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Sample records for aged diabetic rats

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Brain nitric oxides synthase in major pelvic ganglia of aged (LETO) and diabetic (OLETF) rats.

    PubMed

    Salama, N; Tamura, M; Tsuruo, Y; Ishimura, K; Kagawa, S

    2002-01-01

    This study was conducted to evaluate the effects of aging and diabetes mellitus (DM) on brain nitric oxide synthase (bNOS) expression in major pelvic ganglia (MPG) of rats. Otsuka Long Evans Tokushima Fatty rats (12, 30, and 70 weeks old), which are genetic models with non-insulin-dependent DM (NIDDM), and age-matched nondiabetic Long Evans Tokushima Otsuka controls were used. The MPG of all rats in this study were subjected to cryo-sectioning and staining with bNOS polyclonal AB and rhodamine-conjugated rabbit IgG. Fluorescence intensities of the stained neurons were assessed in randomly selected fields per each specimen. Animals of both groups revealed significant decline in the staining intensity of their neurons with aging and the progress of DM, but diabetic rats showed more decline than controls. In conclusion, both aging and NIDDM could decrease bNOS expression in rat MPG. However, NIDDM has a more evident effect than aging on that expression. The decrease in bNOS may cause a disturbance in functions of the target pelvic structures of these ganglia under both conditions. PMID:12230824

  5. Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats.

    PubMed Central

    Stitt, A. W.; Li, Y. M.; Gardiner, T. A.; Bucala, R.; Archer, D. B.; Vlassara, H.

    1997-01-01

    Advanced glycation end products (AGEs), formed from the nonenzymatic glycation of proteins and lipids with reducing sugars, have been implicated in many diabetic complications; however, their role in diabetic retinopathy remains largely unknown. Recent studies suggest that the cellular actions of AGEs may be mediated by AGE-specific receptors (AGE-R). We have examined the immunolocalization of AGEs and AGE-R components R1 and R2 in the retinal vasculature at 2, 4, and 8 months after STZ-induced diabetes as well as in nondiabetic rats infused with AGE bovine serum albumin for 2 weeks. Using polyclonal or monoclonal anti-AGE antibodies and polyclonal antibodies to recombinant AGE-R1 and AGE-R2, immunoreactivity (IR) was examined in the complete retinal vascular tree after isolation by trypsin digestion. After 2, 4, and 8 months of diabetes, there was a gradual increase in AGE IR in basement membrane. At 8 months, pericytes, smooth muscle cells, and endothelial cells of the retinal vessels showed dense intracellular AGE IR. AGE epitopes stained most intensely within pericytes and smooth muscle cells but less in basement membrane of AGE-infused rats compared with the diabetic group. Retinas from normal or bovine-serum-albumin-infused rats were largely negative for AGE IR. AGE-R1 and -R2 co-localized strongly with AGEs of vascular endothelial cells, pericytes, and smooth muscle cells of either normal, diabetic, or AGE-infused rat retinas, and this distribution did not vary with each condition. The data indicate that AGEs accumulate as a function of diabetes duration first within the basement membrane and then intracellularly, co-localizing with cellular AGE-Rs. Significant AGE deposits appear within the pericytes after long-term diabetes or acute challenge with AGE infusion conditions associated with pericyte damage. Co-localization of AGEs and AGE-Rs in retinal cells points to possible interactions of pathogenic significance. Images Figure 1 Figure 2 Figure 3 PMID

  6. Histopathological lesions in the pancreas of the BB Wistar rat as a function of age and duration of diabetes.

    PubMed

    Wright, J; Yates, A; Sharma, H; Thibert, P

    1985-01-01

    Pancreatic histopathology was studied in 121 BBWd, 43 BBWnd, and 33 Wistar rats. Insulitis was the most common inflammatory lesion in both BBW and BBWnd rats. The incidence was inversely associated with age and with duration of diabetes in BBWd rats, but there was no age-related pattern in BBWnd rats. Small end-stage islets were typical of BBWd rats but were not seen in BBWnd rats. Several BBWd rats showed hyperplastic islets months after the onset of diabetes, a pattern that is also seen in a small percentage of human JOD patients. Several non-specific exocrine inflammatory lesions occurred in both BBWd and BBWnd rats: acute and/or chronic pancreatitis, eosinophilic infiltrates, granulomatous lesions and acute and/or chronic interstitial inflammation. Only chronic interstitial inflammation was seen in outbred Wistar rats. PMID:3882779

  7. Peripheral Levels of AGEs and Astrocyte Alterations in the Hippocampus of STZ-Diabetic Rats.

    PubMed

    Nardin, Patrícia; Zanotto, Caroline; Hansen, Fernanda; Batassini, Cristiane; Gasparin, Manuela Sangalli; Sesterheim, Patrícia; Gonçalves, Carlos-Alberto

    2016-08-01

    Diabetic patients and streptozotocin (STZ)-induced diabetes mellitus (DM) models exhibit signals of brain dysfunction, evidenced by neuronal damage and memory impairment. Astrocytes surrounding capillaries and synapses modulate many brain activities that are connected to neuronal function, such as nutrient flux and glutamatergic neurotransmission. As such, cognitive changes observed in diabetic patients and experimental models could be related to astroglial alterations. Herein, we investigate specific astrocyte changes in the rat hippocampus in a model of DM induced by STZ, particularly looking at glial fibrillary acidic protein (GFAP), S100B protein and glutamate uptake, as well as the content of advanced glycated end products (AGEs) in serum and cerebrospinal fluid (CSF), as a consequence of elevated hyperglycemia and the content of receptor for AGEs in the hippocampus. We found clear peripheral alterations, including hyperglycemia, low levels of proinsulin C-peptide, elevated levels of AGEs in serum and CSF, as well as an increase in RAGE in hippocampal tissue. We found specific astroglial abnormalities in this brain region, such as reduced S100B content, reduced glutamate uptake and increased S100B secretion, which were not accompanied by changes in GFAP. We also observed an increase in the glucose transporter, GLUT-1. All these changes may result from RAGE-induced inflammation; these astroglial alterations together with the reduced content of GluN1, a subunit of the NMDA receptor, in the hippocampus may be associated with the impairment of glutamatergic communication in diabetic rats. These findings contribute to understanding the cognitive deficits in diabetic patients and experimental models. PMID:27084774

  8. 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. PMID:27119311

  9. Susceptibility of Diabetic Rats to Pulmonary and Systemic Effects of Inhaled Photochemically-Aged Atmosphere and Ozone (O3)

    EPA Science Inventory

    Susceptibility of Diabetic Rats to Pulmonary and Systemic Effects of Inhaled Photochemically-Aged Atmosphere and Ozone (O3)MC Schladweiler1, SJ Snow2, QT Krantz1, C King1, JD Krug2, N Modak2, A Henriquez3, V Bass4, DJ Miller3, JE Richards1, EH Boykin1, R Jaskot1, MI Gilmour1 and ...

  10. Short-lived diabetes in the young-adult ZDF rat does not exacerbate neuronal Ca(2+) biomarkers of aging.

    PubMed

    Maimaiti, Shaniya; DeMoll, Chris; Anderson, Katie L; Griggs, Ryan B; Taylor, Bradley K; Porter, Nada M; Thibault, Olivier

    2015-09-24

    Results from clinical studies provide evidence that cognitive changes relatively late in life may be traced to antecedent conditions including diabetes, obesity, a sedentary lifestyle, and an atherogenic diet. As such, several traits of Type 2 diabetes (T2DM) could be considered pathogenic factors of aging, contributing to age-dependent cognitive decline and our susceptibility to Alzheimer's disease. It appears that both the duration of metabolic condition and the age of the individual, together can contribute to the potential impact on peripheral as well as brain health. Because of robust evidence that in animal models of aging, Ca(2+) dysregulation alters neuronal health, synaptic plasticity, and learning and memory processes, we tested the hypothesis that peripheral metabolic dysregulation could exacerbate Ca(2+) dysfunction in hippocampal CA1 neurons. Using intracellular/ extracellular electrophysiological and Ca(2+) imaging techniques, we show that Ca(2+)levels at rest or during synaptic stimulation, the Ca(2+)-dependent afterhyperpolarization, baseline field potentials, and short-term synaptic plasticity were not significantly altered in young-adult male Zucker diabetic fatty rats compare to their lean counterparts. Our observations suggest that early phases of T2DM characterized by high levels of glucose and insulin may be too transient to alter hippocampal CA1 physiology in this animal model of diabetes. These results are supported by clinical data showing that longer T2DM duration can have greater negative impact on cognitive functions. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25451110

  11. Soft-shelled turtle eggs inhibit the formation of AGEs in the serum and skin of diabetic rats

    PubMed Central

    Yamanaka, Mikihiro; Shirakawa, Jun-ichi; Ohno, Rei-ichi; Shinagawa, Masatoshi; Hatano, Kota; Sugawa, Hikari; Arakawa, Shoutaro; Furusawa, Chisato; Nagai, Mime; Nagai, Ryoji

    2016-01-01

    Although soft-shelled turtle eggs (STE) have been used as a folk medicine for revitalization and the prevention of lifestyle-related diseases, the scientific evidence to support the use of STE in this manner is scarce. To clarify the physiological evidence, STE was administered to diabetic rats and the inhibitory effects on the formation of advanced glycation end-products (AGEs), which are known to increase with the progression of lifestyle-related diseases, were examined. STE and citric acid were administered to diabetic rats for 3 months, and serum Nε-(carboxymethyl)lysine (CML) contents were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the administration of STE did not affect the body weight, glycoalbumin or ketone body levels, it significantly reduced the serum level of CML. The accumulation of AGEs, which was measured by fluorescence intensity in the auricle skin and the lower gums, was also reduced by the administration of STE to a similar extent to that observed with citric acid. This report provides the first evidence that the oral administration of STE reduces the formation of AGEs, suggesting that one of the health effects of STE may be the inhibition of AGEs formation. PMID:27013779

  12. Soft-shelled turtle eggs inhibit the formation of AGEs in the serum and skin of diabetic rats.

    PubMed

    Yamanaka, Mikihiro; Shirakawa, Jun-Ichi; Ohno, Rei-Ichi; Shinagawa, Masatoshi; Hatano, Kota; Sugawa, Hikari; Arakawa, Shoutaro; Furusawa, Chisato; Nagai, Mime; Nagai, Ryoji

    2016-03-01

    Although soft-shelled turtle eggs (STE) have been used as a folk medicine for revitalization and the prevention of lifestyle-related diseases, the scientific evidence to support the use of STE in this manner is scarce. To clarify the physiological evidence, STE was administered to diabetic rats and the inhibitory effects on the formation of advanced glycation end-products (AGEs), which are known to increase with the progression of lifestyle-related diseases, were examined. STE and citric acid were administered to diabetic rats for 3 months, and serum N (ε)-(carboxymethyl)lysine (CML) contents were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the administration of STE did not affect the body weight, glycoalbumin or ketone body levels, it significantly reduced the serum level of CML. The accumulation of AGEs, which was measured by fluorescence intensity in the auricle skin and the lower gums, was also reduced by the administration of STE to a similar extent to that observed with citric acid. This report provides the first evidence that the oral administration of STE reduces the formation of AGEs, suggesting that one of the health effects of STE may be the inhibition of AGEs formation. PMID:27013779

  13. Diabetes in the Aged

    PubMed Central

    Grobin, Wulf

    1970-01-01

    In keeping with the already known high prevalence of diabetes among residents of the Jewish Home for the Aged, Toronto, annual screening disclosed an average incidence of 25.5% of abnormal glucose tolerance (two-hour post-glucose blood sugars above 140 mg./100 ml.) in residents not known to be diabetic. Forty-five (47%) of the 94 residents with abnormal screening values were considered subsequently to be diabetic according to our criteria. Long-term follow-up, particularly of 81 residents initially normoglycemic in 1964-5, confirmed that the natural course of glucose tolerance in this population was one of progressive deterioration. By contrast, improvement amounting to remission has been demonstrated in nine out of 20 residents several years after they had been declared diabetic, and is thought to have been induced by dietotherapy. Moderate hyperglycemia per se did not cause symptoms in these almost always keto-resistant and usually aglycosuric aged diabetics, who often claimed they felt better when hyperglycemic. Hypoglycemia was an ever present danger when anti-diabetic medication was used; it was the main reason for undertreatment. So far, data from our long-term study have not shown morbidity to be markedly increased in the diabetics, and mortality was found to be evenly distributed among diabetic and non-diabetic male residents. However, in the females there was a clear correlation between mortality rate and the diminished glucose tolerance. What may appear as overdiagnosis of diabetes in the aged is recommended in the hope that early institution of dietary treatment will delay the development of clinical diabetes and the need for anti-diabetic agents. This, in turn, would prevent iatrogenic hypoglycemia. It would also reduce the severity and frequency of spontaneous hypoglycemia which, we believe, occurs more commonly in the early phase of diabetes in the aged than is generally realized. PMID:5476778

  14. Salacia chinensis L. extract ameliorates abnormal glucose metabolism and improves the bone strength and accumulation of AGEs in type 1 diabetic rats.

    PubMed

    Shirakawa, Jun-Ichi; Arakawa, Shoutaro; Tagawa, Tomoya; Gotoh, Kentaroh; Oikawa, Norihisa; Ohno, Rei-Ichi; Shinagawa, Masatoshi; Hatano, Kota; Sugawa, Hikari; Ichimaru, Kenta; Kinoshita, Sho; Furusawa, Chisato; Yamanaka, Mikihiro; Kobayashi, Masakazu; Masuda, Shuichi; Nagai, Mime; Nagai, Ryoji

    2016-06-15

    Although extracts of the roots and stems of Salacia chinensis have been used in folk medicines for chronic diseases such as rheumatism, irregular menstruation, asthma and diabetes mellitus, little is known about the mechanism by which Salacia chinensis extract (SCE) ameliorates these diseases. To clarify whether SCE ameliorates the progression of lifestyle-related diseases, the inhibitory effect of SCE on the formation of advanced glycation end products (AGEs) was analyzed in a rat model of streptozotocin-induced diabetes. Although the oral administration of SCE did not ameliorate the diabetes-induced decrease in body weight, it ameliorated the increase in glycoalbumin levels in diabetic rats. An analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) demonstrated that the levels of N(ε)-(carboxymethyl)lysine (CML) were highest in the femurs and that they increased by the induction of diabetes. The administration of SCE also ameliorated the decreased femur strength and the accumulation of CML. Furthermore, when all of the carbohydrates in the chow of diabetic rats were replaced with free glucose, the administration of SCE significantly ameliorated a diabetes-induced increase in glycoalbumin and decrease in serum creatinine level and body weight. This study provides evidence to support that SCE ameliorates diabetes-induced abnormalities by improving the uptake of glucose by various organs. PMID:27121272

  15. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.

    PubMed

    Rani, Neha; Bharti, Saurabh; Bhatia, Jagriti; Nag, T C; Ray, Ruma; Arya, Dharamvir Singh

    2016-04-25

    AGE-RAGE interaction mediated oxidative stress and inflammation is the key mechanism involved in the pathogenesis of cardiovascular disease in diabetes. Inhibition of AGE-RAGE axis by several PPAR-γ agonists has shown positive results in ameliorating cardio-metabolic disease conditions. Chrysin, a natural flavonoid has shown to possess PPAR-γ agonist activity along with antioxidant and anti-inflammatory effect. Therefore, the present study was designed to evaluate the effect of chrysin in isoproterenol-induced myocardial injury in diabetic rats. In male albino Wistar rats, diabetes was induced by single injection of streptozotocin (70 mg/kg, i.p.). After confirmation of the diabetes, rats were treated with vehicle (1.5 mL/kg, p.o.), chrysin (60 mg/kg, p.o.) or PPAR-γ antagonist GW9662 (1 mg/kg, i.p.) for 28 days. Simultaneously, on 27th and 28th day myocardial injury was induced by isoproterenol (85 mg/kg, s.c.). Chrysin significantly ameliorated cardiac dysfunction as reflected by improved MAP, ±LVdP/dtmax and LVEDP in diabetic rats. This improvement was associated with increased PPAR-γ expression and reduced RAGE expression in diabetic rats. Chrysin significantly decreased inflammation through inhibiting NF-κBp65/IKK-β expression and TNF-α level. Additionally, chrysin significantly reduced apoptosis as indicated by augmented Bcl-2 expression and decreased Bax and caspase-3 expressions. Furthermore, chrysin inhibited nitro-oxidative stress by normalizing the alteration in 8-OHdG, GSH, TBARS, NO and CAT levels and Nox4, MnSOD, eNOS and NT expressions. Co-administration of GW9662 significantly blunted the chrysin mediated cardioprotective effect as there was increase in oxidative stress, inflammation and apoptosis markers. Chrysin significantly ameliorated isoproterenol-induced myocardial injury in diabetic rats via PPAR-γ activation and inhibition of AGE-RAGE mediated oxidative stress and inflammation. PMID:26972669

  16. Effects of α-lipoic acid on endothelial function in aged diabetic and high-fat fed rats

    PubMed Central

    Sena, C M; Nunes, E; Louro, T; Proença, T; Fernandes, R; Boarder, M R; Seiça, R M

    2007-01-01

    Background and purpose: This study was conducted to investigate the effects of α-lipoic acid (α-LA) on endothelial function in diabetic and high-fat fed animal models and elucidate the potential mechanism underlying the benefits of α-LA. Experimental approach: Plasma metabolites reflecting glucose and lipid metabolism, endothelial function, urinary albumin excretion (UAE), plasma and aortic malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated Goto-Kakizaki (GK) diabetic and high-fat fed GK rats (fed with atherogenic diet only, treated with α-LA and treated with vehicle, for 3 months). Vascular eNOS, nitrotyrosine, carbonyl groups and superoxide anion were also assessed in the different groups. Key results: α-LA and soybean oil significantly reduced both total and non-HDL serum cholesterol and triglycerides induced by atherogenic diet. MDA, carbonyl groups, vascular superoxide and 8-OHdG levels were higher in GK and high-fat fed GK groups and fully reversed with α-LA treatment. High-fat fed GK diabetic rats showed significantly reduced endothelial function and increased UAE, effects ameliorated with α-LA. This endothelial dysfunction was associated with decreased NO production, decreased expression of eNOS and increased vascular superoxide production and nitrotyrosine expression. Conclusions and implications: α-LA restores endothelial function and significantly improves systemic and local oxidative stress in high-fat fed GK diabetic rats. Improved endothelial function due to α-LA was at least partially attributed to recoupling of eNOS and increased NO bioavailability and represents a pharmacological approach to prevent major complications associated with type 2 diabetes. PMID:17906683

  17. The attenuation of Moutan Cortex on oxidative stress for renal injury in AGEs-induced mesangial cell dysfunction and streptozotocin-induced diabetic nephropathy rats.

    PubMed

    Zhang, Minghua; Feng, Liang; Gu, Junfei; Ma, Liang; Qin, Dong; Wu, Chan; Jia, Xiaobin

    2014-01-01

    Oxidative stress (OS) has been regarded as one of the major pathogeneses of diabetic nephropathy (DN) through damaging kidney which is associated with renal cells dysfunction. The aim of this study was to investigate whether Moutan Cortex (MC) could protect kidney function against oxidative stress in vitro or in vivo. The compounds in MC extract were analyzed by HPLC-ESI-MS. High-glucose-fat diet and STZ (30 mg kg(-1)) were used to induce DN rats model, while 200 μg mL(-1) AGEs were for HBZY-1 mesangial cell damage. The treatment with MC could significantly increase the activity of SOD, glutathione peroxidase (GSH-PX), and catalase (CAT). However, lipid peroxidation malondialdehyde (MDA) was reduced markedly in vitro or in vivo. Furthermore, MC decreased markedly the levels of blood glucose, serum creatinine, and urine protein in DN rats. Immunohistochemical assay showed that MC downregulated significantly transforming growth factor beta 2 (TGF-β2) protein expression in renal tissue. Our data provided evidence to support this fact that MC attenuated OS in AGEs-induced mesangial cell dysfunction and also in high-glucose-fat diet and STZ-induced DN rats. PMID:24876912

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

    PubMed

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

    2016-05-01

    Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88 ± 5.69 mmol/L vs. 14.79 ± 5.84 mmol/L, p < 0.05), while it was not different in diabetic rats after hypoxic treatment (13.14 ± 5.77 mmol/L vs. 14.79 ± 5.84 mmol/L, p > 0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28 ± 0.11 vs. 1.39 ± 0.11, p < 0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48 ± 0.48 vs. 3.86 ± 0.42, p < 0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular

  19. 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

  20. Distal axonopathy in streptozotocin diabetes in rats.

    PubMed

    Chokroverty, S; Seiden, D; Navidad, P; Cody, R

    1988-05-15

    We noted the earliest morphological changes in the motor endplates 8 weeks after the induction of streptozotocin diabetes in rats. Morphometric measurements showed reduced axonal areas of the lateral plantar and the sciatic nerves in the diabetic rats 28 but not 2 and 8 weeks after the experiment. These findings suggested distal axonopathy. PMID:3371449

  1. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    PubMed

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy. PMID:7699389

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

    PubMed

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

    2015-01-01

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

  3. 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.

  4. Hemodynamic alterations in chronically conscious unrestrained diabetic rats

    SciTech Connect

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

    1987-05-01

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

  5. Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats.

    PubMed

    Hou, Jun; Zheng, Dezhi; Fung, Gabriel; Deng, Haoyu; Chen, Lin; Liang, Jiali; Jiang, Yan; Hu, Yonghe

    2016-03-01

    Given the importance of the aggregation of advanced glycation end products (AGEs) and cardiac inflammation in the onset and progression of diabetic cardiomyopathy (DCM), our objective in this study was to demonstrate the cardioprotective effect of mangiferin, an antidiabetic and anti-inflammatory agent, on diabetic rat model. The DCM model was established by a high-fat diet and a low dose of streptozotocin. DCM rats were treated orally with mangiferin (20 mg/kg) for 16 weeks. Serum and left ventricular myocardium were collected for determination of inflammatory cytokines. AGEs mRNA and protein expression of nuclear factor kappa B (NF-κB) and receptor for AGEs (RAGE) in myocardium were assayed by real-time PCR and Western blot. ROS levels were measured by dihydroethidium fluorescence staining. NF-κB binding activity was assayed by TransAM NF-κB p65 ELISA kit. Chronic treatment with mangiferin decreased the levels of myocardial enzymes (CK-MB, LDH) and inflammatory mediators (TNF-α, IL-1β). Meanwhile, NF-κB is inhibited by the reduction of nuclear translocation of p65 subunit, and mangiferin reduced AGE production and decreased the mRNA and protein expression of RAGE in DCM rats. Our data indicated that mangiferin could significantly ameliorate DCM by preventing the release of inflammatory cytokines, and inhibiting ROS accumulation, AGE/RAGE production, and NF-κB nuclear translocation, suggesting that mangiferin treatment might be beneficial in DCM. PMID:26751764

  6. Diabetes and ageing-induced vascular inflammation.

    PubMed

    Assar, Mariam El; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2016-04-15

    Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor-кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co-exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low-grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes-induced vascular impairment in the elderly. PMID:26435167

  7. 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.

  8. 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. PMID:18557425

  9. Ellagic acid inhibits non-enzymatic glycation and prevents proteinuria in diabetic rats.

    PubMed

    Raghu, G; Jakhotia, Sneha; Yadagiri Reddy, P; Anil Kumar, P; Bhanuprakash Reddy, G

    2016-03-16

    The formation of advanced glycation end products (AGEs) is a characteristic feature of diabetic tissues and accumulation of these products has been implicated in the pathogenesis of micro- and macrovascular complications of diabetes including diabetic nephropathy (DN). Compelling evidence suggests that AGEs mediate progressive alteration in the renal architecture and loss of renal function whereas inhibitors of AGEs prevent the progression of experimental DN. We have investigated the potential of ellagic acid (EA), a polyphenol present abundantly in fruits and vegetables, to prevent in vivo accumulation of AGE and to ameliorate renal changes in diabetic rats. Streptozotocin-induced diabetic rats were fed with either 0.2% or 2% of EA in the diet for 12 weeks. Dietary supplementation of EA to diabetic rats prevented the glycation mediated RBC-IgG-cross-links and HbA1c accumulation. EA inhibited the accumulation of N-carboxymethyl lysine (CML), a predominant AGE in the diabetic kidney. Further, EA also prevented the AGE-mediated loss of expression of podocyte slit diaphragm proteins: nephrin and podocin. By inhibiting CML formation, EA improved renal function in rats as evidenced by urinary albumin and creatinine levels. In conclusion, EA inhibited AGE accumulation in the diabetic rat kidney and ameliorated AGE-mediated pathogenesis of DN. PMID:26902315

  10. Effects of aspartame on diabetic rats and diabetic patients.

    PubMed

    Shigeta, H; Yoshida, T; Nakai, M; Mori, H; Kano, Y; Nishioka, H; Kajiyama, S; Kitagawa, Y; Kanatsuna, T; Kondo, M

    1985-10-01

    The effects of aspartame (L-aspartyl-L-phenylalanine methyl ester) on plasma glucose and insulin levels were investigated in diabetic rats and patients with non-insulin-dependent diabetes mellitus. The oral administration of 0.45 mg aspartame per 100g body weight, which is equivalent to 150 mg of glucose in sweetness, to streptozotocin-induced diabetic rats had no effect on the plasma glucose or insulin levels. Also, 225 mg oral aspartame loading, which is equivalent to 75 g of glucose in sweetness, to patients with non-insulin-dependent diabetes mellitus did not increase plasma glucose or insulin levels, although 75 g of oral glucose loading increased plasma glucose and insulin levels in diabetic patients as expected. Aspartame ingestion for three days at a dose of 24-48 mg per day and the intake of snacks flavored with 240 mg of aspartame also did not increase fasting plasma glucose levels. These results suggest that acute administration of aspartame has no influence on plasma glucose or insulin levels in diabetic rats and patients with non-insulin-dependent diabetes mellitus. PMID:3908628

  11. Glutamate (mGluR-5) gene expression in brain regions of streptozotocin induced diabetic rats as a function of age: role in regulation of calcium release from the pancreatic islets in vitro

    PubMed Central

    2009-01-01

    Metabotrophic glutamate receptors (mGluRs) modulate cellular activities involved in the processes of differentiation and degeneration. In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5) in cerebral cortex, corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I) as a function of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90 weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10-7 M) stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in calcium release has immense therapeutic application in insulin secretion and function. PMID:19903331

  12. Irradiated lymphocytes do not adoptively transfer diabetes or prevent spontaneous disease in the BB/W rat

    SciTech Connect

    Mordes, J.P.; Handler, E.S.; Like, A.A.; Nakano, K.; Rossini, A.A.

    1986-06-01

    Diabetes in the BB/W rat is autoimmune in origin, and lymphocytes from acutely diabetic animals activated by concanavalin A (con A) induce the disease in adoptive recipients. We report that irradiation of these cells prevents adoptive transfer of diabetes. Through 60 days of age, diabetes occurred in none of 47 BB/W rats given irradiated con A cells, but in 21 of 36 (58%) given nonirradiated cells. Between 60 and 130 days of age, however, spontaneous diabetes occurred in 18 of 34 untreated control rats (53%) and 16 of 32 rats (50%) given two injections of irradiated con A activated spleen cells. We conclude that irradiation prevents adoptive transfer of BB/W rat diabetes and that irradiated con A activated lymphocytes from acutely diabetic rats do not protect against spontaneous disease in susceptible recipients.

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

    PubMed Central

    Loganathan, Rajprasad; Bilgen, Mehmet; Al-Hafez, Baraa; Alenezy, Mohammed D; Smirnova, Irina V

    2006-01-01

    Background Diabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy. Methods In this study, we used high field magnetic resonance imaging (MRI) to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched controls. Results Our analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively) compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats. Conclusion Thus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes. PMID:16595006

  14. Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes.

    PubMed

    Stanley, Christopher P; Wheal, Amanda J; Randall, Michael D; O'Sullivan, Saoirse E

    2013-11-15

    Circulating levels of anandamide are increased in diabetes, and cannabidiol ameliorates a number of pathologies associated with diabetes. The aim of the present study was to examine how exposure to anandamide or cannabidiol might affect endothelial dysfunction associated with Zucker Diabetic Fatty rats. Age-matched Zucker Diabetic Fatty and Zucker lean rats were killed by cervical dislocation and their arteries mounted on a myograph at 37 °C. Arteries were incubated for 2h with anandamide, cannabidiol or vehicle, contracted, and cumulative concentration-response curves to acetylcholine were constructed. Anandamide (10 µM, 2h) significantly improved the vasorelaxant responses to acetylcholine in aortae and femoral arteries from Zucker Diabetic Fatty rats but not Zucker lean rats. By contrast, anandamide (1 µM, 2h) significantly blunted acetylcholine-induced vasorelaxation in third-order mesenteric arteries (G3) from Zucker Diabetic Fatty rats. Cannabidiol incubation (10 µM, 2h) improved acetylcholine responses in the arteries of Zucker Diabetic Fatty rats (aorta and femoral) and Zucker lean (aorta, femoral and G3 mesenteric), and this effect was greater in the Zucker Diabetic Fatty rat. These studies suggest that increased circulating endocannabinoids may alter vascular function both positively and negatively in type 2 diabetes, and that part of the beneficial effect of cannabidiol in diabetes may be due to improved endothelium-dependent vasorelaxation. PMID:24120371

  15. Aging, Resistance Training, and Diabetes Prevention

    PubMed Central

    Flack, Kyle D.; Davy, Kevin P.; Hulver, Matthew W.; Winett, Richard A.; Frisard, Madlyn I.; Davy, Brenda M.

    2011-01-01

    With the aging of the baby-boom generation and increases in life expectancy, the American population is growing older. Aging is associated with adverse changes in glucose tolerance and increased risk of diabetes; the increasing prevalence of diabetes among older adults suggests a clear need for effective diabetes prevention approaches for this population. The purpose of paper is to review what is known about changes in glucose tolerance with advancing age and the potential utility of resistance training (RT) as an intervention to prevent diabetes among middle-aged and older adults. Age-related factors contributing to glucose intolerance, which may be improved with RT, include improvements in insulin signaling defects, reductions in tumor necrosis factor-α, increases in adiponectin and insulin-like growth factor-1 concentrations, and reductions in total and abdominal visceral fat. Current RT recommendations and future areas for investigation are presented. PMID:21197110

  16. Oxidative stress in normal and diabetic rats.

    PubMed

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (p<0.001) greater than the control levels. The diabetic animals presented an amount of vitamin E far greater (p<0.0001) than the controls, as was also the case for the vitaminE/polyunsaturated fatty acid (PUFA) and vitaminE/linoleic acid (C18:2) ratios. Greater vitaminE/triglyceride (TG) ratio, however, appeared in the control group. The corresponding vitamin A ratios (vitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected. PMID:10523056

  17. Fine structural abnormalities of the placenta in diabetic rats.

    PubMed

    Gewolb, I H; Merdian, W; Warshaw, J B; Enders, A C

    1986-11-01

    In the streptozocin-induced diabetic rat, the placenta is larger and the fetus is smaller than normal. To study cellular differences that might contribute to the size and functional disparity between diabetic and control placentas, a light- and electron-microscopic analysis was performed on 14-, 18-, and 22-day (term) control and diabetic placentas. Diabetic placentas, especially later in gestation, were marked by the presence of large numbers of glycogen-distended cells in the basal zone. Within the placental labyrinth, the trophoblastic layers of the interhemal membrane were significantly thicker in the diabetic placentas on days 18 and 22, and large accumulations of liid droplets were present, especially in the inner two trophoblastic layers. In normal placentas there is a marked thinning of the placental barrier in the labyrinth by day 22 of gestation, making the thickness of the labyrinthine layers in age-matched diabetic placentas even more impressive. Finally, the labyrinth of 22-day diabetic placentas contained more glycogen and rough endoplasmic reticulum in the inner trophoblastic layer, a feature that is found in less-mature (18-day) control placentas. Thus, the diabetic placentas have a number of features that are consistent with functional immaturity/dysmaturity. Cytologic evidence confirms the presence of increased glycogen and lipid reserves in both the junctional zone and the cellular area between maternal and fetal blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3758495

  18. Effect of cinnamon and its procyanidin-B2 enriched fraction on diabetic nephropathy in rats.

    PubMed

    Muthenna, P; Raghu, G; Kumar, P Anil; Surekha, M V; Reddy, G Bhanuprakash

    2014-10-01

    Non-enzymatic protein glycation and resultant accumulation of advanced glycation endproducts (AGE) are implicated in the pathogenesis of diabetic complications including diabetic nephropathy (DN). It is considered that antiglycating agents offer protection against AGE mediated pathologies including DN. Earlier we characterized procyanidin-B2 (PCB2) as the active component from cinnamon (Cinnamomum zeylanicum) that inhibits AGE formation in vitro. In this study, we have investigated the potential of PCB2-enriched fraction of cinnamon to prevent in vivo accumulation of AGE and to ameliorate renal changes in diabetic rats. Streptozotocin-induced diabetic rats were fed with either 3% cinnamon or 0.002% PCB2-fraction in diet for 12weeks. Biochemical analysis of blood and urine was performed at the end of experiment. Evaluation of glomerular markers that serve as indicators of renal function was done by immunohistochemistry, immunoblotting and qRT-PCR. Supplementation of diabetic rats with cinnamon and PCB2-fraction prevented glycation mediated RBC-IgG cross-links and HbA1c accumulation in diabetes rats. Cinnamon and PCB2-fraction also inhibited the accumulation of N-carboxy methyl lysine (CML), a prominent AGE in diabetic kidney. Interestingly, cinnamon and its PCB2-fraction prevented the AGE mediated loss of expression of glomerular podocyte proteins; nephrin and podocin. Inhibition of AGE by cinnamon and PCB2-fraction ameliorated the diabetes mediated renal malfunction in rats as evidenced by reduced urinary albumin and creatinine. In conclusion, PCB2 from cinnamon inhibited AGE accumulation in diabetic rat kidney and ameliorated AGE mediated pathogenesis of DN. PMID:25199697

  19. Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes

    PubMed Central

    Kondo, Masaki; Kamiya, Hideki; Himeno, Tatsuhito; Naruse, Keiko; Nakashima, Eitaro; Watarai, Atsuko; Shibata, Taiga; Tosaki, Takahiro; Kato, Jiro; Okawa, Tetsuji; Hamada, Yoji; Isobe, Ken-ichi; Oiso, Yutaka; Nakamura, Jiro

    2015-01-01

    Aims/Introduction Recent studies have shown that cell transplantation therapies, such as endothelial precursor cells, bone marrow-derived mononuclear cells (BM-MNCs) and mesenchymal stem cells, are effective on diabetic polyneuropathy through ameliorating impaired nerve blood flow in diabetic rats. Here, we investigated the effects of BM-MNCs transplantation in diabetic polyneuropathy using BM-MNCs derived from adult (16-week-old) diabetic (AD), adult non-diabetic (AN) or young (8-week-old) non-diabetic (YN) rats. Materials and Methods BM-MNCs of AD and AN were isolated after an 8-week diabetes duration. The BM-MNCs were characterized using flow cytometry analysis of cell surface markers and reverse transcription polymerase chain reaction of several cytokines. BM-MNCs or saline were injected into hind limb muscles. Four weeks later, the thermal plantar test, nerve conduction velocity, blood flow of the sciatic nerve and capillary-to-muscle fiber ratio were evaluated. Results The number of CD29+/CD90+ cells that host mesenchymal stem cells in BM-MNCs decreased in AD compared with AN or YN, and transcript expressions of basic fibroblast growth factor and nerve growth factor in BM-MNCs decreased in AD compared with AN or YN. Impaired thermal sensation, decreased blood flow of the sciatic nerve and delayed nerve conduction velocity in 8-week-diabetic rats were significantly ameliorated by BM-MNCs derived from YN, whereas BM-MNCs from AD or AN rats did not show any beneficial effect in these functional tests. Conclusions These results show that cytokine production abilities and the mesenchymal stem cell population of BM-MNCs would be modified by aging and metabolic changes in diabetes, and that these differences could explain the disparity of the therapeutic efficacy of BM-MNCs between young and adult or diabetic and non-diabetic patients in diabetic polyneuropathy. PMID:25802721

  20. Roles of the AGE-RAGE system in vascular injury in diabetes.

    PubMed

    Yamamoto, Y; Yamagishi, S; Yonekura, H; Doi, T; Tsuji, H; Kato, I; Takasawa, S; Okamoto, H; Abedin, J; Tanaka, N; Sakurai, S; Migita, H; Unoki, H; Wang, H; Zenda, T; Wu, P S; Segawa, Y; Higashide, T; Kawasaki, K; Yamamoto, H

    2000-05-01

    This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic. PMID:10865836

  1. Increased Oxidative and Nitrative Stress Accelerates Aging of the Retinal Vasculature in the Diabetic Retina

    PubMed Central

    Lamoke, Folami; Shaw, Sean; Yuan, Jianghe; Ananth, Sudha; Duncan, Michael; Martin, Pamela; Bartoli, Manuela

    2015-01-01

    Hyperglycemia-induced retinal oxidative and nitrative stress can accelerate vascular cell aging, which may lead to vascular dysfunction as seen in diabetes. There is no information on whether this may contribute to the progression of diabetic retinopathy (DR). In this study, we have assessed the occurrence of senescence-associated markers in retinas of streptozotocin-induced diabetic rats at 8 and 12 weeks of hyperglycemia as compared to normoglycemic aging (12 and 14 months) and adult (4.5 months) rat retinas. We have found that in the diabetic retinas there was an up-regulation of senescence-associated markers SA-β-Gal, p16INK4a and miR34a, which correlated with decreased expression of SIRT1, a target of miR34a. Expression of senescence-associated factors primarily found in retinal microvasculature of diabetic rats exceeded levels measured in adult and aging rat retinas. In aging rats, retinal expression of senescence associated-factors was mainly localized at the level of the retinal pigmented epithelium and only minimally in the retinal microvasculature. The expression of oxidative/nitrative stress markers such as 4-hydroxynonenal and nitrotyrosine was more pronounced in the retinal vasculature of diabetic rats as compared to normoglycemic aging and adult rat retinas. Treatments of STZ-rats with the anti-nitrating drug FeTPPS (10mg/Kg/day) significantly reduced the appearance of senescence markers in the retinal microvasculature. Our results demonstrate that hyperglycemia accelerates retinal microvascular cell aging whereas physiological aging affects primarily cells of the retinal pigmented epithelium. In conclusion, hyperglycemia-induced retinal vessel dysfunction and DR progression involve vascular cell senescence due to increased oxidative/nitrative stress. PMID:26466127

  2. Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions

    PubMed Central

    Ishii, Yukihito; Motohashi, Yu; Muramatsu, Makoto; Katsuda, Yoshiaki; Miyajima, Katsuhiro; Sasase, Tomohiko; Yamada, Takahisa; Matsui, Tohru; Kume, Shinichi; Ohta, Takeshi

    2015-01-01

    AIM: To investigate the histological features of the liver in spontaneously diabetic Torii (SDT) fatty rats compared with age-matched Sprague-Dawley (SD) rats. METHODS: Female SDT Leprfa (SDT fatty) rats and age-matched SD rats were fed ad libitum. Body weight and biochemical parameters, such as serum glucose, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as well as fatty acid and TG accumulation in the liver were evaluated at 8 wk of age in the non-fasting state and at 8-wk intervals from 8 to 40 wk of age. Histopathological examinations of the liver were performed using hematoxylin and eosin and Sirius Red staining as well as double staining for ED-1 and toluidine blue. The expression of genes involved in TG synthesis, inflammation, and fibrosis was examined in the liver. RESULTS: SDT fatty rats showed significantly increased body weight compared with SD rats. Serum glucose, TG, and TC levels were significantly higher in SDT fatty rats compared with SD rats. The serum AST and ALT levels in SDT fatty rats were significantly elevated at 8 wk of age compared with the levels in SD rats. Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age. Histopathologically, severe hepatosteatosis accompanied by inflammation was observed at 8 wk of age, and fibrosis started to occur at 32 wk of age. Furthermore, Sirius Red and ED-1 staining were increased in the liver at 32 wk of age. Hepatic gene expression related to TG synthesis, inflammation and fibrosis tended to increase in SDT fatty rats compared with SD rats, and the gene expression related to TG secretion was decreased in SDT fatty rats compared with SD rats. CONCLUSION: Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity. PMID:26290633

  3. Cardioprotection by 6-gingerol in diabetic rats.

    PubMed

    El-Bassossy, Hany M; Elberry, Ahmed A; Ghareib, Salah A; Azhar, Ahmad; Banjar, Zainy Mohammed; Watson, Malcolm L

    2016-09-01

    The current study was conducted to evaluate the effect of 6-gingerol (6G) on cardiac complications in streptozotocin (STZ)-induced diabetic (DM) rats. STZ-induced DM rats (single 50 mg/kg i.p. injection, 15 days prior to drug treatment) or time-matched controls were treated with 6G (75 mg/day route orally). After a further 8 weeks, blood was collected for biochemical analysis and 8-isoprostenol was measured in urine. Cardiac hemodynamics and ECG was assessed. 6G significantly attenuated the increased level of blood glucose in diabetic rats and improved cardiac hemodynamics in including RR interval, max dP/dt, min dP/dt and Tau. In addition, 6G alleviated the elevated ST segment, T amplitude and R amplitude with no significant effect on disturbed levels of adiponectin, TGF-β or 8-isoprostenol induced by diabetes. The results showed that treatment with 6G has an ameliorative effect on cardiac dysfunction induced by diabetes. Which may be not related to its potential antioxidant effect. PMID:27378426

  4. 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.

  5. 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. PMID:25924888

  6. Anti-diabetic Effect of Friedelan Triterpenoids in Streptozotocin Induced Diabetic Rat.

    PubMed

    Mandal, Amitava; Das, Vaskar; Ghosh, Pranab; Ghosh, Shilpi

    2015-10-01

    We herein report the anti-diabetic effect of the natural friedelan tritepenoid, 4-oxa-3, 4-secofriedelan (cerin), isolated from cork tissue of Quercus suber L. and its oxygenated derivative, 4-oxa-3, 4-secofriedelan-3-oic acid (cerin(ox)) in streptozotocin (STZ)-induced diabetic rat. Male Sprague Dawley rats were randomized into four groups: non-diabetic control (Group I), STZ-induced diabetic rats (Group II), STZ-induced diabetic rats treated with cerin (Group III), and STZ-induced diabetic rats treated with cerin(ox), (Group IV). Administration of cerin (3 mg/kg) and cerin(ox), (3 mg/kg) orally to STZ-diabetic rats for three weeks improved the body weight, reduced serum glucose level and activities of alkaline phosphatase, acid phosphatase, glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase, and restored liver antioxidant status. PMID:26669102

  7. Changes in the Fracture Resistance of Bone with the Progression of Type 2 Diabetes in the ZDSD Rat.

    PubMed

    Creecy, Amy; Uppuganti, Sasidhar; Merkel, Alyssa R; O'Neal, Dianne; Makowski, Alexander J; Granke, Mathilde; Voziyan, Paul; Nyman, Jeffry S

    2016-09-01

    Individuals with type 2 diabetes (T2D) have a higher fracture risk compared to non-diabetics, even though their areal bone mineral density is normal to high. Identifying the mechanisms whereby diabetes lowers fracture resistance requires well-characterized rodent models of diabetic bone disease. Toward that end, we hypothesized that bone toughness, more so than bone strength, decreases with the duration of diabetes in ZDSD rats. Bones were harvested from male CD(SD) control rats and male ZDSD rats at 16 weeks (before the onset of hyperglycemia), at 22 weeks (5-6 weeks of hyperglycemia), and at 29 weeks (12-13 weeks of hyperglycemia). There were at least 12 rats per strain per age group. At 16 weeks, there was no difference in either body weight or glucose levels between the two rat groups. Within 2 weeks of switching all rats to a diet with 48 % of kcal from fat, only the ZDSD rats developed hyperglycemia (>250 mg/dL). They also began to lose body weight at 21 weeks. CD(SD) rats remained normoglycemic (<110 mg/dL) on the high-fat diet and became obese (>600 g). From micro-computed tomography (μCT) analysis of a lumbar vertebra and distal femur, trabecular bone volume did not vary with age among the non-diabetic rats but was lower at 29 weeks than at 16 weeks or at 22 weeks for the diabetic rats. Consistent with that finding, μCT-derived intra-cortical porosity (femur diaphysis) was higher for ZDSD following ~12 weeks of hyperglycemia than for age-matched CD(SD) rats. Despite an age-related increase in mineralization in both rat strains (μCT and Raman spectroscopy), material strength of cortical bone (from three-point bending tests) increased with age only in the non-diabetic CD(SD) rats. Moreover, two other material properties, toughness (radius) and fracture toughness (femur), significantly decreased with the duration of T2D in ZDSD rats. This was accompanied by the increase in the levels of the pentosidine (femur). However, pentosidine was not

  8. 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

  9. Association Between Maternal Diabetes in Utero and Age at Offspring's Diagnosis of Type 2 Diabetes

    PubMed Central

    Pettitt, David J.; Lawrence, Jean M.; Beyer, Jennifer; Hillier, Teresa A.; Liese, Angela D.; Mayer-Davis, Beth; Loots, Beth; Imperatore, Giuseppina; Liu, Lenna; Dolan, Lawrence M.; Linder, Barbara; Dabelea, Dana

    2008-01-01

    OBJECTIVE—The purpose of this study was to examine age of diabetes diagnosis in youth who have a parent with diabetes by diabetes type and whether the parent's diabetes was diagnosed before or after the youth's birth. RESEARCH DESIGN AND METHODS—The cohort comprised SEARCH for Diabetes in Youth Study participants (diabetes diagnosis 2001–2005) with a diabetic parent. SEARCH is a multicenter survey of youth with diabetes diagnosed before age 20 years. RESULTS—Youth with type 2 diabetes were more likely to have a parent with either type 1 or type 2 diabetes (mother 39.3%; father 21.2%) than youth with type 1 diabetes (5.3 and 6.7%, respectively, P < 0.001 for each). Type 2 diabetes was diagnosed 1.68 years earlier among those exposed to diabetes in utero (n = 174) than among those whose mothers’ diabetes was diagnosed later (P = 0.018, controlled for maternal diagnosis age, paternal diabetes, sex, and race/ethnicity). Age at diagnosis of type 1 diabetes for 269 youth with and without in utero exposure did not differ significantly (difference 0.96 year, P = 0.403 after adjustment). Controlled for the father's age of diagnosis, father's diabetes before the child's birth was not associated with age at diagnosis (P = 0.078 for type 1 diabetes; P = 0.140 for type 2 diabetes). CONCLUSIONS—Type 2 diabetes was diagnosed at younger ages among those exposed to hyperglycemia in utero. Among youth with type 1 diabetes, the effect of the intrauterine exposure was not significant when controlled for mother's age of diagnosis. This study helps explain why other studies have found higher age-specific rates of type 2 diabetes among offspring of women with diabetes. PMID:18694977

  10. 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

  11. Recombinant advanced glycation end product receptor pharmacokinetics in normal and diabetic rats.

    PubMed

    Renard, C; Chappey, O; Wautier, M P; Nagashima, M; Lundh, E; Morser, J; Zhao, L; Schmidt, A M; Scherrmann, J M; Wautier, J L

    1997-07-01

    Vascular dysfunction in patients with diabetes mellitus is related to advanced glycation end product (AGE) formation. We previously showed that AGEs produce an increase in vascular permeability and generated an oxidant stress after binding to the receptor (RAGE) present on endothelium. RAGE, a 35-kDa protein that belongs to the immunoglobulin superfamily, has been cloned from a rat lung cDNA library, and recombinant rat soluble RAGE (rR-RAGE) has been produced in insect cells. The sequence of RAGE is highly conserved between human and rat. We studied the biological effect of rR-RAGE and pharmacokinetics of 125I-rR-RAGE after intravenous or intraperitoneal administration in normal and streptozotocin-induced diabetic rats. rR-RAGE prevented albumin or inulin transfer through a bovine aortic endothelial cell monolayer, restored the hyperpermeability observed in diabetic rats or induced in normal rats by diabetic rat red blood cells, and corrected the reactive oxygen intermediate production after intravenous or intraperitoneal administration. After intravenous injection of 125I-rR-RAGE, the distribution half-life was longer (p < or = 0.01) in diabetic (0.15 and 4.01 hr) than in normal (0.02 and 0.21 hr) rats, as was the case for the elimination half-lives (diabetic, 57.17 hr; normal, 26.02 hr; p < or = 0.01). Distribution volume was higher in diabetic than in normal rats (6.94 and 3.24 liter/kg, respectively; p = 0.049). Our study showed that rR-RAGE was biologically active in vivo and slowly cleared, which suggests it could be considered as a potential therapy. PMID:9224812

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

    PubMed Central

    Chen, Huayong; Li, Li; Xia, Hui

    2015-01-01

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

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

    PubMed

    Chen, Huayong; Li, Li; Xia, Hui

    2015-01-01

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

  14. Rhizome of Anemarrhena asphodeloides counteracts diabetic ophthalmopathy progression in streptozotocin-induced diabetic rats.

