (poly I:C), an inducer of alpha-interferon, accelerates the development of diabetes in diabetes-prone (DP) BioBreeding (BB) rats. This study investigates the effect of administering poly I:C to a diabetes-resistant (DR) strain of BB rats. We compared the incidence of diabetes, the degree of insulitis, the number of NK cells, helper-inducer cells, cytotoxic-suppressor cells, Ia+ T cells, RT6.1+ T cells, and NK cell bioactivity in DR rats treated with saline and with a 5 micrograms/g body wt (poly-5) dose and a 10 micrograms/g body wt (poly-10) dose of poly I:C. The incidence of diabetes was also compared with that of DP rats receiving poly-5. We found that both doses of poly I:C significantly induce the development of diabetes in the DR BB rat. However, treatment of DR rats with the higher dose induces a greater rate of development of diabetes and earlier onset of diabetes than the lower poly-5 dose. The rate of diabetes development and the mean age of onset were similar in poly-10-treated DR and poly-5-treated DP rats. A significant degree of insulitis occurred in all the poly I:C-treated DR rats, even those not developing diabetes. Peripheral blood NK cell number was greater in poly I:C than in saline-treated rats, after 2 wk of treatment and when killed. The percentage of OX19+ peripheral blood mononuclear cells expressing RT6.1 allotype or Ia antigen were similar in poly I:C- and saline-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed Central

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

    2012-01-01

    Background & objectives: A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Methods: Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. Results: A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. Interpretation & conclusions: The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic

  12. Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin.

    PubMed

    Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Sahin, Nurhan; Kucuk, Osman; Ozercan, Ibrahim H; Juturu, Vijaya; Komorowski, James R

    2013-07-28

    The objective of the present study was to evaluate anti-diabetic effects of chromium picolinate (CrPic) and biotin supplementations in type 2 diabetic rats. The type 2 diabetic rat model was induced by high-fat diet (HFD) and low-dose streptozotocin. The rats were divided into five groups as follows: (1) non-diabetic rats fed a regular diet; (2) diabetic rats fed a HFD; (3) diabetic rats fed a HFD and supplemented with CrPic (80 μg/kg body weight (BW) per d); (4) diabetic rats fed a HFD and supplemented with biotin (300 μg/kg BW per d); (5) diabetic rats fed a HFD and supplemented with both CrPic and biotin. Circulating glucose, cortisol, total cholesterol, TAG, NEFA and malondialdehyde concentrations decreased (P< 0·05), but serum insulin concentrations increased (P< 0·05) in diabetic rats treated with biotin and CrPic, particularly with a combination of the supplements. Feeding a HFD to diabetic rats decreased PPAR-γ expression in adipose tissue and phosphorylated insulin receptor substrate 1 (p-IRS-1) expression of liver, kidney and muscle tissues, while the supplements increased (P< 0·001) PPAR-γ and p-IRS-1 expressions in relevant tissues. Expression of NF-κB in the liver and kidney was greater in diabetic rats fed a HFD, as compared with rats fed a regular diet (P< 0·01). The supplements decreased the expression of NF-κB in diabetic rats (P< 0·05). Results of the present study revealed that supplementing CrPic and biotin alone or in a combination exerts anti-diabetic activities, probably through modulation of PPAR-γ, IRS-1 and NF-κB proteins.

  13. Erythrocyte membrane analysis for type II diabetes detection using Raman spectroscopy in high-wavenumber region

    NASA Astrophysics Data System (ADS)

    Lin, Jinyong; Zeng, Yongyi; Lin, Juqiang; Wang, Jing; Li, Ling; Huang, Zufang; Li, Buhong; Zeng, Haishan; Chen, Rong

    2014-03-01

    Raman spectroscopy was employed to detect lipid variation occurring in type II diabetic erythrocyte membrane (EM) without using exogenous reagents. In high-wavenumber (HW) region, significant Raman spectral differences between diabetic and normal EM are observed at 2850, 2873, 2885, 2935, and 2965 cm-1, which are mainly related to lipid in EM. Based on principal component analysis, the diagnostic accuracy of HW region for diabetes detection is 98.8%, which is much higher than that of low-wavenumber region (82.9%). The results suggest that EM HW Raman region has great promise for the reagent-free and non-invasive detection of type II diabetes.

  14. 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

  15. 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.

  16. Oxidative Stress Status and Placental Implications in Diabetic Rats Undergoing Swimming Exercise After Embryonic Implantation

    PubMed Central

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

    2015-01-01

    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

  17. Wound healing properties of Hylocereus undatus on diabetic rats.

    PubMed

    Perez G, R M; Vargas S, R; Ortiz H, Y D

    2005-08-01

    Aqueous extracts of leaves, rind, fruit pulp and flowers of Hylocereus undatus were studied for their wound healing properties. Wound healing effects were studied on incision (skin breaking strength), excision (percent wound contraction) and the nature of wound granulation tissues, which were removed on day 7 and the collagen, hexosamine, total proteins and DNA contents were determined, in addition to the rates of wound contraction and the period of epithelialization. In streptozotocin diabetic rats, where healing is delayed, topical applications of H. undatus produced increases in hydroxyproline, tensile strength, total proteins, DNA collagen content and better epithelization thereby facilitating healing. H. undatus had no hypoglycemic activity.

  18. Rat1p maintains RNA polymerase II CTD phosphorylation balance

    PubMed Central

    Jimeno-González, Silvia; Schmid, Manfred; Malagon, Francisco; Haaning, Line Lindegaard; Jensen, Torben Heick

    2014-01-01

    In S. cerevisiae, the 5′-3′ exonuclease Rat1p partakes in transcription termination. Although Rat1p-mediated RNA degradation has been suggested to play a role for this activity, the exact mechanisms by which Rat1p helps release RNA polymerase II (RNAPII) from the DNA template are poorly understood. Here we describe a function of Rat1p in regulating phosphorylation levels of the C-terminal domain (CTD) of the largest RNAPII subunit, Rpb1p, during transcription elongation. The rat1-1 mutant exhibits highly elevated levels of CTD phosphorylation as well as RNAPII distribution and transcription termination defects. These phenotypes are all rescued by overexpression of the CTD phosphatase Fcp1p, suggesting a functional relationship between the absence of Rat1p activity, elevated CTD phosphorylation, and transcription defects. We also demonstrate that rat1-1 cells display increased RNAPII transcription kinetics, a feature that may contribute to the cellular phenotypes of the mutant. Consistently, the rat1-1 allele is synthetic lethal with the rpb1-E1103G mutation, causing increased RNAPII speed, and is suppressed by the rpb2-10 mutation, causing slowed transcription. Thus, Rat1p plays more complex roles in controlling transcription than previously thought. PMID:24501251

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

    PubMed

    Ramesh, Balakrishnan; Pugalendi, Kodukkur Viswanathan

    2007-08-01

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

  20. Sodium tungstate alleviates biomechanical properties of diabetic rat femur via modulation of oxidative stress.

    PubMed

    Donmez, Baris O; Ozturk, Nihal; Sarikanat, Mehmet; Oguz, Nurettin; Sari, Ramazan; Ozdemir, Semir

    2014-01-01

    Diabetes mellitus leads to bone disorders such as osteopenia and osteoporosis that can increase fracture risk. On the other hand, sodium tungstate is an inorganic compound which exerts anti-diabetic activity in experimental studies due to its suggested insulin-mimetic or antioxidant activity. Therefore this study was designed to investigate the effect of tungstate on bone quality in diabetic rat femurs. The rats were divided into four groups: Control (C), tungstate-treated control (C+Tung), diabetes (STZ-D) and tungstate-treated diabetes (STZ-D+Tung). Diabetes mellitus was induced by single injection of streptozotocin (50 mg/kg). The treated rats received 150 mg/kg/day of sodium tungstate for 12 weeks. Sodium tungstate achieved a little (17%) but significant reduction on blood glucose levels, while it didn't recover the reduced body weights of diabetic rats. In addition, impaired bone mechanical quality was reversed, despite the unchanged mineral density. Sodium tungstate administration significantly lowered the 2-thiobarbituric acid reactive substances and restored the activity of tissue antioxidant enzymes such as glutathione peroxidase, catalase and superoxide dismutase in diabetic rats. On the other hand, glutathione levels didn't change in either case. These findings indicate that tungstate can improve the reduced mechanical quality of diabetic rat femurs due probably to reduction of reactive oxygen species and modulation of antioxidant enzymes as well as reduction in blood glucose levels.

  1. Antioxidant Activities of Caralluma tuberculata on Streptozotocin-Induced Diabetic Rats.

    PubMed

    Poodineh, Jafar; Khazaei Feizabad, Abdurrashid; Nakhaee, Alireza

    2015-01-25

    Preclinical Research The aim of this study was to elucidate the antioxidant effects of Caralluma tuberculata (C. tuberculata) in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar rats with an intraperitoneal injection of STZ at dose of 60 mg/kg body weight. Three days after diabetes induction, powdered aerial part of plant at doses of 100 and 200 mg/kg body weight were gavaged orally for a period of 45 days. The diabetes significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and level of total thiol in liver, kidney, and heart of animals (P < 0.05). In contrast, a significant increase in the levels of protein carbonyl was observed in diabetic rats compared with control animals (P < 0.05). Oral treatment of diabetic rats with C. tuberculata showed ameliorative effects on blood glucose and markers of oxidative stress in a dose-dependent manner. Altered levels of all oxidative stress parameters in tissues of diabetic rats reverted back to those normal animals after the treatment with dose of 200  mg/kg /day of plant materials. It seems that the appropriate dose of C. tuberculata has both antihyperglycemic and antioxidant activities in STZ-induced diabetic rats. Therefore, it can have preventive properties on oxidative stress-induced diabetic complications. Drug Dev Res, 2014. © 2014 Wiley Periodicals, Inc.

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

    PubMed

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

    2016-05-01

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

  3. The potential of sanrego (Lunasia amara) in enhancing fertility and anti-hyperglycemic effect in diabetic induced male rats

    NASA Astrophysics Data System (ADS)

    Nor Raidah, R.; Mahanem M., N.; Mohd Shazrul Fazry, S.

    2014-09-01

    Study on the effects of Lunasia amara (LA) aqueous extract on male fertility and its anti-hyperglycemic activity was carried out. Twelve adult male Sprague-Dawley rats were divided into two groups for fertility test; control given orally distilled water (n=6) and treatment (n=6) given 60 mg/kg aqueous extract of LA for 42 days. On day 43, all rats were sacrificed and cauda epididymis was isolated for sperm quality analysis that includes parameter of sperm count, motility and viability. Anti-hyperglycemic study was done on five groups of male rats; I-normal control, II-Diabetic control and three other groups induced diabetic given 500 mg/kg metformin, 60 mg/kg LA and 120 mg/kg LA respectively. Diabetes was induced in the male rats by intravenous injection of 55 mg/kg streptozotocin. On day 7, the fasting blood glucose level was measured from blood drawn by tail snip. Results showed that aqueous extract of LA increased significantly (p < 0.05) sperm count (39.88 ± 2.33) × 106, viability 82.46 ± 1.91 % and progressive motility 76.00 ± 1.51and of sperm data in treated group compared to control group. LA aqueous extract at dose 120 mg/kg was significantly reduced the fasting blood glucose in the diabetic rats by 49.53 %. In conclusion, the aqueous extract of LA effective in increasing sperm quality of male rats and suggest that LA may possess anti-hyperglycemic property.

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

    PubMed

    Elmas, Onur; Erbas, Oytun; Yigitturk, Gurkan

    2016-10-01

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

  5. Oxidative damage is ameliorated by curcumin treatment in brain and sciatic nerve of diabetic rats.

    PubMed

    Acar, Abdullah; Akil, Esref; Alp, Harun; Evliyaoglu, Osman; Kibrisli, Erkan; Inal, Ali; Unan, Fatma; Tasdemir, Nebahat

    2012-07-01

    To date, there have not been enough studies about the effects of curcumin against oxidative stress on sciatic nerves caused by streptozotocin (STZ) in diabetic rats. Therefore, this study was undertaken to determine whether curcumin, by virtue of its antioxidant properties, could affect the oxidant/antioxidant balance in the sciatic nerve and brain tissues of streptozotocin (STZ)-induced diabetic rats. A total of 28 rats were randomly divided into four groups of seven rats each: normal controls, only curcumin treated, diabetic controls, and diabetics treated with curcumin. Biomarkers-malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and NO levels-for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. We found a significant increase in MDA, NO, TOS, and OSI, along with a reduction in TAS levels in the brains and sciatic nerves of the STZ-induced diabetic rats (for both parameters p < 0.05). The MDA, TOS, OSI, and NO levels in these tissues were significantly reduced in the curcumin-treated diabetic group compared to the untreated diabetic group. In conclusion, the results of this study suggested that curcumin exhibits neuroprotective effects against oxidative damage in the brain and sciatic tissues of diabetic rats.

  6. Topically applied CMT-2 enhances wound healing in streptozotocin diabetic rat skin.

    PubMed

    Ramamurthy, N S; Kucine, A J; McClain, S A; McNamara, T F; Golub, L M

    1998-11-01

    Delayed wound healing is one of the complications of diabetes mellitus, exhibited by increased wound collagenase and decreased granulation tissues. The current study compared wound healing in normal and diabetic rats, and the effects of topically applied 1% or 3% concentrations of chemically modified tetracycline-2 (CMT-2) on 6-mm circular full-thickness skin wounds healed by secondary intention. On day 7 after wounding, tissues were removed for biochemical analysis and histology. The wound granulation tissue hydroxyproline was less in the untreated diabetic rat with increased collagenase and gelatinase. Treating the diabetic rat wounds with 3% CMT-2 increased the wound hydroxyproline and decreased activities of gelatinase and collagenase. There was a delay in wound filling by granulation tissue in diabetic rats. In CMT-2-treated diabetic rats, the volume of granulation tissue was greater than that in untreated diabetic rats. CMT-2 appears to normalize wound healing in diabetic rats and may be a valuable adjunct in the treatment of chronic wounds.

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

    PubMed

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

    2013-06-15

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

  8. Verification of the antidiabetic effects of cinnamon (Cinnamomum zeylanicum) using insulin-uncontrolled type 1 diabetic rats and cultured adipocytes.

    PubMed

    Shen, Yan; Fukushima, Misato; Ito, Yoshimasa; Muraki, Etsuko; Hosono, Takashi; Seki, Taiichiro; Ariga, Toyohiko

    2010-01-01

    It has long been believed that an intake of cinnamon (Cinnamomum zeylanicum) alleviates diabetic pathological conditions. However, it is still controversial whether the beneficial effect is insulin-dependent or insulin-mimetic. This study was aimed at determining the insulin-independent effect of cinnamon. Streptozotocin-induced diabetic rats were divided into four groups and orally administered with an aqueous cinnamon extract (CE) for 22 d. The diabetic rats that had taken CE at a dose of more than 30 mg/kg/d were rescued from their hyperglycemia and nephropathy, and these rats were found to have upregulation of uncoupling protein-1 (UCP-1) and glucose transporter 4 (GLUT4) in their brown adipose tissues as well as in their muscles. This was verified by using 3T3-L1 adipocytes in which CE upregulates GLUT4 translocation and increases the glucose uptake. CE exhibited its anti-diabetic effect independently from insulin by at least two mechanisms: i) upregulation of mitochondrial UCP-1, and ii) enhanced translocation of GLUT4 in the muscle and adipose tissues.

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2017-02-16

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

  11. 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

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

    PubMed Central

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

    2017-01-01

    This study was conducted to compare the ameliorative effect of Nigella sativa and propolis methanol extract on streptozotocin-induced diabetic male rats and treating diabetic nephropathy. Forty male Albino rats were divided into four groups; the first group was the negative control fed standard diet. The other 30 rats were injected with streptozotocin to induce diabetes by a single intravenous injection and then divided equally into three groups; the second group was the positive diabetic control; the third and the fourth groups were treated orally with 20% w/w Nigella sativa seeds methanol extract and propolis methanol extract (20% w/w), respectively. The rats of the second group showed increased glucose levels and lipid peroxide accompanied with reduction in superoxide dismutase, catalase, and glutathione-S-transferase enzyme activities compared with the negative control. Carboxymethyl lysine, interleukin-6, and immunoglobulins were also increased as a result of diabetes. Kidney function parameters were also elevated, while potassium and sodium levels were decreased. Moreover, tissues of kidney and pancreas showed severe histopathological changes. Treating the diabetic rats with Nigella sativa and propolis methanol extract in the third and fourth groups, respectively, ameliorated all altered biochemical and pathological examinations approaching the negative control. Propolis was more effective than Nigella sativa. PMID:28298934

  13. 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 β-cells and also on the surviving β-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. PMID:26730146

  14. Irbesartan ameliorates diabetic cardiomyopathy by regulating protein kinase D and ER stress activation in a type 2 diabetes rat model.

    PubMed

    Liu, Xiangjuan; Xu, Qun; Wang, Xiaomeng; Zhao, Zhuo; Zhang, Liping; Zhong, Ling; Li, Li; Kang, Weiqiang; Zhang, Yun; Ge, Zhiming

    2015-03-01

    Recent studies demonstrate an important role of protein kinase D (PKD) in the cardiovascular system. However, the potential role of PKD in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. Irbesartan has beneficial effects against diabetes-induced heart damage, while the mechanisms were still poorly understood. Our present study was designed to investigate the effects of irbesartan in DCM and whether the cardioprotective effects of irbesartan were mediated by PKD and endoplasmic reticulum (ER) stress. We induced the type 2 diabetic rat model by high fat diet and low dose streptozotocin injection. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. 8-weeks administration of irbesartan (15, 30 and 45mg/kg/day) was used to evaluate the effect irbesartan in DCM. Diabetic rats revealed severe metabolic abnormalities, left ventricular dysfunction, myocardial fibrosis and apoptosis. PKD and ER stress were excessive activated in the myocardium of diabetic rats. Furthermore, cardiac fibrosis, apoptosis, diastolic dysfunction and ER stress were all significantly related to PKD activation in diabetic rats. Irbesartan treatment attenuated the activation of PKD and ER stress, which paralleled its cardioprotective effects. Our study suggests that irbesartan could ameliorate cardiac remodeling and dysfunction in type 2 diabetes, and these beneficial effects were associated with its ability to suppress the activation of PKD and ER stress.

  15. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

    PubMed

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M

    2015-05-01

    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.

  16. Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Yay, A; Akkuş, D; Yapıslar, H; Balcıoglu, E; Sonmez, M F; Ozdamar, S

    2014-11-01

    Nitric oxide (NO) plays a significant role in the development of diabetic nephropathy. We investigated the effects of an antioxidant, carnosine, on streptozotocin (STZ)-induced renal injury in diabetic rats. We used four groups of eight rats: group 1, control; group 2, carnosine treated; group 3, untreated diabetic; group 4, carnosine treated diabetic. Kidneys were removed and processed, and sections were stained with periodic acid-Schiff (PAS) and subjected to eNOS immunohistochemistry. Examination by light microscopy revealed degenerated glomeruli, thickened basement membrane and glycogen accumulation in the tubules of diabetic kidneys. Carnosine treatment prevented the renal morphological damage caused by diabetes. Moreover, administration of carnosine decreased somewhat the oxidative damage of diabetic nephropathy. Appropriate doses of carnosine might be a useful therapeutic option to reduce oxidative stress and associated renal injury in diabetes mellitus.

  17. 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

  18. Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.

    PubMed

    Sathya, S; Kokilavani, R; Gurusamy, K

    2008-10-01

    The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level.

  19. Evaluation of Δ9-tetrahydrocannabinol metabolites and oxidative stress in type 2 diabetic rats

    PubMed Central

    Coskun, Zeynep Mine; Bolkent, Sema

    2016-01-01

    Objective(s): The object of the study is to examine the effects of Δ9-tetrahydrocannabinol (THC) against oxidative stress in the blood and excretion of THC metabolites in urine of type 2 diabetic rats. Materials and Methods: The control (n=8), THC control (n=6), diabetes (n=8) and diabetes + THC (n=7) groups were created. Type 2 diabetes was induced by nicotinamide (NA, 85 mg/kg) + streptozotocin (STZ, 65 mg/kg). THC was administered intraperitoneally for seven days. The glutathione (GSH) level in erythrocytes and malondialdehyde (MDA) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activities in plasma were measured. THC metabolites were analyzed in urine. Results: The results showed that the erythrocyte GSH levels were significantly increased (P<0.05), but plasma MDA levels were non-significantly decreased in diabetes group treated with THC when compared with the diabetes group. The CAT activity was non-significantly reduced and SOD was significantly increased (P<0.01) in the plasma of diabetes induced by THC in comparison with the diabetic group. The excretion of THC metabolites was higher in the urine of diabetes + THC rats as compared to the THC control rats. Conclusion: These findings highlight that THC treatment may attenuate slightly the oxidative stress in diabetic rats. The excretion rate of THC may vary in the type 2 diabetes mellitus status. PMID:27081459

  20. TRB3 Gene Silencing Alleviates Diabetic Cardiomyopathy in a Type 2 Diabetic Rat Model

    PubMed Central

    Ti, Yun; Xie, Guo-lu; Wang, Zhi-hao; Bi, Xiao-lei; Ding, Wen-yuan; Wang, Jia; Jiang, Gui-hua; Bu, Pei-li; Zhang, Yun; Zhong, Ming; Zhang, Wei

    2011-01-01

    OBJECTIVE Tribbles 3 (TRB3) is associated with insulin resistance, an important trigger in the development of diabetic cardiomyopathy (DCM). We sought to determine whether TRB3 plays a major role in modulating DCM and the mechanisms involved. RESEARCH DESIGN AND METHODS The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of type 2 DCM by serial echocardiography and metabolite tests, Western blot analysis for TRB3 expression, and histopathologic analyses of cardiomyocyte density, lipids accumulation, cardiac inflammation, and fibrosis area. We then used gene silencing to investigate the role of TRB3 in the pathophysiologic features of DCM. RESULTS Rats with DCM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, fibrosis, and TRB3 overexpression. We found that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal–regulated kinase 1/2 and Jun NH2-terminal kinase in DCM was significantly decreased. Conclusions. TRB3 gene silencing may exert a protective effect on DCM by improving selective insulin resistance, implicating its potential role for treatment of human DCM. PMID:21933987

  1. Reduction of Melatonin Level in Patients with Type II Diabetes and Periodontal Diseases.

    PubMed

    Abdolsamadi, Hamidreza; Goodarzi, Mohammad Taghi; Ahmadi Motemayel, Fatemeh; Jazaeri, Mina; Feradmal, Javad; Zarabadi, Mahdiyeh; Hoseyni, Mostafa; Torkzaban, Parviz

    2014-01-01

    Background and aims. Melatonin is a circulating hormone that is mainly released from the pineal gland. It possesses antioxidant, free-radical scavenging, and immune-enhancing properties. A growing number of studies reveal a complex role for melatonin in influencing various diseases, including diabetes and periodontal diseases. The aim of this study was to examine the possible links between salivary melatonin levels and type II diabetes and periodontal diseases. Materials and methods. A total of 30 type II diabetic patients, 30 patients with periodontal diseases, 30 type II diabetic patients with periodontal disease and 30 age- and BMI-matched controls were studied. The periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary melatonin levels were determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Results. The mean of salivary melatonin level was significantly lower in patients with either periodontitis or diabetes compared to healthy subjects (P < 0.05). Salivary melatonin concentration decreased in type II diabetic patients and periodontitis patients, and then decreased reaching the lowest levels in type II diabetic patients with periodontal disease. Conclusion. Based on the results of this study, it can probably be concluded that salivary level of melatonin has an important role in the pathogenesis of diabetes and periodontal diseases. It is also worth noting that this factor could probably be used as a pivotal biological marker in the diagnosis and possible treatment of these diseases, although further research is required to validate this hypothesis.

  2. Antioxidant-Rich Extract from Plantaginis Semen Ameliorates Diabetic Retinal Injury in a Streptozotocin-Induced Diabetic Rat Model

    PubMed Central

    Tzeng, Thing-Fong; Liu, Wayne Young; Liou, Shorong-Shii; Hong, Tang-Yao; Liu, I-Min

    2016-01-01

    Plantaginis semen, the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd. (Plantaginaceae), has been traditionally used to treat blurred vision in Asia. The aim of this work was to investigate the effect of plantaginis semen ethanol extract (PSEE) on the amelioration of diabetic retinopathy (DR) in streptozotocin (STZ)-diabetic rats. PSEE has abundant polyphenols with strong antioxidant activity. PSEE (100, 200 or 300 mg/kg) was oral administrated to the diabetic rats once daily consecutively for 8 weeks. Oral administration of PSEE resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and retinal vascular permeability and leukostasis in diabetic rats. In addition, PSEE administration increased the activities of superoxidase dismutase (SOD) and catalase (CAT), and glutathione peroxidase (GSH) level in diabetic retinae. PSEE treatment inhibited the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) and the phosphorylation of Akt without altering the Akt protein expression in diabetic retinae. PSEE not only down-regulated the gene expression of hypoxia-inducible factor-1α (TNF-α) and interleukin-1β (IL-1β), but also reduced ICAM-1 and VCAM-1 expression in diabetic retinae. Moreover, PSEE reduced the nuclear factor-κB (NF-κB) activation and corrected imbalance between histone deacetylases (HDAC) and histone acetyltransferases (HAT) activities in diabetic retinae. In conclusion, phenolic antioxidants extract from plantaginis semen has potential benefits in the prevention and/or progression of DR. PMID:27649243

  3. Effect of edaravone in diabetes mellitus-induced nephropathy in rats

    PubMed Central

    Lim, Li Xin; Tan, Kelly; Tay, Chai Sze; Teoh, Yi Leng; Akhtar, Shaikh Sohrab; Rupeshkumar, Mani; Chung, Ivy; Abdullah, Nor Azizan; Banik, Urmila; Dhanaraj, Sokkalingam A.; Balakumar, Pitchai

    2016-01-01

    Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats. PMID:27382349

  4. Effect of edaravone in diabetes mellitus-induced nephropathy in rats.

    PubMed

    Varatharajan, Rajavel; Lim, Li Xin; Tan, Kelly; Tay, Chai Sze; Teoh, Yi Leng; Akhtar, Shaikh Sohrab; Rupeshkumar, Mani; Chung, Ivy; Abdullah, Nor Azizan; Banik, Urmila; Dhanaraj, Sokkalingam A; Balakumar, Pitchai

    2016-07-01

    Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.

  5. Effects of vanadate on in vivo myocardial reactivity to norepinephrine in diabetic rats.

    PubMed

    Paulson, D J; Kopp, S J; Tow, J P; Peace, D G

    1987-02-01

    Myocardial contractile function is often depressed in patients with diabetes mellitus. Vanadate is an essential trace element that has purportedly an insulin-like action and has been suggested as a therapeutic agent for the treatment of diabetes mellitus. The purpose of the present study was to compare the prophylactic efficacy of oral vanadate therapy (0.8 mg of sodium orthovanadate per milliliter drinking water) to that of insulin treatment (5 units/day s.c.) in terms of its ability to reduce or prevent the progressive cardiodepression that occurs in untreated diabetes mellitus. Diabetes was induced in male rats by i.v. streptozotocin injection (50 mg/kg). Diabetes rats were assigned randomly to one of three regimens for 8 weeks: untreated, insulin-treated or vanadate-treated. Noninjected rats served as controls. In vivo myocardial contractile function was measured under basal conditions and after i.v. norepinephrine infusions in ketamine-xylazine-anesthetized rats using a miniature catheter-tip pressure transducer inserted in the right carotid artery and advanced into the left ventricle. Vanadate and insulin treatment resulted in comparable increases in body weight and reductions in plasma glucose, which were improved relative to untreated diabetics. These findings suggest that vanadium may possess an insulin-like action. Basal in vivo myocardial contractile performance was depressed significantly in untreated diabetic rats as compared to control and insulin-treated diabetic rats. The contractile performance of vanadate-treated diabetic rats was in between untreated diabetic and control groups. In vivo myocardial reactivity to norepinephrine based on assessments of left intraventricular developed pressure, positive and negative dP/dt and delta dP/dt was depressed significantly in untreated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Ability of bacteriophage in resolving wound infection caused by multidrug-resistant Acinetobacter baumannii in uncontrolled diabetic rats.

    PubMed

    Shivaswamy, VinodKumar Chickmangalure; Kalasuramath, Suneeta Basavaraj; Sadanand, Chethan Kumar; Basavaraju, Abhishek Kilagere; Ginnavaram, Varsha; Bille, Sumanth; Ukken, Sanjay Saju; Pushparaj, Usha Nandini

    2015-04-01

    Acinetobacter baumannii, a substantial nosocomial pathogen, has developed resistance to almost all available antimicrobial drugs. Bacteriophage therapy is a possible alternative treatment for multidrug-resistant (MDR) bacterial infections. In this study, we have successfully isolated bacteriophage active against clinical strains of A. baumannii by enrichment from hospital sewage sludge using representatives of those strains. The bacteriophage isolated against A. baumannii formed plaques against beta-lactamases producing strains of A. baumannii. The utility of bacteriophage specific for A. baumannii to resolve wound infection in uncontrolled diabetic rats was evaluated. Five groups of uncontrolled diabetic rats were used. Group I was noninfected (Control), Group II was infected with MDR A. baumannii and challenged with bacteriophage, Group III was infected with MDR A. baumannii, Group IV was infected with MDR A. baumannii and challenged with antibiotic colistin, and Group V consisted of noninfected rats and sprayed with phage (Phage control). A significant decrease in infection, period of epithelization, and wound contraction was observed in the phage-challenged group when compared with antibiotic-treated uncontrolled diabetic rats and the control group. To conclude the study, new insights are provided into the biology of the broad host range of A. baumannii phage, demonstrating that A. baumannii phage has prospects for the treatment of infections caused by the MDR A. baumannii.

  7. Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat.

    PubMed

    Chadha, Gurkishan S; Morris, Marilyn E

    2015-07-01

    The objective of this research was to assess the effects of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) on the pharmacokinetics of human IgG (hIgG), an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Furthermore, the specific role of T2DM in the altered disposition of hIgG was evaluated by treating diabetic rats with pioglitazone, while the role of chronic kidney disease (CKD) was assessed using 5/6 nephrectomized Sprague Dawley rats. ZDF male (lean non-diabetic control and obese diabetic) and pioglitazone-treated ZDF rats were studied at ages 12-13 weeks (only DM was present), and at ages 29-30 weeks (progression to DN). All animals were dosed with 1 mg/kg of hIgG intravenously (IV) or subcutaneously (SC). ZDF rats had significantly higher blood glucose concentrations and urinary albumin excretion compared to control rats. Significant increases in total clearance (2.5-fold) and renal clearance (100-fold) of hIgG were observed; however the major increase in total clearance was due to increased non-renal clearance. Greater changes in urinary albumin excretion and total and renal clearances of IgG (3.5-fold and 300-fold, respectively) were observed with progression to DN. SC bioavailability of hIgG in all animal groups was similar (>84%). With pioglitazone-treatment, diabetic animals remained euglycemic and treatment was able to reverse the clearance changes, although incompletely. In the CKD group, no difference in hIgG clearance was observed when compared with controls. In conclusion, the increased clearance of hIgG in ZDF diabetic animals, reversal by pioglitazone treatment and lack of effect of CKD, demonstrate the influence of T2DM on hIgG pharmacokinetics.

  8. Beneficial effect of Hypericum perforatum on depression and anxiety in a type 2 diabetic rat model.

    PubMed

    Husain, Gulam Mohammed; Chatterjee, Shyam Sunder; Singh, Paras Nath; Kumar, Vikas

    2011-01-01

    Recent studies have revealed diverse therapeutically interesting pharmacological properties of a standardized Hypericum perforatum extract (HpE) potentially useful for treatments of patients with metabolic and psychiatric disorders. Consequently, the presented experiments were designed to test usefulness of the extract for the treatment of comorbid conditions of mood disturbances and anxiety in diabetic rats. Type 2 diabetes mellitus was induced in overnight fasted rats by a single i.p. injection of streptozotocin (STZ; 65 mg/kg), 15 min after an i.p. injection of nicotinamide (120 mg/kg). HpE was administered orally (100 and 200 mg/kg b.w..) to diabetic animals for 14 days. Anxiolytic activity was evaluated using open-field exploration test (OFT) and elevated plus maze (EPM) test. Antidepressant activity was assessed using Porsolt's forced swim test (FST). Fasting blood glucose levels in different groups were analyzed on the 14th day. Diabetic rats showed significant increase in anxiety in OFT and EPM compared to non diabetic normal control rats. Diabetic rats treated with HpE have shown significant anxiolytic activity in OFT and EPM test. In FST, immobility period of vehicle treated diabetic rats was significantly increased (p < 0.05) compared to normal control rats. Treatment with HpE significantly decreased (p < 0.001) immobility period compared to vehicle treated diabetic control rats. HpE treatment significantly reduced elevated blood glucose levels in diabetic rats. The presented observations strongly suggest that HpE could be suitable alternative therapeutic option for prevention, as well as treatment, of comorbidities caused by, or associated with, depression, anxiety and diabetes.

  9. The Relationship between Serum Carbonic Anhydrase I-II Autoantibody Levels and Diabetic Retinopathy in Type 1 Diabetes Patients

    PubMed Central

    Türk, Adem; Mollamehmetoğlu, Süleyman; Alver, Ahmet; Menteşe, Ahmet; Nuhoğlu, İrfan; Erem, Cihangir; İmamoğlu, Halil İbrahim

    2017-01-01

    Objectives: To investigate the relationship between serum carbonic anhydrase I-II (CA-I and II) autoantibody levels and diabetic retinopathy (DRP) in cases with type 1 diabetes. Materials and Methods: A total of 37 type-1 diabetic patients, 17 with DRP (group 1) and 20 without (group 2), and 38 healthy control subjects (group 3) were included. CA-I and CA-II autoantibody levels were measured in serum samples obtained from each of the three groups and compared statistically. Additionally, the correlation between CA-I and CA-II autoantibody levels and the presence of diabetic macular edema was examined. Results: Mean measured CA-I autoantibody levels were 0.145±0.072, 0.117±0.047, and 0.138±0.061 ABSU in group 1, group 2, and group 3, respectively (p=0.327). The average CA-II autoantibody levels achieved in the same groups were 0.253±0.174, 0.155±0.137, and 0.131±0.085 ABSU, respectively (p=0.005). No significant difference was obtained between the subgroups of group 1, with macular edema (n=8) and without (n=9), in terms of both CA-I and CA-II autoantibody levels (p=0.501, p=0.178, respectively). Conclusion: A significant correlation was observed between the development of DRP and serum CA-II autoantibody levels in type 1 diabetic cases. However, there was no correlation between the autoantibody levels and the presence of diabetic macular edema in cases with DRP.

  10. Biphasic Effect of Diabetes on Neuronal Nitric Oxide Release in Rat Mesenteric Arteries

    PubMed Central

    Sastre, Esther; Caracuel, Laura; Blanco-Rivero, Javier; Callejo, María; Xavier, Fabiano E.; Balfagón, Gloria

    2016-01-01

    Introduction We analysed possible time-dependent changes in nitrergic perivascular innervation function from diabetic rats and mechanisms implicated. Materials and Methods In endothelium-denuded mesenteric arteries from control and four- (4W) and eight-week (8W) streptozotocin-induced diabetic rats the vasoconstriction to EFS (electrical field stimulation) was analysed before and after preincubation with L-NAME. Neuronal NO release was analysed in the absence and presence of L-arginine, tetrahydrobiopterine (BH4) and L-arginine plus BH4. Superoxide anion (O2-), peroxynitrite (ONOO-) and superoxide dismutase (SOD) activity were measured. Expressions of Cu-Zn SOD, nNOS, p-nNOS Ser1417, p-nNOS Ser847, and Arginase (Arg) I and II were analysed. Results EFS response was enhanced at 4W, and to a lesser extent at 8W. L-NAME increased EFS response in control rats and at 8W, but not at 4W. NO release was decreased at 4W and restored at 8W. L-arginine or BH4 increased NO release at 4W, but not 8W. SOD activity and O2- generation were increased at both 4W and 8W. ONOO- decreased at 4W while increased at 8W. Cu-Zn SOD, nNOS and p-NOS Ser1417 expressions remained unmodified at 4W and 8W, whereas p-nNOS Ser847 was increased at 4W. ArgI was overexpressed at 4W, remaining unmodified at 8W. ArgII expression was similar in all groups. Conclusions Our results show a time-dependent effect of diabetes on neuronal NO release. At 4W, diabetes induced increased O2- generation, nNOS uncoupling and overexpression of ArgI and p-nNOS Ser847, resulting in decreased NO release. At 8W, NO release was restored, involving normalisation of ArgI and p-nNOS Ser847 expressions. PMID:27272874

  11. Effect of oxidative stress on Rho kinase II and smooth muscle contraction in rat stomach.

    PubMed

    Al-Shboul, Othman; Mustafa, Ayman

    2015-06-01

    Recent studies have shown that both Rho kinase signaling and oxidative stress are involved in the pathogenesis of a number of human diseases, such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho kinase pathway. The aim of the current study was to investigate the effect of oxidative stress on Rho kinase II and muscle contraction in rat stomach. The peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2), and peroxynitrite were used to induce oxidative stress. Rho kinase II expression and ACh-induced activity were measured in control and oxidant-treated cells via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits, respectively. Single smooth muscle cell contraction was measured via scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632 dihydrochloride. All oxidant agents significantly increased ACh-induced Rho kinase II activity without affecting its expression level. Most important, oxidative stress induced by all three agents augmented ACh-stimulated muscle cell contraction, which was significantly inhibited by Y-27632. In conclusion, oxidative stress activates Rho kinase II and enhances contraction in rat gastric muscle, suggesting an important role in GI motility disorders associated with oxidative stress.

  12. Analysis of serum from type II diabetes mellitus and diabetic complication using surface-enhanced Raman spectra (SERS)

    NASA Astrophysics Data System (ADS)

    Han, H. W.; Yan, X. L.; Dong, R. X.; Ban, G.; Li, K.