    PubMed

    Li, Xuan; Cui, Xiaobing; Wang, Jinjin; Yang, Jie; Sun, Xiaoyu; Li, Xiaodong; Zhu, Quan; Li, Wei

    2013-08-01

    Diabetic ophthalmopathy (DO) impairs patients' eyesight and even causes blindness. Here, we investigated the effect of 60% ethanol extract of the rhizome of Anemarrhenae asphodeloides (ERA), which is commonly used in Chinese medicine formulae in treating diabetes, on DO progression. Blood glucose, insulin, advanced glycation end products (AGE), super oxygen dehydrogenises (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels in serum and sorbitol concentration in the lens were measured. Retinal endothelium/pericyte (E/P) ratio was evaluated, and structural changes of the retina and lens were observed. Effects of mangiferin and neomangiferin, the two major components of ERA, on subnormal growth of pericytes induced by high glucose were also detected. It was found that the activities of SOD and GSH-Px in serum were increased, whereas MDA and AGE levels in serum and sorbitol concentration in the lens were decreased in ERA-treated DO rats. E/P ratio was decreased, and the pathological changes of the lens and retina were alleviated by ERA treatment. Moreover, the subnormal growth of pericytes induced by high glucose was ameliorated by mangiferin and neomangiferin. These results indicated that ERA could effectively prevent DO progression in streptozotocin-induced diabetic rats, and mangiferin and neomangiferin may be the main effective components. PMID:23148017

  15. A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.

    PubMed

    Wen, Jiaming; Wang, Bohan; Du, Chuanjun; Xu, Gang; Zhang, Zhewei; Li, Yi; Zhang, Nan

    2015-01-01

    Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED. PMID:26447087

  16. Incretin attenuates diabetes-induced damage in rat cardiac tissue.

    PubMed

    AbdElmonem Elbassuoni, Eman

    2014-09-01

    Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1 week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect. PMID:25011640

  17. Urinary excretion of guanidinoacetic acid in rats with diabetic nephropathy.

    PubMed

    Kiyatake, I; Nakamura, T; Koide, H

    2006-01-01

    Urinary guanidinoacetic acid (GAA) is a sensitive marker for gentamicin nephrotoxicity in rats. This study assesses the usefulness of GAA concentrations in the diagnosis of renal tubular injury in diabetic nephropathy. Serum, urine, and renal cortex samples were obtained from rats 1, 2, and 3 weeks after streptozotocin injection (65 mg/kg body weight). Guanidinoacetic acid levels were measured by high-performance liquid chromatography. N-acetyl-beta-D-glucosaminidase (NAG) activity in urine was determined by an enzymatic method. GAA levels in serum, urine, and renal cortex were significantly decreased in diabetic rats compared with those in control rats. In contrast, urinary NAG activity was significantly increased in diabetic rats. Decreases in serum, urine, and renal cortical GAA levels were attenuated by insulin treatment. These results indicate that a high serum glucose level may affect GAA synthesis in the renal cortex and that urinary GAA may be a clinically useful indicator of renal tubular injury in diabetic nephropathy. PMID:16538977

  18. Beta-adrenoceptor-mediated vasodilation of retinal blood vessels is reduced in streptozotocin-induced diabetic rats.

    PubMed

    Nakazawa, Taisuke; Sato, Ayumi; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-01-01

    We investigated the effects of epinephrine and dopamine on retinal blood vessels in streptozotocin (STZ, 80 mg/kg, i.p.)-treated rats and age-matched control rats to determine whether diabetes mellitus alters the retinal vascular responses to circulating catecholamines. Experiments were performed 6-8 weeks after treatment with STZ or the vehicle. The fundus images were captured with the digital fundus camera system for small animals we developed and diameters of retinal blood vessels contained in the digital images were measured. Epinephrine increased the diameters of retinal blood vessels, but the vasodilator responses were reduced in diabetic rats. Dopamine produced a biphasic retinal vascular response with an initial vasoconstriction followed by a vasodilation. The vasoconstrictor effects of dopamine on retinal arterioles were enhanced in diabetic rats, whereas the difference between the two groups was abolished by treatment with propranolol. The vasodilator effect of isoproterenol, but not of the activator of adenylyl cyclase colforsin, on retinal blood vessels was reduced in diabetic rats. No difference in vasoconstriction of retinal blood vessels to phenylephrine between non-diabetic and diabetic rats was observed. The vasodilator responses of retinal blood vessels to 1,1-dimethyl-4-phenylpiperazinium, a ganglionic nicotinic receptor agonist, were also attenuated in diabetic rats. These results suggest that diabetes mellitus alters the retinal vascular responses to circulating catecholamines and the impairment of vasodilator responses mediated by beta-adrenoceptors contributes to the alteration. PMID:18585480

  19. Erythrocyte Flow in Choriocapillaris of Normal and Diabetic Rats

    PubMed Central

    Braun, Rod D.; Wienczewski, Christopher A.; Abbas, Asad

    2009-01-01

    The choriocapillaris is a unique capillary bed that provides nutrients to the retinal photoreceptors. It changes anatomically in diabetes, but the impact of these changes on blood flow is unknown. In this study hemodynamic parameters in individual choriocapillaris vessels were compared in normal and diabetic rats. Three groups were studied: normal buffer-injected control rats, streptozotocin (STZ)-injected mildly hyperglycemic (STZ-MH) rats, and STZ-injected diabetic (STZ-D) rats. 7-8 weeks after STZ injection, the rats were anesthetized, and epifluorescent, intravital microscopy was used to record the flow of fluorescent red blood cells (RBC) in the choriocapillaris. Diameter, RBC flux, and RBC velocity were measured in 153 capillary pathways in five control rats, 98 pathways in four STZ-MH rats, and 153 pathways in seven STZ-D rats. There was no difference in capillary diameter among the groups. RBC flux and velocity were lower in the STZ-injected rats compared to the controls (p≤0.023), which is similar to changes found in other capillary beds. RBC velocity and flux were significantly correlated in all three groups, but the correlations in the STZ-injected rats were much stronger than in the controls. This indicates a more heterogeneous distribution of RBCs at upstream arteriolar branchpoints in hyperglycemic rats, which could lead to a decrease in choriocapillaris hematocrit. These changes in the hyperglycemic choriocapillaris could contribute to impaired oxygen delivery to the photoreceptors in diabetic retina. PMID:19269298

  20. Methylglyoxal-derived hydroimidazolone residue of plasma protein can behave as a predictor of prediabetes in Spontaneously Diabetic Torii rats

    PubMed Central

    Chen, Si Jing; Aikawa, Chiwa; Yoshida, Risa; Matsui, Toshiro

    2015-01-01

    Prediabetes, typically defined as impaired glucose tolerance and/or impaired fasting blood glucose, is a high-risk state of developing diabetes. The association of diabetes-related metabolites with prediabetes has not been investigated intensively. This study aimed to get insights into the metabolic behaviors of some typical diabetes-related metabolites in plasma of male Spontaneously Diabetic Torii (SDT) rats during pathogenic progress of diabetes and to assess in vivo if the variation in these metabolites related to the progression of prediabetic stage. To address this question, SDT rats and Sprague Dawley (SD) rats as control were maintained from the age of 7 to 25 weeks. Five typical advanced glycation end products (AGEs) residue of plasma protein and their free adducts were determined by liquid chromatography with tandem mass detection over the duration of the investigation. The SDT rats exhibited impaired glucose tolerance since the age of 12 weeks and developed diabetes with significantly elevated fasting glucose levels after 22 weeks. At the prediabetic stage (12–21 weeks), no significant differences were observed on AGE-free adducts levels of SDT rats compared with SD rats. However, methylglyoxal-derived hydroimidazolone (MG-H1) residue contents of plasma protein were significantly elevated in SDT rats at the age of 16 weeks, whereas other AGE residues of plasma protein did not show marked difference. The present study has revealed significant increase in MG-H1 residue content of plasma protein at the prediabetic stage of a spontaneously diabetic rat model, irrespective of unaltered fasting blood glucose and constant plasma levels of other AGEs. PMID:26265747

  1. Multimodal Highlighting of Structural Abnormalities in Diabetic Rat and Human Corneas

    PubMed Central

    Kowalczuk, Laura; Latour, Gaël; Bourges, Jean-Louis; Savoldelli, Michèle; Jeanny, Jean-Claude; Plamann, Karsten; Schanne-Klein, Marie-Claire; Behar-Cohen, Francine

    2013-01-01

    Purpose This study aimed to highlight structural corneal changes in a model of type 2 diabetes, using in vivo corneal confocal microscopy (CCM). The abnormalities were also characterized by transmission electron microscopy (TEM) and second harmonic generation (SHG) microscopy in rat and human corneas. Methods Goto-Kakizaki (GK) rats were observed at age 12 weeks (n = 3) and 1 year (n = 6), and compared to age-matched controls. After in vivo CCM examination, TEM and SHG microscopy were used to characterize the ultrastructure and the three-dimensional organization of the abnormalities. Human corneas from diabetic (n = 3) and nondiabetic (n = 3) patients were also included in the study. Results In the basal epithelium of GK rats, CCM revealed focal hyper-reflective areas, and histology showed proliferative cells with irregular basement membrane. In the anterior stroma, extracellular matrix modifications were detected by CCM and confirmed in histology. In the Descemet's membrane periphery of all the diabetic corneas, hyper-reflective deposits were highlighted using CCM and characterized as long-spacing collagen fibrils by TEM. SHG microscopy revealed these deposits with high contrast, allowing specific detection in diabetic human and rat corneas without preparation and characterization of their three-dimensional organization. Conclusion Pathologic findings were observed early in the development of diabetes in GK rats. Similar abnormalities have been found in corneas from diabetic patients. Translational Relevance This multidisciplinary study highlights diabetes-induced corneal abnormalities in an animal model, but also in diabetic donors. This could constitute a potential early marker for diagnosis of hyperglycemia-induced tissue changes. PMID:24049714

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

    PubMed

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

    2016-08-01

    We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. PMID:27262608

  3. Proteomic analysis of glycated proteins from streptozotocin-induced diabetic rat kidney.

    PubMed

    Chougale, Ashok D; Bhat, Shweta P; Bhujbal, Swapnil V; Zambare, Mandar R; Puntambekar, Shraddha; Somani, Rahul S; Boppana, Ramanamurthy; Giri, Ashok P; Kulkarni, Mahesh J

    2012-01-01

    Glycation of proteins leading to formation of advanced glycation end products (AGEs) has been considered as one of the important causes of diabetic nephropathy. Therefore, in this study, glycated proteins were detected by anti-AGE antibodies from kidney of streptozotocin-induced diabetic rat showing nephropathic symptoms, by using two dimensional electrophoresis and western blot analysis. These glycated proteins were identified and characterized by using combination of peptide mass finger printing and tandem mass spectrometric approaches. Glycated proteins identified included proteins from metabolic pathways, oxidative stress, cell signaling, and transport. Several of the proteins modified by glycation were involved in glucose metabolism. The extent of glycation was higher in diabetes compared to control, in the glycated proteins that were common to both control and diabetic kidney. Two dimensional electrophoresis proteins profiling of glycated proteins suggest that four of the glycated proteins were significantly up regulated in diabetes. PMID:21516357

  4. Effects of age and diabetes on scleral stiffness.

    PubMed

    Coudrillier, Baptiste; Pijanka, Jacek; Jefferys, Joan; Sorensen, Thomas; Quigley, Harry A; Boote, Craig; Nguyen, Thao D

    2015-07-01

    The effects of diabetes on the collagen structure and material properties of the sclera are unknown but may be important to elucidate whether diabetes is a risk factor for major ocular diseases such as glaucoma. This study provides a quantitative assessment of the changes in scleral stiffness and collagen fiber alignment associated with diabetes. Posterior scleral shells from five diabetic donors and seven non-diabetic donors were pressurized to 30 mm Hg. Three-dimensional surface displacements were calculated during inflation testing using digital image correlation (DIC). After testing, each specimen was subjected to wide-angle X-ray scattering (WAXS) measurements of its collagen organization. Specimen-specific finite element models of the posterior scleras were generated from the experimentally measured geometry. An inverse finite element analysis was developed to determine the material properties of the specimens, i.e., matrix and fiber stiffness, by matching DIC-measured and finite element predicted displacement fields. Effects of age and diabetes on the degree of fiber alignment, matrix and collagen fiber stiffness, and mechanical anisotropy were estimated using mixed effects models accounting for spatial autocorrelation. Older age was associated with a lower degree of fiber alignment and larger matrix stiffness for both diabetic and non-diabetic scleras. However, the age-related increase in matrix stiffness was 87% larger in diabetic specimens compared to non-diabetic controls and diabetic scleras had a significantly larger matrix stiffness (p = 0.01). Older age was associated with a nearly significant increase in collagen fiber stiffness for diabetic specimens only (p = 0.06), as well as a decrease in mechanical anisotropy for non-diabetic scleras only (p = 0.04). The interaction between age and diabetes was not significant for all outcomes. This study suggests that the age-related increase in scleral stiffness is accelerated in eyes with

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

    PubMed Central

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

    2016-01-01

    The aim of the present pilot study was the identification of micro-RNA changes over time during the development and progression of type 2 diabetes (T2D) in Zucker diabetic fatty rats (ZDF rats). T2D is a complex metabolic disorder that is characterized, inter alia, by progressive failure of pancreatic β cells to produce insulin, but also by functional or morphological modifications of others organ, such as liver, adipose tissue and the cardiovascular system. Micro-RNAs are a novel class of biomarkers that have the potential to represent biomarkers of disease progression. In this study, the onset and progression of diabetes was followed in ZDF rats from six weeks until 17 weeks of age. After an initial phase of hyperinsulinemia, the animals developed T2D and lost the capacity to produce sufficient insulin. Circulating miRNAs were measured from plasma samples at four time points: pre-diabetes (six weeks of age), hyperinsulinemia (eight weeks), β cell failure (11 weeks) and late-stage diabetes (17 weeks) using TaqMan miRNA arrays. Bioinformatic analysis revealed distinct changes of circulating miRNAs over time. Several miRNAs were found to be increased over the course of the disease progression, such as miR-122, miR-133, miR-210 and miR-375. The most significantly decreased miRNAs were miR-140, miR-151-3p, miR-185, miR-203, miR-434-3p and miR-450a. Some of the miRNAs have also been identified in type 2 diabetic patients recently and, therefore, may have the potential to be useful biomarkers for the disease progression of T2D and/or the treatment response for anti-diabetic medications. PMID:27153060

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

    PubMed

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

    2016-01-01

    The aim of the present pilot study was the identification of micro-RNA changes over time during the development and progression of type 2 diabetes (T2D) in Zucker diabetic fatty rats (ZDF rats). T2D is a complex metabolic disorder that is characterized, inter alia, by progressive failure of pancreatic β cells to produce insulin, but also by functional or morphological modifications of others organ, such as liver, adipose tissue and the cardiovascular system. Micro-RNAs are a novel class of biomarkers that have the potential to represent biomarkers of disease progression. In this study, the onset and progression of diabetes was followed in ZDF rats from six weeks until 17 weeks of age. After an initial phase of hyperinsulinemia, the animals developed T2D and lost the capacity to produce sufficient insulin. Circulating miRNAs were measured from plasma samples at four time points: pre-diabetes (six weeks of age), hyperinsulinemia (eight weeks), β cell failure (11 weeks) and late-stage diabetes (17 weeks) using TaqMan miRNA arrays. Bioinformatic analysis revealed distinct changes of circulating miRNAs over time. Several miRNAs were found to be increased over the course of the disease progression, such as miR-122, miR-133, miR-210 and miR-375. The most significantly decreased miRNAs were miR-140, miR-151-3p, miR-185, miR-203, miR-434-3p and miR-450a. Some of the miRNAs have also been identified in type 2 diabetic patients recently and, therefore, may have the potential to be useful biomarkers for the disease progression of T2D and/or the treatment response for anti-diabetic medications. PMID:27153060

  7. The spontaneously diabetic torii rat: an animal model of nonobese type 2 diabetes with severe diabetic complications.

    PubMed

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

    2013-01-01

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

  8. A study of myocardial muscarinic receptors in streptozotocin-induced diabetic rats using iodine-123 N-methyl-4-iododexetimide.

    PubMed

    Mardon, K; Kassiou, M; Katsifis, A; Najdovski, L

    1999-07-01

    In previous studies we have shown that iodine-123 N-methyl-4-iododexetimide ([123I]MIDEX) is a suitable single-photon emission tomography radiotracer for the characterisation of myocardial muscarinic acetylcholine receptors (m-AChR) in the normal state. It has been demonstrated that m-AChR are altered as a consequence of diabetes. The aim of the present study was to examine myocardial m-AChR density using [123I]MIDEX in streptozotocin (STZ)-induced diabetic rats. In vitro binding experiments were conducted on left and right ventricle and atrium homogenate membranes of 1-week, 5-week and 10-week STZ-induced diabetic and aged-matched normal rats. The m-AChR densities (Bmax values), as determined by saturation experiments with [123I]MIDEX, revealed no difference in left and right ventricles or atrium in 1-week and 5-week STZ-diabetic rats when compared with normal rats. However, the 10-week STZ-diabetic group revealed a 39% (P<0.001) decrease in m-AChR density in atrium with no change in left and right ventricles. The equilibrium dissociation constant (Kd values) was similar in all groups. In vitro binding autoradiography revealed a 40% decrease in m-AChR density in atrium in the same 10-week diabetic rats. No statistically significant difference was found in 1-week and 5-week diabetic rats compared with normals. Ex vivo autoradiography showed a 50% decrease in [123I]MIDEX uptake in atrium in 5-week diabetic rats and a 60% decrease in 10-week diabetic rats. These results demonstrate the ability of the single-photon agent [123I]MIDEX to measure in vitro and ex vivo alterations in myocardial m-AChR density observed in STZ-induced diabetic rats. PMID:10398822

  9. Strain-Independent Increases of Crystallin Proteins in the Retina of Type 1 Diabetic Rats

    PubMed Central

    Heise, Erich A.; Marozas, Lauren M.; Grafton, Sean A.; Green, Katelyn M.; Kirwin, Stefanie J.; Fort, Patrice E.

    2013-01-01

    Diabetic retinopathy is the leading cause of vision loss in working-age individuals in the United States and is expected to continue growing with the increased prevalence of diabetes. Streptozotocin-induced hyperglycemia in rats is the most commonly used model for diabetic retinopathy. Previous studies have shown that this model can lead to different inflammatory changes in the retina depending on the strain of rat. Our previous work has shown that crystallin proteins, including members of the alpha- and beta/gamma-crystallin subfamilies, are upregulated in the STZ rat retina. Crystallin proteins have been implicated in a number of cellular processes, such as neuroprotection, non-native protein folding and vascular remodeling. In this current study, we have demonstrated that unlike other strain-dependent changes, such as inflammatory cytokines and growth factor levels, in the STZ rat, the protein upregulation of crystallins is consistent across the Brown Norway, Long-Evans and Sprague-Dawley rat strains in the context of diabetes. Taken together, these data illustrate the potential critical role played by crystallins, and especially alpha-crystallins, in the retina in the context of diabetes. PMID:24349305

  10. Histopathological, Ultrastructural and Apoptotic Changes in Diabetic Rat Placenta

    PubMed Central

    Gül, Mehmet; Bayat, Nuray; Çetin, Aslı; Kepekçi, Remziye Aysun; Şimşek, Yavuz; Kayhan, Başak; Turhan, Uğur; Otlu, Ali

    2015-01-01

    Background: The exchange of substances between mother and fetus via the placenta plays a vital role during development. A number of developmental disorders in the fetus and placenta are observed during diabetic pregnancies. Diabetes, together with placental apoptosis, can lead to developmental and functional disorders. Aims: Histological, ultrastructural and apoptotic changes were investigated in the placenta of streptozotocin (STZ) induced diabetic rats. Study Design: Animal experimentation. Methods: In this study, a total of 12 female Wistar Albino rats (control (n=6) and diabetic (n=6)) were used. Rats in the diabetic group, following the administration of a single dose of STZ, showed blood glucose levels higher than 200 mg/dL after 72 hours. When pregnancy was detected after the rats were bred, two pieces of placenta and the fetuses were collected on the 20th day of pregnancy by cesarean incision under ketamine/ xylazine anesthesia from in four rats from the control and diabetic groups. Placenta tissues were processed for light microscopy and transmission electron microscopy (TEM). Hematoxylin-eosin (HE) and periodic acid Schiff-diastase (PAS-D) staining for light microscopic and caspase-3 staining for immunohistochemical investigations were performed for each placenta. Electron microscopy was performed on thin sections contrasted with uranyl acetate and lead nitrate. Results: Weight gain in the placenta and fetuses of diabetic rats and thinning of the decidual layer, thickening of the hemal membrane, apoptotic bodies, congestion in intervillous spaces, increased PAS-D staining in decidual cells and caspase-3 immunoreactivity were observed in the diabetic group. After the ultrastructural examination, the apoptotic appearance of the nuclei of trophoblastic cells, edema and intracytoplasmic vacuolization, glycogen accumulation, dilation of the endoplasmic reticulum and myelin figures were observed. In addition, capillary basement membrane thickening, capillary

  11. AB230. Calpain inhibition improves diabetic erectile dysfunction in rats

    PubMed Central

    Li, Hao; Wang, Tao; Liu, Jihong

    2016-01-01

    Objective Diabetic erectile dysfunction is an intractable disease which results from both vascular and nervous dysfunction in penis. Calpain mediates the vascular dysfunction during hyperglycemia and is involved in some neurodegenerative diseases. This study was designed to investigate the role of calpain inhibition in improving diabetic erectile dysfunction in rats. Methods Type 1 diabetes was induced by intraperitoneal injection of streptozotocin at the dose of 60 mg/kg in rats. After 2 months, diabetic erectile dysfunction was confirmed by apomorphine test. Then the animals were divided into three groups: (I) nondiabetic control groups, (II) diabetic rats + vehicle and (III) diabetic rats + MDL28170. Two weeks later the erectile function was measured by electrical stimulation of the cavernous nerve and the ratio between intracavernosal pressure (ICP) and mean systemic arterial blood pressure (MAP) at the peak of erectile response was calculated. After that penis tissue was harvested. Calpain activity in corpus cavernosum was measured by western blot. Neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) were observed by immunohistochemistry and western blot. The endothelial content in the cavernosum was measured by immunohistochemistry. Results The calpain activity was increased in diabetic rats and inhibited by MDL28170. The erectile function was improved by MDL28170 treatment. The expression of nNOS and eNOS, as well as the content of endothelium in corpus cavernosum were also increased by inhibition of calpain. Conclusions Calpain activation may play a role in the erectile dysfunction of diabetic rats. Inhibition of calpain could improve diabetic erectile dysfunction by increasing expression of nNOS and eNOS in the corpus cavernosum. This could be a novel therapeutic target to protect the erectile function in diabetic patient.

  12. A look inside the diabetic brain: Contributors to diabetes-induced brain aging

    PubMed Central

    Wrighten, Shayna A.; Piroli, Gerardo G.; Grillo, Claudia A.; Reagan, Lawrence P.

    2014-01-01

    Central nervous system (CNS) complications resulting from diabetes is a problem that is gaining more acceptance and attention. Recent evidence suggests morphological, electrophysiological and cognitive changes, often observed in the hippocampus, in diabetic individuals. Many of the CNS changes observed in diabetic patients and animal models of diabetes are reminiscent of the changes seen in normal aging. The central commonalities between diabetes-induced and age-related CNS changes have led to the theory of advanced brain aging in diabetic patients. This review summarizes the findings of the literature as they relate to the relationship between diabetes and dementia and discusses some of the potential contributors to diabetes-induced CNS impairments. PMID:19022375

  13. 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

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

    PubMed Central

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

    2015-01-01

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

  15. DEVELOPMENT OF PERIRADICULAR LESIONS IN NORMAL AND DIABETIC RATS

    PubMed Central

    Armada-Dias, Luci; Breda, Jorge; Provenzano, José Claudio; Breitenbach, Marisa; Rôças, Isabela das Neves; Gahyva, Sérgio Márcio Motta; Siqueira, José Freitas

    2006-01-01

    Evidence suggests that diabetic patients are more significantly affected by problems of endodontic origin. This study sought to radiographically and histologically examine the development of periradicular inflammation in control and in diabetic rats after induction of pulpal infection. The pulps of the mandibular first molars of normal and streptozotocin-induced diabetic rats were exposed and left in contact with their oral cavities for 21 and 40 days. Afterwards, the animals were sacrificed, the mandibles were surgically removed, fixed in formalin and then radiographed in a standardized position. The radiographic images of the periradicular lesions were scanned and computerized images were evaluated for the total area of the lesions using a specific software. Representative specimens were also prepared for histopathological analysis. Radiographic analysis revealed that diabetic rats presented significantly larger periradicular lesions when compared with control rats, regardless of the experimental period (p<0.05). Histopathological examination of representative specimens revealed larger periradicular lesions and more severe inflammatory exudate in the group of diabetic rats when compared with the control group. Data from the present study indicated that diabetic rats can be more prone to develop large periradicular lesions, possibly due to reduction in the defense ability against microbial pathogens. PMID:19089060

  16. UNDERNUTRITION IN EARLY LIFE DOES NOT IMPAIR LEARNING IN YOUNG OR AGING RATS.

    EPA Science Inventory

    Prenatal undernutrition is associated with increased incidence of obesity, heart disease, diabetes. Effects of pre- and post-natal undernutrition on nervous system function in middle-aged and aging male SD rats were examined. Intrauterine growth retardation (IUGR) was induced by ...

  17. Early Renal Histological Changes in Alloxan-Induced Diabetic Rats

    PubMed Central

    Pourghasem, Mohsen; Nasiri, Ebrahim; Shafi, Hamid

    2014-01-01

    Diabetes mellitus is a progressive disease. Most investigators have focused on glomerular changes in diabetic kidney and non-glomerular alterations have been less attended. The present study has been conducted to find early non-glomerular histological changes in diabetic renal tissue. Twenty male Wistar rats weighting 200-250 g were used for the diabetic group. Diabetes mellitus was induced by single injection of Alloxan. After 8 weeks, paraffin embedded blocks of kidneys were prepared for evaluating the histological changes due to diabetes. Histological study showed the deposit of eosinophilic materials in the intermediate substantial of medulla and thickening of renal arterial wall in the kidney of 70% of diabetic rats. The average weight of kidneys increased when compared to non diabetic animals. Furthermore, the amount of blood flow in arteries of all diabetic kidneys has been enhanced. The present study demonstrates some early renal histological changes in diabetes mellitus which were earlier compared to those reported previously. Diabetic nephropathy is a progressive disease and renal care design can help better prognosis achievement. PMID:24551816

  18. Glyoxalase-1 overexpression partially prevents diabetes-induced impaired arteriogenesis in a rat hindlimb ligation model.

    PubMed

    Brouwers, Olaf; Yu, Liang; Niessen, Petra; Slenter, Jos; Jaspers, Karolien; Wagenaar, Allard; Post, Mark; Miyata, Toshio; Backes, Walter; Stehouwer, Coen; Huijberts, Maya; Schalkwijk, Casper

    2016-08-01

    We hypothesize that diabetes-induced impaired collateral formation after a hindlimb ligation in rats is in part caused by intracellular glycation and that overexpression of glyoxalase-I (GLO-I), i.e. the major detoxifying enzyme for advanced-glycation-endproduct (AGE) precursors, can prevent this. Wild-type and GLO-I transgenic rats with or without diabetes (induced by 55 mg/kg streptozotocin) were subjected to ligation of the right femoral artery. Laser Doppler perfusion imaging showed a significantly decreased blood perfusion recovery after 6 days in the diabetic animals compared with control animals, without any effect of Glo1 overexpression. In vivo time-of-flight magnetic resonance angiography at 7-Tesla showed a significant decrease in the number and volume of collaterals in the wild-type diabetic animals compared with the control animals. Glo1 overexpression partially prevented this decrease in the diabetic animals. Diabetes-induced impairment of arteriogenic adaptation can be partially rescued by overexpressing of GLO-I, indicating a role of AGEs in diabetes-induced impaired collateral formation. PMID:27296676

  19. Relations between contractile responses and. beta. -adrenoceptors in gastric fundus of diabetic rats

    SciTech Connect

    Sakai, Yasushi; Inazu, Masato; Aihara, Kazuo; Inoue, Kazuaki; Homma, Ikuo )

    1991-01-01

    Contractile responses to norepinephrine (NE), and the population of {beta}-adrenoceptors, were determined in gastric fundus smooth muscle from rats with diabetes induced by streptozotocin(STZ), and age-matched controls. Relaxation and/or contraction of fundus strips of controls and diabetics were induced by 10{sup {minus}5}M NE. Responses to NE were mainly relaxation in gastric fundus isolated from controls, and contraction in fundus isolated from diabetics. Contraction was blocked by 10{sup {minus}8}M prazosin and relaxation was blocked by 10{sup {minus}6}M propranolol. Relaxation by isoproterenol of contraction induced by 10{sup {minus}6}M acetylcholine was significantly less in fundus from diabetics than in that from controls. The number of {beta}-adrenoceptors, measured with ({sup 125}I)iodocyanopindorol as a ligand, was significantly less in gastic fundus membrane isolated from diabetics than in that from controls, but affinity was no different. The level of plasma catecholamine was higher in diabetics than in controls. Results suggest that depression of gastric fundus relaxation and increase of contraction by NE in diabetics could be due to fewer {beta}-adrenoceptor binding sites caused by down-regulation by higher catecholamine level in diabetic rats.

  20. Aminoguanidine cream ameliorates skin tissue microenvironment in diabetic rats

    PubMed Central

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

    2016-01-01

    Introduction The aim of the study was to explore the effect of aminoguanidine cream on the skin tissue microenvironment in diabetic rats. Material and methods A total of 51 healthy male Sprague Dawley (SD) rats were randomly divided into three groups: the diabetes group (n = 18), the aminoguanidine group (n = 18) and the control group (n = 15). Rats in the diabetes group and aminoguanidine group were injected with 65 mg/kg streptozotocin to induce the diabetes model, and in the control group with citrate buffer. After successful induction of diabetes, the back hair of all rats was stripped by barium sulfide, and the aminoguanidine group was treated with aminoguanidine cream using disinfected cotton swabs twice every day for 40 days, while the diabetes and control groups were treated with the cream matrix. The pathological changes of skin were observed by HE staining, while the content of inflammatory cytokines (TNF-α, IL-8, ICAM and IL-1α) and the antioxidant indexes (T-AOC, GSH-PX, MPO MDA H2O2) were examined using commercial kits. Results After 40 days of treatment, the diabetes group manifested tissue lesions, whereas the aminoguanidine group seemed normal. Compared with the diabetes group, the content of inflammatory cytokines TNF-α, IL-8, ICAM and IL-1α was dramatically lower in the aminoguanidine group. T-AOC in all groups underwent dramatic changes and returned to normal finally. The activities of GSH-PX and MPO and content of H2O2 in the diabetes group were all higher than those in the aminoguanidine group. Conclusions Aminoguanidine may have a good systemic effect on alleviating the pathological changes of skin tissue in diabetic rats, which may be attributed to the regulation of GSH-PX, TNF-α, IL-8, ICAM and IL-1α. PMID:26925135

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

    PubMed Central

    Akkoç, Tolga; Eraslan, Muhsin; Şahin, Özlem; Özkara, Selvinaz; Vardar Aker, Fugen; Subaşı, Cansu; Karaöz, Erdal; Akkoç, Tunç

    2016-01-01

    Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function. PMID:27300133

  2. Inhomogeneous derangement of cardiac autonomic nerve control in diabetic rats.

    PubMed

    Sanyal, Shamarendra Nath; Arita, Makoto; Ono, Katsushige

    2002-03-01

    The present study compared autonomic nervous function in Kob [Spontaneously Diabetic, Bio-Breeding (BB)] rats with control Wistar rats to determine the development of cardiac neuropathy in diabetic rats. Telemetric ECG signals were obtained from an ECG radio-transmitter placed in a dorsal subcutaneous pouch of male Kob and Wistar rats for 30min every 6h at a sample rate of 5kHz. Heart rate (HR) and HR variability (HRV) were analyzed in each group by power spectrograms obtained by a fast Fourier transform algorithm. RR interval, total power (TP), low frequency (LF) power (0.04-0.67 Hz), high frequency (HF) power (0.79-1.48 Hz) and LF/HF ratio were also measured. The Kob rats had lower HRV than the control Wistar rats; HR, TP, and HF power, but not the LF/HF ratio, in the Kob rats were significantly lower than those of the control rats (p<0.001). However, in the Kob rats the response of these parameters to a muscarinic antagonist (atropine: 2mg/kg) was left intact, but their response to a beta-adrenergic antagonist (propranolol: 4mg/kg) was impeded. Autonomic nervous control of HR in spontaneously diabetic rats was inhomogeneously deranged in terms of the balance in sympathetic and parasympathetic tone, not only in the baseline condition, but also in the regulatory systems, including postsynaptic receptor function. PMID:11922279

  3. Standardization of resistance exercise training: effects in diabetic ovariectomized rats.

    PubMed

    Sanches, I C; Conti, F F; Sartori, M; Irigoyen, M C; De Angelis, K

    2014-04-01

    This study was carried out with a 3-fold aim: 1) to standardize a maximal load test (MLT) on ladders for prescription of resistance exercise training (RET) in rats, 2) to prescribe moderate-intensity RET based on this MLT and 3) to test the effect of this RET in diabetic ovariectomized rats. Female Wistar rats were divided into control (C), diabetic ovariectomized sedentary (DOS) and trained (DOT) groups. The MLT was standardized with increased load applied to the rat tail for each climb, and blood lactate was measured to identify lactate threshold in C rats. MLT was applied in the 1st, 4th and 8th week of the protocol. After 8 weeks of RET, the arterial pressure was directly recorded. DOS group reduced performance in MLT, body weight, left ventricular, plantar and soleus muscles mass (vs. C). DOT rats showed an improvement in MLT associated with plantar muscle mass increased (vs. C and DOS), with attenuation of hypotension and bradycardia (vs. DOS). In conclusion, the results provide a useful method for determining the maximal load and applying RET in rats. Moreover, this study showed that moderate intensity RET improves hemodynamic status in diabetic ovariectomized rats, thereby reinforcing the role of RET in diabetes management. PMID:24022577

  4. Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat.

    PubMed

    Oger-Roussel, Stephanie; Behr-Roussel, Delphine; Caisey, Stephanie; Kergoat, Micheline; Charon, Christine; Audet, Annick; Bernabé, Jacques; Alexandre, Laurent; Giuliano, Francois

    2014-01-15

    Despite the fact that urogenito-sexual complications significantly impact the quality of life of diabetic patients, a robust in vivo experimental model is lacking. Bladder and erectile function in the Type 2 diabetic Goto-Kakizaki (GK) rat and responses to standard-of-care treatments for each disorder have been assessed. GK rats (n = 25, 18-wk-old, GK/Par colony) and age-matched Wistar rats (n = 23), characterized for their metabolic parameters, were used. Bladder function was assessed by cystometry in conscious rats treated by intravenous solifenacin (1 mg/kg). Subsequently, erectile function was assessed under anesthesia following electrical stimulation of the cavernous nerve in presence of intravenous sildenafil (0.3 mg/kg). GK rats displayed detrusor overactivity with a significant increase in frequency/amplitude of nonvoiding contractions during the filling phase, together with an increase in bladder capacity, intercontraction interval, voided volume, and maximal pressure of voiding contraction. Solifenacin significantly decreased parameters characterizing voiding contractions without modifying voiding efficiency. Erectile function in GK rats was markedly impaired and remained so after sildenafil treatment despite a significant improvement. GK rats display both bladder and erectile dysfunctions and respond at least partially to standard-of-care treatments for each disorder, thus representing a suitable model to investigate the pathophysiology and assess the efficacy of new therapeutic agents for Type 2 diabetes-associated bladder and erectile complications. PMID:24305064

  5. Cognitive Dysfunction Associated with Diabetic Ketoacidosis in Rats

    PubMed Central

    Glaser, Nicole; Anderson, Steve; Leong, Wesley; Tancredi, Daniel; O’Donnell, Martha

    2012-01-01

    Background Type 1 diabetes mellitus in children may be associated with neurocognitive deficits of unclear cause. A recent retrospective study in children suggested possible associations between diabetic ketoacidosis (DKA) and decreased memory. The current investigation was undertaken to determine whether cognitive deficits could be detected after a single episode of DKA in an animal model. Methods Streptozotocin was used to induce diabetes in juvenile rats, and rats were then treated with subcutaneous insulin injections. In one group, insulin was subsequently withdrawn to allow development of DKA, which was then treated with insulin and saline. After recovery from DKA, subcutaneous insulin injections were re-started. In the diabetes control group, rats continued to receive subcutaneous insulin and underwent sham procedures identical to the DKA group. One week after recovery, cognitive function was tested using the Morris Water Maze, a procedure that requires rats to locate a hidden platform in a water pool using visual cues. During a 10 day period, mean time to locate the platform (latency) during 4 trials per day was recorded. Results Comparison of latency curves demonstrated longer mean latency times on days 7 and 8 in the DKA group indicating delayed learning compared to diabetic controls. Conclusions These data demonstrate that a single DKA episode results in measurable deficits in learning in rats, consistent with findings that DKA may contribute to neurocognitive deficits in children with type 1 diabetes. PMID:22266599

  6. 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. PMID:18274898

  7. Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats.

    PubMed

    Bayramoglu, Gokhan; Senturk, Hakan; Bayramoglu, Aysegul; Uyanoglu, Mustafa; Colak, Suat; Ozmen, Ayse; Kolankaya, Durdane

    2014-03-01

    Little is known about the protective effects of carvacrol on the symptoms of streptozotocin induced diabetes in rats. Hence, this present study was designed to evaluate the protective effect of the strong antioxidant, carvacrol, on the symptoms of streptozotocin induced diabetes in rats. Carvacrol at the doses of 25 and 50 mg/kg body weight were orally administered to diabetic rats for a period of 7 days after the onset of diabetes. Food-water intake and body weight changes were daily recorded. Biochemical parameters such as serum glucose, insulin, total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were measured. Although treatment of diabetic rats with oral administration of carvacrol resulted in a slight reduction in serum glucose level and significant reduction in serum total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase in comparison with diabetic control rats, there were no significant differences in serum insulin levels, food-water intake values and body weight changes. Despite the inadequacy of carvacrol on diabetes treatments, it was determined to have at least a partially protective role on liver enzymes. PMID:23579248

  8. 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

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

    PubMed

    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

  10. Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat

    PubMed Central

    Stabley, John N.; Prisby, Rhonda D.; Behnke, Bradley J.; Delp, Michael D.

    2015-01-01

    Bone health and cardiovascular function are compromised in individuals with type 2 diabetes mellitus (T2DM). The purpose of the present study was to determine whether skeletal vascular control mechanisms are altered during the progression of T2DM in the Zucker diabetic fatty (ZDF) rat. Responses of the principal nutrient artery (PNA) of the femur from obese ZDF rats with prediabetes, short-term diabetes, and long-term diabetes to endothelium-dependent (acetylcholine) and –independent (sodium nitroprusside) vasodilation, and KCl, norepinephrine and myogenic vasoconstrictor were determined in vitro. Few changes in the PNA vasomotor responses occurred in the pre-diabetic and short-term diabetic conditions. Endothelium-dependent and –independent vasodilation were reduced, and norepinephrine and myogenic vasoconstriction were enhanced in obese ZDF rats with long-term diabetes relative to lean age-matched controls. Differences in endothelium-dependent vasodilation of the femoral PNA between ZDF rats and controls were abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. The passive pressure-diameter response of the femoral PNA was also lower across a range of intraluminal pressures with long-term T2DM. Regional bone and marrow perfusion and vascular conductance, measured in vivo using radiolabeled microspheres, were lower in obese ZDF rats with long-term diabetes. These findings suggest that the profound impairment of the bone circulation may contribute to the osteopenia found to occur in long bones with chronic T2DM. PMID:25817711

  11. Zerumbone, a Phytochemical of Subtropical Ginger, Protects against Hyperglycemia-Induced Retinal Damage in Experimental Diabetic Rats

    PubMed Central

    Tzeng, Thing-Fong; Liou, Shorong-Shii; Tzeng, Yu-Cheng; Liu, I-Min

    2016-01-01

    Diabetic retinopathy (DR), the most ordinary and specific microvascular complication of diabetes, is a disease of the retina. Zerumbone (ZER) is a monocyclic sesquiterpene compound, and based on reports, it is the predominant bioactive compound from the rhizomes of Zingiber zerumbet. The aim of the current study is to evaluate the protective effect of zerumbone against DR in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were treated with ZER (40 mg/kg) once a day orally for 8 weeks. ZER administration significantly (p < 0.05) lowered the levels of plasma glucose (32.5% ± 5.7% lower) and glycosylated hemoglobin (29.2% ± 3.4% lower) in STZ-diabetic rats. Retinal histopathological observations indicated that disarrangement and reduction in thickness of retinal layers were reversed in ZER-treated diabetic rats. ZER downregulated both the elevated levels of advanced glycosylated end products (AGEs) and the higher levels of the receptors for AGEs (RAGE) in retinas of diabetic rats. What’s more, ZER significantly (p < 0.05) ameliorated diabetes-induced upregulation of tumor necrosis factor-α, interleukin (IL)-1 and IL-6. ZER also attenuated overexpression of vascular endothelial growth factor and intercellular adhesion molecule-1, and suppressed activation of nuclear factor (NF)-κB and apoptosis in the retinas of STZ-diabetic rats. Our results suggest ZER possesses retinal protective effects, which might be associated with the blockade of the AGEs/RAGE/NF-κB pathway and its anti-inflammatory activity. PMID:27463726

  12. Zerumbone, a Phytochemical of Subtropical Ginger, Protects against Hyperglycemia-Induced Retinal Damage in Experimental Diabetic Rats.

    PubMed

    Tzeng, Thing-Fong; Liou, Shorong-Shii; Tzeng, Yu-Cheng; Liu, I-Min

    2016-01-01

    Diabetic retinopathy (DR), the most ordinary and specific microvascular complication of diabetes, is a disease of the retina. Zerumbone (ZER) is a monocyclic sesquiterpene compound, and based on reports, it is the predominant bioactive compound from the rhizomes of Zingiber zerumbet. The aim of the current study is to evaluate the protective effect of zerumbone against DR in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were treated with ZER (40 mg/kg) once a day orally for 8 weeks. ZER administration significantly (p < 0.05) lowered the levels of plasma glucose (32.5% ± 5.7% lower) and glycosylated hemoglobin (29.2% ± 3.4% lower) in STZ-diabetic rats. Retinal histopathological observations indicated that disarrangement and reduction in thickness of retinal layers were reversed in ZER-treated diabetic rats. ZER downregulated both the elevated levels of advanced glycosylated end products (AGEs) and the higher levels of the receptors for AGEs (RAGE) in retinas of diabetic rats. What's more, ZER significantly (p < 0.05) ameliorated diabetes-induced upregulation of tumor necrosis factor-α, interleukin (IL)-1 and IL-6. ZER also attenuated overexpression of vascular endothelial growth factor and intercellular adhesion molecule-1, and suppressed activation of nuclear factor (NF)-κB and apoptosis in the retinas of STZ-diabetic rats. Our results suggest ZER possesses retinal protective effects, which might be associated with the blockade of the AGEs/RAGE/NF-κB pathway and its anti-inflammatory activity. PMID:27463726

  13. Protective Effects of Lycopene on Furan-treated Diabetic and Non-diabetic Rat Lung.

    PubMed

    Baş, Hatice; Pandir, Dilek

    2016-02-01

    We assessed the effects of furan and lycopene on the histopathological and biochemical changes on lungs, body and lung weights, and food consumption of rats. Furan and diabetes caused histopathological changes, increment in malondialdehyde levels, and decrease in antioxidant enzyme activities. Lycopene showed a protective effect against these damages, except for glutathione-S-transferase and glutathione peroxidase activities. Consequently, furan and diabetes resulted in lung toxicity. Our findings demonstrate that furan treatment resulted in more alterations in histology and biochemical parameters in diabetic rats and lycopene showed protective effects against these alterations. PMID:27003172

  14. Hypoglycemic and antioxidant activities of paeonol and its beneficial effect on diabetic encephalopathy in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Jiping; Wang, Shuyuan; Feng, Liang; Ma, Dongying; Fu, Qiang; Song, Yu; Jia, Xiaobin; Ma, Shiping

    2013-07-01

    Diabetic encephalopathy (DE) is one of the severe complications in patients with diabetes mellitus. Paeonol, an active compound isolated from the root bark of Paeonia suffruticosa, has significant antidiabetic activity in vivo. However, its underlying beneficial effects on DE were unclear. In the present study, the protective activity of paeonol on DE was evaluated in streptozotocin (STZ)-induced diabetic rats. Paeonol at 50 and 100 mg/kg significantly increased body weight and decreased blood glucose levels, glycosylated serum proteins, and serum advanced glycation end products (AGEs) levels. Immunohistochemistry assays and Western blot analysis revealed a significant decrease in expressions on receptor for advanced glycation end products (RAGE) and nuclear factor kappa B (NF-κB) in hippocampus and cerebral cortical neurons after paeonol treatment. Furthermore, paeonol significantly increased glutathione content and remarkedly decreased induced nitric oxide synthase activity in hippocampus tissue. Our findings indicated that paeonol could improve the pathological damage of DE in STZ-induced diabetic rats. It might be associated with the modulating AGEs/RAGE/NF-κB pathway. This study suggested that paeonol might be a promising candidate for the prevention and treatment of DE. PMID:23875897

  15. 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.