    2009-03-01

    In this paper, we show surface-enhanced Raman spectra (SERS) of serums from type II diabetes mellitus and diabetic complication (coronary disease, glaucoma and cerebral infarction), and analyze the SERS through the multivariate statistical methods of principal component analysis (PCA). In particular, we find that there exist many adenines in these serums, which maybe come from DNA (RNA) damage. The relative intensity of the band at 725±2 cm-1 assigned to adenine is higher for patients than for the healthy volunteers; therefore, it can be used as an important ‘fingerprint’ in order to diagnose these diseases. It is also shown that serums from type II diabetes mellitus group, diabetic complication group and healthy volunteers group can be discriminated by PCA.

  13. 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

  14. Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study.

    PubMed

    Erbas, Oytun; Pala, Halil Gursoy; Pala, Emel Ebru; Artunc Ulkumen, Burcu; Akman, Levent; Akman, Tulay; Oltulu, Fatih; Aktug, Huseyin; Yavasoglu, Altug

    2015-05-01

    The aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given) - Group-2 and sunitinib treatment group - Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student's t-test, analysis of variance (ANOVA) and Mann-Whitney's U-test. There was a significant increase in no-medication (water given) diabetic rat's ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats' ovary (Group-1) (p < 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat's ovary (Group-3) when compared with no-medication (water given) diabetic rat's ovary (Group-2) (p < 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans.

  15. 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

  16. Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats

    PubMed Central

    Ahn, Jae Hee; Hong, Ho Cheol; Cho, Myong Jin; Kim, Yoon Jung; Choi, Hae Yoon; Eun, Chai Ryoung; Yang, Sae Jeong; Yoo, Hye Jin; Kim, Hee Young; Seo, Ji A; Kim, Sin Gon; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop

    2012-01-01

    Background Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats. Methods Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks. Results Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups. Conclusion Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug. PMID:22540049

  17. Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats

    PubMed Central

    Gu, Le-Hui; Zhang, Tian-Tian; Li, Yang; Yan, Hong-Jie; Qi, Hui; Li, Fu-Rong

    2015-01-01

    Due to their hypoimmunogenicity and unique immunosuppressive properties, mesenchymal stem cells (MSCs) are considered one of the most promising adult stem cell types for cell therapy. Although many studies have shown that MSCs exert therapeutic effects on several acute and subacute conditions, their long-term effects are not confirmed in chronic diseases. Immunogenicity is a major limitation for cell replacement therapy, and it is not well understood in vivo. We evaluated the immunogenicity of allogeneic MSCs in vivo by transplanting MSCs into normal and diabetic rats via the tail vein or pancreas and found that MSCs exhibited low immunogenicity in normal recipients and even exerted some immunosuppressive effects in diabetic rats during the initial phase. However, during the later stage in the pancreas group, MSCs expressed insulin and MHC II, eliciting a strong immune response in the pancreas. Simultaneously, the peripheral blood mononuclear cells in the recipients in the pancreas group were activated, and alloantibodies developed in vivo. Conversely, in the tail vein group, MSCs remained immunoprivileged and displayed immunosuppressive effects in vivo. These data indicate that different transplanting routes and microenvironments can lead to divergent immunogenicity of MSCs. PMID:25242276

  18. Angiotensin II-noradrenergic interactions in renovascular hypertensive rats.

    PubMed Central

    Zimmerman, J B; Robertson, D; Jackson, E K

    1987-01-01

    This study tested the hypothesis that interactions of endogenous angiotensin II (AII) with the noradrenergic neuroeffector junction are important in renin-dependent hypertension. In the in situ blood-perfused rat mesentery, in normal rats exogenous AII potentiated mesenteric vascular responses to periarterial (sympathetic) nerve stimulation (PNS) more than vascular responses to exogenous norepinephrine (NE). In 2-kidney-1-clip (2K-1C) rats with renovascular hypertension mesenteric vascular responses to PNS and NE were greater than in sham-operated rats, and renovascular hypertension mimicked the effects of exogenous AII with respect to enhancing responses to PNS more than responses to NE. In 2K-1C rats, but not in sham-operated rats, 1-Sar-8-Ile-AII markedly suppressed vascular responses to PNS, without influencing responses to NE. Finally, 1-Sar-8-Ile-AII attenuated sympathetic nerve stimulation-induced neuronal spillover of NE in 2K-1C rats, but not in sham-operated rats. These data indicate that renovascular hypertension enhances noradrenergic neurotransmission, and that this enhancement is mediated in part by AII-induced facilitation of NE release. PMID:3301900

  19. 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.

  20. Hypoglycemic activity of Gymnema sylvestre extracts on oxidative stress and antioxidant status in diabetic rats.

    PubMed

    Kang, Myung-Hwa; Lee, Min Sun; Choi, Mi-Kyeong; Min, Kwan-Sik; Shibamoto, Takayuki

    2012-03-14

    Diabetes mellitus, which is associated with oxidative damage, has a significant impact on health, quality of life, and life expectancy. An ethanol extract of Gymnema sylvestre leaf was examined in vitro and in vivo to investigate the role of antioxidants in diabetic rats. The extract exhibited strong antioxidant activity in the assays, including TBA (56%), SOD-like (92%), and ABTS (54%). Blood glucose levels in the diabetic rats fed G. sylvestre extract decreased to normal levels. The presence of the antihyperglycemic compounds gymnemagenin and gymnemic acids in G. sylvestre extract was detected by LC/MS analysis. Lipid peroxidation levels were decreased by 31.7% in serum, 9.9% in liver, and 9.1% in kidney in the diabetic rats fed the extract. Feeding G. sylvestre extract to the diabetic rats decreased the activity of glutathione peroxidase in cytosolic liver and glutamate pyruvate transaminase in serum to normal levels.

  1. 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

  2. Sitagliptin attenuates cardiomyopathy by modulating the JAK/STAT signaling pathway in experimental diabetic rats

    PubMed Central

    Al-Rasheed, Nouf M; Al-Rasheed, Nawal M; Hasan, Iman H; Al-Amin, Maha A; Al-Ajmi, Hanaa N; Mahmoud, Ayman M

    2016-01-01

    Sitagliptin, a dipeptidyl peptidase-4 inhibitor, has been reported to promote cardioprotection in diabetic hearts by limiting hyperglycemia and hyperlipidemia. However, little is known about the involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway modulation in the cardioprotective effects of sitagliptin. The current study aimed to investigate the protective effects of sitagliptin against diabetic cardiomyopathy (DCM), focusing on the modulation of the JAK/STAT pathway. Diabetes was induced by streptozotocin injection, and rats received sitagliptin orally and daily for 90 days. Diabetic rats exhibited hyperglycemia, hyperlipidemia, and a significant increase in heart-to-body weight (HW/BW) ratio. Serum troponin I and creatine kinase MB, cardiac interleukin-6 (IL-6), lipid peroxidation, and nitric oxide levels showed significant increase in diabetic rats. In contrast, both enzymatic and nonenzymatic antioxidant defenses were significantly declined in the heart of diabetic rats. Histopathological study revealed degenerations, increased collagen deposition in the heart of diabetic rats. Sitagliptin alleviated hyperglycemia, hyperlipidemia, HW/BW ratio, histological architecture, oxidative stress, and inflammation, and rejuvenated the antioxidant defenses. In addition, cardiac levels of pJAK2 and pSTAT3 were increased in diabetic rats, an effect which was remarkably decreased after sitagliptin treatment. In conclusion, these results confer an evidence that sitagliptin has great therapeutic potential on DCM through down-regulation of the JAK/STAT signaling pathway. PMID:27418808

  3. Perfluorononanoic acid disturbed the metabolism of lipid in the liver of streptozotocin-induced diabetic rats.

    PubMed

    Fang, Xuemei; Gao, Guizhen; Zhang, Xingtao; Wang, Haichao

    2015-01-01

    Most studies on the liver toxicity of perfluorinated compounds (PFCs) are focused on healthy individuals, whereas the effects of PFCs on individuals with diabetes mellitus have not been fully characterized. This study aimed to investigate the acute exposure of perfluorononanoic acid (PFNA) on the metabolism of lipid in the liver of streptozotocin-induced diabetic rats. Male diabetic rats were orally dosed by gavage for 7 days with 0, 0.2, 1 and 5 mg/kg/day PFNA. The contents of lipid, the activities of enzyme, the expressions of protein in the liver and the serum parameters were detected. The results indicate that dose-dependent accumulation of triglyceride and total cholesterol occurred in the livers of diabetic rats after PFNA treatment. PFNA increased the activities of lipid synthetase, fatty acid synthease, glucose-6-phosphate dehydrogenase and decreased the activity of lipolytic enzyme, hepatic lipase, in the liver of diabetic rats. The changes of the isocitrate dehydrogenase, malicenzyme and lipoprotein lipase were not obvious. The expressions of protein related to lipid homeostasis, liver X receptor α and apolipoprotein E, were decreased after PFNA administration. Exposure to PFNA also increased the activity of serum alanine aminotransferase in diabetic rats. In conclusion, this study discloses that exposure to PFNA impacts on enzymes and proteins related to liver lipid metabolism and lead to obvious accumulation of lipid in the liver of diabetic rats, which may be responsible for hepatotoxicity of this compound in individuals with diabetes mellitus.

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

    PubMed

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

    2011-08-15

    Urtica dioica L. (Stinging nettle) has already been known for a long time as a medicinal plant in the world. This histopathological and morphometrical study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on testis of streptozotocin-induced diabetic rats. Eighteen male Wistar rats were allocated to equally normal, diabetic and treatment groups. Hyperglycemia was induced by Streptozotocin (80 mg kg(-1)) in animals of diabetic and treatment groups. One week after STZ injection (80 mg kg(-1)), the rats of treatment group received the extract of U. dioica (100 mg/kg/day) IP for 28 days. After 5 weeks of study, all the rats were sacrificed and testes were removed and fixed in bouin and after tissue processing stained with H and E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization and decrease in sperm concentration in seminiferous tubules were seen in diabetic and treatment groups group in comparison with control. External Seminiferous Tubular Diameter (STD) and Seminiferous Epithelial Height (SEH) significantly reduced (p < 0.05) in the diabetic rats compared with controls and these parameters in the treatment group were similar to diabetics animals. This study showed that hydroalcoholic extract of Urtica dioica leaves, after induction of diabetes; has no treatment effect on seminiferous tubules alterations in streptozotocin-induced diabetic rats.

  5. Antidiabetic activity of Artemisia amygdalina Decne in streptozotocin induced diabetic rats.

    PubMed

    Ghazanfar, Khalid; 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 β -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.

  6. Neurofunctional Evaluation of Young Male Offspring of Rat Dams with Diabetes Induced by Streptozotocin

    PubMed Central

    Delascio Lopes, Carla; Sinigaglia-Coimbra, Rita; Mazzola, Jacqueline; Camano, Luiz; Mattar, Rosiane

    2011-01-01

    Diabetes mellitus (DM) is a complex disease, being one of the most prevalent diseases worldwide. As a consequence, pregnancy-associated diabetes is increasingly common. Given the numerous studies about the influence of diabetes on offspring of diabetic rat dams, the neurological outcome is of outmost importance. This paper aimed at evaluating the neurofunctional performance of young male offspring of rat dams with diabetes induced by streptozotocin. Diabetes was induced in Wistar female rats by streptozotocin administration, while control groups received vehicle injection. At two-month survival period, male offspring from each group were randomized to the water maze Morris test, in order to assess their neurofunctional status. There was no significant difference between the groups as assessed by the Morris water maze test for spatial reference task. Our results point to the need of further investigation on the offspring neurofunctional performance. PMID:22363880

  7. Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract.

    PubMed

    Mediani, Ahmed; Abas, Faridah; Maulidiani, M; Khatib, Alfi; Tan, Chin Ping; Ismail, Intan Safinar; Shaari, Khozirah; Ismail, Amin; Lajis, N H

    2016-09-05

    Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus.

  8. Effect of dietary manganese on tissue antioxidants in STZ diabetic rats

    SciTech Connect

    Thompson, K.H.; Lee, M. )

    1991-03-15

    The objective of this experiment was to investigate the effect of Mn deficiency on tissue antioxidant levels under conditions of STZ (streptozotocin)-induced diabetes. Weanling, male Sprague-Dawley rats were assigned randomly to 1 of 6 groups: (1) Mn+ (manganese-sufficient), nondiabetic; (2) Mn{minus} (manganese-deficient), nondiabetic; (3) Mn+, diabetic for 4 weeks; (4) Mn{minus}, diabetic for 4 weeks; (5) Mn+, diabetic for 8 weeks; and (6) Mn{minus}, diabetic for 8 weeks. Decreased Mn levels in all tissues of Mn{minus} rats were accompanied by decreased MnSOD activity in kidney and heart, but not in liver or pancreas. Hepatic vitamin E was progressively increased in 4 and 8-week diabetic rats. Overall, diabetogenic effects of STZ were not amplified by manganese deficiency.

  9. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells

    PubMed Central

    Garcia, MM; Fandel, TM; Lin, G; Shindel, AW; Banie, L; Lin, CS; Lue, TF

    2010-01-01

    Introduction Impotence, or erectile dysfunction (ED), is a major complication of type-II diabetes, and many diabetic men with ED are refractory to common ED therapies. Aim To determine whether autologous adipose tissue derived stem cells (ADSC) injected into the penis of impotent obese type-II diabetic rats survive and improve erectile function. Main outcome measures Intracorporal pressure (ICP) increase with cavernous nerve (CN) electrostimulation, immunohistochemistry, real-time PCR, and serum glucose and testosterone assays. Methods Twenty-two 10-week old male fatty type-II diabetic ZDF rats underwent weight and blood glucose measurement every 2 weeks. At age 22 weeks, all animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence, and paragonadal adipose tissue (5 grams) was harvested and digested to yield 1.5 million ADSC. Impotent animals were randomized to ADSC treatment and sham control groups. At age 23 weeks, treatment group animals underwent penile injection of 1.5 million ADSC; control group animals received only PBS. Erectile function studies were repeated at age 26 weeks, followed by harvest of tissue and serum. Results Pre- and post-treatment stimulation ICP increase was significantly different between groups (p<0.002). In the control group, mean (SD) pre- and post-treatment stimulation ICP increase was 33.8 (15.9) and 31.4 (24.3) cmH2O, respectively, whereas in the treatment group they were 27.4 (14.8) and 65.3 (15.4) cmH2O. BrdU-labeled ADSC were observed within corporal tissue of the treatment group. TUNEL staining (p<0.0001) and caspase-3 m-RNA expression (p<0.05) were significantly higher within corporal tissue of control group versus treatment group animals. Conclusion Autologous ADSCs injected into the penis appear to survive and improve erectile function. Autologous ADSC therapy is a promising approach to treat diabetic impotence. PMID:20104670

  10. Impacts of Hibiscus esculentus extract on glucose and lipid profile of diabetic rats.

    PubMed

    Akbari, Fatemeh; Shahinfard, Najmeh; Mirhoseini, Mahmoud; Shirzad, Hedayatollah; Heidarian, Esfandiar; Hajian, Shabnam; Rafieian-Kopaei, Mahmoud

    2016-01-01

    Introduction:Hibiscus esculentus is capable to produce various molecules including phenolic and flavonoid compounds, phytosteroids with antioxidant property. Therefore, it has the potential to show antidiabetic activities. Objectives: This study was aimed to evaluate the impacts of Hibiscus esculentus extract on glucose and lipid profile of diabetic rats. The flavonoid, flavonol and phenolic components, as well as antioxidant activity of Hibiscus esculentus was also evaluated. Materials and Methods: In a preclinical study, 40 male Wistar rats were designated into four 10-member groups, i.e., control, diabetic control, diabetic Hibiscus esculentus, and diabetic glibenclamide. The Alloxan-induced diabetic rats received extracts orally for four weeks. Then, the serum biochemical factors were measured and compared by analysis of variance (ANOVA). Results: Serum glucose, triglyceride (TG), cholesterol, and low density lipoprotein cholesterol (LDL-C) were significantly decreased and high density lipoprotein cholesterol (HDL-C) increased in diabetic Hibiscus esculentus rats compared to diabetic control ones (P < 0.05). Conclusion: Improving the blood glucose and lipid profile in diabetic rats indicates that Hibiscus esculentus extract might be beneficial in diabetic patients.

  11. Impacts of Hibiscus esculentus extract on glucose and lipid profile of diabetic rats

    PubMed Central

    Akbari, Fatemeh; Shahinfard, Najmeh; Mirhoseini, Mahmoud; Shirzad, Hedayatollah; Heidarian, Esfandiar; Hajian, Shabnam; Rafieian-Kopaei, Mahmoud

    2016-01-01

    Introduction: Hibiscus esculentus is capable to produce various molecules including phenolic and flavonoid compounds, phytosteroids with antioxidant property. Therefore, it has the potential to show antidiabetic activities. Objectives: This study was aimed to evaluate the impacts of Hibiscus esculentus extract on glucose and lipid profile of diabetic rats. The flavonoid, flavonol and phenolic components, as well as antioxidant activity of Hibiscus esculentus was also evaluated. Materials and Methods: In a preclinical study, 40 male Wistar rats were designated into four 10-member groups, i.e., control, diabetic control, diabetic Hibiscus esculentus, and diabetic glibenclamide. The Alloxan-induced diabetic rats received extracts orally for four weeks. Then, the serum biochemical factors were measured and compared by analysis of variance (ANOVA). Results: Serum glucose, triglyceride (TG), cholesterol, and low density lipoprotein cholesterol (LDL-C) were significantly decreased and high density lipoprotein cholesterol (HDL-C) increased in diabetic Hibiscus esculentus rats compared to diabetic control ones (P < 0.05). Conclusion: Improving the blood glucose and lipid profile in diabetic rats indicates that Hibiscus esculentus extract might be beneficial in diabetic patients. PMID:28197508

  12. 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.

  13. Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.

    PubMed

    Valcheva-Kuzmanova, S; Kuzmanov, K; Tancheva, S; Belcheva, A

    2007-03-01

    Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications.

  14. Gene expression profiling in glomeruli of diabetic nephropathy rat.

    PubMed

    Zhang, Qian; Xiao, Xinhua; Li, Ming; Li, Wenhui; Yu, Miao; Zhang, Huabing; Sun, Xiaofang; Mao, Lili; Xiang, Hongding

    2012-08-01

    Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease (ESRD) as the burden of diabetes increases worldwide. To find improved intervention strategies for this disease, it is necessary to investigate the molecular mechanisms involved. To obtain more insight into processes that lead to DN, mRNA expression profiles of diabetic and normal glomeruli from rat kidneys were compared. Rats were divided into a control group and a DN group randomly. The DN group was injected with streptozotocin. Fasting blood glucose (FBG) and weight were measured monthly. On the 12th week, blood samples were collected and analyzed for plasma creatinine and blood urea nitrogen (BUN). Glomeruli were isolated and Illumina Rat Ref-12 V1.0 Expression Beadchip gene array was performed. Quantitative realtime polymerase chain reaction (Q-RT-PCR) was used to confirm the results of gene array for a selected number of genes. We found FBG, 24-h urinary albumin, serum creatinine and BUN were significantly increased, while urinary creatinine and body weight were significantly decreased in the DN group. Glomeruli from the DN group had 624 genes with differential expression. DAVID (Database for Annotation, Visualization and integrated Discovery) analysis showed that the three most enriched terms were 'cytosol' (GO:0005829), 'translational elongation' (GO:0006414) and 'mitochondion' (GO:0005739). Those genes could be mapped to eight pathways. The most common type of enriched pathway was related to 'extracellular matrix (ECM)-receptor interaction'. Other pathways included those for 'ribosome', 'focal adhesion', 'oxidative phosphorylation', 'transforming growth factor (TGF)-beta signaling pathway', 'Parkinson's disease', 'Alzheimer's disease' and 'renin-angiotensin system'. Q-RT-PCR verified that Atp5b (F1-ATPase beta subunit), Col1a1 (collagen type 1 alpha 1), Cox6c (cytochrome c oxidase subunit VIc), Ndufs3 (NADH dehydrogenase [ubiquinone] Fe-S protein 3) and Tgfb1 (transforming

  15. 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 (λ=400-2000nm, 20J/cm2) and G3: Polarized Light (λ=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®, λ400-2000 nm, 40mW; 2.4J/cm2 per minute; Φ +/- 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.

  16. Depression in Patients with Type II Diabetes: Case study at Diabetic Outpatient Clinic, in Samut Prakan

    PubMed Central

    Thongsai, Soontareeporn; Watanabenjasopa, Suntaree; Youjaiyen, Malinee

    2014-01-01

    This descriptive research studied the depression level of patients with diabetes type II at diabetic clinics in Samut Prakarn, and, identified the causes of severe depression in patients with type 2. There were 209 participants enrolled in the study. The samples were selected by opportunistic sampling technique. The data were collected from May 2013 to July 2013, using the CES-D questionnaire, with Cronbach’s coefficient alpha 0.82 and guidelines for interviews. Data were analyzed by descriptive statistics. Research Results: 1. 66 percent of participants had a depression score at a low level. 2. The CES-D showed that, 44 percent were unhappy and 38 percent did not feel that their life was enjoyable. 29 percent felt no hope for the future, 5.6 percent were easily upset and 8.3 percent suffered from insomnia and severe depression. 3. Half of the participants mentioned that troubled family relationships was a main cause of their depression, 42.9 percents felt worrying about their illness, 35.3 percent blamed over work and almost 15 percent identified loss of love as the cause of depression. PMID:24373272

  17. Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats.

    PubMed

    Hussein, Mohamed M A; Mahfouz, Mohamed K

    2016-08-01

    The development of diabetic nephropathy (DN) relays mainly on control of blood glucose and restrains hyperglycemic-induced oxidative stress. Hence, the effect administration of resveratrol (RSV) (5mg/kg) alone or in combination with rosuvastatin (RSU) (10mg/kg) on development and progression of diabetic nephropathy (DN) was evaluated. Oral treatment of diabetic rats with RSV alone or co-administered with RSU improved renal dysfunction indicated by a significant decrease in serum creatinine, urinary protein and urinary TGF-β1 when compared with diabetic control rats. Also, a significant increase in body weight, relative kidney weight with a significant decrease in serum glucose and glycated hemoglobin in diabetic treated groups when compared with diabetic control group. Hyperglycemic-induced oxidative stress in diabetic control rats indicated by a significant decrease in renal activities of catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione level with a significant increase in malondialdehyde levels. However, oral treatment of diabetic rats with RSV alone or co-administered with RSU improved the antioxidant status back to control values. Similarly, mRNA analysis of quantitative real time-PCR substantiated that RSV with RSU notably normalizes the renal expression of TGF-β1, fibronectin, NF-κB/p65, Nrf2, Sirt1 and FoxO1 in the diabetic group of rats. The histopathological observations of the combined treated diabetic rats effectively protect the kidneys from hyperglycemic-induced oxidative damage. These findings confirmed the renoprotective effects of RSV with RSU treatment through improving glycemic control and attenuating oxidative stress damage in renal tissues of diabetic rats.

  18. Glucagon binding and lipolytic response in isolated adipocytes from streptozotocin-diabetic rats.

    PubMed

    Mayor, P; Calle, C

    1988-04-01

    Evidence for pre-receptor, receptor and post-receptor glucagon defects was investigated in adipocytes from streptozotocin-diabetic rats. For this purpose male Wistar rats were injected by cardiac puncture with streptozotocin (65 mg/Kg body-weight) or saline solution and sacrificed after 7 and 15 days of drug administration. Increased glucagon levels and increased glucagon degradation in serum together with a decrease in glucagon binding were found in both groups of diabetic rats. The decrease in glucagon binding was related to a decrease in the number of glucagon receptors/cell rather than to a change in receptor affinity. The lipolytic response of glucagon was increased. However, the ability of glucagon to increase basal or theophylline-stimulated cAMP accumulation in the incubation medium of adipocytes from diabetic rats was decreased. Such alterations could represent a counter-regulatory mechanism of the hyperglucagonemia detected in streptozotocin-diabetic rats.

  19. 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.

  20. 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.

  1. Oxidative stress in streptozocin-diabetic rats: Amelioration by mulberry (Morus Indica L.) leaves.

    PubMed

    Andallu, Bondada; Kumar, Av Vinay; Varadacharyulu, N Ch

    2012-12-22

    OBJECTIVE: To investigate amelioration of oxidative stress by mulberry (Morus indica L.) leaves in streptozocin (STZ)-diabetic rats, as the leaves of mulberry (Morus indica L.) of Moraceae, are reported to be rich in a number of bioactive principles, i.e. antioxidant vitamins, flavonoids and moracins that can fight against oxidative stress in diabetes. METHOD: Normal wistar albino rats and STZ-diabetic rats were treated with dried mulberry leaf powder at 25% in the diet for a period of 8 weeks. The antioxidant role of mulberry was assessed by determining the effect of the leaves on hepatic lipid peroxidation, a marker of oxidative stress and the activity of hepatic antioxidant enzymes and serum antioxidant vitamins in comparison with untreated normal and diabetic rats. RESULTS: Increased oxidative stress as shown by increased lipid peroxidation and increased activity of catalase (CAT) in hepatic tissue, decreased serum ascorbic acid (vitamin C) and tocopherol (vitamin E) in diabetic rats were countered by mulberry leaves. In addition, decreased activities of hepatic antioxidant enzymes, i.e. glucose-6-phosphate dehydrogenase (G6PDH), glutathione peroxidase (GPx), glutathinone-S-tranferase (GST) and superoxide dismutase (SOD) were significantly increased by 34%, 61%, 19% and 53% respectively in mulberry leaves-treated diabetic rats as compared with diabetic control rats. CONCLUSION: Treatment with mulberry leaves protected STZ-diabetic rats from lipid peroxidation and elevated the activities of defense enzymes. This study reveals ameliorating effect of mulberry leaves on oxidative stress in diabetic rats by the synergistic action of a number of bioactive compounds present in mulberry leaves.

  2. Regulation of oxidative stress and somatostatin, cholecystokinin, apelin gene expressions by ghrelin in stomach of newborn diabetic rats.

    PubMed

    Coskun, Zeynep Mine; Sacan, Ozlem; Karatug, Ayse; Turk, Neslihan; Yanardag, Refiye; Bolkent, Sehnaz; Bolkent, Sema

    2013-09-01

    The aim of the study was to determine whether ghrelin treatment has a protective effect on gene expression and biochemical changes in the stomach of newborn streptozotocin (STZ) induced diabetic rats. In this study, four groups of Wistar rats were used: control, ghrelin control, diabetic and diabetic+ghrelin. The rats were sacrificed after four weeks of treatment for diabetes. The gene expressions of: somatostatin, cholecystokinin, apelin and the altered active caspase-3, active caspase-8, proliferating cell nuclear antigen, were investigated in the pyloric region of the stomach and antioxidant parameters were measured in all the stomach. Although ghrelin treatment to diabetic rats lowered the stomach lipid peroxidation levels, the stomach glutathione levels were increased. Exogenous ghrelin caused an increased activities of stomach catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase in diabetic rats. Numbers of somatostatin, cholecystokinin and proliferating cell nuclear antigen immunoreactive cells decreased in the diabetic+ghrelin group compared to the diabetic group. Apelin mRNA expressions were remarkably less in the diabetic+ghrelin rats than in diabetic rats. The results may indicate that ghrelin treatment has a protective effect to some extent on the diabetic rats. This protection is possibly accomplished through the antioxidant activity of ghrelin observed in type 2 diabetes. Consequently exogenous ghrelin may be a candidate for therapeutic treatment of diabetes.

  3. Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats

    PubMed Central

    POMJUNYA, Atchariya; RATTHANOPHART, Jasada; FUNGFUANG, Wirasak

    2017-01-01

    The present study investigated the effects of Vernonia cinerea (VC) on the reproductive function in streptozotocin (STZ)-induced diabetic male rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: group 1, normal control rats; group 2, diabetic untreated rats; group 3, diabetic rats treated with VC (10 mg/kg); and group 4, diabetic rats treated with VC (40 mg/kg). Diabetes mellitus (DM) was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 30 consecutive days. Body weight, blood glucose, food intake, epididymal sperm parameters, testicular microstructure and serum testosterone levels were evaluated. VC treatment significantly restored the sperm motility and testosterone concentration, and decreased the testicular histopathological changes in DM rats. Moreover, high-dose VC exhibited an antidibetic activity and significantly improved the sperm count. In conclusion, we found, for the first time, that administration of VC significantly restored the testicular function and testosterone concentration in diabetic male rats. PMID:28190818

  4. Purification and partial characterization of myosin II from rat testis.

    PubMed

    Dias, Decivaldo dos Santos; Coelho, Milton Vieira

    2007-10-01

    The intent, in this work, was to isolate rat testis myosin II. Testis 40,000 x g x 40' supernatant was frozen at -20 degrees C for 48 h and, after it was thawed and centrifuged. The precipitate, after washed twice, was enriched in three polypeptides bands: p205, p43 and one that migrated together with the front of the gel. These polypeptides were solubilized in pH 10.8 at 27 degrees C and separated in Sephacryl S-400 column. Three low weight polypeptides co-eluted together with p205. The p205 was marked with anti-myosin II, possess actin-stimulated Mg-ATPase activity and co-sedimented with F-actin in the absence, but not in the presence, of ATP. In the present study, we have been developing a method for purification of myosin II from rat testis.

  5. Anti-diabetic and anti-oxidative activity of fixed oil extracted from Ocimum sanctum L. leaves in diabetic rats

    PubMed Central

    SUANARUNSAWAT, THAMOLWAN; ANANTASOMBOON, GUN; PIEWBANG, CHUTCHAI

    2016-01-01

    Ocimum sanctum L. (OS) leaves have been shown to exert diverse potential benefits in a variety of stress conditions. The present study was conducted to elucidate the effects of the fixed oil extracted from OS leaves on the blood glucose levels and serum lipid profile of streptozotocin-induced diabetic rats. In addition, the anti-oxidative activity of OS leaves to protect various organs including the liver, kidney and heart was investigated. The fixed oil of the OS leaves was extracted using hexane, and the various fatty acid contents of the oil were determined using gas chromatography-mass spectrometry. Male Wistar rats were allocated into three groups (n=7 per group): Normal control rats, diabetic rats and diabetic rats fed daily with the fixed oil for three weeks. The results showed that α-linolenic acid was the primary fatty acid contained in the fixed oil of OS. After 3 weeks of diabetic induction, the rats exhibited increased blood glucose levels and serum lipid profile, in addition to elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase MB subunit (CK-MB), creatinine and blood urea nitrogen (BUN). The fixed oil significantly decreased the elevated levels of blood glucose, the serum lipid profile and the levels of serum creatinine and BUN (P<0.001), without exerting significant effects on the elevated serum levels of AST, ALT, LDH and CK-MB. Furthermore, the fixed oil increased the diabetically-reduced levels of serum insulin and decreased the rat kidney weight. Fixed oil suppressed the elevated thiobarbituric acid reactive substances (TBARS) level and increased the activity of various antioxidative enzymes in the rat renal tissue. By contrast, the fixed oil had no effect on the elevated TBARS level and the inhibited activity of the antioxidative enzymes in the rat liver and cardiac tissues. Histopathological results indicated that the fixed oil preserved the renal tissue

  6. Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat.

    PubMed

    Sahin, Kazim; Onderci, Muhittin; Tuzcu, Mehmet; Ustundag, Bilal; Cikim, Gurkan; Ozercan, Ibrahim H; Sriramoju, Vidyasagar; Juturu, Vijaya; Komorowski, James R

    2007-09-01

    Chromium supplements are widely used as an alternative remedy for type 2 diabetes mellitus (T2DM). In vitro study findings show that chromium picolinate (CrPic) may improve insulin sensitivity by enhancing intracellular insulin receptor. In this study, we evaluated the metabolic effects of CrPic in a rat model of T2DM. Male Sprague-Dawley rats (n = 45, 8 weeks old) were divided into 3 groups. The controls (group I) received a standard diet (12% of calories as fat); group II received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were intraperitoneally injected with streptozotocin (STZ, 40 mg/kg; HFD/STZ) on day 14; group III rats were given group II diets with the addition of 80 microg CrPic per kilogram body weight per day. The addition of CrPic in the group III treatment lowered glucose by an average of 63% (P < .001), total cholesterol by 9.7% (P < .001), and triglycerides by 6.6% (P < .001) compared with group II treatment. Compared with group II, CrPic treatment also lowered free fatty acid levels by 24% (P < .001), blood urea by 33% (P < .05), and creatinine level by 25% (P < .01), and reduced the severity of glomerular sclerosis (P < .0001). Histopathologic findings suggest that the CrPic-treated group had normal renal tubular appearance compared with the HFD/STZ-treated group. Normal appearance of hepatocytes was observed in the CrPic-treated group. These results showed that CrPic has marked beneficial effects against microvascular complications. In conclusion, HFD/STZ rats provide a novel animal model for T2DM. Further treatment with CrPic for 10 weeks significantly ameliorated changes in metabolic risk factors including favorable changes in histopathology of the liver, kidney, and pancreas, suggesting its potential role in the management of diabetes.

  7. Minocycline reduces mechanical allodynia and depressive-like behaviour in type-1 diabetes mellitus in the rat.

    PubMed

    Amorim, Diana; Puga, Sónia; Bragança, Rui; Braga, António; Pertovaara, Antti; Almeida, Armando; Pinto-Ribeiro, Filipa

    2017-03-08

    A common and devastating complication of diabetes mellitus is painful diabetic neuropathy (PDN) that can be accompanied by emotional disorders such as depression. A few studies have suggested that minocycline that inhibits microglia may attenuate pain hypersensitivity in PDN. Moreover, a recent study reported that minocycline has an acute antidepressive-like effect in diabetic animals. Here we studied whether (i) prolonged minocycline treatment suppresses pain behaviour in PDN, (ii) the minocycline effect varies with submodality of pain, and (iii) the suppression of pain behaviour by prolonged minocycline treatment is associated with antidepressive-like effect. The experiments were performed in streptozotocin-induced rat model of type-1 diabetes. Pain behaviour was evoked by innocuous (monofilaments) and noxious (paw pressure) mechanical stimulation, innocuous cold (acetone drops) and noxious heat (radiant heat). Depression-like behaviour was assessed using forced swimming test. Minocycline treatment (daily 80mg/kg per os) of three-week duration started four weeks after induction of diabetes. Diabetes induced mechanical allodynia and hyperalgesia, cold allodynia, heat hypoalgesia, and depression-like behaviour. Minocycline treatment significantly attenuated mechanical allodynia and depression-like behaviour, while it failed to produce significant changes in mechanical hyperalgesia, cold allodynia or heat hypoalgesia. The results indicate that prolonged per oral treatment with minocycline has a sustained mechanical antiallodynic and antidepressive-like effect in PDN. These results support the proposal that minocycline might provide a treatment option for attenuating sensory and comorbid emotional symptoms in chronic PDN.

  8. Antidiabetic activity and phytochemical screening of crude extract of Stevia rebaudiana in alloxan-induced diabetic rats

    PubMed Central

    Kujur, R. S.; Singh, Vishakha; Ram, Mahendra; Yadava, Harlokesh Narayan; Singh, K. K.; Kumari, Suruchi; Roy, B. K.

    2010-01-01

    Background: Stevia rebaudiana regulates blood sugar, prevents hypertension and tooth decay. Other studies have shown that it has antibacterial as well as antiviral property. Methods: Preliminary phytochemical screening of aqueous, ether and methanolic extracts of S. rebaudiana was done. Acute and sub-acute toxicity were conducted on twenty four Albino rats, divided into one control (Group I) and three treatment groups viz. aqueous extract (Group II), ether extract (Group III) and methanolic extract (Group IV). For the study of antidiabetic effect of S. rebaudiana rats were divided into seven groups (n=6). Diabetes was induced by a single dose of 5% alloxan monohydrate (125 mg/kg, i.p.) after 24 hour fasting.Blood samples were analysed on day 0, 1, 5, 7, 14 and 28. Results: Phytochemical tests showed presence of different kinds of phyto-constituents in aqueous, ether and methanol extract of Stevia rebaudiana leaves. Daily single dose (2.0 g/kg) administration of aqueous extract (A.E.) , ether extract (E.E.) and methanol extract (M.E.) for 28 days of S. rebaudiana could not show any significant change in ALT and AST levels in rats. Blood sugar level was found to be decreased on day 28 in groups of rats treated with A.E., E.E. and M.E. of S. rebaudiana. Conclusion: The extracts of Stevioside rebaudiana could decrease the blood glucose level in diabetic rats in time dependent manner. PMID:21808578

  9. Guanine nucleotide binding regulatory proteins and adenylate cyclase in livers of streptozotocin- and BB/Wor-diabetic rats. Immunodetection of Gs and Gi with antisera prepared against synthetic peptides.

    PubMed Central

    Lynch, C J; Blackmore, P F; Johnson, E H; Wange, R L; Krone, P K; Exton, J H

    1989-01-01

    Adenylate cyclase in liver plasma membranes from streptozotocin-diabetic (STZ) or BB/Wor spontaneously diabetic rats showed increased responsiveness to GTP, glucagon, fluoroaluminate, and cholera toxin. Basal or forskolin-stimulated activity was unchanged in STZ rats, but increased in BB/Wor rats. No change in the alpha-subunit of Gi (alpha i) was observed in STZ or BB/Wor rats using pertussis toxin-stimulated [32P]ADP-ribosylation. Immunodetection using antibodies against the COOH-terminal decapeptides of alpha T and alpha i-3 showed no change in alpha i in STZ rats and a slight decrease in BB/Wor rats. Angiotensin II inhibition of hepatic adenylate cyclase was not altered in either diabetic rat. In both models of diabetes, Gs alpha-subunits were increased as measured by cholera toxin-stimulated [32P]-ADP-ribosylation of 43-47.5-kD peptides, reconstitution with membranes from S49 cyc- cells or immunoreactivity using antibodies against the COOH-terminal decapeptide of alpha s. These data indicate that STZ-diabetes increases hepatic Gs but does not change Gi or adenylate cyclase catalytic activity. In contrast, BB/Wor rats show increased hepatic Gs and adenylate cyclase. These changes could explain the increase in hepatic cAMP and related dysfunctions observed in diabetes. Images PMID:2498395

  10. Lycopene ameliorates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rat.

    PubMed

    Kuhad, Anurag; Chopra, Kanwaljit

    2008-02-01

    Peripheral neuropathy is one of the common complications of diabetes mellitus. It is frequently associated with debilitating pain. The present study was designed to investigate effect of Lycopene, a carotenoid found in tomatoes, on hyperalgesia and cold allodynia in streptozotocin (STZ) induced diabetic rats. After 4-weeks of STZ injection, diabetic mice exhibited a significant thermal hyperalgesia cold allodynia, hyperglycemia and loss of body weights as compared with control rats. Chronic treatment of lycopene for 4 weeks significantly attenuated the cold allodynia and thermal hyperalgesia. The results emphasize the role of antioxidant such as lycopene as an adjuvant therapy in the treatment of diabetic neuropathy.