  16. Distinct genetic regulation of progression of diabetes and renal disease in the Goto-Kakizaki rat.

    PubMed

    Nobrega, Marcelo A; Solberg Woods, Leah C; Fleming, Stewart; Jacob, Howard J

    2009-09-01

    Goto-Kakizaki (GK) rats develop early-onset type 2 diabetes (T2D) symptoms, with signs of diabetic nephropathy becoming apparent with aging. To determine whether T2D and renal disease share similar genetic architecture, we ran a quantitative trait locus (QTL) analysis in the F2 progeny of a GK x Brown Norway (BN) rat cross. Further, to determine whether genetic components change over time, we ran the QTL analysis on phenotypes collected longitudinally, at 3, 6, 9 and 12 mo, from the same animals. We confirmed three chromosomal regions that are linked to early diabetes phenotypes (chromosomes 1, 5, and 10) and a single region involved in the late progression of the disorder (chromosome 4). A single region was identified for the onset of the renal phenotype proteinuria (chromosome 5). This region overlaps the diabetic QTL, although it is not certain whether similar genes are involved in both phenotypes. A second QTL linked to the progression of the renal phenotype was found on chromosome 7. Linkage for triglyceride and cholesterol levels were also identified (chromosomes 7 and 8, respectively). These results demonstrate that, in general, different genetic components control diabetic and renal phenotypes in a diabetic nephropathy model. Furthermore, these results demonstrate that, over time, different genetic components are involved in progression of disease from those that were involved in disease onset. This observation would suggest that clinical studies collecting participants over a wide age distribution may be diluting genetic effects and reducing power to detect true effects. PMID:19584172

  17. Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes

    PubMed Central

    Fields, Aaron J.; Berg-Johansen, Britta; Metz, Lionel N.; Miller, Stephanie; La, Brandan; Liebenberg, Ellen C.; Coughlin, Dezba G.; Graham, James L.; Stanhope, Kimber L.; Havel, Peter J.; Lotz, Jeffrey C.

    2015-01-01

    Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis and biomechanical behavior. Coccygeal motion segments were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end-product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia-inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress and AGE/RAGE-mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. PMID:25641259

  18. Tempol effects on diabetic nephropathy in male rats

    PubMed Central

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

    2016-01-01

    Introduction: Diabetic nephropathy (DN) is the most common cause of the chronic kidney disease in the world. Oxidative stress on the other hand has a major and well known role in its pathophysiology. Objectives: The aim of the study is to figure out if tempol, a synthetic antioxidant agent, modifies DN and to determine its relevance to changes of serum oxidative biomarkers. Materials and Methods: Twenty-seven male rats were equally divided in to 4 groups (7 rats for each group). Group I (control or C), group II (diabetic or D), groups III (Tempol) which were given tempol (100 mg/kg/day) by gavages for 28 days and group IV (D&T) which includes diabetic rats that also received same dose of tempol. After treatment, blood samples were isolated. Enzymatic scavengers including catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, lipid peroxidation (LPO), total antioxidant capacity (TAC) and total thiol molecules (TTM) were measured. Blood urea nitrogen (BUN), creatinine (Cr) an albumin/Cr ratio were evaluated as well. Statistical differences were assessed with one-way analysis of variance (ANOVA) by SPSS followed by Tukey t test. Results: Oxidative stress biomarkers modified and Alb/Cr ratio increased in diabetic group (II), however, they were altered to normal in group IV (D&T) compared with diabetic group (D). Conclusion: Tempol can modify oxidative stress biomarkers and presumably nephropathy in diabetic rats. PMID:27471738

  19. Homocysteine Metabolism in ZDF (Type 2) Diabetic Rats

    PubMed Central

    Wijekoon, Enoka P.; Hall, Beatrice; Ratnam, Shobhitha; Brosnan, Margaret E.; Zeisel, Steven H.; Brosnan, John T.

    2008-01-01

    Mild hyperhomocysteinemia is a risk factor for many diseases, including cardiovascular disease. We determined the effects of insulin resistance and of type 2 diabetes on homocysteine (Hcy) metabolism using Zucker diabetic fatty rats (ZDF/Gmi fa/fa and ZDF/Gmi fa/?). Plasma total Hcy was reduced in ZDF fa/fa rats by 24% in the pre-diabetic insulin-resistant stage, while in the frank diabetic stage there was a 59% reduction. Hepatic activities of several enzymes that play a role in the removal of Hcy: cystathionine β-synthase (CBS), cystathionine γ-lyase, and betaine:Hcy methyltransferase (BHMT) were increased as was methionine adenosyltransferase. CBS and BHMT mRNA levels and the hepatic level of S-adenosylmethionine were also increased in the ZDF fa/fa rats. Studies with primary hepatocytes showed that Hcy export and the transsulfuration flux in cells from ZDF fa/fa rats were particularly sensitive to betaine. Interestingly, liver betaine concentration was found to be significantly lower in the ZDf fa/fa rats at both 5 and 11 weeks. These results emphasize the importance of betaine metabolism in determining plasma Hcy levels in type 2 diabetes. PMID:16249451

  20. Decreased phosphofructokinase activity in skeletal muscle of diabetic rats.

    PubMed

    Bauer, B A; Younathan, E S

    1984-01-01

    The activities of phosphofructokinase, aldolase and pyruvate kinase were diminished in extracts from skeletal muscle of streptozotocin diabetic rats, whereas the activities of glucose phosphate isomerase and phosphoglucomutase were not changed. Treatment of diabetic rats with insulin restored the activity of phosphofructokinase to normal. A kinetic study of the partially purified enzyme from normal and diabetic rats showed identical Michaelis constants for ATP and equal sensitivity to inhibition by excess of this substrate. Extracts of quick frozen muscle from diabetic rats had higher levels of citrate (an inhibitor of phosphofructokinase) and lower levels of D-fructose-1,6-bisphosphate and D-glucose-1,6-bisphosphate (activators of this enzyme). The levels of D-fructose-6-phosphate, D-glucose-6-phosphate, ATP, ADP and AMP were the same for the two groups. Our data suggest that the in vivo decrease of phosphofructokinase activity in skeletal muscle of diabetic rats is due to a decrease in the level of the enzymatically active protein as well as to an unfavorable change in the level of several of its allosteric modulators. PMID:6237837

  1. Red Cabbage (Brassica oleracea) Ameliorates Diabetic Nephropathy in Rats

    PubMed Central

    Kataya, Hazem A. H.

    2008-01-01

    The protective action against oxidative stress of red cabbage (Brassica oleracea) extract was investigated. Diabetes was induced in male Wistar rats using streptozotocin (60 mg/kg body weight). Throughout the experimental period (60 days), diabetic rats exhibited many symptoms including loss of body weight, hyperglycemia, polyuria, polydipsia, renal enlargement and renal dysfunction. Significant increase in malondialdehyde, a lipid peroxidation marker, was observed in diabetic kidney. This was accompanied by a significant increase in reduced glutathione and superoxide dismutase activity and a decrease in catalase activity and in the total antioxidant capacity of the kidneys. Daily oral ingestion (1 g/kg body weight) of B. oleracea extract for 60 days reversed the adverse effect of diabetes in rats. B. oleracea extract lowered blood glucose levels and restored renal function and body weight loss. In addition, B. oleracea extract attenuated the adverse effect of diabetes on malondialdehyde, glutathione and superoxide dismutase activity as well as catalase activity and total antioxidant capacity of diabetic kidneys. In conclusion, the antioxidant and antihyperglycemic properties of B. oleracea extract may offer a potential therapeutic source for the treatment of diabetes. PMID:18830445

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

    PubMed Central

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

    2016-01-01

    Introduction The present study was taken up to compare and evaluate the effect of Momordica charantia supplementation with pioglitazone on PKC-β and PPAR-γ activity in kidneys of diabetic rats. The hypoglycaemic and lipid lowering effect of Momordica charantia were screened in laboratory animal model and its potency was compared with a Thiazolidinedione (TZD) group antidiabetic drug like pioglitazone. Materials and Methods Adult healthy albino rats of Wistar strain aged 3-4months, weighing between 170-250gm of either sex were divided into 4 groups; Group 1 (normal controls), Group 2 (diabetic controls), Group 3 (diabetic rats treated with pioglitazone) and Group 4 (diabetic rats treated with bitter melon juice). Type 1 Diabetes was induced in rats by intraperitoneal injection of streptozotocin at a dose of 55 mg/kg body weight, following which glucose levels were estimated by Accu chek- active glucometer on day 0, 7, 14, 21 and 28 days to assess the efficacy of Bitter Melon Juice (BMJ) and pioglitazone. After 28 days of treatment, the rats were sacrificed and blood collected from abdominal vena cava was used for estimation of triglycerides by Glycerol 3 phosphate oxidase phenol aminophenazone method and cholesterol by Cholestrol oxidase phenol aminophenazone method. PKC-β and PPAR-γ were estimated in the dissected kidneys by using double sandwich ELISA based kits on an automated plate reader. Results BMJ significantly reduced blood glucose levels in group 4 as compared to diabetic controls (p<0.001). Total cholesterol and triglycerides were significantly reduced in both group 3 and 4. In Group 4, there was reduction in PKC-β levels, when compared to Group 3(p=0.004). PPAR-γ levels were increased in both Group 3 and 4, when compared to Group 2. Conclusion The results suggest that BMJ has hypoglycaemic and lipid lowering effect in diabetic animal models. BMJ increases PPAR-γ activity and decreases PKC-β activity in kidneys of diabetic rats, thereby preventing

  3. Variation in characteristics of islets of Langerhans in insulin-resistant, diabetic and non-diabetic-rat strains

    PubMed Central

    Jones, Huw Bowen; Nugent, David; Jenkins, Richard

    2010-01-01

    Assessment of the histopathological and plasma biochemical characteristics of diabetic and non-diabetic rat strains [Han and AP Wistar, lean and obese Zucker Fatty (ZF), and lean and obese Zucker Diabetic Fatty (ZDF) rats] was performed at 6 or 14 weeks of age. Wistar and lean ZF and ZDF rats showed no or minimal islet pathology or plasma biochemical alterations at both timepoints. Obese ZFs were euglycaemic at both timepoints and mildly and severely hyperinsulinaemic at 6 and 14 weeks respectively. Islet morphology was normal at 6 weeks but at 14 weeks, islet hyperplasia was present with a minority showing degenerative changes namely, β-cell vacuolation, vascular congestion and haemorrhage with minimal mononuclear cell and T lymphocytic infiltration. Obese ZDFs were euglycaemic and moderately hyperinsulinaemic at 6 weeks and severely hyperglycaemic with minor hypoinsulinaemia at 14 weeks. Obese ZDFs at 6 weeks showed mainly normal islets with some displaying degeneration (ranging from β-cell vacuolation alone to the features described above). At 14 weeks, islet degeneration was more severe and widespread: β-cell death was present in numerous islets at low level. Islet β-cell numbers were reduced or absent (with associated reduction in insulin immunostaining) within the islets that now consisted predominantly of fibroblasts, collagen and mononuclear cells. Fibroproliferation consisting of smooth muscle actin-α-positive tissue was associated with mononuclear cell infiltration. Some fibrous scars were visible indicative of lost islets. Islet degeneration in obese ZF and ZDF rats was not accompanied by a reduction in β-cell proliferation or in compensatory proliferation of β-cell neogenic clusters. In the light of recent reports of adaptive and inflammation-mediated degenerative changes in human non-insulin dependent diabetes mellitus (NIDDM) islets, the hypertrophy/hyperplasia of β-cells and islet degeneration involving infiltration by monocyte/macrophages in

  4. Variation in characteristics of islets of Langerhans in insulin-resistant, diabetic and non-diabetic-rat strains.

    PubMed

    Jones, Huw Bowen; Nugent, David; Jenkins, Richard

    2010-06-01

    Assessment of the histopathological and plasma biochemical characteristics of diabetic and non-diabetic rat strains [Han and AP Wistar, lean and obese Zucker Fatty (ZF), and lean and obese Zucker Diabetic Fatty (ZDF) rats] was performed at 6 or 14 weeks of age. Wistar and lean ZF and ZDF rats showed no or minimal islet pathology or plasma biochemical alterations at both timepoints. Obese ZFs were euglycaemic at both timepoints and mildly and severely hyperinsulinaemic at 6 and 14 weeks respectively. Islet morphology was normal at 6 weeks but at 14 weeks, islet hyperplasia was present with a minority showing degenerative changes namely, beta-cell vacuolation, vascular congestion and haemorrhage with minimal mononuclear cell and T lymphocytic infiltration. Obese ZDFs were euglycaemic and moderately hyperinsulinaemic at 6 weeks and severely hyperglycaemic with minor hypoinsulinaemia at 14 weeks. Obese ZDFs at 6 weeks showed mainly normal islets with some displaying degeneration (ranging from beta-cell vacuolation alone to the features described above). At 14 weeks, islet degeneration was more severe and widespread: beta-cell death was present in numerous islets at low level. Islet beta-cell numbers were reduced or absent (with associated reduction in insulin immunostaining) within the islets that now consisted predominantly of fibroblasts, collagen and mononuclear cells. Fibroproliferation consisting of smooth muscle actin-alpha-positive tissue was associated with mononuclear cell infiltration. Some fibrous scars were visible indicative of lost islets. Islet degeneration in obese ZF and ZDF rats was not accompanied by a reduction in beta-cell proliferation or in compensatory proliferation of beta-cell neogenic clusters. In the light of recent reports of adaptive and inflammation-mediated degenerative changes in human non-insulin dependent diabetes mellitus (NIDDM) islets, the hypertrophy/hyperplasia of beta-cells and islet degeneration involving infiltration by

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

    PubMed Central

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

    2013-01-01

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

  6. Advanced glycation end products (AGEs) and diabetic vascular complications.

    PubMed

    Yamagishi, Sho-ichi; Nakamura, Kazuo; Imaizumi, Tsutomu

    2005-02-01

    Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the development and progression of diabetic micro- and macroangiopathy. Among various metabolic derangements implicated in the pathogenesis of diabetic vascular complication, advanced glycation end product (AGE) hypothesis is most compatible with the theory of 'hyperglycemic memory'. In this review, we discuss the molecular mechanisms of diabetic vascular complication, specially focusing on AGEs and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in this devastating disorder are also discussed here. PMID:18220586

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

    PubMed

    Miao, Mingsan; Cheng, Bolin; Li, Min

    2015-01-01

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

  8. 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

  9. Bioburden after S. aureus Inoculation in Type-1 Diabetic Rats Undergoing Internal Fixation

    PubMed Central

    Brown, Nga L.; Rose, Michael B.; Blueschke, Gert; Cho, Eugenia H.; Schoenfisch, Mark H.; Erdmann, Detlev; Klitzman, Bruce

    2014-01-01

    Fracture stabilization in the diabetic patient is associated with higher complication rates, particularly infection and impaired wound healing, which can lead to major tissue damage, osteomyelitis, and higher amputation rates. With an increasing prevalence of diabetes and an aging population, the risks of infection of internal fixation devices are expected to grow. Although numerous retrospective clinical studies have identified a relationship between diabetes and infection, currently there are few animal models that have been used to investigate postoperative surgical site infections associated with internal fixator implantation and diabetes. We therefore refined the protocol for inducing hyperglycemia and compared the bacterial burden in controls to pharmacologically induced type-1 diabetic rats after undergoing internal fracture plate fixation and Staphylococcus aureus surgical site inoculation. Using an initial series of streptozotocin doses, followed by optional additional doses to reach a target blood glucose range of 300–600 mg/dl, we reliably induced diabetes in 100% of the rats (n=16) who maintained a narrow hyperglycemic range 14 days after onset of diabetes (466 ± 16 mg/dl, mean ± SEM; coefficient of variation = 0.15). With respect to our primary endpoint, we quantified a significantly higher infectious burden in inoculated diabetic animals (median 3.2 × 1010 CFU/mg dry tissue) when compared to inoculated non-diabetics (7.2 × 104 CFU/mg dry tissue). These data support our hypothesis that uncontrolled diabetes adversely affects the immune system’s ability to clear S. aureus associated with internal hardware. PMID:25158718

  10. 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. PMID:23640014

  11. Effect of carnosine on erythrocyte deformability in diabetic rats.

    PubMed

    Yapislar, Hande; Aydogan, Sami

    2012-12-01

    It is known that oxidative stress plays an important role in the chronic complications of diabetes. Lipid peroxidation is one of the consequences of oxidative stress. Erythrocyte deformability abilities are reduced as a result of lipid peroxidation. Conversely, a decrease nitric oxide (NO) production seems to be responsible in endothelial dysfunction which occurs in diabetic vascular complications. Carnosine is a molecule with anti-oxidant properties. The aim of this study was to investigate erythrocyte deformability indices and the effects of carnosine on erythrocyte deformability in diabetes and to determine a possible relationship between carnosine and nitric oxide. Male Wistar albino rats were used in the study. Injections were administered to seven groups consisting of eight rats each. The groups were: Control, Carnosine, L-NAME (NG-nitro-L-arginine methyl ester), Diabetic, STZ (Streptozotocin) +Carnosine, STZ+L-NAME and STZ+Carnosine+L-NAME. In addition, glucose, insulin, MDA (Malondialdehyde) and NO levels were measured and erythrocyte deformability indices were calculated in all groups. Erythrocyte deformability indices and NO levels were decreased and MDA levels were found to be increased in diabetic group. It was also found that carnosine can significantly reverse erythrocyte deformability, reduce lipid peroxidation and increase NO levels in diabetes. It can be concluded that carnosine can recover from microvascular circulation problems by increasing erythrocyte deformability, can protect cells and tissues against lipid peroxidation and can be used as a multi-functional anti-oxidant in the treatment of diabetes mellitus to prevent the complications of diabetes. PMID:22946660

  12. 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.

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

    PubMed Central

    Chaturvedi, Padmaja; Kwape, Tebogo Elvis

    2015-01-01

    Objectives: This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. Methods: SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). Results: OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. Conclusion: The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes. PMID:26998385

  14. Xiaokening stimulates endothelial nitric oxide release in diabetic rats

    PubMed Central

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

    2015-01-01

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

  15. Inner Retinal Oxygen Delivery and Metabolism in Streptozotocin Diabetic Rats

    PubMed Central

    Wanek, Justin; Teng, Pang-yu; Blair, Norman P.; Shahidi, Mahnaz

    2014-01-01

    Purpose. The purpose of the study is to report global measurements of inner retinal oxygen delivery (DO2_IR) and oxygen metabolism (MO2_IR) in streptozotocin (STZ) diabetic rats. Methods. Phosphorescence lifetime and blood flow imaging were performed in rats 4 (STZ/4wk; n = 10) and 6 (STZ/6wk; n = 10) weeks following injection of STZ to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F). DO2_IR and MO2_IR were calculated from measurements of F and O2A and of F and the arteriovenous oxygen content difference, respectively. Data in STZ rats were compared to those in healthy control rats (n = 10). Results. Measurements of O2A and O2V were not significantly different among STZ/4wk, STZ/6wk, and control rats (P ≥ 0.28). Likewise, F was similar among all groups of rats (P = 0.81). DO2_IR measurements were 941 ± 231, 956 ± 232, and 973 ± 243 nL O2/min in control, STZ/4wk, and STZ/6wk rats, respectively (P = 0.95). MO2_IR measurements were 516 ± 175, 444 ± 103, and 496 ± 84 nL O2/min in control, STZ/4wk, and STZ/6wk rats, respectively (P = 0.37). Conclusions. Global inner retinal oxygen delivery and metabolism were not significantly impaired in STZ rats in early diabetes. PMID:24550355

  16. Inhibiting Amadori-modified albumin formation improves biomarkers of podocyte damage in diabetic rats

    PubMed Central

    Cohen, Margo P; Shearman, Clyde W

    2013-01-01

    Recent studies have shown that urinary excretion of podocyte proteins is an indicator of podocyte injury, and that podocyte abnormalities and elevated concentrations of Amadori-modified glycated albumin (AGA) are linked to the development of diabetic nephropathy and to each other. We evaluated relationships between urinary markers of podocyte damage, increased AGA and filtration function in rats made diabetic by streptozotocin injection and treated for 8 weeks with a compound that inhibits the formation of AGA, with age-matched nondiabetic and diabetic rats serving as controls. Blood and urine were collected for measurement of glycated albumin, creatinine, albumin, nephrin, podocalyxin, and βig-h3 protein. The elevated circulating concentrations of glycated albumin and higher urinary levels of these podocyte markers as well as of albumin that were observed in diabetic rats compared with nondiabetic controls were significantly reduced in animals receiving test compound, and decrease in urinary biomarkers correlated with reduction in AGA. The results provide evidence that lowering the concentration of AGA, independent of filtration status and hyperglycemia, reduces urinary nephrin, podocalyxin, and βig-h3 protein, linking the increased glycated albumin associated with diabetes to podocyte abnormalities and shedding of podocyte proteins into the urine. PMID:24303153

  17. Myenteric neurons and intestinal mucosa of diabetic rats after ascorbic acid supplementation

    PubMed Central

    de Freitas, Priscila; Natali, Maria Raquel Marçal; Pereira, Renata Virginia Fernandes; Neto, Marcilio Hubner Miranda; Zanoni, Jacqueline Nelisis

    2008-01-01

    AIM: To investigate the effect of ascorbic acid (AA) dietary supplementation on myenteric neurons and epithelial cell proliferation of the jejunum of adult rats with chronic diabetes mellitus. METHODS: Thirty rats at 90 d of age were divided into three groups: Non-diabetic, diabetic and diabetic treated with AA (DA) (1 g/L). After 120 d of treatment with AA the animals were killed. The myenteric neurons were stained for myosin-V and analyzed quantitatively in an area of 11.2 mm2/animal. We further measured the cellular area of 500 neurons per group. We also determined the metaphasic index (MI) of the jejunum mucosa layer of about 2500 cells in the intestinal crypts, as well as the dimensions of 30 villi and 30 crypts/animal. The data area was analyzed using the Olympus BX40 microscope. RESULTS: There was an increase of 14% in the neuronal density (792.6 ± 46.52 vs 680.6 ± 30.27) and 4.4% in the cellular area (303.4 ± 5.19 vs 291.1 ± 6.0) respectively of the diabetic group treated with AA when compared to control diabetic animals. There were no significant differences in MI parameters, villi height or crypt depths among the groups. CONCLUSION: Supplementation with AA in the diabetic animal promoted moderate neuroprotection. There was no observation of alteration of the cellular proliferation of the jejunum mucosa layer of rats with chronic diabetes mellitus with or without supplementation with AA. PMID:19030205

  18. Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

    PubMed Central

    Lee, Eun Soo; Hyun, Miri; Kim, Hong Min; Choi, Yoon Jung; Lee, Eun Young; Yadav, Dhananjay; Chung, Choon Hee

    2014-01-01

    The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n = 10), OLETF rats as diabetic control group (n = 10), and OLETF rats treated with taurine group (n = 10). We treated taurine (200 mg/kg/day) for 20 weeks and treated high glucose (HG, 30 mM) with or without taurine (30 mM) in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS) levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model. PMID:24707287

  19. Spatial memory in sedentary and trained diabetic rats: molecular mechanisms.

    PubMed

    Diegues, João Carlos; Pauli, José Rodrigo; Luciano, Eliete; de Almeida Leme, José Alexandre Curiacos; de Moura, Leandro Pereira; Dalia, Rodrigo Augusto; de Araújo, Michel Barbosa; Sibuya, Clarice Yoshiko; de Mello, Maria Alice Rostom; Gomes, Ricardo José

    2014-06-01

    Diabetes mellitus is a chronic disease that has been associated with memory loss, neurological disorders, and Alzheimer's disease. Some studies show the importance of physical exercise to prevent and minimize various neurological disorders. It is believed that the positive effects of exercise on brain functions are mediated by brain insulin and insulin-like growth factor-1 (IGF-1) signaling. In this study, we investigate the role of swimming exercise training on hippocampus proteins related to insulin/IGF-1 signaling pathway in Type 1 diabetic rats and its effects on spatial memory. Wistar rats were divided into four groups namely sedentary control, trained control, sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32 mg/kg b.w.). The training program consisted in swimming 5 days/week, 1 h/day, per 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. We employed ALX-induced diabetic rats to explore learning and memory abilities using Morris water maze test. At the end of the training period, the rats were sacrificed 48 h after their last exercise bout when blood samples were collected for serum glucose, insulin, and IGF-1 determinations. Hippocampus was extracted to determinate protein expression (IR, IGF-1R, and APP) and phosphorylation (AKT-1, AKT-2, Tau, and β-amyloide proteins) by Western Blot analysis. All dependent variables were analyzed by two-way analysis of variance with significance level of 5%. Diabetes resulted in hyperglycemia and hypoinsulinemia in both SD and TD groups (P < 0.05); however, in the training-induced group, there was a reduction in blood glucose in TD. The average frequency in finding the platform decreased in SD rats; however, exercise training improved this parameter in TD rats. Aerobic exercise decreased Tau phosphorylation and APP expression, and increased some proteins related to insulin/IGF-1 pathway in hippocampus of diabetic rats. Thus, these molecular

  20. Erythropoietin ameliorates hyperglycemia in type 1-like diabetic rats

    PubMed Central

    Niu, Ho-Shan; Chang, Chin-Hong; Niu, Chiang-Shan; Cheng, Juei-Tang; Lee, Kung-Shing

    2016-01-01

    Background Erythropoietin (EPO) is widely used in diabetic patients receiving hemodialysis. The role of EPO in glucose homeostasis remains unclear. Therefore, we investigated the effect of EPO on hyperglycemia in rats with type 1-like diabetes. Methods Rats with streptozotocin-induced type 1-like diabetes (STZ rats) were used to estimate the blood glucose-lowering effects of EPO, and changes in the expression levels of glucose transporter 4 (GLUT4) and the hepatic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were identified by Western blot analysis. Results EPO attenuated the hyperglycemia in the STZ rats in a dose-dependent manner without altering the hematopoietic parameters, including the hematocrit and number of red blood cells. The involvement of the EPO receptor (EPOR) was identified using EPOR-specific antibodies. In addition, injection of EPO enhanced the glucose utilization, which was assessed using an intravenous glucose tolerance test in rats. However, blood insulin was not changed by EPO in this assay, showing the insulinotropic action of EPO. Moreover, EPO treatment increased the insulin sensitivity. Western blots indicated that the phosphorylation of AMP-activated protein kinase was enhanced by EPO to support the signaling caused by EPOR activation. Furthermore, the decrease in the GLUT4 level in skeletal muscle was reversed by EPO, and the increase in the PEPCK expression in liver was reduced by EPO, as shown in STZ rats. Conclusion Taken together, the results show that EPO injection may reduce hyperglycemia in diabetic rats through activation of EPO receptors. Therefore, EPO is useful for managing diabetic disorders, particularly hyperglycemia-associated changes. In addition, EPO receptor will be a good target for the development of antihyperglycemic agent(s) in the future. PMID:27350742

  1. Hypoglycaemic effect of galactooligosaccharides in alloxan-induced diabetic rats.

    PubMed

    Sangwan, Vikas; Tomar, Sudhir K; Ali, Babar; Singh, Ram R B; Singh, Ashish K

    2015-02-01

    This study was conducted to assess the effect of prebiotic galactooligosaccharides (GOS) on alloxan-induced diabetes in male Sprague-Dawley (SD) rats. Diabetes was induced by administration of alloxan (100 mg/kg) and rats were divided in 4 groups: normal control group (NCG), prebiotic control group (PCG), diabetic control group (DCG) and diabetic prebiotic group (DPG). While PCG and DPG were fed with GOS supplemented (10% w/w) diet, NCG and DCG were administered with basal diet. Rats were sacrificed after 42 d for collection of blood and liver. Faecal samples were collected at the interval of 7 d throughout the study for measurement of lactobacilli and coliform count. Feeding of GOS decreased or delayed the severity of diabetes by amelioration of diabetes associated markers including fasting blood glucose, haemoglobin, glycosylated haemoglobin triglycerides, total cholesterol, low density lipoproteins, creatinine and urea. GOS was also found to improve the levels of antioxidative enzymes (superoxide dismutase, catalase and glutathione peroxidase) in liver and blood. Improvement in lactobacilli count along with a concomitant decrease in coliform count was observed in GOS fed groups. PMID:25382051

  2. Metabolic and neurochemical profiles in insulin-treated diabetic rats.

    PubMed

    Bellush, L L; Reid, S G

    1994-01-01

    Plasma glucose concentration was measured at 3-h intervals in streptozotocin-induced diabetic rats placed on various insulin replacement regimens using three different kinds of insulin. High insulin dosages produced at least periodic hypoglycemia, even though there were no overt signs of insulin overdose. Low- and single-dose regimens produced periods of hyperglycemia. Both high and low doses of protamine zinc insulin normalized diabetes-induced reductions in 5-hydroxyindole-3-acetic acid [5-HIAA; the principal metabolite of 5-hydroxytryptamine (5-HT)] and 5-HT turnover (5-HIAA/5-HT), despite the failure of the low-dose regimen to normalize plasma glucose. Diabetic rats evidenced continued hyperphagia and hyperdipsia during insulin treatment, and insulin treatment also induced hyperphagia and excessive weight gain in nondiabetic rats. Insulin treatment only partially normalized diabetes-induced adrenal hypertrophy. Adrenal hypertrophy is an indication of a continued stresslike physiological state in diabetes even during insulin therapy. This state may be involved in the enhanced risk in diabetic humans for development of anxiety disorders and clinical depression. PMID:7508209

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

    PubMed Central

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

    2015-01-01

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

  4. 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.

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

    PubMed

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

    2013-01-01

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

  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. PMID:27109015

  7. Overexpression of GLUT3 placental glucose transporter in diabetic rats.

    PubMed Central

    Boileau, P; Mrejen, C; Girard, J; Hauguel-de Mouzon, S

    1995-01-01

    The localization of the two major placental glucose transporter isoforms, GLUT1 and GLUT3 was studied in 20-d pregnant rats. Immunocytochemical studies revealed that GLUT1 protein is expressed ubiquitously in the junctional zone (maternal side) and the labyrinthine zone (fetal side) of the placenta. In contrast, expression of GLUT3 protein is restricted to the labyrinthine zone, specialized in nutrient transfer. After 19-d maternal insulinopenic diabetes (streptozotocin), placental GLUT3 mRNA and protein levels were increased four-to-fivefold compared to nondiabetic rats, whereas GLUT1 mRNA and protein levels remained unmodified. Placental 2-deoxyglucose uptake and glycogen concentration were also increased fivefold in diabetic rats. These data suggest that GLUT3 plays a major role in placental glucose uptake and metabolism. The role of hyperglycemia in the regulation of GLUT3 expression was assessed by lowering the glycemia of diabetic pregnant rats. After a 5-d phlorizin infusion to pregnant diabetic rats, placental GLUT3 mRNA and protein levels returned to levels similar to those observed in nondiabetic rats. Furthermore, a short-term hyperglycemia (12 h), achieved by performing hyperglycemic clamps induced a fourfold increase in placental GLUT3 mRNA and protein with no concomitant change in GLUT1 expression. This study provides the first evidence that placental GLUT3 mRNA and protein expression can be stimulated in vivo under hyperglycemic conditions. Thus, GLUT3 transporter isoform appears to be highly sensitive to ambient glucose levels and may play a pivotal role in the severe alterations of placental function observed in diabetic pregnancies. Images PMID:7615800

  8. Histopathologic Responses of the Dental Pulp to Calcium-Enriched Mixture (CEM) and Mineral Trioxide Aggregate (MTA) in Diabetic and Non-Diabetic Rats.

    PubMed

    Madani, Zahra Sadat; Haddadi, Azam; Mesgarani, Abbas; Seyedmajidi, Maryam; Mostafazadeh, Amrollah; Bijani, Ali; Ashraphpour, Manouchehr

    2014-01-01

    Diabetes mellitus is a chronic disease which affects the healing ability of the pulp and periodontium. The aim of the present study was to assess the histopathologic response of dental pulp to pulp capping using MTA or CEM cement in diabetic rats. Thirty two Wistar male rats aged between 8 and 10 weeks (weight: 200-250g) were divided into two groups of diabetic (n=16) and healthy (n=16) animals and then subdivided into MTA and CEM subgroups. In each group, 10 MTA treated, 10 CEM treated and 12 intact (without any intervention) teeth were analyzed. Intact teeth were considered as a baseline inflammation control. Then, class I cavity was made in the maxillary first molars teeth with pinpoint pulpal exposure. Either MTA or CEM cement was then placed over exposed pulp as pulp capping agent and the cavities were restored using resin- modified glass ionomer cement. Both teeth of rats in subgroups remained intact without any intervention. After four weeks, the rats were sacrificed and the teeth were subjected to histological evaluation in terms of inflammation intensity, dentin bridge formation and dentin bridge continuity. The CEM cement treated diabetic rats exhibited a significant higher inflammatory response when compared to healthy control group (P=0.004) whereas, MTA treated diabetic rats did not exhibit a significant higher inflammatory response in comparison to healthy controls. There was no significant difference between MTA and CEM cement in the induction of dentin bridge formation in diabetic and healthy controls. This preliminary study suggests that MTA is a superior dental material than CEM cement for pulp therapy in subjects with diabetes. PMID:25635253

  9. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model

    PubMed Central

    Park, Se Eun; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation. PMID:26894429

  10. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

    PubMed

    Park, Se Eun; Park, Cheol-Young; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation. PMID:26894429

  11. 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

  12. Rates of Complications and Mortality in Older Diabetes Patients: The Diabetes and Aging Study

    PubMed Central

    Huang, Elbert S.; Laiteerapong, Neda; Liu, Jennifer Y.; John, Priya M.; Moffet, Howard H.; Karter, Andrew J.

    2014-01-01

    Importance In the coming decades, the population of older adults with diabetes is expected to grow substantially. Understanding the clinical course of diabetes in this population is critical for establishing evidence-based clinical practice recommendations, research priorities, allocating resources, and setting health policies. Objective Contrast rates of diabetes complications and mortality across age and diabetes duration categories. Design, Setting, Participants This cohort study (2004–2010) included 72,310 older (≥60 years of age) patients with type 2 diabetes enrolled in a large, integrated healthcare delivery system. Incidence densities (events per 1000 person-years (pys)) were calculated for each age category (60s, 70s, 80+ years) and duration of diabetes (shorter: 0–9 years vs. longer: 10+ years). Main Outcome Measures Incident acute hyperglycemic events, acute hypoglycemic events (hypoglycemia), microvascular complications [end-stage renal disease (ESRD), peripheral vascular disease, lower extremity amputation, advanced eye disease], cardiovascular complications [coronary artery disease (CAD), cerebrovascular disease (CVD), congestive heart failure (CHF)], and all-cause mortality. Results Among older adults with diabetes of short duration, cardiovascular complications followed by hypoglycemia were the most common non-fatal complications. For example, among 70–79 year olds with short duration of diabetes, CAD and hypoglycemia rates were higher (11.5 and 5.0/1000 pys respectively), compared to ESRD (2.6/1000), amputation (1.3/1000), and acute hyperglycemic events (0.8/1000). We observed a similar pattern among subjects in the same age group with long diabetes duration where CAD and hypoglycemia had some of the highest incidence rates (19.0 and 15.9 /1000 pys respectively), compared to ESRD (7.6/1000), amputation (4.3/1000), and acute hyperglycemic events (1.8/1000). For a given age group, rates of each outcome, particularly hypoglycemia and

  13. 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

  14. Lead exposure causes thyroid abnormalities in diabetic rats

    PubMed Central

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

    2015-01-01

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

  15. 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. PMID:26764087

  16. Lead exposure causes thyroid abnormalities in diabetic rats.

    PubMed

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

    2015-01-01

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

  17. The Effect of Food Hardness on the Development of Dental Caries in Alloxan-Induced Diabetic Rats

    PubMed Central

    Nakahara, Yutaka; Sano, Tomoya; Kodama, Yasushi; Ozaki, Kiyokazu; Matsuura, Tetsuro

    2013-01-01

    We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats. PMID:23762876

  18. 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

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

    PubMed

    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. Altered protein phosphorylation in sciatic nerve from rats with streptozocin-induced diabetes

    SciTech Connect

    Schrama, L.H.; Berti-Mattera, L.N.; Eichberg, J.

    1987-11-01

    The effect of experimental diabetes on the phosphorylation of proteins in the rat sciatic nerve was studied. Nerves from animals made diabetic with streptozocin were incubated in vitro with (/sup 32/P)orthophosphate and divided into segments from the proximal to the distal end, and proteins from each segment were then separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The principal labeled species were the major myelin proteins, P0, and the basic proteins. After 6 wk of diabetes, the incorporation of isotope into these proteins rose as a function of distance along the nerve in a proximal to distal direction and was significantly higher at the distal end compared with incorporation into nerves from age-matched controls. The overall level of isotope uptake was similar in nerves from diabetic animals and weight-matched controls. The distribution of /sup 32/P among proteins also differed in diabetic nerve compared with both control groups in that P0 and the small basic protein accounted for a greater proportion of total label incorporated along the entire length of nerve. In contrast to intact nerve, there was no significant difference in protein phosphorylation when homogenates from normal and diabetic nerve were incubated with (/sup 32/P)-gamma-ATP. The results suggest that abnormal protein phosphorylation, particularly of myelin proteins, is a feature of experimental diabetic neuropathy and that the changes are most pronounced in the distal portion of the nerve.

  1. Stereological study of the diabetic heart of male rats

    PubMed Central

    Noorafshan, Ali; Khazraei, Hajar; Mirkhani, Hossein

    2013-01-01

    The present study aimed to quantitatively compare the normal and diabetic hearts of rats using stereological methods. Diabetic and control rats received streptozotocin (60 mg/kg) and no treatments, respectively. On the 56th day, the hearts were removed and their total volume was estimated using isotropic Cavalieri method. The total volume of the connective tissues and vessels, total length and diameter of the vessels, total number of cardiomyocytes nuclei, and the mean volume of the cardiomyocytes were estimated, as well. In comparison to the control animals, 60 and 43% increase was observed in the total volume of the connective tissue and microvessels of the diabetic rats, respectively (P<0.05). The percent of the vessel profiles with the diameter of 2-4 µm was decreased, while the percent of the vessel profiles with the diameter of 4.1-8 µm was increased in the diabetic hearts (P<0.05). No significant difference was found in the vessels with more than 8 µm diameters. The total number of the cardiomyocytes' nuclei and the number-weighted mean volume were respectively decreased by 37 and 64% in the diabetic group (P<0.01). A significant difference was observed between the two groups concerning the left ventricle volume to body weight ratio as an index for ventricular hypertrophy (P<0.05), while no difference was found regarding the right ventricle to body weight ratio. It can be concluded that diabetes can induce structural changes, including loss and/or atrophy of the cardiomyocytes, accompanied with increase in the connective tissue in the rats' hearts. PMID:23573103

  2. Stereological study of the diabetic heart of male rats.

    PubMed

    Noorafshan, Ali; Khazraei, Hajar; Mirkhani, Hossein; Karbalay-Doust, Saied

    2013-03-01

    The present study aimed to quantitatively compare the normal and diabetic hearts of rats using stereological methods. Diabetic and control rats received streptozotocin (60 mg/kg) and no treatments, respectively. On the 56(th) day, the hearts were removed and their total volume was estimated using isotropic Cavalieri method. The total volume of the connective tissues and vessels, total length and diameter of the vessels, total number of cardiomyocytes nuclei, and the mean volume of the cardiomyocytes were estimated, as well. In comparison to the control animals, 60 and 43% increase was observed in the total volume of the connective tissue and microvessels of the diabetic rats, respectively (P<0.05). The percent of the vessel profiles with the diameter of 2-4 µm was decreased, while the percent of the vessel profiles with the diameter of 4.1-8 µm was increased in the diabetic hearts (P<0.05). No significant difference was found in the vessels with more than 8 µm diameters. The total number of the cardiomyocytes' nuclei and the number-weighted mean volume were respectively decreased by 37 and 64% in the diabetic group (P<0.01). A significant difference was observed between the two groups concerning the left ventricle volume to body weight ratio as an index for ventricular hypertrophy (P<0.05), while no difference was found regarding the right ventricle to body weight ratio. It can be concluded that diabetes can induce structural changes, including loss and/or atrophy of the cardiomyocytes, accompanied with increase in the connective tissue in the rats' hearts. PMID:23573103

  3. Incentive relativity in middle aged rats.

    PubMed

    Justel, N; Mustaca, A; Boccia, M; Ruetti, E

    2014-01-24

    Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion. PMID:24315974

  4. Protective effect of compound K on diabetic rats.

    PubMed

    Shao, Xiaotong; Li, Na; Zhan, Jinzhuo; Sun, Hui; An, Liping; Du, Peige

    2015-02-01

    Purpose: Compound K (CK), the metabolic product of protopanaxadiol saponin in vivo, has many pharmacological activities. In this study, we discuss the preparation of CK, and its protective effect on kidneys of diabetic rats. CK was prepared from ginsenoside Rbt after transformation by 3-glucosidase, separation and purification by silica gel column chromatography. In the present study, we established a rat model of diabetes mellitus using high-fat diet and streptozotocin (STZ). After seven weeks of treatment, the levels of fasting blood glucose (FBG), total cholesterol (TC), total glycerin (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), blood urea nitrogen (BUN), uric acid (UA), serum creatinine (Scr), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) were evaluated in normal and diabetic rats. Also, renal pathomorphism changes were observed by HE stain, and TGF-β1 protein expression in the renal tissue was measured by Western blot. The yield of CK was 14.55 mg/mL, which was higher than that of other methods. After seven weeks, CK could decrease FBG, TC, TG, LDL-C, BUN, UA, Scr and MDA of diabetic rats, while CK also enhanced HDL-C and GSH, SOD and GSH-PX. Additionally, CK improved the pathological changes and decreased TGF-β1 protein expression in the renal tissue. CK improved the pathological changes in the renal tissue, enhanced the antioxidant capacity, reduced the damage of TGF-β1 to renal tissue, and protected the diabetic rats. PMID:25920251

  5. Chymase inhibition protects diabetic rats from renal lesions.

    PubMed

    Zhang, Mei; Huang, Wen; Bai, Jing; Nie, Xiaodong; Wang, Wen

    2016-07-01

    The present study aimed to investigate the effects of a chymase inhibitor on renal injury in diabetic rats. A total of 24 Sprague-Dawley rats were randomly divided into the following groups: The control group (n=7), the diabetes group (DM group; n=7), and the DM + chymase inhibitor group (DM + Chy‑I group; n=10). Diabetes was induced via an intraperitoneal injection of streptozotocin (65 mg/kg). Rats in the DM + Chy‑I group were administered 1 mg/kg chymase inhibitor [Suc-Val-Pro-PheP-(OPh)2] daily for 12 weeks by intraperitoneal injection. Subsequently, kidney weight, various biochemical parameters and blood pressure were measured. In addition, the expression levels of fibronectin (FN), type IV collagen (ColIV), transforming growth factor (TGF)‑β1 and vascular endothelial growth factor (VEGF) were determined by immunohistochemistry and reverse transcription polymerase chain reaction. Compared with in the DM group, the levels of serum cholesterol and urinary albumin/creatinine were decreased in the DM + Chy‑I group (P<0.05). Furthermore, chymase inhibition reduced the overexpression of FN, ColIV, TGF‑β1 and VEGF (P<0.05) in the renal tissue of diabetic rats. These results indicated that chymase inhibition may reduce the excretion of urinary albumin and the deposition of extracellular matrix components in the kidney of diabetic rats. These effects may be mediated by altered expression of the VEGF and TGF‑β1 pathways. In conclusion, chymase inhibition may be considered a potential method for the treatment of renal damage. PMID:27176496

  6. Chymase inhibition protects diabetic rats from renal lesions

    PubMed Central

    ZHANG, MEI; HUANG, WEN; BAI, JING; NIE, XIAODONG; WANG, WEN

    2016-01-01

    The present study aimed to investigate the effects of a chymase inhibitor on renal injury in diabetic rats. A total of 24 Sprague-Dawley rats were randomly divided into the following groups: The control group (n=7), the diabetes group (DM group; n=7), and the DM + chymase inhibitor group (DM + Chy-I group; n=10). Diabetes was induced via an intraperitoneal injection of streptozotocin (65 mg/kg). Rats in the DM + Chy-I group were administered 1 mg/kg chymase inhibitor [Suc-Val-Pro-PheP-(OPh)2] daily for 12 weeks by intraperitoneal injection. Subsequently, kidney weight, various biochemical parameters and blood pressure were measured. In addition, the expression levels of fibronectin (FN), type IV collagen (ColIV), transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) were determined by immunohistochemistry and reverse transcription polymerase chain reaction. Compared with in the DM group, the levels of serum cholesterol and urinary albumin/creatinine were decreased in the DM + Chy-I group (P<0.05). Furthermore, chymase inhibition reduced the overexpression of FN, ColIV, TGF-β1 and VEGF (P<0.05) in the renal tissue of diabetic rats. These results indicated that chymase inhibition may reduce the excretion of urinary albumin and the deposition of extracellular matrix components in the kidney of diabetic rats. These effects may be mediated by altered expression of the VEGF and TGF-β1 pathways. In conclusion, chymase inhibition may be considered a potential method for the treatment of renal damage. PMID:27176496