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

    PubMed Central

    Noriega-Cisneros, Ruth; Ortiz-Ávila, Omar; Esquivel-Gutiérrez, Edgar; Clemente-Guerrero, Mónica; Manzo-Avalos, Salvador; Salgado-Garciglia, Rafael; Cortés-Rojo, Christian; Boldogh, Istvan; Saavedra-Molina, Alfredo

    2012-01-01

    Diabetes mellitus (DM) is a significant risk factor for the development of cardiovascular complications. This study was undertaken to investigate the effect of chronic administration of ethanolic extract of Eryngium carlinae on glucose, creatinine, uric acid, total cholesterol, and triglycerides levels in serum of streptozotocin- (STZ-) induced diabetic rats. Triglycerides, total cholesterol, and uric acid levels increased in serum from diabetic rats. The treatment with E. carlinae prevented these changes. The administration of E. carlinae extract reduced the levels of creatinine, uric acid, total cholesterol, and triglycerides. Thus administration of E. carlinae is able to reduce hyperlipidemia related to the cardiovascular risk in diabetes mellitus. PMID:22162811

  12. Effect of bitter gourd (Momordica charantia) on glycaemic status in streptozotocin induced diabetic rats.

    PubMed

    Shetty, A K; Kumar, G Suresh; Sambaiah, K; Salimath, P V

    2005-09-01

    Bitter gourd (Momordica charantia), a commonly consumed vegetable is used as an adjunct in the management of diabetes mellitus. A study was carried out to examine the effect of edible portion of bitter gourd at 10% level in the diet in streptozotocin induced diabetic rats. To evaluate the glycaemic control of bitter gourd during diabetes, diet intake, gain in body weight, water intake, urine sugar, urine volume, glomerular filtration rate and fasting blood glucose profiles were monitored. Water consumption, urine volume and urine sugar were significantly higher in diabetic controls compared to normal rats and bitter gourd feeding alleviated this rise during diabetes by about 30%. Renal hypertrophy was higher in diabetic controls and bitter gourd supplementation, partially, but effectively prevented it (38%) during diabetes. Increased glomerular filtration rate in diabetes was significantly reduced (27%) by bitter gourd. An amelioration of about 30% in fasting blood glucose was observed with bitter gourd feeding in diabetic rats. These results clearly provided experimental evidence that dried bitter gourd powder in the diet at 10% level improved diabetic status signifying its beneficial effect during diabetes.

  13. Effects of melatonin on biochemical factors and food and water consumption in diabetic rats

    PubMed Central

    Bibak, Bahram; Khalili, Monavareh; Rajaei, Ziba; Soukhtanloo, Mohammad; Hadjzadeh, Mousa-Al-Reza; Hayatdavoudi, Parichehr

    2014-01-01

    Background: Diabetic neuropathy is one of the serious problems due to microvessel vasculopathy in diabetes. It has been reported that hyperglycemia and hypertriglyceridemia are the underlying mechanisms in inducing and progression of diabetic neuropathy. The aim of the present study was to investigate the effects of melatonin on serum glucose and lipid levels, as well as food consumption and water intake in streptozotocin-induced diabetic rats. Materials and Methods: Eighty male Wistar rats were randomly assigned to six groups including; normal control group, diabetic control group and 4 diabetic experimental groups that received melatonin intraperitoneally at doses of 2.5, 5, 10, and 20 mg/kg at the end of sixth week after verification of neuropathy by means of evaluation of sciatic nerve conduction velocity (MNCV), for two weeks. Blood glucose and lipid levels, body weight, the amounts of food consumption, and water intake were determined in all groups at weeks 0 (before diabetes induction), 3, 6, and at the end of eighth week. Results: Treatment with melatonin reduced significantly the serum glucose (P < 0.001) and triglyceride (P < 0.05) levels, food consumption (P < 0.001), and water intake (P < 0.001) in diabetic rats at the end of eighth week. However, melatonin had no significant effect on body weight of diabetic animals. Conclusions: Treatment with melatonin could improve several signs of diabetes, including hyperglycemia, hypertriglyceridemia, polyphagia, and polydipsia. Therefore, melatonin may be used as an adjunct therapy in the treatment of diabetes. PMID:25250287

  14. Exercise pretraining attenuates endotoxin-induced hemodynamic alteration in type I diabetic rats.

    PubMed

    Hung, Ching-Hsia; Chen, Yu-Wen; Shao, Dong-Zi; Chang, Che-Ning; Tsai, Yung-Yuh; Cheng, Juei-Tang

    2008-10-01

    Higher expression of heat shock protein 72 (HSP72) reduces the mortality rate and organ damage in septic shock and prevents cardiac mitochondrial dysfunction due to lipopolysaccharide (LPS). Our hypothesis is that exercise preconditioning may increase the expression of HSP72 in heart and the nucleus tractus solitarii (NTS) of the brain to alleviate the cardiovascular dysfunction in type I diabetic rats receiving endotoxin. Wistar rats were randomly assigned to the following groups: sedentary normal, sedentary type I diabetic rats, and type I diabetic rats with exercise training. The trained rats ran on a treadmill 5 d.week-1, 30-60 min.d-1, at an intensity of 1.0 mile.h-1 (1 mile = 1.6 km) over a 3 week period. Twenty-four hours after the last training session, we compared the temporal profiles of mean arterial pressure, heart rate, cardiac output, stroke volume, and serum tumor necrosis factor alpha level in rats receiving an injection of LPS. In addition, HSP72 expression in heart and NTS from each group was determined. We found that HSP72 expression in the heart and NTS was significantly increased in diabetic rats with exercise training. After administration of LPS, the survival time was significantly longer in diabetic rats with exercise training. Additionaly, serum tumor necrosis factor alpha levels decreased as compared with those rats not receiving exercise training. Exercise training also diminished cardiovascular dysfunction in diabetic rats during endotoxemia. These data suggest that exercise may increase the expression of HSP72 in the heart and NTS to protect against the high mortality rate and attenuate cardiovascular dysfunction in diabetic rats during endotoxemia.

  15. Rosiglitazone is effective to improve renal damage in type-1-like diabetic rats.

    PubMed

    Huang, K-C; Cherng, Y-G; Chen, L-J; Hsu, C-T; Cheng, J-T

    2014-04-01

    A marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats) showing diabetic nephropathy. It has been documented that klotho is the target gene of PPARγ. However, the effect of PPARγ agonist on klotho expression in kidney of STZ rats remains obscure. Thus, we used rosiglitazone (TZD) as PPARγ agonist to investigate the effect on renal dysfunction in STZ rats. Treatment of TZD reversed the lower levels of PPARγ, klotho, and FGFR1 expressions in kidneys of STZ rats without the correction of hyperglycemia. Also, renal functions and structural defeats were improved by TZD treatment. Taken together, oral administration of TZD may improve STZ-induced diabetic nephropathy due to restoration of the expression of klotho axis through an increase in PPARγ expression without changing blood glucose in rats.

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

    PubMed Central

    Luippold, Gerd; Bedenik, Jessica; Voigt, Anke; Grempler, Rolf

    2016-01-01

    The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose-lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ-rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1 diabetes. PMID:27253523

  17. Histological changes in the kidneys of experimental diabetic rats fed with Momordica charantia (bitter gourd) extract.

    PubMed

    Teoh, S L; Abd Latiff, Azian; Das, S

    2010-01-01

    Momordica charantia (MC) or bitter gourd is widely known for its antidiabetic properties. The aim of the present study was to observe the protective effect of MC extract on the kidneys of streptozotocin-induced diabetic rats. Eighteen male Sprague-Dawley rats (n=18) weighing 200+/-50 g were taken for the study. The study comprised of three groups i.e. a non-diabetic, diabetic untreated and diabetic treated with MC extract, with each group comprising of six (n=6) rats. Diabetes was induced in the overnight fasted rats by intramuscular injection of streptozotocin (50 mg/kg body weight). The MC extract (50 mg/kg body weight) was administered via oral gavage. Both the kidneys were collected on the tenth day following treatment. Histological study using Verhoeff's van Gieson (VvG) and Periodic Acid-Schiff (PAS) stains were performed. The kidneys of the diabetic rats showed thickening of the basement membrane of the Bowman's capsule, edema and hypercellurarity of the proximal tubules, necrosis and hyaline deposits. These features were found to be reversed when the MC extract was administered to the experimental animals. The MC extract acted as an antioxidant thereby preventing the oxidative damage involved in the diabetic kidney. The administration of MC extract prevents oxidative damage in diabetic nephropathy.

  18. Antihyperlipidemic Effect of Peucedanum Pastinacifolium Extract in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Movahedian, Ahmad; Zolfaghari, Behzad; Sajjadi, S. Ebrahim; Moknatjou, Reza

    2010-01-01

    INTRODUCTION: Dyslipidemia is one of the most common complications of diabetes mellitus, significantly contributing to cardiovascular morbidity and mortality in diabetic patients. Peucedanum pastinacifolium Boiss. & Hausskn. is commonly used as an antihyperlipidemic vegetable in Iranian folk medicine. MATERIAL AND METHODS: In this study, we examined a hydroalcoholic extract of the aerial parts of Peucedanum pastinacifolium to determine its lipid-lowering activity in normal and streptozotocin (STZ)-induced diabetic rats. Experimental diabetes mellitus was induced by a single intraperitoneal administration of streptozotocin. Normal and streptozotocin-induced diabetic rats were separated into four groups. The groups were fed with 0, 125, 250 or 500 mg/kg body weight of Peucedanum Pastinacifolium hydroalcoholic Extract (PPE) in aqueous solution for 30 days. RESULTS: The results show that there were significant (P < 0.05) increases in total serum cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in streptozotocin-induced diabetic rats. Treatment of diabetic rats with PPE over a period of a month returned these levels close to control levels. CONCLUSION: These results suggest that PPE has hypolipidemic effects in streptozotocin-induced diabetic rats. PMID:20613940

  19. Effect of sodium tungstate on visual evoked potentials in diabetic rats

    PubMed Central

    Bulut, Mehmet; Dönmez, Barış Özgür; Öztürk, Nihal; Başaranlar, Göksun; Kencebay Manas, Ceren; Derin, Narin; Özdemir, Semir

    2016-01-01

    AIM To evaluate the effect of sodium tungstate on visual evoked potentials (VEPs) in diabetic rats. METHODS Wistar rats were randomly divided into three groups as normal control, diabetic control and diabetic rats treated with sodium tungstate. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg). Sodium tungstate [40 mg/(kg·d)] was administered for 12wk and then VEPs were recorded. Additionally, thiobarbituric acid reactive substance (TBARS) levels were measured in brain tissues. RESULTS The latencies of P1, N1, P2, N2 and P3 waves were significantly prolonged in diabetic rats compared with control group. Diabetes mellitus caused an increase in the lipid peroxidation process that was accompanied by changes in VEPs. However, prolonged latencies of VEPs for all components returned to control levels in sodium tungstate-treated group. The treatment of sodium tungstate significantly decreased brain TBARS levels and depleted the prolonged latencies of VEP components compared with diabetic control group. CONCLUSION Sodium tungstate shows protective effects on visual pathway in diabetic rats, and it can be worthy of further study for potential use. PMID:27275420

  20. Study on the use of quantitative ultrasound evaluation of diabetic neuropathy in the rat sciatic nerve.

    PubMed

    Huang, Yunxia; Hu, Bing; Zhu, Jiaan

    2016-12-01

    Ultrasound is an effective tool for peripheral disease with direct imaging of morphological and echogenic changes, but it has limitations when applied to evaluation of diabetic peripheral neuropathy. The aim of this study was to assess the role of ultrasound to quantitatively evaluate diabetic peripheral neuropathy in rat sciatic nerve. In our experiments, ultrasound imaging and electrophysiological examination testing of sciatic nerves were monitored in diabetic and control rats at the period of 1st and 4th month of hyperglycemia. Cross sectional area, intraneural echo intensity, inner diameter, motor nerve conduction velocity, and histological changes were measured and compared between diabetic and control groups. Intraneural hyperechoic were observed in the diabetic rats, and the echo intensity of the sciatic nerve was increased in diabetic rats rather than control lean rats at 4th month of hyperglycemia (p < 0.05), which has shown a similar correlation with functional deficit and histological changes based on the severity of diabetic peripheral neuropathy. We conclude that the echo intensity is potentially useful in detecting diabetic peripheral neuropathy, which can pave the way for more accurate and efficient diagnosis in clinical study.

  1. Pleurotus tuber-regium Polysaccharides Attenuate Hyperglycemia and Oxidative Stress in Experimental Diabetic Rats

    PubMed Central

    Huang, Hui-Yu; Korivi, Mallikarjuna; Chaing, Ying-Ying; Chien, Ting-Yi; Tsai, Ying-Chieh

    2012-01-01

    Pleurotus tuber-regium contains polysaccharides that are responsible for pharmacological actions, and medicinal effects of these polysaccharides have not yet been studied in diabetic rats. We examined the antidiabetic, antihyperlipidemic, and antioxidant properties of P. tuber-regium polysaccharides in experimental diabetic rats. Forty rats were equally assigned as diabetic high-fat (DHF) diet and polysaccharides treated DHF groups (DHF+1P, DHF+2P, and DHF+3P, 20 mg/kg bodyweight/8-week). Diabetes was induced by chronic low-dose streptozotocin injections and a high-fat diet to mimic type 2 diabetes. Polysaccharides (1P, 2P, and 3P) were extracted from three different strains of P. tuber-regium. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels substantially decreased, while serum insulin levels were restored by polysaccharides treatment compared to DHF. Furthermore, plasma total cholesterol, triglycerides, and low-density lipoprotein levels were significantly (P < 0.01) lower in polysaccharide groups. High-density lipoprotein levels were attenuated with polysaccharides against diabetes condition. Polysaccharides inhibited (P < 0.01) the lipid peroxidation index (malondialdehyde), and restored superoxide dismutase and glutathione peroxidase activities in the liver of diabetic rats. The antihyperglycemic property of polysaccharides perhaps boosts the antioxidant system that attenuates oxidative stress. We emphasize that P. tuber-regium polysaccharides can be considered as an alternative medicine to treat hyperglycemia and oxidative stress in diabetic rats. PMID:22973406

  2. Effects of Lonicera japonica Thunb. on Type 2 Diabetes via PPAR-γ Activation in Rats.

    PubMed

    Han, Jae Min; Kim, Mi Hye; Choi, You Yeon; Lee, Haesu; Hong, Jongki; Yang, Woong Mo

    2015-10-01

    Lonicera japonica Thunb. (Caprifoliaceae) is a traditional herbal medicine and has been used to treat diabetic symptoms. Notwithstanding its use, the scientific basis on anti-diabetic properties of L. japonica is not yet established. This study is designed to investigate anti-diabetic effects of L. japonica in type 2 diabetic rats. L. japonica was orally administered at the dose of 100 mg/kg in high-fat diet-fed and low-dose streptozotocin-induced rats. After the treatment of 4 weeks, L. japonica reduced high blood glucose level and homeostatic model assessment of insulin resistance in diabetic rats. In addition, body weight and food intake were restored by the L. japonica treatment. In the histopathologic examination, the amelioration of damaged β-islet in pancreas was observed in L. japonica-treated diabetic rats. The administration of L. japonica elevated peroxisome proliferator-activated receptor gamma and insulin receptor subunit-1 protein expressions. The results demonstrated that L. japonica had anti-diabetic effects in type 2 diabetic rats via the peroxisome proliferator-activated receptor gamma regulatory action of L. japonica as a potential mechanism.

  3. Norepinephrine uptake by rat jejunum: Modulation by angiotensin II

    SciTech Connect

    Suvannapura, A.; Levens, N.R. )

    1988-02-01

    Angiotensin II (ANG II) is believed to stimulate sodium and water absorption from the small intestine by enhancing sympathetic nerve transmission. This study is designed to determine whether ANG II can enhance sympathetic neurotransmission within the small intestine by inhibition norepinephrine (NE) uptake. Intracellular NE accumulation by rat jejunum was concentration dependent and resolved into high- and low-affinity components. The high-affinity component (uptake 1) exhibited a Michaelis constant (K{sub m}) of 1.72 {mu}M and a maximum velocity (V{sub max}) of 1.19 nmol {center dot} g{sup {minus}1} {center dot} 10 min{sup {minus}1}. The low-affinity component (uptake 2) exhibited a K{sub m} of 111.1 {mu}M and a V{sub max} of 37.1 nmol {center dot} g{sup {minus}1} {center dot} 10 min{sup {minus}1}. Cocaine, an inhibitor of neuronal uptake, inhibited the intracellular accumulation of label by 80%. Treatment of animals with 6-hydroxydopamine, which depletes norepinephrine from sympathetic terminals, also attenuated NE uptake by 60%. Thus accumulation within sympathetic nerves constitutes the major form of ({sup 3}H)NE uptake into rat jejunum. ANG II inhibited intracellular ({sup 3}H)NE uptake in a concentration-dependent manner. At a dose of 1 mM, ANG II inhibited intracellular ({sup 3}H)NE accumulation by 60%. Cocaine failed to potentiate the inhibition of ({sup 3}H)NE uptake produced by ANG II. Thus ANG II appears to prevent ({sup 3}H)NE accumulation within rat jejunum by inhibiting neuronal uptake.

  4. Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

    PubMed

    Nishio, Y; Kashiwagi, A; Taki, H; Shinozaki, K; Maeno, Y; Kojima, H; Maegawa, H; Haneda, M; Hidaka, H; Yasuda, H; Horiike, K; Kikkawa, R

    1998-08-01

    Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P < 0.01 and P < 0.05, respectively). Insulin treatment also consistently prevented changes in the mRNA content of heme oxygenase-1. The oral administration of an antioxidant, probucol, to these diabetic rats partially prevented the elevation of the activity of both NF-kappaB and AP-1, and normalized the mRNA content of heme oxygenase-1 without producing any change in the plasma glucose concentration. These results suggest that elevated oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.

  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. Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats.

    PubMed

    Elbe, H; Esrefoglu, M; Vardi, N; Taslidere, E; Ozerol, E; Tanbek, K

    2015-09-01

    In this study, effects of melatonin, quercetin and resveratrol on hepatocellular injury in streptozotocin (STZ)-induced experimental diabetes were aimed to be investigated by histological and biochemical methods. Thirty-five male Wistar albino rats were divided into five groups, namely, control, diabetes (STZ 45 mg/kg/single dose/intraperitoneally (ip)), diabetes + melatonin (10 mg/kg/30 days/ip), diabetes + quercetin (25 mg/kg/30 days/ip) and diabetes + resveratrol (10 mg/kg/30 days/ip). Initial and final blood glucose levels and body weights (BWs) were measured. At the end of the experimentation, following routine tissue processing procedure, sections were stained with haematoxylin-eosin (H-E), periodic acid Schiff and Masson's trichrome. Tissue malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were examined. The diabetic rats had significantly higher blood glucose levels than those of control rats (p = 0.0001). Mean BWs of diabetic rats were significantly decreased when compared with the control rats (p = 0.0013). Histopathological alterations including cellular glycogen depletion, congestion, sinusoidal dilatation, inflammation and fibrosis were detected in diabetes group. On the other hand, histopathological changes markedly reduced in all of the treatment groups (p = 0.001). Mean tissue MDA level was increased but mean tissue CAT and SOD activities and GSH levels were decreased in the diabetes group. Melatonin, quercetin and resveratrol administered diabetic rats showed an increase in CAT activities and GSH levels and a decrease in MDA levels (p < 0.05, for all). Melatonin, quercetin and resveratrol administrations markedly reduced hepatocellular injury in STZ-induced experimental diabetes.

  7. Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats.

    PubMed

    Gong, Jing; Hu, Meilin; Huang, Zhaoyi; Fang, Ke; Wang, Dingkun; Chen, Qingjie; Li, Jingbin; Yang, Desen; Zou, Xin; Xu, Lijun; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2017-01-01

    Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages.

  8. Elevated expression of liver X receptor alpha (LXRα) in myocardium of streptozotocin-induced diabetic rats.

    PubMed

    Cheng, Yongxia; Liu, Guibo; Pan, Qian; Guo, Sufen; Yang, Xianghong

    2011-12-01

    The present study was designed to investigate the myocardial expression of liver X receptor alpha (LXRα) in a streptozotocin (STZ)-induced diabetic rat model. Immunohistochemical staining, quantitative real-time RT-PCR, and Western blot analysis were used to determine the expression of LXRα in the myocardium of STZ-induced diabetic rats. The myocardial expression of LXRα target genes, long-chain acyl-CoA synthetase 3 (ACSL3), fatty acid transporter protein (FAT/CD36), ATP-binding cassette transporter A1 (ABCA1), and ABCG1 were also detected. Bisulfite sequencing analysis was employed to examine the methylation status of the CpG island at the LXRα promoter region in the myocardium of STZ-induced diabetic rats. We found that LXRα mRNA and protein expression in the left ventricles, right ventricles, and atria of diabetic rats were gradually increased during the progression of diabetic cardiomyopathy (DCM). The mRNA expression levels of ACSL3 and FAT/CD36 and the protein expression levels of ABCA1 and ABCG1 were also markedly increased in different heart chambers of diabetic rats. Moreover, there was a significant difference in the methylation status of LXRα gene between the ventricles of control and diabetic rats (P < 0.05). Our findings suggest that elevated expression of LXRα may be involved in the progression of DCM, and demethylation of LXRα is likely to be responsible for its increased expression in myocardial tissues.

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

    PubMed Central

    Wang, Lin-Yu; Chung, Hsien-Hui

    2013-01-01

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

  10. Energy metabolism in the granulation tissue of diabetic rats during cutaneous wound healing.

    PubMed

    Gupta, Asheesh; Raghubir, Ram

    2005-02-01

    The skin cells chiefly depend on carbohydrate metabolism for their energy requirement during cutaneous wound healing. Since the glucose metabolism is greatly hampered in diabetes and this might affect wound repair process. This prompted us to investigate the intermediate steps of energy metabolism by measuring enzyme activities in the wound tissues of normal and streptozotocin-induced diabetic rats following excision-type of cutaneous injury. The activities of key regulatory enzymes namely hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6 phosphate dehydrogenase (G6PD) have been monitored in the granulation tissues of normal and diabetic rats at different time points (2, 7, 14 and 21 days) of postwounding. Interestingly, a significant alteration in all these enzyme activities was observed in diabetic rats. The activity of PFK was increased but HK, LDH and CS showed a decreased activity in the wound tissue of diabetics as compared to normal rats. However G6PD exhibited an elevated activity only at early stage of healing in diabetic rats. Thus, the results suggest that significant alterations in the activities of energy metabolizing enzymes in the wound tissue of diabetic rats may affect the energy availability for cellular activity needed for repair process and this may perhaps be one of the factor responsible for impaired healing in these subjects.

  11. Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats

    PubMed Central

    Gong, Jing; Hu, Meilin; Huang, Zhaoyi; Fang, Ke; Wang, Dingkun; Chen, Qingjie; Li, Jingbin; Yang, Desen; Zou, Xin; Xu, Lijun; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2017-01-01

    Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages. PMID:28217099

  12. Galanin and its receptor system promote the repair of injured sciatic nerves in diabetic rats

    PubMed Central

    Xu, Xiao-feng; Zhang, Dan-dan; Liao, Jin-chi; Xiao, Li; Wang, Qing; Qiu, Wei

    2016-01-01

    Various studies have reported that galanin can promote axonal regeneration of dorsal root ganglion neurons in vitro and inhibit neuropathic pain. However, little is known about its effects on diabetic peripheral neuropathy, and in vivo experimental data are lacking. We hypothesized that repeated applications of exogenous galanin over an extended time frame may also repair nerve damage in diabetic peripheral neuropathy, and relieve pain in vivo. We found that neuropathic pain occurred in streptozotocin-induced diabetic rats and was more severe after sciatic nerve pinch injury at 14 and 28 days than in diabetic sham-operated rats. Treatment with exogenous galanin alleviated the neuropathic pain and promoted sciatic nerve regeneration more effectively in diabetic rats than in non-diabetic rats after sciatic nerve pinch injury. This was accompanied by changes in the levels of endogenous galanin, and its receptors galanin receptor 1 and galanin receptor 2 in the dorsal root ganglia and the spinal dorsal horn when compared with nerve pinch normal rats. Our results show that application of exogenous galanin daily for 28 days can promote the regeneration of injured sciatic nerves, and alleviate neuropathic pain in diabetic rats. PMID:27857760

  13. Gene Expression Profiling in the Type 1 Diabetes Rat Diaphragm

    PubMed Central

    van Lunteren, Erik; Moyer, Michelle

    2009-01-01

    Background Respiratory muscle contractile performance is impaired by diabetes, mechanisms of which included altered carbohydrate and lipid metabolism, oxidative stress and changes in membrane electrophysiology. The present study examined to what extent these cellular perturbations involve changes in gene expression. Methodology/Principal Findings Diaphragm muscle from streptozotocin-diabetic rats was analyzed with Affymetrix gene expression arrays. Diaphragm from diabetic rats had 105 genes with at least ±2-fold significantly changed expression (55 increased, 50 decreased), and these were assigned to gene ontology groups based on over-representation analysis using DAVID software. There was increased expression of genes involved in palmitoyl-CoA hydrolase activity (a component of lipid metabolism) (P = 0.037, n = 2 genes, fold change 4.2 to 27.5) and reduced expression of genes related to carbohydrate metabolism (P = 0.000061, n = 8 genes, fold change −2.0 to −8.5). Other gene ontology groups among upregulated genes were protein ubiquitination (P = 0.0053, n = 4, fold change 2.2 to 3.4), oxidoreductase activity (P = 0.024, n = 8, fold change 2.1 to 6.0), and morphogenesis (P = 0.012, n = 10, fold change 2.1 to 4.3). Other downregulated gene groups were extracellular region (including extracellular matrix and collagen) (P = 0.00032, n = 13, fold change −2.2 to −3.7) and organogenesis (P = 0.032, n = 7, fold change −2.1 to −3.7). Real-time PCR confirmed the directionality of changes in gene expression for 30 of 31 genes tested. Conclusions/Significance These data indicate that in diaphragm muscle type 1 diabetes increases expression of genes involved in lipid energetics, oxidative stress and protein ubiquitination, decreases expression of genes involved in carbohydrate metabolism, and has little effect on expression of ion channel genes. Reciprocal changes in expression of genes involved in

  14. Abnormal levels of histone methylation in the retinas of diabetic rats are reversed by minocycline treatment

    PubMed Central

    Wang, Wenjun; Sidoli, Simone; Zhang, Wenquan; Wang, Qing; Wang, Leilei; Jensen, Ole N.; Guo, Lin; Zhao, Xiaolu; Zheng, Ling

    2017-01-01

    In this study we quantified the alterations of retinal histone post-translational modifications (PTMs) in diabetic rats using a liquid chromatography - tandem mass spectrometry (LC-MS/MS) approach. Some diabetic rats were subsequently treated with minocycline, a tetracycline antibiotic, which has been shown to inhibit the diabetes-induced chronic inflammation in the retinas of rodents. We quantified 266 differentially modified histone peptides, including 48 out of 83 methylation marks with significantly different abundancein retinas of diabetic rats as compared to non-diabetic controls. About 67% of these marks had their relative abundance restored to non-diabetic levels after minocycline treatment. Mono- and di-methylation states of histone H4 lysine 20 (H4K20me1/me2), markers related to DNA damage response, were found to be up-regulated in the retinas of diabetic rats and restored to control levels upon minocycline treatment. DNA damage response biomarkers showed the same pattern once quantified by western blotting. Collectively, this study indicates that alteration of some histone methylation levels is associated with the development of diabetic retinopathy in rodents, and the beneficial effect of minocycline on the retinas of diabetic rodents is partially through its ability to normalize the altered histone methylation levels. PMID:28338045

  15. Diosgenin ameliorates development of neuropathic pain in diabetic rats: Involvement of oxidative stress and inflammation.

    PubMed

    Kiasalari, Zahra; Rahmani, Tayebeh; Mahmoudi, Narges; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

    2017-02-01

    Neuropathic pain is one of the prevalent complications of diabetes mellitus (DM). Oxidative stress and inflammation are the principal determinants for its development. Pharmacological interventions targeted at alleviating or suppressing these pathways are clinically promising. Diosgenin is a natural steroidal saponin with anti-diabetic and multiple protective properties. This study was designed to study the efficacy of chronic diosgenin administration on alleviation of hyperalgesia in streptozotocin (STZ)-diabetic rats. Rats were allocated to control, diosgenin-treated control, diabetic, and diosgenin-treated-diabetic groups. Diosgenin was daily administered at a dose of 40mg/kg for 5 weeks. Nociceptive behavior was assessed using paw pressure, hot tail immersion, and formalin tests. In addition, some oxidative stress and inflammation markers were measured. Diosgenin treatment of diabetic group increased mechanical and thermal nociceptive thresholds and lowered pain score at late phase of the formalin test, but not at its early phase. Biochemical analysis of serum samples and sciatic nerve and dorsal root ganglion (DRG) lysates showed restoration or improvement of nuclear factor-B (NF-κB), malondialdehyde (MDA) level, activity of superoxide dismutase (SOD), catalase, tumor necrosis factor α (TNFα), and interleukin 1β (IL-1β) upon diosgenin treatment of diabetic rats. The obtained results exhibited antinociceptive potential of diosgenin in diabetic rats through lowering oxidative stress and inflammation and improving antioxidant defense system. This suggests possible therapeutic potential of diosgenin for alleviation and management of diabetic neuropathic pain.

  16. Investigation on the effects of the atmospheric pressure plasma on wound healing in diabetic rats

    NASA Astrophysics Data System (ADS)

    Fathollah, Sara; Mirpour, Shahriar; Mansouri, Parvin; Dehpour, Ahmad Reza; Ghoranneviss, Mahmood; Rahimi, Nastaran; Safaie Naraghi, Zahra; Chalangari, Reza; Chalangari, Katalin Martits

    2016-02-01

    It is estimated that 15 percent of individuals with diabetes mellitus suffer from diabetic ulcers worldwide. The aim of this study is to present a non-thermal atmospheric plasma treatment as a novel therapy for diabetic wounds. The plasma consists of ionized helium gas that is produced by a high-voltage (8 kV) and high-frequency (6 kHz) power supply. Diabetes was induced in rats via an intravascular injection of streptozotocin. The plasma was then introduced to artificial xerograph wounds in the rats for 10 minutes. Immunohistochemistry assays was performed to determine the level of transforming growth factor (TGF-β1) cytokine. The results showed a low healing rate in the diabetic wounds compared with the wound-healing rate in non-diabetic animals (P < 0.05). Moreover, the results noted that plasma enhanced the wound-healing rate in the non-diabetic rats (P < 0.05), and significant wound contraction occurred after the plasma treatment compared with untreated diabetic wounds (P < 0.05). Histological analyses revealed the formation of an epidermis layer, neovascularization and cell proliferation. The plasma treatment also resulted in the release of TGF-β1 cytokine from cells in the tissue medium. The findings of this study demonstrate the effect of plasma treatment for wound healing in diabetic rats.

  17. Investigation on the effects of the atmospheric pressure plasma on wound healing in diabetic rats

    PubMed Central

    Fathollah, Sara; Mirpour, Shahriar; Mansouri, Parvin; Dehpour, Ahmad Reza; Ghoranneviss, Mahmood; Rahimi, Nastaran; Safaie Naraghi, Zahra; Chalangari, Reza; Chalangari, Katalin Martits

    2016-01-01

    It is estimated that 15 percent of individuals with diabetes mellitus suffer from diabetic ulcers worldwide. The aim of this study is to present a non-thermal atmospheric plasma treatment as a novel therapy for diabetic wounds. The plasma consists of ionized helium gas that is produced by a high-voltage (8 kV) and high-frequency (6 kHz) power supply. Diabetes was induced in rats via an intravascular injection of streptozotocin. The plasma was then introduced to artificial xerograph wounds in the rats for 10 minutes. Immunohistochemistry assays was performed to determine the level of transforming growth factor (TGF-β1) cytokine. The results showed a low healing rate in the diabetic wounds compared with the wound-healing rate in non-diabetic animals (P < 0.05). Moreover, the results noted that plasma enhanced the wound-healing rate in the non-diabetic rats (P < 0.05), and significant wound contraction occurred after the plasma treatment compared with untreated diabetic wounds (P < 0.05). Histological analyses revealed the formation of an epidermis layer, neovascularization and cell proliferation. The plasma treatment also resulted in the release of TGF-β1 cytokine from cells in the tissue medium. The findings of this study demonstrate the effect of plasma treatment for wound healing in diabetic rats. PMID:26902681

  18. 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

  19. Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry.

    PubMed

    Tahiliani, A G; McNeill, J H

    1984-06-01

    Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.

  20. Renoprotective Effect of Coccinia indica Fruits and Leaves in Experimentally Induced Diabetic Rats

    PubMed Central

    Gurukar, Mallur Somasundra Abignan; Mahadevamma, Siddaiah

    2013-01-01

    Abstract Diabetic nephropathy is one of the secondary complications of diabetes mellitus that is marked by changes in extracellular matrix components leading to end-stage renal failure. Diet plays an important role in managing diabetes. In the present study, the effect of Coccinia indica consumption on diabetes-mediated kidney damage was determined. Both control and diabetic rats were fed with AIN-76 diet supplemented with C. indica fruits and leaves individually at 10% and 5%, respectively, for a period of 2 months. Various parameters, such as fasting blood glucose, urine sugar, albumin excretion, kidney index, and glomerular filtration rate, were ameliorated to various extents by the supplementation of C. indica in the diet. Additionally, diabetic rats fed with diet supplemented with C. indica fruits or leaves showed improvement in glucose tolerance compared to control diabetic rats. They also exhibited beneficial effects on key antioxidant enzymes of the kidney. Furthermore, an increase in laminin and fibronectin as a result of diabetes was alleviated in C. indica-fed rats. These results indicate that the consumption of C. indica is beneficial in partially containing diabetes-mediated deleterious effects on the kidney. PMID:24044493

  1. Increased Clearance and Degradation of [3H]Insulin in Streptozotocin Diabetic Rats

    PubMed Central

    Philippe, Jacques; Halban, Philippe A.; Gjinovci, Asllan; Duckworth, William C.; Estreicher, Jurek; Renold, Albert E.

    1981-01-01

    The role of the insulin-receptor compartment in the pharmacokinetics of intravenously injected insulin in rats was studied. Since streptozotocin-diabetes in rats results in increased insulin binding to tissues in vitro, insulin pharmacokinetics in streptozotocin-diabetic rats were compared to controls, using semisynthetic [3H]insulin as the tracer. The initial distribution volume for [3H]insulin was elevated by 60% in diabetic rats. By contrast, no difference in initial distribution volume for [14C]inulin was observed, and the absolute values were lower than those found for [3H]insulin. The metabolic clearance rate of [3H]insulin was elevated by 44% in diabetic rats. That these differences were the result of increased binding of insulin to a specific receptor compartment in diabetic rats was shown by three additional experiments. The first involved receptor saturation by injection of 10 U native insulin 2 min before the tracer injection, resulting in identical [3H]insulin disappearance rates in the two groups of rats. The second consisted of displacing [3H]insulin from receptors by injecting 10 U unlabeled insulin 6 min after the tracer injection. Displacement of intact [3H]insulin from receptors and subsequent reappearance in the circulation occurred in both control and diabetic animals; however, such displacement was 25% greater in the diabetic rats. Finally, treatment of diabetic rats with insulin for 8 d normalized [3H]insulin clearance even though the tracer was injected at a time when the animals were again hyperglycemic and hypoinsulinemic. This suggests that down-regulation of insulin receptors had occurred during insulin therapy. These results confirm that a specific compartment for insulin exists (the insulin-receptor compartment) and that this compartment plays an important role in insulin clearance. PMID:6451633

  2. Melatonin reduces formalin-induced nociception and tactile allodynia in diabetic rats.

    PubMed

    Arreola-Espino, Rosaura; Urquiza-Marín, Héctor; Ambriz-Tututi, Mónica; Araiza-Saldaña, Claudia Ivonne; Caram-Salas, Nadia L; Rocha-González, Héctor I; Mixcoatl-Zecuatl, Teresa; Granados-Soto, Vinicio

    2007-12-22

    The purpose of this study was to assess the antinociceptive and antiallodynic effect of melatonin as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral administration of melatonin (10-300 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. In addition, K-185 (a melatonin MT(2) receptor antagonist, 0.2-2 mg/kg, s.c.) completely blocked the melatonin-induced antinociception in diabetic rats, whereas that naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) and naltrindole (a selective delta opioid receptor antagonist, 0.5 mg/kg, s.c.), but not 5'-guanidinonaltrindole (a selective kappa opioid receptor antagonist, 1 mg/kg, s.c.), partially reduced the antinociceptive effect of melatonin. Given alone K-185, naltrexone, naltrindole or 5'-guanidinonaltrindole did not modify formalin-induced nociception in diabetic rats. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of melatonin (75-300 mg/kg) dose-dependently reduced tactile allodynia in diabetic rats. Both antinociceptive and antiallodynic effects were not related to motor changes as melatonin did not modify number of falls in the rotarod test. Results indicate that melatonin is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that melatonin MT(2) and delta opioid receptors may play an important role in these effects.