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

    PubMed

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

    2014-10-01

    The present study aims to investigate anti-hyperglycaemic, anti-hyperlipidaemic and toxic effects of long-term consumption of selected green leafy porridges in a streptozotocin-induced diabetic Wistar rat model. Porridges made with Asparagus racemosus Willd. (AR), Hemidesmus indicus (L) R. Br. W. T. Aiton (HI), Scoparia dulcis L. (SD) and coconut milk porridge (CM) were incorporated into diets of diabetic Wistar rats. Diabetic control (DM) and normal control groups (NC) were provided with standard rat diet. Fasting blood glucose (FBG), HbA1c , C reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), liver enzymes and creatinine were measured. Feed and water intake among diabetic groups were significantly high when compared with those of NC (p < 0.05). All rats in SD (mean = 39 ± 19 g) and NC (mean = 114 ± 7 g) groups gained weight, whereas most rats in other diabetic groups lost weight. Among the diabetic groups, SD group had the lowest mean FBG, FBG increment percentage (45%) and HbA1c (5.8 ± 2.1). FBG increment percentage and HbA1c of SD group were not significantly different to those of NC (38%; 4.7 ± 0.7) (p > 0.05). Among the diabetic groups, lowest TC (119 ± 20.6 mg/dL) and highest HDL-C (33 ± 6.3 mg/dL) were also detected in SD group. Alanine transaminase and creatinine were not significantly different (p > 0.05) among diabetic groups but significant when compared with those of NC. When compared with those of NC, aspartate transaminase levels were significantly (p < 0.05) high in SD, CM and DM groups. Body weight : liver weight and body weight : pancreas weight ratios and CRP were not significantly different among all groups. The study proved that SD porridge reduced weight loss, elicited hypoglycaemic and hypolipidaemic properties, and caused no toxicity in diabetes-induced Wistar rats. PMID:24840113

  8. Ultrastructural changes in the hypothalamic supraoptic nucleus of the streptozotocin-induced diabetic rat.

    PubMed Central

    Dheen, S T; Tay, S S; Wong, W C

    1994-01-01

    Ultrastructural and morphometric studies were undertaken on the hypothalamic supraoptic nucleus of streptozotocin-induced diabetic rats over a period of 1 y. At 3 d, a few dendrites showing electron-dense cytoplasm and dilated rER were dispersed in the neuropil among seemingly normal neuronal somata. At 1-6 months, the somata contained numerous vacuoles of various sizes which probably originated from fragmented and dilated rER. Numerous unidentifiable vacuolated and electron-dense neuronal profiles were also seen in the neuropil. At 9-12 months, the number of degenerating electron-dense axon terminals and dendrites was markedly increased in diabetic rats. Glial cells containing electron-dense debris in their cytoplasm were involved in phagocytosis. At all time intervals studied, the mean cross-sectional cell area and mean cross-sectional nuclear area of supraoptic nuclei neurons of diabetic rats were significantly increased in comparison with age-matched controls injected with normal saline. The causative factors for these changes are not clear. However, it is suggested that the osmotic stress caused by chronic dehydration in the diabetic animals may be partly or wholly responsible for these ultrastructural changes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7928649

  9. Effect of Biophytum sensitivum on streptozotocin and nicotinamide-induced diabetic rats

    PubMed Central

    Ananda, Prabu K; Kumarappan, CT; Sunil, Christudas; Kalaichelvan, VK

    2012-01-01

    Objective To investigate the effect of aqueous solution of Biophytum sensitivum leaf extract (BSEt) on normal and streptozotocin (STZ)-nicotinamide-induced diabetic rats. Methods Diabetes was induced in adult male Wistar rats by the administration of STZ-nicotinamide (40, 110 mg/kg b.w., respectively) intraperitoneally. BSEt (200 mg/kg) was administered to diabetic rats for 28 days. The effect of extract on blood glucose, plasma insulin, total haemoglobin, glycosylated haemoglobin, liver glycogen and carbohydrate metabolism regulating enzymes of liver was studied in diabetic rats. Results BSEt significantly reduced the blood glucose and glycosylated haemoglobin levels and significantly increased the total haemoglobin, plasma insulin and liver glycogen levels in diabetic rats. It also increased the hexokinase activity and decreased glucose-6-phosphatase, fructose-1, 6-bisphosphatase activities in diabetic rats. Conclusions The results of our study suggest that BSEt possesses a promising effect on STZ-nicotinamide-induced diabetes. PMID:23569830

  10. AB096. Taurine supplementation improves erectile function in rats with streptozotocin-induced type 1 diabetes via amelioration of penile fibrosis and endothelial dysfunction

    PubMed Central

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

    2016-01-01

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

  11. Antidiabetic activity of zinc oxide and silver nanoparticles on streptozotocin-induced diabetic rats.

    PubMed

    Alkaladi, Ali; Abdelazim, Aaser Mohamed; Afifi, Mohamed

    2014-01-01

    The use of nanoparticles in medicine is an attractive proposition. In the present study, zinc oxide and silver nanoparticles were evaluated for their antidiabetic activity. Fifty male albino rats with weight 120 ± 20 and age 6 months were used. Animals were grouped as follows: control; did not receive any type of treatment, diabetic; received a single intraperitoneal dose of streptozotocin (100 mg/kg), diabetic + zinc oxide nanoparticles (ZnONPs), received single daily oral dose of 10 mg/kg ZnONPs in suspension, diabetic + silver nanoparticles (SNPs); received a single daily oral dose of SNP of 10 mg/kg in suspension and diabetic + insulin; received a single subcutaneous dose of 0.6 units/50 g body weight. Zinc oxide and silver nanoparticles induce a significant reduced blood glucose, higher serum insulin, higher glucokinase activity higher expression level of insulin, insulin receptor, GLUT-2 and glucokinase genes in diabetic rats treated with zinc oxide, silver nanoparticles and insulin. In conclusion, zinc oxide and sliver nanoparticles act as potent antidiabetic agents. PMID:24477262

  12. Effects of High Fat Feeding on Adipose Tissue Gene Expression in Diabetic Goto-Kakizaki Rats

    PubMed Central

    Xue, Bai; Nie, Jing; Wang, Xi; DuBois, Debra C; Jusko, William J; Almon, Richard R

    2015-01-01

    Development and progression of type 2 diabetes is a complex interaction between genetics and environmental influences. High dietary fat is one environmental factor that is conducive to the development of insulin-resistant diabetes. In the present report, we compare the responses of lean poly-genic, diabetic Goto-Kakizaki (GK) rats to those of control Wistar-Kyoto (WKY) rats fed a high fat diet from weaning to 20 weeks of age. This comparison included a wide array of physiological measurements along with gene expression profiling of abdominal adipose tissue using Affymetrix gene array chips. Animals of both strains fed a high fat diet or a normal diet were sacrificed at 4, 8, 12, 16, and 20 weeks for this comparison. The microarray analysis revealed that the two strains developed different adaptations to increased dietary fat. WKY rats decrease fatty acid synthesis and lipogenic processes whereas GK rats increase lipid elimination. However, on both diets the major differences between the two strains remained essentially the same. Specifically relative to the WKY strain, the GK strain showed lipoatrophy, chronic inflammation, and insulin resistance. PMID:26309393

  13. Renal angiotensin-converting enzyme localization in diabetic rats and the effect of low protein diet.

    PubMed

    Mizuiri, S; Kobayashi, M; Nakanishi, T; Yoshikawa, H; Miyagi, M; Tanegashima, M; Sakai, K; Hayashi, I; Fushimi, T; Hasegawa, A

    1997-01-01

    Recent evidence suggests a role of angiotensin-converting enzyme (ACE) in diabetic nephropathy. The effect of diabetes and low protein diet on renal immunohistochemical ACE localization was studied in streptozotocin-induced DM rats. Immunohistochemical ACE localization was reduced in DM rats, and a low protein diet partially resolved this abnormality while inhibiting the progression of diabetic nephropathy. PMID:9200410

  14. Hypercholesterolemia abrogates an increased resistance of diabetic rat hearts to ischemia-reperfusion injury.

    PubMed

    Adameová, A; Kuzelová, M; Andelová, E; Faberová, V; Pancza, D; Svec, P; Ziegelhöffer, A; Ravingerová, T

    2007-01-01

    Both, diabetes mellitus (DM) and hypercholesterolemia (HCH) are known as risk factors of ischemic heart disease, however, the effects of experimental DM, as well as of HCH alone, on ischemia/reperfusion-induced myocardial injury are not unequivocal. We have previously demonstrated an enhanced resistance to ischemia-induced arrhythmias in rat hearts in the acute phase of DM. Our objectives were thus to extend our knowledge on how DM in combination with HCH, a model that is relevant to diabetic patients with altered lipid metabolism, may affect the size of myocardial infarction and susceptibility to arrhythmias. A combination of streptozotocin (STZ; 80 mg/kg, i.p.) and the fat-cholesterol diet (1% cholesterol, 1% coconut oil; FCHD) was used as a double-disease model mimicking DM and HCH simultaneosly occurring in humans. Following 5 days after STZ injection and FCHD leading to increased blood glucose and cholesterol levels, anesthetized open-chest diabetic, diabetic-hypercholesterolemic (DM-HCH) and age-matched control rats were subjected to 6-min ischemia (occlusion of LAD coronary artery) followed by 10 reperfusion to test susceptibility to ventricular arrhythmias in the in vivo experiments and to 30-min ischemia and subsequent 2-h reperfusion for the evaluation of the infarct size (IS) in the Langendorff-perfused hearts. The incidence of the most life-threatening ventricular arrhythmia, ventricular fibrillation, was significantly increased in the DM-HCH rats as compared with non-diabetic control animals (100% vs. 50%; p<0.05). Likewise, arrhythmia severity score (AS) was significantly higher in the DM-HCH rats than in the controls (4.9+/-0.2 vs. 3.5+/-0.5; p<0.05), but was not increased in the diabetic animals (AS 3.7+/-0.9; p>0.05 vs. controls). Diabetic hearts exhibited a reduced IS (15.1+/-3.0% of the area at risk vs. 37.6+/-2.8% in the control hearts; p<0.05), however, a combination of DM and HCH increased the size of myocardial infarction to that observed in

  15. The pituitary - Aging and spaceflown rats

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Grindeland, R. E.

    1991-01-01

    Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: (1) investigation of mechanisms of intracellular hormone packaging, (2) consequences to biological activity of the hormone molecule, and (3) study of intracellular microtubule dynamics.

  16. Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats.

    PubMed

    Yang, Xiu-Ying; Qiang, Gui-Fen; Zhang, Li; Zhu, Xiao-Ming; Wang, Shou-Bao; Sun, Lan; Yang, Hai-Guang; Du, Guan-Hua

    2011-10-01

    Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high-fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs-induced endothelial dysfunction. PMID:21972802

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

    SciTech Connect

    Liu, Z.

    1987-01-01

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

  18. Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats.

    PubMed

    Wautier, J L; Zoukourian, C; Chappey, O; Wautier, M P; Guillausseau, P J; Cao, R; Hori, O; Stern, D; Schmidt, A M

    1996-01-01

    Dysfunctional endothelium is associated with and, likely, predates clinical complications of diabetes mellitus, by promoting increased vascular permeability and thrombogenicity. Irreversible advanced glycation end products (AGEs), resulting from nonenzymatic glycation and oxidation of proteins or lipids, are found in plasma, vessel wall, and tissues and have been linked to the development of diabetic complications. The principal means through which AGEs exert their cellular effects is via specific cellular receptors, one of which, receptor for AGE (RAGE), is expressed by endothelium. We report that blockade of RAGE inhibits AGE-induced impairment of endothelial barrier function, and reverse, in large part, the early vascular hyperpermeability observed in diabetic rats. Inhibition of AGE- and diabetes-mediated hyperpermeability by antioxidants, both in vitro and in vivo, suggested the central role of AGE-RAGE-induced oxidant stress in the development of hyperpermeability. Taken together, these data support the concept that ligation of AGEs by endothelial RAGE induces cellular dysfunction, at least in part by an oxidant-sensitive mechanism, contributing to vascular hyperpermeability in diabetes, and that RAGE is central to this pathologic process. PMID:8550841

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

    PubMed Central

    Liu, Xianchu; Liu, Ming; Mo, Yanzhi; Peng, Huan; Gong, Jingbo; Li, Zhuang; Chen, Jiaxue; Xie, Jingtao

    2016-01-01

    Objective(s): Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ)-induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD). In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. Materials and Methods: Diabetic rats were treated with naringin (100 mg/kg/d) for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)] and inflammatory cytokines (TNF-a, IL-1β, and IL-6) were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARγ were evaluated by real time (RT)-PCR and Western blot analysis. Results: The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-α, IL-1β, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARγ expression. Conclusion: Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD. PMID:27279986

  20. 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

  1. Comparison of effect of resveratrol and vanadium on diabetes related dyslipidemia and hyperglycemia in streptozotocin induced diabetic rats

    PubMed Central

    Mohamad Shahi, Majid; Haidari, Fatemeh; Shiri, Mohamad Reza

    2011-01-01

    Purpose: Resveratrol a natural polyphenolicstilbene derivative has wide variety of biological activities. There is also a large body of evidence demonstrating positive effect of resveratrol in treatment of various metabolic complications including metabolic syndrome, obesity, diabetes and dyslipidemia in adults. The purpose of this study was to investigate anti-hyperglycemic and anti-dyslipidemic effects of resveratrol. Methods: We used 40 diabetic streptozotocin Wistar rats. Rats were randomly divided into 5 treatment groups (n=8 in each) including normal control, normal treated with resveratrol, diabetic control, diabetic treated with vanadium , diabetic treated with resveratrol . Resveratrol (25 mg/kgbw) and vanadate (0.2 mg/kgbw) was orally gavaged for 40 days and blood samples were directly collected from heart. Results: Diabetic rats treated with resveratrol in comparison to control diabetic rats demonstrated a significant (p = 0.001) decline in serum glucose concentration, and high plasma concentrations of total cholesterol and LDL-c were reduced (p = 0.031, p = 0.004 respectively). Furthermore, body weight loss trend that observed in diabetic rats alleviated by resveratrol and vanadate. However triglyceride, VLDL-c and HDL-c levels did not changed significantly. Conclusion: In conclusion Resveratrol ameliorated dyslipidemia and hyperglycemia in diabetic rats. However further investigations in peculiar human studies are required. PMID:24312761

  2. Antidiabetic activity of Terminalia pallida fruit in alloxan induced diabetic rats.

    PubMed

    Kameswara Rao, B; Renuka Sudarshan, P; Rajasekhar, M D; Nagaraju, N; Appa Rao, Ch

    2003-03-01

    Different doses of ethanolic fraction of fruits of Terminalia pallida were evaluated for hypoglycemic and antihyperglycemic activity in normal and alloxan diabetic rats. The oral administration of ethanolic extract at a dosage of 0.5 g/kg body weight exhibited a significant antihyperglycemic activity in alloxan diabetic rats, whereas in normal rats no hypoglycemic activity was observed. PMID:12576217

  3. Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Xianchu; Mo, Yanzhi; Gong, Jingbo; Li, Zhuang; Peng, Huan; Chen, Jiaxue; Wang, Qichao; Ke, Zhaowen; Xie, Jingtao

    2016-04-01

    Previous research has indicated that Diabetes is a high risk of learning and memory deficits. Puerarin, an isoflavonoid extracted from Kudzu roots, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic and anti-diabetic properties which are useful in the treatment of various diseases. Recently, Puerarin was found to have the effects on learning and memory performances in humans and animal models. However, up to now, there is no detailed evidence on the effect of Puerarin on diabetes-associated cognitive decline (DACD). In this study, we designed to assess the effects of Puerarin on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model and exploring its potential mechanism. Diabetic rats were treated with Puerarin (100 mg/kg per d) for 7 days. The learning and memory function was evaluated by morris water maze test. The acetylcholinesterase (AChE), choline acetylase (ChAT), oxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] and inflammatory cytokine (TNF-a, IL-1β and IL-6) were measured in hippocampus by using corresponding commercial kits. mRNA and Protein levels of Bcl-2 were analyzed by RT-PCR and Westernblot. The results showed that supplementation of Puerarin improved the learning and memory performances compared with the STZ group by the morris water maze test. In addition, Puerarin supplement significantly prevented AChE and MDA activities, increased ChAT and SOD activities, and alleviated the protein level of TNF-α, IL-1β and IL-6 in the hippocampus compared with the STZ group. Moreover, the pretreatment with Puerarin also significantly increased the Bcl-2 expression. It is concluded that Puerarin possesses neuroprotection to ameliorate cognitive deficits in streptozotocin-induced diabetic rats by anti-inflammatory, antioxidant and antiapototic effects. PMID:26686502

  4. Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development

    PubMed Central

    2010-01-01

    Background Experimental models are necessary to elucidate diabetes pathophysiological mechanisms not yet understood in humans. Objective: To evaluate the repercussions of the mild diabetes, considering two methodologies, on the pregnancy of Wistar rats and on the development of their offspring. Methods In the 1st induction, female offspring were distributed into two experimental groups: Group streptozotocin (STZ, n = 67): received the β-cytotoxic agent (100 mg STZ/kg body weight - sc) on the 1st day of the life; and Non-diabetic Group (ND, n = 14): received the vehicle in a similar time period. In the adult life, the animals were mated. After a positive diagnosis of pregnancy (0), female rats from group STZ presenting with lower glycemia than 120 mg/dL received more 20 mg STZ/kg (ip) at day 7 of pregnancy (2nd induction). The female rats with glycemia higher than 120 mg/dL were discarded because they reproduced results already found in the literature. In the mornings of days 0, 7, 14 and 21 of the pregnancy glycemia was determined. At day 21 of pregnancy (at term), the female rats were anesthetized and killed for maternal reproductive performance and fetal development analysis. The data were analyzed using Student-Newman-Keuls, Chi-square and Zero-inflated Poisson (ZIP) Tests (p < 0.05). Results STZ rats presented increased rates of pre (STZ = 22.0%; ND = 5.1%) and post-implantation losses (STZ = 26.1%; ND = 5.7%), reduced rates of fetuses with appropriate weight for gestational age (STZ = 66%; ND = 93%) and reduced degree of development (ossification sites). Conclusion Mild diabetes led a negative impact on maternal reproductive performance and caused intrauterine growth restriction and impaired fetal development. PMID:20416073

  5. 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

  6. Ameliorative Potentials of Ginger (Z. officinale Roscoe) on Relative Organ Weights in Streptozotocin induced Diabetic Rats

    PubMed Central

    Eleazu, C. O.; Iroaganachi, M.; Okafor, P. N.; Ijeh, I. I.; Eleazu, K. C.

    2013-01-01

    The ameliorating potentials of ginger incorporated feed (10%) on the relative organ weights of Streptozotocin (STZ) induced diabetic rats was investigated. The experiment lasted for three weeks. Results show that administration of 10% ginger feed to the diabetic rats of group 3, resulted in a 29.81% decrease in their resulting hyperglycemia with a corresponding amelioration of elevated urinary protein, sugars, specific gravity as well as renal growth. In addition, administration of the ginger incorporated feeds to the diabetic rats of group 3, resulted in 9.88% increase in body weight with a corresponding 60.24% increase in growth compared with the non-diabetic rats administered standard rat pellets that had 6.21% increase in weight with a corresponding 60.14% increase in growth unlike the diabetic control rats that recorded 28.62% decrease in body weight with a corresponding 239.9% decrease in growth rates. Analysis of the chemical composition of the flour of the ginger incorporated feed indicated that it contained moderate amounts of moisture, crude fibre, alkaloids, saponins, tannins, Fe and Zn but considerable amounts of proteins, lipids, carbohydrates, ash, flavonoids, calcium, magnesium, potassium, phosphorous and energy value. There was no significant difference (P>0.05) in the liver and relative liver weights of the diabetic control rats and the diabetic -ginger treated rats. In addition, there were no significant differences in the kidney weights of the non-diabetic, diabetic control and diabetic treated rats (P>0.05) while there were significant differences in the relative kidney weights of the non-diabetic rats and the diabetic rats treated with ginger feeds (P<0.05). Results show that the use of ginger in the dietary management of diabetes mellitus could be a breakthrough in the search for novel plants that could prevent the development of diabetic glomerular hypertrophy. PMID:23847458

  7. 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

  8. 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.

  9. Oat Protects against Diabetic Nephropathy in Rats via Attenuating Advanced Glycation End Products and Nuclear Factor Kappa B

    PubMed Central

    Al-Malki, Abdulrahman L.

    2013-01-01

    Oat, a rich source of soluble fiber, was considered to have a possible preventive effect on the progression of diabetic nephropathy. The present study aimed to assess this preventive activity in a rat model of diabetic nephropathy. Adult Wister rats were injected by streptozotocin (65 mg/kg). Animals were fed with normal diet or with a diet containing 20% oat (W/W) for 21 weeks. At the end of 21 weeks, all the kidney tissues were collected for various examinations. Our results suggested that oat could decrease the Scr and glucose level in blood of diabetic rats significantly (P < 0.05), and increase the creatinine clearance (P < 0.01). In histopathological examination, oat-fed rats showed a significant decrease in glomerulus segmented sclerosis and incidence of tubule vacuolar degeneration. By ELISA, we reported that oat feeding resulted in decreasing the levels of IL-6 and AGE in serum and kidney homogenate. In addition, the levels of oxidative stress markers were markedly improved as a result of oat feeding. Furthermore, using EMSA, we showed that oat attenuated the activation of NF-κB. Using RT-PCR, we found that oat could downregulate the TGF-β1 and RAGE expression at mRNA levels. This study suggests that oat can suppress diabetic nephropathy in rats effectively and may slow down the renal fibrosis by the disruption of the detrimental AGE-RAGE-NFκB axis. PMID:24223616

  10. The role of AGEs and AGE inhibitors in diabetic cardiovascular disease.

    PubMed

    Thomas, M C; Baynes, J W; Thorpe, S R; Cooper, M E

    2005-06-01

    Prolonged hyperglycemia, dyslipidemia and oxidative stress in diabetes result in the production and accumulation of AGEs. It is now clear that AGEs contribute to the development and progression of cardiovascular disease in diabetes, as well as other complications. AGEs are thought to act through receptor-independent and dependent mechanisms to promote vascular damage, fibrosis and inflammation associated with accelerated atherogenesis. As a result, novel therapeutic agents to reduce the accumulation of AGEs in diabetes have gained interest as potential cardioprotective approaches. A variety of agents have been developed which are examined in detail in this review. These include aminoguanidine, ALT-946, pyridoxamine, benfotiamine, OPB-9195, alagebrium chloride, N-phenacylthiazolium bromide and LR-90. In addition, it has been demonstrated that a number of established therapies have the ability to reduce the accumulation of AGEs in diabetes including ACE inhibitors, angiotensin receptor antagonists, metformin, peroxisome proliferators receptor agonists, metal chelators and some antioxidants. The fact that many of these inhibitors of AGEs are effective in experimental models, despite their disparate mechanisms of action, supports the keystone role of AGEs in diabetic vascular damage. Nonetheless, the clinical utility of AGE inhibition remains to be firmly established. Optimal metabolic and blood pressure control, that is achieved early and sustained indefinitely, remains the best recourse for inhibition of AGEs until more specific interventions become a clinical reality. PMID:16026265

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

    PubMed

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

    2015-03-01

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

  12. Anti-diabetic activity of alcoholic extract of Celosia argentea Linn. seeds in rats.

    PubMed

    Vetrichelvan, Thangarasu; Jegadeesan, Maniappan; Devi, Bangaru Adigalar Uma

    2002-04-01

    Celosia argentea Linn. commonly known as "Cocks Comb" and its seeds are widely used in Indian folk medicine for the treatment of diabetes mellitus. This study was undertaken to evaluate the effect of an alcoholic extract of Celosia argentea seeds (ACAS) on blood glucose and body weight in alloxan-induced diabetic rats. ACAS was found to reduce the increase of blood glucose in alloxan-induced diabetic rats (27.8% at 250 mg/kg and 38.8% at 500 mg/kg body weight). Chronic administration of ACAS significantly (p<0.01) reduced the blood glucose in alloxan-induced diabetic rats for two weeks. Also the extract prevented a decrease in body weight in alloxan-induced diabetic rats. These results suggest that the ACAS possesses anti-diabetic activity in alloxan-induced diabetic rats. PMID:11995938

  13. Altered magnesium transport in slices of kidney cortex from chemically-induced diabetic rats

    SciTech Connect

    Hoskins, B.

    1981-10-01

    The uptake of magnesium-28 was measured in slices of kidney cortex from rats with alloxan-diabetes and from rats with streptozotocin-diabetes of increasing durations. In both forms of chemically-induced diabetes, magnesium-28 uptake by kidney cortex slices was significantly increased over uptake measured in kidney cortex slices from control rats. Immediate institution of daily insulin therapy to the diabetic rats prevented the diabetes-induced elevated uptake of magnesium without controlling blood glucose levels. Late institution of daily insulin therapy was ineffective in restoring the magnesium uptake to control values. These alterations in magnesium uptake occurred prior to any evidence of nephropathy (via the classic indices of proteinuria and increased BUN levels). The implications of these findings, together with our earlier demonstrations of altered calcium transport by kidney cortex slices from chemically-induced diabetic rats, are discussed in terms of disordered divalent cation transport being at least part of the basic pathogenesis underlying diabetic nephropathy.

  14. 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

  15. 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. PMID:21808536

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

    PubMed Central

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

    2014-01-01

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

  17. Alternanthera sessilis Red Ethyl Acetate Fraction Exhibits Antidiabetic Potential on Obese Type 2 Diabetic Rats

    PubMed Central

    Tan, Kok Keong; Kim, Kah Hwi

    2013-01-01

    The antidiabetic potential of Alternanthera sessilis Red was investigated using the obese type 2 diabetic rats induced by high fat diet and streptozotocin. Three fractions (hexane, ethyl acetate, and water) were obtained from the crude ethanol extract of Alternanthera sessilis Red. Alternanthera sessilis Red ethyl acetate fraction (ASEAF) was found to possess the most potent antihyperglycemic effect through oral glucose tolerance test. The ASEAF was subsequently given to the diabetic rats for two weeks. It was found that two-week administration of ASEAF reduces the fasting blood glucose level, triglyceride level, and free fatty acid level of the rats. ASEAF-treated diabetic rats showed higher pancreatic insulin content and pancreatic total superoxide dismutase activity compared to the untreated diabetic rats. Also, the insulin sensitivity indexes suggested that ASEAF ameliorates the insulin resistant state of the diabetic rats. In conclusion, ASEAF could be developed into a potential antidiabetic agent for the management of type 2 diabetes. PMID:23606892

  18. PROGRAMMING OF GROWTH, INSULIN RESISTANCE AND VASCULAR DYSFUNCTION IN OFFSPRING OF LATE GESTATION DIABETIC RATS

    PubMed Central

    Segar, Emily M.; Norris, Andrew W.; Yao, Jian-Rong; Hu, Shanming; Koppenhafer, Stacia L.; Roghair, Robert D.; Segar, Jeffrey L.; Scholz, Thomas D.

    2010-01-01

    The offspring of diabetic mothers (ODM) have an increased risk of developing metabolic and cardiovascular dysfunction. However, few studies have focused on susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late-gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg, i.p.) in pregnant rats on gestational day 13 and partially controlled by twice-daily injections of insulin. At 2 months of age, ODM had slightly better glucose tolerance than controls (p < 0.05), however, by 6 months of age this trend reversed. Hyperinsulinemic-euglycemic clamp revealed insulin resistance in male ODM (p < 0.05). In 6-8 mo old female ODM, aortas showed significantly enhanced contractility to potassium chloride (KCl), endothelin-1 (ET-1) and noradrenaline (NA). No differences in responses to endothelin-1 and noradrenaline were apparent with co-administration of NG-nitro-L-arginine (L-NNA). Relaxation to acetylcholine but not nitroprusside was significantly impaired in female ODM. In contrast, males displayed no between group differences in response to vasoconstrictors while relaxation to nitroprusside and acetylcholine was greater in ODM compared to control animals. Thus, development of diabetes during pregnancy programs gender specific insulin resistance and vascular dysfunction in adult offspring. PMID:19203348

  19. Glucose transporter levels in tissues of spontaneously diabetic Zucker fa/fa rat (ZDF/drt) and viable yellow mouse (Avy/a).

    PubMed

    Slieker, L J; Sundell, K L; Heath, W F; Osborne, H E; Bue, J; Manetta, J; Sportsman, J R

    1992-02-01

    We used antibodies to the fat/muscle glucose transporter (GLUT4) and the liver glucose transporter (GLUT2) to measure levels of these proteins in various tissues of two rodent models of non-insulin-dependent (type II) diabetes mellitus: the obese spontaneously diabetic male Zucker fa/fa rat (ZDF/drt) and the male viable yellow Avy/a obese diabetic mouse. The ZDF/drt strain generally develops overt diabetes associated with decreased plasma insulin levels. Depending on the age of the animals, the ZDF/drt rats can be arbitrarily segregated into age-matched obese, mildly diabetic (blood glucose less than 11 mM) and obese, and severely diabetic (blood glucose greater than 20 mM) groups. Avy/a mice are comparably hyperglycemic but unlike the ZDF/drt rats are severely hyperinsulinemic. In both groups of diabetic animals, GLUT4 in adipose tissue, heart, and skeletal muscle was reduced 25-55%, and GLUT2 in liver was increased 30-40%, relative to lean, age-matched controls. However, when the mildly diabetic ZDF/drt rats were compared to the lean controls, the only significant difference was a 25% reduction of GLUT4 in heart. Within all of the ZDF/drt rats (excluding the lean controls), GLUT2 in liver and GLUT4 in adipose tissue, heart, and skeletal muscle correlated significantly with glycemia. These data suggest that, in these two models of type II diabetes, glucose transporter levels in muscle, adipose tissue, and liver are regulated in a tissue-selective manner in response to changes in insulin and glucose. Furthermore, at least in the ZDF/drt rat, alterations in GLUT2 and/or GLUT4 protein levels appear not to be associated with obesity per se but appear to be secondary to the severely diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1733808

  20. 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

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

    PubMed

    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

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

    PubMed

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

    2013-01-01

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

  3. 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

    2016-01-01

    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. PMID:27517894

  4. 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. PMID:26180820

  5. 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

  6. Myocardial metabolism of pantothenic acid in chronically diabetic rats.

    PubMed

    Beinlich, C J; Naumovitz, R D; Song, W O; Neely, J R

    1990-03-01

    Transport and metabolism of [3H]pantothenic acid ([3H]Pa) was investigated in hearts from control and streptozotocin-induced diabetic rats. In isolated perfused hearts from control animals, the transport of [3H]Pa was linear over 3 h of perfusion when 11 mM glucose was the only exogenous substrate. The in vitro transport of [3H]Pa by hearts from 48-h diabetic rats was reduced by 65% compared to controls and was linear over 2 h of perfusion with no further accumulation of Pa during the third hour. The defect in transport observed in vitro could be corrected by in vivo treatment with 4 U Lente insulin/day for 2 days. In vitro addition of insulin in the presence of 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate had no effect on [3H]Pa transport in hearts from 48-h diabetic rats during 3 h of perfusion. Accumulation of [3H]Pa was not inhibited by inclusion of 0.7 mM amino acids, 1 mM carnitine, 50 microM mersalic acid or 1 mM panthenol, pantoyllactone or pantoyltaurine. Uptake was inhibited by 1 mM nonanoic, octanoic or heptanoic acid, 0.1 mM biotin or 0.25 mM probenecid, suggesting a requirement for the terminal carboxyl group for transport. Transport of pantothenic acid was reduced in hearts from diabetic rats within 24 h of injection of streptozotocin. In vitro accumulation of [3H]Pa decreased to 10% of control 1 week after streptozotocin injection and then remained at 30% of the control value over 10 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141362

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

    PubMed

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

    2015-08-01

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

  8. Protective effect of potato peel powder in ameliorating oxidative stress in streptozotocin diabetic rats.

    PubMed

    Singh, Nandita; Kamath, Vasudeva; Rajini, P S

    2005-06-01

    The potential of dietary potato peel (PP) powder in ameliorating oxidative stress (OS) and hyperglycemia was investigated in streptozotocin (STZ)-induced diabetic rats. In a 4-week feeding trial, incorporation of potato peel powder (5 and 10%) in the diet of diabetic rats was found to significantly reduce the plasma glucose level and also reduce drastically the polyuria of STZ diabetic rats. The total food intake was significantly reduced in the diabetic rats fed 10% PP powder compared to the control diabetic rats. However, the body weight gain over 28 days was nearly four times greater in PP powder supplemented diabetic rats (both at 5 and 10%) compared to the control diabetic rats. PP powder in the diet also decreased the elevated activities of serum transaminases (ALT and AST) and nearly normalized the hepatic MDA and GSH levels as well as the activities of specific antioxidant enzymes in liver of diabetic rats. The result of these studies clearly establishes the modulatory propensity of PP against diabetes induced alterations. Considering that potato peels are discarded as waste and not effectively utilized, these results suggest the possibility that PP waste could be effectively used as an ingredient in health and functional food to ameliorate certain disease states such as diabetes. PMID:16021831

  9. Reversal of Diabetes Through Gene Therapy of Diabetic Rats by Hepatic Insulin Expression via Lentiviral Transduction

    PubMed Central

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

    2012-01-01

    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 × 109 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. PMID:22354377

  10. Immunologic and genetic studies of diabetes in the BB rat.

    PubMed

    Parfrey, N A; Prud'homme, G J; Colle, E; Fuks, A; Seemayer, T A; Guttmann, R D; Ono, S J

    1989-01-01

    The spontaneous development of diabetes in the Bio-Breeding (BB) rat is an excellent model of human insulin-dependent diabetes mellitus (IDDM). Disease expression is dependent on several genetically determined abnormalities, including specific major histocompatibility complex (MHC) genes. At least one MHC class II locus of the U haplotype is a necessary, but not sufficient, condition for disease expression. The immune system of BB rats is markedly abnormal. There is a striking reduction in the number and function of mature cytotoxic/suppressor T cells, a poor proliferative response to mitogens and in mixed lymphocyte culture, poor interleukin-2 production, and a reduced ability to reject skin allografts. While these immune system abnormalities are closely related to the development of diabetes, the immune recognition and effector mechanisms resulting in islet cell destruction are still poorly understood. The hypothesis that MHC class II induction on pancreatic beta cells serves to target these lymphokines, natural killer (NK) cells, macrophages, etc.) have been implicated in islet cell killing. The incidence of IDDM is reduced by immunosuppressive therapy in both rats and humans, further supporting the role of immune mechanisms in this disease. PMID:2651002

  11. In vivo and in vitro evidence of altered nitric oxide metabolism in the spontaneously diabetic, insulin-dependent BB/Edinburgh rat.

    PubMed

    Lindsay, R M; Peet, R S; Wilkie, G S; Rossiter, S P; Smith, W; Baird, J D; Williams, B C

    1997-01-01

    1. Altered vasoreactivity may contribute significantly to the pathogenesis of diabetic vascular complications. This study investigated the effect of (a) insulin-related diabetes, and (b) chronic in vivo administration of N(omega)-nitro-L-arginine ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on mean arterial pressure and in vitro vascular reactivity to noradrenaline in mesenteric arterial bed preparations from spontaneously diabetic, insulin-dependent and treated BB rats, the best animal model of insulin-dependent mellitus (IDDM) currently available. Four groups of animals from the Edinburgh colony (BB/E) of spontaneous diabetic BB rats were studied: age-matched (mean +/- s.e. mean = 156 +/- 2d) non-diabetic (glycated haemoglobin = 3.8 +/- 0.1%) and insulin-treated diabetic (glycated haemoglobin = 6.2 +/- 0.5%; duration of diabetes = 56 +/- 4 d) groups were either L-NAME treated (oral dose = 27 +/- 1 mg kg-1 d-1; duration of treatment from 30 until 153 days of age) or untreated. Although our diabetic BB/E rats do not achieve overall normoglycaemia, individual adjustment of the daily insulin dose administered to every diabetic rat achieves better glycaemic control than previous groups studying altered vascular reactivity and endothelial dysfunction in this animal model of diabetes. 2. Mean arterial pressure (measured directly via indwelling carotid arterial cannulae) was not significantly different between non-diabetic (116 +/- 3 mmHg; n = 10) and diabetic (122 +/- 2 mmHg; n = 12) BB/E rats. L-NAME treatment significantly (P < 0.001) increased mean arterial pressure in both groups (165 +/- 6 mmHg; n = 9 and 142 +/- 4 mmHg; n = 6 respectively) but the degree of hypertension observed in L-NAME-treated diabetic rats was significantly (P < 0.01) attenuated compared to non-diabetic rats treated with L-NAME. 3. Mesenteric arterial bed preparations were cannulated under anesthesia, excised and intralumenally perfused ex vivo with noradrenaline (0.2-20 micro

  12. Lowering plasma 1-deoxysphingolipids improves neuropathy in diabetic rats.

    PubMed

    Othman, Alaa; Bianchi, Roberto; Alecu, Irina; Wei, Yu; Porretta-Serapiglia, Carla; Lombardi, Raffaella; Chiorazzi, Alessia; Meregalli, Cristina; Oggioni, Norberto; Cavaletti, Guido; Lauria, Giuseppe; von Eckardstein, Arnold; Hornemann, Thorsten

    2015-03-01

    1-Deoxysphingolipids (1-deoxySLs) are atypical neurotoxic sphingolipids that are formed by the serine-palmitoyltransferase (SPT). Pathologically elevated 1-deoxySL concentrations cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), an axonal neuropathy associated with several missense mutations in SPT. Oral L-serine supplementation suppressed the formation of 1-deoxySLs in patients with HSAN1 and preserved nerve function in an HSAN1 mouse model. Because 1-deoxySLs also are elevated in patients with type 2 diabetes mellitus, L-serine supplementation could also be a therapeutic option for diabetic neuropathy (DN). This was tested in diabetic STZ rats in a preventive and therapeutic treatment scheme. Diabetic rats showed significantly increased plasma 1-deoxySL concentrations, and L-serine supplementation lowered 1-deoxySL concentrations in both treatment schemes (P < 0.0001). L-serine had no significant effect on hyperglycemia, body weight, or food intake. Mechanical sensitivity was significantly improved in the preventive (P < 0.01) and therapeutic schemes (P < 0.001). Nerve conduction velocity (NCV) significantly improved in only the preventive group (P < 0.05). Overall NCV showed a highly significant (P = 5.2E-12) inverse correlation with plasma 1-deoxySL concentrations. In summary, our data support the hypothesis that 1-deoxySLs are involved in the pathology of DN and that an oral L-serine supplementation could be a novel therapeutic option for treating DN. PMID:25277395

  13. Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Lelkes, P. I.; Hillard, C. J.

    1993-01-01

    Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

  14. 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. PMID:27600979

  15. The impacts of diabetes in pregnancy on hippocampal synaptogenesis in rat neonates.

    PubMed

    Vafaei-Nezhad, S; Hami, J; Sadeghi, A; Ghaemi, K; Hosseini, M; Abedini, M R; Haghir, H

    2016-03-24

    Diabetes during the pregnancy period impairs hippocampal development, and is associated with neurocognitive and neurobehavioral problems in the offspring. Synaptogenesis is one of the most important events in the development of the nervous system, and is known as a mechanism by which the memory process takes place. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles in the hippocampus involved also in learning and memory. The present study aimed to examine the effects of maternal diabetes on the expression and distribution pattern of SYP, as a marker of synaptogenesis, in the developing rat hippocampus using Immunofluorescence staining and real-time PCR. Wistar female rats were maintained as diabetic from a week before pregnancy through parturition and male offspring was euthanized at postnatal day (P) 0, 7, and 14. Our results showed a significant down-regulation in mRNA expression of SYP in the offspring born to diabetic animals at P7, and P14 (P ⩽ 0.05 each). Regarding to the density of SYP expressing hippocampal neurons, we found a marked decrease in the distribution pattern of SYP in all hippocampal subfields of Streptozotocin (STZ)-D group rat neonates, especially in one and two weeks of age (P ⩽ 0.05 each). Moreover, the results revealed no significant changes in either gene expression or distribution pattern of SYP--positive neurons in insulin-treated group compared with the controls. The present study demonstrated that diabetes in pregnancy has negative impacts on synaptogenesis in the offspring's hippocampus. Furthermore, the rigid maternal glycaemia control by insulin treatment in most cases normalized these effects. PMID:26794272

  16. Modeling the Disease Progression from Healthy to Overt Diabetes in ZDSD Rats.

    PubMed

    Choy, Steve; de Winter, Willem; Karlsson, Mats O; Kjellsson, Maria C

    2016-09-01

    Studying the critical transitional phase between healthy to overtly diabetic in type 2 diabetes mellitus (T2DM) is of interest, but acquiring such clinical data is impractical due to ethical concerns and would require a long study duration. A population model using Zucker diabetic Sprague-Dawley (ZDSD) rats was developed to describe this transition through altering insulin sensitivity (IS, %) as a result of accumulating excess body weight and β-cell function (BCF, %) to affect glucose-insulin homeostasis. Body weight, fasting plasma glucose (FPG), and fasting serum insulin (FSI) were collected biweekly over 24 weeks from ZDSD rats (n = 23) starting at age 7 weeks. A semi-mechanistic model previously developed with clinical data was adapted to rat data with BCF and IS estimated relative to humans. Non-linear mixed-effect model estimation was performed using NONMEM. Baseline IS and BCF were 41% compared to healthy humans. BCF was described with a non-linear rise which peaked at 14 weeks before gradually declining to a negligible level. A component for excess growth reflecting obesity was used to affect IS, and a glucose-dependent renal effect exerted a two- to sixfold increase on the elimination of glucose. A glucose-dependent weight loss effect towards the end of experiment was implemented. A semi-mechanistic model to describe the dynamics of glucose and insulin was successfully developed for a rat population, transitioning from healthy to advanced diabetes. It is also shown that weight loss can be modeled to mimic the glucotoxicity phenomenon seen in advanced hyperglycemia. PMID:27245226

  17. Cardiac and thermal homeostasis in the aging Brown Norway rat.

    EPA Science Inventory

    The Brown Norway (BN) rat is a popular strain for aging studies. There is little information on effects of age on baseline cardiac and thermoregulatory parameters in undisturbed BN rats even though cardiac and thermal homeostasis is linked to many pathological deficits in the age...

  18. 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

    2016-06-01

    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. PMID:27012991

  19. Altered glucose kinetics in diabetic rats during Gram-negative infection

    SciTech Connect

    Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J. )

    1987-08-01

    The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge.

  20. Injury to the Endothelial Surface Layer Induces Glomerular Hyperfiltration Rats with Early-Stage Diabetes

    PubMed Central

    Zhang, Chunyang; Meng, Yao; Liu, Qi; Xuan, Miao; Zhang, Lanyu; Deng, Bo; Zhang, Keqin; Liu, Zhimin; Lei, Tao

    2014-01-01

    Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidence in vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes. PMID:24812636

  1. 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

  2. CARBONYLATION OF MYOSIN HEAVY CHAINS IN RAT HEARTS DURING DIABETES

    PubMed Central

    Shao, Chun-Hong; Rozanski, George J.; Nagai, Ryoji; Stockdale, Frank E.; Patel, Kaushik P.; Wang, Mu; Singh, Jaipaul; Mayhan, William G.; Bidasee, Keshore R.

    2010-01-01

    Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for six weeks, while the other group received no treatment. After eight weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca2+- and Mg2+-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-α to MHC-β ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-α and MHC-β. Aminoguandine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca2+-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes. PMID:20359464

  3. 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

  4. Plasma Kallikrein Mediates Retinal Vascular Dysfunction and Induces Retinal Thickening in Diabetic Rats

    PubMed Central

    Clermont, Allen; Chilcote, Tamie J.; Kita, Takeshi; Liu, Jia; Riva, Priscilla; Sinha, Sukanto; Feener, Edward P.

    2011-01-01

    OBJECTIVE Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats. RESEARCH DESIGN AND METHODS We investigated the effects of a selective PK inhibitor, ASP-440, and C1 inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography. RESULTS Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P < 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks’ diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks’ diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 ± 10 μm to 223 ± 13 μm) compared with nondiabetic rats (from 182 ± 8 μm to 193 ± 9 μm). CONCLUSIONS These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening. PMID:21444925

  5. 6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation.

    PubMed

    Ghareib, Salah A; El-Bassossy, Hany M; Elberry, Ahmed A; Azhar, Ahmad; Watson, Malcolm L; Banjar, Zainy Mohammed

    2015-01-01

    The aim of the present study is to investigate the effect and potential mechanism of action of 6-gingerol on alterations of vascular reactivity in the isolated aorta from diabetic rats. Male Wistar rats were divided into two experimental groups, control and diabetics. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg kg(-1)), and the rats were left for 10 weeks to develop vascular complications. The effect of in vitro incubation with 6-gingerol (0.3-3 μM) on the vasoconstrictor response of the isolated diabetic aortae to phenylephrine and the vasodilator response to acetylcholine was examined. Effect of 6-gingerol was also examined on aortae incubated with methylglyoxal as an advanced glycation end product (AGE). To investigate the mechanism of action of 6-gingerol, the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride (100 μM), guanylate cyclase inhibitor methylene blue (5 μM), calcium-activated potassium channel blocker tetraethylammonium chloride (10 mM), and cyclooxygenase inhibitor indomethacin (5 μM) were added 30 minutes before assessing the direct vasorelaxant effect of 6-gingerol. Moreover, in vitro effects of 6-gingerol on NO release and the effect of 6-gingerol on AGE production were examined. Results showed that incubation of aortae with 6-gingerol (0.3-10 μM) alleviated the exaggerated vasoconstriction of diabetic aortae to phenylephrine in a concentration-dependent manner with no significant effect on the impaired relaxatory response to acetylcholine. Similar results were seen in the aortae exposed to methylglyoxal. In addition, 6-gingerol induced a direct vasodilation effect that was significantly inhibited by Nω-nitro-l-arginine methyl ester hydrochloride and methylene blue. Furthermore, 6-gingerol stimulated aortic NO generation but had no effect on AGE formation. In conclusion, 6-gingerol ameliorates enhanced vascular contraction in diabetic aortae, which may be partially

  6. Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

    PubMed Central

    Hu, Ji; Song, Zhen-Yuan; Zhang, Hong-Hong; Qin, Xin; Hu, Shufen; Jiang, Xinghong; Xu, Guang-Yin

    2016-01-01

    Background/Aims Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. Methods Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. Results STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. Conclusions Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes. PMID:26459453

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

    PubMed

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

    2015-10-01

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

  8. Goshajinkigan (Chinese herbal medicine niu-che-sen-qi-wan) improves insulin resistance in diabetic rats via the nitric oxide pathway.