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

    PubMed

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

    2011-03-01

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

  4. Antihyperglycemic and Antihyperlipidemic Activity of Plectranthus Amboinicus on Normal and Alloxan-Induced Diabetic Rats

    PubMed Central

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

    2011-01-01

    The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg). Normal as well as diabetic rats were divided into groups (n=6) receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg) of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 μg/kg) was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect. PMID:22303055

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

    PubMed

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

    2016-12-01

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

  6. Efficacy of Annona squamosa L in the synthesis of glycosaminoglycans and collagen during wound repair in streptozotocin induced diabetic rats.

    PubMed

    Ponrasu, Thangavel; Suguna, Lonchin

    2014-01-01

    The aim of this work was to find out the effects of Annona squamosa on the formation of glycosaminoglycans and collagen during wound healing in normal and diabetic rats. Diabetes induced rats were segregated into 4 groups, each containing six animals. Groups I and III served as the normal and diabetic control while groups II and IV served as normal and diabetic treated. The animals were treated with 200 μL of Annona squamosa extract topically. The granulation tissues formed were removed on the 8th day and the amount of glycosaminoglycans (GAGs) and collagen formed was evaluated by sequential extraction and SDSPAGE, respectively. Histological evaluation was also carried out using Masson's trichrome stain. In vitro wound healing efficacy of A. squamosa in human dermal fibroblast culture (HDF) was also carried out. The fibroblasts treated with varying concentrations of A. squamosa were examined for proliferation and closure of the wound area and photographed. A. squamosa increased cellular proliferation in HDF culture. The granulation tissues of treated wounds showed increased levels of glycosaminoglycans (P < 0.05) and collagen which were also confirmed by histopathology. The results strongly substantiate the beneficial effects of A. squamosa on the formation of glycosaminoglycans and collagen during wound healing.

  7. Efficacy of Annona squamosa L in the Synthesis of Glycosaminoglycans and Collagen during Wound Repair in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Ponrasu, Thangavel

    2014-01-01

    The aim of this work was to find out the effects of Annona squamosa on the formation of glycosaminoglycans and collagen during wound healing in normal and diabetic rats. Diabetes induced rats were segregated into 4 groups, each containing six animals. Groups I and III served as the normal and diabetic control while groups II and IV served as normal and diabetic treated. The animals were treated with 200 μL of Annona squamosa extract topically. The granulation tissues formed were removed on the 8th day and the amount of glycosaminoglycans (GAGs) and collagen formed was evaluated by sequential extraction and SDSPAGE, respectively. Histological evaluation was also carried out using Masson's trichrome stain. In vitro wound healing efficacy of A. squamosa in human dermal fibroblast culture (HDF) was also carried out. The fibroblasts treated with varying concentrations of A. squamosa were examined for proliferation and closure of the wound area and photographed. A. squamosa increased cellular proliferation in HDF culture. The granulation tissues of treated wounds showed increased levels of glycosaminoglycans (P < 0.05) and collagen which were also confirmed by histopathology. The results strongly substantiate the beneficial effects of A. squamosa on the formation of glycosaminoglycans and collagen during wound healing. PMID:25003104

  8. Gestational Age, Infant Birth Weight, and Subsequent Risk of Type 2 Diabetes in Mothers: Nurses' Health Study II

    MedlinePlus

    ... Birth Weight, and Subsequent Risk of Type 2 Diabetes in Mothers: Nurses’ Health Study II Navigate This ... as 10 pounds or more at term. Gestational diabetes In the NHSII 1989 baseline questionnaire and subsequent ...

  9. Dental caries prevalence among type II diabetic and nondiabetic adults attending a hospital

    PubMed Central

    Malvania, Ekta A.; Sheth, Sona A.; Sharma, Ashish S.; Mansuri, Saloni; Shaikh, Faizan; Sahani, Saloni

    2016-01-01

    Objectives: Diabetes mellitus (DM) is a common chronic metabolic disorder which affects millions of people. At present, India has the highest incidence of diabetes worldwide. Several oral lesions and conditions are associated with diabetes. However, there is a lack of consensus among researchers regarding the relationship between DM and dental caries. Hence, the present study was carried out to assess the dental caries prevalence among type II diabetic and nondiabetic adults attending a hospital in Ahmedabad city. Materials and Methods: A hospital-based cross-sectional study was conducted. One hundred and twenty diabetics individuals attending the diabetic Outpatient Department (OPD) and age and sex-matched 120 nondiabetic individuals from general OPD were included in the study. The data were gathered through semi-close-ended questionnaire and clinical examination. Dental caries was assessed by using the World Health Organization's 2013 proforma. Data was analyzed by applying Student's independent t-test or one-way analysis of variance. Results: Dental caries prevalence among the diabetic group was 73.33% and 33.33% among the nondiabetic group. Dental caries prevalence and mean dental caries was significantly higher among uncontrolled diabetic individuals than that among controlled diabetic individuals. Duration of the disease and dental caries prevalence did not show any significant difference. Conclusion: Dental caries prevalence was significantly high among diabetic individuals compared with nondiabetic individuals. Close collaboration between the patients, healthcare units, and oral health professionals could be a way of improving diabetic patients' general and oral health. PMID:28217542

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

    PubMed

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

    2016-01-01

    Diabetic patients are at risk of acquiring infections. Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Diabetes causes generation of reactive oxygen species that increases oxidative stress, which may play a role in the development of complications as immune-deficiency and bacterial infection. The study aimed to investigate the role of a natural antioxidant, cumin, in the improvement of immune functions in diabetes. Diabetes was achieved by interperitoneal injection of streptozotocin (STZ). Bacterial infection was induced by application of Staphylococcus aureus suspension to a wound in the back of rats. The antioxidant was administered for 6 weeks. Results revealed a decrease in blood glucose levels in diabetic rats (p < 0.001), in addition to improving immune functions by decreasing total IgE approaching to the normal control level. Also, inflammatory cytokine (IL-6, IL-1β and TNF) levels, as well as total blood count decreased in diabetic rats as compared to the control group. Thus, cumin may serve as anti-diabetic treatment and may help in attenuating diabetic complications by improving immune functions. Therefore, a medical dietary antioxidant supplementation is important to improve the immune functions in diabetes.

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

    PubMed Central

    Embaby, Mohamed A.; Doleib, Nada M.; Taha, Mona M.

    2016-01-01

    Diabetic patients are at risk of acquiring infections. Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Diabetes causes generation of reactive oxygen species that increases oxidative stress, which may play a role in the development of complications as immune-deficiency and bacterial infection. The study aimed to investigate the role of a natural antioxidant, cumin, in the improvement of immune functions in diabetes. Diabetes was achieved by interperitoneal injection of streptozotocin (STZ). Bacterial infection was induced by application of Staphylococcus aureus suspension to a wound in the back of rats. The antioxidant was administered for 6 weeks. Results revealed a decrease in blood glucose levels in diabetic rats (p < 0.001), in addition to improving immune functions by decreasing total IgE approaching to the normal control level. Also, inflammatory cytokine (IL-6, IL-1β and TNF) levels, as well as total blood count decreased in diabetic rats as compared to the control group. Thus, cumin may serve as anti-diabetic treatment and may help in attenuating diabetic complications by improving immune functions. Therefore, a medical dietary antioxidant supplementation is important to improve the immune functions in diabetes. PMID:27536197

  12. Germinated Thai Black Rice Extract Protects Experimental Diabetic Rats from Oxidative Stress and Other Diabetes-Related Consequences

    PubMed Central

    Chaiyasut, Chaiyavat; Sivamaruthi, Bhagavathi Sundaram; Pengkumsri, Noppawat; Keapai, Waranya; Kesika, Periyanaina; Saelee, Manee; Tojing, Parichart; Sirilun, Sasithorn; Chaiyasut, Khontaros; Peerajan, Sartjin; Lailerd, Narissara

    2016-01-01

    Background: Diabetes mellitus (DM), particularly type 2 DM (T2DM), is one of the most common metabolic disorder worldwide. The prevention measures and treatment strategies for DM are improving steadily. The current study explains the impact of germination on phytochemical content of Thai black rice (BR), and the influence of germinated BR extract (GBRE) supplementation on diabetic conditions in rats. Methods: BR was germinated and the phenolic, anthocyanin, and γ-aminobutyric acid (GABA) content of the extract were analyzed using HPLC and spectrophotometric methods. Streptozotocin-induced diabetic rats were supplemented with high and low doses of GBRE. The plasma glucose, insulin, cholesterol, triglyceride levels, antioxidant status, and antioxidant enzyme levels of treated animals were assessed using ELISA and spectrophotometric methods. Results: Germination enhanced the GABA content of BR, and GBRE intervention improved the total antioxidant capacity and antioxidant enzymes levels in diabetic rats. The plasma glucose, cholesterol, triglyceride levels, insulin resistance and glucose tolerance were reduced, and the degree of insulin secretion in rat plasma was significantly increased upon GBRE treatment. Both pre and post-treatment approaches showed the anti-diabetic ability of GBRE. In most of the analyzed parameters, GBRE was quite equal to the performance of drug-metformin. Conclusions: GBRE supplementation helps prevent and manage the consequences of DM. PMID:28036014

  13. Renal podocyte apoptosis in Zucker diabetic fatty rats: involvement of methylglyoxal-induced oxidative DNA damage.

    PubMed

    Kim, J; Sohn, E; Kim, C-S; Kim, J S

    2011-01-01

    Methylglyoxal (MGO) is a cytotoxic metabolite produced by in-vivo glycolysis that may result in diabetic complications. The aim of this study was to determine whether MGO and oxidative stress caused apoptosis of renal podocytes in the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes mellitus. Male ZDF rats aged 21 weeks developed marked hyperglycaemia with proteinuria and albuminuria. Immunohistochemical evaluation of sections of kidney demonstrated expression of MGO and 8-hydroxydeoxyguanosine (8-OHdG) in the podocytes of both normoglycaemic and diabetic rats. Podocyte apoptosis was shown through application of the TUNEL method. These findings suggest that expression of MGO and 8-OHdG is caused by hyperglycaemia, and that this expression is associated with the observed apoptosis of podocytes and is related to diabetic nephropathy.

  14. Decreased autophosphorylation of EGF receptor in insulin-deficient diabetic rats

    SciTech Connect

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

    1988-04-01

    The authors have previously reported that despite an increase in receptor concentration, there is a decrease in autophosphorylation and tyrosine kinase activity of the insulin receptor in insulin-deficient diabetic rats. To determine if other tyrosine kinases might be altered, they have studied the epidermal growth factor (EGF) receptor kinase in wheat germ agglutinin-purified, Triton X-100-solubilized liver membranes from streptozotocin (STZ)-induced diabetic rats and the insulin-deficient BB rat. They find that autophosphorylation of EGF receptor is decreased in proportion to the severity of the diabetic state in STZ rats with a maximal decrease of 67%. A similar decrease in autophosphorylation was observed in diabetic BB rats that was partially normalized by insulin treatment. Separation of tryptic phosphopeptides by reverse-phase high-performance liquid chromatography revealed a decrease in labeling at all sites of autophosphorylation. A parallel decrease in EGF receptor phosphorylation was also found by immunoblotting with an antiphosphotyrosine antibody. EGF receptor concentration, determined by Scatchard analysis of {sup 125}I-labeled EGF binding, was decreased by 39% in the STZ rat and 27% in the diabetic BB rat. Thus autophosphorylation of EGF receptor, like that of the insulin receptor, is decreased in insulin-deficient rat liver. In the case of EGF receptor, this is due in part to a decrease in receptor number and in part to a decrease in the specific activity of the kinase.

  15. Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats.

    PubMed

    Lu, Li; Zhijian, Huang; Lei, Li; Wenchuan, Chen; Zhimin, Zhu

    2015-01-01

    This study evaluated the effects of berberine in combination with insulin on early osseointegration of implants in diabetic rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: healthy rats were used as control (HC), and streptozotocin-induced diabetic rats were treated with insulin, berberine, berberine + insulin (IB), or no treatment. Each rat received one machined-surface cp-Ti implant into the right tibia and was given insulin injection and/or gavage feeding with berberine daily for 8 weeks until being sacrificed. Serum levels of alkaline phosphatase (ALP) and bone gamma-carboxyglutamic acid-containing protein (BGP) were analyzed in each group. Peri-implant mineral apposition was marked by fluorochrome double-labeling and osseointegration was histomorphologically examined. The ALP and BGP levels decreased in diabetic rats but were successfully corrected by insulin and berberine combined treatment. Moreover, untreated diabetic rats had less labeled mineral apposition and impaired osseointegration. In contrast, Groups I, B, and IB were observed with increased peri-implant bone formation. The combination treatment of insulin and berberine was more effective than each administrated as a monotherapy. These results suggest that berberine combined with insulin could promote osseointegration in diabetic rats, thereby highlighting its potential application to patients, though further studies are needed.

  16. Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats

    PubMed Central

    Lu, Li; Zhijian, Huang; Lei, Li; Wenchuan, Chen; Zhimin, Zhu

    2015-01-01

    This study evaluated the effects of berberine in combination with insulin on early osseointegration of implants in diabetic rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: healthy rats were used as control (HC), and streptozotocin-induced diabetic rats were treated with insulin, berberine, berberine + insulin (IB), or no treatment. Each rat received one machined-surface cp-Ti implant into the right tibia and was given insulin injection and/or gavage feeding with berberine daily for 8 weeks until being sacrificed. Serum levels of alkaline phosphatase (ALP) and bone gamma-carboxyglutamic acid-containing protein (BGP) were analyzed in each group. Peri-implant mineral apposition was marked by fluorochrome double-labeling and osseointegration was histomorphologically examined. The ALP and BGP levels decreased in diabetic rats but were successfully corrected by insulin and berberine combined treatment. Moreover, untreated diabetic rats had less labeled mineral apposition and impaired osseointegration. In contrast, Groups I, B, and IB were observed with increased peri-implant bone formation. The combination treatment of insulin and berberine was more effective than each administrated as a monotherapy. These results suggest that berberine combined with insulin could promote osseointegration in diabetic rats, thereby highlighting its potential application to patients, though further studies are needed. PMID:26783411

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

    PubMed Central

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

    2011-01-01

    Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man. PMID:21784987

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

    PubMed

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

    2011-10-01

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

  19. 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

  20. Early photocoagulation in patients with either type I or type II diabetes.

    PubMed Central

    Ferris, F

    1996-01-01

    OBJECTIVE: To determine the benefits of early photocoagulation in patients with type I versus type II diabetes. DESIGN: One eye of each of 3,711 patients was randomly assigned to early photocoagulation; the other was assigned to deferral of photocoagulation, with follow-up visits scheduled every 4 months and photocoagulation to be carried out promptly if high-risk proliferative retinopathy developed. Patients were categorized by age and type of diabetes. MAIN OUTCOME MEASURES: Best corrected visual acuity was measured at each study visit scheduled at 4-month intervals. Stereoscopic fundus photographs were taken and evaluated at baseline, 4 months, and yearly thereafter. Retinopathy severity was assessed from fundus photographs. Severe visual loss was defined as visual acuity of worse than 5/200 for at least two consecutive study visits. RESULTS: Previously published results of the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated a statistically significant benefit of early photocoagulation in preventing severe vision loss. Further analyses demonstrate that this benefit of early photocoagulation is greater in patients with type II diabetes than in those with type I. The relative benefit of early photocoagulation in patients with type II diabetes is also seen for other outcomes (development of high-risk proliferative retinopathy, development of the combined end point [severe visual loss or vitrectomy], development of moderate visual loss, or development of legal blindness). The patients most likely to benefit from early photocoagulation had severe nonproliferative retinopathy or early proliferative retinopathy. Analyses from the Diabetic Retinopathy Study confirm the relative benefit of scatter photocoagulation for type II patients. Because of the high correlation between age and type of diabetes, analyses sub-grouped by age show similar results. CONCLUSION: These analyses suggest that patients with type II diabetes, or older patients with diabetes

  1. Anti-Diabetic and Hepato-Renal Protective Effects of Ziyuglycoside II Methyl Ester in Type 2 Diabetic Mice

    PubMed Central

    Son, Dong Ju; Hwang, Seock Yeon; Kim, Myung-Hyun; Park, Un Kyu; Kim, Byoung Soo

    2015-01-01

    Type 2 diabetes is a metabolic disorder caused by abnormal carbohydrate metabolism, and closely associated with abnormal lipid metabolism and hepato-renal dysfunction. This study investigated the anti-diabetic and hepato-renal protective properties of ziyuglycoside I (ZG01) derivative on type 2 diabetes. ZG01 was isolated from roots of Sanguisorba officinalis and chemically modified by deglycosylation and esterification to obtained ziyuglycoside II methyl ester (ZG02-ME). Here, we showed that ZG02-ME has stronger anti-diabetic activity than the original compound (ZG01) through decreasing blood glucose, glycated hemoglobin (HbA1c), and insulin levels in a mouse model of type 2 diabetes (db/db mice). We further found that ZG02-ME treatment effectively ameliorated serum insulin, leptin and C-peptide levels, which are key metabolic hormones, in db/db mice. In addition, we showed that elevated basal blood lipid levels were decreased by ZG02-ME treatment in db/db mice. Furthermore, treatment of ZG02-ME significantly decreased serum AST, ALT, BUN, creatinine, and liver lipid peroxidation in db/db mice. These results demonstrated that compared to ZG01, chemically modified ZG02-ME possess improved anti-diabetic properties, and has hepato-renal protective activities in type 2 diabetes. PMID:26198246

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

    PubMed

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

    2014-06-01

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

  3. Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats.

    PubMed

    Zhou, Jiyin; Du, Xiaohuang; Long, Min; Zhang, Zuo; Zhou, Shiwen; Zhou, Jianyun; Qian, Guisheng

    2016-03-05

    The mechanisms leading to diabetic neuropathy are complex. As an active component in several traditional Chinese medicines, berberine has a beneficial effect in the treatment of diabetes with hyperlipidemia. This study evaluated the protective effects of berberine on diabetic neuropathy induced by streptozotocin and a high-carbohydrate/high-fat diet in rats. Diabetic neuropathy was induced in rats by intraperitoneal injection of 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Two weeks after diabetes induction, rats were treated with berberine (100 mg/kg) and rosiglitazone (4 mg/kg) for 24 weeks. Rats were studied using evoked potentials, the Morris water maze, transmission electron microscopy, real-time PCR, and Western blotting. Blood glucose, glycated hemoglobin, lipid profile, body weight, evoked potentials, and memory were altered in diabetic rats, as was the hippocampal expression of neuritin mRNA, p38 mitogen-activated protein kinase mRNA, c-Jun N-terminal kinase (JNK) mRNA, extracellular signal-regulated kinase mRNA and the phospho-proteins of p38, JNK, and extracellular signal-regulated kinase. In diabetic rats, berberine decreased body weight and the blood levels of glucose, glycated hemoglobin, triglyceride, and total cholesterol, improved memory and affected evoked potential by decreasing latency. Berberine decreased the mRNA expression of neuritin, p38, and JNK and the protein expression of neuritin, p-p38, and p-JNK. Slight micropathological changes were observed in the hippocampus of berberine-treated diabetic rats. These findings suggest that berberine has a beneficial effect against diabetic neuropathy by improving micropathology and increasing neuritin expression via the mitogen-activated protein kinase signaling pathway.