    PubMed

    Hu, Xiaochen; Sato, Juichi; Bajotto, Gustavo; Khookhor, Oyun; Ohsawa, Isao; Oshida, Yoshiharu; Sato, Yuzo

    2010-02-01

    Goshajinkigan (GJG), an aqueous extract of a combination of 10 herbal medicines, is widely used for the treatment of diabetic neuropathy in Japan. In this study, the effect of GJG on insulin-induced glucose disposal in normal and streptozotocin (STZ) diabetic rats was analyzed using the euglycemic clamp technique. Male Wistar rats, aged 9 weeks, were randomly assigned to six groups: group NS, normal rats receiving saline; group NG, normal rats receiving GJG (800 mg x kg(-1) x day(-1), p.o.); group NGL, normal rats receiving GJG + N(G)-monomethyl-L-arginine (L-NMMA, 1 mg x kg(-1) x min(-1), i.v.); group DS, diabetic rats receiving saline; group DG, diabetic rats receiving GJG; group DGL, diabetic rats receiving GJG + L-NMMA. After daily oral administrations of saline or GJG for one week, euglycemic clamp experiments were performed. The metabolic clearance rates of glucose (MCR) in the DS, DG, and DGL groups (8.7 +/- 2.9, 18.2 +/- 2.5, and 8.1 +/- 1.8 ml x kg(-1) x min(-1), respectively) were significantly lower than those in the NS, NG, and NGL groups (24.1 +/- 4.5, 24.5 +/- 3.1, and 22.2 +/- 2.1 ml x kg(-1) x min(-1), respectively). In addition, the MCR in the DG group was significantly higher than that in the DS and DGL groups, while no significant difference was detected among the NS, NG, and NGL groups. Furthermore, the amelioration of insulin resistance by GJG in diabetic rats was hampered by L-NMMA infusion. These results suggest that daily GJG administrations ameliorate insulin resistance in STZ-diabetic rats, and that the nitric oxide pathway may mediate the effect of GJG. PMID:20229701

  9. Effects of acupuncture stimulation on blood glucose concentration in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model for type-2 diabetes mellitus

    PubMed Central

    Nakamura, Hironori; Ishigami, Tatsuyo; Kawase, Yosihyuki; Yamada, Atsushi; Minagawa, Munenori; Fukuta, Hiroyasu; Kurono, Yasuzo; Suzuki, Hikaru

    2014-01-01

    Background Effects of acupuncture stimulation on blood glucose concentration and body weight were investigated in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model for type-2 diabetes. Material/Methods Three groups of rats were used: OLETF, acupuncture-treated OLETF (AcOLETF), and Long-Evans Tokushima Otsuka (LETO) rats (as control for the OLETF rats). In AcOLETF rats, acupuncture stimulation was applied twice a week to 6 points (zhongwan, tianshu, qihai, ganshu, pishu, shenshu) and changes in blood glucose concentration and body weight were measured. Results Initially, at 6 weeks old, there was no significant difference in blood glucose levels between groups. Blood glucose levels increased with age in each group, reaching a maximum of about 430 mg/dl at 37 weeks in OLETF rats. In AcOLETF rats, blood glucose levels increased at a slower rate than in OLETF rats, reaching a maximum concentration of about 280 mg/dl at 37 weeks of age, significantly lower than that in OLETF rats. The concentration of blood glucose in LETO rats had stabilized at a maximum value of 120~140 mg/dl by 16 weeks, remaining at this level for up to 39 weeks. In each group, body weight increased with age and was not affected by acupuncture treatment. Conclusions In OLETF rats, acupuncture treatment significantly reduced blood glucose levels, but not their body weight, suggesting that acupuncture therapy was effective in preventing the development of type-2 diabetes mellitus. PMID:24841896

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

    PubMed Central

    2012-01-01

    Background Traditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of C. papaya leaves in diabetic rats. Several studies have reported that some parts of the C. papaya plant exert hypoglycemic effects in both animals and humans. Methods Diabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ). The aqueous extract of C. papaya was administered in three different doses (0.75, 1.5 and 3 g/100 mL) as drinking water to both diabetic and non-diabetic animals during 4 weeks. Results The aqueous extract of Carica papaya (0.75 g and 1.5 g/100 mL) significantly decreased blood glucose levels (p<0.05) in diabetic rats. It also decreased cholesterol, triacylglycerol and amino-transferases blood levels. Low plasma insulin levels did not change after treatment in diabetic rats, but they significantly increased in non-diabetic animals. Pancreatic islet cells were normal in non-diabetic treated animals, whereas in diabetic treated rats, C. papaya could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, C. papaya prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of C. papaya extract was also detected in diabetic rats. Conclusions This study showed that the aqueous extract of C. papaya exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas. PMID:23190471

  11. Streptozotocin induced diabetes as a model of phrenic nerve neuropathy in rats.

    PubMed

    Rodrigues Filho, Omar Andrade; Fazan, Valéria Paula Sassoli

    2006-03-15

    Phrenic neuropathies are increasingly recognized in peripheral neuropathies but reports on experimental models of the phrenic nerves diabetic neuropathy are scanty. In the present study, we investigated the phrenic nerve neuropathy, due to experimental diabetes induced by streptozotocin (STZ) and the evolution of this neuropathy in diabetic rats treated with insulin. Proximal and distal segments of the left and right phrenic nerves were morphologically and morphometrically evaluated, from rats rendered diabetic for 12 weeks, by injection of STZ. Control rats received vehicle. Treated rats received a single subcutaneous injection of insulin on a daily basis. The nerves were prepared for light microcopy study by means of conventional techniques. Morphometry was carried out with the aid of computer software. The phrenic nerves of diabetic rats showed smaller myelinated axon diameters compared to controls. The g ratio was significantly smaller for myelinated fibers from diabetic rats compared to controls. Insulin treatment prevented these alterations. Histograms of size distribution for myelinated fibers and axons from control rats were bimodal. For diabetic animals, the myelinated fiber histogram was bimodal while the axon distribution turned to be unimodal. Insulin treatment also prevented these alterations. Our results confirm the phrenic nerve neuropathy in this experimental model of diabetes and suggest that conventional insulin treatment was able to prevent and/or correct the myelinated axon commitment by diabetes. PMID:16125783

  12. Stress and behavior in streptozotocin diabetic rats: biochemical correlates of passive avoidance learning.

    PubMed

    Bellush, L L; Rowland, N E

    1989-02-01

    Retention of one-trial passive avoidance training was compared in diabetic and nondiabetic rats. Also compared were corticosterone concentrations associated with both training and retention testing, catecholamine excretion related to training, and regional brain catecholamine concentrations accompanying retention testing. Diabetic rats showed significantly better retention for the task than did nondiabetic rats. Associated with retention differences, diabetic rats had higher epinephrine excretion and nondiabetic rats had lower excretion after footshock training relative to baseline measures. Norepinephrine excretion was elevated in diabetics both in baseline measurement and during the 24 hr following footshock training. No differences were found in baseline or stimulated corticosterone concentration between diabetic and nondiabetic rats. Diabetic rats had higher concentrations of norepinephrine (NE) and dopamine (DA) and lower 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in hypothalamus and higher NE in brain stem and amygdala than did nondiabetics, although both diabetic and nondiabetic rats had reduced DA and NE following retention testing. The results indicate that there are biochemical alterations in diabetes that may have important behavioral impact. PMID:2522305

  13. Ameliorative anti-diabetic activity of dangnyosoko, a Chinese herbal medicine, in diabetic rats.

    PubMed

    Kim, Jong-Dae; Kang, Seock-Man; Park, Mee-Yeon; Jung, Tae-Young; Choi, Hae-Yun; Ku, Sae-Kwang

    2007-06-01

    The preventive anti-diabetic effect of dangnyosoko (DNSK), a Chinese herbal medicine, was evaluated in STZ-induced diabetic rats. DNSK was orally administered once a day from 3 d after STZ-induction at 100, 200, and 500 mg/kg for 4 weeks, and the results were compared to those for glibenclamide. Dramatic decreases in body weight and plasma insulin levels and increases in blood and urine glucose levels were detected in STZ-induced diabetic animals with disruption and disappearance of pancreatic islets and increases in glucagon- and decreases in insulin-producing cells. However, these diabetic changes were significantly and dose-dependently inhibited by treatment with DNSK, and DNSK at 100 mg/kg showed more favorable effects than glibenclamide at 5 mg/kg. Based on these results, it is thought that DNSK has favorable effects in ameliorating changes in blood and urine glucose levels and body weight, and that histopathological changes in the pancreas in STZ induce diabetes. PMID:17587685

  14. Functional and biochemical characteristics of urinary bladder muscarinic receptors in long-term alloxan diabetic rats

    PubMed Central

    Rocha, Jeová Nina

    2015-01-01

    Objective To re-examine the function of the urinary bladder in vivo as well as to determine the functional and biochemical characteristics of bladder muscarinic receptors in long-term alloxan-induced diabetes rats. Methods Two-month-old male Wistar rats were injected with alloxan and the animals showing blood glucose levels >300mg/dL together with age-paired untreated animals were kept for 11 months. Body weight, bladder weight, blood glucose, and urinary volume over a period of 24 hours were determined in both groups of animals. A voiding cystometry in conscious control and diabetic rats was performed to determine maximal micturition pressure, micturition contraction interval and duration as well as voided and post-voiding residual volume. In addition, concentration-response curves for bethanechol in isolated bladder strips, as well as [3H]-N methyl-scopolamine binding site characteristics in bladder homogenates were determined. Results Mean bladder weight was 162.5±21.2mg versus 290±37.9mg in control and treated animals, respectively (p<0.05). Micturition contraction amplitude (34.6±4.7mmHg versus 49.6±2.5mmHg), duration (14.5±1.7 seconds versus 23.33±4.6 seconds) and interval (87.5±17.02 seconds versus 281.11±20.24 seconds) were significantly greater in alloxan diabetic rats. Voided urine volume per micturition contraction was also significantly higher in diabetic animals. However the post-voiding residual volume was not statistically different. Bethanechol potency (EC50 3µM versus 5µM) and maximal effect (31.2±5.9g/g versus 36.1±6.8g/g) in isolated bladder strips as well as number (169±4fmol/mg versus 176±3fmol/mg protein) and affinity (0.69±0.1nM versus 0.57±0.1nM) of bladder muscarinic receptors were also not statistically different. Conclusion Bladder function in vivo is altered in chronic alloxan-induced diabetes rats without changes in functional and biochemical characteristics of bladder muscarinic receptors. PMID:26466064

  15. Effect of Vanadate on Elevated Blood Glucose and Depressed Cardiac Performance of Diabetic Rats

    NASA Astrophysics Data System (ADS)

    Heyliger, Clayton E.; Tahiliani, Arun G.; McNeill, John H.

    1985-03-01

    The trace element vanadium has an unclear biological function. Vanadate, an oxidized form of vanadium, appears to have an insulin-like action. The effect of vanadate on blood glucose and cardiac performance was assessed in female Wistar rats 6 weeks after they were made diabetic with streptozotocin. When vanadate was administered for a 4-week period to the diabetic rats, their blood glucose was not significantly different from that of nondiabetic controls despite a low serum insulin. In contrast, blood glucose was increased about threefold in the diabetic rats that were not treated with vanadate; these rats also had low insulin levels. Cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the vanadate-treated diabetic animals was not significantly different from that of nondiabetic controls. Thus vanadate controlled the high blood glucose and prevented the decline in cardiac performance due to diabetes.

  16. Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression.

    PubMed

    Siddiqui, Shabeena; Ahsan, Haseeb; Khan, Mohammad Rashid; Siddiqui, Waseem A

    2013-12-01

    Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175-200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. PMID:24041758

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

    PubMed Central

    Qinna, Nidal A; Badwan, Adnan A

    2015-01-01

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

  18. Measurement of Retinal Blood Flow Rate in Diabetic Rats: Disparity Between Techniques Due to Redistribution of Flow

    PubMed Central

    Leskova, Wendy; Watts, Megan N.; Carter, Patsy R.; Eshaq, Randa S.; Harris, Norman R.

    2013-01-01

    Purpose. Reports of altered retinal blood flow in experimental models of type I diabetes have provided contrasting results, which leads to some confusion as to whether flow is increased or decreased. The purpose of our study was to evaluate early diabetes-induced changes in retinal blood flow in diabetic rats, using two distinctly different methods. Methods. Diabetes was induced by injection of streptozotocin (STZ), and retinal blood flow rate was measured under anesthesia by a microsphere infusion technique, or by an index of flow based on the mean circulation time between arterioles and venules. Measurements in STZ rats were compared to age-matched nondiabetic controls. In addition, the retinal distribution of fluorescently-labeled red blood cells (RBCs) was viewed by confocal microscopy in excised flat mounts. Results. Retinal blood flow rate was found to decrease by approximately 33% in the STZ rats compared to controls (P < 0.001) as assessed by the microsphere technique. However, in striking contrast, the mean circulation time through the retina was found to be almost 3× faster in the STZ rats (P < 0.01). This contradiction could be explained by flow redistribution through the superficial vessels of the diabetic retina, with this possibility supported by our observation of significantly fewer RBCs flowing through the deeper capillaries. Conclusions. We conclude that retinal blood flow rate is reduced significantly in the diabetic rat, with a substantial decrease of flow through the capillaries due to shunting of blood through the superficial layer, allowing rapid transit from arterioles to venules. PMID:23572104

  19. 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

  20. Evaluation of neonatally-induced mild diabetes in rats: Maternal and fetal repercussions

    PubMed Central

    2010-01-01

    Many experimental studies have been performed to evaluate mild diabetes effects. However, results are divergent regarding glycemia and insulin measurement, fetal macrossomia, and placental weights. The aim was to investigate repercussions of neonatally-induced mild diabetes on the maternal organism and presence of congenital defects in their offspring in other mild diabetes model. On the day of birth, female offspring were distributed into two groups: Group streptozotocin (STZ): received 100 mg STZ/kg body weight, and Control Group: received vehicle in a similar time period. Maternal weights and glycemias were determined at days 0, 7, 14 and 21 of pregnancy. At day 21 of pregnancy, the rats were anesthetized and a laparotomy was performed to weigh and analyze living fetuses and placentas. The fetuses were classified as small (SPA), appropriate (APA) and large (LPA) for pregnancy age. Fetuses were also analyzed for the presence of external anomalies and processed for skeletal anomaly and ossification sites analysis. Statistical significance was considered as p < 0.05. In STZ group, there was increased glycemia at 0 and 14 days of pregnancy, lower weights throughout pregnancy, higher placental weight and index, an increased proportion of fetuses classified as SPA and LPA, and their fetuses presented with an increased frequency of abnormal sternebra, and absent cervical nuclei, which were not enough to cause the emergence of skeletal anomalies. Thus, this study shows that mild diabetes altered fetal development, characterized by intrauterine growth restriction. Further, the reached glycemia does not lead to any major congenital defects in the fetuses of streptozotocin-induced mild diabetic rats. PMID:20529353

  1. DNA aptamer raised against advanced glycation end products (AGEs) improves glycemic control and decreases adipocyte size in fructose-fed rats by suppressing AGE-RAGE axis.

    PubMed

    Ojima, A; Matsui, T; Nakamura, N; Higashimoto, Y; Ueda, S; Fukami, K; Okuda, S; Yamagishi, S

    2015-04-01

    Advanced glycation end products (AGEs) decrease adiponectin expression and suppress insulin signaling in cultured adipocytes through the interaction with a receptor for AGEs (RAGE) via oxidative stress generation. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. This study examined the effects of AGE-aptamer on adipocyte remodeling, AGE-RAGE-oxidative stress axis, and adiponectin expression in fructose-fed rats. Although AGE-aptamer treatment by an osmotic mini pump for 8 weeks did not affect serum insulin levels, it significantly decreased average fasting blood glucose and had a tendency to inhibit body weight gain in fructose-fed rats. Furthermore, AGE-aptamer significantly suppressed the increase in adipocyte size and prevented the elevation in AGEs, RAGE, and an oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), levels in adipose tissues of fructose-fed rats at 14-week-old, while it restored the decrease in adiponectin mRNA levels. Our present study suggests that AGE-aptamer could improve glycemic control and prevent adipocyte remodeling in fructose-fed rats partly by suppressing the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for fructose-induced metabolic derangements. PMID:25105541

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

    PubMed Central

    Zhao, TingTing; Sun, SiFan; Zhang, HaoJun; Huang, XiaoRu; Yan, MeiHua; Dong, Xi; Wen, YuMin; Wang, Hua; Lan, Hui Yao; Li, Ping

    2016-01-01

    Objective Inflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF), a traditional Chinese medicine, on DN. Research Design and Methods Protective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined. Results We found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-κB signaling, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1β, TNFα), chemokine (MCP-1), and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-β/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-β/Smad3 and NF-κB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7. Conclusions The present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-κB-driven renal inflammation and TGF-β/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN. PMID:26807792

  3. Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

    SciTech Connect

    Siddiqui, Shabeena; Ahsan, Haseeb; Khan, Mohammad Rashid; Siddiqui, Waseem A.

    2013-12-01

    Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. - Highlights: • The nephroprotective effect of TRF in type-2 diabetic rats was investigated. • Treatment with TRF improved glycemic status, lipid profile and renal functions in rats

  4. 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. PMID:26102179

  5. 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

  6. 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

  7. S-Allyl cysteine improves nonalcoholic fatty liver disease in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats via regulation of hepatic lipogenesis and glucose metabolism

    PubMed Central

    Takemura, Shigekazu; Minamiyama, Yukiko; Kodai, Shintaro; Shinkawa, Hiroji; Tsukioka, Takuma; Okada, Shigeru; Azuma, Hideki; Kubo, Shoji

    2013-01-01

    It is important to prevent and improve diabetes mellitus and its complications in a safe and low-cost manner. S-Allyl cysteine, an aged garlic extract with antioxidant activity, was investigated to determine whether S-allyl cysteine can improve type 2 diabetes in Otsuka Long-Evans Tokushima Fatty rats with nonalcoholic fatty liver disease. Male Otsuka Long-Evans Tokushima Fatty rats and age-matched Long-Evans Tokushima Otsuka rats were used and were divided into two groups at 29 weeks of age. S-Allyl cysteine (0.45% diet) was administered to rats for 13 weeks. Rats were killed at 43 weeks of age, and detailed analyses were performed. S-Allyl cysteine improved hemoglobinA1c, blood glucose, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, S-allyl cysteine normalized plasma insulin levels. S-Allyl cysteine activated the mRNA and protein expression of both peroxisome proliferator-activated receptor α and γ, as well as inhibiting pyruvate dehydrogenase kinase 4 in Otsuka Long-Evans Tokushima Fatty rat liver. Sterol regulatory element-binding protein 1c and forkhead box O1 proteins were normalized by S-allyl cysteine in Otsuka Long-Evans Tokushima Fatty rat liver. In conclusions, these findings support the hypothesis that S-allyl cysteine has diabetic and nonalcoholic fatty liver disease therapeutic potential as a potent regulating agent against lipogenesis and glucose metabolism. PMID:24062606

  8. Antihyperglycaemic and anti-oxidant properties of Anoectochilus formosanus in diabetic rats.

    PubMed

    Shih, Chun-Ching; Wu, Yueh-Wern; Lin, Wen-Chuan

    2002-08-01

    1. In the present study, we investigated aqueous extracts of Anoectochilus formosanus (AFE) for antihyperglycaemic and anti-oxidant effects in diabetic rats induced by streptozotocin (STZ). 2. Diabetic rats were randomly divided into groups and treated orally by gavage with vehicle (distilled water) or AFE (1 and 2 g/kg), once a day for 21 days. 3. At the end of the 21 day period, AFE (2 g/kg) significantly reduced fasting blood glucose, serum fructosamine, triglycerides and total cholesterol compared with vehicle-treated diabetic rats. In vehicle-treated diabetic rats, levels of renal lipid peroxidation were increased, whereas glutathione concentrations were not affected. Renal lipid peroxidation levels were significantly lower and renal reduced glutathione (GSH) concentrations were significantly higher in AFE-treated diabetic rats compared with vehicle-treated diabetic rats. The diabetic kidney in the vehicle-treated group showed a decrease in catalase, but the activity of glutathione peroxidase (GSH-Px) was increased. 4. The activity of catalase, but not GSH-Px, was significantly reversed by AFE treatment. These results indicate that AFE (1 and 2 g/kg) not only possesses an antihyperglycemic effect, but that it may also reduce oxidative stress in diabetic rats. PMID:12100000

  9. FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy

    PubMed Central

    Deliyanti, Devy; Zhang, Yuan; Khong, Fay; Berka, David R.; Stapleton, David I.; Kelly, Darren J.; Wilkinson-Berka, Jennifer L.

    2015-01-01

    Diabetic retinopathy features inflammation as well as injury to glial cells and the microvasculature, which are influenced by hypertension and overactivity of the renin-angiotensin system. FT011 is an anti-inflammatory and anti-fibrotic agent that has been reported to attenuate organ damage in diabetic rats with cardiomyopathy and nephropathy. However, the potential therapeutic utility of FT011 for diabetic retinopathy has not been evaluated. We hypothesized that FT011 would attenuate retinopathy in diabetic Ren-2 rats, which exhibit hypertension due to an overactive extra-renal renin-angiotensin system. Diabetic rats were studied for 8 and 32 weeks and received intravitreal injections of FT011 (50 μM) or vehicle (0.9% NaCl). Comparisons were to age-matched controls. In the 8-week study, retinal inflammation was examined by quantitating vascular leukocyte adherence, microglial/macrophage density and the expression of inflammatory mediators. Macroglial Müller cells, which exhibit a pro-inflammatory and pro-angiogenic phenotype in diabetes, were evaluated in the 8-week study as well as in culture following exposure to hyperglycaemia and FT011 (10, 30, 100 μM) for 72 hours. In the 32-week study, severe retinal vasculopathy was examined by quantitating acellular capillaries and extracellular matrix proteins. In diabetic rats, FT011 reduced retinal leukostasis, microglial density and mRNA levels of intercellular adhesion molecule-1 (ICAM-1). In Müller cells, FT011 reduced diabetes-induced gliosis and vascular endothelial growth factor (VEGF) immunolabeling and the hyperglycaemic-induced increase in ICAM-1, monocyte chemoattractant protein-1, CCL20, cytokine-induced neutrophil chemoattractant-1, VEGF and IL-6. Late intervention with FT011 reduced acellular capillaries and the elevated mRNA levels of collagen IV and fibronectin in diabetic rats. In conclusion, the protective effects of FT011 in cardiorenal disease extend to key elements of diabetic retinopathy and

  10. Suggested mechanism for the selective excretion of glucosylated albumin. The effects of diabetes mellitus and aging on this process and the origins of diabetic microalbuminuria.

    PubMed

    Kowluru, A; Kowluru, R; Bitensky, M W; Corwin, E J; Solomon, S S; Johnson, J D

    1987-11-01

    In previous studies in the Sprague-Dawley rat, Williams and coworkers reported the phenomenon of selective urinary excretion of glucosylated albumin (editing, i.e., the percent glucosylation of urinary albumin is more than that of plasma albumin) by the mammalian kidney. Ghiggeri and coworkers subsequently found that the extent of editing is reduced in human diabetics. Moreover, the reduction in editing in diabetes correlates inversely with levels of microalbuminuria. We also find reduction in the extent of editing in diabetic humans. We find a striking inverse correlation not only with the magnitude of microalbuminuria but also with the extent of plasma albumin glucosylation. In contrast, we found little correlation between the reduction in editing and the duration of diabetes in human subjects. Stz induced diabetes in the Sprague-Dawley rat is associated with a striking and rapid reduction in editing which develops virtually with the same kinetics exhibited by the appearance of hyperglycemia. This loss of editing is rapidly reversed by daily administration of insulin but not by aldose reductase inhibitors. Mannitol infusion in anesthetized Wistar rats resulted in an increase in urine volume, GFR, and microalbuminuria, and was also accompanied by a marked reduction in editing. This reduction was rapidly reversed by a cessation of mannitol infusion. We propose here that glucosylated albumin (in contrast to unmodified albumin) is not reabsorbed by the proximal tubule, and thus, is preferentially excreted in the urine. We postulate that the increase in GFR which emerges as a consequence of increased plasma osmolality in diabetes mellitus delivers more albumin to the proximal tubule than can be reabsorbed. This results in a dilution of excreted glucosylated albumin molecules by excreted unmodified albumin, which appears as the early microscopic albuminuria of diabetes. Paradoxically, the fall in apparent editing is accompanied by an absolute increase in the total

  11. GP-1447, an inhibitor of aldose reductase, prevents the progression of diabetic cataract in rats.

    PubMed

    Kawakubo, Ken; Mori, Asami; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2012-01-01

    We examined the effects of GP-1447 (3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]-5-methylphenyl acetic acid) on existing cataracts and sorbitol content in the lens in rats with streptozotocin-induced diabetes. GP-1447 is an inhibitor of aldose reductase, which is the first enzyme in the polyol pathway. Cataracts in the central region of the lens were observed in 7 of 14 eyes (50%) by the fifth week after induction of diabetes, and development of mature cataracts was observed in most lenses by the ninth week. In diabetic rats that received GP-1447 treatment beginning in the fifth week after induction of diabetes, progression of cataracts was observed for 1 week after initiation of treatment. Thereafter, the severity of cataracts did not change substantially. Sorbitol levels in the lens peaked during the first week of diabetes, and this increase was maintained during the 9-week observation period. Elevated sorbitol levels in the lenses of diabetic rats gradually declined after GP-1447 treatment was started on the fifth week after induction of diabetes. Cataracts and sorbitol elevation were not observed in the lenses of controls or diabetic rats treated with GP-1447 immediately after induction of diabetes. These results suggest that the polyol pathway plays an important role in both the appearance and progression of cataracts in diabetic rats. Inhibition of aldose reductase could significantly prevent progression of existing cataracts. PMID:22687477

  12. [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. PMID:26904817

  13. 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

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

    PubMed Central

    2014-01-01

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

  15. 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. PMID:20873419

  16. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    SciTech Connect

    Bass, V.; Gordon, C.J.; Jarema, K.A.; MacPhail, R.C.; Cascio, W.E.; Phillips, P.M.; Ledbetter, A.D.; Schladweiler, M.C.; Andrews, D.; Miller, D.; Doerfler, D.L.; Kodavanti, U.P.

    2013-12-15

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α{sub 2}-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone

  17. 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. PMID:25539049

  18. Oral hypoglycaemic activity of Ipomoea aquatica in streptozotocin-induced, diabetic wistar rats and Type II diabetics.

    PubMed

    Malalavidhane, T S; Wickramasinghe, S M D N; Perera, M S A; Jansz, E R

    2003-11-01

    Ipomoea aquatica Forsk is a common green leafy vegetable consumed in many parts of the world. The present study was designed to investigate the oral hypoglycaemic activity of Ipomea aquatica in streptozotocin induced diabetic Wistar rats, and Type II diabetic patients. Experimental diabetes was induced with streptozotocin in Wistar rats. The rats were then divided into test and control groups. In addition to the standard feed given to both groups the test was fed with the shredded leaves of Ipomoea aquatica (3.4 g/kg) for one week. Type II diabetic patients were subjected to a glucose challenge before and after a single dose of blended I. aquatica. Patients acted as their own controls. The results revealed that consumption of the shredded, fresh, edible portion of I. aquatica for one week, effectively reduced the fasting blood sugar level of streptozotocin-induced diabetic rats (p = 0.01). When subjected to a glucose challenge, the Type II diabetic subjects showed a significant reduction (p = 0.001) in the serum glucose concentration 2 h after the glucose load. However, it was not significantly reduced at 1 h (p < 0.09) post glucose load. There was a 29.4% decrease in the serum glucose concentration of the diabetic patients when treated with the plant extract. PMID:14595595

  19. 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

  20. Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

    PubMed Central

    2011-01-01

    Background Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF). Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. Methods After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28%) or a high-salt diet (5.5%) starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food) (ZDF+S+E), hydralazine (25 mg/kg per day) (ZDF+S+H), or no treatment (ZDF+S). Rats on normal salt-diet were assigned to eplerenone (ZDF+E) or no treatment (ZDF). Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL) or high-salt diet (ZL+S) serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio) and vascular stiffness (strain and stress) were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. Results Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition with less

  1. 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

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

    PubMed Central

    Sha, Hong; Zhao, Dong; Tong, Xiaolin; Zhao, Jingbo

    2016-01-01

    Previous study demonstrated that Chang Run Tong (CRT) could partly restore the colon remodeling in streptozotocin- (STZ-) induced diabetic rats. Here we investigated the mechanisms of such effects of CRT. Diabetes was induced by a single injection of 40 mg/kg of STZ. CRT was poured into the stomach by gastric lavage once daily for 60 days. The remodeling parameters were obtained from diabetic (DM), CRT treated diabetic (T1, 50 g/kg; T2, 25 g/kg), and normal (Con) rats. Expressions of advanced glycation end product (AGE), AGE receptor, transforming growth factor-β1 (TGF-β1), and TGF-β1 receptor in the colon wall were immunochemically detected and quantitatively analyzed. The association between the expressions of those proteins and the remodeling parameters was analyzed. The expressions of those proteins were significantly higher in different colon layers in the DM group (P < 0.05, P < 0.01) and highly correlated to the remodeling parameters. Furthermore, the expressions of those proteins were significantly decreased in the T1 group (P < 0.05, P < 0.01) but not in the T2 group (P > 0.05). The corrective effect on the expressions of those proteins is likely to be one molecular pathway for the improvement of CRT on the diabetes-induced colon remodeling. PMID:26839890

  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. Antihyperglycemic activity of Catharanthus roseus leaf powder in streptozotocin-induced diabetic rats

    PubMed Central

    Rasineni, Karuna; Bellamkonda, Ramesh; Singareddy, Sreenivasa Reddy; Desireddy, Saralakumari

    2010-01-01

    Catharanthus roseus Linn (Apocynaceae), is a traditional medicinal plant used to control diabetes, in various regions of the world. In this study we evaluated the possible antidiabetic and hypolipidemic effect of C. roseus (Catharanthus roseus) leaf powder in diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 55 mg/kg body wt) to male Wistar rats. The animals were divided into four groups: Control, control-treated, diabetic, and diabetic-treated group. Diabetic-treated and control-treated rats were treated with C. roseus leaf powder suspension in 2 ml distilled water, orally (100 mg/kg body weight/day/60 days). In diabetic rats (D-group) the plasma glucose was increased and the plasma insulin was decreased gradually. In the diabetic-treated group lowering of plasma glucose and an increase in plasma insulin were observed after 15 days and by the end of the experimental period the plasma glucose had almost reached the normal level, but insulin had not. The significant enhancement in plasma total cholesterol, triglycerides, LDL and VLDL-cholesterol, and the atherogenic index of diabetic rats were normalized in diabetic-treated rats. Decreased hepatic and muscle glycogen content and alterations in the activities of enzymes of glucose metabolism (glycogen phosphorylase, hexokinase, phosphofructokinase, pyruvate kinase, and glucose-6-phosphate dehydrogenase), as observed in the diabetic control rats, were prevented with C. roseus administration. Our results demonstrated that C. roseus with its antidiabetic and hypolipidemic properties could be a potential herbal medicine in treating diabetes. PMID:21808566

  5. Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia.

    PubMed

    Liang, Wei; Luo, Zhonghua; Ge, Shuhua; Li, Mo; Du, Junjie; Yang, Min; Yan, Ming; Ye, Zhengxu; Luo, Zhuojing

    2011-11-16

    Diabetic osteopenia can result in an increased incidence of bone fracture and a delay in fracture healing. Quercetin, one of the most widely distributed flavonoids in plants, possesses antioxidant property and beneficial effect on osteoporosis in ovariectomized mice. All these properties make quercetin a potential candidate for controlling the development of diabetic osteopenia. Therefore, the present study was designed to investigate the putative beneficial effect of quercetin on diabetic osteopenia in rats. Diabetes mellitus was induced by streptozotocin. The diabetic rats received daily oral administration of quercetin (5mg/kg, 30 mg/kg and 50mg/kg) for 8 weeks, which was started at 4 weeks after streptozotocin injection. Quercetin at 5mg/kg showed little effect on diabetic osteopenia, while quercetin at 30 mg/kg and 50mg/kg could increase the decreased serum osteocalcin, serum alkaline phosphatase activity, and urinary deoxypyridinoline in diabetic rats. In addition, quercetin (30 mg/kg and 50mg/kg) could partially reverse the decreased biomechanical quality and the impaired micro-architecture of the femurs in diabetic rats. Histomorphometric analysis showed that both decreased bone formation and resorption were observed in diabetic rats, which was partially restored by quercetin (30 mg/kg and 50mg/kg). Further investigations showed that quercetin significantly lowered the oxidative DNA damage level, up-regulated the total serum antioxidant capability and the activity of serum antioxidants in diabetic rats. All those findings indicate the beneficial effect of quercetin on diabetic osteopenia in rats, and raise the possibility of developing quercetin as potential drugs or an ingredient in diet for controlling diabetic osteopenia. PMID:21914440

  6. Selective inhibition of NADPH oxidase reverses the over contraction of diabetic rat aorta.

    PubMed

    Rehman, Atif Ur; Dugic, Elma; Benham, Chris; Lione, Lisa; Mackenzie, Louise S

    2014-01-01

    Abnormal vascular responsiveness in diabetes has been attributed to a number of changes in contractile pathways, affected in part by the overproduction of reactive oxygen species (ROS). It has been reported that NADPH oxidase (NOX) is increased in diabetic (streptozotocin treated; STZ) rat arteries; however the pharmacological agents used to inhibit NOX activity are known to be unsuitable for in vitro studies and have a high level of non-selectivity. Here we have used the highly selective NOX inhibitor VAS2870 in diabetic rat aorta and compared its effects with apocynin, SOD, and allopurinol on phenylephrine and U46619 induced contraction. Male Wistar rats were injected intraperitoneally with 65mg/kg STZ and development of diabetes was confirmed by testing blood glucose levels. Rats were killed by CO2 asphyxiation, and the thoracic aorta removed and mounted in an organ bath under a tension of 1g. Diabetic rat aortas exhibit a greatly increased response to phenylephrine, which was reduced to a level consistent with control rat aorta by 10(-5)M VAS2870 and 150U/ml SOD. Incubation with VAS2870 led to an increase in normal rat aorta contraction, but led to a significant reduction in phenylephrine and U46619 induced tone in diabetic rat aorta, which indicates that ROS in diabetic rats directly contributes to these contractile responses. Apocynin and allopurinol had no effect on contraction in diabetic or normal rat aorta. This data is the first to show that selective inhibition of NOX reduces diabetic arterial contraction in direct comparison with inhibition of other known contributors of ROS. PMID:25460721

  7. Effects of Cichorium intybus linn on blood glucose, lipid constituents and selected oxidative stress parameters in streptozotocin-induced diabetic rats.

    PubMed

    Samarghandian, Saeed; Borji, Abasalt; Tabasi, Seyed Hidar

    2013-12-01

    The efficacy of herbal medicine has been confirmed in treatment of diabetes mellitus (DM) by amelioration of oxidative stress. The present study was designed to investigate protective effects of Cichorium intybus extract (CIE) against oxidative damage in diabetic rats. In this study, the rats were divided into the control (C), diabetic (D), D + CIE- treated (125 mg/kg/day) groups. Male Sprague-Dawley rats aged 9 weeks (160 ± 15 g) were administered with streptozotocin (STZ, 60 mg/kg) intraperitoneally (ip) to induce experimental diabetes. From 3 days after STZ administration to the end of the study (4 weeks) the ethanolic extract of CIE was administered (i.p) to diabetic rats. Body weight and blood glucose were measured weekly. At the end of the 4-week period, blood was drawn for biochemical assay, in order to determine the changes of cellular antioxidant defense system, serum oxidative damage and serum lipid were measured profile. CIE injection to diabetic rats resulted in significant reduction in blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels and significant elevation high density lipoprotein cholesterol (HDL-C) level as well as increase in the body weight as compared with the rats treated with STZ alone. In the treated diabetic group, we also observed the significant increase in reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) with decline in malondialdehyde (MDA) level compared with the non-treated diabetic group. These results suggest that the Cichorium intybus extract has antioxidant properties and prevents diabetes complications by modulation of oxidative stress system. PMID:24304233

  8. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    PubMed Central

    Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

    2015-01-01

    Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

  9. 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.

  10. β-Adrenergic Responsive Induction of Insulin Resistance in Liver of Aging Rats.

    PubMed

    Muscogiuri, Giovanna; Kamat, Amrita; Balas, Bogdan; Giaccari, Andrea; Defronzo, Ralph A; Musi, Nicolas; Katz, Michael S

    2011-01-01

    INTRODUCTION. We previously demonstrated increases in β-adrenergic receptor (β-AR) density in rat liver, in association with increased β-AR-mediated stimulation of glucose output in rat hepatocytes, during senescent aging. We therefore hypothesized that pharmacologic β-adrenergic stimulation might induce insulin resistance and glucose output in liver of aging rats in vivo. METHODS. In this study, pancreatic clamps were performed on young adult (4-month-old) and senescent (24-month-old) Fischer 344 male rats by infusing somatostatin (3 μg/kg/min) at time 0 to inhibit insulin secretion, and then infusing insulin (1 mU/kg/min) to replace basal insulin concentrations. At time 0 rats also received either the β-AR agonist isoproterenol (100 ng/kg/min) or saline (control). After 120 min the insulin infusion rate was increased to 4 mU/kg/min for an additional 120 min. Tritiated glucose was infused throughout the study to measure glucose turnover rates. RESULTS AND CONCLUSION. The results of the pancreatic clamp studies demonstrated that under saline control conditions hepatic glucose production (HGP) was suppressed during hyperinsulinemia in both young and old rats, with a trend toward reduced insulin sensitivity in the older animals. Isoproterenol infusion impaired insulin-induced suppression of HGP in both age groups. The results suggest that β-AR stimulation by isoproterenol increases HGP and acutely induces hepatic insulin resistance in both young and old rats. A similar role for β-adrenergic-mediated hepatic insulin resistance in aging humans would suggest a novel therapeutic target for the treatment or prevention of glucose dysregulation and diabetes developing with advancing age. PMID:21438725

  11. Ischemia-induced Angiogenesis is Attenuated in Aged Rats

    PubMed Central

    Tang, Yaohui; Wang, Liuqing; Wang, Jixian; Lin, Xiaojie; Wang, Yongting; Jin, Kunlin; Yang, Guo-Yuan

    2016-01-01

    To study whether focal angiogenesis is induced in aged rodents after permanent distal middle cerebral artery occlusion (MCAO), young adult (3-month-old) and aged (24-month-old) Fisher 344 rats underwent MCAO and sacrificed up to two months after MCAO. Immunohistochemistry and synchrotron radiation microangiography were performed to examine the number of newly formed blood vessels in both young adult and aged rats post-ischemia. We found that the number of capillaries and small arteries in aged brain was the same as young adult brain. In addition, we found that after MCAO, the number of blood vessels in the peri-infarct region of ipsilateral hemisphere in aged ischemic rats was significantly increased compared to the aged sham rats (p<0.05). We also confirmed that ischemia-induced focal angiogenesis occurred in young adult rat brain while the blood vessel density in young adult ischemic brain was significantly higher than that in the aged ischemic brain (p<0.05). Our data suggests that focal angiogenesis in aged rat brain can be induced in response to ischemic brain injury, and that aging impedes brain repairing and remodeling after ischemic stroke, possible due to the limited response of angiogenesis. PMID:27493831

  12. 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. PMID:22360666

  13. Ultrastructural investigations on protective effects of NCX 4016 (nitroaspirin) on macrovascular endothelium in diabetic Wistar rats.

    PubMed

    Ambrosini, M V; Mariucci, G; Rambotti, M G; Tantucci, M; Covarelli, C; De Angelis, L; Del Soldato, P

    2005-08-01

    The effect of a nitric oxide-donating aspirin derivative, 2-acetoxy-benzoate 3-(nitroxy-methyl)phenyl ester (NCX 4016), and aspirin on the aortic endothelium of diabetic rats was investigated by using scanning and transmission electron microscopy. Control and streptozotocin-treated rats were used. Metabolic control was assessed by measuring blood and urine metabolites, and 24-h urine volume. The ultrastructural study was performed after 7 weeks of diabetes and 6 weeks of therapy. Streptozotocin treatment induced a persistent hyperglycemia which was not influenced by the pharmacological treatments. Values of blood metabolites were in line with the diabetic status. Both scanning and transmission electron microscopy revealed that aortic endothelium was severely damaged in all diabetic rats except for the NCX 4016 treated ones. Our data document the protective effects of NCX 4016 on the vascular endothelium of diabetic rats. Since aspirin had no protective action, NCX 4016 may have exerted its beneficial action by releasing nitric oxide. PMID:16335593

  14. Effects of Solanum malacoxylon on duodenal calcium binding protein in the diabetic rat.

    PubMed

    Schneider, L E; Schedl, H P

    1977-04-01

    Duodenal calcium absorption and calcium binding protein (CaBP) are depressed in uncontrolled experimental (alloxan and streptozotocin) diabeties in the rat. Administration of an aqueous extract of the South American plant Solanum malacoxylon to diabetic rats restores duodenal calcium absorption to control levels. Since CaBP is thought to play a role in intestinal calcium transport, we isolated CaBP from duodenal mucosa of control, diabetic, and S. malacoxylon-treated diabetic rats. CaBP, whose concentration is about half normal in mucosal extracts from diabetic rats by treatment of diabetics with Smalacoxylon extracts. Hence these studies provide a further correlation between duodenal calcium absorption and levels of duodenal CaBP. In addition, a new purification procedure is described which produces a 17-fold increase in purity of CaBP above that attainable by our previously reported method. PMID:138586

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

    PubMed

    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

  16. 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

  17. Antidiabetic Activity of Artemisia amygdalina Decne in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Ganai, Bashir A.; Akbar, Seema; Mubashir, Khan; Dar, Showkat Ahmad; Dar, Mohammad Younis; Tantry, Mudasir A.

    2014-01-01

    Artemisia species have been extensively used for the management of diabetes in folklore medicine. The current study was designed to investigate the antidiabetic and antihyperlipidemic effects of Artemisia amygdalina. Petroleum ether, ethyl acetate, methanol, and hydroethanolic extracts of Artemisia amygdalina were tested for their antidiabetic potentials in diabetic rats. The effect of extracts was observed by checking the biochemical, physiological, and histopathological parameters in diabetic rats. The hydroethanolic and methanolic extracts each at doses of 250 and 500 mg/kg b. w significantly reduced glucose levels in diabetic rats. The other biochemical parameters like cholesterol, triglycerides, low density lipoproteins (LDL), serum creatinine, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatise (ALP), were found to be reduced by the hydroethanolic and methanolic extracts. The extracts also showed reduction in the feed and water consumption of diabetic rats when compared with the diabetic control. The histopathological results of treated groups showed the regenerative/protective effect on 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. PMID:24967338

  18. Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats.

    PubMed

    El-Demerdash, F M; Yousef, M I; El-Naga, N I Abou

    2005-01-01

    The present study was carried out to investigate the effects of onion (Allium cepa Linn) and garlic (Allium sativum Linn) juices on biochemical parameters, enzyme activities and lipid peroxidation in alloxan-induced diabetic rats. Alloxan was administered as a single dose (120 mg/kg BW) to induce diabetes. A dose of 1 ml of either onion or garlic juices/100 g body weight (equivalent to 0.4 g/100 g BW) was orally administered daily to alloxan-diabetic rats for four weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (p<0.05) increased in plasma of alloxan-diabetic rats compared to the control group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline and acid phosphatases (AlP, AcP) activities were significantly (p<0.05) increased in plasma and testes of alloxan-diabetic rats, while these activities were decreased in liver compared with the control group. Brain LDH was significantly (p<0.05) increased. The concentration of thiobarbituric acid reactive substances and the activity of glutathione S-transferase in plasma, liver, testes, brain, and kidney were increased in alloxan-diabetic rats. Treatment of the diabetic rats with repeated doses of either garlic or onion juices could restore the changes of the above parameters to their normal levels. The present results showed that garlic and onion juices exerted antioxidant and antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes. PMID:15582196

  19. 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

  20. 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

    2016-09-01

    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. PMID:27318080

  1. 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.

  2. 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. PMID:17440626

  3. Antihyperglycemic effect of aporphines and their derivatives in normal and diabetic rats.

    PubMed

    Chi, Tzong-Cherng; Lee, Shoei-Sheng; Su, Ming-Jai

    2006-10-01

    The antihyperglycemic actions of some aporphines and their derivatives in normal Wistar, streptozotocin (STZ)-induced diabetic (IDDM) and nicotinamide-STZ induced diabetic (NIDDM) rats were investigated in this study. These compounds included thaliporphine, glaucine, boldine, N-methyllaurotetanine, and predicentrine and the derivatives, N-[2-(2-methoxyphenoxy)ethyl]norglaucine and diacetyl- N-allylsecoboldine. Bolus intravenous injection of these compounds decreased the plasma glucose levels in a dose-dependent manner in both normal and diabetic rats. Among them, thaliporphine was found to have the most potent antihyperglycemic effect in both NIDDM and IDDM diabetic rats. It was found that thaliporphine could stimulate the release of insulin in both normal and diabetic rats, and a dose of 1 mg per kg thaliporphine could significantly attenuate the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. Similar treatment with thaliporphine significantly increased the skeletal muscle glycogen synthesis in both normal and diabetic rats. Hence, the hypoglycemic effect of thaliporphine in diabetic rats could be attributed to the stimulation of insulin release and the increase of glucose utilization. PMID:16924583

  4. Impact of Ellagic Acid in Bone Formation after Tooth Extraction: An Experimental Study on Diabetic Rats

    PubMed Central

    Al-Obaidi, Mazen M. Jamil; Al-Bayaty, Fouad Hussain; Hussaini, Jamal; Khor, Goot Heah

    2014-01-01

    Objectives. To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction. Methods. Twenty-four Sprague Dawley male rats weighing 250–300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test. Results. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat. Conclusion. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction. PMID:25485304

  5. Light-induced pH changes in the intact retinae of normal and early diabetic rats.

    PubMed

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

    2016-04-01

    Double-barreled H(+)-selective microelectrodes were used to measure local extracellular concentration of H(+) ([H(+)]o) in the retina of dark-adapted anesthetized Long-Evans rats. The microelectrode advanced in steps of 30 μm throughout the retina from the vitreal surface to retinal pigment epithelium and then to the choroid, recording changes in [H(+)]o evoked by light stimulation. Recordings were performed in diabetic rats 1-3 months after intraperitoneal injection of streptozotocin and the results were compared with data obtained in age-matched control animals. Brief light stimulation (2.5 s) evoked changes of [H(+)]o with amplitudes of a few nM. Throughout the retina, there was a transient initial acidification for ∼200 ms followed by steady alkalinization, although amplitudes and kinetics of these components were slightly variable in different retinal layers. No significant difference was found when the light-induced [H(+)]o changes recorded in various retinal layers of early diabetic rats were compared with the [H(+)]o changes from corresponding layers of control animals. Also, when H(+)-selective microelectrodes were located in the retinal pigment epithelium (RPE) layer, an increase in H(+) was recorded, whose time course and amplitude were similar in control and diabetic rats. However, a striking difference between light-induced [H(+)]o changes in controls and diabetics was observed in the choriocapillaris, in the thin layer (10-20 μm) distal to the basal membrane of the RPE. In control rats, choroidal [H(+)]o decreased in a few cases, but much more often practically did not change. In contrast, diabetic rats demonstrated either an increase (in half of the cases) or no change in choroidal [H(+)]o. The data suggest that the active participation of the choroidal blood supply in stabilization of [H(+)]o could be partially compromised already at early stages of diabetes in rats. Interestingly, it appeared that the acid removal by the choroidal

  6. Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide bioavailability in diabetic rat aortas.

    PubMed

    Machha, Ajay; Achike, Francis I; Mustafa, Ali Mohd; Mustafa, Mohd Rais

    2007-06-01

    The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood glucose level in diabetic rats. Impaired relaxations to endothelium-dependent vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings were restored to euglycemic levels by quercetin treatment. Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue (10microM) completely blocked but indomethacin (10microM) did not affect relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic rats. PE-induced vasoconstriction with an essentially similar magnitude in vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased superoxide dismutase activity and total antioxidant capacity in diabetic rats. From the present study, it can be concluded that quercetin administration to diabetic rats restores vascular function, probably through enhancement in the bioavailability of endothelium-derived nitric oxide coupled to reduced blood glucose level and oxidative stress. PMID:17513143

  7. 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. PMID:27470412

  8. Converting enzyme inhibition and the glomerular hemodynamic response to glycine in diabetic rats.

    PubMed

    Slomowitz, L A; Peterson, O W; Thomson, S C

    1999-07-01

    GFR normally increases during glycine infusion. This response is absent in humans and rats with established diabetes mellitus. In diabetic patients, angiotensin-converting enzyme inhibition (ACEI) restores the effect of glycine on GFR. To ascertain the glomerular hemodynamic basis for this effect of ACEI, micropuncture studies were performed in male Wistar-Froemter rats after 5 to 6 wk of insulin-treated streptozotocin diabetes. The determinants of single-nephron GFR (SNGFR) were assessed in each rat before and during glycine infusion. Studies were performed in diabetics, diabetics after 5 d of ACEI (enalapril in the drinking water), and weight-matched controls. Diabetic rats manifest renal hypertrophy and glomerular hyperfiltration but not glomerular capillary hypertension. ACEI reduced glomerular capillary pressure, increased glomerular ultrafiltration coefficient, and did not mitigate hyperfiltration. In controls, glycine increased SNGFR by 30% due to increased nephron plasma flow. In diabetics, glycine had no effect on any determinant of SNGFR. In ACEI-treated diabetics, the SNGFR response to glycine was indistinguishable from nondiabetics, but the effect of glycine was mediated by greater ultrafiltration pressure rather than by greater plasma flow. These findings demonstrate that: (1) The absent response to glycine in established diabetes does not indicate that renal functional reserve is exhausted by hyperfiltration; and (2) ACEI restores the GFR response to glycine in established diabetes, but this response is mediated by increased ultrafiltration pressure rather than by increased nephron plasma flow. PMID:10405200

  9. Antioxidative and hypolipidemic efficacy of alcoholic seed extract of Swietenia macrophylla in streptozotocin diabetic rats.

    PubMed

    Kalpana, Kalaivanan; Pugalendi, Kodukkur Viswanathan

    2011-01-01

    The present study was designed to examine the antioxidative potential and antihyperlipidemic activity of Swietenia macrophylla in streptozotocin diabetic rats. The experimental groups were rendered diabetic by intraperitoneal injection of a single dose of streptozotocin (STZ; 40 mg/kg body weight, BW). Rats with glucose levels >200 mg/dL were considered diabetic and were divided into five groups. Three groups of diabetic animals were orally administered daily with seed extract (SME) at a dosage of 50, 100 and 200 mg/kg BW. One group of STZ rats was treated as diabetic control and another group orally administered 600 μg/kg BW glibenclamide daily. Repeated daily oral administration of S. macrophylla significantly reduced blood glucose levels after 45 days of treatment. The lipid peroxidation products such as thiobarbituric acid reactive substances and lipid hydroperoxides of SME treated rats decreased in the plasma, liver and kidney. Glutathione peroxidase, superoxide dismutase and catalase activity were significantly increased in SME treated rats. Antioxidants such as reduced glutathione level in the plasma, liver and kidney and vitamins C and E levels in the plasma increased in SME treated rats. Total cholesterol, triglycerides, phospholipids and free fatty acids and lipoproteins levels increased. Altered lipid profile of treated rats lead to normality with treatment of S. macrophylla. Thus, our results indicate that the administration of 100 mg/kg BW SME restores near normal blood glucose, redox status and lipid profile in STZ-diabetic rats. PMID:22865358

  10. 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. PMID:23566555

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

    PubMed

    Badole, Sachin L; Jangam, Ganesh B; Chaudhari, Swapnil M; Ghule, Arvindkumar E; Zanwar, Anand A

    2014-01-01

    The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o.), II: diabetic control (distilled water, 10 ml/kg, p.o.), III: L-glutamine (500 mg/kg, p.o.) and IV: L-glutamine (1000 mg/kg, p.o.). All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity. PMID:24651718

  12. Effect of Nicotinic Acid (Vitamin B3 or Niacin) on the lipid profile of diabetic and non – diabetic rats

    PubMed Central

    Zeb Shah, Talmeez; Ali, Abdul Basit; Ahmad Jafri, Saghir; Qazi, M.H.

    2013-01-01

    Objective: To determine the efficacy of nicotinic acid on the lipid profile of diabetic and non diabetic rats. Methods: This was an experimental study done at the Institute of Molecular Biology and Biotechnology, The University of Lahore, Pakistan between May 2010 to July 2010. Nicotinic acid was administered to a hypercholesterolemic group and a hypercholesterolemic + diabetic Group of Albino rats for 42 days and response to therapy was recorded on day 21 and day 42 of the experiment. Comparison among these two groups as well as three control groups was determined by Analysis of Variance (ANOVA) and differences were considered significant at (P<0.05). A total of 50 rats were included in the study. Results: Lipid profile of the hypercholesterolemic group as well as hypercholesterolemic + diabetic group as compared with the control groups showed highly significant improvement on the day 21 and day 42 of the experiment. The values of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) cholesterol and total lipids (TL) showed highly significant decrease whereas serum high density lipoprotein (HDL) cholesterol showed highly significant increase. Conclusion: Nicotinic acid is the most effective agent available in increasing HDL cholesterol and lowering serum TC, triglycerides (TG), LDL cholesterol and TL in hypercholesterolemic Diabetic and hypercholesterolemic non-diabetic Albino rats. PMID:24353732

  13. Diabetic Nephropathy Amelioration by a Low-Dose Sitagliptin in an Animal Model of Type 2 Diabetes (Zucker Diabetic Fatty Rat)

    PubMed Central

    Mega, Cristina; Teixeira de Lemos, Edite; Vala, Helena; Fernandes, Rosa; Oliveira, Jorge; Mascarenhas-Melo, Filipa; Teixeira, Frederico; Reis, Flávio

    2011-01-01

    This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl peptidase 4 inhibitor, on metabolic profile and on renal lesions aggravation in a rat model of type-2 diabetic nephropathy, the Zucker diabetic fatty (ZDF) rat. Diabetic and obese ZDF (fa/fa) rats and their controls ZDF (+/+) were treated for 6 weeks with vehicle (control) or sitagliptin (10 mg/kg/bw). Blood/serum glucose, HbA1c, insulin, Total-c, TGs, urea, and creatinine were assessed, as well as kidney glomerular and tubulointerstitial lesions (interstitial fibrosis/tubular atrophy), using a semiquantitative rating from 0 (absent/normal) to 3 (severe and extensive damage). Vascular lesions were scored from 0–2. Sitagliptin in the diabetic rats promoted an amelioration of glycemia, HbA1c, Total-c, and TGs, accompanied by a partial prevention of insulinopenia. Furthermore, together with urea increment prevention, renal lesions were ameliorated in the diabetic rats, including glomerular, tubulointerstitial, and vascular lesions, accompanied by reduced lipid peroxidation. In conclusion, chronic low-dose sitagliptin treatment was able to ameliorate diabetic nephropathy, which might represent a key step forward in the management of T2DM and this serious complication. PMID:22203828

  14. Enhanced Post-Ischemic Neurogenesis in Aging Rats

    PubMed Central

    Tan, Yao-Fang; Preston, Edward; Wojtowicz, J. Martin

    2010-01-01

    Hippocampal neurogenesis persists in adult mammals, but its rate declines dramatically with age. Evidence indicates that experimentally-reduced levels of neurogenesis (e.g., by irradiation) in young rats has profound influence on cognition as determined by learning and memory tests. In the present study we asked whether in middle-aged, 10- to 13-months-old rats, cell production can be restored toward the level present in young rats. To manipulate neurogenesis we induced bilateral carotid occlusion with hypotension. This procedure is known to increase neurogenesis in young rats, presumably in a compensatory manner, but until now, has never been tested in aging rats. Cell production was measured at 10, 35, and 90 days after ischemia. The results indicate that neuronal proliferation and differentiation can be transiently restored in middle-aged rats. Furthermore, the effects are more pronounced in the dorsal as opposed to ventral hippocampus thus restoring the dorso-ventral gradient seen in younger rats. Our results support previous findings showing that some of the essential features of the age-dependent decline in neurogenesis are reversible. Thus, it may be possible to manipulate neurogenesis and improve learning and memory in old age. PMID:20877422

  15. 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

  16. Raloxifene prevents endothelial dysfunction in aging ovariectomized female rats.

    PubMed

    Wong, Chi Ming; Yao, Xiaoqiang; Au, Chak Leung; Tsang, Suk Ying; Fung, Kwok Pui; Laher, Ismail; Vanhoutte, Paul M; Huang, Yu

    2006-05-01

    Lack of an appropriate animal model has delayed the better understanding of mechanisms related to higher cardiovascular risk in women after menopause. The aging female rat may share some menopausal changes observed in women. However, most studies have attempted to mimic menopause by ovariectomizing young (6-12 weeks old) animals without taking into accounts the influence of aging and of declining ovarian function. Therefore, the present study examined changes in vascular reactivity in the aging (15 months old) female rat after ovariectomy and the effects of chronic raloxifene therapy on vascular reactivity and eNOS protein expression. Aortic rings were prepared from the three experimental groups of rats: sham-operated control, ovariectomized and ovariectomized aging rats receiving daily oral administration of raloxifene for 3 months. Aortic rings were suspended in organ baths for the measurement of isometric tension. Rings with endothelium contracted significantly more to phenylephrine after inhibition of nitric oxide/cyclic GMP-signaling pathway by L-NAME or ODQ (as an index of basal nitric oxide release) in control and raloxifene-treated ovariectomized rats than in ovariectomized rats. This effect was abolished upon mechanical removal of the endothelium. Phenylephrine induced greater contractions only in rings with endothelium from ovariectomized rats as compared with control rats and raloxifene treatment normalized this response. In the presence of L-NAME or ODQ, phenylephrine-induced contraction was similar in rings from the three groups. Rings relaxed more to thapsigargin and acetylcholine in raloxifene-treated ovariectomized rats than in ovariectomized rats. There was no significant difference in aortic eNOS protein contents among the different groups. These results suggest that chronic oral administration of raloxifene to aging ovariectomized female rats augmented the bioavailability of endothelial nitric oxide in isolated aortic rings without altering e

  17. Antidiabetic Activity of Vinca rosea Extracts in Alloxan-Induced Diabetic Rats

    PubMed Central

    Ahmed, Mohammed Fazil; Kazim, Syed Mohammed; Ghori, Syed Safiullah; Mehjabeen, Syeda Sughra; Ahmed, Shaik Rasheed; Ali, Shaik Mehboob; Ibrahim, Mohammed

    2010-01-01

    The present study was carried out to evaluate the antidiabetic activity of Vinca rosea methanolic whole plant extracts in alloxan induced diabetic rats for 14 days. The methanolic whole plant extract at high dose (500 mg/kg) exhibited significant anti-hyperglycemic activity than whole plant extract at low dose (300 mg/kg) in diabetic rats. The methanolic extracts also showed improvement in parameters like body weight and lipid profile as well as regeneration of β-cells of pancreas in diabetic rats. Histopathological studies reinforce the healing of pancreas, by methanolic Vinca rosea extracts, as a possible mechanism of their antidiabetic activity. PMID:20652054

  18. Antidiabetic Activity of Vinca rosea Extracts in Alloxan-Induced Diabetic Rats.

    PubMed

    Ahmed, Mohammed Fazil; Kazim, Syed Mohammed; Ghori, Syed Safiullah; Mehjabeen, Syeda Sughra; Ahmed, Shaik Rasheed; Ali, Shaik Mehboob; Ibrahim, Mohammed

    2010-01-01

    The present study was carried out to evaluate the antidiabetic activity of Vinca rosea methanolic whole plant extracts in alloxan induced diabetic rats for 14 days. The methanolic whole plant extract at high dose (500 mg/kg) exhibited significant anti-hyperglycemic activity than whole plant extract at low dose (300 mg/kg) in diabetic rats. The methanolic extracts also showed improvement in parameters like body weight and lipid profile as well as regeneration of beta-cells of pancreas in diabetic rats. Histopathological studies reinforce the healing of pancreas, by methanolic Vinca rosea extracts, as a possible mechanism of their antidiabetic activity. PMID:20652054

  19. Preliminary studies on the hypoglycaemic effect ofAbroma augusta in alloxan diabetic rats.

    PubMed

    Eshrat, H; Hussain, M A; Jamil, K; Rao, M

    2001-01-01

    The hypoglycemic effect of the aqueous extract ofAbroma augusta (Family: Steculiceae) was studied in normal as well as alloxan diabetic rats. Treatement of diabetic rats with 4 ml (4gm dry weight) of agueous extract ofA. augusta for 16 weeks resulted in gradual but significant fall in fasting blood glucose and improvement in glucose tolerance. Serum total and LDL cholesterol and triacylglycerol which increased in diabetic rats showed improvement. These results show that the water extract ofA. augusta has both hypoglycemic and hypocholesterolemic effects. PMID:23105296

  20. 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

  1. Effect of cyclosporin A on bone mineral metabolism in experimental diabetes mellitus in the rat.

    PubMed

    Epstein, S; Takizawa, M; Stein, B; Katz, I A; Joffe, I I; Romero, D F; Liang, X G; Li, M; Ke, H Z; Jee, W S

    1994-04-01

    Cyclosporin A (CsA) is widely used in diabetic transplant patients and early type I diabetes mellitus. Diabetes produces a low-turnover osteopenia, and CsA conversely induces high-turnover osteopenia in rats. We investigated whether CsA would exacerbate diabetic osteopenia. Four groups of 10-week-old male Sprague-Dawley rats (n = 11/group) were studied: On day -6, groups A and C received saline and groups B and D received intravenous streptozotocin (55 mg/kg) to induce diabetes. From day 0, groups A and B received CsA vehicle and C and D received CsA (15 mg/kg) by daily gavage. Rats were bled on days -6, 0, 11, and 22 for serum bone gla protein (BGP), 1,25-(OH)2D, PTH, blood ionized Ca, and blood glucose determinations. Double tetracycline labeling was performed on days 9 and 20 for bone histomorphometry. After sacrifice on day 22, histomorphometric analysis was performed. Serum BGP, 1,25-(OH)2D, and PTH levels were significantly decreased in the diabetic alone (B) and diabetic plus CsA (D) groups and significantly increased in the CsA alone (group C). CsA alone (group C) induced cancellous bone loss by stimulated bone resorption. Cancellous bone loss in the diabetic alone rats (group B) was caused primarily by inhibited bone formation. No differences were found in cancellous bone mass, formation, or resorption parameters between diabetic alone (group B) and CsA-treated diabetic rats (group D). Neither CsA alone (group C) nor diabetic alone (group B) nor their combination affected cortical bone mass. CsA alone (group C) stimulated periosteal bone formation and endocortical bone resorption and inhibited endocortical formation, and diabetic alone (group B) inhibited both periosteal and endocortical bone formation. No parameters of tibial diaphyses in CsA-treated diabetic rats (group D) were different from diabetic alone. Thus the addition of CSA to the diabetic treated rats (group D) could not stimulate remodeling and appeared not to worsen significantly some of the

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

    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

  5. Influence of diabetes on liver injury induced by antitubercular drugs and on silymarin hepatoprotection in rats.

    PubMed

    Srivastava, R K; Sharma, S; Verma, S; Arora, B; Lal, H

    2008-12-01

    Isoniazid, rifampicin and pyrazinamide during short-course chemotherapy for tuberculosis can result in liver injury. The coexistence of tuberculosis and diabetes is common in patients who receive inadequate treatment. The risk of hepatotoxicity from many toxicants is increased in diabetic rats. Silymarin provides protection against liver injury caused by many hepatotoxicants, including antitubercular drugs (ATDs). In the wake of increased severity of ATD-induced hepatotoxicity in diabetes we report here the results of a study on the influence of diabetes on silymarin hepatoprotection in rats. Rats with diabetes induced via intraperitoneally injected streptozotocin (50 mg/kg), nondiabetic rats and insulin-treated diabetic rats received isoniazid (7.5 mg/kg/day), rifampicin (10 mg/kg/day) and pyrazinamide (35 mg/kg/day) orally (p.o.) with or without silymarin (100 mg/kg/day p.o.) treatment for 45 days. Compared to nondiabetic rats, liver function tests and histological changes of liver revealed exaggerated liver injury in diabetic rats caused by ATDs which was evident by 5- to 8-fold increases in serum levels of marker enzymes (aspartate and alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase) and 1- to 2-fold increases in bilirubin accompanied by a 2-fold decrease in total serum proteins, intense fatty and inflammatory infiltrations, necrosis and fibrosis. Coadministration of silymarin provided protection against ATD hepatotoxicity in all animals. However, insulin-treated diabetic animals showed greater silymarin-induced hepatoprotection against ATD-induced liver injury, which was characterized by near normal levels of marker enzymes, an increase in total proteins and normal hepatic structure. These results thus indicate that diabetes exaggerates ATD-induced liver injury and attenuates silymarin-induced hepatoprotection. However, insulin treatment for diabetes offers greater silymarin-induced hepatoprotection against ATD-induced liver

  6. 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

  7. 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

  8. 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. PMID:20191126

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

    PubMed Central

    Yan, Shu; Zheng, Cui; Chen, Zhi-qi; Liu, Rong; Li, Gui-gang; Hu, Wei-kun; Pei, Han; Li, Bin

    2012-01-01

    Recent reports show that ER stress plays an important role in diabetic retinopathy (DR), but ER stress is a complicated process involving a network of signaling pathways and hundreds of factors, What factors involved in DR are not yet understood. We selected 89 ER stress factors from more than 200, A rat diabetes model was established by intraperitoneal injection of streptozotocin (STZ). The expression of 89 ER stress-related factors was found in the retinas of diabetic rats, at both 1- and 3-months after development of diabetes, by quantitative real-time polymerase chain reaction arrays. There were significant changes in expression levels of 13 and 12 ER stress-related factors in the diabetic rat retinas in the first and third month after the development of diabetes, Based on the array results, homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1(HERP), and synoviolin(HRD1) were studied further by immunofluorescence and Western blot. Immunofluorescence and Western blot analyses showed that the expression of HERP was reduced in the retinas of diabetic rats in first and third month. The expression of Hrd1 did not change significantly in the retinas of diabetic rats in the first month but was reduced in the third month. PMID:21904541

  10. 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

  11. 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

  12. 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. PMID:26174209

  13. Aging changes agonist induced contractile responses in permeabilized rat bladder.

    PubMed

    Durlu-Kandilci, N Tugba; Denizalti, Merve; Sahin-Erdemli, Inci

    2015-08-01

    Aging alters bladder functions where a decrease in filling, storage and emptying is observed. These changes cause urinary incontinence, especially in women. The aim of this study is to examine how aging affects the intracellular calcium movements due to agonist-induced contractions in permeabilized female rat bladder. Urinary bladder isolated from young and old female Sprague-Dawley rats were used. Small detrusor strips were permeabilized with β-escin. The contractile responses induced with agonists were compared between young and old groups. Carbachol-induced contractions were decreased in permeabilized detrusor from old rats compared to young group. Heparin and ryanodine decreased carbachol-induced contractions in young rats where only heparin inhibited these contractions in olds. Caffeine-induced contractions but not inositol triphosphate (IP3)-induced contractions were decreased in old group compared to youngs. The cumulative calcium response curves (pCa 8-4) were also decreased in old rats. Carbachol-induced calcium sensitization responses did not alter by age where GTP-β-S and GF-109203X but not Y-27632 inhibited these responses. Carbachol-induced contractions decrease with aging in rat bladder detrusor. It can be postulated as IP3-induced calcium release (IICR) is primarily responsible for the contractions in older rats where the decrease in carbachol contractions in aging may be as a result of a decrease in calcium-induced calcium release (CICR), rather than carbachol-induced calcium sensitization. PMID:26153091

  14. Amla (Emblica officinalis Gaertn.) extracts reduce oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Rao, T P; Sakaguchi, N; Juneja, L R; Wada, E; Yokozawa, T

    2005-01-01

    The antioxidant properties of amla extracts and their effects on the oxidative stress in streptozotocin-induced diabetes were examined in rats. Amla in the form of either the commercial enzymatic extract SunAmla (Taiyo Kagaku Co. Ltd., Yokkaichi, Japan) (20 or 40 mg/kg of body weight/day) or a polyphenol-rich fraction of ethyl acetate extract (10 or 20 mg/kg of body weight/day) was given orally for 20 days to the streptozotocin-induced diabetic rats. Amla extracts showed strong free radical scavenging activity. Amla also showed strong inhibition of the production of advanced glycosylated end products. The oral administration of amla extracts to the diabetic rats slightly improved body weight gain and also significantly alleviated various oxidative stress indices of the serum of the diabetic rats. The elevated serum levels of 5-hydroxymethylfurfural, which is a glycosylated protein that is an indicator of oxidative stress, were significantly reduced dose-dependently in the diabetic rats fed amla. Similarly, the serum level of creatinine, yet another oxidative stress parameter, was also reduced. Furthermore, thiobarbituric acid-reactive substances levels were significantly reduced with amla, indicating a reduction in lipid peroxidation. In addition, the decreased albumin levels in the diabetic rats were significantly improved with amla. Amla also significantly improved the serum adiponectin levels. These results form the scientific basis supporting the efficacy of amla for relieving the oxidative stress and improving glucose metabolism in diabetes. PMID:16176148

  15. 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

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

    PubMed Central

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

    2015-01-01

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

  17. Advanced Glycation End Products Impair Voltage-Gated K+ Channels-Mediated Coronary Vasodilation in Diabetic Rats

    PubMed Central

    Su, Wen; Li, Weiping; Chen, Hui; Liu, Huirong; Huang, Haixia; Li, Hongwei

    2015-01-01

    Background We have previously reported that high glucose impairs coronary vasodilation by reducing voltage-gated K+ (Kv) channel activity. However, the underlying mechanisms remain unknown. Advanced glycation end products (AGEs) are potent factors that contribute to the development of diabetic vasculopathy. The aim of this study was to investigate the role of AGEs in high glucose-induced impairment of Kv channels-mediated coronary vasodilation. Methods Patch-clamp recording and molecular biological techniques were used to assess the function and expression of Kv channels. Vasodilation of isolated rat small coronary arteries was measured using a pressurized myograph. Treatment of isolated coronary vascular smooth muscle cells (VSMCs) and streptozotocin-induced diabetic rats with aminoguanidine, the chemical inhibitor of AGEs formation, was performed to determine the contribution of AGEs. Results Incubation of VSMCs with high glucose reduced Kv current density by 60.4 ± 4.8%, and decreased expression of Kv1.2 and Kv1.5 both at the gene and protein level, whereas inhibiting AGEs formation or blocking AGEs interacting with their receptors prevented high glucose-induced impairment of Kv channels. In addition, diabetic rats manifested reduced Kv channels-mediated coronary dilation (9.3 ± 1.4% vs. 36.9 ± 1.4%, P < 0.05), which was partly corrected by the treatment with aminoguanidine (24.4 ± 2.2% vs. 9.3 ± 1.4%, P < 0.05). Conclusions Excessive formation of AGEs impairs Kv channels in VSMCs, then leading to attenuation of Kv channels-mediated coronary vasodilation. PMID:26562843

  18. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    PubMed Central

    Rice, K. M.; Fannin, J. C.; Gillette, C.; Blough, E. R.

    2014-01-01

    Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging. PMID:25610649

  19. Diabetes and alcohol: Double jeopardy with regard to oxidative toxicity and sexual dysfunction in adult male Wistar rats.

    PubMed

    Himabindu, B; Madhu, P; Reddy, P Sreenivasula

    2015-01-01

    The aim of this study was to test whether diabetic rats exposed to alcohol demonstrate a higher degree of reproductive toxicity and suffer with elevated oxidative toxicity when compared with alcohol exposed control rats. Diabetes was induced by injecting single dose of streptozotocin and alcohol was administered through orogastric tube once daily for a period of 55 days. Daily sperm production, epididymal sperm count, motile, viable and HOS-tail coiled sperms, serum testosterone levels and testicular 3β- and 17β-hydroxysteroid dehydrogenase activity levels were significantly decreased in diabetic rats. Significant reduction in testicular and epididymal superoxide dismutase and catalase activity levels, and elevation in lipid peroxidation products were observed in diabetic rats. Similar reproductive and oxidative toxicity was observed in alcohol treated control rats. Further, alcohol exposed diabetic rats showed additional deterioration in reproductive endpoints and noteworthy elevation in oxidative toxicity suggesting that treatment with alcohol further deteriorates sexual dysfunction in STZ-induced diabetic rats. PMID:25541261

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

    SciTech Connect

    Binz, K.; Joller, P.; Froesch, P.; Binz, H.; Zapf, J.; Froesch, E.R. )

    1990-05-01

    Atrophy of the thymus is one of the consequences of severe insulin deficiency. The authors describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. They also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less ({sup 3}H)thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased ({sup 3}H)thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-1 antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. They conclude that IGF-I has important effects on the thymocyte number and the presence of CD4{sup +}/CD8{sup +} immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state.

  1. An Observational Assessment Method for Aging Laboratory Rats

    PubMed Central

    Phillips, Pamela M; Jarema, Kimberly A; Kurtz, David M; MacPhail, Robert C

    2010-01-01

    The rapid growth of the aging human population highlights the need for laboratory animal models to study the basic biologic processes of aging and susceptibility to disease, drugs, and environmental pollutants. Methods are needed to evaluate the health of aging animals over time, particularly methods for efficiently monitoring large research colonies. Here we describe an observational assessment method that scores appearance, posture, mobility, and muscle tone on a 5-point scale that can be completed in about 1 min. A score of 1 indicates no deterioration, whereas a score of 5 indicates severe deterioration. Tests were applied to male Brown Norway rats between 12 and 36 mo of age (n = 32). The rats were participating concurrently in experiments on the behavioral effects of intermittent exposure (approximately every 4 mo) to short-acting environmental chemicals. Results demonstrated that aging-related signs of deterioration did not appear before 18 mo of age. Assessment scores and variability then increased with age. Body weights increased until approximately 24 mo, then remained stable, but decreased after 31 mo for the few remaining rats. The incidence of death increased slightly from 20 to 28 mo of age and then rose sharply; median survival age was approximately 30 mo, with a maximum of 36 mo. The results indicate that our observational assessment method supports efficient monitoring of the health of aging rats and may be useful in studies on susceptibility to diseases, drugs, and toxicants during old age. PMID:21205442

  2. 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

  3. Diabetes induces stromal remodelling and increase in chondroitin sulphate proteoglycans of the rat ventral prostate

    PubMed Central

    Ribeiro, Daniele Lisboa; Taboga, Sebastião Roberto; Góes, Rejane Maira

    2009-01-01

    Extracellular matrix (ECM) remodelling is an important process involved in prostate cancer progression. Alterations in ECM caused by diabetes in different tissues such as kidney is well described; however, it is poorly investigated in prostate. The aim of this study was to evaluate changes in ECM of rat prostate showing gland atrophy caused by diabetes and their implications in development of malignant lesions. Diabetes was induced in Wistar rats using alloxan (45 mg/kg bw). After 90 days of diabetes onset, animals were killed and ventral prostate was removed and prepared for light microscopy following immunoreaction for fibronectin, chondroitin sulphate and Picrossirius staining for collagen fibres. Proteoglycans (PG) were identified at transmission electron microscopy after fixation with Cuprolinic Blue. Diabetes led to a thickening of 25% in the acinar basement membrane accompanied by increase and disorganization of its proteoglycans (P1). Three additional populations of prostatic stromal PGs were identified: collagen fibril linked (P2) and interstitial (P3) and (P4) PGs. Diabetes increased P3 and mainly P4 which had higher dimension and accumulated around the smooth muscle cells. In addition, an increase in chondrotin sulphate (33%, mainly in sites where P4 were noted) and collagen (44%) was noted in diabetic rats, whereas fibronectin did not change. Atrophic changes observed in rat ventral prostate after diabetes are accompanied by stromal remodelation related to increase in collagen and chondroitin sulphate proteoglycans. Thus, diabetes can promote a stromal microenvironment rich in elements that could favour cell migration, proliferation and pathological process. PMID:19659898

  4. Light adaptation does not prevent early retinal abnormalities in diabetic rats

    PubMed Central

    Kur, Joanna; Burian, Michael A.; Newman, Eric A.

    2016-01-01

    The aetiology of diabetic retinopathy (DR), the leading cause of blindness in the developed world, remains controversial. One hypothesis holds that retinal hypoxia, exacerbated by the high O2 consumption of rod photoreceptors in the dark, is a primary cause of DR. Based on this prediction we investigated whether early retinal abnormalities in streptozotocin-induced diabetic rats are alleviated by preventing the rods from dark adapting. Diabetic rats and their non-diabetic littermates were housed in a 12:12 hour light-dim light photocycle (30 lux during the day and 3 lux at night). Progression of early retinal abnormalities in diabetic rats was assessed by monitoring the ERG b-wave and oscillatory potentials, Müller cell reactive gliosis, and neuronal cell death, as assayed by TUNEL staining and retinal thickness at 6 and 12 weeks after diabetes induction. Maintaining diabetic animals in a dim-adapting light did not slow the progression of these neuronal and glial changes when compared to diabetic rats maintained in a standard 12:12 hour light-dark photocycle (30 lux during the day and 0 lux at night). Our results indicate that neuronal and glial abnormalities in early stages of diabetes are not exacerbated by rod photoreceptor O2 consumption in the dark. PMID:26852722

  5. Investigation on the effects of the atmospheric pressure plasma on wound healing in diabetic rats.

    PubMed

    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

  6. 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

  7. The Ethanol Extract of Zingiber zerumbet Attenuates Streptozotocin-Induced Diabetic Nephropathy in Rats

    PubMed Central

    Tzeng, Thing-Fong; Liou, Shorong-Shii; Chang, Chia Ju; Liu, I-Min

    2013-01-01

    The ethanol extract from the rhizome of Zingiber zerumbet (L.) Smith (EEZZR) has been indicated to possess an insulin-like property by ameliorating hyperglycemia in diabetes. We aimed to investigate whether EEZZR exerts an ameliorative effect on renal damage in diabetes induced by streptozotocin (STZ). Diabetic rats were treated orally with EEZZR (200 and 300 mg kg−1 per day) or metformin (100 mg kg−1 per day) for 8 weeks. The plasma glucose, creatinine, and blood urea nitrogen as well as urine protein levels and the ratio of kidney weight to body weight were significantly elevated in diabetic rats. EEZZR displayed similar characteristics to those of metformin in reducing hyperglycemia and renal dysfunction in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following the treatment with EEZZR. In addition, the protein expressions of renal nephrin and podocin in diabetic rats were significantly increased following the treatment with EEZZR. The AMP-activated protein kinase (AMPK) protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. EEZZR treatment significantly rescued the AMPK phosphorylation compared to nontreated diabetic group. This study suggested that the renoprotective effects of EEZZR may be similar, with the action of metformin, to the prevention of AMPK dephosphorylation and upregulate the expressions of renal nephrin and podocin. PMID:23476687

  8. 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.

  9. Morphometric and quantitative evaluation of the NADH-diaphorase positive myenteric neurons of the jejunum of streptozotocin-diabetic rats supplemented with acetyl-L-carnitine.

    PubMed

    De Miranda Neto, M H; Defani, M A; Fregonesi, C E P T; Natali, M R M; Pereira, A

    2005-06-01

    Summary In this study we investigated the effect of the acetyl-L-carnitine (ALC) supplementation on the myenteric neurons of the jejunum of rats made diabetic at the age of 105 days by streptozotocin (35 mg/kg body weight). Four groups were used: non-diabetic (C), non-diabetic supplemented with ALC (CC), diabetic (D), diabetic supplemented with ALC (DC). After 15 weeks of diabetes induction the blood was collected by cardiac puncture to evaluate glycaemia and glycated haemoglobin. Next the animals were killed and the jejunum was collected and subjected to whole-mount preparation to evidence the myenteric neurons through the histochemical technique of the NADH-diaphorase. The neuronal counts were made in 80 microscopic fields, in tissue samples of five animals of each group. The profiles of the cell bodies of 1000 neurons per group were analysed. Diabetes induced a significant increase in the area of the cell body and decrease in the number of NADH-diaphorase positive myoenteric neurons. ALC suplementation to the diabetic group promoted smaller hypertrophic effects and less neuronal loss than in the myoenteric neurons of the diabetic rats, and in addition diminished the body weight decrease and reduced the fasting glycaemia. PMID:15929729

  10. Attenuation of aortic injury by ursolic acid through RAGE-Nox-NFκB pathway in streptozocin-induced diabetic rats.

    PubMed

    Xiang, Min; Wang, Jianmei; Zhang, Yaqin; Ling, Jing; Xu, Xiaoyue

    2012-05-01

    Vascular complications are the leading causes of morbidity and mortality in diabetes mellitus (DM). The RAGE (receptor for advanced glycation end products)-NADPH oxidase-NF-κB signal transduction pathway plays an important role in the development of oxidative stress-related vascular complications in DM. Ursolic acid (UA), a pentacyclic triterpenoid derived from plants, has been reported to have multiple pharmacological effects, including a potent antioxidant activity. This study aimed to investigate both the effect of UA on aortic injury in streptozotocin (STZ)-induced diabetic rats and the drug's mechanism of action. STZ-induced diabetic animals were randomized in one of the following 4 groups: no treatment (diabetic model group), aminoguanidine (AG, 100 mg/kg), high-dose UA (50 mg/kg), and low-dose UA (25 mg/kg). A non-diabetic control group was followed concurrently. After 8 weeks, the diabetic model rats exhibited: severe aortic arch injury, histologically elevated serum glucose, fructosamine, and glycosylated hemoglobin; and accumulation of advanced glycation end products (AGEs) in the arota. In addition, the levels of RAGE protein, transcription factor NF-κB p65, and the p22phox subunit of NADPH oxidase were increased, as were the serum levels of malondialdehyde and tumor necrosis factor-alpha (TNF-α; p < 0.01 vs control), suggesting that the mechanisms of oxidative stress contributed to vascular injury in the diabetic model group. In contrast, rats treated with UA (50 mg/kg) had a markedly less vascular injury and significantly improved biochemical parameters. Oxidative balance was also normalized in the UA-treated rats, and a marked reduction in the levels of RAGE and p22phox paralleled the reduced activation of NF-κB p65 and TNF-α (p < 0.01 and p < 0.05, respectively, vs diabetic model). These findings suggest that UA may suppress oxidative stress, thus blunting activation of the RAGE-NADPH oxidase-NF-κB signal transduction pathway, to ameliorate

  11. Anti-diabetic activities of the methanol leaf extracts of Hymenocardia acida (tul.) in alloxan-induced diabetic rats.

    PubMed

    Ezeigbo, Ihechiluru I; Asuzu, Isaac U

    2012-01-01

    The effect of methanolic extract of Hymenocardia acida leaves on diabetes and associated lipidemia were investigated on experimentally-induced diabetic rats. The extract did not demonstrate any acutely toxic effect in rats within the dose range (250 mg/kg - 2000 mg/kg) employed in the study; hence it was well tolerated by the rats. In all experiments, the anti-diabetic effects were dose-dependent and comparable to that of glibenclamide (2 mg/kg) standard. At a dose of 500 mg/kg, lipid profile markers such as the serum total cholesterol (TC) levels, LDL-C, triglycerides and HDL-C were significantly lower (p <0.05) than those of both the treated and untreated controls. PMID:23983336

  12. 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. PMID:22303055

  13. 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

  14. Protocatechuic Acid Restores Vascular Responses in Rats With Chronic Diabetes Induced by Streptozotocin.

    PubMed

    Semaming, Yoswaris; Kukongviriyapan, Upa; Kongyingyoes, Bunkerd; Thukhammee, Wipawee; Pannangpetch, Patchareewan

    2016-02-01

    Oxidative stress has been shown to play an important role in development of vascular dysfunction in diabetes. Protocatechuic acid (PCA) has been reported to exert antioxidant and anti-hyperglycemic activities. Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of 50 mg/kg streptozotocin (STZ). The rats were maintained in a state of hyperglycemia for 12 weeks. Then, PCA (50 or 100 mg/kg/day) was administered orally or insulin (4 U/kg/day) was subcutaneous injected to the rats for 6 weeks. Blood pressure, vascular responses to vasoactive agents, vascular superoxide production, blood glucose, insulin, malondialdehyde, nitric oxide and antioxidant enzymes were examined. The diabetic rats showed weight loss, insulin deficiency, hyperglycemia, increased oxidative stress, decreased plasma nitric oxide, elevated blood pressure, increased vascular response to phenylephrine and decreased vascular responses to acetylcholine and sodium nitroprusside. PCA significantly decreased blood glucose and oxidative stress, and increased plasma nitric oxide in diabetic rats. Interestingly, PCA treatment restored blood pressure and vascular reactivity, and antioxidant enzyme activity diabetic rats. This study provides the first evidence of the efficacy of PCA in restoring the vascular reactivity of diabetic rats. The mechanism of action may be associated with an alleviation of oxidative stress. PMID:26575211

  15. Alterations in Glutathione Redox Metabolism, Oxidative Stress, and Mitochondrial Function in the Left Ventricle of Elderly Zucker Diabetic Fatty Rat Heart

    PubMed Central

    Raza, Haider; John, Annie; Howarth, Frank C.

    2012-01-01

    The Zucker diabetic fatty (ZDF) rat is a genetic model in which the homozygous (FA/FA) male animals develop obesity and type 2 diabetes. Morbidity and mortality from cardiovascular complications, due to increased oxidative stress and inflammatory signals, are the hallmarks of type 2 diabetes. The precise molecular mechanism of contractile dysfunction and disease progression remains to be clarified. Therefore, we have investigated molecular and metabolic targets in male ZDF (30–34 weeks old) rat heart compared to age matched Zucker lean (ZL) controls. Hyperglycemia was confirmed by a 4-fold elevation in non-fasting blood glucose (478.43 ± 29.22 mg/dL in ZDF vs. 108.22 ± 2.52 mg/dL in ZL rats). An increase in reactive oxygen species production, lipid peroxidation and oxidative protein carbonylation was observed in ZDF rats. A significant increase in CYP4502E1 activity accompanied by increased protein expression was also observed in diabetic rat heart. Increased expression of other oxidative stress marker proteins, HO-1 and iNOS was also observed. GSH concentration and activities of GSH-dependent enzymes, glutathione S-transferase and GSH reductase, were, however, significantly increased in ZDF heart tissue suggesting a compensatory defense mechanism. The activities of mitochondrial respiratory enzymes, Complex I and Complex IV were significantly reduced in the heart ventricle of ZDF rats in comparison to ZL rats. Western blot analysis has also suggested a decreased expression of IκB-α and phosphorylated-JNK in diabetic heart tissue. Our results have suggested that mitochondrial dysfunction and increased oxidative stress in ZDF rats might be associated, at least in part, with altered NF-κB/JNK dependent redox cell signaling. These results might have implications in the elucidation of the mechanism of disease progression and designing strategies for diabetes prevention. PMID:23203193

  16. Importance of maternal diabetes on the chronological deregulation of the intrauterine development: an experimental study in rat.