  4. Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre-diabetic rats.

    PubMed

    Huisamen, Barbara; Genis, Amanda; Marais, Erna; Lochner, Amanda

    2011-02-01

    Cardiovascular risk is closely associated with insulin resistance and type 2 diabetes. Therapy based on the actions of GLP-1 is currently seen as a novel approach to treat this disease. The aims of this study was therefore to use an animal model to determine whether (i) pre-treatment of obese, insulin resistant but pre-diabetic rats with a DPP4 inhibitor, PFK275-055, could protect the heart from ischaemia/reperfusion injury and (ii) the possible mechanisms involved in such protection. Obese, pre-diabetic rats (DIO) were treated for 4 weeks with 10 mg/kg/day of the DPP4 inhibitor PFK275-055. Ex vivo perfusion was used to subject hearts to ischaemia/reperfusion to determine infarct size, functional recovery and post-ischaemic activation of proteins associated with cardiac protection. Adult ventricular cardiomyocytes were isolated to determine insulin sensitivity. Other assessments included body weight, intra-peritoneal fat weight, insulin and GLP-1 levels as well as histological evaluation of the pancreata. Results showed that DIO animals had higher body mass and intra-peritoneal fat mass than chow-fed animals. They presented with elevated plasma insulin levels and lower GLP-1 levels. Treatment with the DPP4 inhibitor resulted in smaller infarct size development in hearts from DIO rats after ischaemia/reperfusion accompanied by activation of cardioprotective kinases. GLP-1 levels were elevated and plasma insulin levels lower after treatment. In addition, the beta-cell to alpha-cell ratio of the pancreas was improved. We conclude that treatment with PFK275-055 for 4 weeks protected the heart against ischaemia/reperfusion injury, elevated GLP-1 levels and improved metabolic control in obese, pre-diabetic rats.

  5. 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

  6. Beneficial effects of quercetin on sperm parameters in streptozotocin-induced diabetic male rats.

    PubMed

    Khaki, Arash; Fathiazad, Fatemeh; Nouri, Mohammad; Khaki, Amirafshin; Maleki, Navid A; Khamnei, Hossein Jabbari; Ahmadi, Porya

    2010-09-01

    Quercetin (QR) is a strong antioxidant and has been shown to reduce oxidative stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in animal models. Antioxidants have significant effects on spermatogenesis, sperm biology and oxidative stress, and changes in antioxidant capacity are considered to be involved in the pathogenesis of chronic diabetes mellitus. The present study aims to examine the influence of QR on spermatogenesis in STZ-induced diabetes in male Wistar rats. Animals (n = 50) were allocated into five groups: Group 1: Control rats given 0.5 ml of 20% glycerol in 0.9% normal saline. Group 2: Control rats given buffer (pH4.0).Group 3: diabetic controls. Group 4: rats given QR 15 mg/kg/day (i.p.). Group 5: STZ + QR rats. Animals were kept in standard conditions. At the end of the experiment (28th day), blood samples were taken for determination of testosterone, total antioxidant capacity, and levels of malondialdehyde and oxidized low-density lipoprotein. All rats were euthanized, testes were dissected out and spermatozoa were collected from the epididymis for analysis. Sperm numbers, percentages of sperm viability and motility, and total serum testosterone increased significantly in QR-treated diabetic rats (P < 0.05) compared with control groups. In histopathology, degeneration and inflammation in testes cells associated with diabetes were improved and testes weights in the QR-treated diabetic group decreased significantly in comparison with controls (P < 0.05). We conclude that QR has significant beneficial effects on the sperm viability, motility, and serum total testosterone and could be effective for maintaining healthy sperm parameters and male reproductive function in diabetic rats.

  7. [Exploring the mechanism of rhizoma coptidis in treating type II diabetes mellitus based on metabolomics by gas chromatography-mass spectrometry].

    PubMed

    Wang, Jing; Yuan, Zimin; Kong, Hongwei; Li, Yong; Lu, Xin; Xu, Guowang

    2012-01-01

    Metabolomics was used to explore the mechanism of Rhizoma coptidis in treating type II diabetes mellitus. The rat model of type II diabetes mellitus was constructed by an injection of streptozocin (40 mg/kg), along with diets of fat emulsion. The rats were divided into four groups, the control group, the model group, the Rhizoma coptidis group (10 g/kg) and the metformin group (0.08 g/kg). After the treatment for 30 d, blood samples were collected to test biomedical indexes, and 24 h urine samples were collected for the metabolomics experiment. In the Rhizoma coptidis group, fasting blood glucose (FBG), total cholesterol (TC) and total plasma triglycerides (TG) were significantly decreased by 59.26%, 58.66% and 42.18%, respectively, compared with those in the model group. Based on gas chromatography-mass spectrometry, a urinary metabolomics method was used to study the mechanism of Rhizoma coptidis in treating diabetes mellitus. Based on the principal component analysis, it was found that the model group and control group were separated into two different clusters. The Rhizoma coptidis group was located between the model group and the control group, closer to the control group. Twelve significantly changed metabolites of diabetes mellitus were detected and identified, including 4-methyl phenol, benzoic acid, aminomalonic acid, and so on. After diabetic rats were administered with Rhizoma coptidis, 7 metabolites were significantly changed, and L-ascorbic acid and aminomalonic acid which related with the oxidative stress were significantly regulated to normal. The pharmacological results showed that Rhizoma coptidis could display anti-hyperglycemic and anti-hyperlipidemic effects. The Rhizoma coptidis had antioxidation function in preventing the occurrence of complications with diabetes mellitus to some extent. The work illustrates that the metabolomics method is a useful tool to study the treatment mechanism of traditional Chinese medicine.

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

    PubMed

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

    2014-10-01

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

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

    PubMed Central

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

    2009-01-01

    Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral. PMID:19812703

  10. Sodium tungstate attenuate oxidative stress in brain tissue of streptozotocin-induced diabetic rats.

    PubMed

    Nakhaee, Alireza; Bokaeian, Mohammad; Akbarzadeh, Azim; Hashemi, Mohammad

    2010-08-01

    High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms.

  11. The effect of combined photobiomodulation and metformin on open skin wound healing in a non-genetic model of type II diabetes.

    PubMed

    Asghari, Mohammadali; Kanonisabet, Ali; Safakhah, Mandanad; Azimzadeh, Zahra; Mostafavinia, Ataroalsadat; Amini, Abdollah; Ghorishi, Seyed Kamran; JalaliFiroozkohi, Reza; Bayat, Sahar; Bayat, Mohammad

    2017-03-06

    This study intended to examine the combined influences of photobiomodulation (PBM) and metformin on the microbial flora and biomechanical parameters of wounds in a non-genetic model of type II diabetes mellitus (TII DM). We induced a non-genetic model of TII DM in 20 rats by feeding them a 10% fructose solution for 2weeks followed by an injection of streptozotocin (STZ, 40mg/kg). After 21days from the injection of STZ, we induced one full-thickness skin wound in each of the diabetic rats. We randomly divided the rats into four groups: i) placebo; ii) pulsed wave laser (890nm, 80Hz, 0.324J/cm(2)); iii) metformin; and iv) laser+metformin. Rats received daily intraperitoneal injections of metformin (50mg/kg). On days 7and 15 we inspected the microbial flora of each wound. On day 15 we obtained a standard sample from each healing wound for biomechanical analyses. PBM significantly decreased colony-forming units (CFUs) 7days after wound infliction compared to the placebo group (LSD test, p=0.012). Metformin significantly enhanced the biomechanical property (stress high load) of the wounds compared to the placebo group (LSD test, p=0.028). We observed the same significant result for PBM compared to the placebo group (LSD test, p=0.047). PBM significantly accelerated the wound healing process and significantly reduced CFUs of bacteria in a non-genetic rat model of TII DM.

  12. Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats

    PubMed Central

    Lupachyk, Sergey; Watcho, Pierre; Shevalye, Hanna; Vareniuk, Igor; Obrosov, Alexander; Obrosova, Irina G.

    2013-01-01

    Evidence for an important role for Na+/H+ exchangers in diabetic complications is emerging. The aim of this study was to evaluate whether Na+/H+ exchanger 1 inhibition reverses experimental peripheral diabetic neuropathy. Control and streptozotocin-diabetic rats were treated with the specific Na+/H+ exchanger 1 inhibitor cariporide for 4 wk after 12 wk without treatment. Neuropathy end points included sciatic motor and sensory nerve conduction velocities, endoneurial nutritive blood flow, vascular reactivity of epineurial arterioles, thermal nociception, tactile allodynia, and intraepidermal nerve fiber density. Advanced glycation end product and markers of oxidative stress, including nitrated protein levels in sciatic nerve, were evaluated by Western blot. Rats with 12-wk duration of diabetes developed motor and sensory nerve conduction deficits, thermal hypoalgesia, tactile allodynia, and intraepidermal nerve fiber loss. All these changes, including impairment of nerve blood flow and vascular reactivity of epineurial arterioles, were partially reversed by 4 wk of cariporide treatment. Na+/H+ exchanger 1 inhibition was also associated with reduction of diabetes-induced accumulation of advanced glycation endproduct, oxidative stress, and nitrated proteins in sciatic nerve. In conclusion, these findings support an important role for Na+/H+ exchanger 1 in functional, structural, and biochemical manifestations of peripheral diabetic neuropathy and provide the rationale for development of Na+/H+ exchanger 1 inhibitors for treatment of diabetic vascular and neural complications. PMID:23736542

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

    PubMed Central

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

    2017-01-01

    Due to substantial morbidity and complications including nephropathy, a search for alternative treatment of diabetes mellitus is urgently required. The present study aimed to investigate the hypoglycemic and anti-diabetic nephropathy activities of polysaccharides separated from Auricularia auricular (AAP). Diet streptozotocin (STZ)-induced diabetic Sprague-Dawley rats were orally treated with metformin (100 mg/kg; positive control) and AAP (100 and 400 mg/kg) for four weeks, and parameters in the serum and liver associated with blood glucose, free radicals and nephropathy were determined. Similar to metformin, AAP treatment strongly reduced blood glucose levels by promoting glucose metabolism. The anti-oxidative activity of AAP, which was indicated by the modulation of superoxide dismutase, glutathione peroxidase, reactive oxygen species and methane dicarboxylic aldehyde levels in serum, was observed in diabetic rats. Furthermore, the regulatory effects of AAP on blood urea nitrogen, creatinine, uric protein and inflammatory-related factors revealed its protection against diabetic nephropathy. The present data suggests that AAP-mediated anti-diabetic and anti-nephritic effects are partially associated with their modulations on the anti-oxidative system and nuclear factor kappa B-related signaling pathway. In conclusion, AAP has potential to be a novel source of treatments for diabetes. PMID:28123514

  14. Simvastatin treatment restores vasoconstriction and the inhibitory effect of LPC on endothelial relaxation via affecting oxidizing metabolism in diabetic rats.

    PubMed

    Ceylan, A; Karasu, C; Aktan, F; Ozansoy, G

    2004-08-01

    Oxidative stress and dyslipidaemia play an important role in the development of diabetes-induced vascular complications. The aim of this study was to examine the reversal effects of simvastatin on some metabolic and oxidative parameters, and vascular functions in diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.). Eight weeks after STZ induction, some of the diabetic and control rats were treated with simvastatin (10 mg/kg rat/d) for 4 weeks. Plasma glucose, triglyceride and total cholesterol concentrations were significantly increased in 12-week diabetic rats. Simvastatin treatment stopped the loss of body weight, completely normalized the increase of plasma lipids and partially reduced the hyperglycaemia in diabetic rats. Increased malondialdehyde levels, catalase and glutathione peroxidase activities were normalised by simvastatin treatment in diabetic aorta. Phenylephrine (PE)-induced contractility in aorta rings was unaffected by diabetes, but was markedly decreased after simvastatin treatment in both control and diabetic rats. Reduction of endothelium-dependent vasorelaxation in diabetes was significantly ameliorated by simvastatin treatment. Incubation of aorta rings with lysophosphatidylcholine, a component of the oxidized LDL, did not significantly affect PE-induced contractions, but reduced endothelium-dependent relaxations more in untreated-diabetic rats than in other experimental groups. The endothelium-independent vasorelaxations were similar in all ring preparations. These results indicate that simvastatin treatment may ameliorate diabetes-induced abnormal vasoconstriction and endothelial dysfunction via affecting general and oxidizing metabolism, nitric oxide disability and intracellular calcium mobilisation.

  15. 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.

  16. Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study.

    PubMed

    Nurulain, Syed M; Shafiullah, Mohamed; Yasin, Javed; Adem, Abdu; Kaabi, Juma Al; Tariq, Saeed; Adeghate, Ernest; Ojha, Shreesh

    2016-06-01

    Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide. The present study investigates the cardiac effect of no observable dose of a metabolite of terbufos, terbufos-sulfone (TS), under non-diabetic and streptozotocin-induced diabetic condition. One hundred nanomoles per rat (1/20 of LD50) was administered intraperitoneally to adult male Wister rats daily for fifteen days. The left ventricle was collected for ultrastructural changes by transmission electron microscopy. The blood samples were collected for biochemical tests including RBC acetylcholinesterase, creatinine kinase (CK), lactate dehydrogenase (LDH), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, ALT, AST, and GGT. The study revealed about 10 % inhibition of RBC-AChE in two weeks of TS treatment in non-diabetic rats whereas RBC-AChE activity was significantly decreased in diabetic TS treated rats. CK, LDH, and triglycerides were significantly higher in diabetic TS treated rats. Electron microscopy of the heart showed derangement and lesions of the mitochondria of cardiomyocytes in the TS treated groups. The present study concludes that a non-lethal dose of TS causes cardiac lesions which exacerbate under diabetic condition. Biochemical tests confirmed the ultrastructural changes. It is concluded that a non-lethal dose of TS may be a risk factor for a cardiovascular disease, which may be fatal under diabetic condition.

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

    PubMed

    Jia, Yanglei; Xu, Gang; Zhou, Wenjing; Wang, Zhenzheng; Meng, Linlin; Zhou, Songnan; Xu, Xia; Yuan, Huiqing; Tian, Keli

    2014-01-01

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

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

    PubMed

    Tuzcu, Mehmet; Baydas, Giyasettin

    2006-05-10

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

  19. Effects of physical training on the immune system in diabetic rats

    PubMed Central

    Crespilho, Daniel Maciel; de Almeida Leme, José Alexandre Curiacos; de Mello, Maria Alice Rostom; Luciano, Eliete

    2010-01-01

    Aims: This study aims to investigate the influence of physical training on the immune system of diabetic rats. Materials and Methods: Adult male Wistar rats were distributed into Sedentary Control (SC), Trained Control (TC), Sedentary Diabetic (SD) and Trained Diabetic (TD) groups were used. Diabetes was induced by alloxan (32 mg/bw-i.v.). Training protocol consisted of swimming, at 32 ± 1°C, one hour/day, five days/week, supporting an overload equivalent to 5% of the body weight, during four weeks. At the end of the experiment the rats were sacrificed by decapitation and blood samples were collected for glucose, insulin, albumin, hematocrit determinations, total and differential leukocyte counting. Additionally, liver samples for glycogen analyses were obtained. Results: The results were analyzed by one way at a significance level of 5%. Diabetes reduced blood insulin, liver glycogen stores and increased blood glucose and neutrophil count. Physical training restored glycemia, liver glycogen levels, neutrophils and lymphocytes count in diabetic rats. Conclusions: In summary, physical training was able to improve metabolic and immunological aspects in the experimental diabetic rats. PMID:20431804

  20. Improvement in Serum Biochemical Alterations and Oxidative Stress of Liver and Pancreas following Use of Royal Jelly in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ghanbari, Elham; Nejati, Vahid; Khazaei, Mozafar

    2016-01-01

    Objective This study aimed to evaluate the effects of royal jelly (RJ) on serum biochemical alterations and oxidative stress status in liver and pancreas of streptozotocin (STZ)- induced diabetic rats. Materials and Methods In this experimental study, thirty two male Wistar rats were divided into the following four groups (n=8/group): i. Control (C), ii. Diabetic (D), iii. Royal jelly (R), and iv. Royal jelly-treated diabetic (D/R) groups. Diabetes was induced by single intraperitoneal (IP) injection of STZ (60 mg/kg). The RJ [100 mg/kg body weight (BW)] was administered orally for 42 days. Blood samples were used to determine serum levels of insulin, high density lipoprotein cholesterol (HDL-c), total protein (TP), albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and fasting blood glucose (FBG). Also, the antioxidant status was evaluated by determining the levels of malondialdehyde (MDA), catalase (CAT) and ferric reducing antioxidant power (FRAP) in liver and pancreas. Data were analyzed by one-way analysis of variance (ANOVA) with P<0.05 as the significant level. Results STZ-induced diabetic rats showed a significant elevation in the serum levels of AST, ALT, ALP and FBG, whereas there was a significant decrease in serum levels of insulin, albumin, HDL-c and TP (P<0.05). Treatment of the diabetic rats with RJ restored the changes of the above parameters to their normal levels (P<0.05). In addition, RJ significantly improved reduced levels of FRAP and CAT as well as high MDA level in liver and pancreas (P<0.05). Conclusion RJ improves oxidative damage induced by STZ in the liver and pancreas of rats; therefore, it can be considered as an effective and alternative treatment for diabetes. PMID:27602318

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

    PubMed

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

    2016-01-01

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

  2. Antidiabetic and neuroprotective effects of Trigonella foenum-graecum seed powder in diabetic rat brain.

    PubMed

    Kumar, P; Kale, R K; McLean, P; Baquer, N Z

    2012-01-01

    Trigonella foenum-graecum seed powder (TSP) has been reported to have hypoglycemic and hyperinsulinemic action. The objective of the study was to examine the antidiabetic and neuroprotective role of TSP in hyperglycemiainduced alterations in blood glucose, insulin levels and activities of membrane linked enzymes (Na+K+ATPase, Ca2+ATPase), antioxidant enzymes (superoxide dismutase, glutathione S-transferase), calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in the diabetic rat brain. Female Wistar rats weighing between 180 and 220 g were made diabetic by a single injection of alloxan monohydrate (15 mg/100 g body weight), diabetic rats were given 2 IU insulin, per day with 5% TSP in the diet for three weeks. A significant increase in lipid peroxidation was observed in diabetic brain. The increased lipid peroxidation following chronic hyperglycemia was accompanied with a significant increase in the neurolipofuscin deposition and Ca2+ levels with decreased activities of membrane linked ATPases and antioxidant enzymes in diabetic brain. A decrease in synaptosomal membrane fluidity may influence the activity of membrane linked enzymes in diabetes. The present study showed that TSP treatment can reverse the hyperglycemia induced changes to normal levels in diabetic rat brain. TSP administration amended effect of hy