    PubMed

    Salazar García, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, María Cristina; Villavicencio Guzmán, Laura; Reyes López, Alfonso; Sánchez-Gómez, Concepción

    2015-01-01

    We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells. PMID:25756053

  17. Importance of Maternal Diabetes on the Chronological Deregulation of the Intrauterine Development: An Experimental Study in Rat

    PubMed Central

    Salazar García, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, María Cristina; Villavicencio Guzmán, Laura; Reyes López, Alfonso; Sánchez-Gómez, Concepción

    2015-01-01

    We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells. PMID:25756053

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

    PubMed

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

    2005-04-29

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

  19. The Laboratory Rat: Relating Its Age With Human's

    PubMed Central

    Sengupta, Pallav

    2013-01-01

    By late 18th or early 19th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years). Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor. PMID:23930179

  20. 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

  1. Biomechanical and histomorphometric colon remodelling in STZ-induced diabetic rats.

    PubMed

    Zhao, Jingbo; Nakaguchi, Toshiya; Gregersen, Hans

    2009-08-01

    The histomorphologic and passive biomechanical properties were studied in the mid-colon of 16 non-diabetic and 20 streptozotocin (STZ)-induced diabetic rats (50 mg/kg STZ, ip). The diabetic rats were divided into groups living 4 and 8 weeks after the induction of diabetes (n = 10 for each group). The mechanical test was a ramp distension of fluid into the colon in vitro. The colon diameter and length were obtained from digitized images of the segments at pre-selected pressures and at the no-load and zero-stress states. Circumferential and longitudinal stresses and strains were computed from the length, diameter, and pressure data and from the zero-stress state geometry. The blood glucose level increased 3-4-fold in the diabetic rats compared with the controls (P < 0.001). Diabetes generated pronounced increases in the colon weight per length, wall thickness, and wall cross-sectional area (P < 0.001). Histologically, the thickness of all layers was increased during diabetes (P < 0.05), especially the mucosa layer. The opening angle, and absolute values of residual strain increased in the diabetic group (P < 0.05 and P < 0.01, respectively). Furthermore, diabetes increased the circumferential and longitudinal stiffness of the colon wall (P < 0.001). The observed changes in residual strain, opening angle, and stress-strain relation may be contributing factors to colonic dysfunction and abdominal pain in diabetic patients. PMID:18989775

  2. Evaluating retinal circulation using video fluorescein angiography in control and diabetic rats.

    PubMed

    Bursell, S E; Clermont, A C; Shiba, T; King, G L

    1992-04-01

    Video fluorescein angiography has been used to evaluate retinal circulatory parameters in diabetic and non-diabetic Sprague-Dawley rats. Video fluorescein angiograms were recorded from the retina using a modified retinal fundus camera following a 5 ul bolus injection of sodium fluorescein dye into the jugular vein. Retinal circulatory parameters were measured using computer assisted image analysis. These analyses were performed on 25 diabetic rats with 1 week duration of diabetes and 26 matched, non-diabetic, rats. There was a significant (p = .0001) increase in retinal Mean Circulation Time (MCT) in the diabetic group (1.83 +/- 0.40 s) compared to the control group (1.09 +/- 0.27 s). There were no significant differences in arterial or venous diameters comparing diabetic and control groups. In a separate paired experiment, measurements were made from the same animals both before and after one week duration of diabetes. A paired t-test analysis demonstrated significantly increased MCT times in the 6 diabetic animals (p = .001) while there was no significant differences detected in the 4 corresponding control animals. These results indicate that significant increases in retinal circulation times can be measured as early as 1 week after streptozotocin induced diabetes in this animal model. PMID:1388117

  3. 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

  4. GLP-1(7-36)amide binding in skeletal muscle membranes from streptozotocin diabetic rats.

    PubMed

    Villanueva-Peñacarrillo, M L; Delgado, E; Vicent, D; Mérida, E; Alcántara, A I; Valverde, I

    1995-09-01

    A higher specific binding of GLP-1(7-36)amide is found in skeletal muscle plasma membranes from adult streptozotocin (STZ)-treated rats (insulin-dependent diabetes mellitus model) and from neonatal STZ-treated rats (non insulin-dependent diabetes mellitus model), as compared to that in normal controls; no apparent change in the affinity was observed, that indicating the presence in both diabetic models of an increased number of high affinity binding sites for the peptide. The maximal specific GLP-1(7-16)amide binding in the non insulin-dependent diabetes mellitus model was found to be significantly higher than that in the insulin-dependent diabetes mellitus model. As GLP-1(7-36)amide exerts a glycogenic effect in the rat skeletal muscle, the present data suggest that the action of the peptide in the muscle glucose metabolism may be increased in states of insulin deficiency accompanied or not by insulin resistance. PMID:21153227

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

    PubMed Central

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

    2014-01-01

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

  6. Role of GABAB Receptor and L-Arg in GABA-Induced Vasorelaxation in Non-diabetic and Streptozotocin-Induced Diabetic Rat Vessels

    PubMed Central

    Kharazmi, Fatemah; Soltani, Nepton; Rezaei, Sana; Keshavarz, Mansoor; Farsi, Leila

    2015-01-01

    Background: Hypertension is considered an independent risk factor for cardiovascular mortality in diabetic patients. The present study was designed to determine the role of gamma amino butyric acid B (GABAB) receptor and L-arginine (L-Arg) in GABA-induced vasorelaxation in normal and streptozotocin-induced diabetic rat vessels. Methods: Diabetes was induced by a single i.p. injection of streptozotocin (STZ, 60 mg/kg). Eight weeks later, superior mesenteric arteries of all groups were isolated and perfused according to the McGregor method. Results: Baseline perfusion pressure of STZ diabetic rats was significantly higher than non-diabetic rats in both intact and denuded endothelium. In the presence of faclofen, a selective GABAB receptor blocker, GABA-induced relaxation in intact and denuded endothelium mesenteric beds of STZ diabetic rats was suppressed, but this response in non-diabetic rats was not suppressed. Our results showed that in the presence of L-Arg, a nitric oxide precursor, GABA induced vasorelaxation in both diabetic and non-diabetic vessels. Conclusion: From the results of this study, it may be concluded that the vasorelaxatory effect of GABA in diabetic vessel is mediated by the GABAB receptor and nitric oxide, but it seems that in non-diabetic vessel GABAB receptor does not play any role in GABA-induced vasorelaxation, but nitric oxide induced GABA relaxation in non-diabetic vessel. PMID:25864813

  7. Rapid Determination of the Thermal Nociceptive Threshold in Diabetic Rats

    PubMed Central

    Alshahrani, Saeed; Fernandez-Conti, Filipe; Araujo, Amanda; DiFulvio, Mauricio

    2012-01-01

    Painful diabetic neuropathy (PDN) is characterized by hyperalgesia i.e., increased sensitivity to noxious stimulus, and allodynia i.e., hypersensitivity to normally innocuous stimuli1. Hyperalgesia and allodynia have been studied in many different rodent models of diabetes mellitus2. However, as stated by Bölcskei et al, determination of "pain" in animal models is challenging due to its subjective nature3. Moreover, the traditional methods used to determine behavioral responses to noxious thermal stimuli usually lack reproducibility and pharmacological sensitivity3. For instance, by using the hot-plate method of Ankier4, flinch, withdrawal and/or licking of either hind- and/or fore-paws is quantified as reflex latencies at constant high thermal stimuli (52-55 °C). However, animals that are hyperalgesic to thermal stimulus do not reproducibly show differences in reflex latencies using those supra-threshold temperatures3,5. As the recently described method of Bölcskei et al.6, the procedures described here allows for the rapid, sensitive and reproducible determination of thermal nociceptive thresholds (TNTs) in mice and rats. The method uses slowly increasing thermal stimulus applied mostly to the skin of mouse/rat plantar surface. The method is particularly sensitive to study anti-nociception during hyperalgesic states such as PDN. The procedures described bellow are based on the ones published in detail by Almási et al5 and Bölcskei et al3. The procedures described here have been approved the Laboratory Animal Care and Use Committee (LACUC), Wright State University. PMID:22643870

  8. 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

  9. 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

    2016-03-01

    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 35mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Two weeks after diabetes induction, rats were treated with berberine (100mg/kg) and rosiglitazone (4mg/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. PMID:26849937

  10. Cardiac and thermal homeostasis in the aging Brown Norway rat.

    PubMed

    Gordon, Christopher J

    2008-12-01

    The cardiovascular and thermoregulatory systems are considered to be susceptible in the aged population, but little is known about baseline cardiac and thermoregulatory homeostasis in rodent models of aging. Radiotransmitters were implanted in male, Brown Norway rats obtained at 4, 12, and 24 months to monitor the electrocardiogram (ECG), interbeat interval (IBI), heart rate (HR), core temperature (Tc), and motor activity (MA). There was no significant effect of age on resting HR and MA. Daytime Tc of the 24-month-old rats was significantly elevated above those of the 4- and 12-month-old groups. Variability of the IBI was highest in the 24-month-old rats. The elevation in daytime Tc beginning around 8 months of age may be a physiological biomarker of aging and may be an important factor to consider in studies using caloric restriction-induced hypothermia to increase longevity. PMID:19126843

  11. The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats.

    PubMed

    Kong, Wei-Yuan; Tong, Li-Quan; Zhang, Hai-Jun; Cao, Yong-Gang; Wang, Gong-Chen; Zhu, Jin-Zhi; Zhang, Feng; Sun, Xue-Ying; Zhang, Tie-Hui; Zhang, Lin-Lin

    2016-01-01

    Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men. PMID:26387585

  12. The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

    PubMed Central

    Kong, Wei-Yuan; Tong, Li-Quan; Zhang, Hai-Jun; Cao, Yong-Gang; Wang, Gong-Chen; Zhu, Jin-Zhi; Zhang, Feng; Sun, Xue-Ying; Zhang, Tie-Hui; Zhang, Lin-Lin

    2016-01-01

    Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg−1) in Wistar rats. Animals then received GdCl3 (an agonist of CaSR, 8.67 mg kg−1), NPS-2390 (an antagonist of CaSR, 0.20 g kg−1), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men. PMID:26387585

  13. Tocotrienol improves learning and memory deficit of aged rats

    PubMed Central

    Kaneai, Nozomi; Sumitani, Kazumi; Fukui, Koji; Koike, Taisuke; Takatsu, Hirokatsu; Urano, Shiro

    2016-01-01

    To define whether tocotrienol (T-3) improves cognitive deficit during aging, effect of T-3 on learning and memory functions of aged rats was assessed. It was found that T-3 markedly counteracts the decline in learning and memory function in aged rats. Quantitative analysis of T-3 content in the rat brain showed that the aged rats fed T-3 mixture-supplemented diet revealed the transport of α- and γ-T-3 to the brain. In contrast, normal young rats fed the same diet did not exhibit brain localization. Furthermore, the T-3 inhibited age-related decreases in the expression of certain blood brain barrier (BBB) proteins, including caludin-5, occludin and junctional adhesion molecule (JAM). It was found that the activation of the cellular proto-oncogene c-Src and extracellular signal-regulated protein kinase (ERK), in the mitogen-activated protein kinase (MAPK) cell signaling pathway for neuronal cell death, was markedly inhibited by T-3. These results may reveal that aging induces partial BBB disruption caused by oxidative stress, thereby enabling the transport of T-3 through the BBB to the central nervous system, whereupon neuronal protection may be mediated by inhibition of c-Src and/or ERK activation, resulting in an improvement in age-related cognitive deficits. PMID:27013777

  14. Tocotrienol improves learning and memory deficit of aged rats.

    PubMed

    Kaneai, Nozomi; Sumitani, Kazumi; Fukui, Koji; Koike, Taisuke; Takatsu, Hirokatsu; Urano, Shiro

    2016-03-01

    To define whether tocotrienol (T-3) improves cognitive deficit during aging, effect of T-3 on learning and memory functions of aged rats was assessed. It was found that T-3 markedly counteracts the decline in learning and memory function in aged rats. Quantitative analysis of T-3 content in the rat brain showed that the aged rats fed T-3 mixture-supplemented diet revealed the transport of α- and γ-T-3 to the brain. In contrast, normal young rats fed the same diet did not exhibit brain localization. Furthermore, the T-3 inhibited age-related decreases in the expression of certain blood brain barrier (BBB) proteins, including caludin-5, occludin and junctional adhesion molecule (JAM). It was found that the activation of the cellular proto-oncogene c-Src and extracellular signal-regulated protein kinase (ERK), in the mitogen-activated protein kinase (MAPK) cell signaling pathway for neuronal cell death, was markedly inhibited by T-3. These results may reveal that aging induces partial BBB disruption caused by oxidative stress, thereby enabling the transport of T-3 through the BBB to the central nervous system, whereupon neuronal protection may be mediated by inhibition of c-Src and/or ERK activation, resulting in an improvement in age-related cognitive deficits. PMID:27013777

  15. Antidiabetic activity of levan polysaccharide in alloxan-induced diabetic rats.

    PubMed

    Dahech, Imen; Belghith, Karima Srih; Hamden, Khaled; Feki, Abdelfattah; Belghith, Hafedh; Mejdoub, Hafedh

    2011-11-01

    This study aims to examine the effects of polysaccharide levan on oxidative stress and hyperglycemia in alloxan-induced diabetic rats. Levan, used in this study, was a microbial levan synthetisized by a non pathogenic bacteria recently isolated and identified as Bacillus licheniformis. Animals were allocated into four groups of six rats each: a control group (Control), diabetic group (Diab.), normal rats received levan (L) and diabetic rats fed with levan (DL). Treated diabetic rats were administrated with levan in drinking water through oral gavage for 60 days. The administration of polysaccharide levan in diabetic rats caused a significant increase in glycogen level by 52% and a decrease in glucose level in plasma by 52%. Similarly, the administration of polysaccharide levan in diabetic rats caused a decrease in the thiobarbituric acid-reactive substances (TBARS) by 31%, 41%, 39% and 25%, an increase in superoxide dismutase (SOD) by 40%, 50%, 44% and 34%, and in catalase (CAT) by 18%, 20%, 12% and 18% in liver, kidney, pancreas and heart, respectively. Furthermore, a significant decrease in hepatic and renal indices toxicity was observed, i.e. alkalines phosphatases (ALP), aspartate and lactate transaminases (AST and ALT) activities, total bilirubin, creatinine and urea levels by 19%, 31%, 32%, 36%, 37% and 23%, respectively. The results show that administration of polysaccharide levan can restore abnormal oxidative indice near normal levels. This study demonstrates, for the first time, that polysaccharide levan is efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggests that levan supplemented to diet may be helpful in preventing diabetic complications in adult rats. PMID:21782842

  16. 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

  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. 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. PMID:23236955

  19. Aging and the disposition and toxicity of mercury in rats.

    PubMed

    Bridges, Christy C; Joshee, Lucy; Zalups, Rudolfs K

    2014-05-01

    Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg(2+)), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg(2+) in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5μmol·kg(-1) non-nephrotoxic or a 2.5μmol·kg(-1) nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats. PMID:24548775

  20. Gum Arabic extracts protect against hepatic oxidative stress in alloxan induced diabetes in rats.

    PubMed

    Ahmed, Abdelkareem A; Fedail, Jaafar S; Musa, Hassan H; Kamboh, Asghar Ali; Sifaldin, Amal Z; Musa, Taha H

    2015-12-01

    Gum Arabic (GA) from Acacia seyal and Acacia senegal is a branched-chain polysaccharide which has strong antioxidant properties, and has been used to reduce the experimental toxicity. Yet, the effects of GA on oxidative stress in type I diabetic rats have not been reported. The aim of the study was to investigate the effects of GA on oxidative stress in Alloxan induced diabetes in rats. The rats were divided into 3 groups (n=20 of each): control group, diabetic group injected with allaoxan, and diabetic group given 15% GA in drinking water for 8 weeks. Oxidative damage to liver tissue was evaluated by measurement of key hepatic enzymes, lipid peroxidation, antioxidant enzymes and expression of oxidative stress genes. Activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were significantly (P<0.05) increased in GA group compared to diabetic and control groups. Treatment of GA decreased liver malondialdehyde (MDA), and increased glutathione (GSH). In addition, GA was significantly (P<0.05) reduced the activities of key liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST). SOD, GPx and heat shock protein 70 (HSP70) mRNA were significantly increased in GA group compared to control and diabetic groups. Liver of all diabetic rats showed marked degeneration whereas slight degeneration was observed in GA treated rats compared to control. The results suggest that GA may protect liver by modulating the expression of oxidative stress genes, and thus can improve antioxidant status. PMID:26321624

  1. 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. PMID:27331300

  2. 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.

  3. 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

  4. Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats.

    PubMed

    Lupachyk, Sergey; Watcho, Pierre; Shevalye, Hanna; Vareniuk, Igor; Obrosov, Alexander; Obrosova, Irina G; Yorek, Mark A

    2013-08-01

    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

  5. Polysaccharides from Enteromorpha prolifera Improve Glucose Metabolism in Diabetic Rats

    PubMed Central

    Lin, Wenting; Wang, Wenxiang; Liao, Dongdong; Chen, Damiao; Zhu, Pingping; Cai, Guoxi; Kiyoshi, Aoyagi

    2015-01-01

    This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600 mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of islet β-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM. PMID:26347892

  6. RNA sequencing reveals retinal transcriptome changes in STZ-induced diabetic rats

    PubMed Central

    LIU, YUAN-JIE; LIAN, ZHI-YUN; LIU, GENG; ZHOU, HONG-YING; YANG, HUI-JUN

    2016-01-01

    The present study aimed to investigate changes in retinal gene expression in streptozotocin (STZ)-induced diabetic rats using next-generation sequencing, utilize transcriptome signatures to investigate the molecular mechanisms of diabetic retinopathy (DR), and identify novel strategies for the treatment of DR. Diabetes was chemically induced in 10-week-old male Sprague-Dawley rats using STZ. Flash-electroretinography (F-ERG) was performed to evaluate the visual function of the rats. The retinas of the rats were removed to perform high throughput RNA sequence (RNA-seq) analysis. The a-wave, b-wave, oscillatory potential 1 (OP1), OP2 and ∑OP amplitudes were significantly reduced in the diabetic group, compared with those of the control group (P<0.05). Furthermore, the implicit b-wave duration 16 weeks post-STZ induction were significantly longer in the diabetic rats, compared with the control rats (P<0.001). A total of 868 genes were identified, of which 565 were upregulated and 303 were downregulated. Among the differentially expressed genes (DEGs), 94 apoptotic genes and apoptosis regulatory genes, and 19 inflammatory genes were detected. The results of the KEGG pathway significant enrichment analysis revealed enrichment in cell adhesion molecules, complement and coagulation cascades, and antigen processing and presentation. Diabetes alters several transcripts in the retina, and RNA-seq provides novel insights into the molecular mechanisms underlying DR. PMID:26781437

  7. Curcumin attenuates diabetic neuropathic pain by downregulating TNF-α in a rat model.

    PubMed

    Li, Yue; Zhang, Yong; Liu, De-bao; Liu, Hai-ying; Hou, Wu-gang; Dong, Yu-shu

    2013-01-01

    The mechanisms involved in diabetic neuropathic pain are complex and involve peripheral and central pathophysiological phenomena. Proinflammatory tumour necrosis factor α (TNF-α) and TNF-α receptor 1, which are markers of inflammation, contribute to neuropathic pain. The purpose of this experimental study was to evaluate the effect of curcumin on diabetic pain in rats. We tested 24 rats with diabetes induced by a single intraperitoneal injection of streptozotocin and 24 healthy control rats. Twelve rats in each group received 60 mg/kg oral curcumin daily for 28 days, and the other 12 received vehicle. On days 7, 14, 21, and 28, we tested mechanical allodynia with von Frey hairs and thermal hyperalgesia with radiant heat. Markers of inflammation in the spinal cord dorsal horn on day 28 were estimated with a commercial assay and Western blot analysis. Compared to control rats, diabetic rats exhibited increased mean plasma glucose concentration, decreased mean body weight, and significant pain hypersensitivity, as evidenced by decreased paw withdrawal threshold to von Frey hairs and decreased paw withdrawal latency to heat. Curcumin significantly attenuated the diabetes-induced allodynia and hyperalgesia and reduced the expression of both TNF-α and TNF-α receptor 1. Curcumin seems to relieve diabetic hyperalgesia, possibly through an inhibitory action on TNF-α and TNF-α receptor 1. PMID:23471081

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

    PubMed

    Raish, Mohammad; Ahmad, Ajaz; Jan, Basit L; Alkharfy, Khalid M; Ansari, Mushtaq Ahmad; Mohsin, Kazi; Jenoobi, Fahad Al; Al-Mohizea, Abdullah

    2016-10-01

    Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway. PMID:27238589

  9. Antidiabetic effect of Merremia emarginata Burm. F. in streptozotocin induced diabetic rats

    PubMed Central

    Gandhi, G Rajiv; Sasikumar, P

    2012-01-01

    Objective To investigate the antidiabetic property of Merremia emarginata (M. emarginata) Burm. F. plant in streptozotocin induced diabetic rats. Methods The dose dependent effects of 28 days oral treatment with methanol extract (100, 200 and 400 mg/kg) from the plant of M. emarginata on blood glucose level, body weight, insulin, total hemoglobin, glycosylated haemoglobin (HbA1C), total protein, serum urea, serum creatinine and carbohydrate metabolizing enzymes were evaluated in streptozotocin induced diabetic rats. Histology of pancreas was also studied. Results A significant decrease in blood glucose, serum urea and serum creatinine and significant increase in body weight, insulin and protein level were observed in diabetic rats treated with M. emarginata. Treatment with M. emarginata resulted in a significant reduction of HbA1C and an increase in total hemoglobin level. The activities of carbohydrate metabolizing enzymes such as hexokinase were significantly increased whereas glucose-6-phosphatase, fructose-1, 6-bisphosphatase were significantly decreased by the administration of M. emarginata in diabetic rats. Histology of diabetic rats treated with M. emarginata showed the pancreatic β-cells regeneration. Conclusions These findings suggest that M. emarginata has potent antidiabetic activity in streptozotocin induced diabetic rats. PMID:23569914

  10. Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Sundaram, Ramalingam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2014-05-15

    The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide - a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential. PMID:24629597

  11. RNA sequencing reveals retinal transcriptome changes in STZ‑induced diabetic rats.

    PubMed

    Liu, Yuan-Jie; Lian, Zhi-Yun; Liu, Geng; Zhou, Hong-Ying; Yang, Hui-Jun

    2016-03-01

    The present study aimed to investigate changes in retinal gene expression in streptozotocin (STZ)‑induced diabetic rats using next‑generation sequencing, utilize transcriptome signatures to investigate the molecular mechanisms of diabetic retinopathy (DR), and identify novel strategies for the treatment of DR. Diabetes was chemically induced in 10‑week‑old male Sprague‑Dawley rats using STZ. Flash‑electroretinography (F‑ERG) was performed to evaluate the visual function of the rats. The retinas of the rats were removed to perform high throughput RNA sequence (RNA‑seq) analysis. The a‑wave, b‑wave, oscillatory potential 1 (OP1), OP2 and ∑OP amplitudes were significantly reduced in the diabetic group, compared with those of the control group (P<0.05). Furthermore, the implicit b‑wave duration 16 weeks post‑STZ induction were significantly longer in the diabetic rats, compared with the control rats (P<0.001). A total of 868 genes were identified, of which 565 were upregulated and 303 were downregulated. Among the differentially expressed genes (DEGs), 94 apoptotic genes and apoptosis regulatory genes, and 19 inflammatory genes were detected. The results of the KEGG pathway significant enrichment analysis revealed enrichment in cell adhesion molecules, complement and coagulation cascades, and antigen processing and presentation. Diabetes alters several transcripts in the retina, and RNA‑seq provides novel insights into the molecular mechanisms underlying DR. PMID:26781437

  12. Evaluation of Antidiabetic and Antihyperlipidemic Effects of Peganum harmala Seeds in Diabetic Rats

    PubMed Central

    Komeili, Gholamreza; Hashemi, Mohammad; Bameri-Niafar, Mohsen

    2016-01-01

    The present study was carried out to investigate the antidiabetic and antihyperlipidemic properties of hydroalcoholic extract of Peganum harmala in streptozotocin-induced diabetic male rats. In an experimental study, 64 normal Wistar albino male rats (200–230 g) were randomly divided into 8 groups. Control and diabetic rats were treated with normal saline and three different doses (30, 60, and 120 mg/kg) of hydroalcoholic extract of Peganum harmala seeds for 4 weeks orally. At the end of treatment, blood samples were taken and glucose, triglycerides, total cholesterol, LDL-c, HDL-c, malondialdehyde (MDA), total antioxidant capacity (TCA), ALT, AST, GGT, bilirubin, and glycosylated hemoglobin (HbA1C) were determined. STZ-induced diabetic rats showed significant changes in the values of glucose, triglycerides, total cholesterol, LDL-c, MDA, TAC, ALT, AST, GGT, bilirubin, and HbA1C in comparison with normal rats. Administration of the extract to diabetic rats resulted in a remarkable decrease in glucose, lipid profiles, MDA, ALT, AST, GGT, bilirubin, and HbA1C levels and increase in TAC relative to diabetic group. The results of this study indicated that hydroalcoholic extract of Peganum harmala seeds possesses antidiabetic and hypolipidemic activities and could be useful in treatment of diabetes. PMID:27190643

  13. Malignant lesions in the ventral prostate of alloxan-induced diabetic rats

    PubMed Central

    Ribeiro, Daniele Lisboa; Marques, Silvio Fernando Guideti; Alberti, Sandra; Spadella, César Tadeu; Manzato, Antônio José; Taboga, Sebastião Roberto; Dizeyi, Nishtman; Abrahamsson, Per-Anders; Góes, Rejane Maira

    2008-01-01

    The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra-epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl-2-positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology. PMID:18715471

  14. Heat stress attenuates skeletal muscle atrophy of extensor digitorum longus in streptozotocin-induced diabetic rats.

    PubMed

    Nonaka, K; Une, S; Akiyama, J

    2015-09-01

    To investigate whether heat stress attenuates skeletal muscle atrophy of the extensor digitorum longus (EDL) muscle in streptozotocin-induced diabetic rats, 12-week-old male Wistar rats were randomly assigned to four groups (n = 6 per group): control (Con), heat stress (HS), diabetes mellitus (DM), and diabetes mellitus/heat stress (DM + HS). Diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg). Heat stress was induced in the HS and DM + HS groups by immersion of the lower half of the body in hot water at 42 °C for 30 min; it was initiated 7 days after injection of streptozotocin, and was performed once a day, five times a week for 3 weeks. The muscle fiber cross-sectional area of EDL muscles from diabetic and non-diabetic rats was determined; heat stress protein (HSP) 72 and HSP25 expression levels were also analyzed by western blotting. Diabetes-induced muscle fiber atrophy was attenuated upon heat stress treatment in diabetic rats. HSP72 and HSP25 expression was upregulated in the DM + HS group compared with the DM group. Our findings suggest that heat stress attenuates atrophy of the EDL muscle by upregulating HSP72 and HSP25 expression. PMID:26551745

  15. [Effect and mechanism of icariin on myocardial ischemia-reperfusion injury model in diabetes rats].

    PubMed

    Hu, Yan-wu; Liu, Kai; Yan, Meng-tong

    2015-11-01

    To study the therapeutic effect and possible mechanism of icariin on myocardial ischemia-reperfusion injury ( MIRI) model in diabetes rats. The model of diabetic rats were induced by Streptozotocin (STZ), then the model of MIRI was established by ligating the reversible left anterior descending coronary artery for 30 min, and then reperfusing for 120 min. totally 40 male SD were randomly divided into five groups: the control group (NS), the ischemia reperfusion group (NIR), the diabetes control group (MS), the diabetic ischemia reperfusion group (MIR) and the diabetic ischemia reperfusion with icariin group (MIRI). The changes in blood glucose, body weight and living status were observed; the enzyme activity of serum CK-MB, LDH, GSH-Px and myocardium SOD and the content MDA and NO in myocardium were detected; the myocardial pathological changes were observed by HE staining; the myocardial Caspase-3, the Bcl-2, Bax protein expressions were detected by Western blot. The result showed that the diabetes model was successfully replicated; myocardial ischemia-reperfusion injury was more serious in diabetes rats; icariin can increase NO, SOD, GSH-Px, Bcl-2 protein expression, decrease MDA formation, CK-MB and LDH activities and Caspase-3 and Bcl-2 protein expressions and myocardial damage. The result suggested that icariin may play a protective role against ischemia reperfusion myocardial injury in diabetes rats by resisting oxidative stress and inhibiting cell apoptosis. PMID:27071263

  16. Hypolipidemic, Hepatoprotective and Renoprotective Effects of Cydonia Oblonga Mill. Fruit in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Mirmohammadlu, Mansur; Hosseini, Seyed Hojjat; Kamalinejad, Mohammad; Esmaeili Gavgani, Majid; Noubarani, Maryam; Eskandari, Mohammad Reza

    2015-01-01

    Diabetes mellitus is associated with complications in several different systems of the body, and the incidence of diabetes is rapidly increasing worldwide. The objective of the present study was to evaluate the effect of aqueous extract of Cydonia oblonga Mill. Fruit on lipid profile and some biochemical parameters in streptozotocin-induced diabetic rats. The extract showed anti hyper lipidemic activity as evidenced by significant decreases in serum triglyceride, total cholesterol, and low density lipoprotein cholesterol (LDL-C) levels along with the elevation of high density lipoprotein cholesterol (HDL-C) in the diabetic rats. The biochemical liver functional tests were also analyzed and it was shown that serum biomarkers of liver dysfunction, including alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were significantly reduced in aqueous extract of Cydonia oblonga Mill. treated diabetic rats. In addition, our results showed that the oral administration of the extract prevented diabetes-induced increase in serum urea and creatinine levels as the markers of renal dysfunction. In conclusion, the present study indicates that aqueous extract of Cydonia oblonga Mill. Is able to improve some of the symptoms associated with diabetes and possesses hypolipidemic, hepatoprotective, and renoprotective effects in streptozotocin-induced diabetic rats. PMID:26664388

  17. Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function.

    PubMed

    Picke, Ann-Kristin; Salbach-Hirsch, Juliane; Hintze, Vera; Rother, Sandra; Rauner, Martina; Kascholke, Christian; Möller, Stephanie; Bernhardt, Ricardo; Rammelt, Stefan; Pisabarro, M Teresa; Ruiz-Gómez, Gloria; Schnabelrauch, Matthias; Schulz-Siegmund, Michaela; Hacker, Michael C; Scharnweber, Dieter; Hofbauer, Christine; Hofbauer, Lorenz C

    2016-07-01

    Bone fractures in patients with diabetes mellitus heal poorly and require innovative therapies to support bone regeneration. Here, we assessed whether sulfated hyaluronan included in collagen-based scaffold coatings can improve fracture healing in diabetic rats. Macroporous thermopolymerized lactide-based scaffolds were coated with collagen including non-sulfated or sulfated hyaluronan (HA/sHA3) and inserted into 3 mm femoral defects of non-diabetic and diabetic ZDF rats. After 12 weeks, scaffolds coated with collagen/HA or collagen/sHA3 accelerated bone defect regeneration in diabetic, but not in non-diabetic rats as compared to their non-coated controls. At the tissue level, collagen/sHA3 promoted bone mineralization and decreased the amount of non-mineralized bone matrix. Moreover, collagen/sHA3-coated scaffolds from diabetic rats bound more sclerostin in vivo than the respective controls. Binding assays confirmed a high binding affinity of sHA3 to sclerostin. In vitro, sHA3 induced BMP-2 and lowered the RANKL/OPG expression ratio, regardless of the glucose concentration in osteoblastic cells. Both sHA3 and high glucose concentrations decreased the differentiation of osteoclastic cells. In summary, scaffolds coated with collagen/sHA3 represent a potentially suitable biomaterial to improve bone defect regeneration in diabetic conditions. The underlying mechanism involves improved osteoblast function and binding sclerostin, a potent inhibitor of Wnt signaling and osteoblast function. PMID:27131598

  18. Hypolipidemic, Hepatoprotective and Renoprotective Effects of Cydonia Oblonga Mill. Fruit in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Mirmohammadlu, Mansur; Hosseini, Seyed Hojjat; Kamalinejad, Mohammad; Esmaeili Gavgani, Majid; Noubarani, Maryam; Eskandari, Mohammad Reza

    2015-01-01

    Diabetes mellitus is associated with complications in several different systems of the body, and the incidence of diabetes is rapidly increasing worldwide. The objective of the present study was to evaluate the effect of aqueous extract of Cydonia oblonga Mill. Fruit on lipid profile and some biochemical parameters in streptozotocin-induced diabetic rats. The extract showed anti hyper lipidemic activity as evidenced by significant decreases in serum triglyceride, total cholesterol, and low density lipoprotein cholesterol (LDL-C) levels along with the elevation of high density lipoprotein cholesterol (HDL-C) in the diabetic rats. The biochemical liver functional tests were also analyzed and it was shown that serum biomarkers of liver dysfunction, including alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were significantly reduced in aqueous extract of Cydonia oblonga Mill. treated diabetic rats. In addition, our results showed that the oral administration of the extract prevented diabetes-induced increase in serum urea and creatinine levels as the markers of renal dysfunction. In conclusion, the present study indicates that aqueous extract of Cydonia oblonga Mill. Is able to improve some of the symptoms associated with diabetes and possesses hypolipidemic, hepatoprotective, and renoprotective effects in streptozotocin-induced diabetic rats. PMID:26664388

  19. L-tryptophan suppresses rise in blood glucose and preserves insulin secretion in type-2 diabetes mellitus rats.

    PubMed

    Inubushi, Tomoko; Kamemura, Norio; Oda, Masataka; Sakurai, Jun; Nakaya, Yutaka; Harada, Nagakatsu; Suenaga, Midori; Matsunaga, Yoichi; Ishidoh, Kazumi; Katunuma, Nobuhiko

    2012-01-01

    Ample evidence indicates that a high-protein/low-carbohydrate diet increases glucose energy expenditure and is beneficial in patients with type-2 diabetes mellitus (T2DM). The present study was designed to investigate the effects of L-tryptophan in T2DM. Blood glucose was measured by the glucose dehydrogenase assay and serum insulin was measured with ELISA in both normal and hereditary T2DM rats after oral glucose administration with or without L-D-tryptophan and tryptamine. The effect of tryptophan on glucose absorption was examined in the small intestine of rats using the everted-sac method. Glucose incorporation in adipocytes was assayed with [(3)H]-2-deoxy-D-glucose using a liquid scintillation counter. Indirect computer-regulated respiratory gas-assay calorimetry was applied to assay energy expenditure in rats. L-Tryptophan suppressed both serum glucose and insulin levels after oral glucose administration and inhibited glucose absorption from the intestine. Tryptamine, but not L-tryptophan, enhanced insulin-stimulated [(3)H]-glucose incorporation into differentiated adipocytes. L-Tryptophan increased glucose-associated energy expenditure in rats in vivo. L-Tryptophan-rich chow consumed from a young age preserved the secretion of insulin and delayed the progression of T2DM in hereditary diabetic rats. The results suggested that L-tryptophan suppresses the elevation of blood glucose and lessens the burden associated with insulin secretion from β-cells. PMID:23419400

  20. Hypoglycemic and Hepatoprotective Activity of Fermented Fruit Juice of Morinda citrifolia (Noni) in Diabetic Rats

    PubMed Central

    Nayak, B. Shivananda; Marshall, Julien R.; Isitor, Godwin; Adogwa, Andrew

    2011-01-01

    Morinda citrifolia is a medicinal plant used to treat diabetes and liver diseases. The fermented fruit juice of the M. Citrifolia (optical density = 1.25) was used to study the hypoglycemic and hepatoprotective properties in diabetes-induced rats. The rats were randomly distributed into 4 groups (control, diabetic experimental, diabetic standard, and diabetic untreated) of 6 each. Diabetes was induced by administering Streptozotocin (50 mg/kg body weight). Fasting blood glucose, body mass, liver tissue glycogen content, and the extent of liver degeneration were assessed. Diabetic experimental animals were treated with M. citrifolia juice (2 ml/kg, twice a day) and diabetic standard with reference hypoglycemic drug, glibenclamide orally for 20 days. Both the groups exhibited a significant reduction in blood glucose level of 150 mg/dl ±15.88 and 125 mg/dl ±3.89, respectively, as compared to diabetic untreated with FBS = 360.0 mg/dl ±15.81, (P < .003). On 10th day of experiment, diabetic experimental animals exhibited a decrease in body mass (10.2 g, 5.11%) which increased significantly by the 20th day (6 g, 3.0%, P < .022). Histological study of liver tissue obtained from untreated diabetic animals revealed significant fatty degeneration as compared to other three groups. The data of this study proved the hypoglycemic and hepatoprotective activity of M. citrifolia. PMID:20981320

  1. Antidiabetic and antihyperlipidaemic activity of ethanol extract of Melastoma malabathricum Linn. leaf in alloxan induced diabetic rats

    PubMed Central

    Balamurugan, Karuppasamy; Nishanthini, Antony; Mohan, Veerabahu Ramasamy

    2014-01-01

    Objective To evaluate the antidiabetic and antihyperlipidaemic effect of ethanol extract of Melastoma malabathricum (M. malabathricum) Linn. leaf in alloxan induced diabetic rats. Methods Diabetes was induced in albino rats by administration of alloxan monohydrate (150 mg/kg i.p). the ethanol extracts of M. malabathricum at a dose of 150 and 300 mg/kg of body weight were administrated at a single dose per day to diabetes induced rats for a period of 14 d. The effect of ethanol extract of M. malabathricum leaf extract on blood glucose, plasma insulin, creatinine, glycosylated haemoglobin, urea serum lipid profile [total cholesterol, triglycerides, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and phospholipid, serum protein, albumin, globulin, serum enzymes (serum glutamate pyruvate transaminases), serum glutamate oxaloacetate transaminases, and alkaline phosphatase] were measured in the diabetic rats. Results In the acute toxicity study, ethanol extract of M. malabathricum leaf was non-toxic at 2 000 mg/kg in rats. The increased body weight, decreased blood glucose, glycosylated haemoglobin and other biochemical parameters level were observed in diabetic rats treated with both doses of ethanol extract of M. malabathricum leaf compared to diabetic control rats. In diabetic rats, ethanol extract of M. malabathricum leaf administration, altered lipid profiles were reversed to near normal than diabetic control rats. Conclusions Ethanol extract of M. malabathricum leaf possesses significant antidiabetic and antihyperlipidaemic activity in diabetic rats. PMID:25183126

  2. Effects of chlorogenic acid, caffeine, and coffee on behavioral and biochemical parameters of diabetic rats.

    PubMed

    Stefanello, Naiara; Schmatz, Roberta; Pereira, Luciane Belmonte; Rubin, Maribel A; da Rocha, João Batista Teixeira; Facco, Graziela; Pereira, Maria Ester; Mazzanti, Cinthia Melazzo de Andrade; Passamonti, Sabina; Rodrigues, Marília Valvassori; Carvalho, Fabiano Barbosa; da Rosa, Michelle Melgarejo; Gutierres, Jessie Martins; Cardoso, Andréia Machado; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2014-03-01

    Diabetes mellitus (DM) is associated with brain alterations that may contribute to cognitive dysfunctions. Chlorogenic acid (CGA) and caffeine (CA), abundant in coffee (CF), are natural compounds that have showed important actions in the brain. The present study aimed to evaluate the effect of CGA, CA, and CF on acetylcholinesterase (AChE), Na(+), K(+)-ATPase, aminolevulinate dehydratase (δ-ALA-D) activities and TBARS levels from cerebral cortex, as well as memory and anxiety in streptozotocin-induced diabetic rats. Animals were divided into eight groups (n = 5-10): control; control/CGA 5 mg/kg; control/CA 15 mg/kg; control/CF 0.5 g/kg; diabetic; diabetic/CGA 5 mg/kg; diabetic/CA 15 mg/kg; and diabetic/CF 0.5 g/kg. Our results demonstrated an increase in AChE activity and TBARS levels in cerebral cortex, while δ-ALA-D and Na(+), K(+)-ATPase activities were decreased in the diabetic rats when compared to control water group. Furthermore, a memory deficit and an increase in anxiety in diabetic rats were observed. The treatment with CGA and CA prevented the increase in AChE activity in diabetic rats when compared to the diabetic water group. CGA, CA, and CF intake partially prevented cerebral δ-ALA-D and Na(+), K(+)-ATPase activity decrease due to diabetes. Moreover, CGA prevented diabetes-induced TBARS production, improved memory, and decreased anxiety. In conclusion, among the compounds studied CGA proved to be a compound which acts better in the prevention of brain disorders promoted by DM. PMID:24370728

  3. Histophysiology of the obesity-diabetes syndrome in sand rats.

    PubMed

    Hahn von Dorsche, H; Schäfer, H; Titlbach, M

    1994-01-01

    Insulin, glucagon, somatostatin, and PP cells were found by immunotopochemical and electron-optical techniques in the islets of Langerhans of the sand rat, proving that the islets in this species also contain the four basic cell types known to be found in the islets in mammals in general. The ratio of A cells to B cells was 1:4 (19.1% A cells to 80.9% B cells). The pancreas of the sand rat contained assemblages of various numbers of neurons in the intralobal and interlobular connective tissue. They did not seem related in any regular fashion to specific blood vessels or branches of the pancreatic ducts. No bundles of nerve fibers were found by either light or electron microscopy. Nonmyelinated nerve fibers were detected by electron microscopy in the stroma of the islets. In the sand rat the neuroinsular complexes are formed by the penetration of single nerve cells into the pancreatic islets. In the NH or long-term group the islets exhibited signs of stimulation. The number of islets was higher than normal (polynesia), with the islets themselves enlarged (macronesia). Double islets in the secretory ducts of the exocrine pancreas were frequent. The increase in islet size was due to hyperplasia of the B cells. The numbers of beta-granules in the B cells varied considerably. Glycogen was demonstrated in some islets. The fusion of beta-granules was shown in electron microscopic pictures. The electron-opaque centers of these granules were brighter than the others and appeared to have partly dissolved. The organelles of the B cells (ER, Golgi apparatus, and mitochondria) were well developed, this also being a sign of cell stimulation. No changes were observed in the B and PP cells. Stimulation of the islet cells was even more pronounced in the diabetic group. Due to hyperplasia, the islets in this group were significantly larger not only than those in the control group, but also than those in the NH group. The pancreata of this group of sand rats contained numerous small

  4. Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats

    PubMed Central

    Soni, Hardik; Patel, Sejal; Patel, Ghanshyam; Paranjape, Archana

    2014-01-01

    Background: Glucova Active Tablet is a proprietary Ayurvedic formulation with ingredients reported for anti-hyperglycemic, anti-hyperlipidemic activity and antioxidant properties. Objective: Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats. Materials and Methods: Experimental Type I diabetes was induced in 24 albino rats with intra-peritoneal injection of streptozotocin (50 mg/kg). Type II diabetes was induced in 18 albino rats by intra-peritoneal injection of streptozotocin (35 mg/kg) along with high fat diet. The rats were divided in 5 groups for Type I model and 4 groups for Type II model. Normal control group was kept common for both experimental models. Glucova Active Tablet (108 mg/kg) treatment was provided for 28 days twice daily orally. Fasting blood glucose level, serum lipid profile and liver anti-oxidant parameters like superoxide dismutase and reduced glutathione was carried out in both experimental models. Pancreas histopathology was also done. Statistical analysis were done by ‘analysis of variance’ test followed by post hoc Tukey's test, with significant level of P < 0.05. Results and Discussion: Glucova Active Tablet showed significant effect on fasting blood glucose level. It also showed significant alteration in lipid profile and antioxidant parameters. Histopathology study revealed restoration of beta cells in pancreas in Glucova Active Tablet treated group. Conclusion: Finding of this study concludes that Glucova Active Tablet has shown promising anti-diabetic activity in Type I and Type II diabetic rats. It was also found showing good anti-hyperlipidemic activity and anti-oxidant property. PMID:24948860

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

    PubMed Central

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

    2016-01-01

    Background: Makaradhwaja a gold containing mercurial preparation used for diabetes mellitus in indigenous system of medicine. It is a popular aphrodisiac and rejuvenator traditional medicine. It is prepared by using processed gold, mercury and sulfur in different ratios by applying intermittent heating pattern in Valuka Yantra. Objectives: The aim of the study was to evaluate anti-diabetic effect of Shadguna Balijarita Makaradhwaja (SBM) on streptozotocin (STZ) induced diabetic rats. Materials and Methods: Diabetes was induced to normal rats by injecting STZ in dose 40 mg/kg. Powdered SBM and dried extract of Tinospora cordifolia were mixed with honey and administered orally for 20 days at dose 2.63 mg/kg and 42.34 mg/kg body weight, respectively. The effects of treatment on body weight changes and blood glucose levels were quantified on day 1, 5, 10, 15 and 21 of the experiments. On the 21st day, animals were sacrificed and gross histopathological changes in liver, kidney and pancreas were illustrated. Blood sugar level, glyacated hemoglobin, blood urea, serum cholesterol, serum creatinine, serum triglyceride and serum protein were estimated with standard methods. The study was conducted in the year 2011. Results: Test drug observed significant decrease (P < 0.001) in glyacated hemoglobin level compared to diabetic control rats. Blood sugar level of test drug group shown a significant decrease (279.11 ± 57.95) compared with diabetic rats. Conclusion: The present study demonstrates that SBM and dried extract of T. cordifolia with honey significantly reduces the blood glucose level and shows anti-diabetic effect. PMID:27104037

  6. Protection against Myocardial Ischemia-Reperfusion Injury at Onset of Type 2 Diabetes in Zucker Diabetic Fatty Rats Is Associated with Altered Glucose Oxidation

    PubMed Central

    Povlsen, Jonas Agerlund; Løfgren, Bo; Dalgas, Christian; Birkler, Rune Isak Dupont; Johannsen, Mogens; Støttrup, Nicolaj Brejnholt; Bøtker, Hans Erik

    2013-01-01

    Background Inhibition of glucose oxidation during initial reperfusion confers protection against ischemia-reperfusion (IR) injury in the heart. Mitochondrial metabolism is altered with progression of type 2 diabetes (T2DM). We hypothesized that the metabolic alterations present at onset of T2DM induce cardioprotection by metabolic shutdown during IR, and that chronic alterations seen in late T2DM cause increased IR injury. Methods Isolated perfused hearts from 6 (prediabetic), 12 (onset of T2DM) and 24 (late T2DM) weeks old male Zucker diabetic fatty rats (ZDF) and their age-matched heterozygote controls were subjected to 40 min ischemia/120 min reperfusion. IR injury was assessed by TTC-staining. Myocardial glucose metabolism was evaluated by glucose tracer kinetics (glucose uptake-, glycolysis- and glucose oxidation rates), myocardial microdialysis (metabolomics) and tissue glycogen measurements. Results T2DM altered the development in sensitivity towards IR injury compared to controls. At late diabetes ZDF hearts suffered increased damage, while injury was decreased at onset of T2DM. Coincident with cardioprotection, oxidation of exogenous glucose was decreased during the initial and normalized after 5 minutes of reperfusion. Metabolomic analysis of citric acid cycle intermediates demonstrated that cardioprotection was associated with a reversible shutdown of mitochondrial glucose metabolism during ischemia and early reperfusion at onset of but not at late type 2 diabetes. Conclusions The metabolic alterations of type 2 diabetes are associated with protection against IR injury at onset but detrimental effects in late diabetes mellitus consistent with progressive dysfunction of glucose oxidation. These findings may explain the variable efficacy of cardioprotective interventions in individuals with type 2 diabetes. PMID:23704975

  7. Increased sensitivity to transient global ischemia in aging rat brain.

    PubMed

    Xu, Kui; Sun, Xiaoyan; Puchowicz, Michelle A; LaManna, Joseph C

    2007-01-01

    Transient global brain ischemia induced by cardiac arrest and resuscitation (CAR) results in reperfusion injury associated with oxidative stress. Oxidative stress is known to produce delayed selective neuronal cell loss and impairment of brainstem function, leading to post-resuscitation mortality. Levels of 4-hydroxy-2-nonenal (HNE) modified protein adducts, a marker of oxidative stress, was found to be elevated after CAR in rat brain. In this study we investigated the effects of an antioxidant, alpha-phenyl-tert-butyl-nitrone (PBN) on the recovery following CAR in the aged rat brain. Male Fischer 344 rats (6, 12 and 24-month old) underwent 7-minute cardiac arrest before resuscitation. Brainstem function was assessed by hypoxic ventilatory response (HVR) and HNE-adducts were measured by western blot analysis. Our data showed that in the 24-month old rats, overall survival rate, hippocampal CAl neuronal counts and HVR were significantly reduced compared to the younger rats. With PBN treatment, the recovery was improved in the aged rat brain, which was consistent with reduced HNE adducts in brain following CAR. Our data suggest that aged rats are more vulnerable to oxidative stress insult and treatment with PBN improves the outcome following reperfusion injury. The mechanism of action is most likely through the scavenging of reactive oxygen species resulting in reduced lipid peroxidation. PMID:17727265

  8. Stimulation of insulin secretion by Viscum album (mistletoe) leaf extract in streptozotocin-induced diabetic rats.

    PubMed

    Eno, A E; Ofem, O E; Nku, C O; Ani, E J; Itam, E H

    2008-06-01

    Twenty male white rats (250-300 g) of Wistar strain were randomly divided into two batches, the normoglycaemic batch and the streptozotocin-induced diabetic batch often rats each. Animals in each batch were further divided into two groups of five rats per group. After an overnight fast (12 hrs), animals in each group received D-glucose load (2.0 g/kg.i.v) under pentobarbital anaesthesia, with or without the crude extract (100 mg/kg/iv). Blood samples were collected intravenously at 15 min intervals for 3 hrs. for analysis of glucose, insulin and glucagon levels. From the results, the extract (100 mg/kg) did not appear to have any significant effect on the blood glucose level of normal rats, but produced about 35.3% decrease in the diabetic rats. Despite the apparent lack of action on glucose level of normal rats, the extract stimulated insulin secretion by about 92.9% (% control) in this group, and about 81.5% in the diabetic group (% control). The glucagon level was not altered by the extract in the normal rats. In the diabetic group, there was mild but significant suppression ofglucagon level after the first 1 hr. which lasted for about 50 min. We suggest that this extract from V. album leaves may possess antihyperglycaemic, insulinotropic, and possibly, mild glucagonostatic agent(s) and may therefore be a candidate for the anti-diabetic drugs. PMID:18939397

  9. Inhibition of α-Glucosidase by Thiosulfinate as a Target for Glucose Modulation in Diabetic Rats

    PubMed Central

    2016-01-01

    Postprandial hyperglycemia is a predisposing factor for vascular dysfunction and organ damage. α-glucosidase is a hydrolytic enzyme that increases the glucose absorption rate and subsequently elevates blood glucose levels. Garlic (Allium sativum L.) is a rich source of several phytonutrients, including thiosulfinate (THIO). The aim of this study was to evaluate the ability of THIO, a potent inhibitor of intestinal α-glucosidase, to reduce postprandial blood glucose. Male albino rats were randomly assigned to five different groups (n = 10/group). Group 1 served as the control group. Groups 2–5 were injected intraperitoneally with a single dose of streptozotocin (STZ) to induce diabetes. Group 2 comprised untreated diabetic rats. Groups 3 and 4 contained diabetic rats that were given THIO orally (20 mg/kg body weight/day and 40 mg/kg body weight/day, resp.). Group 5 was the positive control having diabetic rats treated orally with acarbose (10 mg/kg body weight/day; positive control). Diabetic rats treated with THIO displayed a significant blood glucose reduction (p < 0.001 and < 0.01 by analysis of variance, resp.) and a significant elevation in insulin compared with that of untreated rats. THIO is an effective noncompetitive intestinal α-glucosidase inhibitor that promotes hypoglycemic action (p < 0.001) in STZ-injected rats. THIO is a promising agent for the management of postprandial hyperglycemia. PMID:27051452

  10. Inhibition of α-Glucosidase by Thiosulfinate as a Target for Glucose Modulation in Diabetic Rats.

    PubMed

    Al-Malki, Abdulrahman L

    2016-01-01

    Postprandial hyperglycemia is a predisposing factor for vascular dysfunction and organ damage. α-glucosidase is a hydrolytic enzyme that increases the glucose absorption rate and subsequently elevates blood glucose levels. Garlic (Allium sativum L.) is a rich source of several phytonutrients, including thiosulfinate (THIO). The aim of this study was to evaluate the ability of THIO, a potent inhibitor of intestinal α-glucosidase, to reduce postprandial blood glucose. Male albino rats were randomly assigned to five different groups (n = 10/group). Group 1 served as the control group. Groups 2-5 were injected intraperitoneally with a single dose of streptozotocin (STZ) to induce diabetes. Group 2 comprised untreated diabetic rats. Groups 3 and 4 contained diabetic rats that were given THIO orally (20 mg/kg body weight/day and 40 mg/kg body weight/day, resp.). Group 5 was the positive control having diabetic rats treated orally with acarbose (10 mg/kg body weight/day; positive control). Diabetic rats treated with THIO displayed a significant blood glucose reduction (p < 0.001 and < 0.01 by analysis of variance, resp.) and a significant elevation in insulin compared with that of untreated rats. THIO is an effective noncompetitive intestinal α-glucosidase inhibitor that promotes hypoglycemic action (p < 0.001) in STZ-injected rats. THIO is a promising agent for the management of postprandial hyperglycemia. PMID:27051452

  11. Protective effect of yacon leaves decoction against early nephropathy in experimental diabetic rats.

    PubMed

    Honoré, Stella M; Cabrera, Wilfredo M; Genta, Susana B; Sánchez, Sara S

    2012-05-01

    Nephropathy is the most common cause of morbidity and mortality in diabetic patients. Prevention of this complication has a major relevance. Smallanthus sonchifolius (yacon) leaves have been shown to ameliorate hyperglycemia in streptozotocin-induced diabetic rats. We examined the beneficial effects of yacon leaves decoction on diabetic nephropathy and explored the possible underlying action mechanism. Streptozotocin-diabetic rats were orally administered 10% yacon leaves water decoction (70mg dry extract/kg body weight) once a day for 4weeks. Biochemical parameters in blood and urine were analyzed and immunohistochemistry staining, western immunoblotting and qRT-PCR were assessed. Yacon decoction significantly decreased high blood glucose level in diabetic rats and improved insulin production. Diabetic-dependent alterations in urinary albumin excretion, creatinine clearance, kidney hypertrophy and basement membrane thickening were attenuated by yacon decoction. These findings were associated with a marked decrease in TGF-β1/Smad2/3 signaling. The expression of molecular markers of diabetic nephropathy such as collagen IV, laminin-1, fibronectin and collagen III were also diminished in the yacon-treated group compared to control diabetic group. These results suggest that yacon leaves decoction is a protective agent against renal damage in diabetic nephropathy, whose action can be mediated by TGF-β/Smads signals. PMID:22406203

  12. Enhanced autophagy signaling in diabetic rats with ischemia-induced seizures.

    PubMed

    Xia, Luoxing; Lei, Zhigang; Shi, Zhongshan; Guo, Dave; Su, Henry; Ruan, Yiwen; Xu, Zao C

    2016-07-15

    Seizures are among the most common neurological sequelae of stroke, and ischemic insult in diabetes notably increases the incidence of seizures. Recent studies indicated that autophagy influences the outcome of stroke and involved in epileptogenesis. However, the association of autophagy and post-ischemic seizures in diabetes remains unclear. The present study aimed to reveal the involvement of autophagy in the seizures following cerebral ischemia in diabetes. Diabetes was induced in adult male Wistar rats by intraperitoneal injection of streptozotocin (STZ). The diabetic rats were subjected to transient forebrain ischemia. The neuronal damage was assessed using hematoxylin-eosin staining. Western blotting and immunohistochemistry were performed to investigate the alteration of autophagy marker microtubule-associated protein light chain 1B (LC3B). The results showed that all diabetic animals developed seizures after ischemia. However, no apparent cell death was observed in the hippocampus of seizure rats 12h after the insult. The expression of LC3B was significantly enhanced in naïve animals after ischemia and was further increased in diabetic animals after ischemia. Immunofluorescence double-labeling study indicated that LC3B was mainly increased in neurons. Our study demonstrated, for the first time, that autophagy activity is significantly increased in diabetic animals with ischemia-induced seizures. Further studies are needed to explore the role of autophagy in seizure generation after ischemia in diabetic conditions. PMID:27125597

  13. Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats

    PubMed Central

    Chang, Eugene; Kim, Lisa; Park, Se Eun; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Park, Cheol-Young

    2015-01-01

    AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe (10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides (TG), free fatty acids (FFA), and total cholesterol (TC) in blood and TG, FFA, and TG in liver tissue were measured. mRNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe (10 μmol/L) together with or without palmitic acid (PA, 0.5 mmol/L, 24 h). Transmission electron microscopy (TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression. RESULTS: In the OLETF rats that received ezetimibe (10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight (P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls (P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe (P < 0.05). In addition, autophagy-related mRNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3 (LC3) were significantly increased in the liver in rats that received ezetimibe (P < 0.05). Likewise, for hepatocytes

  14. Acai fruit improves motor and cognitive function in aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks that require the use of spatial learning and memory. In previous studies, we have shown the beneficial effects of various berry fruits (blueberries, strawberries, and blackberries) in reversing age-related deficits in behavioral and ne...

  15. Tart cherries improve working memory in aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on cognitive tasks that require the use of spatial learning and memory. In previous studies, we have shown the beneficial effects of various dark-colored berry fruits (blueberries, strawberries, and blackberries) in reversing age-related deficits in behavioral and...

  16. Red raspberries can improve motor function in aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Many foods rich in antioxidant and anti-inflammatory compounds have been shown to increase health and reduce markers of aging. A number of berry fruits high in polyphenols are known to ameliorate age-related declines in cellular, cognitive and behavioral function in rats. OBJECTIVES: Thi...

  17. Neuropathic pain in aged rats: behavioral responses and astrocytic activation.

    PubMed

    Stuesse, S L; Crisp, T; McBurney, D L; Schechter, J B; Lovell, J A; Cruce, W L

    2001-03-01

    We used the Bennett and Xie (1988) model of chronic neuropathic pain to study the effect of age on thermal and tactile sensitivity and on astrocytic activation in the dorsal horn of the spinal cord after nerve injury. Fischer 344 FBNF1 hybrid rats in three age groups, 4-6, 14-16, and 24-26 months, were studied. Rats were either unligated (day 0, control) or the left sciatic nerve was loosely ligated to cause a chronic constriction injury (CCI). CCI causes a neuropathic pain condition characterized by tactile allodynia and thermal hyperalgesia. Rats were behaviorally assessed for tactile and thermal sensitivity of their ligated and unligated hind paws up to 35 days postligation. Rats were sacrificed before or at various days postligation, and activated astrocytes were identified at the L4-L5 levels of their spinal cords by use of an antibody to glial fibrillary acid protein (GFAP). The number of GFAP-ir astrocytes in the dorsal horn of the spinal cord in the control, uninjured condition decreased with age (P < or = 0.001) but increased after CCI in all three age groups. After CCI, astrocytic activation in the cord was less robust in aged rats than in younger ones (P < or = 0.01). Not all the CCI rats displayed hyperalgesia to touch and to heat. Rats with an increased sensitivity to heat had increased levels of GFAP-ir in their cords; however, rats with decreased thermal sensitivity also displayed increased GFAP-ir. Thus the presence of activated astrocytes was not correlated with a single behavioral manifestation of neuropathic pain. PMID:11315551

  18. Tinospora cordifolia consumption ameliorates changes in kidney chondroitin sulphate/dermatan sulphate in diabetic rats.

    PubMed

    Joladarashi, Darukeshwara; Chilkunda, Nandini D; Salimath, Paramahans V

    2012-01-01

    Diabetes is known to alter kidney extracellular matrix (ECM) components. Chondroitin sulphate (CS)/dermatan sulphate (DS), an ECM component, which plays an essential role in kidney is altered during diabetes. The focus of this study has been to examine the effect of Tinospora cordifolia (TC) consumption, a potent plant widely used to treat diabetes, on kidney CS/DS. Experimentally induced diabetic rats were fed with diet containing TC at 2·5 and 5 % levels and the effect of it on kidney CS/DS was examined. The CS/DS content and CS:heparan sulphate ratio which was decreased during diabetic condition were ameliorated in TC-fed groups. Disaccharide composition analysis of CS/DS by HPLC showed that decreases in 'E' units and degree of sulphation were modulated in 5 % TC-fed groups. Apparent molecular weight of purified CS/DS from the control rat kidney was found to be 38 kDa which was decreased to 29 kDa in diabetic rat kidney. Rats in 5 % TC-fed groups showed chain length of 38 kDa akin to control rats. Expression of chondroitin 4-O-sulfotransferase-1, dermatan 4-O-sulfotransferase-1 and N-acetylgalactosamine 4 sulphate 6-O-sulfotransferase, enzymes involved in the synthesis of 'E' units which was reduced during diabetic condition, was significantly contained in the 5 % TC-fed group. Purified CS/DS from 5 % TC-fed group was able to bind higher amounts of ECM components, namely type IV collagen and laminin, when compared with untreated diabetic rats. The present results demonstrate that consumption of a diet containing TC at the 5 % level modulates changes in kidney CS/DS which were due to diabetes. PMID:25191554

  19. Effect of Stem Cell Therapy on Induced Diabetic Keratopathy in Albino Rat

    PubMed Central

    Zickri, Maha Baligh; Ahmad, Nagwa Abdel Wahab; Maadawi, Zeinab Mohamad El; Mohamady, Yasmin Kamal; Metwally, Hala Gabr

    2012-01-01

    Background and Objectives: Type 2 diabetes mellitus (DM) is a prevalent disorder. Diabetic keratopathy is a well-known ocular complication secondary to type 2 DM. Topical insulin application did not affect apoptosis and necrosis levels in corneal epithelium. Autologous cell transplantation is not a viable option for diabetic patients with bilateral limbal stem cell deficiency. The present study aimed at assessing the possible effect of hemopoeitic stem cell (HSC) therapy on induced diabetic keratopathy in albino rat. Methods and Results: Fifteen male albino rats were divided into control group of 2 rats, diabetic group of 8 rats receiving single intraperitoneal (IP) injection of 50 mg/kg streptozotocin (STZ). 3 animals were sacrificed 6 weeks following confirmation of diabetes to confirm keratopathy and 5 rats were sacrificed 4 weeks following confirmation of keratopathy. SC therapy group included 5 rats injected with HSCs 6 weeks following confirmation of diabetes and sacrificed 4 weeks following SC therapy. Cord blood collection, stem cells isolation and labeling were performed. Eye specimens were subjected to histological, histochemical, immunohistochemical, morphometric and statistical studies. In diabetic group, the central cornea showed multiple cells with vacuolated cytoplasm and dark nuclei, focal epithelial discontinuity, reduced corneal thickness and less number of layers of corneal and conjunctival epithelia. In stem cell therapy group, few cells with vacuolated cytoplasm and dark nuclei were found in the corneal and conjunctival epithelia with more number of epithelial layers. Conclusions: A definite ameliorating effect of HSC therapy was detected on diabetic keratopathy. The therapeutic cells were effective in limiting corneal epithelial changes. PMID:24298355

  20. Nigella sativa seed decreases endothelial dysfunction in streptozotocin-induced diabetic rat aorta

    PubMed Central

    Abbasnezhad, Abbasali; Niazmand, Saeed; Mahmoudabady, Maryam; Soukhtanloo, Mohammad; Rezaee, Seyed Abdolrahim; Mousavi, Seyed Mojtaba

    2016-01-01

    Objective: Diabetes is an important risk factor for cardiovascular events. The great percent of morbidity in patients with diabetes is due to endothelial dysfunction. The present study investigated the effects of hydroalcholic extract of Nigella sativa (N. sativa) on contractile and dilatation response of isolated aorta in streptozotocin (STZ)-induced diabetic rat. Materials and Methods: Rats were divided into six experimental groups (control, untreated STZ-diabetic, and N. sativa hydroalcholic extract or metformin-treated diabetic rats). Treated rats received N. sativa extract (100, 200, and 400 mg/kg) or metformin (300 mg/kg) by gavage, daily for 6 weeks. Isolated rat thoracic rings were mounted in an organ bath system then contractile and dilatation responses induced by phenylephrine (PE), acetylcholine (ACh), potassium chloride (KCl), and sodium nitroprusside (SNP) were evaluated in different situations. Results: The lower concentrations of N. sativa seed extract (DE 100 and DE 200) and metformin significantly reduced the contractile responses to higher concentrations of PE (10-6 - 10-5 M) compared to diabetic group (p<0.05 to p<0.01). The relaxation response to Ach 10-8 M, was increased in DE 200 and metformin groups compared to diabetic group (p<0.05). The relaxation responses to Ach 10-7 - 10-5 M were significantly higher in all treated groups compared to diabetic group (p<0.05 to p<0.001). Conclusion: Chronic administration of N. sativa seed extract has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats. PMID:27247923

  1. Response of thymus lymphocytes to streptozotocin-induced diabetes and exogenous vitamin C administration in rats.

    PubMed

    Ozerkan, Dilşad; Ozsoy, Nesrin; Cebesoy, Suna

    2014-12-01

    Diabetes causes oxidative stress, which in turn generates excessive free radicals resulting in cellular damage. Vitamin C is an antioxidant that protects tissues and organs from oxidative stress. The thymus is one of the most important lymphoid organs, which regulates T-lymphocyte proliferation and maturation. The aim of this study is to investigate the protective effects of vitamin C on the thymus of streptozotocin (STZ)-induced diabetic rats. The mitotic activity and cell integrity of thymic lymphocytes were explored. Wistar Albino rats were divided into three groups: control (Group 1), STZ-diabetes (Group 2) and vitamin C-treated STZ-diabetics (Group 3). Rats received a single intraperitoneal injection of 45 mg/kg STZ to induce diabetes. Vitamin C (20 mg/kg) was administered intragastrically. Semithin and ultrathin sections were examined under a light or an electron microscope, respectively. Considerable numbers of mitotic lymphocytes were observed in the thymus of control rats. In the diabetic rats, however, numbers of mitotic lymphocytes decreased to ∼57% of controls, and cell division abnormalities were observed. Additionally, diabetic rats showed degeneration in the structure of the thymus including trabecular thickening, accumulation of lipid vacuoles, heterochromatic nuclei and loss of mitochondrial cristae. Degradation of medullar and cortical integrity was also detected. In the vitamin C-treated STZ-diabetic group, the structure of the thymus and mitotic activity of the lymphocytes were similar to the control group. These results suggest that vitamin C protects the thymus against injury caused by diabetes and restores thymocyte mitotic activity. PMID:25145646

  2. Tinospora cordifolia consumption ameliorates changes in kidney chondroitin sulphate/dermatan sulphate in diabetic rats

    PubMed Central

    Joladarashi, Darukeshwara; Chilkunda, Nandini D.; Salimath, Paramahans V.

    2012-01-01

    Diabetes is known to alter kidney extracellular matrix (ECM) components. Chondroitin sulphate (CS)/dermatan sulphate (DS), an ECM component, which plays an essential role in kidney is altered during diabetes. The focus of this study has been to examine the effect of Tinospora cordifolia (TC) consumption, a potent plant widely used to treat diabetes, on kidney CS/DS. Experimentally induced diabetic rats were fed with diet containing TC at 2·5 and 5 % levels and the effect of it on kidney CS/DS was examined. The CS/DS content and CS:heparan sulphate ratio which was decreased during diabetic condition were ameliorated in TC-fed groups. Disaccharide composition analysis of CS/DS by HPLC showed that decreases in ‘E’ units and degree of sulphation were modulated in 5 % TC-fed groups. Apparent molecular weight of purified CS/DS from the control rat kidney was found to be 38 kDa which was decreased to 29 kDa in diabetic rat kidney. Rats in 5 % TC-fed groups showed chain length of 38 kDa akin to control rats. Expression of chondroitin 4-O-sulfotransferase-1, dermatan 4-O-sulfotransferase-1 and N-acetylgalactosamine 4 sulphate 6-O-sulfotransferase, enzymes involved in the synthesis of ‘E’ units which was reduced during diabetic condition, was significantly contained in the 5 % TC-fed group. Purified CS/DS from 5 % TC-fed group was able to bind higher amounts of ECM components, namely type IV collagen and laminin, when compared with untreated diabetic rats. The present results demonstrate that consumption of a diet containing TC at the 5 % level modulates changes in kidney CS/DS which were due to diabetes. PMID:25191554

  3. Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced diabetic rats.

    PubMed

    Nakazawa, Taisuke; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-02-01

    Adenosine is a potent vasodilator of retinal blood vessels and is implicated to be a major regulator of retinal blood flow during metabolic stress, but little is known about the impact of diabetes on the role of adenosine in regulation of retinal hemodynamics. Therefore, we examined how diabetes affects adenosine-induced vasodilation of retinal arterioles. Male Wistar rats were treated with streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6-8 weeks later. Rats were treated with tetrodotoxin (50 microg/kg, intravenously [i.v.]) to eliminate any nerve activity and prevent movement of the eye and infused with methoxamine continuously to maintain adequate systemic circulation. Fundus images were captured with a digital camera that was equipped with a special objective lens, and diameters of retinal arterioles were measured. Adenosine increased diameters of retinal arterioles and decreased systemic blood pressure. These responses were significantly attenuated by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.) and the adenosine triphosphate-dependent K+ (K(ATP)) channel blocker glibenclamide (20 mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats, whereas diabetes did not alter vasodilation of retinal arterioles to adenosine. In contrast, both depressor response and vasodilation of retinal arteriole to acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to adenosine and acetylcholine observed in diabetic rats were diminished by N(G)-nitro-L-arginine methyl ester. There were no differences in the responses to pinacidil, a K(ATP) channel opener, between the diabetic and nondiabetic rats. These results suggest that both the activation of nitric oxide synthase and opening of K(ATP) channels contribute to the vasodilator effects of adenosine in rats in vivo. However, diabetes has no significant impact on the vasodilation mediated by these mechanisms in

  4. 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

  5. Effects of exposure to cigarette smoke prior to pregnancy in diabetic rats

    PubMed Central

    2011-01-01

    Background The purpose of this study was to evaluate the effects of cigarette smoke exposure before pregnancy on diabetic rats and their offspring development. Methods Diabetes was induced by streptozotocin and cigarette smoke exposure was conducted by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Diabetic female Wistar rats were randomly distributed in four experimental groups (n minimum = 13/group): nondiabetic (ND) and diabetic rats exposed to filtered air (D), diabetic rats exposed to cigarette smoke prior to and into the pregnancy period (DS) and diabetic rats exposed to cigarette smoke prior to pregnancy period (DSPP). At day 21 of pregnancy, rats were killed for maternal biochemical determination and reproductive outcomes. Results The association of diabetes and cigarette smoke in DSPP group caused altered glycemia at term, reduced number of implantation and live fetuses, decreased litter and maternal weight, increased pre and postimplantation loss rates, reduced triglyceride and VLDL-c concentrations, increased levels of thiol groups and MDA. Besides, these dams presented increased SOD and GSH-Px activities. However, the increased antioxidant status was not sufficient to prevent the lipid peroxidation observed in these animals. Conclusion Despite the benefits stemming from smoking interruption during the pregnancy of diabetic rats, such improvement was insufficient to avoid metabolic alterations and provide an adequate intrauterine environment for embryofetal development. Therefore, these results suggest that it is necessary to cease smoking extensive time before planning pregnancy, since stopping smoking only when pregnancy is detected may not contribute effectively to fully adequate embryofetal development. PMID:21851636

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

    PubMed

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

    2010-09-01

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

  7. Constitutively Elevated Blood Serotonin Is Associated with Bone Loss and Type 2 Diabetes in Rats.

    PubMed

    Erjavec, Igor; Bordukalo-Niksic, Tatjana; Brkljacic, Jelena; Grcevic, Danka; Mokrovic, Gordana; Kesic, Maja; Rogic, Dunja; Zavadoski, William; Paralkar, Vishwas M; Grgurevic, Lovorka; Trkulja, Vladimir; Cicin-Sain, Lipa; Vukicevic, Slobodan

    2016-01-01

    Reduced peripheral serotonin (5HT) in mice lacking tryptophan hydroxylase (TPH1), the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton. However, in other studies TPH1 deletion either had no bone effect or an age dependent inhibition of osteoclastic bone resorption. The role of 5HT in bone therefore remains poorly understood. To address this issue, we used selective breeding to create rat sublines with constitutively high (high-5HT) and low (low-5HT) platelet 5HT level (PSL) and platelet 5HT uptake (PSU). High-5HT rats had decreased bone volume due to increased bone turnover characterized by increased bone formation and mineral apposition rate, increased osteoclast number and serum C-telopeptide level. Daily oral administration of the TPH1 inhibitor (LX1032) for 6 weeks reduced PSL and increased the trabecular bone volume and trabecular number of the spine and femur in high-5HT rats. High-5HT animals also developed a type 2 diabetes (T2D) phenotype with increased: plasma insulin, glucose, hemoglobin A1c, body weight, visceral fat, β-cell pancreatic islets size, serum cholesterol, and decreased muscle strength. Serum calcium accretion mediated by parathyroid hormone slightly increased, whereas treatment with 1,25(OH)2D3 decreased PSL. Insulin reduction was paralleled by a drop in PSL in high-5HT rats. In vitro, insulin and 5HT synergistically up-regulated osteoblast differentiation isolated from high-5HT rats, whereas TPH1 inhibition decreased the number of bone marrow-derived osteoclasts. These results suggest that constitutively elevated PSL is associated with bone loss and T2D via a homeostatic interplay between the peripheral 5HT, bone and insulin. PMID:26907598

  8. Constitutively Elevated Blood Serotonin Is Associated with Bone Loss and Type 2 Diabetes in Rats

    PubMed Central

    Brkljacic, Jelena; Grcevic, Danka; Mokrovic, Gordana; Kesic, Maja; Rogic, Dunja; Zavadoski, William; Paralkar, Vishwas M.; Grgurevic, Lovorka; Trkulja, Vladimir; Cicin-Sain, Lipa; Vukicevic, Slobodan

    2016-01-01

    Reduced peripheral serotonin (5HT) in mice lacking tryptophan hydroxylase (TPH1), the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton. However, in other studies TPH1 deletion either had no bone effect or an age dependent inhibition of osteoclastic bone resorption. The role of 5HT in bone therefore remains poorly understood. To address this issue, we used selective breeding to create rat sublines with constitutively high (high-5HT) and low (low-5HT) platelet 5HT level (PSL) and platelet 5HT uptake (PSU). High-5HT rats had decreased bone volume due to increased bone turnover characterized by increased bone formation and mineral apposition rate, increased osteoclast number and serum C-telopeptide level. Daily oral administration of the TPH1 inhibitor (LX1032) for 6 weeks reduced PSL and increased the trabecular bone volume and trabecular number of the spine and femur in high-5HT rats. High-5HT animals also developed a type 2 diabetes (T2D) phenotype with increased: plasma insulin, glucose, hemoglobin A1c, body weight, visceral fat, β-cell pancreatic islets size, serum cholesterol, and decreased muscle strength. Serum calcium accretion mediated by parathyroid hormone slightly increased, whereas treatment with 1,25(OH)2D3 decreased PSL. Insulin reduction was paralleled by a drop in PSL in high-5HT rats. In vitro, insulin and 5HT synergistically up-regulated osteoblast differentiation isolated from high-5HT rats, whereas TPH1 inhibition decreased the number of bone marrow-derived osteoclasts. These results suggest that constitutively elevated PSL is associated with bone loss and T2D via a homeostatic interplay between the peripheral 5HT, bone and insulin. PMID:26907598

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

    PubMed Central

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

    2015-01-01

    Aim To assess the effects of protein C activator (PCA) from Agkistrodon halys snake venom on cardiac fibrosis in streptozotocin (STZ) induced diabetic rat model, and investigate the mechanisms of its action. Methods PCA was identified by one-dimensional reversed phase liquid chromatography – mass spectrometry/mass spectrometry. Male Sprague-Dawley rats (120-140 g) were randomly assigned to negative control (NC) and diabetic group. Diabetes was induced by STZ in high-fat diet fed rats. Diabetic group was subdivided into three groups: diabetic group (DM), diabetic group treated with PCA (0.5, 2, and 8 mg/kg), and diabetic group treated with metformin (5 mg/kg, positive control). NC and DM groups received the same volume of distilled water. Left ventricular mass index (LVWI) and collagen volume fraction were measured by hematoxylin and eosin and Masson staining. Transforming growth factor beta-1 (TGF-β1) and interleukin 1 beta (IL-1β) levels were determined by enzyme-linked immunosorbent assay. Results The diabetic rat model was successfully established by STZ induction and high-fat diet. Glucose level, LVWI, TGF-β1 and IL-1β level, and collagen volume fraction were significantly reduced in diabetic rats treated by PCA in a dose-dependent manner (P < 0.050), especially in the high dose (8 mg/kg) group (P < 0.010), compared to diabetes group. The high dose PCA had the same effect as metformin positive control in reducing the level of fasting blood glucose. PCA decreased the expression of MMP-2 and reduced that of TIMP-2. Conclusion Our results indicate that PCA has anti-fibrotic effects and that it may be used to treat myocardial fibrosis. PMID:26526881

  10. Sesame effects on testicular damage in streptozotocin-induced diabetes rats

    PubMed Central

    Khaneshi, Fereshteh; Nasrolahi, Ozra; Azizi, Shahriar; Nejati, Vahid

    2013-01-01

    Objective(s): Reproductive dysfunction is a consequence of diabetes. Diabetes is associated with changes in testicular tissue. Sesame oil contains large amounts of polyunsaturated fatty acids and lignin with antioxidant activity, vitamin E, and monounsaturated fatty acid (MUFA). The present study investigated the effects of sesame on testis histology and male reproductive parameters in streptozotocin-induced diabetic rats. Materials and Methods: Thirty mature male Wistar rats were randomly divided into three groups, i.e., control (C), diabetic-control (DC), and sesame-treated diabetic rats (SD). Diabetes was induced by a single dose of streptozotocin (65 mg/kg; i.p). The animals were treated by a single intraperitoneal sesame extract injection (100 mg/kg b.w.) once daily for 6 weeks. Results: The biochemical analysis revealed that the diabetes resulted in significant (p<0.05) reduction in spermiogenesis, testosterone, LH, and FSH levels. Light microscopic analysis showed remarkable (p<0.05) reduction in STD (seminiferous tubules diameter), SPI (spermatogenesis index) thickness of the epithelium, and significant increase in thickness of the interstitial tissue in the diabetic group compared with the control group. Simultaneous administration of the sesame could fairly up-regulate testosterone, LH, and FSH of the animals in this group. However, some differences were manifested with improved histological features as thickness of the epithelium, seminiferous tubules diameter, and spermatogenesis index. Conclusion: These data demonstrated that sesame significantly improved diabetes complication in rat testis. This study suggested that sesame might have a protective effect against oxidative stress-induced impaired testicular functions in diabetic rats. PMID:25050292

  11. Therapeutic effects of sericin on diabetic keratopathy in Otsuka Long-Evans Tokushima Fatty rats.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa

    2013-12-15

    An Otsuka Long-Evans Tokushima Fatty (OLETF) rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus. We investigated the effects of sericin on corneal wound healing in OLETF rats. Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X. Sericin was instilled into the eyes of rats five times a day following corneal abrasion. The plasma levels of glucose, triglycerides, cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats (LETO rats), and the rate of corneal wound healing in OLETF rats was slower than in normal rat, probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels. The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72 h after corneal epithelial abrasion. On the other hand, the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion. The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy. PMID:24379918

  12. Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats

    PubMed Central

    Niwa, Atsuko; Tajiri, Takashi; Higashino, Hideaki

    2011-01-01

    Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg−1 d−1), Agaricus blazei (1 g kg−1 d−1) or Smallanthus sonchifolius (4 g kg−1 d−1) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass. PMID:21562638

  13. Augmented insulin effects on plasma glucose by cranberry procyanidins in streptozotocin-induced diabetic rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives of this study were to determine if cranberry proanthocyanidins (CPACs) had an antihyperglycemic effect in the presence or absence of insulin in male diabetic Sprague-Dawley rats. Rats (approximately 250 g)(n=6-10/ trt) were given a single intraperitoneal (ip) injection of freshly prepared...

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

    PubMed Central

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

    2015-01-01

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

  15. Impaired reductive regeneration of ascorbic acid in the Goto-Kakizaki diabetic rat.

    PubMed Central

    Kashiba, M; Oka, J; Ichikawa, R; Kageyama, A; Inayama, T; Kageyama, H; Ishikawa, T; Nishikimi, M; Inoue, M; Inoue, S

    2000-01-01

    Ascorbic acid (AA) is a naturally occurring major antioxidant that is essential for the scavenging of toxic free radicals in both plasma and tissues. AA levels in plasma and tissues have been reported to be significantly lower than normal in diabetic animals and humans, and might contribute to the complications found at the late stages of diabetes. In this study, plasma and hepatic AA levels and AA regeneration were studied in the Goto-Kakizaki diabetic rat (GK rat) to elucidate the mechanism of decreasing plasma and hepatic AA levels in diabetes. AA concentrations in the plasma and liver were significantly lower in GK than in control rats. AA levels in primary cultured hepatocytes derived from GK rats were lower than those derived from control Wistar rats with or without dehydroascorbic acid (DHA) in the medium. Among various enzyme activities that reduce DHA to AA, the NADPH-dependent regeneration of AA in the liver was significantly suppressed in GK rats. Northern blot analysis revealed that only the expression of 3-alpha-hydroxysteroid dehydrogenase (AKR) was significantly suppressed in these rats. These results suggest that decreased AA-regenerating activity, probably through decreased expression of AKR, contributes to the decreased AA levels and increased oxidative stress in GK rats. PMID:11023815

  16. Preventive effects of garlic (Allium sativum) on oxidative stress and histopathology of cardiac tissue in streptozotocin-induced diabetic rats.

    PubMed

    Naderi, R; Mohaddes, G; Mohammadi, M; Alihemmati, A; Badalzadeh, R; Ghaznavi, R; Ghyasi, R; Mohammadi, Sh

    2015-12-01

    Since some complications of diabetes mellitus may be caused or exacerbated by an oxidative stress, the protective effects of garlic (Allium sativum) were investigated in the blood and heart of streptozotocin-induced diabetic rats. Twenty-eight male Wistar rats were randomly divided into four groups: control, garlic, diabetic, and diabetic+garlic. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (50 mg/kg) in male rats. Rats were fed with raw fresh garlic homogenate (250 mg/kg) six days a week by gavage for a period of 6 weeks. At the end of the 6th week blood samples and heart tissues were collected and used for determination of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and histological evaluation. Induction of diabetes increased MDA levels in blood and homogenates of heart. In diabetic rats treated with garlic, MDA levels decreased in blood and heart homogenates. Treatment of diabetic rats with garlic increased SOD, GPX and CAT in blood and heart homogenates. Histopathological finding of the myocardial tissue confirmed a protective role for garlic in diabetic rats. Thus, the present study reveals that garlic may effectively modulate antioxidants status in the blood and heart of streptozotocin induced-diabetic rats. PMID:26690030

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

    PubMed Central

    Mota, Marcelo Mendonça; da Silva, Tharciano Luiz Teixeira Braga; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos; de Oliveira, Antônio Cesar Cabral; Wichi, Rogério Brandão; Santos, Márcio Roberto Viana

    2014-01-01

    Background Resistance exercise effects on cardiovascular parameters are not consistent. Objectives The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Methods Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. Results A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Conclusions Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats. PMID:25120082

  18. Centrophenoxine activates acetylcholinesterase activity in hippocampus of aged rats.

    PubMed

    Sharma, D; Singh, R

    1995-05-01

    Age-related changes in the acetylcholinesterase activity were measured in the hippocampus, brain stem and cerebellum of rats (aged 4, 8, 16 and 24 months). The age-dependent decrease in the enzyme activity first appeared in the hippocampus; the brain stem was affected later while the cerebellum remained unaffected. Centrophenoxine, usually considered as an ageing reversal drug and also regarded as a neuroenergeticum in human therapy, increased the acetylcholinesterase activity in the hippocampus of aged rats, the activity was also elevated in the brain stem but no in the cerebellum. The acetylcholinesterase-stimulating influence of the drug is likely to be implicated in the pharmacological reversal of the age related decline of the cholinergic system. This effect of the drug may also mediate its effects on cognitive and neuronal synaptic functions. PMID:7558197

  19. Anti-diabetic effects of a series of vanadium dipicolinate complexes in rats with streptozotocin-induced diabetes.

    PubMed

    Willsky, Gail R; Chi, Lai-Har; Godzala, Michael; Kostyniak, Paul J; Smee, Jason J; Trujillo, Alejandro M; Alfano, Josephine A; Ding, Wenjin; Hu, Zihua; Crans, Debbie C

    2011-10-01

    The effects of oral treatment of rats with streptozotocin-induced diabetes with a range of vanadium dipicolinate complexes (Vdipic) and derivatives are reviewed. Structure-reactivity relationships are explored aiming to correlate properties such as stability, to their insulin-enhancing effects. Three types of modifications are investigated; first, substitutions on the aromatic ring, second, coordination of a hydroxylamido group to the vanadium, and third, changes in the oxidation state of the vanadium ion. These studies allowed us to address the importance of coordination chemistry, and redox chemistry, as modes of action. Dipicolinate was originally chosen as a ligand because the dipicolinatooxovanadium(V) complex (V5dipic), is a potent inhibitor of phosphatases. The effect of vanadium oxidation state (3, 4 or 5), on the insulin-enhancing properties was studied in both the Vdipic and VdipicCl series. Effects on blood glucose, body weight, serum lipids, alkaline phosphatase and aspartate transaminase were selectively monitored. Statistically distinct differences in activity were found, however, the trends observed were not the same in the Vdipic and VdipicCl series. Interperitoneal administration of the Vdipic series was used to compare the effect of administration mode. Correlations were observed for blood vanadium and plasma glucose levels after V5dipic treatment, but not after treatment with corresponding V4dipic and V3dipic complexes. Modifications of the aromatic ring structure with chloride, amine or hydroxyl groups had limited effects. Global gene expression was measured using Affymetrix oligonucleotide chips. All diabetic animals treated with hydroxyl substituted V5dipic (V5dipicOH) and some diabetic rats treated with vanadyl sulfate had normalized hyperlipidemia yet uncontrolled hyperglycemia and showed abnormal gene expression patterns. In contrast to the normal gene expression profiles previously reported for some diabetic rats treated with vanadyl

  20. Prospective evaluation of aminopeptidase activities in plasma and peripheral organs of streptozotocin-induced diabetic rats.

    PubMed

    Zambotti-Villela, L; Yamasaki, S C; Villarroel, J S; Alponti, R F; Silveira, P F

    2008-06-01

    The cleavage of peptides by aminopeptidase enzyme types could be among the mechanisms related to certain disruptions on mediator and modulatory functions in diabetes mellitus. In order to examine this hypothesis, we measured representative aminopeptidase activities in tissues of peripheral organs of control and streptozotocin-diabetic rats. None of the examined aminopeptidase activities differed between diabetics and controls in plasma, ileum, stomach or lung. Soluble and membrane-associated alanyl, and membrane-associated cystyl aminopeptidase activities were higher in the kidney of diabetics. Decreased activity was observed in soluble and membrane-associated aspartyl and soluble dipeptidyl-peptidase IV, while increased activity was observed in soluble alanyl, arginyl, and cystyl aminopeptidases in the pancreas of diabetics. In the jejunum, soluble cystyl aminopeptidase increased in diabetics. Soluble arginyl and type-1-pyroglutamyl aminopeptidase and membrane-associated dipeptidyl-peptidase IV activities increased in the liver of diabetics. Membrane-associated dipeptidyl-peptidase IV and alanyl aminopeptidase activities in the spleen were higher in diabetics than in controls. Membrane-associated alanyl aminopeptidase activity also increased in the heart of diabetics. All these changes in streptozotocin-treated rats were avoided by the administration of insulin. Our comparative analysis of a diverse array of aminopeptidase activities supported the proposal that the regulation of peptide cleavage by these enzyme types is associated with the effects of streptozotocin-diabetes mellitus on peripheral organs. PMID:18591879

  1. Attenuation of nonenzymatic glycation, hyperglycemia, and hyperlipidemia in streptozotocin-induced diabetic rats by chloroform leaf extract of Azadirachta indica

    PubMed Central

    Gutierrez, Rosa Martha Pérez; Gómez, Yolanda Gómez Y.; Guzman, Mónica Damián

    2011-01-01

    Background: The hypoglycemic effects of hexane, chloroform and methanol extracts of leaves of Azadirachta indica (AI) were evaluated by oral administration in streptozotocin-induced severe diabetic rats (SD). Materials and Methods: The effect of chronic oral administration of the extract for 28 days was evaluated in streptozotozin diabetic rats. Lipid peroxidation, glycogen content of liver and skeletal muscles, insulin, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), oxidized glutathione (GSSG) levels were determined. In addition, advanced glycation end product formation (AGEs) was evaluated. Results: The most active extracts were obtained with chloroform. Chloroform extract from AI shows increased levels of SOD, GSH, GSSG and CAT, hepatic glycogen content, glucose-6-phosphatase and insulin plasma levels, which also decreased the glucokinase (GK), lipid peroxidation and insulin resistance. The chloroform extract exhibited significant inhibitory activity against advanced glycation end product formation with an IC50 average range of 79.1 mg/ml. Conclusion: Azadirachta indica can improve hyperlipidemia and hyperinsulinema in streptozocin-induced diabetic rats and, therefore, AI can be potentially considered to be an antidiabetic-safe agent. PMID:21969798

  2. Antihyperglycemic, antihyperlipidemic and antiglycation effects of Byrsonima crassifolia fruit and seed in normal and streptozotocin-induced diabetic rats.

    PubMed

    Perez-Gutierrez, Rosa Martha; Muñiz-Ramirez, Alethia; Gomez, Yolanda Gomez; Ramírez, Esther Bautista

    2010-12-01

    The hypoglycemic effects of hexane, chloroform and methanol extracts from fruits and seeds of Byrsonima crassifolia were evaluated by oral administration to normoglycemic and streptozotocin-induced severe diabetic rats (SD). The anti-diabetic effect was examined by blood glucose, triglycerides, lipid peroxidation, total cholesterol levels in the serum, glycogen content of liver and skeletal muscles, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and oxidized glutathione (GSSG) levels. The most active extracts were obtained with hexane. Hexane and chloroform extracts from fruits and seeds of Byrsonima crassifolia increased the levels of SOD, GSH, GSSG and CAT, hepatic glycogen content, glucose-6-phosphatase (G6Pase) and the plasma insulin levels. They also decreased glucokinase (GK) and TBAR (thiobarbituric acid assay). In conclusion, Byrsonima crassifolia possesses significant antihyperglycemic properties after 4 h of a single oral dose. It can also improve hyperlipidemia and hyperinsulinemia in streptozotocin-induced diabetic rats. Both extracts exhibited significant inhibitory activity against AGEs (advanced glycation end products) formation with IC(50) values ranging from 94.3 to 138.7 μg/ml. Therefore, B. crassifolia can be considered as a potential safe anti-diabetic agent. PMID:20734144

  3. Anti-diabetic effects of Monascus purpureus NTU 568 fermented products on streptozotocin-induced diabetic rats.

    PubMed

    Shi, Yeu-Ching; Pan, Tzu-Ming

    2010-07-14

    Red-mold-fermented products have the unique ability to economically produce many secondary metabolites and are known to improve blood circulation. Diabetes mellitus is a chronic disease that is characterized by hyperglycemia caused by insufficient insulin action. In the current study, we examine the effect of Monascus purpureus NTU 568 fermented products on fasting blood glucose and oral glucose tolerance testing (OGTT) in streptozotocin-induced diabetic rats. After 8 weeks of being fed with red-mold-fermented products at a dose of 200 mg/kg, the experimental results indicate that oral administration of red-mold-fermented products can delay the development of the plasma glucose level in rats. A significant reduction was found in urine sugar and urine protein levels. The study scientifically validates the widely claimed use of red-mold-fermented products as an ethnomedicine to treat diabetes mellitus. PMID:20557124

  4. Antihyperglycemic, antihyperlipidemic and antioxidant effects of Dihar, a polyherbal ayurvedic formulation in streptozotocin induced diabetic rats.

    PubMed

    Patel, Snehal S; Shah, Rajendra S; Goyal, Ramesh K

    2009-07-01

    Present investigation was undertaken to evaluate antihyperglycemic, antihyperlipidemic and antioxidant activities of Dihar, a polyherbal formulation containing drugs from eight different herbs viz., Syzygium cumini, Momordica charantia, Emblica officinalis, Gymnema sylvestre, Enicostemma littorale, Azadirachta indica, Tinospora cordifolia and Curcuma longa in streptozotocin (STZ, 45 mg/kg iv single dose) induced type 1 diabetic rats. STZ produced a significant increase in serum glucose, cholesterol, triglyceride, very low density lipoprotein, low density lipoprotein, creatinine, and urea levels in diabetic rat. Treatment with Dihar (100 mg/kg) for 6 weeks produced decrease in STZ induced serum glucose and lipids levels and increased insulin levels as compared to control. Dihar produced significant decrease in serum creatinine and urea levels in diabetic rats. There was a significant decrease in reduced glutathione, superoxide dismutase, catalase levels and increase in thiobarbituiric acid reactive species levels in the liver of STZ-induced diabetic rats. Administration of Dihar to diabetic rats significantly reduced the levels of lipid paroxidation and increased the activities of antioxidant enzymes. The results suggest Dihar to be beneficial for the treatment of type 1 diabetes. PMID:19761040

  5. Metformin Ameliorates Podocyte Damage by Restoring Renal Tissue Podocalyxin Expression in Type 2 Diabetic Rats

    PubMed Central

    Zhai, Limin; Gu, Junfei; Yang, Di; Wang, Wei; Ye, Shandong

    2015-01-01

    Podocalyxin (PCX) is a signature molecule of the glomerular podocyte and of maintaining integrity of filtration function of glomerulus. The aim of this study was to observe the effect of different doses of metformin on renal tissue PCX expression in type 2 diabetic rats and clarify its protection on glomerular podocytes. Type 2 diabetic Sprague-Dawley (SD) rats in which diabetes was induced by high-fat diet/streptozotocin (HFD-STZ) were treated with different doses of metformin (150, 300, and 500 mg/kg per day, resp.) for 8 weeks. Various biochemical parameters, kidney histopathology, and renal tissue PCX expression levels were examined. In type 2 diabetic rats, severe hyperglycemia and hyperlipidemia were developed. Urinary albumin and PCX were markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, protein and mRNA expression of renal tissue PCX were highly decreased. However, treatment of rats with different doses of metformin restored all these changes to a varying degree. These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence. PMID:26075281

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

    PubMed

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

    2015-06-30

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

  7. Antiperoxidative and antioxidant effects of Casearia esculenta root extract in streptozotocin-induced diabetic rats.

    PubMed Central

    Prakasam, A.; Sethupathy, S.; Pugalendi, K. V.

    2005-01-01

    Oxidative stress is currently suggested to play as a pathogenesis in the development of diabetes mellitus. The present study was designed to evaluate the effect of Casearia esculenta root extract on oxidative stress-related parameters in streptozotocin (STZ) -induced diabetic rats. Antidiabetic treatment with C. esculenta root extract (45 days) significantly (p < .05) decreased thiobarbituric acid reactive substances (TBARS) and remarkably improved tissue antioxidants status such as glutathione (GSH), ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) in liver and kidney of STZ-diabetic rats. In diabetics rats, the activities of enzymatic antioxidants such as superoxide dismutase (SOD, EC 1.11.1.1) catalase (CAT, EC 1.11.1.6) were decreased significantly while the activity of glutathione peroxidase (GPx, EC 1.11.1.9) decreased in the liver and increased in the kidney. The treatment of diabetic rats with C. esculenta root extract over a 45-day period returned these levels close to normal. These results suggest that C. esculenta root extracts exhibit antiperoxidative as well as antioxidant effects in STZ-induced diabetic rats. PMID:16197726

  8. Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abedi, Hassan Ali

    2014-01-01

    Objective(s): Diabetes plays an important role in the induction of the liver injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal properties against oxidative stress. In this study we evaluated antioxidant effects of GSP on liver in streptozotocin-induced diabetic rats. Materials and Methods: Thirty male Sprague–Dawley rats were divided into three groups: control, untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were administered via oral gavage (200 mg/kg) for 4 weeks. Results: GSP produced significant hepatoprotective effects by decreasing activities of serum aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde and bilirubin (P<0.05) levels. It increased liver superoxide dismutase, catalase and glutathione peroxidase activities and albumin level (P<0.05). Administration of GSP significantly ameliorated structural changes induced in liver of diabetic rats. Conclusion: GSP have protective effects against hepatic tissue injury due to antioxidant properties. PMID:25140209

  9. Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats

    PubMed Central

    Zhang, Zhenwen; Fang, Penghua; He, Biao; Guo, Lili; Runesson, Johan; Langel, Ülo; Shi, Mingyi; Zhu, Yan; Bo, Ping

    2016-01-01

    Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebrove