Sample records for stz-induced diabetic rats

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

    PubMed

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

    2013-10-01

    Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permeability of glomerular basement membrane plays an important role in DN pathogenesis. This study was performed to assess the effect of arctiin, the lignan constituent from Arctium lappa L., on metabolic profile and aggravation of renal lesions in a rat model of streptozotocin (STZ)-induced DN. STZ-induced diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via intraperitoneal injection for 8 weeks. Blood glucose and 24-h urinary albumin content were measured, and kidney histopathological changes were monitored. RT-PCR and immunohistochemistry were used to detect the mRNA and protein levels of nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats, respectively. Treatment with arctiin significantly decreased the levels of 24-h urinary albumin, prevented the sclerosis of glomeruli and effectively restored the glomerular filtration barrier damage by up-regulating the expression of nephrin and podocin and down-regulating HPSE level. Our studies suggest that arctiin might be beneficial for DN. The effects of arctiin on attenuating albuminuria and glomerulosclerosis are possibly mediated by regulating the expression of nephrin and podocin and HPSE in STZ-induced diabetic rats. PMID:23147865

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

    PubMed Central

    2013-01-01

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

  3. Effects of STZ-induced diabetes and its treatment with vanadyl sulphate on cyclosporine A-induced nephrotoxicity in rats

    Microsoft Academic Search

    Sherif Y. Saad; Tawfeeg A. O. Najjar

    2005-01-01

    The aim of this study was to analyze the effect of streptozotocin (STZ)-induced diabetic state and the insulin-like acting, vanadyl sulphate (VS) on cyclosporine A (CyA) related nephrotoxicity in rats. Male Wistar rats were divided into six groups, of 12 animals each: The control, diabetic rats and diabetic rats whose drinking VS in the drinking water in a concentration of

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

    PubMed

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

    2015-07-25

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

  5. Effects of STZ-induced diabetes and its treatment with vanadyl sulphate on cyclosporine A-induced nephrotoxicity in rats.

    PubMed

    Saad, Sherif Y; Najjar, Tawfeeg A O

    2005-09-01

    The aim of this study was to analyze the effect of streptozotocin (STZ)-induced diabetic state and the insulin-like acting, vanadyl sulphate (VS) on cyclosporine A (CyA) related nephrotoxicity in rats. Male Wistar rats were divided into six groups, of 12 animals each: The control, diabetic rats and diabetic rats whose drinking VS in the drinking water in a concentration of 1 mg/ml. Another three similarly treated groups were injected intra-peritoneally (ip) with CyA in a dose of 25 mg/kg/day for ten doses, 10 days after diabetic induction by using a single dose of STZ of 65 mg/kg. Rats were sacrificed 48 h after the last CyA dose and serum as well as kidneys were isolated and analyzed. Treatment with CyA to control normoglycemic rats resulted in significant increases in kidney weight, serum creatinine, urea nitrogen, cholesterol and triglycerides (TG) levels. Also, the kidney tissue of CyA-treated control animals showed significant increases in total nitrate/nitrite (NO(x)) concentration and malondialdehyde (MDA) production level as well as depletion of glutathione (GSH) content and glutathione peroxidase (GSH-P(x)) activity level. Histopathologic evaluation of CyA-treated control rats revealed tubular atrophy, hyaline casts and focal tubular necrosis. However, treatment of diabetic rats with CyA showed significant reduction in serum creatinine and elevation in TG level as well as reductions in the kidney NO(x) concentration and MDA production level and increase in GSH concentration compared to CyA-treated control rats. Moreover, histopathology of the kidney of CyA-treated diabetics showed typical changes of the diabetic controls revealing glomerular hypertrophy and tubular dilation. On the other hand, treatment with CyA to those diabetic animals administered VS in the drinking water resulted in exacerbation of renal dysfunction, manifested by significant increases in serum indices of nephrotoxicity, cholesterol, TG and bilirubin levels. Also, VS administration to CyA-treated diabetics showed significant increase in kidney NO(x) concentration compared to those CyA-treated diabetics drinking plain tap water, and to a level significantly lower than those CyA-treated controls. Histopathologically, kidney of CyA/VS-treated diabetic showed marked CyA related changes. In conclusion, STZ-induced diabetes might provide partial protection against CyA-induced renal dysfunction. Also, treatment of hyperglycemia with VS might exacerbate CyA related nephrotoxicity. PMID:15940472

  6. Effects of parsley ( Petroselinum crispum ) on the aorta and heart of Stz induced diabetic rats

    Microsoft Academic Search

    Göksel Sener; Özlem Saçan; Refiye Yanardag; Gül Ayanoglu-Dülger

    2003-01-01

    Parsley is one of the medicinal herbs used by diabetics in Turkey. It has been reported to reduce blood glucose levels. In this study the effects of feeding parsley on diabetes-induced free radical mediated injury in rat aorta and heart tissues were investigated. Swiss albino rats were divided into six groups: Control, diabetic, parsley, diabetic + parsley, glibornurid, and diabetic

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

    PubMed

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

    2015-03-01

    Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of ?-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats. PMID:24689449

  8. The Puerarin improves renal function in STZ-induced diabetic rats by attenuating eNOS expression.

    PubMed

    Zhang, Yong; Wang, Hongya; Yu, Li; Chen, Jimin

    2015-05-01

    Diabetic nephropathy (DN) is a serious complication and it leads to kidney failure. The endothelial nitric oxide synthases (eNOS) seems to be involved in the development and progression of DN. The Puerarin is a well-known Chinese traditional formula, which is widely used in clinical practice for the treatment of kidney disease. The present study was designed to investigate the renal protective effects of Puerarin on streptozotocin (STZ)-induced diabetic rats. Thirty Sprague-Dawley (SD) male rats were divided into three groups at random. The diabetic group and the Puerarin-treated group were intraperitoneally injected with STZ 65?mg/kg and the Puerarin-treated rats were intraperitoneally injected Puerarin 100?mg/kg/day for 4 weeks. The results showed the Puerarin could improve body weight, blood sugar, BUN and SCr levels, and reduce ultrastructural changes of kidney in diabetic rats. It also attenuated eNOS expression in glomerular endothelial cells and tubular cells of diabetic rats with Puerarin treatment (p?diabetic nephropathy, possibly through regulating eNOS expression, and it may be used as a potential therapeutic reagent. PMID:25707518

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

    PubMed

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

    2013-09-01

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

  10. Aggravation by vanadium of magnesium deficiency in STZ-induced diabetic rats.

    PubMed

    Bermúdez-Peña, M C; López-Chaves, C; Llopis, J; Guerrero-Romero, F; Montes-Bayón, M; Sanz-Medel, A; Sánchez-González, C

    2013-01-01

    This study examined changes in the metabolism of magnesium (Mg), and related serum parameters, following treatment with vanadium (V) in streptozotocin-diabetic rats. Over a period of five weeks, four groups were examined: control, diabetic, diabetic-treated with 1 mg V/day or 3 mg V/day. The V was supplied in drinking water as bis(maltolato)oxovanadium(IV). The Mg levels were measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, heart and femur. Albumin, uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides, aspartate-aminotransferase and alkaline-phosphatase were determined in serum. In the diabetic group, Mg retained and Mg content in serum and femur decreased, while levels of uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides and alkaline-phosphatase and aspartate-aminotransferase activity increased compared with control rats. In the diabetic group treated with 1 mg?V/day, Mg retained, serum levels of Mg, urea and triglycerides, and alkaline-phosphatase activity remained unchanged, while levels of uric acid, total-cholesterol and LDL-cholesterol increased and the Mg content in femur and aspartate-aminotransferase activity decreased compared with the diabetic untreated group. In the diabetic rats treated with 3 mg?V/day, food intake and glycaemia were normal. In this group, Mg content in serum, kidney and femur, levels of urea and aspartate-aminotransferase and alkaline-phosphatase activity decreased, whereas LDL-cholesterol increased, uric acid and total-cholesterol levels remained unchanged in comparison with untreated diabetic rats. In conclusion, although treatment with 3 mg V/day normalised the glycaemia, the hypomagnesaemia and tissue depletion of Mg seen in the diabetic rats, caused by the treatment with V, could have partially contributed to the fact that V did not normalise other serum parameters altered by the diabetes. PMID:23823277

  11. Effect of Pimpinellatirupatiensison Oxidative Enzymes in STZ-induced Diabetic Rat Kidney

    PubMed Central

    RajeswaraReddy, Saddala; Lavany, Thopireddy; Narasimhulu, Ganapathi; SathyaveluReddy, Kesireddy

    2012-01-01

    The present study was aimed to evaluate the therapeutic potential of Pimpinellatirupatiensis(Pt) by assaying the activities of selective mitochondrial enzymes in streptozotocin induced diabetic rats. Diabetic rats showed a significant (p < 0.01) reduction in the activities of oxidative enzymes Succinate dehydrogenase (SDH), Malate dehydrogenase (MDH), Glutamate dehydrogenase (GDH) and isocitrate dehydrogenase (ICDH). Lactate dehydrogenase (LDH) activity was significantly (p < 0.01) increased in diabetic rats. The daily oral treatment of Pimpinellatirupatiensisethyl alcohol extract (750 mg/kg body weight/day) to diabetic rats for 30 days reversed the above changes in a significant (p < 0.01) manner. From our observations, we conclude that administration of Pt altered the activities of oxidative enzymes, thereby suggesting its role in mitochondrial energy production. The obtained results were compared with Glibenclamide, a standard anti diabetic drug. Thus, the modulatory effects of Pt on altering these enzymes activities afford a promise for widespread use for treatment of diabetes in the future. PMID:24250450

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

    PubMed Central

    Badavi, Mohammad; Abedi, Hassan Ali; Dianat, Mahin; Sarkaki, Ali Reza

    2013-01-01

    Background: Exercise Training (ET) and Grape Seed Extract (GSE) as an antioxidant have many positive effects on controlling diabetes mellitus and its complications. Objectives: This study aimed to determine the effects of GSE alone or combined with ET on body weight, plasma lipid profile, blood pressure, and heart rate in STZ-induced diabetic rats. Methods: In this study, male Wistar rats were randomly assigned to five groups: sedentary control, sedentary diabetic, trained diabetic, GSE treated sedentary diabetic, and GSE treated trained diabetic. ET was conducted on the treadmill daily for 8 weeks. One way ANOVA followed by LSD test was used for statistical analysis. Results: Reduction of body weight, high density lipoproteins, heart rate, and systolic blood pressure and increment of total cholesterol, triglyceride, low density lipoprotein, and very low density lipoproteins were observed after STZ injection. Co-administration of GSE and ET had more positive effects on lipid profile compared to each method alone. In addition, GSE and ET modified heart rate partially, while their combination was more effective in improvement of heart rat in conscious rats. On the other hand, administration of ET or GSE alone did not affect systolic blood pressure and body weight, while their combination restored systolic blood pressure completely and improved body weight partially. Conclusions: The study findings indicated that ET combined with GSE had more beneficial effects compared to each one alone on the complications of STZ induced diabetes. This may constitute a convenient and inexpensive therapeutic approach to diabetic complications. PMID:24757634

  13. Improvement in nutrient handling in STZ induced diabetic rats treated with Ocimum gratissimum

    PubMed Central

    Okon, Uduak Akpan; Davies, Koofreh Godwin; Olubobokun, Titilope Helen

    2015-01-01

    Objective: Alteration in digestive and absorptive enzymatic activities has been reported in diabetes mellitus (DM), but not with Ocimum gratissimum (OG) treatment. This study was, therefore, designed to indirectly assess the effect of DM and treatment with OG on nutrient digestion and absorption, through estimation of their fecal excretion. Materials and Methods: Animals were randomly assigned into three groups of six per group for control, DM and diabetic mellitus treated (DMT). Diabetes was induced by single intraperitoneal injection of 65 mg/kg streptozotocin in the test groups. OG was administered to the DMT group at dose of 1500 mg/kg once daily for 28 days. Fecal glucose, protein and cholesterol were determined. Results: Fecal glucose was significantly (P < 0.001) lower in the DM group compared to the control and DMT groups, with the DMT groups significantly (P < 0.001) lower than the control. Fecal protein was significantly (P < 0.001) lower in the DM group than the control whereas it was significantly lower in the DMT groups than the DM. Fecal cholesterol was significantly (P < 0.001) higher in the DM than the DMT and control groups with DMT significantly (P < 0.01) higher than the control. Conclusion: This result indicates the propensity of OG to reverse impairment of nutrient digestion and absorption in DM. PMID:25664269

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

    PubMed

    Singh, Jyotsna; Kakkar, Poonam

    2013-12-01

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

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

    PubMed Central

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

    2015-01-01

    Diabetes mellitus (DM) is characterized by hyperglycemia and alterations in the metabolism of lipids, carbohydrates, and proteins. Due to its hypoglycemic effect Vochysia rufa is frequently used in Uberlandia, Brazil, to treat DM. Despite its popularity, there is little information about its effect on hepatic tissue. Therefore, we evaluated the histoarchitecture, oxidative stress parameters, and polyploidy of liver tissue from streptozotocin- (STZ-) induced diabetic rats treated with aqueous extract of Vochysia rufa (AEV). Histology was determined by fixing the livers, processing, and staining with HE. Oxidative stress was determined by evaluating CAT, GPx, and SOD activity in liver homogenates and hepatic mitochondria fraction and by measuring GST, GSH levels and lipid peroxidation (MDA). Polyploidy was determined by subjecting isolated hepatocyte nuclei to flow cytometry. In the diabetic group, GST activity and GSH rates decreased whereas liver homogenate analysis showed that GPx, SOD activity and MDA increased. AEV treatment restored all parameters to normal levels. The oxidative stress analysis of hepatic mitochondria fraction showed similar results. Lower polyploid cell populations were found in the diabetic rat livers, even after glibenclamide treatment. Thus, AEV treatment efficiently reduced hepatic oxidative stress caused by STZ-induced diabetes and produced no morphological changes in the histological analysis. PMID:25763088

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

    PubMed Central

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

    2013-01-01

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

  17. Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: a mechanistic study.

    PubMed

    Arya, Aditya; Al-Obaidi, Mazen M Jamil; Shahid, Nayiar; Bin Noordin, Mohamed Ibrahim; Looi, Chung Yeng; Wong, Won Fen; Khaing, Si Lay; Mustafa, Mohd Rais

    2014-09-01

    The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids. PMID:24953551

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

    PubMed Central

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

    2013-01-01

    Curculigo latifolia fruit is used as alternative sweetener while root is used as alternative treatment for diuretic and urinary problems. The antidiabetic and hypolipidemic activities of C. latifolia fruit:root aqueous extract in high fat diet (HFD) and 40?mg streptozotocin (STZ) induced diabetic rats through expression of genes involved in glucose and lipid metabolisms were investigated. Diabetic rats were treated with C. latifolia fruit:root extract for 4 weeks. Plasma glucose, insulin, adiponectin, lipid profiles, alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), urea, and creatinine levels were measured before and after treatments. Regulations of selected genes involved in glucose and lipid metabolisms were determined. Results showed the significant (P < 0.05) increase in body weight, high density lipoprotein (HDL), insulin, and adiponectin levels and decreased glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), urea, creatinine, ALT, and GGT levels in diabetic rats after 4 weeks treatment. Furthermore, C. latifolia fruit:root extract significantly increased the expression of IRS-1, IGF-1, GLUT4, PPAR?, PPAR?, AdipoR1, AdipoR2, leptin, LPL, and lipase genes in adipose and muscle tissues in diabetic rats. These results suggest that C. latifolia fruit:root extract exerts antidiabetic and hypolipidemic effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats. PMID:23762147

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. Comparing the Effects of Ginger and Glibenclamide on Dihydroxybenzoic Metabolites Produced in Stz-Induced Diabetic Rats

    PubMed Central

    Ahmadi, Ramesh; Pishghadam, Saeede; Mollaamine, Fatemeh; Zand Monfared, Mohammad Reza

    2013-01-01

    Background: The aim of the present study was to investigate the effect of ginger and glibenclamide on oxidative stress markers. Oxidative stress is caused by an unbalance between a relative overload of oxidants and depletion of antioxidants, as implicated in the pathogenesis of several chronic diseases, including atherosclerosis and diabetes mellitus. Regarding the role of oxidative stress in the pathogenesis of diabetes mellitus, we investigated the effect of ginger and glibenclamide in diabetic rats induced bystreptozocin (STZ). Objectives: This study assessed the effects of ginger and glibenclamide on dihydroxybenzoic acid metabolites in diabetic rats. Materials and Methods: In this study 30 Wistar strain male rats were divided into five groups: Group 1: Normal control receiving normal saline (0.9 0/0), Group 2: control DMSO (Dimethyl sulfoxide) (as solvent of glibenclamide), Group 3: Diabetic control receiving Streptozocin (STZ ) (50 mg/kg) ,Group 4: diabetic+ Ginger Extract: this group received ginger ethanolic extract (200 mg/kg) via IP (Intraperitoneally) injection for 30 days, and Group 5 diabetic rats received glibenclamide (0.5 m/kg). Production of hydroxyl radicals was examined in the diabetic rats induced by streptozocin. Hydroxyl radicals were generated in plasma of the hyperglycemic rats, and were quantitatively assayed by trapping hydroxyl radicals with salicylic acid so as to produce 2,3-and 2,5-dihydroxybenzoic acid. Results: Production of hydroxyl radicals increased; therefore, by using salicylic acid, hydroxyl radicals were trapped and 2,3dihydroxybenzoic acid and 2,5dihydroxybenzoic acid metabolites were formed then measured by HPLC and spectrophotometer. Rats receiving ginger extract and glibenclamide showed decreased level of metabolites compared to the diabetic controls (P <0/001). This means that antioxidants act as scavenger of free radicals. Conclusions: Comparative effect of ginger and glibenclamide also showed that glibenclamide has antioxidant effect as a scavenger of free radical, but ginger is more capable of eliminating them. PMID:24719624

  3. The Effect of Angipars on Diabetic Neuropathy in STZ-Induced Diabetic Male Rats: A Study on Behavioral, Electrophysiological, Sciatic Histological and Ultrastructural Indices

    PubMed Central

    Zangiabadi, Nasser; Mohtashami, Hossein; Hojatipour, Mahboobeh; Jafari, Mandana; Asadi-Shekaari, Majid; Shabani, Mohammad

    2014-01-01

    Diabetes mellitus is the most common metabolic disease with a high prevalence rate in human society that eventually leads to the peripheral nervous system complications in a great number of patients. In the present study, the effects of Angipars on nerve conduction velocity, histological alterations, and behavioral indices were investigated. Diabetes was induced in male rats by intraperitoneal injection of streptozotocin (STZ). Six weeks after STZ injection, animals were divided into five groups control, vehicle, and 3 experimental groups. The vehicle group received 1?mL distilled water daily for two weeks and three experimental groups received, respectively, intraperitoneal injection of 5, 10, and 20?mg/kg Angipars daily for two weeks. Intraperitoneal injection of Angipars, in some extent, could significantly improve behavioral indices of the experimental groups as compared to the vehicle group. Furthermore, mean nerve conduction velocity in the vehicle group showed significant difference with that in the control and the 2nd experimental groups; therefore, Angipars could increase nerve conduction velocity in neuropathic rats. Overall, Angipars exerted positive effects on the treatment and reduction of physiologic symptoms and improvement of sciatic morphological injuries in neuropathic rats. PMID:25614895

  4. The effect of Angipars on diabetic neuropathy in STZ-induced diabetic male rats: a study on behavioral, electrophysiological, sciatic histological and ultrastructural indices.

    PubMed

    Zangiabadi, Nasser; Mohtashami, Hossein; Hojatipour, Mahboobeh; Jafari, Mandana; Asadi-Shekaari, Majid; Shabani, Mohammad

    2014-01-01

    Diabetes mellitus is the most common metabolic disease with a high prevalence rate in human society that eventually leads to the peripheral nervous system complications in a great number of patients. In the present study, the effects of Angipars on nerve conduction velocity, histological alterations, and behavioral indices were investigated. Diabetes was induced in male rats by intraperitoneal injection of streptozotocin (STZ). Six weeks after STZ injection, animals were divided into five groups control, vehicle, and 3 experimental groups. The vehicle group received 1 mL distilled water daily for two weeks and three experimental groups received, respectively, intraperitoneal injection of 5, 10, and 20 mg/kg Angipars daily for two weeks. Intraperitoneal injection of Angipars, in some extent, could significantly improve behavioral indices of the experimental groups as compared to the vehicle group. Furthermore, mean nerve conduction velocity in the vehicle group showed significant difference with that in the control and the 2nd experimental groups; therefore, Angipars could increase nerve conduction velocity in neuropathic rats. Overall, Angipars exerted positive effects on the treatment and reduction of physiologic symptoms and improvement of sciatic morphological injuries in neuropathic rats. PMID:25614895

  5. Co-administration of Grape Seed Extract and Exercise Training Improves Endothelial Dysfunction of Coronary Vascular Bed of STZ-Induced Diabetic Rats

    PubMed Central

    Badavi, Mohammad; Abedi, Hassan Ali; Sarkaki, Ali Reza; Dianat, Mahin

    2013-01-01

    Background One of the known complications of diabetes mellitus is vascular dysfunction. Inability of the coronary vascular response to cardiac hyperactivity might cause a higher incidence of ischemic heart disease in diabetic subjects. It has been indicated that regular exercise training and antioxidants could prevent diabetic cardiovascular problems enhanced by vascular damage. Objectives The aim of this study was to determine the effects of grape seed extract (as antioxidant), with and without exercise training on coronary vascular function in streptozotocin induced diabetic rats. Materials and Methods Fifty male Wistar rats weighing 200 – 232 grams were randomly divided into five groups of 10 rats each: sedentary control, sedentary diabetic, trained diabetic, grape seed extract (200 mg/kg) treated sedentary diabetic and, grape seed extract treated trained diabetic. Diabetes was induced by one intraperitoneal injection of streptozotocin. After eight weeks, coronary vascular responses to vasoactive agents were determined. Results The endothelium dependent vasorelaxation to acetylcholine was reduced significantly in diabetic animals; exercise training or grape seed extract administration partially improves this response. However, exercise training in combination with grape seed extract restores endothelial function completely. The endothelium independent vasorelaxation to sodium nitroprusside was improved by combination of exercise training and grape seed extract. On the other hand, the basal perfusion pressure and vasoconstrictive response to phenylephrine did not change significantly. Conclusions The data indicated that co-administration of grape seed extract and exercise training had more significant effects than exercise training or grape seed extract alone; this may constitute a convenient and inexpensive therapeutic approach to diabetic vascular complications. PMID:24693368

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

    PubMed Central

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

    2014-01-01

    The role of vanadium as a micronutrient and hypoglycaemic agent has yet to be fully clarified. The present study was undertaken to investigate changes in the metabolism of iron and in antioxidant defences of diabetic STZ rats following treatment with vanadium. Four groups were examined: control; diabetic; diabetic treated with 1?mgV/day; and Diabetic treated with 3?mgV/day. The vanadium was supplied in drinking water as bis(maltolato) oxovanadium (IV) (BMOV). The experiment had a duration of five weeks. Iron was measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, and femur. Superoxide dismutase, catalase, NAD(P)H: quinone-oxidoreductase-1 (NQO1) activity, and protein carbonyl group levels in the liver were determined. In the diabetic rats, higher levels of Fe absorbed, Fe content in kidney, muscle, and femur, and NQO1 activity were recorded, together with decreased catalase activity, in comparison with the control rats. In the rats treated with 3?mgV/day, there was a significant decrease in fasting glycaemia, Fe content in the liver, spleen, and heart, catalase activity, and levels of protein carbonyl groups in comparison with the diabetic group. In conclusion BMOV was a dose-dependent hypoglycaemic agent. Treatment with 3?mgV/day provoked increased Fe deposits in the tissues, which promoted a protein oxidative damage in the liver. PMID:24511298

  7. The effect of insulin treatment and of islet transplantation on the resistance artery function in the STZ-induced diabetic rat.

    PubMed Central

    Heygate, K. M.; Davies, J.; Holmes, M.; James, R. F.; Thurston, H.

    1996-01-01

    1. This study was designed to investigate the influence of insulin treatment and islet transplantation on the smooth muscle contractility and endothelium-dependent and independent relaxation of resistance arteries in the chemically induced streptozotocin (STZ) diabetic rat after 6-8 weeks, and 12-14 weeks of diabetes, compared to non-diabetic age-matched controls. 2. The morphology, and contractile responses to high potassium physiological salt solution (KPSS), KPSS containing 10(-5) M noradrenaline (NAK), and concentration-response curves to noradrenaline (NA) of mesenteric resistance arteries were recorded, along with the endothelium-dependent relaxation responses to acetylcholine (ACh) and bradykinin (BK), and endothelium-independent relaxation to sodium nitroprusside (SNP). Concentration-response curves were then repeated in the presence of a nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NOARG). 3. Insulin-treated diabetic rats in the 12 week study demonstrated enhanced vascular contractility to KPSS, NAK and NA, compared to age-matched non-diabetic controls. 4. Incubation with L-NOARG resulted in both a significant increase in maximum contractile response, and sensitivity (pD2) to NA in the untreated diabetic group (6 weeks). A significant shift in sensitivity was also seen in the insulin-treated diabetic group. In the 12 week study, incubation with L-NOARG resulted in an increased maximum contractile response and sensitivity to NA in the insulin-treated diabetics. An increase in sensitivity was also observed in the untreated diabetic group. 5. Endothelium-dependent relaxation to ACh was significantly augmented in the untreated diabetics (6-weeks), compared to the control group. In the 12-week study, relaxation to both ACh and BK was not significantly different in any of the experimental groups when compared to the sham-operated non-diabetic controls. 6. Incubation with L-NOARG resulted in a significant attenuation of the maximum relaxation response to ACh and BK in all of the experimental groups, in the 6- and the 12-week study. 7. There was no significant difference in the maximum relaxation response or sensitivity to sodium nitroprusside between the diabetic groups and their age-matched controls in either the 6-week or the 12-week study. 8. The results of this study suggest an enhanced release of nitric oxide in the early stages of diabetes, which is more evident in the untreated diabetic rats than the insulin treated, and appears to normalize as the duration of diabetes progresses. This study also shows that the alteration in vascular reactivity of the resistance arteries can be restored to within normal limits by the transplantation of islets of Langerhans, and that islet transplantation is an effective strategy in the correction of the metabolic abnormalities associated with insulin-dependent diabetes. PMID:8894169

  8. Antihyperglycemic and antihyperlipidemic activities of 2-(4-[(2-hydroxybenzyl) amino]-phenyl amino-methyl)-phenol in STZ induced diabetic rats.

    PubMed

    Sirasanagandla, Swapna; Kasetti, Ramesh Babu; Shaik, Abdul Nabi; Natava, Rajesh; Surtineni, Venkata Prasad; Cirradur, Suresh Reddy; Chippada, Apparao

    2013-08-01

    Oral administration of 2-(4-[(2-hydroxybenzyl) amino]-phenyl amino-methyl)-phenol (HBPMP) (30 mg/kg) to Streptozotocin (STZ) rats produced significant antidiabetic activity after 6 h of HBPMP administration. Treatment of the STZ rats with HBPMP (30 mg/kg/day) for 30 days resulted in a significant decrease in their Fasting Blood Glucose (FBG), Serum Total Cholesterol (TC), Low Density Lipoprotein-Cholesterol (LDL-C), Very Low Density Lipoprotein-Cholesterol (VLDL-C) and triglycerides (TG) along with an increase in serum High Density Lipoprotein-Cholesterol (HDL-C) levels. Activities of Serum Aspartate transaminase (AST), Alanine transaminase (ALT) and Alkaline phosphatase (ALP) and levels of blood urea and creatinine were improved to near normal levels in the treated STZ rats indicating the protective role of the HBPMP against liver and kidney damage and its non-toxic property. In conclusion, HBPMP possesses antihyperglycemic and antihyperlipidemic activities. PMID:23827180

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

    PubMed

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

    2013-05-01

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

  10. Antidiabetic activity of mycelia selenium-polysaccharide from Catathelasma ventricosum in STZ-induced diabetic mice.

    PubMed

    Liu, Yuntao; Sun, Jun; Rao, Shengqi; Su, Yujie; Li, Junhua; Li, Caiming; Xu, Shude; Yang, Yanjun

    2013-12-01

    Se-polysaccharide from Catathelasma ventricosum (SPC-2) was purified by DEAE-52 and Sephadex G-100 column chromatography. The average size of SPC-2 was 1.6×10(5) Da, and it was mainly composed of glucose (87.4%) with the conformation of ?-pyran ring. The branched structure of SPC-2 was proved intuitively by atomic force microscope (AFM). The antidiabetic potential of SPC-2 was tested in STZ-induced diabetic mice. After STZ-induced diabetic mice being administered of SPC-2 for 30 days, SPC-2 treatment significantly reduced the levels of malondialdehyde (MDA) and low-density lipoprotein cholesterol (LDL-C) that were increased by the STZ treatment. Further, the SPC-2 treatment led to increased activity of antioxidant enzymes in liver and kidney and high-density lipoprotein cholesterol (HDL-C) that were decreased by the STZ. The results of histopathology also showed SPC-2 protected tissues (pancreas, liver and kidney) against peroxidation damage and maintained tissue integrity. PMID:24007742

  11. Effect of the magnetized water supplementation on blood glucose, lymphocyte DNA damage, antioxidant status, and lipid profiles in STZ-induced rats.

    PubMed

    Lee, Hye-Jin; Kang, Myung-Hee

    2013-02-01

    This study investigated the effects of magnetized water supplementation on blood glucose, DNA damage, antioxidant status, and lipid profiles in streptozotocin (STZ)-induced diabetic rats. There were three groups of 4-week-old male Sprague-Dawley rats used in the study: control group (normal control group without diabetes); diabetes group (STZ-induced diabetes control); and magnetized water group (magnetized water supplemented after the induction of diabetes using STZ). Before initiating the study, diabetes was confirmed by measuring fasting blood glucose (FBS > 200 dl), and the magnetized water group received magnetized water for 8 weeks instead of general water. After 8 weeks, rats were sacrificed to measure the fasting blood glucose, insulin concentration, glycated hemoglobin level, degree of DNA damage, antioxidant status, and lipid profiles. From the fourth week of magnetized water supplementation, blood glucose was decreased in the magnetized water group compared to the diabetes group, and such effect continued to the 8th week. The glycated hemoglobin content in the blood was increased in the diabetes group compared to the control group, but decreased significantly in the magnetized water group. However, decreased plasma insulin level due to induced diabetes was not increased by magnetized water supplementation. Increased blood and liver DNA damages in diabetes rats did significantly decrease after the administration of magnetized water. In addition, antioxidant enzyme activities and plasma lipid profiles were not different among the three groups. In conclusion, the supplementation of magnetized water not only decreased the blood glucose and glycated hemoglobin levels but also reduced blood and liver DNA damages in STZ-induced diabetic rats. From the above results, it is suggested that the long-term intake of the magnetized water over 8 weeks may be beneficial in both prevention and treatment of complications in diabetic patients. PMID:23423956

  12. EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model.

    PubMed

    Liang, Dandan; Zhong, Peng; Hu, Jie; Lin, Feng; Qian, Yuanyuan; Xu, Zheng; Wang, Jingying; Zeng, Chunlai; Li, Xiaokun; Liang, Guang

    2015-05-01

    Diabetes mellitus is strongly associated with cardiomyopathy. The underlying mechanisms for the development of diabetic cardiomyopathy are complex and not completely understood. Recent studies showed that epidermal growth factor receptors (EGFRs) are involved in diabetes-induced cardiac injury. However, the role of EGFR in the diabetic heart has yet to be confirmed. The aim of the present study is to further determine the role of EGRF in the pathogenesis of diabetic heart injury. The type 1 diabetic mice induced by streptozotocin were treated with EGFR inhibitors (AG1478 and 451) for 8 weeks, respectively. It was observed that diabetes induced phospohorylation of EGFR and AKT, increased cardiac ROS levels, and ultimately led to cardiac remodeling including cardiac hypertrophy, disorganization, apoptosis, and fibrosis, while all these molecular and pathological alterations were attenuated by the treatment with EGFR inhibitors. In vitro, either pharmacological inhibition of EGFR/AKT or sh-RNA silencing of EGFR significantly inhibited high concentration glucose (HG)-induced ROS generation and subsequently cell apoptosis in both cardiac H9C2 cells and primary rat cardiomyocytes, respectively. The ROS reduction by EGFR inhibitor was associated with the decreased NADPH oxidase activity and expression in H9c2 cells. HG-induced cardiomyocyte injuries were also reduced by NAC, an inhibitor of ROS. This study provides evidence that EGFR has a key role in the pathogenesis of STZ-induced diabetic cardiac damage and remodeling via ROS generation, and suggests that EGFR may be a potential target in treating diabetic cardiomyopathy. PMID:25758431

  13. Anti-diabetic effects of polysaccharides from Talinum triangulare in streptozotocin (STZ)-induced type 2 diabetic male mice.

    PubMed

    Xu, Wei; Zhou, Qing; Yin, Jiao-jiao; Yao, Yong; Zhang, Jiu-liang

    2015-01-01

    The present study evaluated the anti-diabetic effects of the polysaccharides obtained from Talinum triangulare (TTP). Two TTP doses (150 mg/kg and 300 mg/kg · bw/d) were administered orally to normal and streptozotocin (STZ)-induced type 2 diabetic male Kunming mice, respectively. The TTP hypoglycemic and hypolipidemic effects were evaluated by testing the fast blood glucose (FBG) level, fasting serum insulin (FINS), and serum lipids (TC, TG, HDL, LDL) as well as the body, hepar and kidney weights. After four weeks administration, the low-dose group 150 mg/kg · bw/d) and high-dose group (300 mg/kg · bw/d) showed a marked FBG fall rate of 29.85% and 41.18% (FBG fall rate% = ((Diabetic control--TTP group)/Diabetic control) × 100%). The results of FBG and serum lipids indicate that TTP possess significant hypoglycemic effect, but no significant hypolipidemic effect. These results suggest the potential use of TTP as a functional food for the treatment of type 2 diabetic mellitus (T2DM). PMID:25236607

  14. Antidiabetic Activity of Some Herbal Plants in Streptozotocin Induced Diabetic Albino Rats

    Microsoft Academic Search

    S. K. Prasad; Alka Kulshreshtha; Taj N. Qureshi

    2009-01-01

    Aqueous extract of leaves of 3 herbs (Murraya koenigii, MK; Psidium guajava, PG and Catharanthus roseus, CR) were used to test their antidiabetic activity in Streptozotocin (STZ) induced diabetic albino rats. MK, PG and CR are given to the STZ induced diabetic rats at the concentration of 500 mg\\/kg body weight in different groups of 6 diabetic rats each orally

  15. Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat

    Microsoft Academic Search

    I. Ahmed; E. Adeghate; E. Cummings; A. K. Sharma; J. Singh

    2004-01-01

    This study investigated the beneficial effects and mechanism of action of the juice of Momordica charantia in streptozotocin (STZ)-induced diabetes mellitus in rats. Diabetes mellitus was associated with significant (p p M. charantia juice by STZ-induced diabetic rats partially reversed all the diabetes-induced effects measured. Daily oral administration of M. charantia juice to STZ-induced diabetic rates significantly (p +- and

  16. Hypoglycemic Effect of Sargassum ringgoldianum Extract in STZ-induced Diabetic Mice

    PubMed Central

    Lee, Chae-Won; Han, Ji-Sook

    2012-01-01

    This study was designed to investigate whether Sargassum ringgoldianum extract may inhibit ?-glucosidase and ?-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. The IC50 values of Sargassum ringgoldianum extract against ?-glucosidase and ?-amylase were 0.12 mg/mL and 0.18 mg/mL, respectively, which evidenced higher activities than those of acarbose. The blood glucose levels of the Sargassum ringgoldianum extract administered group were significantly lower compared to the control group in the streptozotocin-induced diabetic mice. Moreover, the area under the two-hour blood glucose response curve was significantly reduced and the absorption of dietary carbohydrates was delayed after administration of Sargassum ringgoldianum extract in the diabetic mice. Therefore, these results indicated that Sargassum ringgoldianum extract may help decrease the postprandial blood glucose level via inhibiting ?-glucosidase. PMID:24471057

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

    PubMed

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

    2014-04-01

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

  18. Neuroprotective effect of cyclooxygenase inhibitors in ICV-STZ induced sporadic Alzheimer's disease in rats.

    PubMed

    Dhull, Dinesh Kumar; Jindal, Ankur; Dhull, Rakesh K; Aggarwal, Saurabh; Bhateja, Deepak; Padi, Satyanarayana S V

    2012-01-01

    Sporadic Alzheimer's disease is an age-related neurological and psychiatric disorder characterized by impaired energy metabolism. Oxidative stress and neuroinflammation have been implicated in pathophysiology of sporadic type of dementia. The central streptozotocin administration induces behavioral and biochemical alterations resembling those in sporadic type of Alzheimer's patients. The present study was designed to investigate the effects of chronic pretreatment with cyclooxygenase-1 or cyclooxygenase-2 or cyclooxygenase-3 selective inhibitors on cognitive dysfunction and oxidative stress markers in intracerebroventricular streptozotocin-treated rats. Chronic treatment with valeryl salicylate (5 and 10 mg/kg, i.p.) and etoricoxib (5 and 10 mg/kg, i.p.) on a daily basis for a period of 21 days, beginning 1 h prior to first intracerebroventricular streptozotocin injection, significantly improved streptozotocin-induced cognitive impairment. However, phenacetin (20 and 40 mg/kg, i.p.) failed to restore the cognitive performances of streptozotocin-treated rats. Besides, improving cognitive dysfunction, chronic administration of highly selective cyclooxygenase-1 and/or cyclooxygenase-2 inhibitors (valeryl salicylate and etoricoxib, respectively), but not cyclooxygenase-3 inhibitor (phenacetin), significantly reduced elevated malondialdehyde, nitrite levels, and restored reduced glutathione and superoxide dismutase levels. Furthermore, cyclooxygenase-1 and/or cyclooxygenase-2 inhibitors significantly increased the survival of pyramidal neurons. In summary, we demonstrate for the first time that both cyclooxygenase-1 and cyclooxygenase-2 isoforms, but not cyclooxygenase-3, are involved in the progression of neuronal damage in intracerebroventricular streptozotocin-treated rats. PMID:21701788

  19. Probucol Protects Against Atherosclerosis Through Lipid-lowering and Suppressing Immune Maturation of CD11c+ Dendritic Cells in STZ-induced Diabetic LDLR-/- Mice.

    PubMed

    Zhu, Hong; Jin, Xueting; Zhao, Jingjing; Dong, Zhen; Ma, Xin; Xu, Fang; Huang, Wei; Liu, George; Zou, Yunzeng; Wang, Keqiang; Hu, Kai; Sun, Aijun; Ge, Junbo

    2015-06-01

    Probucol, an agent characterized by lipid-lowering and antioxidant property, retards atherosclerosis effectively. To test the hypothesis that probucol might act its antiatherosclerotic role by suppressing immune maturation of dendritic cells (DCs), 7-week-old LDLR mice were rendered diabetic with streptozotocin (STZ) and then fed either a high-fat diet only or added with 0.5% (wt/wt) probucol for 4 months, and human monocyte-derived dendritic cells were preincubated with or without probucol and stimulated by oxidized low-density lipoprotein. In STZ-induced diabetic LDLR mice, probucol treatment significantly lowered plasma total cholesterol and high-density lipoprotein-cholesterol levels; regressed aortic atherosclerotic lesions; reduced splenic CD40, CD80, CD86, MHC-II expression, and plasma IL-12p70 production; and decreased the expression of CD11c DCs within atherosclerotic lesions. In vitro, oxidized low-density lipoprotein promoted human monocyte-derived dendritic cells maturation; stimulated CD40, CD86, CD1a, HLA-DR expression; increased tumor necrosis factor-? production; and decreased IL-4 production. However, these effects were obviously inhibited by probucol pretreatment. In conclusion, our study indicated that probucol effectively retarded atherosclerosis at least partly through lipid-lowering and inhibiting immune maturation of CD11c DCs in STZ-induced diabetic LDLR mice. PMID:25714599

  20. Probucol Protects Against Atherosclerosis Through Lipid-lowering and Suppressing Immune Maturation of CD11c+ Dendritic Cells in STZ-induced Diabetic LDLR?/? Mice

    PubMed Central

    Zhu, Hong; Jin, Xueting; Zhao, Jingjing; Dong, Zhen; Ma, Xin; Xu, Fang; Huang, Wei; Liu, George; Zou, Yunzeng; Wang, Keqiang; Hu, Kai; Sun, Aijun

    2015-01-01

    Abstract: Probucol, an agent characterized by lipid-lowering and antioxidant property, retards atherosclerosis effectively. To test the hypothesis that probucol might act its antiatherosclerotic role by suppressing immune maturation of dendritic cells (DCs), 7-week-old LDLR?/? mice were rendered diabetic with streptozotocin (STZ) and then fed either a high-fat diet only or added with 0.5% (wt/wt) probucol for 4 months, and human monocyte-derived dendritic cells were preincubated with or without probucol and stimulated by oxidized low-density lipoprotein. In STZ-induced diabetic LDLR?/? mice, probucol treatment significantly lowered plasma total cholesterol and high-density lipoprotein-cholesterol levels; regressed aortic atherosclerotic lesions; reduced splenic CD40, CD80, CD86, MHC-II expression, and plasma IL-12p70 production; and decreased the expression of CD11c+ DCs within atherosclerotic lesions. In vitro, oxidized low-density lipoprotein promoted human monocyte–derived dendritic cells maturation; stimulated CD40, CD86, CD1a, HLA-DR expression; increased tumor necrosis factor-? production; and decreased IL-4 production. However, these effects were obviously inhibited by probucol pretreatment. In conclusion, our study indicated that probucol effectively retarded atherosclerosis at least partly through lipid-lowering and inhibiting immune maturation of CD11c+ DCs in STZ-induced diabetic LDLR?/? mice. PMID:25714599

  1. A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia.

    PubMed

    Agrawal, Rahul; Tyagi, Ethika; Shukla, Rakesh; Nath, Chandishwar

    2009-03-01

    In the present study, role of brain insulin receptors (IRs) in memory functions and its correlation with acetylcholinesterase (AChE) activity and oxidative stress in different brain regions were investigated in intracerebroventricular (ICV) streptozotocin (STZ) induced dementia model. Rats were treated with STZ (3 mg/kg, ICV) on day 1 and 3. Donepezil (5 mg/kg po) and melatonin (20 mg/kg ip) were administered in pre- and post-treatment schedules. Morris water maze test was done on day 14 and animals were sacrificed on day 21 from 1st STZ injection. Memory deficit was found in STZ group as indicated by no significant decrease in latency time antagonized by donepezil and melatonin. IR protein level was found significantly increased in trained group as compared to control, whereas STZ decreased IR level significantly as compared to trained rats in hippocampus which indicates that IR is associated with memory functions. STZ induced decrease in IR was reversed by melatonin but not by donepezil. Melatonin per se did not show any significant change in IR level as compared to control. AChE activity (DS and SS fraction) was found to be increased in hippocampus in STZ group as compared to trained which was inhibited by donepezil and melatonin. Increase in MDA level and decrease in GSH level were obtained in STZ group indicating oxidative stress, which was attenuated by donepezil and melatonin. Effectiveness of antioxidant, melatonin but not of anti-cholinesterase, donepezil against STZ induced changes in IR indicates that IR is more affected with oxidative stress than cholinergic changes. PMID:19705549

  2. In vivo hypoglycaemic effect and inhibitory mechanism of the branch bark extract of the mulberry on STZ-induced diabetic mice.

    PubMed

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

    2014-01-01

    Branch bark extract (BBE) derived from the mulberry cultivar Husang 32 (Morus multicaulis L.) with aqueous alcohol solution has been investigated as an inhibitor of ?-glycosidase in vitro. Mulberry BBE was orally administered to STZ-induced diabetic mice for three weeks, and it improved the weight gain and ameliorated the swelling of liver and kidney in diabetic mice. Obviously, mulberry BBE not only can reduce the abnormally elevated levels of serum insulin and ameliorate insulin resistance induced by STZ, but also it regulates dyslipidemia in diabetic mice. To understand this therapeutic effect and the regulatory mechanisms of BBE in diabetic mice, a qRT-PCR experiment was performed, indicating that the mulberry BBE can regulate the mRNA expression of glycometabolism genes in diabetic mice, including glucose-6-phosphatase (G6Pase), glucokinase (GCK), and phosphoenolpyruvate carboxykinase (PEPCK), thereby regulating sugar metabolism and reducing the blood glucose level in diabetic mice. The mulberry BBE can increase the mRNA expression of the genes Ins1, Ins2 and pancreatic duodenal homeobox-1 (PDX-1) and may decrease the insulin resistance in diabetic mice. Those results provide an important basis for making the best use of mulberry branch resources and producing biomedical drugs with added value. PMID:25177729

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

    PubMed Central

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

    2014-01-01

    Branch bark extract (BBE) derived from the mulberry cultivar Husang 32 (Morus multicaulis L.) with aqueous alcohol solution has been investigated as an inhibitor of ?-glycosidase in vitro. Mulberry BBE was orally administered to STZ-induced diabetic mice for three weeks, and it improved the weight gain and ameliorated the swelling of liver and kidney in diabetic mice. Obviously, mulberry BBE not only can reduce the abnormally elevated levels of serum insulin and ameliorate insulin resistance induced by STZ, but also it regulates dyslipidemia in diabetic mice. To understand this therapeutic effect and the regulatory mechanisms of BBE in diabetic mice, a qRT-PCR experiment was performed, indicating that the mulberry BBE can regulate the mRNA expression of glycometabolism genes in diabetic mice, including glucose-6-phosphatase (G6Pase), glucokinase (GCK), and phosphoenolpyruvate carboxykinase (PEPCK), thereby regulating sugar metabolism and reducing the blood glucose level in diabetic mice. The mulberry BBE can increase the mRNA expression of the genes Ins1, Ins2 and pancreatic duodenal homeobox-1 (PDX-1) and may decrease the insulin resistance in diabetic mice. Those results provide an important basis for making the best use of mulberry branch resources and producing biomedical drugs with added value. PMID:25177729

  4. Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats

    Microsoft Academic Search

    A. Tone; K. Shikata; M. Sasaki; S. Ohga; K. Yozai; S. Nishishita; H. Usui; R. Nagase; D. Ogawa; S. Okada; Y. Shikata; J. Wada; H. Makino

    2005-01-01

    Aims\\/hypothesis  Recent studies have shown that the inflammatory process is involved in the pathogenesis of diabetic nephropathy. Fourteen-membered ring macrolides, including erythromycin, have anti-inflammatory, as well as antibacterial effects. The aim of this study was to investigate the renoprotective effects of erythromycin in streptozotocin (STZ)-induced diabetic rats.Methods  STZ-induced diabetic rats were treated orally with erythromycin (5 mg\\/kg body weight) or vehicle every day

  5. Alterations in atrial natriuretic peptide and its receptors in streptozotocin-induced diabetic rat kidneys

    Microsoft Academic Search

    Enyioma N. Obineche; Ernest Adeghate; Irwin S. Chandranath; Sheela Benedict; Laila S. Al Gafri; Abdu Adem

    2004-01-01

    In this study the effect of diabetes mellitus on atrial natriuretic peptide (ANP) receptors in streptozotocin- (STZ-) induced diabetic rat kidneys was studied. Moreover, plasma ANP concentration was evaluated in diabetic and control rats by using radioimmunoassay. In addition, the expression of ANP in the kidneys of control and diabetic rats was evaluated by immunohistochemistry. Body-weight loss and increased glucose

  6. Minocycline attenuates pain by inhibiting spinal microglia activation in diabetic rats.

    PubMed

    Sun, Jin-Shan; Yang, Yu-Jie; Zhang, Yong-Zhen; Huang, Wen; Li, Zhao-Shen; Zhang, Yong

    2015-08-01

    The mechanisms associated with diabetes?induced neuropathic pain are complex and poorly understood. In order to understand the involvement of spinal microglia activity in diabetic pain, the present study investigated whether minocycline treatment is able to attenuate diabetic pain using a rat model. Diabetes was induced using a single intraperitoneal injection of streptozotocin (STZ). Minocycline was then intrathecally administered to the rats. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested weekly. The expression of OX?42, Iba?1, phospho?p38 mitogen?activated protein kinase (MAPK), tumor necrosis factor?? (TNF??), interleukin?1? (IL?1?) and inducible nitric oxide synthase (iNOS), were examined in the spinal cord in order to evaluate the activation of microglia. The present study demonstrated that rats with STZ?induced diabetes exhibited increased mean plasma glucose concentration, decreased mean body weight and significant pain hypersensitivity compared with control rats. PWT and PWL values of rats with STZ?induced diabetes increased following treatment with minocycline. No differences were observed in expression levels of the microglial activity markers (OX?42, Iba?1 and phospho?p38 MAPK) between rats with STZ?induced diabetes and control rats. However, TNF??, IL?1? and iNOS expression levels were higher in rats with STZ?induced diabetes compared with control rats. Following treatment with minocycline markers of microglial activation, including cytokines and iNOS, were downregulated in rats with STZ?induced diabetes. The results of the present study indicated that minocycline treatment may inhibit spinal microglial activation and attenuate diabetic pain in rats with STZ?induced diabetes. PMID:25955348

  7. Beneficial effects of dietary L-arginine supplementation to diabetic rats

    E-print Network

    Kohli, Ripla

    2004-09-30

    dysfunction. In experiment I, streptozotocin (STZ) induced-diabetic male Sprague Dawley (SD) rats (a model of type-I diabetes) were individually pair-fed a casein-based diet on the basis of feed intake (per kg body weight) of non-diabetic SD rats. Addition...

  8. Antioxidant role of Umbelliferone in STZ-diabetic rats

    Microsoft Academic Search

    B. Ramesh; K. V. Pugalendi

    2006-01-01

    The objective of the study was to investigate the role of Umbelliferone (UMB) on lipid peroxidation, nonenzymic and enzymic antioxidants in the plasma and liver of streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180–200 g, were induced diabetes by administration of STZ (40 mg\\/kg b.wt.) intraperitoneally. The normal and diabetic rats were treated with UMB

  9. Tocotrienol-Rich Fraction from Palm Oil Prevents Oxidative Damage in Diabetic Rats

    PubMed Central

    Matough, Fatmah A.; Budin, Siti B.; Hamid, Zariyantey A.; Abdul-Rahman, Mariati; Al-Wahaibi, Nasar; Mohammed, Jamaludine

    2014-01-01

    Objectives: This study was carried out to determine the effects of tocotrienol-rich fraction (TRF) (200 mg/Kg) on biomarkers of oxidative stress on erythrocyte membranes and leukocyte deoxyribonucleic acid (DNA) damage in streptozotocin (STZ)-induced diabetic rats. Methods: Male rats (n = 40) were divided randomly into four groups of 10: a normal group; a normal group with TRF; a diabetic group, and a diabetic group with TRF. Following four weeks of treatment, fasting blood glucose (FBG) levels, oxidative stress markers and the antioxidant status of the erythrocytes were measured. Results: FBG levels for the STZ-induced diabetic rats were significantly increased (P <0.001) when compared to the normal group and erythrocyte malondialdehyde levels were also significantly higher (P <0.0001) in this group. Decreased levels of reduced glutathione and increased levels of oxidised glutathione (P <0.001) were observed in STZ-induced diabetic rats when compared to the control group and diabetic group with TRF. The results of the superoxide dismutase and glutathione peroxidase activities were significantly lower in the STZ-induced diabetic rats than in the normal group (P <0.001). The levels of DNA damage, measured by the tail length and tail moment of the leukocyte, were significantly higher in STZ-induced diabetic (P <0.0001). TRF supplementation managed to normalise the level of DNA damage in diabetic rats treated with TRF. Conclusion: Daily supplementation with 200 mg/Kg of TRF for four weeks was found to reduce levels of oxidative stress markers by inhibiting lipid peroxidation and increasing the levels of antioxidant status in a prevention trial for STZ-induced diabetic rats. PMID:24516761

  10. The Effects of Vanadium (V) Absorbed by Coprinus comatus on Bone in Streptozotocin-induced Diabetic Rats

    Microsoft Academic Search

    Yi Pei; Qin Fu

    The purpose of this study was to evaluate the effects of vanadium absorbed by Coprinus comatus (VACC) treatment on bone in streptozotocin (STZ)-induced diabetic rats. Forty-five Wistar female rats used were divided into\\u000a three groups: (1) normal rats (control), (2) diabetic rats, and (3) diabetic rats treated with VACC. Normal and diabetic rats\\u000a were given physiological saline, and VACC-treated rats

  11. Long-term effects of Cinnamomum zeylanicum Blume oil on some physiological parameters in streptozotocin-diabetic and non-diabetic rats (Efectos a largo plazo del aceite esencial de Cinnamomum zeylanicum Blume en algunos parametros fisiológicos en ratas diabéticas inducidas por estreptozotocina)

    Microsoft Academic Search

    Talal A. ZARI; Ayed Sh

    2009-01-01

    The long-term effects of Cinnamomum zeylanicum Blume oil on some physiological parameters were investigated in streptozotocin (STZ)-induced diabetic and non-diabetic male Wistar rats. STZ-induced diabetic rats showed significant increases in the levels of blood glucose, triglycerides, cholesterol, low density lipoprotein LDL-cholesterol, urea, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) while high density lipoprotein HDL- cholesterol, total protein and uric acid

  12. Characteristics of dendroaspis natriuretic peptide and its receptor in streptozotocin?induced diabetic rats.

    PubMed

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

    2015-08-01

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

  13. Dark-Cycle Video Surveillance of Sexual Performances of Normal and Diabetic Rats

    Microsoft Academic Search

    Yat-Ching Tong; Ying-Cho Hung; Shinn-Nan Lin; Juei-Tang Cheng

    1996-01-01

    Clinically, a 59% prevalence of impotence was reported among diabetic male patients. Neurological, vascular, endocrinologic and psychological factors are probably involved. Previous reports with the rat model found deterioration of sexual behavior and reproductive function caused by streptozotocin (STZ)- induced diabetes. The purpose of the present study was to develop the dark-cycle video recording methodology for the observation of rat

  14. Beta Cell Protective Effects of Sodium Tungstate in Streptozotocin-Induced Diabetic Rats: Glycemic Control, Blockage of Oxidative Stress and Beta Cell Histochemistry

    Microsoft Academic Search

    Zahra Heidari; Mehdi Harati; Hamid Reza Mahmoudzadeh-Sagheb; Bita Moudi

    2008-01-01

    Background: Diabetes is a major public health problem. The development of new therapies that are able to improve glycemia management and even to cure diabetes is of great interest. In this study, protective effects of sodium tungstate against STZ-induced beta-cell damages were investigated. Methods: Sixty rats were divided into six groups: control, diabetic, sodium tungstate treated diabetic rats from one

  15. Immunohistochemical detection of hepatic GM1 and GM2 gangliosides in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Adela V. Abregú; Susana B. Genta; Alicia N. Sánchez Riera; Sara S. Sánchez

    2002-01-01

    This study was undertaken to investigate the consequences of diabetes on the expression of GM1 and GM2 gangliosides in rat liver. Experimental diabetes was induced by treatment with Streptozotocin (STZ) in adult male Sprague–Dawley rats. Two-dimensional thin-layer chromatography of total ganglioside preparations of liver tissues from STZ-induced diabetic rats showed an increased amount of GM1, while GM2 could not be

  16. Antidiabetic effects of sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Ming Li; Jason J. Smee; Wenjun Ding; Debbie C. Crans

    2009-01-01

    The evaluation of the anti-diabetic effects of an organic vanadium(V) complex in streptozotocin (STZ)-induced diabetic rats was investigated. The STZ-induced diabetic rats were orally administrated with sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate (V5dipic-NH2), a vanadium(V) coordination compound. The compound was administered through drinking water at a concentration of 0.1mg\\/mL for 20 days, and then the concentration was increased to 0.3mg\\/mL for the following

  17. Regulation of cardiac oxidative stress and lipid peroxidation in streptozotocin-induced diabetic rats treated with aqueous extract of Pimpinella tirupatiensis tuberous root

    Microsoft Academic Search

    Rajeswara Reddy Saddala; Lavanya Thopireddy; Narasimhulu Ganapathi; Sathyavelu Reddy Kesireddy

    Plants with antidiabetic activities provide important source for the development of new drugs in the management of diabetes mellitus. The main aim of this study was to evaluate the protective effect of aqueous extract (AE) of Pimpinella tirupatiensis (Pt) tuberous root on cardiac oxidative stress and lipid peroxidation (LPO) in non-diabetic and streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in

  18. Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    I. Ahmed; M. S. Lakhani; M. Gillett; A. John; H. Raza

    2001-01-01

    Momordica charantia (karela) is commonly used as an antidiabetic and antihyperglycemic agent in Asian, Oriental and Latin American countries. This study was undertaken to investigate the effects of long term feeding (10 weeks) of M. charantia fruit extract on blood plasma and tissue lipid profiles in normal and streptozotocin (STZ) -induced Type 1 diabetic rats. The results show that there

  19. Antihyperglycemic and Antihyperlipidemic Effects of Fruit Aqueous Extract of Berberis integerrima Bge. in Streptozotocin-induced Diabetic Rats.

    PubMed

    Ashraf, Hossein; Heidari, Reza; Nejati, Vahid

    2014-01-01

    Use of medicinal plants for attenuation of hyperglycemia and restoration of lipids disorder to normal level is clinically very important. The aim of present study was to evaluate the effects of Berberis integerrima Bge. fruit aqueous extract (BIFAE) on blood glucose and lipid profile in streptozotocin (STZ) - induced diabetic rats. The STZ-induced diabetic rats were treated by fruit aqueous extract of Berberis integerrima Bge. at doses (250 and 500 mg/Kg bw) and glibenclamide (0.6 mg/Kg bw) for 42 days by gavage. Blood glucose levels and body weights of rats were measured on weeks 0, 2, 4 and 6. Total lipid levels were determined in normal and STZ-induced diabetic rats after administration of the BIFAE and glibenclamide for 42 days. STZ-induced diabetic rats showed a significant (P<0.001) increases in the levels of blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C) while body weight and high density lipoprotein HDL-cholesterolan (HDL-C) were significantly(P<0.001) decreased compared to normal rats. Daily administration of BIFAE did not possess the hypoglycemic and hypolipidaemic activity in STZ- diabetic rats during 6-week treatment period. Results indicate the usage of BIFAE in traditional medicine for the treatment of diabetes may need more investigation. PMID:25587320

  20. Increased atrial natriuretic peptide mRNA expression in the kidney of diabetic rats

    Microsoft Academic Search

    Shyi-Jang Shin; Yau-Jiunn Lee; Mian-Shin Tan; Tusty-Jiuan Hsieh; Juei-Hsiung Tsai

    1997-01-01

    Increased atrial natriuretic peptide mRNA expression in the kidney of diabetic rats. To investigate whether renal synthesis of atrial natriuretic peptide (ANP) is influenced in diabetes, we measured renal ANP mRNA levels, urine volume, urinary ANP and sodium excretion rates in streptozotocin (STZ)-induced diabetic rats. By using reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis, we found that

  1. Sodium Tungstate Attenuate Oxidative Stress in Brain Tissue of Streptozotocin-Induced Diabetic Rats

    Microsoft Academic Search

    Alireza Nakhaee; Mohammad Bokaeian; Azim Akbarzadeh; Mohammad Hashemi

    2010-01-01

    High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of\\u000a cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated\\u000a effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced\\u000a diabetic rats. Rats were divided into four

  2. Effect of Lycopene Administration on Plasma Glucose, Oxidative Stress and Body Weight in Streptozotocin Diabetic Rats

    Microsoft Academic Search

    Vesile Duzguner; Altug Kucukgul; Suat Erdogan; Sefa Celik; Kazim Sahin

    2008-01-01

    Duzguner, V., Kucukgul, A., Erdogan, S., Celik, S. and Sahin, K. 2008. Effect of lycopene administration on plasma glucose, oxidative stress and body weight in streptozotocin diabetic rats. J. Appl. Anim. Res., 33: 17–20.To evaluate the role of lycopene, a carotenoid antioxidant, on streptozotocin (STZ)-induced diabetic rats, 12 female rats received a single intraperitonial injection of STZ at a dose

  3. Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats

    Microsoft Academic Search

    Jie Jia; Xi Zhang; Yong-Shan Hu; Yi Wu; Qing-Zhi Wang; Na-Na Li; Qing-Chuan Guo; Xin-Cun Dong

    2009-01-01

    Effect of Ganoderma lucidum polysaccharides treatment on blood glucose, serum insulin level, lipid peroxidation, nonenzymic and enzymic antioxidants in the plasma and liver of streptozotocin (STZ)-induced diabetic rats was studied. Adult male rats of Wistar strain, weighing 195 to 250g, were randomized into control and experimental groups. Experiment group rats were induced diabetes by administration of STZ (45mg\\/kgb.wt.) intraperitoneally. The

  4. A quantitative study of sodium tungstate protective effect on pancreatic beta cells in streptozotocin-induced diabetic rats.

    PubMed

    Heidari, Zahra; Mahmoudzadeh-Sagheb, Hamidreza; Moudi, Bita

    2008-12-01

    Diabetes is a major public health problem. Development of new therapies that are able to improve glycemia management, cure diabetes, and can even protect from it, are of great interest. This study investigated the protective effect of sodium tungstate against STZ-induced beta-cell damages by means of stereological methods. Sixty rats were divided into six groups: control (C), tungstate-treated control (TC), STZ-induced diabetic (D), STZ-induced diabetic rats were treated by sodium tungstate from 1 week before STZ injection (TDB), food-restricted diabetic (FRD), and diabetic rats treated with sodium tungstate 1 week after STZ administration (TDA). Stereological estimation of pancreas volume, islets volume density, volume-weighted mean islets volume and mass of beta cells, islets, and pancreas and total number of islets were done. Islets volume density, volume-weighted mean islets volume, and mass of beta cells, islets, and pancreas of TDB group was significantly higher than D, FRD and TDA groups (P<0.001) and was comparable to controls (C and TC groups). Total number of islets, pancreas wet weight and volume did not show any significant changes between these groups (P>0.05). Results suggested that sodium tungstate preserves pancreatic beta cells from STZ-induced damages and diabetes induction in rats. PMID:18400503

  5. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats

    Microsoft Academic Search

    Uma Bhandari; Raman kanojia; K. K. Pillai

    2005-01-01

    The lipid lowering and antioxidant potential of ethanolic extract of Zingiber officinale Roscoe (family, Zingiberaceae) was evaluated in streptozotocin (STZ)-induced diabetes in rats. Ethanolic extract of Zingiber officinale (200mg\\/kg) fed orally for 20 days produced, significant antihyperglycaemic effect (P<0.01) in diabetic rats. Further, the extract treatment also lowered serum total cholesterol, triglycerides and increased the HDL-cholesterol levels when compared with

  6. The Effects of Combined Treatment of Antioxidants on the Liver Injury in STZ Diabetic Rats

    Microsoft Academic Search

    Selda Gezginci-Oktayoglu; Hasan Basaraner; Refiye Yanardag; Sehnaz Bolkent

    2009-01-01

    The aim of this study was to examine whether an antioxidant combination of vitamin C, vitamin E, and sodium selenate (Se)\\u000a has an effect on the liver of diabetic rats. Vitamin C, vitamin E, and Se were administered for 30 days to streptozotocin\\u000a (STZ)-induced diabetic and control groups. In the STZ diabetic group, blood glucose levels, liver lipid peroxidation (LPO),\\u000a and

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

    PubMed

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

    2015-08-01

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

  8. Serial changes of sensory nerve conduction velocity and minimal F-wave latency in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Noriaki Kato; Mitsuhiro Makino; Kuniharu Mizuno; Tsunemasa Suzuki; Masaomi Shindo

    1998-01-01

    We studied the serial changes of sensory nerve conduction velocity (SNCV) in the caudal nerve of streptozotocin (STZ)-induced diabetic rats using a new technical method. Minimal F-wave latency was also studied by stimulating the tibial nerve. The SNCV in the diabetic rats was slower than that in the normal rats 2 weeks after STZ injection, and minimal F-wave latency was

  9. Short-term bioaccumulation of vanadium when ingested with a tea decoction in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Andrea L. Edel; Melanie Kopilas; Tod A. Clark; Floribeth Aguilar; Pallub K. Ganguly; Clayton E. Heyliger; Grant N. Pierce

    2006-01-01

    Sodium orthovanadate suspended in a lichee black tea decoction effectively regulates blood glucose levels in rats with insulin-dependent, streptozotocin (STZ)-induced diabetes. The primary advantage of vanadate delivery with the tea decoction over conventional systems that use water suspensions of vanadate is a significant reduction in the toxic side effects of vanadate. It is unknown if the tea alters the bioavailability

  10. Antihyperglycemic and antihyperlipidemic effects of n-hexane fraction from the hydro-methanolic extract of sepals of Salmalia malabarica in streptozotocin-induced diabetic rats.

    PubMed

    De, Debasis; Ali, Kazi Monjur; Chatterjee, Kausik; Bera, Tushar Kanti; Ghosh, Debidas

    2012-01-01

    Bio-efficacy of n-hexane fraction of sepal of Salmalia malabarica was evaluated covering the biochemical sensors for the management of hyperglycemic and hyperlipidemic effects. Evaluation of n-hexane fraction of Salmalia malabarica (SMH) from hydro-methanolic (2:3) extract at the dose of 0.1 gm/kg body weight twice a day were investigated in normal and streptozotocin (STZ) induced diabetic rats. Normal and STZ-induced diabetic rats were divided into five groups. The effect of the fraction on fasting blood glucose (FBG), serum insulin, hemoglobin, glycated hemoglobin, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc), phospholipids, free fatty acids, urea, uric acid, creatinine, albumin and transaminases were investigated in STZ-induced diabetic rat. A significant reduction of FBG level was observed after SMH treatment in STZ-induced diabetic rat. Treatment of diabetic rats with n-hexane fraction of this plant restored the levels of the above biochemical sensors significantly (p<0.001) in respect to the control. Histological studies of pancreas showed a qualitative diminution in the area of the islet's of Langerhans in diabetic group which was recovered by said fraction. Phytochemical screening of the fraction revealed the presence of flavonoids, terpenoids and steroids. PMID:22732718

  11. Evaluation of antioxidants in the kidney of streptozotocin induced diabetic rats.

    PubMed

    Gomathi, D; Kalaiselvi, M; Ravikumar, G; Devaki, K; Uma, C

    2014-04-01

    Diabetes mellitus is one of the most common endocrine metabolic disorders. Dual endocrine deficits of impaired insulin action (insulin resistance) and inadequate insulin secretion create an environment of chronic hyperglycemia and general metabolic disarray. Oxidative stress plays an important role in diabetic pathogenesis. Oxidative stress induced by streptozotocin (STZ) has been shown to damage pancreatic beta cell and produce hyperglycemia in rats. The present study was made to evaluate the antioxidant activity of ethanolic extract of the Evolvulus alsinoides in STZ induced rats. The antioxidant activities were done by using standard protocols. For histopathological analysis, the pancreatic tissues of all experimental groups were fixed with 10 % formalin for 24 h then the samples were stained with hematoxylin-eosin for the microscopic observation. Our results showed the significant decrease in lipid peroxidation and increases in the antioxidant (both enzymatic and nonenzymatic) levels after treatment with standard as well as the E. alsinoides. There is no significant difference between control and plant alone group rats. The histopathology reports also revealed non-toxic effect and protective effect of E. alsinoides in the kidney of STZ induced diabetic rats. Our result indicated that the E. alsinoides extract effectively increased the antioxidant level thereby it prevents oxidative stress during diabetes mellitus and also it showed the protective effect on kidney of STZ induced rats. Hence it can be used to maintain the antioxidant level during diabetes mellitus. PMID:24757306

  12. The vasorelaxant effect of hydrogen sulfide is enhanced in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Merve Denizalti; Turgut Emrah Bozkurt; U?ur Akpulat; Inci Sahin-Erdemli; Nurettin Abac?o?lu

    2011-01-01

    Hydrogen sulfide (H2S) is an endogenous gas which has potent relaxant effect in vascular and nonvascular smooth muscles. In the present study,\\u000a we have investigated how streptozotocin (STZ)-induced diabetes affected the relaxant effect of H2S in rat isolated thoracic aorta and mesenteric and pulmonary arteries. Diabetes was induced by IV injection of STZ (35 mg\\/kg).\\u000a Insulin treatment was applied by using

  13. Effects of diabetes, vanadium, and insulin on glycogen synthase activation in Wistar rats

    Microsoft Academic Search

    Sabina Semiz; Chris Orvig; John H. McNeill

    2002-01-01

    In vivo effects of insulin and vanadium treatment on glycogen synthase (GS), glycogen synthase kinase-3 (GSK-3) and protein phosphatase-1 (PP1) activity were determined in Wistar rats with streptozotocin (STZ)-induced diabetes. The skeletal muscle was freeze-clamped before or following an insulin injection (5 U\\/kg i.v.). Diabetes, vanadium, and insulin in vivo treatment did not affect muscle GSK-3ß activity as compared to

  14. Elevated plasma endothelin-1 level in streptozotocin-induced diabetic rats and responsiveness of the mesenteric arterial bed to endothelin-1

    PubMed Central

    Makino, Ayako; Kamata, Katsuo

    1998-01-01

    Both the plasma endothelin-1 (ET-1) levels and the plasma glucose levels were markedly elevated in streptozotocin (STZ)-induced diabetic rats.The maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasodilatation induced by the ETB-receptor agonist IRL-1620 in the mesenteric arterial bed was significantly reduced in STZ-induced diabetic rats.ET-1 (10?8?M) caused a transient vasodilatation followed by a marked vasoconstriction in methoxamine-preconstricted mesenteric arterial beds. The ET-1-induced vasodilatation was significantly larger in beds from diabetic rats than in those from age-matched controls. By contrast, the ET-1-induced vasoconstriction was significantly smaller in STZ-induced diabetic rats than in the controls.Both removal of the endothelium with Triton X-100 and preincubation with BQ-788 (10?6?M) (ETB-receptor antagonist) abolished the ET-1-induced vasodilatation. Preincubation with BQ-485 (10?6?M) or BQ-123 (3×10?6) (ETA-receptor antagonist) significantly augmented the ET-1-induced vasodilatation in control mesenteric arterial beds, but not that in beds from diabetic rats.These results demonstrate that marked increases not only in plasma glucose, but also in plasma ET-1 occur in STZ-induced diabetic rats. We suggest that the decreased contractile response and the increased vasodilator response of the mesenteric arterial bed to ET-1 may both be due to desensitization of ETA receptors, though ETB receptors may also be desensitized. This desensitization may result from the elevation of the plasma ET-1 levels seen in STZ-induced diabetic rats. PMID:9559887

  15. Effect of lignin-derived lignophenols on vascular oxidative stress and inflammation in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Yuuka Mukai; Toshio Norikura; Shuzo Fujita; Keigo Mikame; Masamitsu Funaoka; Shin Sato

    2011-01-01

    Lignophenols (LP) are the derivatives of native lignin, which is an abundant organic polymer in the plant kingdom. This study\\u000a investigated whether LP can attenuate vascular oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic\\u000a rats. The diabetic rats induced by a single intravenous injection of STZ were randomly divided into two groups fed either\\u000a 0 or 1.0% LP-containing diet. After

  16. Dark-cycle video surveillance of sexual performances of normal and diabetic rats.

    PubMed

    Tong, Y C; Hung, Y C; Lin, S N; Cheng, J T

    1996-01-01

    Clinically, a 59% prevalence of impotence was reported among diabetic male patients. Neurological, vascular, endocrinologic and psychological factors are probably involved. Previous reports with the rat model found deterioration of sexual behavior and reproductive function caused by streptozotocin (STZ)-induced diabetes. The purpose of the present study was to develop the dark-cycle video recording methodology for the observation of rat sexual activities and to study the effect of STZ-induced diabetes on sexual performances of the rat. Adult male Wistar rats were rendered diabetic with intraperitoneal injection of STZ (60 mg/kg body weight). In the 4th week a diabetic rat or a control rat was caged with an adult ovariectomized female rat during the dark cycle. The female had been brought into behavioral estrus with intramuscular injection of 0.1 mg estradiol benzoate 3 days before and 1.0 mg progesterone 3 h before testing. Infrared-light-illuminated video recording was performed to evaluate the sexual performances. The mounting latency and frequency, intromission latency and frequency, the hit rate as well as the post-ejaculatory period of the diabetic rats were significantly deteriorated when compared with the controls (p < 0.05). However, the ejaculatory latency showed no significant difference between the two groups (p > 0.05). In conclusion, it has been demonstrated that with this methodology, behavioral studies on nocturnal animals like the rat can be carried out conveniently. It was shown that the sexual arousal mechanism and copulation-ejaculatory mechanism were both depressed in STZ-induced diabetic rats. The same study model can be used for further pathophysiological and pharmacological researches on the sexual behaviors of diabetic rats. PMID:8776815

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

    PubMed Central

    Ma, Jing; Liu, Yan; Tan, Rongshao; Liu, Houqiang; Lao, Gancheng

    2014-01-01

    Aim. Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN). Meanwhile, low protein diet (LPD) retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ-) induced diabetic rats. Methods. STZ-induced and control rats were both fed with LPD (5%) and normal protein diet (18%), respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. Results. Diabetic rats developed into constantly high levels of serum UA (SUA), creatinine (SCr) and 24?h amounts of urinary albumin excretion (UAE), creatintine (UCr), urea nitrogen (UUN), and uric acid (UUA). LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-? in tubulointerstitium significantly decreased in LPD-fed diabetic rats. Conclusion. LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats. PMID:24772444

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

    PubMed

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

    2014-11-01

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

  19. Effect of melatonin on phagocytic activity and intracellular free calcium concentration in testicular macrophages from normal and streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Joanna Pawlak; Jaipaul Singh; Robert W. Lea; Krystyna Skwarlo-Sonta

    2005-01-01

    This study examined the effect of melatonin (MLT) on in vitro phagocytosis of testicular macrophages taken from control and streptozotocin (STZ)-induced diabetic rats and the possible mechanism of its action. The phagocytic activity was measured as a number of latex beads ingested by 100 macrophages (PI, phagocytic index) in consecutive time points of the incubation. Changes in intracellular free calcium

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

    Microsoft Academic Search

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

    2006-01-01

    Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression

  1. An early diagnostic tool for diabetic peripheral neuropathy in rats.

    PubMed

    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

  2. Role of inducible nitric oxide synthase in induction of RhoA expression in hearts from diabetic rats

    Microsoft Academic Search

    Hesham Soliman; Graham P. Craig; Prabhakar Nagareddy; Violet G. Yuen; Guorong Lin; Ujendra Kumar; John H. McNeill; Kathleen M. MacLeod

    2008-01-01

    Aims Recent studies from our laboratory demonstrated that increased expression of the small GTP- binding protein RhoA and activation of the RhoA\\/rho kinase (ROCK) pathway play an important role in the contractile dysfunction associated with diabetic cardiomyopathy in hearts from streptozotocin (STZ)-induced diabetic rats. Nitric oxide (NO) has been reported to be a positive regulator of RhoA expression in vascular

  3. Protective effects of the volatile oil of Nigella sativa seeds on ?-cell damage in streptozotocin-induced diabetic rats: a light and electron microscopic study

    Microsoft Academic Search

    Mehmet Kanter; Meryem Akpolat; Cevat Aktas

    2009-01-01

    The aim of this study was to evaluate the possible protective effects of the volatile oil of Nigella sativa (NS) seeds on insulin immunoreactivity and ultrastructural changes of pancreatic ?-cells in STZ-induced diabetic rats. STZ\\u000a was injected intraperitoneally at a single dose of 50 mg\\/kg to induce diabetes. The rats in NS treated groups were given NS\\u000a (0.2 ml\\/kg) once a day

  4. The effects of acarbose and Rumex patientia L. on ultrastructural and biochemical changes of pancreatic B cells in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Irfan Degirmenci; M. Cengiz Ustuner; Yusuf Kalender; Suna Kalender; Hasan Veysi Gunes

    2005-01-01

    This study was performed to observe the effects of acarbose and Rumex patientia on morphological change of pancreatic B cells in streptozotocin (STZ)-induced diabetic (type 2) rats. Two-day-old Wistar albino rats were intraperitoneally injected with 100mg\\/kg of STZ or vehicle alone for control. Vehicle and STZ given rats were divided into six groups (1st, 2nd and the 3rd groups are

  5. The effects of dexpanthenol in streptozotocin-induced diabetic rats: histological, histochemical and immunological evidences.

    PubMed

    Gulle, K; Ceri, N G; Akpolat, M; Arasli, M; Demirci, B

    2014-10-01

    This study was designed to investigate the effects of Dexpanthenol (Dxp) on liver and pancreas histology and cytokine levels in streptozotocine (STZ)-induced diabetic rats. Twenty-four Wistar albino male rats were divided into four groups: control, Dxp, STZ-induced diabetic (STZ) and diabetic treatment with Dexpanthenol (STZ-Dxp) groups. Experimental diabetes was induced by single dose STZ (50 mg/kg) intraperitoneally (i.p.). After administration of STZ, the STZ-Dxp group began to receive a 300 mg/kg/day i.p. dose of Dxp for 6 weeks. Liver and pancreas tissues of the control group were in normal morphology. Liver tissue of STZ group showed vacuolisation of hepatocytes in the liver parenchyma with enlargement of sinusoidal spaces and increasing amounts of connective tissue in the portal area. Pancreatic section of STZ group displayed ?-cells with of cytoplasmic mass, reduction of islet size, and atrophy. The STZ-Dxp group that received Dxp treatment exhibit partially normal hepatic parenchyma. Histochemical examinations revealed that the diabetes-induced glycogen depletion markedly improved with the Dxp treatment (p?0.001). The severity of degenerative alteration was lessened by Dxp supplementation in the STZ-Dxp group. Induction of STZ presented a significant increase both in interleukin-1? (IL-1?) (p=0.033) and monocyte chemotactic protein-1 (MCP-1) (p=0.011) levels, when compared with the control rats. DXP-treated diabetic rats' IL-1? and MCP-1 levels were similar to control value. This evidence suggests that Dxp is effective in reducing STZ-induced, diabetic-related complications and may be beneficial for the treatment of diabetic patients. PMID:24733664

  6. Preferential Elevation of Protein Kinase C Isoform betaII and Diacylglycerol Levels in the Aorta and Heart of Diabetic Rats: Differential Reversibility to Glycemic Control by Islet Cell Transplantation

    Microsoft Academic Search

    Toyoshi Inoguchi; Ruggero Battan; Eugene Handler; J. Richard Sportsman; William Heath; George L. King

    1992-01-01

    In the present study, we have measured protein kinase C (PKC) specific activities and total diacylglycerol (DAG) level in the aorta and heart of rats, which showed that after 2 weeks of streptozotocin (STZ)-induced diabetes, membranous PKC specific activity and total DAG content were increased significantly by 88% and 40% in the aorta and by 21% and 72% in the

  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. Improved glycemic control, pancreas protective and hepatoprotective effect by traditional poly-herbal formulation “Qurs Tabasheer” in streptozotocin induced diabetic rats

    PubMed Central

    2013-01-01

    Background The present study was undertaken to evaluate the antihyperglycemic, antihyperlipidemic and hepatoprotective effect of a traditional unani formulation “Qurs Tabasheer” in streptozotocin (STZ) induced diabetic wistar rats. Up till now no study was undertaken to appraise the efficacy of “Qurs Tabasheer” in the diabetic rats. Qurs Tabasheer is a unani formulation restraining preparations from five various herbs namely Tukhme Khurfa (Portulaca oleracea seed), Gule Surkh (Rosa damascena flower), Gulnar (Punica granatum flower), Tabasheer (Bambusa arundinasia dried exudate on node), Tukhme Kahu (Lactuca sativa Linn seed). Methods Effect of Qurs Tabasheer was assessed in STZ (60 mg/kg, i.p single shot) induced diabetic wistar rats. STZ produced a marked increase in the serum glucose, Total Cholesterol, LDL cholesterol, VLDL Cholesterol, Triglycerides and trim down the HDL level. We have weighed up the effect of Qurs Tabasheer on hepatic activity through estimating levels of various liver enzymes viz. Hexokinase, Glucose-6-Phosphatase and Fructose-1-6-biphosphatase in STZ diabetic wistar rats. Results In STZ-induced diabetic wistar rats level of Hexokinase, and Glucose-6-Phosphatase was decreased to a significant level while the level of fructose-1-6-biphophatase was augmented. Therapy with Qurs Tabasheer for 28 days to STZ-induced diabetic rats significantly reduces the level of serum glucose, total cholesterol, triglycerides, glucose-6-phosphatase and fructose-1-6-biphosphatase, while magnitude of HDL cholesterol and hexokinase was amplified. Conclusion Antihyperglycemic, antihyperlipidemic activity of Qurs Tabasheer extract in STZ- induced wistar rats was found to be more effective than standard oral hypoglycemic drug Glimepiride. PMID:23305114

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

    PubMed Central

    Wang, Jing; Liu, Huaide; Li, Ning; Zhang, Quanbin; Zhang, Hong

    2014-01-01

    Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the ?2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications. PMID:24886867

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

    PubMed Central

    Arokiyaraj, S; Balamurugan, R; Augustian, P

    2011-01-01

    Objective To evaluate the antihyperglycemic activity of ethyl acetate extract of Hypericum perforatum (H. perforatum) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity and oral glucose tolerance test were performed in normal rats. Male albino rats were rendered diabetic by STZ (40 mg/kg, intraperitoneally). H. perforatum ethyl acetate extract was orally administered to diabetic rats at 50, 100 and 200 mg/kg doses for 15 days to determine the antihyperglycemic activity. Biochemical parameters were determined at the end of the treatment. Results H. perforatum ethyl acetate extract showed dose dependant fall in fasting blood glucose (FBG). After 30 min of extract administration, FBG was reduced significantly when compared with normal rats. H. perforatum ethyl acetate extract produced significant reduction in plasma glucose level, serum total cholesterol, triglycerides, glucose-6-phosphatase levels. Tissue glycogen content, HDL-cholesterol, glucose-6-phosphate dehydrogenase were significantly increased compared with diabetic control. No death or lethal effect was observed in the toxic study. Conclusions The results demonstrate that H. perforatum ethyl acetate extract possesses potent antihyperglycemic activity in STZ induced diabetic rats. PMID:23569798

  11. Effects of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat

    Microsoft Academic Search

    I Ahmed; E Adeghate; A. K Sharma; D. J Pallot; J Singh

    1998-01-01

    An investigation was made of the effect of Momordica charantia fruit juice on the distribution and number of ?, ? and ? cells in the pancreas of streptozotocin (STZ)-induced diabetic rats using immunohistochemical methods. The results indicated that there was a significant (Student's t-test, P<0.004) increase in the number of ? cells in M. charantia-treated animals when compared with untreated

  12. 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 3?- and 17?-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

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

    PubMed Central

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

    2013-01-01

    The aim of this study was to evaluate the protective effects of Fufang Xueshuantong (FXT) on diabetic retinopathy in rats induced by streptozotocin (STZ). Diabetes was induced in Sprague-Dawley rats by a single injection of 60?mg/kg STZ. One week after STZ, FXT 0.525?g/kg or 1.05?g/kg was administrated to the rats by intragastric gavage (ig) once daily consecutively for 24 weeks. The control rats and untreated STZ rats received vehicle the same way. At the end of the experiment, the erythrocyte aggregation and blood viscosity were assayed. The retina vessel morphology was observed in retinal digestive preparations. Expression of occludin and intercellular adhesion molecule-1 (ICAM-1) in retina was measured by western blotting. Expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in retina was detected by immunohistochemistry. The activity of aldose reductase in retina was investigated with a NADPH oxidation method. The results showed that, in STZ rats, there were distinct lesions in retinal vessel, including decrease of pericytes and increase of acellular capillaries, together with dilatation of retinal veins. The expression of VEGF and ICAM-1 increased, while the expression of PEDF and occludin decreased. The activity of aldose reductase elevated, and the whole blood viscosity, plasma viscosity, and erythrocyte aggregation also increased after STZ stimulation. FXT 0.525?g/kg and 1.05?g/kg demonstrated significant protective effects against STZ induced microvessel lesion in the retina with increased pericytes and reduced acellular capillaries. FXT also reduced the expression of VEGF and ICAM-1 and enhanced the expression of PEDF and occludin in STZ insulted rats. The activity of aldose reductase, the whole blood viscosity, plasma viscosity, and erythrocyte aggregation also decreased after FXT treatment. The results demonstrated that FXT has protective effect on STZ induced diabetic retinopathy in rats. PMID:24204392

  14. Antihyperglycemic and antihyperlipidemic activities of aqueous extract of Hericium erinaceus in experimental diabetic rats

    PubMed Central

    2013-01-01

    Background Hericium erinaceus, as a commonly used medicine or food, has attracted much attention due to its health effects when used as a home remedy for some diseases. The aim of this work was to investigate the hypoglycemic and hypolipidemic effects of aqueous extract of Hericium erinaceus (AEHE) in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes was induced in Wistar rats by the administration of STZ (55 mg/kg BW.) intraperitoneally. AEHE (100 and 200 mg/kg BW.) was administered for a period of 28 days. The effects of AEHE on glucose, insulin, and lipid files in blood, and oxidative stress parameters in the liver were evaluated. The body weights of rats were recorded at day 0, 14 and 28th days. Results The administration of AEHE for 28 days in STZ diabetic rats resulted in a significant decrease in serum glucose level and a significant rise in serum insulin level. AEHE treatment attenuated lipid disorders. In addition, AEHE administration increased the activities of CAT, SOD, and GSH-Px, and GSH level, and reduced MDA level in the liver tissue significantly. Conclusion Our results suggest that AEHE possesses hypoglycemic, hypolipidemic, and antioxidant properties in STZ-induced diabetes rats. PMID:24090482

  15. Rosiglitazone is effective to improve renal damage in type-1-like diabetic rats.

    PubMed

    Huang, K-C; Cherng, Y-G; Chen, L-J; Hsu, C-T; Cheng, J-T

    2014-04-01

    A marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats) showing diabetic nephropathy. It has been documented that klotho is the target gene of PPAR?. However, the effect of PPAR? agonist on klotho expression in kidney of STZ rats remains obscure. Thus, we used rosiglitazone (TZD) as PPAR? agonist to investigate the effect on renal dysfunction in STZ rats. Treatment of TZD reversed the lower levels of PPAR?, klotho, and FGFR1 expressions in kidneys of STZ rats without the correction of hyperglycemia. Also, renal functions and structural defeats were improved by TZD treatment. Taken together, oral administration of TZD may improve STZ-induced diabetic nephropathy due to restoration of the expression of klotho axis through an increase in PPAR? expression without changing blood glucose in rats. PMID:24136780

  16. Investigation of Antidiabetic, Antihyperlipidemic, and In Vivo Antioxidant Properties of Sphaeranthus indicus Linn. in Type 1 Diabetic Rats: An Identification of Possible Biomarkers

    PubMed Central

    Ramachandran, S.; Asokkumar, K.; Uma Maheswari, M.; Ravi, T. K.; Sivashanmugam, A. T.; Saravanan, S.; Rajasekaran, A.; Dharman, J.

    2011-01-01

    The present investigation was aimed to study the antidiabetic, antihyperlipidemic, and in vivo antioxidant properties of the root of Sphaeranthus indicus Linn. in streptozotocin- (STZ-) induced type 1 diabetic rats. Administration of ethanolic extract of Sphaeranthus indicus root (EESIR) 100 and 200?mg/kg to the STZ-induced diabetic rats showed significant (P < .01) reduction in blood glucose and increase in body weight compared to diabetic control rats. Both the doses of EESIR-treated diabetic rats showed significant (P < .01) alteration in elevated lipid profile levels than diabetic control rats. The EESIR treatment in diabetic rats produced significant increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and decrease in thiobarbituric acid reactive substances (TBARS) levels than diabetic control rats. Administration of EESIR 200?mg/kg produced significant (P < .01) higher antioxidant activity than EESIR 100?mg/kg. The high performance liquid chromatography (HPLC) analysis of EESIR revealed the presence of biomarkers gallic acid and quercetin. In conclusion, EESIR possess antidiabetic, antihyperlipidemic, and in vivo antioxidant activity in type 1 diabetic rats. Its antioxidant and lipid lowering effect will help to prevent diabetic complications, and these actions are possibly due to presence of above biomarkers. PMID:20953435

  17. 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.

  18. 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

  19. The effects of acarbose and Rumex patientia L. on ultrastructural and biochemical changes of pancreatic B cells in streptozotocin-induced diabetic rats.

    PubMed

    Degirmenci, Irfan; Ustuner, M Cengiz; Kalender, Yusuf; Kalender, Suna; Gunes, Hasan Veysi

    2005-03-21

    This study was performed to observe the effects of acarbose and Rumex patientia on morphological change of pancreatic B cells in streptozotocin (STZ)-induced diabetic (type 2) rats. Two-day-old Wistar albino rats were intraperitoneally injected with 100mg/kg of STZ or vehicle alone for control. Vehicle and STZ given rats were divided into six groups (1st, 2nd and the 3rd groups are control; the 4th, 5th and 6th groups are STZ groups). The 1st and the 4th groups received water, the 2nd and the 5th groups received 40 mg acarbose/100 g feed, the 3rd and the 6th groups received 2% decoction of Rumex patientia grain. During experimentation period, blood glucose levels were checked periodically, and HbA1c level was measured from cardiac blood at the end of the experiment. Pancreas tissues were examined by electron microscope. Glucose and HbA1c levels increased by STZ were decreased by acarbose and Rumex patientia. Morphologically, we found a mitochondrial vacuolization and swelling as well as dilatation of the endoplasmic reticulum in the B cells of STZ-induced diabetic rats. Also, a decrease in the secretory granules of B cells was observed in the STZ-induced diabetic group. No pathological changes were observed in the STZ+acarbose group. In the STZ+Rumex patientia group, a weak swelling in the B cells was observed in the some of the mitochondria. PMID:15740895

  20. Synergistic Effects of d-Chiro-Inositol and Manganese on Blood Glucose and Body Weight of Streptozotocin-Induced Diabetic Rats

    Microsoft Academic Search

    Gilbert Gluck; Tatiana Anguelova; Douglas Heimark; Joseph Larner

    2010-01-01

    d-chiro-inositol (DCI) and manganese were administered orally singly and together to streptozotocin (STZ)- induced diabetic rats for 21 days and blood glucose values and body weights determined. At blood glucose values above 500 mg\\/dL, values were unchanged with DCI, manganese sulfate, or both over ten days. Insulin was administered to reduce the hyperglycemia to approximately 300 mg\\/dL. Over 12 days,

  1. Insulinotropic effect of aqueous extract of Brassica nigra improves glucose homeostasis in streptozotocin induced diabetic rats.

    PubMed

    Anand, P; Murali, Y K; Tandon, V; Murthy, P S; Chandra, R

    2009-06-01

    Aqueous extract of BRASSICA NIGRA (AEBN) has been shown to have good antidiabetic effect along with significant decrease (p<0.01) of abnormal serum lipid levels in our previous study. To understand the mechanism of action, effect of oral administration of AEBN for two months on glycolytic and gluconeogenic enzymes was studied in liver and kidney tissues of rats with streptozotocin (STZ) induced diabetes mellitus. The activities of gluconeogenic enzymes were higher and of glycolytic enzymes were decreased in both the liver and kidney tissues during diabetes. However, in diabetic rats treated with AEBN for two months, decrease of serum glucose, increase of serum insulin and release of insulin from pancreas (shown in vitro from isolated pancreas) along with the restoration of key regulatory enzyme activities of carbohydrate metabolism and glycogen content were observed. The therapeutic role of AEBN in STZ induced diabetes as exemplified in this study can be attributed to the release of insulin from pancreas and change of glucose metabolizing enzyme activities to normal levels, thus stabilizing glucose homeostasis in the liver and kidney. The LD50 was found to be more than 15 times the effective dose (ED) implying higher margin of safety for AEBN. These biochemical effects indicate that AEBN could be a possible new therapeutic agent for the treatment of diabetes. PMID:18726874

  2. 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

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

    PubMed Central

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

    2012-01-01

    Objective To study the antioxidant efficacy of Commiphora mukul (C. mukul) gum resin ethanolic extract in streptozotocin (STZ) induced diabetic rats. Methods The male Wistar albino rats were randomly divided into four groups of eight animals each: Control group (C), CM-treated control group (C+CMEE), Diabetic control group (D), CM- treated diabetic group (D+CMEE). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg/ bwt). After being confirmed the diabetic rats were treated with C. mukul gum resin ethanolic extract (CMEE) for 60 days. The biochemical estimations like antioxidant, oxidative stress marker enzymes and hepatic marker enzymes of tissues were performed. Results The diabetic rats showed increased level of enzymatic activities aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) in liver and kidney and oxidative markers like lipid peroxidation (LPO) and protein oxidation (PO) in pancreas and heart. Antioxidant enzyme activities were significantly decreased in the pancreas and heart compared to control group. Administration of CMEE (200 mg/kg bw) to diabetic rats for 60 days significantly reversed the above parameters towards normalcy. Conclusions In conclusion, our data indicate the preventive role of C. mukul against STZ-induced diabetic oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of diabetes and aggravated antioxidant status. PMID:23569867

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

    PubMed

    Giribabu, Nelli; Srinivasarao, Nelli; Swapna Rekha, Somesula; Muniandy, Sekaran; Salleh, Naguib

    2014-01-01

    Diabetes mellitus has been reported to affect functions of the hippocampus. We hypothesized that Centella asiatica, a herb traditionally being used to improve memory, prevents diabetes-related hippocampal dysfunction. Therefore, the aim of this study was to investigate the protective role of C. asiatica on the hippocampus in diabetes. Methods. Streptozotocin- (STZ-) induced adult male diabetic rats received 100 and 200?mg/kg/day body weight (b.w) C. asiatica leaf aqueous extract for four consecutive weeks. Following sacrifice, hippocampus was removed and hippocampal tissue homogenates were analyzed for Na(+)/K(+)-, Ca(2+)- and Mg(2+)-ATPases activity levels. Levels of the markers of inflammation (tumor necrosis factor, TNF-?; interleukin, IL-6; and interleukin, IL-1?) and oxidative stress (lipid peroxidation product: LPO, superoxide dismutase: SOD, catalase: CAT, and glutathione peroxidase: GPx) were determined. The hippocampal sections were visualized for histopathological changes. Results. Administration of C. asiatica leaf aqueous extract to diabetic rats maintained near normal ATPases activity levels and prevents the increase in the levels of inflammatory and oxidative stress markers in the hippocampus. Lesser signs of histopathological changes were observed in the hippocampus of C. asiatica leaf aqueous extract treated diabetic rats. Conclusions. C. asiatica leaf protects the hippocampus against diabetes-induced dysfunction which could help to preserve memory in this condition. PMID:25161691

  5. MiR-29b protects dorsal root ganglia neurons from diabetic rat.

    PubMed

    Zhang, Xiaona; Gong, Xu; Han, Shuhai; Zhang, Yang

    2014-11-01

    Accumulated evidences implicated that microRNAs may be involved in diabetic neuropathy. Here, we investigated miR-29's roles in primary isolated dorsal root ganglion (DRG) neurons from STZ-induced diabetic rats. First, miR-29b was found down-regulated after STZ-injection. Inhibitions were increased with time course. Down-regulation of miR-29b was associated with higher apoptosis rate and more serious axonal swelling. Meanwhile, axonogeneration genes were inhibited, whereas neurodegenerative genes were stimulated. Restoration of miR-29b by mimic experiment could reverse the above neuropathy. Furthermore, western blot analysis disclosed that miR-29b could abolish Smad3 activation. In conclusion, the present study identifies that miR-29b could protect DRG from diabetic rats. This protective effects suggested potential therapeutic application of miR-29b in diabetic neuropathy. PMID:24819309

  6. Antidiabetic and hypolipidemic activities of Kigelia pinnata flowers extract in streptozotocin induced diabetic rats

    PubMed Central

    Kumar, S; Kumar, V; Prakash, OM

    2012-01-01

    Objective To evaluate antidiabetic and hypolipidemic activities of Kigelia pinnata methanolic flowers extract in streptozotocin (STZ) induced diabetic wistar rat. Methods Rats were made diabetic by a single dose of STZ at 60 mg/kg body weight i.p. The blood glucose level was checked before and 72 h after STZ injection to confirm the development of diabetes. The flower extract and glibenclamide were administered orally at the doses of 250 and 500 mg/kg body weight for 21 days. Results Daily oral treatment with the extract and standard drug for 21 days significantly reduced blood glucose, serum cholesterol and triglycerides levels. High density lipoprotein-cholesterol level was found to be improved (P<0.01) as compared to diabetic control group. Conclusions It is concluded that Kigellia pinnata flowers extract have significant antidiabetic and hypolipidemic effect. PMID:23569967

  7. Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.

    PubMed

    Lemberg, A; Fernández, M A; Ouviña, G; Rodríguez, R R; Peredo, H A; Susemihl, C; Villarreal, I; Filinger, E J

    2007-12-01

    The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes. The increase in brain CK possibly expresses alterations in energy production. The decrease in CK activity caused by V and T treatment in diabetic rats suggests that both agents tend to normalize energy consumption. It is also possible that V and T-induced hypoglycemic effects cause metabolic alterations in brain. PMID:18038759

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

    PubMed Central

    2015-01-01

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

  9. Glycemic control and anti-osteopathic effect of propolis in diabetic rats

    PubMed Central

    Al-Hariri, M; Eldin, T Gamal; Abu-Hozaifa, B; Elnour, A

    2011-01-01

    The aim of the study was to explore the possibility that propolis can control diabetes mellitus and prevent diabetic osteopathy in rats. The study compared 60 streptozotocin (STZ)-induced diabetic rats, with ten nondiabetic rats used as a negative control. The experimental design comprised seven groups (n = 10 rats per group): (1) nondiabetic, used as a negative control; (2) nontreated, used as a positive control; (3) treated with insulin alone; (4) treated with a single dose of propolis alone; (5) treated with a double dose of propolis; (6) treated with insulin and a single dose of propolis; and (7) treated with insulin and a double dose of propolis. After 6 weeks of treatment, the rats were sacrificed. Ratios of femur ash to femur weight and of femur weight to body weight (FW/BW) were calculated and calcium (Ca), phosphorus (P), and magnesium (Mg) concentrations in femur ash were estimated and analyzed. Fasting blood glucose (FBG), plasma insulin and glucagon, serum thiobarbituric acid reactive substances (TBARS), plasma parathyroid hormone (PTH), and calcitonin levels were also estimated and analyzed. There was significant reduction in FBG in all diabetic treated rats. Similarly, higher plasma insulin levels were observed in diabetic rats treated with propolis and insulin than in nontreated diabetic rats, although plasma insulin was not comparatively higher in diabetic rats treated with insulin alone. Serum TBARS was significantly lower in the propolis treated rats than the diabetic nontreated rats. No differences in PTH and calcitonin levels were observed among treatment groups. The FW/BW ratio was significantly higher in diabetic treated groups than in control groups. Furthermore, diabetic rats treated with propolis and insulin had significantly higher Ca, P, and Mg concentrations in femoral ash than nontreated diabetic rats and diabetic rats treated with insulin alone. In conclusion, propolis has a remarkable effect on glucose homeostasis and bone mineralization. PMID:22253535

  10. 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

  11. The effects of vanadium (V) absorbed by Coprinus comatus on bone in streptozotocin-induced diabetic rats.

    PubMed

    Pei, Yi; Fu, Qin

    2011-09-01

    The purpose of this study was to evaluate the effects of vanadium absorbed by Coprinus comatus (VACC) treatment on bone in streptozotocin (STZ)-induced diabetic rats. Forty-five Wistar female rats used were divided into three groups: (1) normal rats (control), (2) diabetic rats, and (3) diabetic rats treated with VACC. Normal and diabetic rats were given physiological saline, and VACC-treated rats were administered VACC intragastrically at doses of 0.18 mg vanadium/kg body weight once daily. Treatments were performed over a 12-week period. At sacrifice, one tibia and one femur were removed, subjected to micro computed tomography (micro-CT) for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. Another femoral was used for mechanical testing. In addition, bone samples were collected to evaluate the content of mineral substances in bones. Treatment with VACC increased trabecular bone volume fraction in diabetic rats. Vanadium-treated animals had significant increases in ultimate load, trabecular thickness, and osteoblast surface. However, vanadium treatment did not seem to affect bone stiffness, bone energy absorption, trabecular separation, and osteoclast number. P levels in the femurs of diabetic rats treated with VACC were significantly higher than those of diabetic animals. Ca levels in diabetic and diabetic rats treated with vanadium showed no obvious changes. In conclusion, our results provide an important proof of concept that VACC may represent a powerful approach to treating or reversing diabetic osteopathy in humans. PMID:20734239

  12. GABA tea prevents cardiac fibrosis by attenuating TNF-alpha and Fas/FasL-mediated apoptosis in streptozotocin-induced diabetic rats.

    PubMed

    Cherng, Shur-Hueih; Huang, Chih-Yang; Kuo, Wei-Wen; Lai, Shue-Er; Tseng, Chien-Yu; Lin, Yueh-Min; Tsai, Fuu-Jen; Wang, Hsueh-Fang

    2014-03-01

    GABA tea is a tea product that contains a high level of gamma-aminobutyric acid (GABA). This study investigated the effects of GABA tea on the heart in a diabetic rat model. Male Wistar rats were injected with 55mg/kg streptozotocin (STZ) to induce diabetes for 2weeks and then orally given dosages of 4.55 and 45.5mg/kg/day GABA tea extract for 6weeks. The results revealed that fasting blood glucose levels returned to normal levels in GABA tea-treated diabetic rats, but not in the untreated diabetic rats. Additionally, GABA tea effectively inhibited cardiac fibrosis induced by STZ. Further experiments showed that the STZ-induced protein levels of tumor necrosis factor-alpha (TNF-alpha), Fas, activated caspase-8 and caspase-3 were significantly inhibited by the GABA tea treatment. Therefore, our data suggest that the inhibiting effect of GABA tea on STZ-induced cardiac fibrosis in diabetic rats may be mediated by reducing blood glucose and further attenuating TNF-alpha expression and/or Fas/Fas ligand (FasL)-mediated apoptosis. These findings will provide implications for the potential anti-diabetic properties of GABA tea. PMID:24374093

  13. Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats

    PubMed Central

    Jorge, Luciana; da Pureza, Demilto Y.; Dias, Danielle da Silva; Conti, Filipe Fernandes; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2012-01-01

    The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP), heart rate (HR), and baroreflex sensitivity (BRS) in STZ-induced diabetic rats. Male Wistar rats were divided into control (n = 8) and diabetic (n = 8) groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR) responses to AP changes, were evaluated at rest (R) and postexercise session (PE) on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103 ± 2 versus PE: 111 ± 3?mmHg) and HR (R: 290 ± 7 versus PE: 328 ± 10?bpm) reductions and BR dysfunction (R: ?0.70 ± 0.06 versus PE: ?1.21 ± 0.09?bpm/mmHg) was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes. PMID:22203833

  14. Anti-diabetic effects of sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate in streptozotocin-induced diabetic rats.

    PubMed

    Li, Ming; Smee, Jason J; Ding, Wenjun; Crans, Debbie C

    2009-04-01

    The evaluation of the anti-diabetic effects of an organic vanadium(V) complex in streptozotocin (STZ)-induced diabetic rats was investigated. The STZ-induced diabetic rats were orally administrated with sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate (V5dipic-NH(2)), a vanadium(V) coordination compound. The compound was administered through drinking water at a concentration of 0.1mg/mL for 20 days, and then the concentration was increased to 0.3mg/mL for the following 20 days. At the end of the experiment, V5dipic-NH(2) statistically significantly reduced the levels of blood glucose (P<0.01), serum total cholesterol (P<0.01), triglycerides (P<0.01) and the activities of serum aspartate amino transferase (P<0.05) and alkaline phosphatase (P<0.01) compared to untreated diabetic animals. After treatment with 0.3mg/mL V5dipic-NH(2), the oral glucose tolerance was improved in diabetic animals (P<0.01). In addition, the daily intake of elemental vanadium was markedly decreased in V5dipic-NH(2)-treated diabetic rats compared to vanadyl sulfate (VOSO(4))-treated diabetic rats, which suggested that the anti-diabetic activity of the element vanadium was elevated after being modified with an organic ligand. These results suggested that V5dipic-NH(2), as an organic vanadium compound, is more effective than inorganic vanadium salt at alleviating the symptoms of diabetes. PMID:19203797

  15. Renal response to volume expansion in streptozotocin-induced diabetic rats: influence of calcium channel blockade.

    PubMed

    Patel, K P; Zhang, P L; Zeigler, D W; Kauker, M L

    1997-03-01

    The renal response to volume expansion (VE) has been shown to be impaired in streptozotocin (STZ)-induced diabetes. This may contribute to the abnormal maintenance of fluid balance in diabetics. Since calcium channel blockade (CaCb) has been shown to improve renal hemodynamic and tubular functions, the present studies were designed to examine the ability of CaCb to enhance the response of kidneys from diabetic rats to a volume load. Rats were made diabetic by a single injection of STZ (65 mg i.p.), while the control rats received only a vehicle injection. Nisoldipine, a CaCb agent was given to half of the diabetic rats in a dose of 0.015 microgram/kg per min during the acute experiment. The left kidney was denervated in each rat while the right kidney remained innervated. Glomerular filtration rate (GFR) was elevated during VE in all of the rats except in the denervated kidneys of diabetic rats. Nisoldipine improved GFR in most cases. Urine flow increased markedly during VE. This response was enhanced by denervation but depressed in the diabetic rats. Nisoldipine improved the defective volume reflex in primarily the denervated kidneys. Changes in net urinary excretion of water and sodium during VE were significantly lower in the diabetic rats than in the control group. In the nisoldipine treated diabetic rats the VE induced changes in water and sodium excretion returned toward normal in the denervated, but not in the innervated kidneys. The data are consistent with a blunted volume reflex in the diabetic rats that may be improved by CaCb. Impaired sympatho-inhibition in diabetic rats appears to oppose the effects of VE and nisoldipine treatment. CaCb may contribute to the volume reflex by enhanced filtration as well as by reduced tubular reabsorption. PMID:9179460

  16. Antiatherosclerotic Potential of Active Principle Isolated from Eugenia jambolana in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Tanwar, Reenu Singh; Sharma, Suman Bala; Singh, Usha Rani; Prabhu, Krishna Madhava

    2011-01-01

    The aim of the present study was to investigate the antiatherosclerotic effect of active principle (FIIc) isolated from aqueous fruit pulp extract of Eugenia jambolana. Crude aqueous extract of E. jambolana was subjected to purification using chromatographic techniques which yielded purified active compound (FIIc). Purity of FIIc was tested by HPLC. Phytochemical investigation of FIIc by NMR, IR, and UV spectra showed that the purified compound is ?-hydroxy succinamic acid. The streptozotocin- (STZ-) induced diabetic rats were fed atherosclerotic (Ath) diet containing 1.5?mL olive oil containing 8?mg (3, 20,000 IU) vitamin D2 and 40?mg cholesterol for 5 consecutive days. The STZ-induced diabetic rats receiving Ath diet were orally administered FIIc at doses of 10, 15, and 20?mg/kg, and results were compared with reference drug, that is, glibenclamide (600??g/mg) and healthy control. 30-day treatment with FIIc resulted in significant (P < .001) improvement in blood glucose, serum lipid profile, apolipoproteins (Apo A1 and apoB100), and endothelial dysfunction parameters. Histomorphological studies also confirmed biochemical findings. Our results showed that FIIc has protective effect on hyperglycemia-induced atherosclerosis. PMID:21584267

  17. Effects of ursolic acid derivatives on Caco-2 cells and their alleviating role in streptozocin-induced type 2 diabetic rats.

    PubMed

    Wu, Panpan; He, Ping; Zhao, Suqing; Huang, Tianming; Lu, Yujing; Zhang, Kun

    2014-01-01

    In this study, the effect and mechanism of a series of ursolic acid (UA) derivatives on glucose uptake were investigated in a Caco-2 cells model. Their effect on hyperglycemia, hyperlipidemia and oxidative stress were also demonstrated in streptozocin (STZ)-induced diabetic rats. 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-glucose (2-NBDG) was used as a fluorescein in Caco-2 cells model to screen UA derivatives by glucose uptake and expression of glucose transporter protein (SGLT-1, GLUT-2). Moreover, STZ-induced diabetic rats were administered with these derivatives for 4 weeks of treatment. The fasting blood glucose (FBG), insulin levels, biochemical parameters, lipid levels, and oxidative stress markers were finally evaluated. The results of this study indicated that compounds 10 and 11 significantly inhibited 2-NBDG uptake under both Na+-dependent and Na+-independent conditions by decreasing SGLT-1 and GLUT-2 expression in the Caco-2 cells model. Further in vivo studies revealed that compound 10 significantly reduced hyperglycemia by increasing levels of serum insulin, total protein, and albumin, while the fasting blood glucose, body weight and food intake were restored much closer to those of normal rats. Compounds 10 and 11 showed hypolipidemic activity by decreasing the total amounts of cholesterol (TC) and triglycerides (TG). Furthermore, compound 10 showed antioxidant potential which was confirmed by elevation of glutathione (GSH) and superoxide dismutase (SOD) and reduction of malondialdehyde (MDA) levels in the liver and kidney of diabetic rats. It was concluded that compound 10 caused an apparent inhibition of intestinal glucose uptake in Caco-2 cells and hypoglycemia, hypolipidemia and augmented oxidative stress in STZ-induced diabetic rats. Thus, compound 10 could be developed as a potentially complementary therapeutic or prophylactic agent for diabetics mellitus and its complications. PMID:25153871

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

    PubMed Central

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

    2015-01-01

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

  19. Improvement of glycemic control in streptozotocin-induced diabetic rats by Atlantic salmon skin gelatin hydrolysate as the dipeptidyl-peptidase IV inhibitor.

    PubMed

    Hsieh, C H; Wang, T Y; Hung, C C; Chen, M C; Hsu, K C

    2015-06-10

    In our previous study, Atlantic salmon skin gelatin hydrolysed with flavourzyme possessed 42.5% dipeptidyl-peptidase (DPP)-IV inhibitory activity at a concentration of 5 mg mL(-1). The oral administration of the hydrolysate (FSGH) at a single dose of 300 mg per day in streptozotocin (STZ)-induced diabetic rats for 5 weeks was evaluated for its antidiabetic effect. During the 5-week experiment, body weight increased, and the food and water intake was reduced by FSGH in diabetic rats. The daily administration of FSGH for 5 weeks was effective for lowering the blood glucose levels of diabetic rats during an oral glucose tolerance test (OGTT). After the 5-week treatment, plasma DPP-IV activity was inhibited; the plasma activity of glucagon-like peptide-1 (GLP-1), insulin, and the insulin-to-glucagon ratio were increased by FSGH in diabetic rats. The results indicate that FSGH has the function of inhibiting GLP-1 degradation by DPP-IV, resulting in the enhancement of insulin secretion and improvement of glycemic control in STZ-induced diabetic rats. PMID:25946069

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

    PubMed

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

    2010-07-01

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

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

    PubMed Central

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

    2010-01-01

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

  2. Neuroprotective effect of RYGB in Zucker fatty diabetic rats

    PubMed Central

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

    2014-01-01

    The aim of this study is to explore the therapeutic potential of RYGB, a common used bariatric surgery, on diabetic polyneuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats. In animal model experiments, rats were made diabetic by STZ administration, and after 12 weeks of diabetes, two groups were studied: RYGB and sham surgery control (PF). Change in oral glucose tolerance, insulin sensitivity, and the plasma concentrations of insulin, glucagon, glucagon-like peptide-1 (GLP-1) were measured. Peripheral nerve function was determined by the current perception threshold. Sciatic nerve blood flow (SNBF) and intraepidermal nerve fiber densities (IENFDs) also were evaluated. The results indicated that glucose tolerance and insulin sensitivity were significantly improved in the RYGB group. Fasting total GLP-1 were increased in the RYGB group. The increase seen in current perception threshold vales in RYGB group was reduced. The decreased IENFDs in sole skins of RYGB group were ameliorated by RYGB. In conclusion, the findings indicate that RYGB ameliorates the severity of DPN, which may be associated with increased GLP-1 and improved insulin sensitivity/action. PMID:25419361

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

    PubMed

    Topal, Gökçe; Koç, Ebru; Karaca, Cetin; Altu?, Tuncay; Ergin, Bülent; Demirci, Cihan; Meliko?lu, Gülay; Meriçli, Ali H; Kucur, Mine; Ozdemir, Osman; Uyde? Do?an, B Sönmez

    2013-03-01

    Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65?mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4?weeks of diabetes, CM extract (100?mg/kg) was administrated to diabetic rats for 4?weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5) ?M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-? and IL-6 and by preventing lipid peroxidation. PMID:22585450

  4. 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

  5. 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

  6. L-Glutamine Supplementation Prevents the Development of Experimental Diabetic Cardiomyopathy in Streptozotocin-Nicotinamide Induced Diabetic Rats

    PubMed Central

    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

  7. Selective Inhibition of Protein Kinase C ?2 Attenuates Inducible Nitric Oxide Synthase–Mediated Cardiovascular Abnormalities in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Nagareddy, Prabhakara Reddy; Soliman, Hesham; Lin, Guorong; Rajput, Padmesh S.; Kumar, Ujendra; McNeill, John H.; MacLeod, Kathleen M.

    2009-01-01

    OBJECTIVE Impaired cardiovascular function in diabetes is partially attributed to pathological overexpression of inducible nitric oxide synthase (iNOS) in cardiovascular tissues. We examined whether the hyperglycemia-induced increased expression of iNOS is protein kinase C-?2 (PKC?2) dependent and whether selective inhibition of PKC? reduces iNOS expression and corrects abnormal hemodynamic function in streptozotocin (STZ)-induced diabetic rats. RESEARCH DESIGN AND METHODS Cardiomyocytes and aortic vascular smooth muscle cells (VSMC) from nondiabetic rats were cultured in low (5.5 mmol/l) or high (25 mmol/l) glucose or mannitol (19.5 mmol/l mannitol + 5.5 mmol/l glucose) conditions in the presence of a selective PKC? inhibitor, LY333531 (20 nmol/l). Further, the in vivo effects of PKC? inhibition on iNOS-mediated cardiovascular abnormalities were tested in STZ-induced diabetic rats. RESULTS Exposure of cardiomyocytes to high glucose activated PKC?2 and increased iNOS expression that was prevented by LY333531. Similarly, treatment of VSMC with LY333531 prevented high glucose–induced activation of nuclear factor ?B, extracellular signal–related kinase, and iNOS overexpression. Suppression of PKC?2 expression by small interference RNA decreased high-glucose–induced nuclear factor ?B and extracellular signal–related kinase activation and iNOS expression in VSMC. Administration of LY333531 (1 mg/kg/day) decreased iNOS expression and formation of peroxynitrite in the heart and superior mesenteric arteries and corrected the cardiovascular abnormalities in STZ-induced diabetic rats, an action that was also observed with a selective iNOS inhibitor, L-NIL. CONCLUSIONS Collectively, these results suggest that inhibition of PKC?2 may be a useful approach for correcting abnormal hemodynamics in diabetes by preventing iNOS mediated nitrosative stress. PMID:19587355

  8. Ganoderma lucidum polysaccharides exert anti-hyperglycemic effect on streptozotocin-induced diabetic rats through affecting ?-cells.

    PubMed

    Zheng, Jusheng; Yang, Bin; Yu, Yinghua; Chen, Qi; Huang, Tao; Li, Duo

    2012-08-01

    Previous studies have demonstrated that Ganoderma lucidum polysaccharides (Gl-PS) exhibited potential antihyperglycemic effect in rats. The aim of the present study was to investigate the mechanism of the hypoglycemic effect of a low- molecular-weight Gl-PS in streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rats. Gl-PS was extracted and purified from Ganodema lucidum fruiting body. 50 male SD rats were included in the study; 10 were taken as healthy controls; 40 were induced to diabetes by a single injection of 65 mg/kg STZ, of which 30 were selected as successful diabetic rat models. The 30 diabetic rats were divided into three groups: Gl-PS (200 mg/kg Gl-PS), metformin (100 mg/kg metformin) and diabetic control (n = 10 per group). After eight weeks' oral administration, plasma concentrations of fasting glucose, triacylglyceride, total cholesterol and nitric oxide were significantly decreased in Gl-PS and metformin groups. Pancreatic superoxide dismutase, catalase and glutathione peroxidase were significantly increased in Gl-PS and metformin groups. Histopathological results showed that Gl-PS and metformin had protective effect on ?-cells. The mRNA expressions of Bcl-2 and PDX-1 in pancreas were up-regulated, but Bax, iNOS and Casp-3 down-regulated in Gl- PS and metformin groups compared to diabetic control group. The present results suggested that Gl-PS had a hypoglycemic effect in STZ-induced diabetic rats through preventing apoptosis of pancreatic ?-cells and enhancing ?-cells regeneration. PMID:22329512

  9. Hypoglycemic and hypolipidemic effects of oxymatrine in high-fat diet and streptozotocin-induced diabetic rats.

    PubMed

    Guo, Changrun; Zhang, Chunfeng; Li, Lu; Wang, Zhenzhong; Xiao, Wei; Yang, Zhonglin

    2014-05-15

    Oxymatrine, a quinolizidine alkaloid, has been widely used for the treatment of hepatitis. In this study, we investigated the hypoglycemic and hypolipidemic effects and new pharmacological activities of oxymatrine, in a high-fat diet and streptozotocin (STZ)-induced diabetic rats. The results demonstrated that oxymatrine could significantly decrease fasting blood glucose, glycosylated hemoglobin (GHb), food and water intake, non-esterified fatty acid (NEFA), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol levels (LDL-c), and increase serum insulin, liver and muscle glycogen, high density lipoprotein cholesterol (HDL-c), glucagon-like peptide-1 (GLP-1) and muscle glucose transporter-4 (GLUT-4) content in diabetic rats. The results of the histological examinations of the pancreas and liver show that oxymatrine protected the islet architecture and prevented disordered structure of the liver. This study displays that oxymatrine can alleviate hyperglycemia and hyperlipemia in a high-fat diet and STZ-induced diabetic rats might by improving insulin secretion and sensitivity. PMID:24680614

  10. Ileal apical Na+-dependent bile acid transporter ASBT is upregulated in rats with diabetes mellitus induced by low doses of streptozotocin

    PubMed Central

    Annaba, Fadi; Ma, Ke; Kumar, Pradeep; Dudeja, Amish K.; Kineman, Rhonda D.; Shneider, Benjamin L.; Saksena, Seema; Gill, Ravinder K.

    2010-01-01

    Increased intestinal bile acid absorption and expansion of the bile acid pool has been implicated in the hypercholesterolemia associated with diabetes mellitus. However, the molecular basis of the increase in bile acid absorption in diabetes mellitus is not fully understood. The ileal apical Na+-dependent bile acid transporter (ASBT) is primarily responsible for active reabsorption of the majority of bile acids. Current studies were designed to investigate the modulation of ASBT function and expression in streptozotocin (STZ)-induced diabetes mellitus in rats and to examine the effect of insulin on rat ASBT promoter by insulin. Diabetes mellitus was induced in Sprague-Dawley rats by intraperitoneal injection of low doses of STZ (20 mg/kg body wt) on five consecutive days. Human insulin (10 U/day) was given to a group of diabetic rats for 3 days before euthanasia. RNA and protein were extracted from mucosa isolated from the small intestine and ASBT expression was assessed by real-time quantitative RT-PCR and Western blotting. Our data showed that ASBT mRNA and protein expression were significantly elevated in diabetic rats. Insulin treatment of diabetic rats reversed the increase in ASBT protein expression to control levels. Consistently, ileal Na+-dependent [3H]taurocholic uptake in isolated intestinal epithelial cells was significantly increased in diabetic rats. In vitro studies utilizing intestinal epithelial Caco-2 cells demonstrated that ASBT expression and promoter activity were significantly decreased by insulin. These studies demonstrated that insulin directly influences ASBT expression and promoter activity and that ASBT function and expression are increased in rats with STZ-induced diabetes mellitus. The increase in ASBT expression may contribute to disturbances in cholesterol homeostasis associated with diabetes mellitus. PMID:20651004

  11. Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats.

    PubMed

    Jang, Y Y; Song, J H; Shin, Y K; Han, E S; Lee, C S

    2000-10-01

    Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. Several antioxidants have been described as beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1, 10-dimethoxyaporphine) is a major alkaloid found in the leaves and bark of boldo (Peumus boldus Molina), and has been shown to possess antioxidant activity and anti-inflammatory effects. From this point of view, the possible anti-diabetic effect of boldine and its mechanism were evaluated. The experiments were performed on male rats divided into four groups: control, boldine (100 mg kg(-1), daily in drinking water), diabetic [single dose of 80 mg kg(-1)of streptozotocin (STZ), i.p.] and diabetic simultaneously fed with boldine for 8 weeks. Diabetic status was evaluated periodically with changes of plasma glucose levels and body weight in rats. The effect of boldine on the STZ-induced diabetic rats was examined with the formation of malondialdehydes and carbonyls and the activities of endogenous antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in mitochondria of the pancreas, kidney and liver. The scavenging action of boldine on oxygen free radicals and the effect on mitochondrial free-radical production were also investigated. The treatment of boldine attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. The levels of malondialdehyde (MDA) and carbonyls in liver, kidney and pancreas mitochondria were significantly increased in STZ-treated rats and decreased after boldine administration. The activities of mitochondrial manganese superoxide dismutase (MnSOD) in the liver, pancreas and kidney were significantly elevated in STZ-treated rats. Boldine administration decreased STZ-induced elevation of MnSOD activity in kidney and pancreas mitochondria, but not in liver mitochondria. In the STZ-treated group, glutathione peroxidase activities decreased in liver mitochondria, and were elevated in pancreas and kidney mitochondria. The boldine treatment restored the altered enzyme activities in the liver and pancreas, but not the kidney. Boldine attenuated both STZ- and iron plus ascorbate-induced MDA and carbonyl formation and thiol oxidation in the pancreas homogenates. Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner. The alkaloid significantly attenuated the production of superoxide anions, hydrogen peroxide and nitric oxide caused by liver mitochondria. The results indicate that boldine may exert an inhibitory effect on STZ-induced oxidative tissue damage and altered antioxidant enzyme activity by the decomposition of reactive oxygen species and inhibition of nitric oxide production and by the reduction of the peroxidation-induced product formation. Boldine may attenuate the development of STZ-induced diabetes in rats and interfere with the role of oxidative stress, one of the pathogeneses of diabetes mellitus. PMID:10987997

  12. Interleukin-6 (IL-6) mediated the increased contraction of distal colon in streptozotocin-induced diabetes in rats via IL-6 receptor pathway

    PubMed Central

    Chang, Xin-Wen; Qin, Ying; Jin, Zhi; Xi, Tao-Fang; Yang, Xiao; Lu, Ze-Hao; Tang, Yu-Ping; Cai, Wen-Ting; Chen, Shao-Jun; Xie, Dong-Ping

    2015-01-01

    Colonic dysmotility occurs in diabetes and blood plasma interleukin (IL)-6 levels are significantly elevated in type 1 diabetes mellitus. The aim of this study was to investigate whether IL-6 and the IL-6 receptor pathway mediates colonic dysfunction in type 1 diabetes mellitus. Male SD rats were treated with a single intraperitoneally injected dose of streptozotocin (STZ), and those displaying sustained high blood glucose were selected as diabetes mellitus models. Longitudinal muscle strips of colon were prepared to monitor colonic contraction in vitro. Contractile responses of strips of colon were recorded following treatment with IL-6 in control animals, and following anti IL-6 antibody treatment in STZ-induced diabetes in rats. Concentration of IL-6 in plasma and colon were determined by ELISA. Expressions of IL-6 ?-receptor and IL-6 ?-receptor in colon tissues were determined by immunohistochemistry or Western blot analysis. The non-diabetes rats treated with IL-6 and the untreated diabetes rats showed increased contraction of distal colon, whereas the diabetes rats treated with anti-IL-6 antibody showed decreased contraction of distal colon compared with the untreated diabetes rats. The IL-6 levels of plasma but not colon increased in diabetes rats. The expression of IL-6 ?-receptor increased in diabetes rats. These results indicate that diabetes rats show an increase in the contractions of distal colon partly via the IL-6-IL-6 receptor pathway.

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

    PubMed Central

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

    2013-01-01

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

  14. Short-term effects of vanadate treatment in diabetic rats

    SciTech Connect

    Oster, M.H.; Llobet, J.M.; Domingo, J.L.; Keen, C.L. (Univ. of California, Davis (United States) Univ. of Barcelona (Spain))

    1991-03-11

    Based on findings that vanadium (V) can produce normoglycemia in diabetic rats, V has been proposed as a treatment for diabetics. However, since V is a strong prooxidant, its potential toxicity needs to be evaluated prior to human trials. STZ-induced diabetic (Diab) rats were given one of four water treatments: saline (S), or 0.12, 0.25, or 0.49 mM NaVO3 (V) in 80mM NaCl for one month. Six V rats, 2 from each group, died prior to one month. All V rats had lower plasma glucose and lower food and fluid intake compared to S rats. S rats had higher kidney Cu levels compared to V rats. RBC SOD activity decreased as the level of V increased. Liver TBAR production was evaluated with (+) and without (-) the addition of Fe. While homogenate -Fe TBARS were higher in the 0.12 V group compared to the S and 0.60 V groups, mitochondrial and microsomal -Fe TBARS were unaffected by V treatment. In the presence of Fe, homogenate and mitochondrial TBARS were higher in the 0.12 V group compared to other groups. Microsomal +Fe TBARS were similar among groups. To summarize, low levels of V may have a protective effect on membrane composition, possibly by altering PUFA content. However, higher levels of V may induce peroxidation causing conjugated diene formation which may alter membrane structure and function. Thus, V may have both prooxidant and antioxidant activity which depends on the V level, membrane integrity, and physiological state.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  17. Mangiferin from Salacia chinensis prevents oxidative stress and protects pancreatic ?-cells in streptozotocin-induced diabetic rats.

    PubMed

    Sellamuthu, Periyar Selvam; Arulselvan, Palanisamy; Muniappan, Balu Periamallipatti; Fakurazi, Sharida; Kandasamy, Murugesan

    2013-08-01

    Oxidative stress in diabetic tissues is a consequence of free radical accumulation with concurrently impaired natural antioxidants status and results in oxidative tissue damage. The present study investigated the protective effects of mangiferin against pancreatic ?-cell damage and on the antioxidant defense systems in streptozotocin (STZ)-induced diabetic rats. Diabetes was experimentally induced by a single intraperitoneal injection of STZ. Oxidative stress biomarkers such as tissue malondialdehyde, hydroperoxides, reduced glutathione (GSH) content, and nonenzymatic antioxidants were measured. Biochemical observations were further substantiated with histological examination and ultrastructural studies in the pancreas of diabetic, glibenclamide and mangiferin-treated diabetic rats (dosage of 40 mg/kg body weight daily for 30 days). Oral administration of mangiferin and glibenclamide to diabetic rats significantly decreased the level of blood glucose and increased levels of insulin. Additionally, mangiferin treatment significantly modulated the pancreatic nonenzymatic antioxidants status (vitamin C, vitamin E, ceruloplasmin, and reduced GSH content) and other oxidative stress biomarkers. The histoarchitecture of diabetic rats showed degenerated pancreas with lower ?-cell counts, but mangiferin treatment effectively regenerated insulin secreting islet cells. The electron microscopic study revealed damaged nuclear envelope and mitochondria and fewer secretory granules in pancreas of diabetic rats; however, mangiferin treatment nearly normalized pancreatic architecture. The present findings suggest that mangiferin treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and protecting against pancreatic ?-cell damage, which may be attributable to its antioxidative properties. PMID:23957355

  18. Modulating efficacy of Rebaudioside A, a diterpenoid on antioxidant and circulatory lipids in experimental diabetic rats.

    PubMed

    Saravanan, Ramalingam; Ramachandran, Vinayagam

    2013-09-01

    The present study was to evaluate the protective effects of Rebaudioside A (Reb A) on antioxidant status and lipid profile in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats by a single intraperitoneal administration of STZ (40mg/kg b.w). Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, hydroperoxides and decreased levels of insulin. The activity of enzymatic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and the levels of non enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were decreased in diabetic rats. The levels of total cholesterol (TC), triglycerides (TGs), free fatty acids (FFAs), phospholipids (PLs), low density lipoproteins (LDL-cholesterol) and very low-density lipoproteins (VLDL-cholesterol) in the plasma significantly increased, while plasma high-density lipoproteins (HDL-cholesterol) were significantly decreased in diabetic rats. Oral administration of Reb A (200mg/kg b.w) brought back plasma glucose, insulin, lipid peroxidation products, enzymatic, non-enzymatic antioxidants and lipid profile levels to near normal. The results of the present investigation suggests that Reb A, a natural sweetener exhibits antilipid peroxidative, antihyperlipidemic and antioxidant properties. PMID:23792234

  19. Time-Course Effect of Electrical Stimulation on Nerve Regeneration of Diabetic Rats

    PubMed Central

    Lin, Yu-Ching; Kao, Chia-Hong; Chen, Chung-Chia; Ke, Cherng-Jyh; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2015-01-01

    Background Electrical stimulation (ES) has been shown to promote nerve regeneration in rats with experimental diabetes induced using streptozotocin (STZ). However, the time-course effect of ES on nerve regeneration of diabetic animals has not been reported in previous studies. The present study attempted to examine the effect of different timing of ES after peripheral nerve transection in diabetic rats. Methodology/Findings Fifty Sprague-Dawley rats were used in the study. They were classified into five groups. STZ-induced diabetes was created in groups A to D. Normal animals in group E were used as the non-diabetic controls. The sciatic nerve was transected and repaired using a silicone rubber conduit across a 10-mm gap in all groups. Groups A to C received ES for 15 minutes every other day for 2 weeks. Stimulation was initiated on day 1 following the nerve repair for group A, day 8 for group B, and day 15 for group C. The diabetic control group D and the normal control group E received no ES. At 30 days after surgery in group A, histological evaluations showed a higher success percentage of regeneration across the 10-mm nerve gap, and the electrophysiological results showed significantly larger mean values of evoked muscle action potential area and amplitude of the reinnervated gastrocnemius muscle compared with group D. Conclusions/Significance It is concluded that an immediate onset of ES may improve the functional recovery of large nerve defect in diabetic animals. PMID:25689049

  20. Partial preservation of pancreatic ?-cells by vanadian: Evidence for long-term amelioration of diabetes

    Microsoft Academic Search

    M. C. Cam; W. M. Li; J. H. McNeill

    1997-01-01

    Streptozotocin (STZ)-diabetic rats treated with vanadium can remain euglycemic for up to 20 weeks following withdrawal from vanadium treatment. In this study, we examined the effects of short-term vanadium treatment in preventing or reversing the STZ-induced diabetic state. Male Wistar rats were untreated (D) or treated (DT) with vanadyl sulfate for 1 week before administering STZ. Treatment was subsequently maintained

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

    PubMed Central

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

    2015-01-01

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

  2. Expression and Activity of SGLT2 in Diabetes Induced by Streptozotocin: Relationship with the Lipid Environment

    Microsoft Academic Search

    María F. Albertoni Borghese; Mónica P. Majowicz; María C. Ortiz; María del Rosario Passalacqua; Norma B. Sterin Speziale; Norberto A. Vidal

    2009-01-01

    Background\\/Aims: Diabetes mellitus may impact on the regulation of renal Na+-glucose cotransporter type 2 (SGLT2), however, previous studies have yielded conflicting results on the effects of streptozotocin (STZ)-induced diabetes on SGLT-mediated glucose transport. Methods: Diabetes was induced in male Wistar rats. The studies were performed at 3 (D3), 7 (D7) and 14 (D14) days after a single i.p. injection of

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

    PubMed Central

    Sabitha, V.; Ramachandran, S.; Naveen, K. R.; Panneerselvam, K.

    2011-01-01

    Objectives: The present investigation was aimed to study the antidiabetic and antihyperlipidemic potential of Abelmoschus esculentus peel and seed powder (AEPP and AESP) in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Acute toxicity of AEPP and AESP was studied in rats at 2000 mg/kg dose and diabetes was induced in rats by administration of STZ (60 mg/kg, i.p.). After 14 days of blood glucose stabilization, diabetic rats received AEPP, AESP, and glibenclamide up to 28 days. The blood samples were collected on day 28 to estimate the hemoglobin (Hb), glycosylated hemoglobin (HbA1c), serum glutamate-pyruvate transferase (SGPT), total protein (TP), and lipid profile levels. Results: In acute toxicity study, AESP and AESP did not show any toxicity or death up to a dose of 2000 mg/kg. Therefore, to assess the antidiabetic action, one by fifth and one by tenth dose of both powders were selected. Administration of AEPP and AESP at 100 and 200 mg/kg dose in diabetic rats showed significant (P < 0.001) reduction in blood glucose level and increase in body weight than diabetic control rats. A significant (P < 0.001) increased level of Hb, TP, and decreased level of HbA1c, SGPT were observed after the treatment of both doses of AEPP and AESP. Also, elevated lipid profile levels returned to near normal in diabetic rats after the administration of AEPP and AESP, 100 and 200 mg/kg dose, compared to diabetic control rats. Conclusion: The present study results, first time, support the antidiabetic and antihyperlipidemic potential of A. esculentus peel and seed powder in diabetic rats. PMID:21966160

  4. Puerarin Attenuated Early Diabetic Kidney Injury through Down-Regulation of Matrix Metalloproteinase 9 in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Zhong, Yifei; Zhang, Xianwen; Cai, Xianfan; Wang, Ke; Chen, Yiping; Deng, Yueyi

    2014-01-01

    Radix puerariae, a traditional Chinese herbal medication, has been used successfully to treat patients with early stage of diabetic nephropathy. However, the underlined mechanism of this renal protective effect has not been determined. In the current study, we investigated the effects and the mechanism of puerarin in Streptozotocin (STZ)-induced diabetic rats. We treated STZ-rats with either puerarin or losartan, an angiotensin II receptor blocker, as compared to those treated with vehicle. We found that both puerarin and losartan attenuated kidney hypertrophy, mesangial expansion, proteinuria, and podocyte foot process effacement in STZ rats. In addition, both puerarin and losartan increased expression of podocyte slit diaphragm proteins such as nephrin and podocin. Interestingly, we found that puerarin treatment induced a more pronounced suppression of oxidative stress production and S-nitrosylation of proteins in the diabetic kidneys as compared to losartan treatment. Furthermore, we found that matrix metalloproteinase-9 (MMP-9), which is known to be activated by oxidative stress and S-nitrosylation of proteins, was also suppressed more extensively by puerarin than losartan. In conclusion, these data provide for the first time the potential mechanism to support the use of puerarin in the treatment of early diabetic nephropathy. PMID:24454919

  5. 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. (State Univ. of New York, Buffalo (USA))

    1991-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. 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

  8. Effects of Phenolic Compounds of Fermented Thai Indigenous Plants on Oxidative Stress in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Chaiyasut, Chaiyavat; Kusirisin, Winthana; Lailerd, Narissara; Lerttrakarnnon, Peerasak; Suttajit, Maitree; Srichairatanakool, Somdet

    2011-01-01

    We investigated the effects of antioxidant activity of fermentation product (FP) of five Thai indigenous products on oxidative stress in Wistar rats with streptozotocin (STZ)-induced diabetes type II. The rats were fed with placebo and with the FP (2 and 6?mL/kg body weight/day) for 6 weeks. Rutin, pyrogallol and gallic acid were main compounds found in the FP. Plasma glucose levels in diabetic rats receiving the higher dose of the FP increased less when compared to the diabetic control group as well as the group receiving the lower FP dose (13.1%, 29%, and 21.1%), respectively. A significant dose-dependent decrease in plasma levels of thiobarbituric acid reactive substance (P < .05) was observed. In addition, the doses of 2 and 6?mL FP/kg/day decreased the levels of erythrocyte ROS in diabetic rats during the experiment, but no difference was observed when compared to the untreated diabetic rat group. Results imply that FP decreased the diabetes-associated oxidative stress to a large extent through the inhibition of lipid peroxidation. The FP also improved the abnormal glucose metabolism slightly but the difference was not statistically significant. Thus, FP may be a potential therapeutic agent by reducing injury caused by oxidative stress associated with diabetes. PMID:21423638

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

    PubMed

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

    2014-01-01

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

  10. Altered retinol status and expression of retinol-related proteins in streptozotocin-induced type 1 diabetic model rats.

    PubMed

    Takitani, Kimitaka; Inoue, Keisuke; Koh, Maki; Miyazaki, Hiroshi; Inoue, Akiko; Kishi, Kanta; Tamai, Hiroshi

    2015-05-01

    Diabetes is a metabolic disorder characterized by chronic hyperglycemia. Advanced diabetes is associated with severe complications and impaired nutritional status. Here, we assessed the expression of retinol-associated proteins, including ?-carotene 15,15'-monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), and cytochrome P450 26A1 (CYP26A1), and measured retinol levels in the plasma and liver of streptozotocin (STZ)-induced type 1 diabetic model rats. Compared to the levels in the control rats, retinol levels in the plasma and liver of STZ rats were decreased and increased, respectively. Hepatic expression of the LRAT gene in STZ rats was lower than that in the controls. In the liver of STZ rats, the expression of ALDH1A1, a retinal metabolizing enzyme was higher, whereas ALDH1A2 expression was lower than in the controls. Hepatic CYP26A1 expression in STZ rats was significantly higher than in the control rats. BCMO expression levels in the liver and intestine of STZ rats were much lower than those of the controls. Altered BCMO expression might affect retinol status. It is considered that the metabolic availability of retinol was lessened despite the accelerated catabolism of retinol; therefore, retinol mobilization may be unbalanced in the liver of rats in the type 1 diabetic state. PMID:26060349

  11. Altered retinol status and expression of retinol-related proteins in streptozotocin-induced type 1 diabetic model rats

    PubMed Central

    Takitani, Kimitaka; Inoue, Keisuke; Koh, Maki; Miyazaki, Hiroshi; Inoue, Akiko; Kishi, Kanta; Tamai, Hiroshi

    2015-01-01

    Diabetes is a metabolic disorder characterized by chronic hyperglycemia. Advanced diabetes is associated with severe complications and impaired nutritional status. Here, we assessed the expression of retinol-associated proteins, including ?-carotene 15,15'-monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), and cytochrome P450 26A1 (CYP26A1), and measured retinol levels in the plasma and liver of streptozotocin (STZ)-induced type 1 diabetic model rats. Compared to the levels in the control rats, retinol levels in the plasma and liver of STZ rats were decreased and increased, respectively. Hepatic expression of the LRAT gene in STZ rats was lower than that in the controls. In the liver of STZ rats, the expression of ALDH1A1, a retinal metabolizing enzyme was higher, whereas ALDH1A2 expression was lower than in the controls. Hepatic CYP26A1 expression in STZ rats was significantly higher than in the control rats. BCMO expression levels in the liver and intestine of STZ rats were much lower than those of the controls. Altered BCMO expression might affect retinol status. It is considered that the metabolic availability of retinol was lessened despite the accelerated catabolism of retinol; therefore, retinol mobilization may be unbalanced in the liver of rats in the type 1 diabetic state.

  12. Effect of chronic treatment with Bis(maltolato)oxovanadium (IV) in rat model of non-insulin-dependent-diabetes.

    PubMed

    Shinde, U A; Mehta, A A; Goyal, R K

    2001-09-01

    Effect of chronic treatment with Bis(maltolato)oxovanadium (IV) (BMOV) was studied in streptozotocin (STZ)-induced neonatal non-insulin-dependent-diabetic (NIDDM) rats. Intraperitoneal injection of STZ (90 mg kg(-1)) in Wistar rat pups (day 2 old) produced mild hyperglycemia, impaired glucose tolerance and insulin resistance at the age of 3 months. Treatment with BMOV (0.23 mM kg(-1)) in drinking water for 6 weeks produced a significant decrease in elevated serum glucose levels without any significant change in serum insulin levels in diabetic rats. BMOV treatment significantly decreased integrated area under the glucose curve without any significant change in integrated area under the insulin curve indicating improved glucose tolerance. Treatment also significantly increased K(ITT) value of diabetic rats indicating increased insulin sensitivity. BMOV treatment significantly reduced hypercholesterolemia in diabetic rats. Treatment also significantly decreased serum triglyceride levels in both diabetic and non-diabetic rats. The data suggest that chronic BMOV treatment improves glucose and lipid homeostasis. These effects appear to be due to the insulin sensitizing action of vanadium. PMID:11831366

  13. Protective Nature of Mangiferin on Oxidative Stress and Antioxidant Status in Tissues of Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Sellamuthu, Periyar Selvam; Arulselvan, Palanisamy; Kamalraj, Subban; Fakurazi, Sharida; Kandasamy, Murugesan

    2013-01-01

    Oxidative stress plays an important role in the progression of diabetes complications. The aim of the present study was to investigate the beneficial effect of oral administration of mangiferin in streptozotocin (STZ)-induced diabetic rats by measuring the oxidative indicators in liver and kidney as well as the ameliorative properties. Administration of mangiferin to diabetic rats significantly decreased blood glucose and increased plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were significantly (P < 0.05) decreased while increases in the levels of lipidperoxidation (LPO) markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with mangiferin (40?mg/kg?b.wt/day) for a period of 30 days showed significant ameliorative effects on all the biochemical and oxidative parameters studied. Diabetic rats treated with mangiferin restored almost normal architecture of liver and kidney tissues, which was confirmed by histopathological examination. These results indicated that mangiferin has potential ameliorative effects in addition to its antidiabetic effect in experimentally induced diabetic rats. PMID:24167738

  14. Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy.

    PubMed

    Li, Yang-Jun; Zhang, Jie; Han, Jing; DU, Zhao-Jiang; Wang, Ping; Guo, Yong

    2015-01-01

    This study used a streptozotocin (STZ)-induced rat model of diabetes to investigate whether Ras-related C3 botulinum toxin substrate 1 (Rac1) was involved in the pathogenesis of diabetic retinopathy. The effects of Rac1 inhibition on vascular endothelial (VE)-cadherin and ?-catenin expression in high glucose-induced rat retinal endothelial cells (RRECs) were additionally examined. Rac1 activation in the retinas from STZ-induced diabetic rats and in high glucose-induced RRECs was measured by reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. The expression levels of VE-cadherin and ?-catenin were also examined with or without Rac1 inhibition through small interfering (si)RNA transfection. STZ-induced diabetes was associated with an increase in the vascular permeability of the retina. Furthermore, Rac1 activation was increased in the retina of STZ-induced diabetic rats and in high glucose-induced RRECs compared with that in the controls. Immunohistochemistry showed that immunostaining of Rac1 was localized in the outer plexiform, inner nuclear, inner plexiform and ganglion cell layers and in the retinal microvasculature of rats. The expression of ?-catenin was increased in the retinas of the diabetic rats at four, eight and 12 weeks after the induction of diabetes compared with that in the controls. Additionally, Rac1 activation was required for the high glucose-induced VE-cadherin expression decrease and for ?-catenin expression in high glucose-induced RRECs. Rac1 inhibition by Rac1-siRNA transfection effectively prevented hyperpermeability, ?-catenin expression and the VE-cadherin expression decrease in high glucose-induced RRECs. In conclusion, diabetes affects the expression of Rac1 in the retina. Rac1 may be involved in the diabetes-induced damage and/or alterations to the blood-retinal barrier through changes in VE-cadherin and ?-catenin expression. PMID:25452781

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

    PubMed Central

    2014-01-01

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

  16. Influence of vanadium supplementation on oxidative stress factors in the muscle of STZ-diabetic rats.

    PubMed

    Kurt, Ozlem; Ozden, Tugba Yilmaz; Ozsoy, Nurten; Tunali, Sevim; Can, Ayse; Akev, Nuriye; Yanardag, Refiye

    2011-10-01

    In recent years, the role of free radical damage consequent to oxidative stress is widely discussed in diabetic complications. In this aspect, the protection of cell integrity by trace elements is a topic to be investigated. Vanadium is a trace element believed to be important for normal cell function and development. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the muscle tissue of diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) to male Swiss albino rats. The rats were randomly divided into 4 groups: Group I, control; Group II, vanadyl sulfate control; Group III, STZ-diabetic untreated; Group IV, STZ-diabetic treated with vanadyl sulfate. Vanadyl sulfate (100 mg/kg) was given daily by gavage for 60 days. At the last day of the experiment, rats were killed, muscle tissues were taken, homogenized in cold saline to make a 10% (w/v) homogenate. Body weights and blood glucose levels were estimated at 0, 30 and 60th days. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), as well as carbonic anhydrase (CA), myeloperoxidase (MPO) activities and protein carbonyl content (PCC) were determined in muscle tissue. Vanadyl sulfate administration improved the loss in body weight due to STZ-induced diabetes and decreased the rise in blood glucose levels. It was shown that vanadium supplementation to diabetic rats significantly decrease serum antioxidant enzyme levels, which were significantly raised by diabetes in muscle tissue showing that this trace element could be used as preventive for diabetic complications. PMID:21479831

  17. Antihyperglycemic and antihyperlipidemic effects of newly synthesized glibenclamide analogues on streptozotocin-diabetic rats.

    PubMed

    Ahmadi, A; Khalili, M; Farsadrooh, M; Ghiasi, M; Nahri-Niknafs, B

    2013-12-01

    In this study, new glibenclamide analogues (5a-d) with substituted pharmacological triethoxysilyl propan, allyl and ethoxyphenyl groups for cyclohexyl moiety have been synthesized by condensing sulfonamide (4) with related isocyanate or isothiocyanate's compounds. The newly synthesized drugs were evaluated for their antihyperglycemic and antihyperlipidemic activities with streptozotocin (STZ)-induced diabetic rats. All showed hypoglycemic and hypolipidemic activities compared to the control animals but 5c and 5d exhibited more and significant lowering blood activities similar to glibenclamide. This was concerned with identical affinities to bind with SUR1 receptor. Moreover, the new drugs displayed high efficiency for reducing serum LDL level which resulted in a high HDL/LDL ratio as a good lipid profile compared to other groups. PMID:23828271

  18. Role of glucagon-like peptide-1 analogues on insulin receptor regulation in diabetic rat hearts.

    PubMed

    Hantouche, Christine M; Bitar, Khalil M; Nemer, Georges M; Obeid, Mounir Y; Kadi, Lina N; Der-Boghossian, Asdghig H; Bikhazi, Anwar B

    2010-01-01

    This study focused on the regulation and affinity modulation of the insulin receptor of coronary endothelium and cardiomyocytes in nondiabetic and STZ-induced type 1 diabetic rats. Male rats were divided into the following 9 groups: nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co-treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). After the rats were treated for 1 month, a first-order Bessel function was employed to estimate the insulin binding affinity (with time constant tau = 1/k-n) to its receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated and CHAPS-treated heart perfusion, respectively. The results showed that diabetes (D) decreased the tau value on the coronary endothelium and increased it on cardiomyocytes compared with the nondiabetic group (N). Treatment with insulin and (or) exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, increased tau on the coronary endothelium only. On the coronary endothelium, tau values of DI and DIDp were normalized. Western blots of the insulin receptor showed upregulation in D, downregulation in DI, and normalization in DE and DDp. Immunohistochemistry and RT-PCR findings indicated atrial natriuretic factor (ANF) in all diabetic ventricles, thus ascertaining hypertrophy. Therefore, negative myocardial effects related to the insulin receptor were diminished in diabetic rats treated with DPP-IV inhibitor and, more efficiently, by exendin-4. PMID:20130739

  19. Insulin treatment normalizes retinal neuroinflammation but not markers of synapse loss in diabetic rats.

    PubMed

    Masser, Dustin R; VanGuilder Starkey, Heather D; Bixler, Georgina V; Dunton, Wendy; Bronson, Sarah K; Freeman, Willard M

    2014-08-01

    Diabetic retinopathy is one of the leading causes of blindness in developed countries, and a majority of patients with type I and type II diabetes will develop some degree of vision loss despite blood glucose control regimens. The effects of different insulin therapy regimens on early metabolic, inflammatory and neuronal retinal disease processes such as retinal neuroinflammation and synapse loss have not been extensively investigated. This study compared 3 months non-diabetic and streptozotocin (STZ)-induced diabetic Sprague Dawley rats. Diabetic rats received either no insulin treatment, systemic insulin treatment beginning after 1 week uncontrolled diabetes (early intervention, 11 weeks on insulin), or after 1.5 months uncontrolled diabetes (late intervention, 6 weeks on insulin). Changes in both whole animal metabolic and retinal inflammatory markers were prevented by early initiation of insulin treatment. These metabolic and inflammatory changes were also normalized by the later insulin intervention. Insulin treatment begun 1 week after diabetes induction ameliorated loss of retinal synapse markers. Synapse markers and presumably synapse numbers were equivalent in uncontrolled diabetes and when insulin treatment began at 1.5 months of diabetes. These findings are in agreement with previous demonstrations that retinal synapses are lost within 1 month of uncontrolled diabetes and suggest that synapses are not regained with glycemic control and restoration of insulin signaling. However, increased expression of metabolic and inflammatory markers associated with diabetes was reversed in both groups of insulin treatment. This study also emphasizes the need for insulin treatment groups in diabetic retinopathy studies to provide a more faithful modeling of the human condition. PMID:24931083

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

    PubMed

    El-Akabawy, Gehan; El-Kholy, Wael

    2014-05-01

    Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-?, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain. PMID:24680376

  1. Evaluation of antioxidant efficacy of vanadium-3-hydroxyflavone complex in streptozotocin-diabetic rats.

    PubMed

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

    2013-07-01

    Since 1985, when Heyliger et al., first demonstrated that oral administration of sodium orthovanadate (0.8mg/ml) to STZ induced diabetic rats resulted in normoglycemia, numerous extensive studies have been reported on the antidiabetic actions of vanadium. The acceptance of vanadium compounds as promising therapeutic antidiabetic drugs has been slowed due to the concern for chronic toxicity associated with vanadium accumulation. In order to circumvent the toxic effects of vanadium, a combinational approach wherein a novel V3HF complex was synthesized, characterized and its toxic as well as antidiabetic potential were evaluated in STZ diabetic rats. Experimental and clinical studies suggest that hyperglycemia-induced oxidative stress primarily contributes to the pathogenesis and progression of both primary as well as secondary complications of diabetes. It is possible to reduce the risks caused by excessive generation of free radicals by either enhancing the body's natural antioxidant defenses or by supplementing with proven antioxidants. The present study was aimed to study the role of V3HF complex on hyperglycemia mediated oxidative stress in STZ-diabetic rats and the results indicate that the complex improves pancreatic beta cell function. Histological and ultrastructural studies also evidenced that the complex protect the beta cells from hyperglycemia-induced oxidative stress. PMID:23665085

  2. Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats

    PubMed Central

    Yang, Chun; Zhu, Bin; Ding, Jie; Wang, Zhi-Gang

    2014-01-01

    Several lines of evidence demonstrate that isoflurane anesthesia would be a great risk factor for the patients undergoing surgeries to suffer from postoperative cognitive dysfunction (POCD). Additionally, diabetes is also an important pathogenic factor for the emergence of cognitive dysfunction. If patient is suffering from diabetes, the incidence of cognitive dysfunction greatly increased. We therefore aimed to investigate the effects of isoflurane anesthesia on cognitive dysfunction in a diabetic rat model induced by a single injection of streptozotocin (STZ). Wistar rats received 2 h of 2% isoflurane or oxygen exposure 1 month after a single intraperitoneal injection of 60 mg/kg of STZ or the vehicle. The results showed that isoflurane anesthesia significantly aggravates STZ-induced an increase of the latency to the platform and a decrease of the proportion of time spent in the target quadrant of rats in Morris water maze test. In addition to the expression of amyloid-? (A?), superoxide dismutase (SOD), malonyldialdehyde (MDA), tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?), isoflurane anesthesia significantly increased as compared with a single injection of STZ. However, isoflurane anesthesia had no effect on the blood glucose and leptin. In conclusion, our results suggested that isoflurane anesthesia aggravating cognitive impairment induced by STZ is probably related to the activation of oxidative stress and inflammatory response in rat hippocampus. PMID:24955160

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

    PubMed Central

    2014-01-01

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

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

    PubMed Central

    2012-01-01

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

  5. Effect of experimental diabetes on GABA-mediated inhibition of neurally induced contractions in rat isolated trachea.

    PubMed

    Ozdem, S S; Sadan, G; Usta, C; Ta?atargil, A

    2000-04-01

    1. In the present study, we investigated the effect of GABA and selective GABA agonists and antagonists on neurally induced tracheal contractions in streptozotocin (STZ) diabetic rats. 2. Contractile responses to electrical field stimulation (EFS) in rat tracheal rings were completely abolished by atropine and tetrodotoxin, but were unaffected by the ganglion blocker hexamethonium, indicating that they were mediated via neuronal release of acetylcholine (ACh). 3. Contractions induced by EFS, but not by exogenous ACh, were inhibited by GABA and the selective GABA(B) receptor agonist baclofen, but not by the selective GABA(A) receptor agonist 3-aminopropane sulphonic acid. The inhibitory effects of GABA or baclofen were not affected by the GABA(A) antagonist bicuculline, but were significantly reversed by the GABA(B) antagonist phaclofen. 4. The inhibitory effects of both GABA and baclofen were found to be significantly greater in trachea from control rats compared with tissues from diabetic rats. 5. Non-adrenergic, non-cholinergic relaxation responses elicited by EFS in precontracted tracheal rings from diabetic and control rats were similar in magnitude and were unaffected by GABA or GABA analogues. 6. These results suggest that GABA decreases the response to EFS by directly inhibiting the evoked release of ACh through GABA(B) receptors in rat trachea and that STZ-induced diabetes causes an impairment in the inhibitory effect of GABA on neurally induced contractions in this tissue. PMID:10779129

  6. Role of tissue transglutaminase in the pathogenesis of diabetic cardiomyopathy and the intervention effect of rutin

    PubMed Central

    GAO, HAI-CHENG; ZHU, KUN; GAO, HAI-MEI; MIAO, CHUN-SHENG; ZHANG, LE-NING; LIU, WEI; XIN, HUA

    2015-01-01

    The aim of this study was to investigate the role of tissue transglutaminase (tTG) in the pathogenesis of diabetic cardiomyopathy (DCM) and the intervention effect of rutin. DCM was induced in rats by the injection of streptozotocin (STZ; 25 mg/kg). After a preliminary examination, the rats were randomly divided into four groups: Control (n=8), STZ-induced DCM (n=8), STZ + positive drug (captopril; n=6) and STZ + rutin (n=8) groups. The DCM model was evaluated using blood sugar values, serum enzyme levels, hematoxylin and eosin staining and Masson’s staining, ex vivo. The protein and mRNA expression of tTG was assessed with immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The rat model of DCM was successfully established by STZ administration, and the expression levels of tTG were significantly increased in the DCM model. Following the injection of captopril or rutin, the blood sugar values, collagen content and expression levels of tTG were gradually reduced and serum enzyme levels were increased, as compared with those in the STZ-induced DCM group. In conclusion, tTG plays an important role in STZ-induced DCM. In addition, rutin may inhibit the expression of tTG and regulate myocardial injury in STZ-induced DCM. PMID:25780394

  7. Multiple Antioxidants Improve Cardiac Complications and Inhibit Cardiac Cell Death in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Kumar, Santosh; Prasad, Sahdeo; Sitasawad, Sandhya L.

    2013-01-01

    Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. Since diabetic cardiomyopathy is now known to have a high prevalence in the asymptomatic diabetic patient, prevention at the earliest stage of development by existing molecules would be appropriate in order to prevent the progression of heart failure. In this study, we investigated the protective role of multiple antioxidants (MA), on cardiac dysfunction and cardiac cell apoptosis in streptozotocin (STZ)-induced diabetic rat. Diabetic cardiomyopathy in STZ-treated animals was characterized by declined systolic, diastolic myocardial performance, oxidative stress and apoptosis in cardiac cells. Diabetic rats on supplementation with MA showed decreased oxidative stress evaluated by the content of reduced levels of lipid per-oxidation and decreased activity of catalase with down-regulation of heme-oxygenase-1 mRNA. Supplementation with MA also resulted in a normalized lipid profile and decreased levels of pro-inflammatory transcription factor NF-kappaB as well as cytokines such as TNF-?, IFN-?, TGF-?, and IL-10. MA was found to decrease the expression of ROS-generating enzymes like xanthine oxidase, monoamine oxidase-A along with 5-Lipoxygenase mRNA and/or protein expression. Further, left ventricular function, measured by a microtip pressure transducer, was re-established as evidenced by increase in ±dp/dtmax, heart rate, decreased blood pressure, systolic and diastolic pressure as well as decrease in the TUNEL positive cardiac cells with increased Bcl-2/Bax ratio. In addition, MA supplementation decreased cell death and activation of NF-kappaB in cardiac H9c2 cells. Based on our results, we conclude that MA supplementation significantly attenuated cardiac dysfunction in diabetic rats; hence MA supplementation may have important clinical implications in terms of prevention and management of diabetic cardiomyopathy. PMID:23843977

  8. Multiple antioxidants improve cardiac complications and inhibit cardiac cell death in streptozotocin-induced diabetic rats.

    PubMed

    Kumar, Santosh; Prasad, Sahdeo; Sitasawad, Sandhya L

    2013-01-01

    Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. Since diabetic cardiomyopathy is now known to have a high prevalence in the asymptomatic diabetic patient, prevention at the earliest stage of development by existing molecules would be appropriate in order to prevent the progression of heart failure. In this study, we investigated the protective role of multiple antioxidants (MA), on cardiac dysfunction and cardiac cell apoptosis in streptozotocin (STZ)-induced diabetic rat. Diabetic cardiomyopathy in STZ-treated animals was characterized by declined systolic, diastolic myocardial performance, oxidative stress and apoptosis in cardiac cells. Diabetic rats on supplementation with MA showed decreased oxidative stress evaluated by the content of reduced levels of lipid per-oxidation and decreased activity of catalase with down-regulation of heme-oxygenase-1 mRNA. Supplementation with MA also resulted in a normalized lipid profile and decreased levels of pro-inflammatory transcription factor NF-kappaB as well as cytokines such as TNF-?, IFN-?, TGF-?, and IL-10. MA was found to decrease the expression of ROS-generating enzymes like xanthine oxidase, monoamine oxidase-A along with 5-Lipoxygenase mRNA and/or protein expression. Further, left ventricular function, measured by a microtip pressure transducer, was re-established as evidenced by increase in ±dp/dtmax, heart rate, decreased blood pressure, systolic and diastolic pressure as well as decrease in the TUNEL positive cardiac cells with increased Bcl-2/Bax ratio. In addition, MA supplementation decreased cell death and activation of NF-kappaB in cardiac H9c2 cells. Based on our results, we conclude that MA supplementation significantly attenuated cardiac dysfunction in diabetic rats; hence MA supplementation may have important clinical implications in terms of prevention and management of diabetic cardiomyopathy. PMID:23843977

  9. Dual Blockade of Renin Angiotensin System in Reducing the Early Changes of Diabetic Retinopathy and Nephropathy in a Diabetic Rat Model

    PubMed Central

    Thangaraju, Pugazhenthan; Chakrabarti, Amitava; Banerjee, Dibyajyoti; Hota, Debasish; Tamilselvan; Bhatia, Alka; Gupta, Amod

    2014-01-01

    Background: Diabetes mellitus is a real pandemic of the modern world and the incidence of the disease is increasing at a tremendous rate with a number of complications involving major systems of the human body. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy and retinopathy. Aim: The study was designed to evaluate and compare effects of ramipril (angiotensin-converting enzyme inhibitor-ACEI) and telmisartan (angiotensin II receptor blocker - ARBs) combinations on the progression of retinopathy and nephropathy in the streptozotocin (STZ) induced diabetic model. Materials and Methods: Diabetic state in rats was induced by chemical method using STZ 55 mg/kg intraperitoneally. Diabetic renal tubulopathy and interstitial inflammatory changes were done. Diabetic retinopathy manifested in the form of vacuolar changes in the inner plexiform and the ganglionic layers of the retina was observed. Results: Treatments with ACEI and ARBs reduced the incidence of the occurrence of cataract. The effect of combinational drugs of ACEI (ramipril) and AT1 receptor blocker (Telmisartan) was evaluated. The drugs used in combinations showed improvement in the histopathological and biochemical changes of the diabetic animals, both for the retina and kidney. Conclusion: The efficacy of the drugs suggests a pivotal role of the local RAS system in the pathogenesis of tubulopathy in the kidney and neuronal damage in the retina of the diabetic animals. PMID:25599050

  10. Evaluation of Antihyperglycemic Activity of Citrus limetta Fruit Peel in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    KunduSen, Sriparna; Haldar, Pallab K.; Gupta, Malaya; Mazumder, Upal K.; Saha, Prerona; Bala, Asis; Bhattacharya, Sanjib; Kar, Biswakanth

    2011-01-01

    The present paper aims to evaluate antihyperglycemic activity of methanol extract of Citrus limetta fruit peel (MECL) in streptozotocin-induced (STZ; 65?mg/kg b.w.) diabetic rats. Three days after STZ induction, diabetic rats received MECL orally at 200 and 400?mg kg?1 body weight daily for 15 days. Glibenclamide (0.5?mg kg?1 p. o.) was used as reference drug. Blood glucose levels were measured on 0th, 4th, 8th, and 15th days of study. Serum biochemical parameters namely, SGOT, SGPT and ALP were estimated. The TBARS and GSH levels of pancreas, kidney, and liver were determined. MECL significantly (P < 0.001) and dose dependently normalized blood glucose levels and serum biochemical parameters, decreased lipid peroxidation, and recovered GSH as compared to those of STZ control. The present paper infers that in STZ-induced diabetic Wistar rats, C. limetta fruit peel demonstrated a potential antihyperglycemic effect which may be attributed to its antioxidant property. PMID:22363893

  11. Insulin treatment restores glutamate (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor function in the hippocampus of diabetic rats.

    PubMed

    Viswaprakash, Nilmini; Vaithianathan, Thirumalini; Viswaprakash, Ajitan; Judd, Robert; Parameshwaran, Kodeeswaran; Suppiramaniam, Vishnu

    2015-09-01

    Type 1 diabetes is associated with cognitive dysfunction. Cognitive processing, particularly memory acquisition, depends on the regulated enhancement of expression and function of glutamate receptor subtypes in the hippocampus. Impairment of memory was been detected in rodent models of type 1 diabetes induced by streptozotocin (STZ). This study examines the functional properties of synaptic ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the expression of synaptic molecules that regulate glutamatergic synaptic transmission in the hippocampus of STZ-diabetic rats. The AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and single-channel properties of synaptosomal AMPA receptors were examined after 4 weeks of diabetes induction. Results show that amplitude and frequency of mEPSCs recorded from CA1 pyramidal neurons were decreased in diabetic rats. In addition, the single-channel properties of synaptic AMPA receptors from diabetic rat hippocampi were different from those of controls. These impairments in synaptic currents gated by AMPA receptors were accompanied by decreased protein levels of AMPA receptor subunit GluR1, the presynaptic protein synaptophysin, and the postsynaptic anchor protein postsynaptic density protein 95 in the hippocampus of diabetic rats. Neural cell adhesion molecule (NCAM), an extracellular matrix molecule abundantly expressed in the brain, and the polysialic acid (PSA) attached to NCAM were also downregulated in the hippocampus of diabetic rats. Insulin treatment, when initiated at the onset of diabetes induction, reduced these effects. These findings suggest that STZ-induced diabetes may result in functional deteriorations in glutamatergic synapses in the hippocampus of rats and that these effects may be reduced by insulin treatment. © 2015 Wiley Periodicals, Inc. PMID:25807926

  12. Prevention of diabetes-induced myocardial dysfunction in rats using the juice of the Emblica officinalis fruit

    PubMed Central

    Patel, Snehal S; Goyal, Ramesh K

    2011-01-01

    Normalization of hyperglycemia, hyperlipidemia and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. The present study investigated the effects of the fruit juice obtained from Emblica officinalis on myocardial dysfunction in diabetic rats. Diabetes was induced by streptozotocin (STZ), and the rats were treated with E officinalis fruit juice for eight weeks. Injection of STZ produced loss of body weight, polydypsia, polyphagia, hyperglycemia, hypoinsulinemia and dyslipidemia. It also produced hypertension, bradycardia, hypertrophy and myocardial functional alterations associated with an increase in serum lactate dehydrogenase and creatinine kinase-MB levels. Treatment with the fruit juice not only prevented STZ-induced loss of body weight, increases in water and food intake, increases in serum glucose levels and disturbed lipid profile, but also an increase in serum lactate dehydrogenase and creatinine kinase-MB levels, and increased myocardial hypertrophy and cardiomyopathy. There was an increase in the area under the curve (AUC) for glucose, and a decrease in AUCinsulin was observed in diabetic rats; treatment decreased AUCglucose but not AUCinsulin or hyperinsulinemia. There was a decrease in antioxidant enzyme levels (in superoxide dismutase, reduced glutathione and catalase) in diabetic hearts, which could be improved by treatment with fruit juice. The present data suggest that fruit juice may be beneficial for the treatment of myocardial damage associated with type 1 diabetes mellitus. The activity of E officinalis fruit juice can be attributed to the concentration of polyphenol present. PMID:22065939

  13. Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis

    PubMed Central

    Satheesan, S; Figarola, J L; Dabbs, T; Rahbar, S; Ermel, R

    2014-01-01

    BACKGROUND AND PURPOSE We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on the progression of aortic pathology. EXPERIMENTAL APPROACH STZ-induced diabetic rats were treated with or without LR-90 (50 mg L-1 in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross-linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra. KEY RESULTS LR-90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR-90 did not affect arterial BP, but prevented the diabetes-induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR-90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR-90 inhibited collagen cross-linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats. CONCLUSIONS AND IMPLICATIONS Treatment with LR-90 may impart significant protection against diabetes-induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications. PMID:24611770

  14. Antidiabetic and Hypolipidemic Effect of Salacia Oblonga in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Bhat, Bhagyajyothi M.; C.V., Raghuveer; D’Souza, Vivian; Manjrekar, Poornima A.

    2012-01-01

    Objectives The present study was conducted to evaluate the effect of a standardized hydroalcoholic root extract of Sala¬cia oblonga (SOE) on the Random Blood Glucose (RBG) levels, serum insulin, glycated haemoglobin (HbA1c) and the serum lipid profile in long standing, experimentally induced Diabetes Mellitus (DM) with glibenclamide (Glb) as the standard. Materials and Methods Streptozotocin (STZ) induced, dia-betic, Wistar rats of either sex were treated with two oral doses of SOE, 100 and 50mg/kg body wt /day, for a period of 16 weeks. The RBG was estimated at day-1 and at the end of the 16 weeks by using a glucometer. The fasting serum insulin was determined by an ELISA technique. The plasma HbA1c was evaluated by a Turbidimetric Inhibition Immunoassay (TINIA) and the lipid profile was estimated enzymatically. Results and Analysis A 45% decrease in the RBG was seen after the treatment with the higher dose of SOE, whereas a 44% decrease was observed with the lower dose as com¬pared to the diabetic control. Serum insulin was significantly increased (P<0.05) in all the treated groups as compared to the diabetic control. Plasma HbA1c was significantly decreased (P<0.05). The serum Triacyl Glycerol (TG) levels were signifi¬cantly decreased (P<0.05) in the treated rats as compared to the diabetic control. A significant increase in HDL-cholesterol (P<0.05) in the diabetic rats as a result of the 100mg/kg SOE treatment was a remarkable finding. Conclusion SOE improves the glycaemic parameters in diabetic rats after a prolonged treatment. The serum TG levels were normalized on treatment. A higher dose of the extract could not alter the parameters significantly, except for HDL-C. PMID:23373028

  15. Simvastatin ameliorates low-dose streptozotocin-induced type 2 diabetic nephropathy in an experimental rat model

    PubMed Central

    Zhang, Siwei; Xu, Huali; Yu, Xiaofeng; Wang, Yuchen; Sun, Fanfan; Sui, Dayuan

    2015-01-01

    The present study aims to study the possible renal protective effect of simvastatin in the development and progression of type 2 diabetic nephropathy. A rat model of T2DN was induced by high-fat diet together with single low-dose of streptozotocin. The diabetic rats were either given treatment or vehicle control for 13 weeks to develop nephropathy. At the end of treatment, parameters of renal function were determined. Kidney samples were collected for histological studies and generated homogenates for biochemical analysis. In T2DN rats, severe hyperglycemia was developed, FBG were markedly elevated. Diabetes induced significant alterations in renal structure, such as severe reduction of glomerular tufts, increase in Bowman’s spaces, thickening of GBM. In addition, and SCr, UAER and BUN are elevated, accompanied with reduction in UCr and CCr, indicating obvious renal failure. On the other hand, endogenous antioxidants SOD, GSH-Px were reduced, whereas MDA was increased. However, treatment of T2DN rats with simvastatin restored renal changes in different aspects. Our results showed that STZ-induced T2DN could be attenuated by simvastatin. The renoprotective effects of simvastatin was indicated by improvements in kidney function parameters, and was attributed by its lipid-lowering effect as well as its anti-oxidative stress, anti-inflammatory properties without having noticeable influence on glycemic control. Simvastatin ameliorates low-dose Streptozotocin-induced type 2 diabetic nephropathy in an experimental rat model.

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

    PubMed Central

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

    2015-01-01

    Background: Medicinal plants, owing to their different mechanisms such as antioxidants effects, may improve learning and memory impairments in diabetic rats. Calendula officinalis (CO), has a significant antioxidant activity. Aims: To examine the effect of hydroalcoholic extract of CO on passive avoidance learning (PAL) and memory in streptozotocin (STZ)-induced diabetic male rats. Settings and Design: A total of 32 adult male Wistar rats were randomly allocated to four groups: Control, diabetic, control + extract of CO and diabetic control + extract of CO groups with free access to regular rat diet. Subjects and Methods: Diabetes in diabetic rats was induced by single intraperitoneal injection of 60 mg/kg STZ. After confirmation of diabetes, oral administration of 300 mg/kg CO extract to extract-treated groups have been done. PAL was tested 8 weeks after onset of treatment, and blood glucose and body weight were measured in all groups at the beginning and end of the experiment. Statistical Analysis Used: The statistical analysis of data was performed by ANOVA followed by least significant difference post-hoc analysis. Results: Diabetes decreased learning and memory. Effect of CO extract in retention test (after 24 and 48 h) has been shown a significant decrease in step-through latency and increase in time spent in the dark compartment part. Also the extract partially improved hyperglycemia and reduced body weight. Conclusion: Taken together, CO extract can improve PAL and memory impairments in STZ-diabetic rats. This improvement may be due to its antioxidant, anticholinergic activities or its power to reduce hyperglycemia. PMID:26120230

  17. Antidiabetic and antihyperlipidemic activity of asiatic acid in diabetic rats, role of HMG CoA: in vivo and in silico approaches.

    PubMed

    Ramachandran, Vinayagam; Saravanan, Ramalingam; Senthilraja, Poomalai

    2014-02-15

    Hyperlipidemia is an associated complication of diabetes and also a major risk factor for cardiovascular diseases. The present study was designed to examine the antihyperlipidemic effect of asiatic acid (AA) in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40 mg/kg b.w.). Diabetic rats show increased plasma glucose, total cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density liprotein, atherogenic index and decreased insulin and high density lipoprotein in diabetic rats. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase increased significantly in contrast to the activities of lipoprotein lipase and lecithin cholesterol acyltransferase. In addition, the molecular docking of AA against HMG CoA reductase involved in cholesterol biosynthesis using Argus software. Diabetic rats were treated with AA shifted all these parameters towards normalcy. AA has shown best ligand binding energy 11.8122 kcal/mol. The antihyperlipidemic effect of AA was compared with glibenclamide; a well-known antihyperglycemic drug. In conclusion, this study indicates that AA showed an antihyperlipidemic effect in addition to its antidiabetic effect in experimental diabetes. PMID:24075211

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2015-06-01

    Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to abnormalities in either insulin secretion or action. A range of vanadium complexes have been synthesized and demonstrated to be effective in lowering hyperglycemia. Thiamine administration was also reported to prevent deterioration in fasting glucose and insulin levels, and to improve glucose tolerance in hyperglycemic patients. This study has been conducted to evaluate the ionic vanadyl(II) thiamine hydrochloride complex (VC) as a new anti-diabetic candidate. The new complex was characterized by infrared spectroscopy (FT-IR), electronic spectra, magnetic susceptibility, electron spin resonance (ESR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The anti-diabetic effect of VC was investigated in comparison to vanadium sulfate in streptozotocin (STZ)-induced diabetic rats. Treatment of diabetic rats with VC versus vanadyl sulfate showed a more potent effect on reducing serum glucose and cholesterol close to normal levels. VC suppressed the diabetes-induced upregulation of hepatic glucose transporter (GLUT)-2, Phosphoenol pyruvate carboxykinase (PEPCK), and hormone-sensitive lipase (HSL) more significantly than vanadyl sulfate. Either vanadyl sulfate or VC restored hepatic sterol regulatory element-binding protein transcription factor-1c (SREBP-1c) and muscle hexokinase (HK) mRNA expression that was downregulated in diabetic group. Pyruvate kinase (PK) mRNA expression was restored more significantly in VC-treated than vanadyl sulfate-treated diabetic rats. These results indicate that the newly synthesized VC could be an effective anti-diabetic candidate as the anti-diabetic activity of the ionic vanadium was enhanced after being modified with the organic ligand, thiamin. The results also suggest that VC achieves its effect most likely through modulating the transcription of energy metabolizing enzymes. PMID:25816395

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

    PubMed Central

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

    2015-01-01

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

  3. Antihyperglycemic and hypolipidemic activity of methanolic extract of Amaranthus viridis leaves in experimental diabetes

    PubMed Central

    Krishnamurthy, Girija; Lakshman, Kuruba; Pruthvi, Nagaraj; Chandrika, Pulla Udaya

    2011-01-01

    To investigate the antihyperglycemic and hypolipidemic effects of methanolic extract of leaves of Amaranthus viridis (MEAV) in normal and Streptozotocin (STZ) induced diabetic rats. The anti-hyperglycemic and hypolipidemic activity of methanolic extract of leaves of Amaranthus viridis was evaluated by using normal and STZ induced diabetic rats at dose of 200 mg/kg and 400 mg/kg by mouth per day for 21 days. Blood glucose levels and body weight was monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed. The statistical data indicated a significant increase in the body weight, decrease in the blood glucose, total cholesterol and serum triglycerides after treatment with MEAV. High density lipoprotein (HDL) cholesterol level was significantly increased when treated with extract. Histologically, focal necrosis was observed in the diabetic rat pancreas; however, was less obvious in treated groups. The MEAV has beneficial effects in reducing the elevated blood glucose level and body weight changes, and improves the lipid profile of STZ induced rats. PMID:21845004

  4. Comparison of effects of vanadium absorbed by Coprinus comatus with those of inorganic vanadium on bone in streptozotocin-diabetic rats.

    PubMed

    Wang, Guangbin; He, Ming; Yi, Pei; Wang, Jiashi; Li, Bin; Li, Jianjun; Fu, Yonghui; Bai, Lunhao; Fu, Qin

    2012-12-01

    The purpose of this study was to compare the effect of vanadium absorbed by Coprinus comatus (VACC) with inorganic vanadium (vanadium nitrate, IV) in preventing diabetes-related osteopenia in streptozotocin-diabetic rats. Sixty Wistar female rats used were divided into four groups: (1) normal rats (control), (2) diabetic rats, (3) diabetic rats treated with VACC, and (4) diabetic rats treated with vanadium nitrate. A standardized type 1-like diabetes model was induced by injection of streptozotocin. After the rats were treated orally with VACC and IV respectively, plasma glucose, body weights, micro-CT, biomechanical testing, and histomorphometry were examined. In addition, bone samples were obtained to evaluate the content of mineral substances in bones. Treatments were performed over a 12-week period. Both VACC and IV have a positive effect on plasma glucose and body weights of STZ-induced diabetic rats. However, treatment with IV only caused a 39.6 % decrease in glucose levels and a 14.6 % increase in body weights, whereas VACC decreased plasma glucose and increased body weights by up to 52.2 and 24.5 %, respectively. At the same time, VACC significantly improved trabecular microstructure and mechanical strength, while IV did not exhibit desirable such effects. Also, bone Ca and bone P were not significantly increased by IV. These results indicated that both VACC and IV have hypoglycemic activity on diabetic rats, while IV did not improve bone properties. In conclusion, this study suggests that VACC improves diabetes-related bone dysfunction, primarily by improving the diabetic states. PMID:22549703

  5. Adenosine monophosphate-activated protein kinase activation mediates the leptin-induced attenuation of cognitive impairment in a streptozotocin-induced rat model

    PubMed Central

    ZHU, BIN; JIANG, RI-YUE; YANG, CHUN; LIU, NING

    2015-01-01

    Several lines of evidence have shown that the incidence of cognitive impairment in diabetic patients is significantly higher than that in healthy individuals, but the exact pathogenesis has not been fully elucidated. Furthermore, it has been suggested that leptin may have a therapeutic effect in cognitive dysfunction. The aim of the present study was to observe the effect of leptin on cognitive dysfunction in streptozotocin (STZ)-induced diabetic rats, and to explore whether adenosine monophosphate-activated protein kinase (AMPK) activation was involved in any potential therapeutic effect of leptin. Compared with control rats, STZ rats exhibited decreased levels of AMPK and a poor performance in the Morris water maze, while these changes were reversed by leptin. Furthermore, Compound C, an AMPK antagonist, significantly attenuated the leptin-induced cognitive function improvement in the STZ rats. In conclusion, these results suggest that AMPK activation may play a critical role in the leptin-induced attenuation of STZ-induced cognitive impairment.

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

    PubMed

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

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man. PMID:14578206

  7. Antioxidant icariside II combined with insulin restores erectile function in streptozotocin-induced type 1 diabetic rats

    PubMed Central

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

    2015-01-01

    Erectile dysfunction (ED) worsens in patients with diabetes mellitus (DM) despite good control of blood glucose level with insulin. Recent studies imply that diabetic vascular stresses (e.g. oxidative stress) persist in spite of glucose normalization, which is defined as metabolic memory. Studies suggest that the interaction between advanced glycation end products (AGEs) and their receptor (RAGE) mediates the development of metabolic memory. To investigate the effects of the antioxidant icariside II plus insulin on erectile function in streptozotocin (STZ)- induced type 1 diabetic rats. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into five groups: normal control, diabetic, insulin-treated diabetic, icariside II-treated diabetic, and insulin plus icariside II-treated diabetic. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, icariside II was administered by gastric lavage once a day (5 mg/kg) for 6 weeks; and 2–6 units of intermediate-acting insulin were given to maintain normal glycemia for 6 weeks. The main outcome measures were the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP); histology of penile endothelial cells and smooth muscle cells; neural nitric oxide synthase, AGEs and RAGE expression; malondialdehyde concentration; superoxide dismutase activity; and apoptosis index. Diabetic rats demonstrated a significantly lower ICP/MAP ratio, reduced penile endothelial cells, reduced smooth muscle cells, increased AGEs and RAGE, and increased apoptosis. Insulin and icariside II monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed significantly better erectile parameters, cytological components and biochemistry, similar to those in the normal control group. These results suggest that, although insulin can effectively control glycemic levels, it does not completely alter the pathological changes in erectile tissues. Better efficacy could be expected with tight glycemic control plus the antioxidant icariside II. The proposed combination therapy might have the potential to eliminate metabolic memory by down-regulating the AGEs-RAGE-oxidative stress axis. PMID:25781208

  8. Antioxidant icariside II combined with insulin restores erectile function in streptozotocin-induced type 1 diabetic rats.

    PubMed

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

    2015-05-01

    Erectile dysfunction (ED) worsens in patients with diabetes mellitus (DM) despite good control of blood glucose level with insulin. Recent studies imply that diabetic vascular stresses (e.g. oxidative stress) persist in spite of glucose normalization, which is defined as metabolic memory. Studies suggest that the interaction between advanced glycation end products (AGEs) and their receptor (RAGE) mediates the development of metabolic memory. To investigate the effects of the antioxidant icariside II plus insulin on erectile function in streptozotocin (STZ)- induced type 1 diabetic rats. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into five groups: normal control, diabetic, insulin-treated diabetic, icariside II-treated diabetic, and insulin plus icariside II-treated diabetic. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, icariside II was administered by gastric lavage once a day (5 mg/kg) for 6 weeks; and 2-6 units of intermediate-acting insulin were given to maintain normal glycemia for 6 weeks. The main outcome measures were the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP); histology of penile endothelial cells and smooth muscle cells; neural nitric oxide synthase, AGEs and RAGE expression; malondialdehyde concentration; superoxide dismutase activity; and apoptosis index. Diabetic rats demonstrated a significantly lower ICP/MAP ratio, reduced penile endothelial cells, reduced smooth muscle cells, increased AGEs and RAGE, and increased apoptosis. Insulin and icariside II monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed significantly better erectile parameters, cytological components and biochemistry, similar to those in the normal control group. These results suggest that, although insulin can effectively control glycemic levels, it does not completely alter the pathological changes in erectile tissues. Better efficacy could be expected with tight glycemic control plus the antioxidant icariside II. The proposed combination therapy might have the potential to eliminate metabolic memory by down-regulating the AGEs-RAGE-oxidative stress axis. PMID:25781208

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

    PubMed

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

    2013-01-01

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

  10. The biochemical and histological effects of lichens in normal and diabetic rats.

    PubMed

    Deniz, Gülsah Yildiz; Geyikoglu, Fatime; Türkez, Hasan; Bakir, Tülay Özhan; Colak, Suat; Aslan, Ali

    2013-11-01

    Oxidative stress plays an important role in causing diabetes; however, no studies have thoroughly reported on the toxic and beneficial effects of lichen extracts in patients with diabetes mellitus (DM). This study covers a previously unrecognized effect of two well-known lichen species Cetraria islandica and Pseudevernia furfuracae in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250-500 mg/kg /day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anaesthetized, and metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of liver was examined using three different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), and reticulin and Sudan Black B. Our experimental data showed that increasing doses of C. islandica and P. furfuracae alone did not have any detrimental effects on studied parameters and the malondialdehyde level of liver. C. islandica extract showed positive results for antioxidant capacity compared to doses of P. furfuracae extract. However, the protective effect of C. islandica extract on diabetes-induced disorders and hepatic damages is still unclear. Moreover, unfortunately, animals subjected to DM therapy did not benefit from the usage of increasing lichen doses due to their unchanged antioxidant activity in tissues. The results obtained in present study suggested that C. islandica and P. furfuracae is safe but the power of these is limited because of intensive oxidative stress in liver of type 1 diabetic rats. It is also implied that C. islandica extract is especially suitable for different administration routes in DM animals. PMID:24193057

  11. Investigation of in vivo antioxidant property of Abelmoschus esculentus (L) moench. fruit seed and peel powders in streptozotocin-induced diabetic rats

    PubMed Central

    Sabitha, Vijayakumar; Ramachandran, Subramaniam; Naveen, Koikaramparambil Robert; Panneerselvam, Kaliyamoorthy

    2012-01-01

    Background: Abelmoschus esculentus (L.) Moench. fruit is a commonly consumed vegetable in many countries due to its rich medicinal value. However, till date, in vivo antioxidant property of A. esculentus has not been scientifically documented in animal models. Objective: The present investigation was aimed to evaluate the in vivo antioxidant property of A. esculentus (L.) Moench. peel and seed powder (AEPP and AESP) in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: In rats, acute toxicity assessment of AEPP and AESP at 2 g/kg did not show any toxicity. Diabetes was induced by STZ (60 mg/kg, i.p.) injection and diabetic rats received AEPP (100 and 200 mg/kg) as well as AESP (100 and 200 mg/ kg) orally up to 28 days. At the end of the 28 day, diabetic rats were killed and liver, kidney and pancreas were collected to determine superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation level. Results: In diabetic rats, significant (P < 0.001) reduction of liver, kidney and pancreas SOD, CAT, GPx, GSH levels and increase in thiobarbituric acid reactive substances (TBARS) were observed as compared to normal control rats. Administration of both doses of AEPP and AESP significantly (P < 0.001 and P < 0.01) increased liver, kidney and pancreas SOD, CAT, GPx, GSH levels and decreased TBARS (P < 0.001) levels in diabetic rats compared to diabetic control rats. Conclusion: Our findings confirmed that A. esculentus peel and seed powder has significant in vivo antioxidant property in diabetic rats. PMID:23326089

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

    PubMed Central

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

    2015-01-01

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

  13. Effect of the Combination of Gelam Honey and Ginger on Oxidative Stress and Metabolic Profile in Streptozotocin-Induced Diabetic Sprague-Dawley Rats

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Bakir, Tülay Özhan; Geyikoglu, Fatime; Colak, Suat; Türkez, Hasan; Aslan, Ali; Bakir, Murat

    2013-07-01

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

  15. Serum Biochemical, Histopathology and SEM Analyses of the Effects of the Indian Traditional Herb Wattakaka Volubilis Leaf Extract on Wistar Male Rats

    PubMed Central

    Gopal, Velmani; Mandal, Vivekananda; Tangjang, Sumpam; Mandal, Subhash C.

    2014-01-01

    Objectives: The present study investigated the protective effect of Wattakaka (W.) volubilis leaf extract against streptozotocin (STZ)-induced diabetes in rats. Methods: Male Wistar rats were divided into five groups (with six rats in each group) and were fed ad libitum. The rats were fasted for sixteen hours before diabetes was induced by injecting a single dose of 90 mg/kg body weight of STZ in 0.9-percent normal saline through an intraperitoneal route. The five groups were as follows: Group 1: normal control (saline-treated), Group 2: untreated diabetic rats, Groups 3 and 4: diabetic rats treated orally with petroleum ether cold maceration extract (PEME) of W. volubilis(50 and 100 mg/kg body weight), and Group 5: diabetic rats treated orally with metformin (250 mg/kg body weight). All rats received treatment for 21 days. For the STZ-induced diabetic rats, the blood-glucose, ?-amylase, total protein and alanine transaminase (ALT) levels were measured on days 7,14 and 21 of the treatment with PEME of W. volubilis and the treatment with metformin. Histopathological changes in the liver were examined with hematoxylin-eosin staining. Morphological changes in the liver were also examined with glutaraldehyde fixation. Results: The treatments with PEME of W. volubilis and with metformin in experimental rats by oral injections for 21 days produced reductions in the levels of serum biochemical markers. Histopathology and scanning electron microscopy results showed that the administrations of PEME of W. volubilis and of metformin suppressed the generation of abnormal liver cells in the STZ-treated rats. Conclusion: These results suggest that both PEME of W. volubilis and metformin have a protective effect against STZ-induced diabetes. PMID:25780685

  16. Impact of gestational diabetes and lactational insulin replacement on structure and secretory function of offspring rat ventral prostate.

    PubMed

    Santos, Sérgio A A; Rinaldi, Jaqueline C; Martins, Amanda E; Camargo, Ana C L; Leonelli, Carina; Delella, Flávia K; Felisbino, Sérgio L; Justulin, Luis A

    2014-09-15

    Clinical and experimental studies have shown that exposure to adverse conditions during the critical stages of embryonic, fetal or neonatal development lead to a significantly increased risk of later disease. Diabetes during pregnancy has been linked to increased risk of obesity and diabetes in offspring. Here, we investigated whether mild gestational diabetes mellitus (GDM) followed or not by maternal insulin replacement affects the ventral prostate (VP) structure and function in male offspring at puberty and adulthood. Pregnant rats were divided into the following 3 groups: control (CT); streptozotocin (STZ)-induced diabetes (D); and D plus insulin replacement during lactation (GDI). The male offspring from different groups were euthanized at postnatal day (PND) 60 and 120. Biometrical parameters, hormonal levels and prostates were evaluated. Mild-GDM promoted reduction in the glandular parenchyma and increased collagen deposition. Insulin replacement during lactation restored the VP morphology. Most importantly, mild-GDM decreased the androgen-induced secretory function as determined by prostatein expression, and insulin replacement reversed this effect. Our results demonstrated that mild GDM impairs VP parenchyma maturation, which is associated with an increase in the fibromuscular stroma compartment. Functionally, the reduction in the VP parenchyma decreases the glandular secretory activity as demonstrated by low expression of prostatein, a potent immunosuppressor factor that protects sperm from immunologic damage into the feminine reproductive tract. This change could lead to impairment of reproductive function in male offspring from diabetic mothers. Maternal insulin replacement during the weaning period apparently restores the prostate function in male offspring. PMID:24983773

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

    PubMed Central

    2014-01-01

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

  18. Streptozotocin-induced dynamic metabonomic changes in rat biofluids.

    PubMed

    Xu, Wenxin; Wu, Junfang; An, Yanpeng; Xiao, Chaoni; Hao, Fuhua; Liu, Hongbing; Wang, Yulan; Tang, Huiru

    2012-06-01

    Diabetes mellitus is a complex polygenic disease caused by gene-environment interactions with multiple complications, and metabonomic analysis is crucial for pathogenesis, early diagnosis, and timely interventions. Here, we comprehensively analyzed the dynamic metabolic changes in rat urine and plasma, which were induced by the well-known diabetogenic chemical streptozotocin (STZ), using (1)H NMR spectroscopy in conjunction with multivariate data analysis. The results showed that a single intraperitoneal injection of STZ with a moderate dosage (55 mg/kg) induced significant urinary metabonomic changes within 24 h. These changes showed time-dependence and heterogeneity among the treated animals with an animal recovered within 11 days. STZ-induced metabonomic alterations were related to suppression of glycolysis and TCA cycle, promotion of gluconeogenesis and oxidation of amino acids, alterations in metabolisms of basic amino acids associated with diabetic complications, and disruption of lipid metabolism and gut microbiota functions. With diffusion-edited NMR spectral data, we further observed the STZ-induced significant elevation of monounsaturated fatty acids and total unsaturated fatty acids together with reductions in PUFA-to-MUFA ratio in the blood plasma. These findings provided details of the time-dependent metabonomic changes in the progressive development of the STZ-induced diabetes mellitus and showed the possibility of detecting the biochemical changes in the early stage of type 1 diabetic genesis. PMID:22563680

  19. Limiting prolonged inflammation during proliferation and remodeling phases of wound healing in streptozotocin-induced diabetic rats supplemented with camel undenatured whey protein

    PubMed Central

    2013-01-01

    Background Impaired diabetic wound healing occurs as a consequence of excessive reactive oxygen species (ROS) and inflammatory cytokine production. We previously found that whey protein (WP) was able to normally regulate the ROS and inflammatory cytokines during the inflammatory phase (first day) in streptozotocin (STZ)-diabetic wound healing. This study was designed to assess the effect of WP on metabolic status, the inflammation and anti-inflammation response, oxidative stress and the antioxidant defense system during different phases of the wound healing process in diabetic rats. WP at a dosage of 100 mg/kg of body weight, dissolved in 1% CMC, was orally administered daily to wounded normal (non-diabetic) and STZ-induced diabetic rats for 8 days starting from the 1st day after wounding. Results The data revealed that WP enhanced wound closure and was associated with an increase in serum insulin levels in diabetic rats and an alleviation of hyperglycemic and hyperlipidemic states in diabetic animals. The increase in insulin levels as a result of WP administration is associated with a marked multiplication of ?-cells in the core of islets of Langerhans. WP induced a reduction in serum TNF-?, IL-1? and IL-6 levels and an increase in IL-10 levels, especially on the 4th day after wounding and treatment. WP also suppressed hepatic lipid peroxidation and stimulated the antioxidant defense system by increasing the level of glutathione and the activity of glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (SOD) in wounded diabetic rats. Conclusions WP was observed to enhance wound closure by improving the diabetic condition, limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats. PMID:23883360

  20. Efficacy of asiatic acid, a pentacyclic triterpene on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Ramachandran, Vinayagam; Saravanan, Ramalingam

    2013-02-15

    Asiatic acid (AA), a triterpenoid derivative of Centella asiatica, has shown significant biological effects of antioxidant and anti-inflammatory activities. Aim of this investigation was to evaluate the antihyperglycemic effect of AA on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. To induce diabetes mellitus, rats were injected with streptozotocin intraperitoneally at a single dose of 40 mg/kg b.w. Diabetic rats showed significant (p<0.05) increased in plasma glucose, glycosylated hemoglobin and significant (p<0.05) decreased in circulating insulin and hemoglobin. The altered activities of key enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase of carbohydrate metabolism significantly (p<0.05) increased whereas hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and glycogen content significantly (p<0.05) decreased in the liver of diabetic rats and also increased activities of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). Oral administration of AA (5, 10 and 20 mg/kg b.w.) and glibenclamide (600 ?g/kg b.w.) to diabetic rats for 45 days prevented the above alteration and reverted to near normalcy. Protection of body weight loss of diabetic rats by AA was also observed. No significant effect was observed in normal rats treated with AA (20 mg/kg b.w.). In this search, AA found to be potential bioactive compound to regulate the carbohydrate metabolism by modulating the key regulatory enzymes in diabetic rats. These findings merit further research in this field. PMID:23102509

  1. The Antidiabetic Effect of Garlic Oil is Associated with Ameliorated Oxidative Stress but Not Ameliorated Level of Pro-inflammatory Cytokines in Skeletal Muscle of Streptozotocin-induced Diabetic Rats

    PubMed Central

    Liu, Cheng-Tzu; Hsu, Tien-Wei; Chen, Ke-Ming; Tan, Ya-Ping; Lii, Chong-Kuei; Sheen, Lee-Yan

    2012-01-01

    Oxidative stress and inflammatory condition has been broadly accepted being associated with the progression of diabetes. On the other hand, garlic (?? dà suàn, bulb of Allium sativum) has been shown to possess both antioxidant and anti-inflammatory action in several clinical conditions. Our previous study demonstrated that treatment with garlic oil improves oral glucose tolerance and insulin tolerance and improves the insulin-stimulated utilization of glucose to synthesize glycogen in skeletal muscle in streptozotocin (STZ)-induced diabetes, in vivo and ex vivo, respectively. The aim of the present study is to investigate the antioxidant and anti-inflammatory effects of garlic oil (GO) in the skeletal muscle of diabetic rats. Rats with STZ-induced diabetes received GO (10, 50, or 100 mg/kg body weight) or corn oil by gavage every other day for 3 weeks. Control rats received corn oil only. GO dose-dependently improved insulin sensitivity, as assessed by the insulin tolerance test, and oral glucose tolerance. GO significantly elevated total glutathione and glutathione peroxidase activity and lowered the nitrate/nitrite content in skeletal muscle at 50 and 100 mg/kg and significantly elevated glutathione reductase activity and lowered lipid peroxidation at 100 mg/kg. By contrast, GO did not reverse diabetes-induced elevation of IL-1? and TNF-? in skeletal muscle at any tested dose. On the other hand, GO elevated the expression of GLUT4 in skeletal muscle along with glycogen content as observed with PAS staining. In conclusion, the antidiabetic effect of garlic oil is associated with ameliorated oxidative stress in skeletal muscle. PMID:24716126

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Javidanpour, Somaye; Fatemi Tabtabaei, Seyed Reza; Siahpoosh, Amir; Morovati, Hasan; Shahriari, Ali

    2012-01-01

    There is some report about the hypoglycemic effect of Juglans rejia L. leaf in alloxan induced diabetic rats and hypoglycemic effect of its fruit peel administered intra peritoneally. Thirty male Wistar rats divided into five groups, to evaluate the hypoglycemic and pancreas ?-cells regenerative effects of oral methanolic extracts of leaf and fruit peel of walnut. Rats were made diabetic by intravenous (IV) injection of 50 mg kg-1 streptozotocin (STZ). Negative control group did not get STZ and any treatment. Positive control, leaf extract, peel extract and insulin groups were treated orally by extract solvent, 200 mg kg-1 leaf extract, 200 mg kg-1 peel extract and 5 IU kg-1 of subcutaneous neutral protamine Hagedorn (NPH) insulin, respectively. Four weeks later, blood was collected for biochemical analysis and pancreases were removed for ?-cells counts in histological sections. Diabetes leads to increase of fast blood sugar (FBS) and HbA1c, and decrease of ?-cell number and insulin. FBS decreased only in leaf extract group. HbA1c decreased in leaf extract and insulin groups. The ?-cells number increased in leaf and peel extract groups. Insulin increased moderately in all treatment groups. We showed the proliferative properties of leaves and peel of Juglans regia L. methanolic extract in STZ- induced diabetic rats, which was accompanied by hypoglycemic effect of leaf extract. PMID:25653767

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

    PubMed Central

    2010-01-01

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

  5. Short-term bioaccumulation of vanadium when ingested with a tea decoction in streptozotocin-induced diabetic rats.

    PubMed

    Edel, Andrea L; Kopilas, Melanie; Clark, Tod A; Aguilar, Floribeth; Ganguly, Pallub K; Heyliger, Clayton E; Pierce, Grant N

    2006-02-01

    Sodium orthovanadate suspended in a lichee black tea decoction effectively regulates blood glucose levels in rats with insulin-dependent, streptozotocin (STZ)-induced diabetes. The primary advantage of vanadate delivery with the tea decoction over conventional systems that use water suspensions of vanadate is a significant reduction in the toxic side effects of vanadate. It is unknown if the tea alters the bioavailability of vanadate. Male Sprague-Dawley rats were administered an intravenous injection of STZ to induce diabetes. Four days later, the diabetic rats were treated by oral gavage with 40 mg of Na-orthovanadate suspended in double-distilled, deionized water (V/H2O), tea/vanadate (TV) decoction, or were treated with the tea decoction alone. Vanadium concentrations were measured in blood and various tissues at 1 to 24 hours posttreatment using graphite furnace atomic absorption spectrophotometry. With the exception of bone, maximal vanadium concentration in plasma and tissue samples were observed 2 hours after ingestion, but steadily decreased after that. Plasma vanadium levels continued to decrease until 16 hours. In contrast, vanadium steadily accumulated in bone over the 24-hour period. Overall, rats treated with V/H2O contained similar or significantly higher concentrations of vanadium in all tissues compared with TV treatment. The pattern of vanadium accumulation was also similar over time in both treatment groups. Vanadium levels were highest in bone > kidney > liver > pancreas > lung > heart > muscle > brain in both TV- and V/H2O-treated animals. This study demonstrates that the accumulation of vanadium in diabetic rats is reduced when coadministered with a black tea decoction in comparison to administration of vanadium in water. However, this effect is unlikely to be of a magnitude to explain the full capacity of TV to reduce the toxic side effects of vanadate. PMID:16423636

  6. (4-Hydroxypyridine-2,6-dicarboxylato)oxovanadate(V)—a new insulin-like compound: chemistry, effects on myoblast and yeast cell growth and effects on hyperglycemia in rats with STZ-induced diabetes

    Microsoft Academic Search

    Debbie C. Crans; Luqin Yang; Josephine A. Alfano; Lai-Har Chi; Wenzheng Jin; Mohammad Mahroof-Tahir; Karen Robbins; Masoud M. Toloue; Leong K. Chan; Andrew J. Plante; Rebecca Z. Grayson; Gail R. Willsky

    2003-01-01

    A new insulin mimetic vanadium(V) complex is introduced: (4-hydroxypyridine-2,6-dicarboxylato)oxovanadate(V). The compound was designed based on the desire to make a compound with more favorable chemical and insulin-enhancing properties than the parent (pyridine-2,6-dicarboxylato)oxovanadate(V). The solution chemistry was characterized and the complex was found to be more stable at neutral pH and to have a different lability pattern than the parent complex.

  7. Curcumin ameliorates macrophage infiltration by inhibiting NF-?B activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy

    Microsoft Academic Search

    Vivian Soetikno; Flori R Sari; Punniyakoti T Veeraveedu; Rajarajan A Thandavarayan; Meilei Harima; Vijayakumar Sukumaran; Arun Prasath Lakshmanan; Kenji Suzuki; Hiroshi Kawachi; Kenichi Watanabe

    2011-01-01

    Background  Chronic inflammation plays an important role in the progression of diabetic nephropathy (DN) and that the infiltration of\\u000a macrophages in glomerulus has been implicated in the development of glomerular injury. We hypothesized that the plant polyphenolic\\u000a compound curcumin, which is known to exert potent anti-inflammatory effect, would ameliorate macrophage infiltration in streptozotocin\\u000a (STZ)-induced diabetic rats.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Diabetes was induced with STZ

  8. Synthesis, characterization and anti-diabetic therapeutic potential of a new benzyl acid-derivatized kojic acid vanadyl complex.

    PubMed

    Wei, Yong-Biao; Yang, Xiao-Da

    2012-12-01

    Vanadium complexes are potent hypoglycemic agents and of great potential for therapeutical treatment of diabetes. In the present work, a novel vanadium compound, bis ((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl benzoatato) oxovanadium (IV) (BBOV) has been synthesized. Treatment of STZ-induced diabetic rats with BBOV restored the blood glucose to normal level and ameliorated glucose tolerance. The hypoglycemic effect of BBOV is similar to that of bis (maltolato) oxovanadium but is less toxic in median lethal dose. Overall, the present work will provide useful information for further development of new anti-diabetic vanadium compounds. PMID:23015214

  9. Functional and Molecular Characterization of Hyposensitive Underactive Bladder Tissue and Urine in Streptozotocin-Induced Diabetic Rat

    PubMed Central

    Chuang, Yao-Chi; Lee, Wei-Chia; Yoshimura, Naoki; Huang, Chao-Cheng; Rajaganapathy, Bharathi; Chancellor, Michael B.

    2014-01-01

    Background The functional and molecular alterations of nerve growth factor (NGF) and Prostaglandin E2 (PGE2) and its receptors were studied in bladder and urine in streptozotocin (STZ)-induced diabetic rats. Methodology/Principal Findings Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p) in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI) and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP)1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12. Conclusions/Significance DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder. PMID:25050870

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Kim, Young-Giun; Lim, Hyung-Ho; Lee, Suh-Ha; Shin, Mal-Soon; Kim, Chang-Ju; Yang, Hyeon Jeong

    2015-08-01

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

  13. Upregulation of insulin secretion and downregulation of pro-inflammatory cytokines, oxidative stress and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats by Pseuduvaria monticola bark extract.

    PubMed

    Taha, Hairin; Arya, Aditya; Paydar, Mohammadjavad; Looi, Chung Yeng; Wong, Won Fen; Vasudeva Murthy, C R; Noordin, M I; Ali, Hapipah Mohd; Mustafa, A M; Hadi, A Hamid A

    2014-04-01

    The current study aimed to ascertain the antidiabetic potential of Pseuduvaria monticola bark methanolic extract (PMm) using in vitro mechanistic study models. In particular, the study determined the effect of PMm on cellular viability, 2-NBDG glucose uptake, insulin secretion, and NF-?B translocation in mouse pancreatic insulinoma cells (NIT-1). Furthermore, in vivo acute toxicity and antidiabetic studies were performed using streptozotocin (STZ)-induced type 1 and STZ-nicotinamide-induced type 2 diabetic rat models to evaluate various biochemical parameters and markers of oxidative stress and pro-inflammatory cytokines. Five isoquinoline alkaloids and three phenolic compounds were tentatively identified in the PMm by LC/MS Triple TOF. The study results showed that PMm is non-toxic to NIT-1 cells and significantly increased the glucose uptake and insulin secretion without affecting the translocation of NF-?B. Moreover, the non-toxic effects of PMm were confirmed through an in vivo acute toxicity study, which revealed that the serum insulin and C-peptide levels were significantly upregulated in type 2 diabetic rats and that no significant changes were observed in type 1 diabetic rats. Similarly, PMm was found to downregulate the levels of oxidative stress and pro-inflammatory cytokines in type 2 diabetic rats by alleviating hyperglycemia. Therefore, we conclude that PMm may be developed as an antidiabetic agent for the treatment of type 2 diabetes-associated conditions. PMID:24518542

  14. Streptozotocin-Induced Early Thermal Hyperalgesia is independent of Glycemic State of Rats: Role of Transient Receptor Potential Vanilloid 1(TRPV1) and Inflammatory mediators

    PubMed Central

    2011-01-01

    Background Streptozotocin (STZ) is used as a common tool to induce diabetes and to study diabetes-induced complications including diabetic peripheral neuropathy (DPN). Previously, we have reported that STZ induces a direct effect on neurons through expression and function of the Transient receptor potential vanilloid 1 (TRPV1) channel in sensory neurons resulting in thermal hyperalgesia, even in non-diabetic STZ-treated mice. In the present study, we investigated the role of expression and function of TRPV1 in the central sensory nerve terminals in the spinal cord in STZ-induced hyperalgesia in rats. Results We found that a proportion of STZ-treated rats were normoglycemic but still exhibited thermal hyperalgesia and mechanical allodynia. Immunohistochemical data show that STZ treatment, irrespective of glycemic state of the animal, caused microglial activation and increased expression of TRPV1 in spinal dorsal horn. Further, there was a significant increase in the levels of pro-inflammatory mediators (IL-1?, IL-6 and TNF-?) in spinal cord tissue, irrespective of the glycemic state. Capsaicin-stimulated release of calcitonin gene related peptide (CGRP) was significantly higher in the spinal cord of STZ-treated animals. Intrathecal administration of resiniferatoxin (RTX), a potent TRPV1 agonist, significantly attenuated STZ-induced thermal hyperalgesia, but not mechanical allodynia. RTX treatment also prevented the increase in TRPV1-mediated neuropeptide release in the spinal cord tissue. Conclusions From these results, it is concluded that TRPV1 is an integral component of initiating and maintaining inflammatory thermal hyperalgesia, which can be alleviated by intrathecal administration of RTX. Further, the results suggest that enhanced expression and inflammation-induced sensitization of TRPV1 at the spinal cord may play a role in central sensitization in STZ-induced neuropathy. PMID:21794120

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

    PubMed

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

    2014-04-15

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

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

    PubMed Central

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

    2015-01-01

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

  17. Type 2 diabetes-induced cardiovascular complications: comparative evaluation of spironolactone, atenolol, metoprolol, ramipril and perindopril.

    PubMed

    Patel, Bhoomika M; Bhadada, Shraddha V

    2014-01-01

    The present study was carried out to study the effect of spironolactone, atenolol, metoprolol, ramipril and perindopril on cardiovascular complications in neonatal model of diabetes in rats, induced by administering 90?mg/kg streptozotocin (STZ), i.p. in 2-day-old rats. Our data suggest that spironolactone, metoprolol and perindopril prevent not only the STZ-induced metabolic abnormalities but also cardiovascular complications as evident from the reduction in cholesterol, triglyceride and decrease in cardiac hypertrophy which are the initial symptoms of congestive heart failure. Metoprolol and perindopril appears to be beneficial agents as compared to atenolol and ramipril. PMID:24047125

  18. The effects of acarbose and Rumex patientia on liver ultrastructure in streptozotocin-induced diabetic (type II) rats.

    PubMed

    Degirmenci, I; Kalender, S; Ustuner, M C; Kalender, Y; Gunes, H V; Unal, N; Basaran, A

    2002-01-01

    The aim of this study was to investigate the effects of acarbose and Rumex patientia on liver ultrastructure in streptozotocin (STZ)-induced diabetic (type II) rats. Forty-two-day-old, neonatal Wistar albino rats were used. They were divided into six groups. STZ was injected into groups 4, 5 and 6 on postnatal day 2. Groups 1 and 5 received water, groups 2 and 6 received 2% decoction of R. patientia grain and groups 3 and 4 received 40 mg acarbose/100 g feed. During the experimental period, blood glucose levels were checked periodically and HbA1c levels were measured from cardiac blood at the end of the experiment. In addition, liver tissue was examined by electron microscopy. Our results showed that glucose and HbA1c levels, which are increased by STZ, were decreased by acarbose and R. patientia. In group 5, most of the mitochondria of hepatocytes were swollen and some hepatocytes contained lipid granules in their cytoplasm. In group 4, no pathological changes were observed in hepatocytes, but some lysosomes were found in their cytoplasms. In group 6, mitochondrial changes were minimal compared with those in group 5, and no lipid granules were observed in hepatocytes. PMID:12776576

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

    SciTech Connect

    Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting, E-mail: BTZhu@kumc.ed

    2010-11-15

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

  20. Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress.

    PubMed

    Comelli, Francesca; Bettoni, Isabella; Colleoni, Mariapia; Giagnoni, Gabriella; Costa, Barbara

    2009-12-01

    Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain. Repeated treatment with cannabis extract significantly relieved mechanical allodynia and restored the physiological thermal pain perception in streptozotocin (STZ)-induced diabetic rats without affecting hyperglycemia. In addition, the results showed that eCBD increased the reduced glutathione (GSH) content in the liver leading to a restoration of the defence mechanism and significantly decreased the liver lipid peroxidation suggesting that eCBD provides protection against oxidative damage in STZ-induced diabetes that also strongly contributes to the development of neuropathy. Finally, the nerve growth factor content in the sciatic nerve of diabetic rats was restored to normal following the repeated treatment with eCBD, suggesting that the extract was able to prevent the nerve damage caused by the reduced support of this neurotrophin. These findings highlighted the beneficial effects of cannabis extract treatment in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and a specific action upon nerve growth factor. PMID:19441010

  1. Effect of N-acetylcysteine on the early expression of inflammatory markers in the retina and plasma of diabetic rats

    PubMed Central

    Tsai, Gina Y; Cui, Jing Z; Syed, Husnain; Xia, Zhengyuan; Ozerdem, Ugur; McNeill, John H; Matsubara, Joanne A

    2014-01-01

    Purpose The aim of this study is to investigate markers of inflammation and oxidative stress in an early model of diabetic retinopathy, correlate retinal and plasma results and evaluate the influence of treatment by N-acetylcysteine (NAC), a free radical scavenger. Methods Four groups were studied: control (C), streptozotocin (STZ)-induced diabetic rats (D), STZ rats following 8 weeks of NAC (DT), and control rats following 8 weeks of NAC (CT). Plasma levels of free 15-F2t-isoprostane (15-F-2t-IsoP), superoxide dismutase (SOD) and tumour necrosis factor-alpha (TNF-?) were obtained. Primary antibodies against macrophages (ED-1), microglia (Ox-42), pericytes (NG-2), endothelial and perivascular cells (IB-4), haem oxygenase 1 (HO-1) and vascular endothelial growth factor (VEGF) were used. Results Expression of NG-2 was robust in C, CT, DT, and mild in D. The intensity of IB-4 was higher in D and DT compared with the C and CT. Ox-42 and ED-1 expression was higher in the D than in the DT, C or CT. Expression of VEGF and HO-1 was non-specific across the four groups. Plasma levels of 15-F-2t-IsoP and TNF-? were higher in the D as compared with the C, CT and DT. SOD levels were lower in the D when compared with the C, CT and D. Conclusions Macrophage/microglia activation, pericyte loss and endothelial/perivascular cell changes occur early in the pathogenesis of DR. These changes are associated with an increase in plasma markers of oxidative stress and inflammation and are minimized by treatment with NAC. The results suggest that therapies that reduce free radicals will help minimize the early events in diabetic retinopathy in the STZ model. PMID:19723131

  2. Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier Through Differential Regulation of VEGF-A and Its Receptors in Early Diabetic Rat Retinas

    PubMed Central

    Zhang, Xinyuan; Bao, Shisan; Lai, Donna; Rapkins, Robert W.; Gillies, Mark C.

    2008-01-01

    OBJECTIVE To elucidate the mechanism of the unique beneficial effect of intravitreal steroid therapy on diabetic macular edema, we investigated the effect of locally administered triamcinolone acetonide (TA) on the expression of vascular endothelial growth factor (VEGF)-A and its receptors in retinas of rats with streptozotocin (STZ)-induced diabetes. We then correlated the expression of these proteins with breakdown of the blood-retinal barrier (BRB). RESEARCH DESIGN AND METHODS Thirty-two eyes of 16 diabetic and nondiabetic rats were divided into four groups. TA was injected into the vitreous of the right eye, and saline was injected into the left eye (control) 3.5 weeks after induction of diabetes. Retinas were harvested 48 h following treatment. mRNA and protein expression of VEGF-A, VEGF-A receptor 1 (fms-like tyrosine kinase [FLT]-1), and VEGF-A receptor 2 (fetal liver kinase [FLK]-1) were determined by real-time RT-PCR and immunohistochemistry. BRB permeability was quantitated by measuring extravasated endogenous albumin and retinal thickness. RESULTS Diabetes-induced retinal thickness and albumin extravasation were significantly reduced in TA-treated diabetic retinas to a level similar to that in sham-treated nondiabetic eyes. A close correlation between albumin leakage and increased expression of both Vegf-a and Flk-1 was noted in the diabetic retinas. TA downregulated the expression of Vegf-a and Flk-1 but upregulated the expression of Flt-1. TA did not alter the expression of these genes in nondiabetic retinas. CONCLUSIONS Intravitreal injection of TA stabilizes the BRB in association with regulation of Vegf-a, Flk-1, and Flt-1 expression in retinas in the early stages of diabetes. PMID:18174522

  3. Effective control of blood glucose status and toxicity in streptozotocin-induced diabetic rats by orally administration of vanadate in an herbal decoction.

    PubMed

    Zhang, L; Zhang, Y; Xia, Q; Zhao, X M; Cai, H X; Li, D W; Yang, X D; Wang, K; Xia, Z L

    2008-09-01

    Vanadium compounds have been well recognized for hypoglycemic effects, but questions remain on gastrointestinal disturbance and possible tissue vanadium accumulation thus slowing the acceptance of vanadium compounds as diabetic therapeutic agents. Our intestinal permeability and toxicity studies of vanadium compounds have suggested that the co-administration of vanadate with Salvia miltiorrhiza Bunge decoction could benefit the therapeutic use of hypoglycemic vanadium compounds. In the present paper, we tested the hypoglycemic effects of vanadate ingested in an aqueous extract of S. Bunge using a streptozocin (STZ)-induced diabetic rat model. Oral administration of vanadate in S. Bunge herbal decoction produced a stable (free of hypoglycemic shock) and long-lasting ( approximately 70day) control of blood glucose status. Effective protection of animal organs from hyperglycemic damage was also observed. As expected, the herbal extract significantly alleviated vanadium toxicity, i.e. GI stress and metal accumulation. In addition, the result suggesting that vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of the pancreatic beta-cells which initially survived STZ-toxicity. These studies provide new insight into the therapeutic treatment of diabetics with vanadium compounds. PMID:18601969

  4. Choline-deprivation alters crucial brain enzyme activities in a rat model of diabetic encephalopathy.

    PubMed

    Liapi, Charis; Kyriakaki, Argyro; Zarros, Apostolos; Galanopoulou, Panagiota; Al-Humadi, Hussam; Dontas, Ismene; Voumvourakis, Konstantinos; Tsakiris, Stylianos

    2010-09-01

    Diabetic encephalopathy describes the moderate cognitive deficits, neurophysiological and structural central nervous system changes associated with untreated diabetes. It involves neurotoxic effects such as the generation of oxidative stress, the enhanced formation of advanced glycation end-products, as well as the disturbance of calcium homeostasis. Due to the direct connection of choline (Ch) with acetylcholine availability and signal transduction, a background of Ch-deficiency might be unfavorable for the pathology and subsequently for the treatment of several metabolic brain diseases, including that of diabetic encephalopathy. The aim of this study was to shed more light on the effects of adult-onset streptozotocin (STZ)-induced diabetes and/or Ch-deprivation on the activities of acetylcholinesterase (AChE) and two important adenosine triphosphatases, namely Na(+),K(+)-ATPase and Mg(2+)-ATPase. Male adult Wistar rats were divided into four main groups, as follows: control (C), diabetic (D), Ch-deprived (CD), and Ch-deprived diabetic (D+CD). Deprivation of Ch was provoked through the administration of Ch-deficient diet. Both the induction of diabetes and the beginning of dietary-mediated provoking of Ch-deprivation occurred at the same day, and rats were killed by decapitation after 30 days (1 month; groups C1, D1, CD1 and D1+CD1) and 60 days (2 months; groups C2, D2, CD2 and D2+CD2, respectively). The adult rat brain AChE activity was found to be significantly increased by both diabetes (+10%, p < 0.001 and +11%, p < 0.01) and Ch-deprivation (+19%, p < 0.001 and +14%, p < 0.001) when compared to the control group by the end of the first (C1) and the second month (C2), respectively. However, the Ch-deprived diabetic rats' brain AChE activity was significantly altered only after a 60-day period of exposure, resulting in a +27% increase (D2+CD2 vs. C2, p < 0.001). Although the only significant change recorded in the brain Na(+),K(+)-ATPase activity after the end of the first month is attributed to Ch-deprivation (+21%, p < 0.05, CD1 vs. C1), all groups of the second month exhibited a statistically significant decrease in brain Na(+),K(+)-ATPase activity (-24%, p < 0.01, D2 vs. C2; -21%, p < 0.01, CD2 vs. C2; -22%, p < 0.01, D2+CD2 vs. C2). As concerns Mg(2+)-ATPase, the enzyme's activity demonstrates no significant changes, with the sole exception of the D2+CD2 group (+21%, p < 0.05, D2+CD2 vs. C2). In addition, statistically significant time-dependent changes concerning the brain Mg(2+)-ATPase activity were recorded within the diabetic (p < 0.05, D2 vs. D1) and the Ch-deprived (p < 0.05, CD2 vs. CD1) rat groups. Our data indicate that Ch-deprivation seems to be an undesirable background for the above-mentioned enzymatic activities under untreated diabetes, in a time-evolving way. Further studies on the issue should focus on a region-specific reevaluation of these crucial enzymes' activities as well as on the possible oxidative mechanisms involved. PMID:20838865

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

    SciTech Connect

    Luo Zhifeng [Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Feng Bing, E-mail: fxb12@yahoo.com.c [Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Mu Jiao; Qi Wei; Zeng Wei; Guo Yanhong; Pang Qi; Ye Zilin; Liu Li; Yuan Fahuan [Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China)

    2010-07-15

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

  6. 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.

  7. Arginine metabolism in enterocytes of diabetic rats 

    E-print Network

    Morrow, Natalie Anne

    2002-01-01

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

  8. Nrf2 and NF-?B modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes.

    PubMed

    Negi, Geeta; Kumar, Ashutosh; Sharma, Shyam S

    2011-11-01

    High glucose driven reactive oxygen intermediates production and inflammatory damage are recognized contributors of nerve dysfunction and subsequent damage in diabetic neuropathy. Sulforaphane, a known chemotherapeutic agent holds a promise for diabetic neuropathy because of its dual antioxidant and anti-inflammatory activities. The present study investigated the effect of sulforaphane in streptozotocin (STZ) induced diabetic neuropathy in rats. For in vitro experiments neuro2a cells were incubated with sulforaphane in the presence of normal (5.5 mM) and high glucose (30 mM). For in vivo studies, sulforaphane (0.5 and 1 mg/kg) was administered six weeks post diabetes induction for two weeks. Motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and pain behavior were improved and malondialdehyde (MDA) level was reduced by sulforaphane. Antioxidant effect of sulforaphane is derived from nuclear erythroid 2-related factor 2 (Nrf2) activation as demonstrated by increased expression of Nrf2 and downstream targets hemeoxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1) in neuro2a cells and sciatic nerve of diabetic animals. Nuclear factor-kappa B (NF-?B) inhibition seemed to be responsible for antiinflammatory activity of sulforaphane as there was reduction in NF-?B expression and I?B kinase (IKK) phosphorylation along with abrogation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and tumor necrosis factor-? (TNF-?) and interleukine-6 (IL-6) levels. Here in this study we provide an evidence that sulforaphane is effective in reversing the various deficits in experimental diabetic neuropathy. This study supports the defensive role of Nrf2 in neurons under conditions of oxidative stress and also suggests that the NF-?B pathway is an important modulator of inflammatory damage in diabetic neuropathy. PMID:22023613

  9. Paeoniflorin Prevents Diabetic Nephropathy in Rats

    PubMed Central

    Fu, Jianfang; Li, Yuan; Wang, Li; Gao, Bin; Zhang, Nanyan; Ji, Qiuhe

    2009-01-01

    The aim of this study was to test the hypothesis that paeoniflorin prevents the progression of diabetic nephropathy by modulating the inflammatory process. Sprague–Dawley rats were divided into 5 groups: nondiabetic control rats; untreated diabetic model (DM) rats; and DM rats treated with 5, 10, or 20 mg/kg paeoniflorin in drinking water once daily. Rats received a single intravenous injection of streptozotocin to induce diabetes; 9 wk after injection, rats began the 8-wk daily paeoniflorin treatment regimen. Compared with that of nonDM controls, the urinary albumin:creatinine ratio was increased significantly in untreated DM rats; this ratio was decreased in DM rats treated with 5, 10, or 20 mg/kg paeoniflorin compared with that of untreated DM rats. In addition, paeoniflorin treatment effectively suppressed glomerular hypertrophy; blood glucose; the expression of transforming growth factor ?, type IV collagen, and intercellular adhesion molecule 1; and renal infiltration of macrophages compared with levels in untreated DM rats. Furthermore, renal nuclear factor ?B activity was increased in untreated but not paeoniflorin-treated DM rats. In conclusion, our data suggest that the preventive effects of paeoniflorin may be mediated by its antiinflammatory actions. PMID:20034431

  10. A new salicylic acid-derivatized kojic acid vanadyl complex: synthesis, characterization and anti-diabetic therapeutic potential.

    PubMed

    Wei, Yongbiao; Zhang, Chengyue; Zhao, Pan; Yang, Xiaoda; Wang, Kui

    2011-08-01

    The molecular mechanisms of vanadium toxicity suggest that incorporation of antioxidant groups in the structure of vanadium complexes could be a preferable strategy in designing novel hypoglycemic vanadium complexes with proper efficacy and safety. By conjugating a pyrone skeleton to provide a coordination group and antioxidative motifs, we synthesized a novel complex of bis ((5-hydroxy-4-oxo-4H-pyran-2-yl) methyl 2-hydroxy- benzoatato) oxovanadium (IV) (BSOV). Evaluation of the anti-diabetic effects of BSOV using streptozotocin (STZ)-induced diabetic rats with bis (maltolato) oxovanadium (BMOV) as a positive control showed that BSOV effectively lowered blood glucose level, ameliorated damages of hepatic and renal function in diabetic rats and improved lipid metabolism. The signs of potential alteration of renal function caused by BSOV and BMOV were observed and are discussed. Overall, the experimental results suggest BSOV as a potent hypoglycemic agent and further studies using this strategy for anti-diabetic agents. PMID:21726771

  11. N-Acetylcysteine and Allopurinol Confer Synergy in Attenuating Myocardial Ischemia Injury via Restoring HIF-1?/HO-1 Signaling in Diabetic Rats

    PubMed Central

    Mao, Xiaowen; Wang, Tingting; Liu, Yanan; Irwin, Michael G.; Ou, Jing-song; Liao, Xiao-long; Gao, Xia; Xu, Yuan; Ng, Kwok F. J.; Vanhoutte, Paul M.; Xia, Zhengyuan

    2013-01-01

    Objectives To determine whether or not the antioxidants N-acetylcysteine (NAC) and allopurinol (ALP) confer synergistic cardioprotection against myocardial ischemia/reperfusion (MI/R) injury by stabilizing hypoxia inducible factor 1? (HIF-1?)/heme oxygenase 1 (HO-1) signaling in diabetic myocardium. Methods Control or diabetic [streptozotocin (STZ)-induced] Sprague Dawley rats received vehicle or NAC, ALP or their combination for four weeks starting one week after STZ injection. The animals were then subjected to thirty minutes of coronary artery occlusion followed by two hours reperfusion in the absence or presence of the selective HO-1 inhibitor, tin protoporphyrin-IX (SnPP-IX) or the HIF-1? inhibitor 2-Methoxyestradiol (2ME2). Cardiomyocytes exposed to high glucose were subjected to hypoxia/re-oxygenation in the presence or absence of HIF-1? and HO-1 achieved by gene knock-down with related siRNAs. Results Myocardial and plasma levels of 15-F2t-isoprostane, an index of oxidative stress, were significantly increased in diabetic rats while cardiac HO-1 protein and activity were reduced; this was accompanied with reduced cardiac protein levels of HIF-1?, and increased post-ischemic myocardial infarct size and cellular injury. NAC and ALP given alone and in particular their combination normalized cardiac levels of HO-1 and HIF-1? protein expression and prevented the increase in 15-F2t-isoprostane, resulting in significantly attenuated post-ischemic myocardial infarction. NAC and ALP also attenuated high glucose-induced post-hypoxic cardiomyocyte death in vitro. However, all the above protective effects of NAC and ALP were cancelled either by inhibition of HO-1 or HIF-1? with SnPP-IX and 2ME2 in vivo or by HO-1 or HIF-1? gene knock-down in vitro. Conclusion NAC and ALP confer synergistic cardioprotection in diabetes via restoration of cardiac HIF-1? and HO-1 signaling. PMID:23874823

  12. Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii rat

    Microsoft Academic Search

    H. Yamada; E. Yamada; A. Higuchi; M. Matsumura

    2005-01-01

    Aims\\/hypothesis  The spontaneously diabetic Torii (SDT) rat has recently been established as a model of type 2 human diabetes mellitus. Male SDT rats develop severe diabetic ocular complications. This study investigated the nature of the ocular complications in this model and addressed the question of whether the SDT rat is a good model of human proliferative diabetic retinopathy.Methods  Male SDT rats aged

  13. Spatio-Temporal Expression and Functional Involvement of Transient Receptor Potential Vanilloid 1 in Diabetic Mechanical Allodynia in Rats

    PubMed Central

    Wu, Huang-Hui; Qi, Jian; Shi, Juan; Li, Yun-Qing

    2014-01-01

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

  14. 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

  15. Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes

    PubMed Central

    Yamaleyeva, Liliya M.; Gilliam-Davis, Shea; Almeida, Igor; Brosnihan, K. Bridget; Lindsey, Sarah H.

    2012-01-01

    We examined the impact of early diabetes on the circulating and kidney renin-angiotensin system (RAS) in male and female mRen2.Lewis (mRen2) hypertensive rats. Diabetes (DB) was induced by streptozotocin (STZ; 65 mg/kg) at 11 wk of age for 4 wk without insulin replacement. Systolic blood pressures were not increased in DB males or females compared with controls (CON). Circulating angiotensin-converting enzyme 2 (ACE2) increased ninefold (P < 0.05) in DB females and threefold (P < 0.05) in DB males, but circulating ACE and ANG II were higher in the DB groups. Serum C-reactive protein was elevated in DB females but not DB males, and the vascular responses to acetylcholine and estradiol were attenuated in the DB females. Proteinuria, albuminuria, and angiotensinogen excretion increased to a similar extent in both DB females and males. Glomerular VEGF expression also increased to a similar extent in both DB groups. Renal inflammation (CD68+cells) increased only in DB females although males exhibited greater inflammation that was not different with DB. Cortical ACE2 did not change in DB females but was reduced (30%) in DB males. Renal neprilysin activity (>75%, P < 0.05) was markedly reduced in the DB females to that in the DB and CON males. ACE activity was significantly lower in both female (75%, P < 0.05) and male (50%; P < 0.05) DB groups, while cortical ANG II and Ang-(1-7) levels were unchanged. In conclusion, female mRen2 rats are not protected from vascular damage, renal inflammation, and kidney injury in early STZ-induced diabetes despite a marked increase in circulating ACE2 and significantly reduced ACE within the kidney. PMID:22378820

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

    PubMed

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

    2015-10-01

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

  17. Arginine metabolism in enterocytes of diabetic rats

    E-print Network

    Morrow, Natalie Anne

    2002-01-01

    , and diabetic plus insulin-treated rats. Cells were incubated at 37°C in the presence of 2 mM arginine, 2 mM glutamine, or 2 mM proline plus 2 mM glutamine. Amino acids were quantified by high-performance liquid chromatography. The results indicated...

  18. Anti-diabetic molecules from Cycas pectinata Griff. traditionally used by the Maiba-Maibi.

    PubMed

    Laishram, S; Sheikh, Y; Moirangthem, D S; Deb, L; Pal, B C; Talukdar, N C; Borah, J C

    2015-01-15

    Bioactivity guided chemical investigation on active anti-diabetic constituents of the fruits of Cycas pectinata Griff. (FCP) characterized EAFr-5 as the most potent sub fraction which significantly reduced the blood glucose level to normal in STZ induced diabetic rats. It was shown to contain the biflavonoids amentoflavone (1) and 2,3-dihydroamentoflavone (2) which exhibited significantly high inhibitory potency against ?-glucosidase (IC50 8.09 ± 0.023 and 9.77 ± 0.032 ?M, respectively) and ?-amylase (IC50 73.6 ± 0.48 and 39.69 ± 0.39 ?M, respectively). This is the first report of bioactivity guided isolation of anti-diabetic constituents from the traditionally used fruits of Cycas pectinata Griff. PMID:25636866

  19. The effects of vanadium treatment on bone in diabetic and non-diabetic rats.

    PubMed

    Facchini, D M; Yuen, V G; Battell, M L; McNeill, J H; Grynpas, M D

    2006-03-01

    Vanadium-based drugs lower glucose by enhancing the effects of insulin. Oral vanadium drugs are being tested for the treatment of diabetes. Vanadium accumulates in bone, though it is not known if incorporated vanadium affects bone quality. Nine- to 12-month-old control and streptozotocin-induced diabetic female Wistar rats were given bis(ethylmaltolato)oxovanadium(IV) (BEOV), a vanadium-based anti-diabetic drug, in drinking water for 12 weeks. Non-diabetic rats received 0, 0.25 or 0.75 mg/ml BEOV. Groups of diabetic rats were either untreated or treated with 0.25-0.75 mg/ml BEOV as necessary to lower blood glucose in each rat. In diabetic rats, this resulted in a Controlled Glucose group, simulating relatively well-managed diabetes, and an Uncontrolled Glucose group, simulating poorly managed diabetes. Plasma insulin, glucose and triglyceride assays assessed the diabetic state. Bone mineral density (BMD), mechanical testing, mineral assessment and histomorphometry measured the effects of diabetes on bone and the effects of BEOV on non-diabetic and diabetic bone. Diabetes decreased plasma insulin and increased plasma glucose and triglycerides. In bone, diabetes decreased BMD, strength, mineralization, bone crystal length, and bone volume and connectivity. Treatment was effective in incorporating vanadium into bone. In all treated groups, BEOV increased osteoid volume. In non-diabetic bone, BEOV increased cortical bone toughness, mineralization and bone formation. In controlled glucose rats, BEOV lowered plasma glucose and improved BMD, mechanical strength, mineralization, bone crystal length and bone formation rate. In poorly controlled rats, BEOV treatment slightly lowered plasma glucose but did not improve bone properties. These results suggest that BEOV improves diabetes-related bone dysfunction primarily by improving the diabetic state. BEOV also appeared to increase bone formation. Our study found no negative effects of vanadium accumulation in bone in either diabetic or non-diabetic rats at the dose given. PMID:16256449

  20. Rat Models of Type 1 Diabetes: Genetics, Environment, and Autoimmunity

    Microsoft Academic Search

    John P. Mordes; Rita Bortell; Elizabeth P. Blankenhorn; Aldo A. Rossini; Dale L. Greiner

    For many years, the vast amount of data gathered from analysis of nonobese diabetic (NOD) and congenic NOD mice has eclipsed interest in the rat for the study of type 1 diabetes. The study of rat models has continued, however, and recently there has been a reanimation of interest for several reasons. First, genetic analysis of the rat has accel-

  1. Appropriateness of the Zucker Diabetic Fatty rat as a model for diabetic microvascular late complications.

    PubMed

    Hempe, J; Elvert, R; Schmidts, H-L; Kramer, W; Herling, A W

    2012-01-01

    Male obese Zucker Diabetic Fatty (ZDF) rats develop type 2 diabetes around eight weeks of age, and are widely used as a model for human diabetes and its complications. The objective of the study was to test whether the complications manifested in the kidney and nerves of ZDF rats really correspond to human diabetic complications in their being related to the hyperglycaemic state. Four groups of ZDF rats were used. One lean (Fa/?) and one obese (fa/fa) untreated group served as non-diabetic and diabetic controls. In two further groups of obese (fa/fa) rats, diabetes was prevented by pioglitazone or delayed by food restriction. All rats were monitored up to 35 weeks of age with respect to their blood glucose, HbA1c and insulin levels, their kidney function (urinary glucose excretion, renal glucose filtration, glomerular filtration rate, albumin/creatinine ratio), and their nerve function (tactile and thermal sensory threshold and nerve conduction velocity). Pioglitazone prevented the development of diabetes, while food restriction delayed its onset for 8-10 weeks. Accordingly, kidney function parameters were similar to lean non-diabetic rats in pioglitazone-treated rats and significantly improved in food-restricted rats compared with obese controls. Kidney histology paralleled the functional results. By contrast, nerve functional evaluations did not mirror the differing blood glucose levels. We conclude that the ZDF rat is a good model for diabetic nephropathy, while alterations in nerve functions were not diabetes-related. PMID:22087029

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

    PubMed Central

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

    2013-01-01

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

  3. Therapeutic Potential of Nrf2 Activators in Streptozotocin-Induced Diabetic Nephropathy

    E-print Network

    Wong, Pak Kin

    Therapeutic Potential of Nrf2 Activators in Streptozotocin-Induced Diabetic Nephropathy Hongting of streptozotocin (STZ)-induced diabetic nephropathy. RESEARCH DESIGN AND METHODS--Diabetes was induced in Nrf2). Markers of diabetes including blood glucose, insulin, polydipsia, polyuria, and weight loss were mea

  4. Adoptive Transfer of Autoimmune Diabetes and Thyroiditis to Athymic Rats

    Microsoft Academic Search

    Una McKeever; John P. Mordes; Dale L. Greiner; Michael C. Appel; Jan Rozing; Eugene S. Handler; Aldo A. Rossini

    1990-01-01

    We describe the induction of autoimmune diabetes, insulitis, and thyroiditis in athymic rats following injections of major histocompatibility complex compatible spleen cells. Lymphocytes with these capabilities were found in normal rats of the YOS, WAG, PVG, and diabetes-resistant BB strains, and in diabetes-prone BB rats. Adoptive transfer was facilitated by prior in vivo depletion of RT6.1^+ regulatory T cells and

  5. Melatonin improves spatial navigation memory in male diabetic rats

    PubMed Central

    Babaei-Balderlou, Farrin; Zare, Samad

    2012-01-01

    The aim of the present study was to evaluate the effect of melatonin as an antioxidant on spatial navigation memory in male diabetic rats. Thirty-two male white Wistar rats weighing 200 ± 20 g were divided into four groups, randomly: control, melatonin, diabetic and melatonin-treated diabetic. Experimental diabetes was induced by intraperitoneal injection of 50 mg kg-1 streptozotocin. Melatonin was injected (10 mg kg-1 day-1, ip) for 2 weeks after 21 days of diabetes induction. At the end of administration period, the spatial navigation memory of rats was evaluated by cross-arm maze. In this study lipid peroxidation levels, glutathione-peroxidase and catalase activities were measured in hippocampus. Diabetes caused to significant decrease in alternation percent in the cross-arm maze, as a spatial memory index, compared to the control group (p < 0.05), whereas administration of melatonin prevented the spatial memory deficit in diabetic rats. Also melatonin injection significantly increased the spatial memory in intact animals compared to the control group (p < 0.05). Assessment of hippocampus homogenates indicated an increase in lipid peroxidation levels and a decrease in GSH-Px and CAT activities in the diabetic group compared to the control animals, while melatonin administration ameliorated these indices in diabetic rats. In conclusion, diabetes induction leads to debilitation of spatial navigation memory in rats, and the melatonin treatment improves the memory presumably through the reduction of oxidative stress in hippocampus of diabetic rats. PMID:25610567

  6. 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

  7. Boldine prevents renal alterations in diabetic rats.

    PubMed

    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

  8. Vanadyl sulfate protects against streptozotocin-induced morphological and biochemical changes in rat aorta.

    PubMed

    Akgün-Dar, Kadriye; Bolkent, Sehnaz; Yanardag, Refiye; Tunali, Sevim

    2007-01-01

    The aim of this study was to investigate the protective effects of vanadyl sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats, morphologically and biochemically. The animals were made diabetic by an intraperitoneal injection of streptozotocin (65 mg/kg) and vanadyl sulfate (100 mg/kg) that was given every day for 60 days by gavage technique to rats. Under the light and transmission electron microscopes, hypertrophy of the vessel wall, focal disruption in the elastic lamellae, an increase in thickness of total aortic wall, tunica intima, subendothelial space and adventitial layer, and a disorganization in smooth muscular cells of the tunica media were observed in diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly increased and the aorta glutathione (GSH) levels were significantly reduced in STZ diabetic rats. In diabetic rats administered vanadyl sulfate for 60 days, aorta LPO levels significantly decreased and the aorta GSH level significantly increased. In conclusion, in vivo treatment with vanadyl sulfate of diabetic rats prevented the morphological and biochemical changes observed in thoracic aorta of diabetic animals. PMID:16892454

  9. Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema.

    PubMed

    Inoue, Takayuki; Morita, Masataka; Tojo, Takashi; Yoshihara, Kousei; Nagashima, Akira; Moritomo, Ayako; Ohkubo, Mitsuru; Miyake, Hiroshi

    2013-03-01

    Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema. In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC(50) of 230 nM; rat IC(50) of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats. PMID:23337801

  10. Antihyperglycaemic effect of 'Ilogen-Excel', an ayurvedic herbal formulation in streptozotocin-induced diabetes mellitus.

    PubMed

    Umamaheswari, Selvaraj; Mainzen Prince, Ponnaian Stanely

    2007-01-01

    'Ilogen-Excel', an Ayurvedic herbal formulation is composed of eight medicinal plants (Curcuma longa, Strychnos potatorum, Salacia oblonga, Tinospora cordifolia, Vetivelia zizanioides, Coscinium fenestratum, Andrographis paniculata and Mimosa pudica). The present study evaluates the antihyperglycemic effect of 'Ilogen-Excel' in streptozotocin induced diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg/kg body weight). Oral administration of 'Ilogen-Excel' (50 mg/kg and 100 mg/kg) for 60 days resulted in significantly lowered levels of blood glucose and significantly increased levels of plasma insulin, hepatic glycogen and total hemoglobin. 'Ilogen-Excel' administration also decreased the levels of glycosylated hemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and vitamin E in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of 'Ilogen-Excel'. Administration of insulin normalized all the biochemical parameters studied in diabetic rats. The effect at a dose of 100 mg/kg was more pronounced than 50 mg/kg and brought back all the parameters to near normal levels. Thus, our study shows the antihyperglycemic effects of 'Ilogen-Excel' in STZ-induced diabetic rats. Our study also shows that combined therapy is better than individual therapy. PMID:17665851

  11. Sodium selenate corrects glucose tolerance and heart function in STZ diabetic rats

    Microsoft Academic Search

    Mary L. Battell; Heather L. M. Delgatty; John H. McNeill

    1998-01-01

    Sodium selenate, administered intraperitoneally (i.p.), resulted in an improvement in glucose tolerance in treated diabetic rats. Fed rat plasma glucose levels were reduced by selenate treatment in streptozotocin diabetic rats. The lowest values of blood glucose were reached within 3 weeks of beginning the treatment. Food and fluid consumption was reduced in treated compared to untreated diabetic rats. Diabetic treated

  12. Metallothionein metabolism in the streptozotocin-diabetic rat

    SciTech Connect

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

    1986-03-05

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

  13. Amelioration of diabetic dyslipidemia by macrocyclic binuclear oxovanadium complex on streptozotocin induced diabetic rats

    Microsoft Academic Search

    Balasubramanian Ramachandran; Sorimuthu Subramanian

    2005-01-01

    Diabetic dyslipidemia, the main causative factor for the progression of vascular complications in diabetes, is caused due to hyperglycemia and excess mobilisation of fatty acids. Recently we have reported on a novel macrocyclic binuclear oxovanadium (MBOV) complex synthesized by us with significant hypoglycemic efficacy and without any apparent toxicity on streptozotocin induced diabetic rats. In the present study, streptozotocin induced

  14. Cannabinoid functions in the amygdala contribute to conditioned fear memory in streptozotocin-induced diabetic mice: Interaction with glutamatergic functions.

    PubMed

    Ikeda, Hiroko; Ikegami, Megumi; Kai, Misa; Kamei, Junzo

    2015-07-01

    The role of cannabinoid systems in conditioned fear memory was investigated in streptozotocin (STZ)-induced diabetic mice. The cannabinoid receptor agonist WIN-55,212-2 (1mg/kg, i.p.), when injected into normal mice after conditioning, significantly prolonged the duration of freezing behavior. This effect was significantly inhibited by the cannabinoid CB1 receptor antagonist AM 251 (3mg/kg, s.c.), but not by the cannabinoid CB2 receptor antagonist AM 630 (1mg/kg, s.c.). The duration of freezing in STZ-induced diabetic mice was significantly longer than that in non-diabetic mice. The injection of WIN-55,212-2 (1mg/kg, i.p.) after conditioning significantly prolonged the duration of freezing in non-diabetic mice, but not in STZ-induced diabetic mice. In contrast, the injection of AM 251 (3mg/kg, s.c.) after conditioning significantly shortened the duration of freezing in STZ-induced diabetic mice, but not in non-diabetic mice. The injection of AM 251 (3mg/kg, s.c.) before conditioning or before testing did not significantly affect the duration of freezing in STZ-induced diabetic mice. The protein levels of cannabinoid CB1 receptors in the amygdala were increased in STZ-induced diabetic mice. In contrast, the protein levels of cannabinoid CB2 receptors and diacylglycerol lipase ?, the enzyme that synthesizes endocannabinoid 2-arachidonoylglycerol, in the amygdala did not differ between non-diabetic and STZ-induced diabetic mice. None of these proteins in the hippocampus was different between non-diabetic and STZ-induced diabetic mice. The injection of AM 251 (50ng/side) into the basolateral amygdala significantly inhibited the duration of freezing in STZ-induced diabetic mice. Since endocannabinoid is controlled by glutamatergic function, we further examined the role of glutamatergic function in the increased fear memory in STZ-induced diabetic mice. The amounts of glutamine and glutamic acid in the amygdala of STZ-induced diabetic mice were significantly increased compared to those in non-diabetic mice. The AMPA receptor antagonist NBQX (40ng/side), when injected into the basolateral amygdala, significantly inhibited the duration of freezing in STZ-induced diabetic mice. Finally, AMPA (40ng, i.c.v.) significantly prolonged the duration of freezing in normal mice, and this effect was inhibited by AM 251 (3mg/kg, s.c.). These results suggest that cannabinoid functions in the amygdala are increased in diabetic mice and that enhanced glutamatergic function in the amygdala of diabetic mice activates the endocannabinoid system, which enhances fear memory via cannabinoid CB1 receptors. PMID:25929688

  15. 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

  16. Intestinal absorption of cephalexin in diabetes mellitus model rats.

    PubMed

    Watanabe, Kazuhiro; Terada, Kazuaya; Sato, Juichi

    2003-06-01

    We investigated the intestinal absorption and pharmacokinetics of cephalexin, as well as the intestinal H+/oligopeptide transporter PEPT1 mRNA and protein levels in type 1 and type 2 diabetic rats. Cephalexin disappearance from the duodenum loop was significantly lower in streptozotocin-induced type 1 diabetic rats and higher in hyperinsulinemic type 2 diabetic GK and Zucker-fa/fa (Zucker) rats, than in control rats. These results were speculated to be due to the enhancement of intestinal absorption of cephalexin in GK and Zucker rats. Intestinal PEPT1 mRNA levels were not significantly different between control and diabetic rats; however, the brush-border membrane vesicle PEPT1 protein levels were increased in GK and Zucker rats. After oral administration of cephalexin, plasma cephalexin concentrations and pharmacokinetic parameters, area under the concentration versus time curve from 0 to infinity, AUC(0-->infinity), and maximum plasma concentration, Cmax, in GK and Zucker rats were markedly higher than in control rats. From these findings, it is considered that intestinal absorption of drugs mediated by PEPT1 may be enhanced in hyperinsulinemic type 2 diabetes mellitus rats. PMID:12791410

  17. [Simvastatin'S effect on insulin resistance in rats with diabetes mellitus].

    PubMed

    Iskakova, S; Zharmakhanova, G; Bekmukhambetov, Y; Dworacka, M; Dworacki, G

    2015-05-01

    The aim of this experimental study was to estimate the effect of Simvastatin on glycemic variability-related insulin resistance in the course of diabetes mellitus (DM) in rats. Fifty seven male Wistar rats were divided into four groups: I - rats with diabetes mellitus and glycemic variability treated with Simvastatin (20 mg/kg body weight, intragastral during 8 weeks); II - placebo-treated rats with DM and glycemic variability; III - placebo treated rats with DM and IV - nondiabetic control rats. DM was induced by feeding rats with high-fat diet (61%) during five weeks and low-dose of Streptozotocin (30 mg/kg, intraperitoneally). Daily glucose excursions were stimulated by feeding animals twice a day. We measured fasting blood glucose, glycated hemoglobin (HbA1c), insulin and HOMAIR was calculated. Higher insulin resistance in diabetic rats is related to greater daily glycemic variability. In our study was installed significant increasing HOMAIR in diabetics rats with glycemic excursions comparison with the control. Our results showed that the simvastatin-treatment decreases the indices glycemic variability and HOMA in diabetic rats with glycemic excursions. PMID:26042451

  18. Reduced beta 2 glycoprotein I improves diabetic nephropathy via inhibiting TGF-?1-p38 MAPK pathway

    PubMed Central

    Wang, Tong; Chen, Si-Si; Chen, Rui; Yu, De-Min; Yu, Pei

    2015-01-01

    Purpose: Beta 2 glycoprotein I (?2GPI) has been shown the positive effect on diabetic atherosclerosis and retinal neovascularization. ?2GPI can be reduced by thioredoxin-1, resulting in the reduced state of ?2GPI. The possible protective effects of ?2GPI and reduced ?2GPI on diabetic nephropathy (DN) are not fully elucidated. The purpose of this study was to test a hypothesis that ?2GPI and reduced ?2GPI would improve DN in streptozotocin (STZ) induced diabetic mice and high-glucose (HG) exposed rat mesangial cell (RMC). Methods: The STZ-induced Balb/c mice and HG exposed RMCs were administrated with ?2-GPI and reduced ?2-GPI at different time and concentrations gradient respectively. The changes of glomerular structure and expression of collagen IV, TGF-?1, p38 MAPK and phospho-p38 MAPK in renal cortical and mesangial cells were observed by immunohistochemical techniques, quantitative real-time PCR and western blot with or without the treatment of ?2-GPI and reduced ?2-GPI. Results: ?2GPI and reduced ?2GPI improved early clinical and pathological changes of DN in STZ-diabetic mice. Treatment with ?2GPI and reduced ?2GPI in the STZ-diabetic mice and HG exposed RMCs resulted in decrease expression levels of TGF-?1 and collagen IV, with concomitant decrease in phospho-p38 MAPK expression. Conclusions: ?2GPI and reduced ?2GPI improved renal structural damage and kidney function. The renoprotective and antifibrosis effects of ?2GPI and reduced ?2GPI on DN were closely associated with suppressing the activation of the TGF-?1-p38 MAPK pathway.

  19. Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats.

    PubMed Central

    Ramesh, B.; Pugalendi, K. V.

    2005-01-01

    The aim of the study was to evaluate blood glucose and lipid lowering effects of Umbelliferone (UMB) in streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180 to 200 g) were induced diabetes by administration of STZ (40 mg/kg) intraperitonially. Normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had increased plasma glucose and decreased insulin, total proteins (TP), and albumin in addition to decreased food intake and body weight. Elevation in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL), and reduction in high density lipoprotein cholesterol (HDL-C) in the plasma were observed. Liver and kidney tissues of diabetic rats had elevation in the levels of TC, TG, FFA, and PL. Treatment with UMB decreased plasma glucose and increased insulin, TP, and albumin apart from food intake and body weight. In UMB-treated diabetic rats, plasma and tissue TC, TG, PL and FFA, and plasma LDL-C, VLDL-C, and HDL-C reversed to near normal. Thus, reduction of blood glucose and lipid profiles indicates that UMB has antidiabetic and antihyperlipidemic effects in diabetic rats. PMID:16720013

  20. Basal ganglia calcification in BB/E rats with diabetes.

    PubMed

    Lammie, G A; Kelly, P A T; Baird, J D; Smith, W; Chatterjee, S; Frier, B M; Strachan, M W J

    2005-01-01

    Human diabetes is associated with cognitive impairment and structural abnormalities in the brain such as cerebral atrophy. The aetiology of these abnormalities is not known. The BB/E rat is a well-established model of type 1 (insulin dependent) diabetes. A cohort of 34 BB/E rats with diabetes was divided into three sub-groups according to age (and duration of diabetes). Basal ganglia calcification (BGC) was present in the brains of more than 50% of diabetic animals, but not in any of 37 non-diabetic BB/E rats. BGC occurred more commonly in those animals which had the longest duration of diabetes (p=0.001), such that BGC was present in only 8% of animals with diabetes for 20 weeks, but in 100% of animals with diabetes for 60 weeks. There were no other significant light microscopic neuropathologic changes in diabetic animals. It will be important to investigate the mechanism of brain calcification, whether a similar process occurs in humans with diabetes, and its possible relationship to cognitive decline. PMID:15639413

  1. The anti-diabetic effects and pharmacokinetic profiles of bis(maltolato)oxovanadium in non-diabetic and diabetic rats.

    PubMed

    Zhang, Shuang-Qing; Zhong, Xu-Ying; Chen, Guo-Hua; Lu, Wan-Liang; Zhang, Qiang

    2008-01-01

    The purpose of this study was to evaluate the anti-diabetic effects and pharmacokinetics of bis(maltolato)oxovanadium (BMOV) in rats. The anti-diabetic study was carried out in non-diabetic and diabetic rats by single-dose subcutaneous and intragastric administration. Pharmacokinetic investigation was performed using non-diabetic rats. Results showed that BMOV significantly decreased plasma glucose levels in diabetic rats at all given doses, and restored hyperglycaemic values to normal values after subcutaneous injections at doses of 4 and 8 mg vanadium (V)/kg or after intragastric administration at doses of 14 and 28 mgV/kg, respectively, but did not affect the plasma glucose level in non-diabetic rats. BMOV could be rapidly absorbed, slowly eliminated from plasma, widely distributed in various tissues and accumulated to a greater extent in the femur tissue. The average absolute bioavailability for intragastric administration at a single dose of 3, 6 and 12 mgV/kg was 28.1%, 33.7% and 21.4%, respectively. The presence of the peak vanadium level in the plasma was not coincident with that of the maximum effect of lowering plasma glucose levels. In conclusion, at the present dosing levels and administration routes, BMOV was effective in lowering plasma glucose levels in diabetic rats. BMOV has a promising outlook as an oral glucose-lowering drug. PMID:18088510

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

    PubMed

    Vasudevan, Harish; McNeill, John H

    2007-04-01

    Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 +/- 2 gm) compared to controls (482 +/- 3 gm). Body weight was further reduced by cobalt treatment (290 +/- 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 +/- 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 +/- 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose. PMID:16802070

  3. Antihyperglycemic activity of Momordica cymbalaria in alloxan diabetic rats.

    PubMed

    Rao, B K; Kesavulu, M M; Apparao, C

    2001-11-01

    Aqueous, ethanolic and hexane fractions of Momordica cymbalaria fruits were prepared and given individually at different doses to different batches of rats (both normal and alloxan diabetic rats) after an overnight fast. The blood glucose levels were measured at 0, 1, 3, 5 and 7 h after the treatment. The aqueous extract of Momordica cymbalaria at a dosage of 0.5 g/kg b.w. is showing maximal blood glucose lowering effect in diabetic rats. The same dosage did not produce any hypoglycemic activity in normal rats. The antihyperglycemic activity of Momordica cymbalaria fruit was compared with the treatment of Glibenclamide, an oral hypoglycemic agent. PMID:11585690

  4. Camel milk attenuates the biochemical and morphological features of diabetic nephropathy: inhibition of Smad1 and collagen type IV synthesis.

    PubMed

    Korish, Aida A; Abdel Gader, Abdel Galil; Korashy, Hesham M; Al-Drees, Abdul Majeed; Alhaider, Abdulqader A; Arafah, Maha M

    2015-03-01

    Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM) that worsens its morbidity and mortality. There is evidence that camel milk (CM) improves the glycemic control in DM but its effect on the renal complications especially the DN remains unclear. Thus the current study aimed to characterize the effects of CM treatment on streptozotocin (STZ)-induced DN. Using STZ-induced diabetes, we investigated the effect of CM treatment on kidney function, proteinuria, renal Smad1, collagen type IV (Col4), blood glucose, insulin resistance (IR), lipid peroxidation, the antioxidant superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH). In addition renal morphology was also examined. The current results showed that rats with untreated diabetes exhibited marked hyperglycemia, IR, high serum urea and creatinine levels, excessive proteinuria, increased renal Smad1 and Col4, glomerular expansion, and extracellular matrix deposition. There was also increased lipid peroxidation products, decreased antioxidant enzyme activity and GSH levels. Camel milk treatment decreased blood glucose, IR, and lipid peroxidation. Superoxide dismutase and CAT expression, CAT activity, and GSH levels were increased. The renoprotective effects of CM were demonstrated by the decreased serum urea and creatinine, proteinuria, Smad1, Col4, and preserved normal tubulo-glomerular morphology. In conclusion, beside its hypoglycemic action, CM attenuates the early changes of DN, decreased renal Smad1 and Col4. This could be attributed to a primary action on the glomerular mesangial cells, or secondarily to the hypoglycemic and antioxidant effects of CM. The protective effects of CM against DN support its use as an adjuvant anti-diabetes therapy. PMID:25617480

  5. Somatostatin and diabetic retinopathy: current concepts and new therapeutic perspectives.

    PubMed

    Hernández, Cristina; Simó-Servat, Olga; Simó, Rafael

    2014-06-01

    Somatostatin (SST) is abundantly produced by the human retina, and the main source is the retinal pigment epithelium (RPE). SST exerts relevant functions in the retina (neuromodulation, angiostatic, and anti-permeability actions) by interacting with SST receptors (SSTR) that are also expressed in the retina. In the diabetic retina, a downregulation of SST production does exist. In this article, we give an overview of the mechanisms by which this deficit of SST participates in the main pathogenic mechanisms involved in diabetic retinopathy (DR): neurodegeneration, neovascularization, and vascular leakage. In view of the relevant SST functions in the retina and the reduction of SST production in the diabetic eye, SST replacement has been proposed as a new target for treatment of DR. This could be implemented by intravitreous injections of SST analogs or gene therapy, but this is an aggressive route for the early stages of DR. Since topical administration of SST has been effective in preventing retinal neurodegeneration in STZ-induced diabetic rats, it seems reasonable to test this new approach in humans. In this regard, the results of the ongoing clinical trial EUROCONDOR will provide useful information. In conclusion, SST is a natural neuroprotective and antiangiogenic factor synthesized by the retina which is downregulated in the diabetic eye and, therefore, its replacement seems a rational approach for treating DR. However, clinical trials will be needed to establish the exact position of targeting SST in the treatment of this disabling complication of diabetes. PMID:24627166

  6. [Treatment of diabetes in experimental animals by metallocomplexes].

    PubMed

    Sakurai, Hiromu

    2008-03-01

    The number of patients suffered from diabetes mellitus has increased over the decades probably because of both lifestyle- and diet-changes. There are two types of diabetes mellitus. Type 1 diabetes mellitus is due to the autoimmune-mediated destruction of pancreatic B cells, which results in absolute insulin deficiency, thus the patients require insulin injections. Type 2 diabetes mellitus is due to the insulin resistance and abnormal insulin secretion, thus the patients require exercise, diet control and/or oral hypoglycemic medicines. Each treatment, however, has some problems involving physical and mental burden, and formation of self-antibodies for insulin injections, and the severe side effects and discontinuation of insulin synthesis in the pancreas for hypoglycemic medicines. To overcome these important problems and find the replacements for the insulin injections and synthetic medicines, we attempted to develop new antidiabetic metallocomplexes with novel structures and mechanisms. In 1990, we first presented orally active vanadyl (+4 oxidation state of oxo-vanadium) complexes including vanadyl-cysteine methyl ester complex, which normalized hyperglycemia in the streptozocin (STZ)-induced type 1 diabetic rats. Based on these findings, we have developed a wide variety of vanadyl complexes with different coordination environments around vanadyl ion. Following the study, we also challenged to develop orally active zinc complexes since 2002. This review focuses on our recent development of vanadyl and zinc complexes for anti-diabetic and anti-metabolic syndromes, together with the propose for the possible action mechanism of these complexes in adipocytes. PMID:18311049

  7. The effects of Syzygium aromaticum-derived oleanolic acid on kidney function of male Sprague-Dawley rats and on kidney and liver cell lines.

    PubMed

    Madlala, Hlengiwe P; Masola, Bubuya; Singh, Moganavelli; Musabayane, Cephas T

    2012-01-01

    Studies indicate that Syzygium spp-derived oleanolic acid (OA) enhances renal function of streptozotocin (STZ)-induced diabetic rats as evidenced by its reversal of the previously reported inability of the kidney to excrete Na(+) in these animals. We postulated that OA influences Na(+) excretion in the proximal tubule, the site where two-thirds of filtered NaCl is reabsorbed through a process mediated by transport proteins. Therefore, the study investigated the effects of OA on proximal tubular Na(+) handling in male Sprague-Dawley rats using renal lithium clearance (C(Li)). Renal C(Li) has been used widely in animal and clinical studies to assess proximal tubular function. Sub-chronic doses of OA were administered to rats twice every third day for 5 weeks. Rats treated with deionized water served as control animals. Cytotoxicity of OA on kidney and liver cell lines was assessed by the MTT and comet assays. OA increased Na(+) excretion of conscious male Sprague-Dawley rats from week 3 to week 5. By the end of the 5-week experimental period, OA treatment significantly reduced (p < 0.05) plasma creatinine concentration of STZ-induced diabetic rats with a concomitant elevation in glomerular filtration rate (GFR). Acute OA infusion was also associated with increases in fractional excretion of sodium (FE(Na)) and lithium (FE(Li)) in anesthetized rats in the absence of significant changes in GFR. The MTT assay studies demonstrated that OA increased the metabolic activity of kidney and liver cell lines. Taken together with previous observations, this study implicates the proximal tubule in OA-evoked increases in urinary Na(+) output. PMID:22512664

  8. Antidiabetic effect of alcoholic extract of Caralluma sinaica L. on streptozotocin-induced diabetic rabbits

    Microsoft Academic Search

    Mohammed Habibuddin; Hassan Ali Daghriri; Touseef Humaira; Mohammed Saeed Al Qahtani; Ali Al Hasan Hefzi

    2008-01-01

    People of Asir region of Saudi Arabia chew Caralluma sinaica (CS) to lower glucose level. To establish its utility in diabetes mellitus we have under taken this study. The effect of CS on streptozotocin (STZ)-induced diabetic model as well as effect on oral glucose tolerance test were studied. The extract was shown to have positive test for possessing following chemical

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

    PubMed

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

    2014-05-01

    The present study was designed to investigate the effect of vanadium in alloxan-induced diabetes and cataract in rats. Different doses of vanadium was administered once daily for 8 weeks to alloxan-induced diabetic rats. To know the mechanism of action of vanadium, lens malondialdehyde (MDA), protein carbonyl content, activity of superoxide dismutase (SOD), activities of aldose reductase (AR), and sorbitol levels were assayed, respectively. Supplementation of vanadium to alloxan-induced diabetic rats decreased the blood glucose levels due to hyperglycemia, inhibited the AR activity, and delayed cataract progression in a dose-dependent manner. The observed beneficial effects may be attributed to polyol pathway activation but not decreased oxidative stress. Overall, the results of this study demonstrate that vanadium could effectively reduce the alloxan-induced hyperglycemia and diabetic cataracts in rats. PMID:24604151

  10. Insulin treatment prevents diabetes mellitus but not thyroiditis in RT6-depleted diabetes resistant BB\\/Wor rats

    Microsoft Academic Search

    P. A. Gottlieb; E. S. Handler; M. C. Appel; D. L. Greiner; J. P. Mordes; A. A. Rossini

    1991-01-01

    Summary  Prophylactic insulin administration is known to prevent hyperglycaemia in diabetes prone BB rats and non-obese diabetic mice. This study investigated the effect of insulin treatment on the development of overt diabetes, clinically inapparent anti-islet autoreactivity, and thyroiditis in RT6-depleted diabetes resistant BB rats. Fewer than 1% of these animals develop spontaneous diabetes, but if depleted of RT6+ T cells >50%

  11. A new diabetic strain of rat (WBN\\/Kob)

    Microsoft Academic Search

    M. Tsuchitani; T. Saegusa; I. Narama; T. Nishikawa; T. Gonda

    1985-01-01

    Summary A new, spontaneously occurring diabetic syndrome has been observed in the aged males of an inbred strain of Wistar rats, WBN\\/Kob. The main clinical sign, glycosuria, was first detected at about 60 weeks of age, and thereafter some animals developed hyperlipidaemia and gradual emaciation. Prior to the onset of glucosuria, male rats showed impaired glucose tolerance after a glucose

  12. Protective effect of herbomineral formulation (Dolabi) on early diabetic nephropathy in streptozotocin-induced diabetic rats.

    PubMed

    Baig, Mirza A; Gawali, Vikas B; Patil, Rajesh R; Naik, Suresh R

    2012-07-01

    The effect of a herbomineral formulation (HMF) on early diabetic nephropathy was investigated. Diabetes was induced in Wistar rats by administering streptozotocin (55 mg/kg, intraperitoneally). The occurrence of early diabetic nephropathy in rats was revealed by high plasma glucose and depleted liver glycogen, decreased glucose uptake by peripheral tissue, impaired renal function, increased antioxidants and lipid peroxidation in kidney. These changes were accompanied by elevated malondialdehyde, glutathione and superoxide dismutase activity in kidney. Furthermore, increased total urine volume, urinary albumin excretion rate, urinary albumin to creatinine ratio, increased relative kidney weight, decreased glomerular filtration rate (GFR) and urinary creatinine were also observed in diabetic nephropathy rats. HMF treatment significantly lowered blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen, triglycerides, total cholesterol, serum albumin level, total urine volume, urinary albumin excretion rate, urinary albumin to creatinine ratio and relative kidney weight, and increased urinary creatinine and GFR. Altered levels of antioxidants, viz. lipid peroxidation, glutathione and superoxide dismutase (SOD), in kidney of diabetic nephropathy rats were restored. Histopathological findings indicated dense mesangial matrix in the glomeruli of diabetic nephropathy rats, which may be due to over-activation of matrix metalloproteinases and was reduced following HMF treatment. Our experimental findings clearly demonstrate that HMF has an ability to prevent the progression of early diabetic nephropathy. Such protective effect of HMF might be due to the presence of flavonoids (catechin, quercetin, rutin) and triterpene saponins (oleanolic acid and gymnemic acid) which are known to possess potent antioxidant properties. PMID:22116744

  13. Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats

    Microsoft Academic Search

    Lina Åkesson; Johan Trygg; Jessica M. Fuller; Rasmus Madsen; Jon Gabrielsson; Stephen Bruce; Hans Stenlund; Terry Tupling; Ranae Pefley; Torbjörn Lundstedt; Åke Lernmark; Thomas Moritz

    The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period\\u000a of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing\\u000a the serum metabolite profile detected with combined gas chromatography\\/mass spectrometry (GC\\/MS) and liquid chromatography\\/mass\\u000a spectrometry (LC\\/MS). We found that the

  14. The effects of vanadium treatment on bone in diabetic and non-diabetic rats

    Microsoft Academic Search

    D. M. Facchini; V. G. Yuen; M. L. Battell; J. H. McNeill; M. D. Grynpas

    2006-01-01

    Vanadium-based drugs lower glucose by enhancing the effects of insulin. Oral vanadium drugs are being tested for the treatment of diabetes. Vanadium accumulates in bone, though it is not known if incorporated vanadium affects bone quality. Nine- to 12-month-old control and streptozotocin-induced diabetic female Wistar rats were given bis(ethylmaltolato)oxovanadium(IV) (BEOV), a vanadium-based anti-diabetic drug, in drinking water for 12 weeks.

  15. Extracellular HSP70 levels in diabetic environment in rats.

    PubMed

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

    2015-07-01

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

  16. The effect of dietary Cu and diabetes on indices of Cu nutriture in the rat

    SciTech Connect

    Rucker, R.B.; Uriu-Hare, J.Y.; Tinker, D.; Keen, C.L. (Univ. of California, Davis (United States))

    1991-03-11

    The uptake-retention of 67Cu is affected by dietary Cu and diabetes. Consequently, the functional activities of select enzymes and tissue Cu status were assessed. STZ-diabetic and control rats were fed Cu suppl. or def. diets. Rats were gavaged with 28 {mu}Ci 67Cu, and killed 8, 16, 24, 32, 64, or 128 h later. Diabetic rats were hyperphagic, hyperglycemic and hypoinsulinemic; with no effect of diet. Plasma ceruloplasmin activity (Cp) was lower in Cu def. rats; diabetic rats tended to have higher Cp than controls. Cu def. rats had low Cu levels in liver, kidney and plasma. Cu suppl. diabetic rats had higher liver and kidney Cu compared to Cu def. diabetic rats. Gel chromatography of liver showed that with time, there was a transfer of 67Cu from low to higher MW ligands. In nondiabetic rats, more 67Cu was associated with the higher MW ligands. The converse was observed for diabetic rats. There was no effect of diabetes on liver 67Cu localization. Diabetic rats had higher metallothionein (MT) concentrations in liver and kidney compared to controls Cu deficiency lowered MT values in both diabetic and control rats. CuZn SOD Cu activity was lowered with Cu def. and diabetes, while Mn SOD activity was similar among groups. Plasma lipid peroxide levels were lower in diabetic rats than controls. The results show that Cu metabolism is affected in diabetes, and the changes are functionally significant.

  17. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    PubMed Central

    Okamura, Tadashi; Pei, Xiang Yuan; Miyoshi, Ichiro; Shimizu, Yukiko; Takanashi-Yanobu, Rieko; Mototani, Yasumasa; Kanai, Takao; Satoh, Jo; Kimura, Noriko; Kasai, Noriyuki

    2013-01-01

    Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6?months of age and 86% at 14?months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300?mg/dl at 120?min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of ?-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus. PMID:23691528

  18. Effects of combined neutral endopeptidase 24-11 and angiotensin-converting enzyme inhibition on femoral vascular conductance in streptozotocin-induced diabetic rats

    PubMed Central

    Arbin, V; Claperon, N; Fournié-Zaluski, M -C; Roques, B P; Peyroux, J

    2000-01-01

    The successive effects of the angiotensin-converting enzyme inhibitor captopril (CAP, 2?mg?kg?1+1?mg?kg?1 30?min?1 infusion) and the neutral endopeptidase 24-11 inhibitor retrothiorphan (RT, 25?mg?kg?1+12.5?mg?kg?1 30?min?1 infusion) were studied on femoral vascular conductance (FVC) in streptozotocin-induced diabetic (STZ-SD) and control Sprague-Dawley (C-SD) rats. The role of the kinin-nitric oxide (NO) pathway was assessed by (1) using pre-treatments: a bradykinin (BK) B2 receptor antagonist (Hoe-140, 300??g?kg?1), a NO-synthase inhibitor (N?-nitro-L-arginine methyl ester, L-NAME, 10?mg?kg?1), a kininase I inhibitor (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, MGTA, 10?mg?kg?1+20?mg?kg?1 20?min?1 infusion) and (2) comparing the effects in STZ-induced diabetic (STZ-BN) and control Brown-Norway kininogen-deficient (C-BN) rats.In C-SDs, CAP and CAP+RT increased FVC similarly. In STZ-SDs, FVC and FBF were decreased compared to C-SDs. CAP+RT increased them more effectively than CAP alone.In both C-SDs and STZ-SDs, the femoral bed vasodilatation elicited by CAP was inhibited by Hoe-140 and L-NAME. The FVC increase elicited by CAP+RT was not significantly reduced by Hoe-140 but was inhibited by L-NAME and Hoe-140+MGTA.In C-BNs, the vasodilatator responses to CAP and CAP+RT were abolished and highly reduced, respectively. In STZ-BNs, these responses were abolished.These results show that in STZ-SDs, CAP+RT improve FBF and FVC more effectively than CAP alone. These effects are linked to an increased activation of the kinin-NO pathway. BK could lead to NO production by BK B2 receptor activation and another pathway in which kininase I may be involved. PMID:10903969

  19. Inhibition of diabetic-cataract by vitamin K1 involves modulation of hyperglycemia-induced alterations to lens calcium homeostasis.

    PubMed

    Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, Ramar

    2014-11-01

    This study investigated the potential of vitamin K1 against streptozotocin-induced diabetic cataract in Wistar rats. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, accumulation of sorbitol and formation of advanced glycation end product (AGE) in eye lens. Hyperglycemia in lens also resulted in superoxide anion and hydroxyl radical generation and less reduced glutathione suggesting oxidative stress in lens. Hyperglycemia also resulted in increase in lens Ca2+ and significant inhibition of lens Ca2+ ATPase activity. These changes were associated with cataract formation in diabetic animals. By contrast treatment of diabetic rats with vitamin K1 (5 mg/kg, sc, twice a week) resulted in animals with partially elevated blood glucose and with transparent lenses having normal levels of sorbitol, AGE, Ca2+ ATPase, Ca2+, and oxidative stress. Vitamin K 1 may function to protect against cataract formation in the STZ induced diabetic rat by affecting the homeostasis of blood glucose and minimizing subsequent oxidative and osmotic stress. Thus, these results show that Vitamin K1 inhibits diabetic-cataract by modulating lens Ca2+ homeostasis and its hypoglycemic effect through its direct action on the pancreas. PMID:25257692

  20. Ghrelin reverses experimental diabetic neuropathy in mice

    SciTech Connect

    Kyoraku, Itaru; Shiomi, Kazutaka [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)] [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan)] [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Nakazato, Masamitsu, E-mail: nakazato@med.miyazaki-u.ac.jp [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)] [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)

    2009-11-20

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  1. Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity

    SciTech Connect

    Sawant, Sharmilee P. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Sugar Hall 306, Monroe, LA 71209-0470 (United States); Dnyanmote, Ankur V. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Sugar Hall 306, Monroe, LA 71209-0470 (United States); Warbritton, Alan [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Latendresse, John R. [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Mehendale, Harihara M. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Sugar Hall 306, Monroe, LA 71209-0470 (United States)]. 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.

  2. Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus

    Microsoft Academic Search

    Irina C. Chis; Marius I. Ungureanu; Adriana Marton; Ramona Simedrea; Adriana Muresan; Ion-Dan Postescu; Nicoleta Decea

    2009-01-01

    In the present study we investigated the anti-hyperglycaemic and antioxidant effect of grape seed extract, a polyphenolic flavonoid, in normal and streptozotocin-induced diabetic Wistar rats. Adult male Wistar rats were divided into three groups: Group I: non-diabetic control; Group II: diabetic control; Group III: diabetic rats treated with grape seed extract, administered via an intragastric tube (0.6 ml\\/rat), at a

  3. Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus

    Microsoft Academic Search

    Irina C. Chis; Marius I. Ungureanu; Adriana Marton; Ramona Simedrea; Adriana Muresan; Ion-Dan Postescu; Nicoleta Decea

    2010-01-01

    In the present study we investigated the anti-hyperglycaemic and antioxidant effect of grape seed extract, a polyphenolic flavonoid, in normal and streptozotocin-induced diabetic Wistar rats. Adult male Wistar rats were divided into three groups: Group I: non-diabetic control; Group II: diabetic control; Group III: diabetic rats treated with grape seed extract, administered via an intragastric tube (0.6 ml\\/rat), at a

  4. Muscle glutamine production in diabetic ketoacidotic rats.

    PubMed Central

    Goldstein, L; Perlman, D F; McLaughlin, P M; King, P A; Cha, C J

    1983-01-01

    The mechanism of activation of glutamine production by the hindlimb during diabetic ketoacidosis (DKA) was investigated in rats. Muscle glutamine production was estimated to account for over 90% of the total glutamine produced by the hindlimb. DKA produced significant increases in the concentrations of NH4+ and IMP in hindlimb muscles, suggesting that AMP deaminase is activated by DKA. NH4Cl- and HCl-induced acidosis did not produce these changes, indicating either that acidosis itself is not the stimulus for increased AMP deaminase activity or that the more severe degree of acidosis accompanying DKA is necessary for activation. Muscle glutamine concentrations were depressed in DKA. Experiments with isolated epitrochlearis muscle showed that the transport and permeability properties of the muscle cells (as judged by uptake and release of alpha-aminoisobutyrate and glutamine) were not altered by DKA. However, glutamine uptake by muscle cells was significantly inhibited by L-leucine, the concentration of which, along with other branched-chain amino acids, is markedly elevated in DKA. PMID:6414461

  5. Acetylsalicylic acid protects erectile function in diabetic rats.

    PubMed

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

    2014-01-01

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

  6. Spironolactone improves endothelial dysfunction in streptozotocin-induced diabetic rats.

    PubMed

    Adel, Heba; Taye, Ashraf; Khalifa, Mohamed M A

    2014-12-01

    Endothelial dysfunction is a critical initiator for developing diabetic vascular complications. Substantial clinical and experimental evidence suggests that aldosterone plays a crucial role in its pathogenesis. The present study aimed to investigate the effect of the mineralocorticoid receptor (MR) blocker, spironolactone, on diabetes-associated endothelial dysfunction and address the underlying mechanism(s) involved in this setting. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) to rats and spironolactone was orally administered (50 mg/kg/day). Our results showed a marked increase in aortic malondialdehyde (MDA) level and upregulation of the catalytic NADPH oxidase subunit, NOX2 gene expression alongside reducing catalase enzyme capacity, and the serum nitric oxide (NO) bioavailability in diabetic rats. This was associated with a significant reduction in endothelial nitric oxide synthase (eNOS) immunoreactivity and gene expression in diabetic aorta. The transforming growth factor-? (TGF-?) protein and the MR gene expression levels were significantly increased in the diabetic rat aorta. Moreover, the diabetic aorta showed a marked impairment in acetylcholine-mediated endothelium-dependent relaxation. Additionally, spironolactone significantly inhibited the elevated MDA, TGF-?, NOX2, and MR levels alongside correcting the dysregulated eNOS expression and the defective antioxidant function as well as NO bioavailability. Spironolactone markedly reversed the impaired endothelial function in the diabetic aorta. Collectively, our study demonstrates that spironolactone ameliorated the vascular dysfunction of diabetic aorta, at least partially via its anti-inflammatory and anti-oxidative effects alongside correcting the dysregulated eNOS and TGF-? expression. Thus, blockade of MR may represent a useful therapeutic approach against diabetic vasculopathy. PMID:25238812

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

    PubMed Central

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

    2014-01-01

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

  8. Effect of bis[curcumino]oxovanadium complex on non-diabetic and streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Jayesh B. Majithiya; R. Balaraman; Rajani Giridhar; Mange Ram Yadav

    2005-01-01

    The effect of the vanadium complex bis[curcumino]oxovanadium (BCOV) on blood glucose level, serum lipid levels, blood pressure and vascular reactivity were studied in non-diabetic and streptozotocin-induced diabetic (STZ-diabetic) rats and compared to that of vanadyl sulfate. Blood glucose level, serum lipid levels, and blood pressure were significantly increased in STZ-diabetic rats. Vascular reactivity to various agonists such as noradrenaline and

  9. Pharmacodynamics and pharmacokinetics of the insulin-mimetic agent vanadyl acetylacetonate in non-diabetic and diabetic rats

    Microsoft Academic Search

    Shuang-Qing Zhang; Xu-Ying Zhong; Wan-Liang Lu; Li Zheng; Xuan Zhang; Feng Sun; Gui-Ying Fu; Qiang Zhang

    2005-01-01

    The objectives of this study were to evaluate the pharmacodynamics and pharmacokinetics of vanadyl acetylacetonate (VAC) in rats. Pharmacodynamic study was carried out using non-diabetic and diabetic rats by subcutaneous (s.c.) and intragastric (i.g.) administrations at single dose or multiple doses. Pharmacokinetic study was performed using non-diabetic rats. Results showed that VAC resulted in a significant decrease of plasma glucose

  10. 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.

  11. In vivo anti-diabetic, antioxidant and molecular docking studies of 1, 2, 8-trihydroxy-6-methoxy xanthone and 1, 2-dihydroxy-6-methoxyxanthone-8-O-?-D-xylopyranosyl isolated from Swertia corymbosa.

    PubMed

    Mahendran, G; Manoj, M; Murugesh, E; Sathish Kumar, R; Shanmughavel, P; Rajendra Prasad, K J; Narmatha Bai, V

    2014-09-25

    1, 2, 8-trihydroxy-6-methoxy xanthone (1) and 1, 2- dihydroxy-6-methoxyxanthone-8-O-?-d-xylopyranosyl (2) are the main constituents of petroleum ether and ethyl acetate extracts from Swertia corymbosa (Gentinaceae), a medicinal plant used in Indian traditional system for the treatment of diabetes. The present study was designed to examine the antihypoglycemic, antihyperlipidemic and antioxidant effect of compounds 1 and 2 in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (60 mg/kg b.w.). The isolated compounds 1 and 2 at a dose of 50 mg/kg b.w., produced the maximum fall of 83% in the blood glucose level in the diabetic rats after 3h of the treatment. The administration of 1 and 2 (50 mg/kgb.w.) daily for 28 days in STZ induced diabetic rats, resulted in a significant decrease in blood glucose, glycosylated hemoglobin, SGOT, SGPT, ALP serum urea and creatinine with significant rise in plasma insulin level. Test compounds 1 and 2 showed antihyperlipidemic activities as evidenced by significant decrease in serum TC, TG, LDL-C, VLDL-C levels coupled together with elevation of HDL-C level in diabetic treated rats when compared to diabetic untreated rats, indicate the protective role against liver and kidney damage. The results of histopathology also showed 1 and 2 protected tissues (pancreas, liver and kidney) against peroxidation damage and maintained tissue integrity. Further, the molecular interaction study of the ligands 1, 2 and glibenclamide with various diabetes mellitus related protein targets like glucokinase (PDB ID: 1V4S), fructose-1, 6-bisphosphatase 1 (PDB ID: 2JJK) 11-?-hydroxysteroid dehydrogenase (PDB ID: 2BEL) and modeled protein sulfonylurea receptor 1 (SUR1) showed that ligand 1 and 2 possess binding affinity with all protein targets except for 2BEL target protein for which ligand 1 has no interaction. The ligand pose with 2BEL and SUR1 protein target of ligand 2 gave the best binding conformation. Hence 1 and 2 can be considered for developing into a potent antidiabetic drug. PMID:25172785

  12. MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy.

    PubMed

    Li, X; Du, N; Zhang, Q; Li, J; Chen, X; Liu, X; Hu, Y; Qin, W; Shen, N; Xu, C; Fang, Z; Wei, Y; Wang, R; Du, Z; Zhang, Y; Lu, Y

    2014-01-01

    Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which can result in cardiac hypertrophy and subsequent heart failure, associated with pyroptosis, the pro-inflammatory programmed cell death. MicroRNAs (miRNAs), small endogenous non-coding RNAs, have been shown to be involved in diabetic cardiomyopathy. However, whether miRNAs regulate pyroptosis in diabetic cardiomyopathy remains unknown. Our study revealed that mir-30d expression was substantially increased in streptozotocin (STZ)-induced diabetic rats and in high-glucose-treated cardiomyocytes as well. Upregulation of mir-30d promoted cardiomyocyte pyroptosis in diabetic cardiomyopathy; conversely, knockdown of mir-30d attenuated it. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic property of mir-30d, we found that forced expression of mir-30d upregulated caspase-1 and pro-inflammatory cytokines IL-1? and IL-18. Moreover, mir-30d directly repressed foxo3a expression and its downstream protein, apoptosis repressor with caspase recruitment domain (ARC). Furthermore, silencing ARC by siRNA mimicked the action of mir-30d: upregulating caspase-1 and inducing pyroptosis. These findings promoted us to propose a new signaling pathway leading to cardiomyocyte pyroptosis under hyperglycemic conditions: mir-30d??foxo3a?? ARC??caspase-1??IL-1?, IL-18??pyroptosis?. Therefore, mir-30d may be a promising therapeutic target for the management of diabetic cardiomyopathy. PMID:25341033

  13. MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy

    PubMed Central

    Li, X; Du, N; Zhang, Q; Li, J; Chen, X; Liu, X; Hu, Y; Qin, W; Shen, N; Xu, C; Fang, Z; Wei, Y; Wang, R; Du, Z; Zhang, Y; Lu, Y

    2014-01-01

    Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which can result in cardiac hypertrophy and subsequent heart failure, associated with pyroptosis, the pro-inflammatory programmed cell death. MicroRNAs (miRNAs), small endogenous non-coding RNAs, have been shown to be involved in diabetic cardiomyopathy. However, whether miRNAs regulate pyroptosis in diabetic cardiomyopathy remains unknown. Our study revealed that mir-30d expression was substantially increased in streptozotocin (STZ)-induced diabetic rats and in high-glucose-treated cardiomyocytes as well. Upregulation of mir-30d promoted cardiomyocyte pyroptosis in diabetic cardiomyopathy; conversely, knockdown of mir-30d attenuated it. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic property of mir-30d, we found that forced expression of mir-30d upregulated caspase-1 and pro-inflammatory cytokines IL-1? and IL-18. Moreover, mir-30d directly repressed foxo3a expression and its downstream protein, apoptosis repressor with caspase recruitment domain (ARC). Furthermore, silencing ARC by siRNA mimicked the action of mir-30d: upregulating caspase-1 and inducing pyroptosis. These findings promoted us to propose a new signaling pathway leading to cardiomyocyte pyroptosis under hyperglycemic conditions: mir-30d??foxo3a?? ARC??caspase-1??IL-1?, IL-18??pyroptosis?. Therefore, mir-30d may be a promising therapeutic target for the management of diabetic cardiomyopathy. PMID:25341033

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

    PubMed Central

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

    2015-01-01

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

  15. Diabetes mellitus effect on rat corneal dielectric properties.

    PubMed

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

    2012-03-01

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

  16. The reno-protective effect of aqueous extract of Carum carvi (black zeera) seeds in streptozotocin induced diabetic nephropathy in rodents.

    PubMed

    Sadiq, Soban; Nagi, Abdul Hannan; Shahzad, Muhammad; Zia, Azam

    2010-11-01

    To assess the effect of aqueous extract of Carum carvi seeds in experimentally induced diabetic nephropathy (DN) in rodents, we studied 48 adult male Wistar rats divided into 4 groups: normal controls (group A), diabetes positive control (group B), and experimental (groups C and D). They received Carum carvi extract as a renoprotective agent. Rats having fasting blood glucose levels over 280 mg/dL were included in this study. Group C rats received STZ (60 mg/kg) and aqueous extract of Carum carvi at 30 mg/kg of body weights. On the other hand group D rats received STZ (60 mg/kg) and aqueous extract of Carum carvi at 60 mg/kg of body weight. Blood samples were collected on the 60 th day, and kidneys were also extracted for examination. The diabetic group rats showed a variable increase in the serum levels of glucose, urea, creatinine, total urinary protein and microalbuminuric levels. Body weight decreased and urine volume increased in the diabetic groups. 30 mg/kg body weight of Carum carvi dose decreased the levels of these parameters in rats. On the other hand, 60 mg/kg body weight of Carum carvi dose significantly decreased the levels of the biochemical parameters. The morphological examination of group C rats showed no changes whereas the rats in group D showed moderate changes. Carum carvi constituents, especially flavonoids and carvone have strong anti-oxidant activity, which provides reno-protection against diabetes and its complications. In conclusion, high dose of Carum carvi aqueous seeds extract (60 mg/kg) showed reno-protection against STZ induced dia-betic nephropathy in rats. PMID:21060174

  17. Proinsulin processing in the diabetic Goto-Kakizaki rat

    Microsoft Academic Search

    P. Guest; D J Gross; A Clark; V Poitout; R Amaria; C-G Ostenson; J C Hutton

    2002-01-01

    The biosynthesis and processing of proinsulin was inves- tigated in the diabetic Goto-Kakizaki (GK) rat. Immuno- fluorescence microscopy comparing GK and Wistar control rat pancreata revealed marked changes in the distribution of -cells and pronounced -cell heterogen- eity in the expression patterns of insulin, prohormone convertases PC1, PC2, carboxypeptidase E (CPE) and the PC-binding proteins 7B2 and ProSAAS. Western blot

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

    PubMed Central

    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

  19. Kidney involvement in a nongenetic rat model of type 2 diabetes

    Microsoft Academic Search

    Ratna S. Danda; Nusrath M. Habiba; HERNAN RINCON-CHOLES; BASANT K BHANDARI; JEFFREY L BARNES; HANNA E ABBOUD; PABLO E PERGOLA

    2005-01-01

    Kidney involvement in a nongenetic rat model of type 2 diabetes.BackgroundRats fed a high fat diet and given a low dose of streptozotocin (STZ) (35 mg\\/kg) develop type 2 diabetes with insulin resistance, hyperinsulinemia, moderate hyperglycemia, hyperlipidemia, and salt-sensitive hypertension. We postulated that rats with noninsulinopenic (type 2) diabetes develop lesions of diabetic nephropathy significantly more prominent than those seen

  20. Rat Models for Bariatric Surgery and Surgery for Type 2 Diabetes Mellitus

    Microsoft Academic Search

    Sheetal Bharat Mistry; Juan J. Omana; Subhash Kini

    2009-01-01

    Type 2 diabetes mellitus being one of the most prevalent diseases in the world has led to a variety of research using animal\\u000a models. This review focuses on various rat models to study the effect that surgical procedures have on type 2 diabetes mellitus\\u000a and obesity. Rat models can be classified as Obese Diabetic, Non-Obese Diabetic, Obese Non-Diabetic, and Non-Obese

  1. Antihyperglycemic and antihyperlipidemic effect of Rumex patientia seed preparation in streptozotocin-diabetic rats

    Microsoft Academic Search

    Reza Sedaghat; Mehrdad Roghani; Maedeh Ahmadi; Faezeh Ahmadi

    2011-01-01

    Background and objective:Rumex patientia (RP) could exert beneficial health effects to ameliorate metabolic diseases. The effect of subchronic feeding of RP seeds was evaluated on serum glucose and lipid profile in streptozotocin (STZ)-diabetic rats. Methods: Wistar rats were divided into control, RP-treated control, diabetic, glibenclamide-treated diabetic, and RP-treated diabetic groups. For induction of diabetes, streptozotcin was administered at a dose

  2. Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress

    Microsoft Academic Search

    Yu-Jung Chen; Jing Li; John Quilley

    2008-01-01

    Abstract We confirmed that release of 20-HETE from the isolated perfused kidney of diabetic rats is greatly reduced when compared,to age-matched control rats. The present studies were undertaken to examine potential mechanisms,for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3-4 weeks duration. A role for oxidative stress was excluded as treatment of diabetic rats with tempol,

  3. Lectins binding during alloxan-induced diabetes in rat soleus muscle

    Microsoft Academic Search

    Nursel Gül; Suna Cebesoy; Nesrin Özsoy

    Membrane structural changes of soleus muscle of alloxan-diabetic rats were detected with a panel of six biotinylated lectins. Samples of muscles were obtained from normal and diabetic rats. The biotinylated lectins in staining were detected by avidin-peroxidase complex. Lectin stainning of soleus muscle cryostat sections from alloxan-diabetic rats were compared with similar cryostat sections from normal rats. All lectins were

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

    SciTech Connect

    Vikram, A.; Tripathi, D.N.; Ramarao, P. [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062 (India); Jena, G.B. [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062 (India)], E-mail: gbjena@gmail.com

    2008-01-01

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

  5. Heme oxygenase-1 enhances renal mitochondrial transport carriers and cytochrome C oxidase activity in experimental diabetes.

    PubMed

    Di Noia, Maria Antonietta; Van Driesche, Sarah; Palmieri, Ferdinando; Yang, Li-Ming; Quan, Shuo; Goodman, Alvin I; Abraham, Nader G

    2006-06-01

    Up-regulation of heme oxygenase (HO-1) by either cobalt protoporphyrin (CoPP) or human gene transfer improves vascular and renal function by several mechanisms, including increases in antioxidant levels and decreases in reactive oxygen species (ROS) in vascular and renal tissue. The purpose of the present study was to determine the effect of HO-1 overexpression on mitochondrial transporters, cytochrome c oxidase, and anti-apoptotic proteins in diabetic rats (streptozotocin, (STZ)-induced type 1 diabetes). Renal mitochondrial carnitine, deoxynucleotide, and ADP/ATP carriers were significantly reduced in diabetic compared with nondiabetic rats (p < 0.05). The citrate carrier was not significantly decreased in diabetic tissue. CoPP administration produced a robust increase in carnitine, citrate, deoxynucleotide, dicarboxylate, and ADP/ATP carriers and no significant change in oxoglutarate and aspartate/glutamate carriers. The increase in mitochondrial carriers (MCs) was associated with a significant increase in cytochrome c oxidase activity. The administration of tin mesoporphyrin (SnMP), an inhibitor of HO-1 activity, prevented the restoration of MCs in diabetic rats. Human HO-1 cDNA transfer into diabetic rats increased both HO-1 protein and activity, and restored mitochondrial ADP/ATP and deoxynucleotide carriers. The increase in HO-1 by CoPP administration was associated with a significant increase in the phosphorylation of AKT and levels of BcL-XL proteins. These observations in experimental diabetes suggest that the cytoprotective mechanism of HO-1 against oxidative stress involves an increase in the levels of MCs and anti-apoptotic proteins as well as in cytochrome c oxidase activity. PMID:16595661

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

    PubMed

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

    2015-08-01

    The present study was aimed to investigate the metabolomics of sulfur amino acids in Zucker diabetic fatty (ZDF) rats, an obese type 2 diabetic animal model. Plasma levels of total cysteine, homocysteine and methionine, but not glutathione (GSH) were markedly decreased in ZDF rats. Hepatic methionine, homocysteine, cysteine, betaine, taurine, spermidine and spermine were also decreased. There are no significant difference in hepatic S-adenosylmethionine, S-adenosylhomocysteine, GSH, GSH disulfide, hypotaurine and putrescine between control and ZDF rats. Hepatic SAH hydrolase, betaine-homocysteine methyltransferase and methylene tetrahydrofolate reductase were up-regulated while activities of gamma-glutamylcysteine ligase and methionine synthase were decreased. The area under the curve (AUC) of methionine and methionine-d4 was not significantly different in control and ZDF rats treated with a mixture of methionine (60mg/kg) and methionine-d4 (20mg/kg). Moreover, the AUC of the increase in plasma total homocysteine was comparable between two groups, although the homocysteine concentration curve was shifted leftward in ZDF rats, suggesting that the plasma total homocysteine after the methionine loading was rapidly increased and normalized in ZDF rats. These results show that the AUC of plasma homocysteine is not responsive to the up-regulation of hepatic BHMT in ZDF rats. The present study suggests that the decrease in hepatic methionine may be responsible for the decreases in its metabolites, such as homocysteine, cysteine, and taurine in liver and consequently decreased plasma homocysteine levels. PMID:26047850

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-11-01

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

  9. Cilostazol minimizes venous ischemic injury in diabetic and normal rats

    PubMed Central

    Wajima, Daisuke; Nakamura, Mitsutoshi; Horiuchi, Kaoru; Takeshima, Yasuhiro; Nishimura, Fumihiko; Nakase, Hiroyuki

    2011-01-01

    We evaluated the effects of cilostazol on venous infarction produced by a photothrombotic two-vein occlusion (2VO) model in diabetic and control rats. The cerebral blood flow (CBF) between the occluded veins was measured by laser Doppler flowmetry for 4?hours after 2VO. Infarct size and immunohistochemistry were evaluated 24, 48, 96, and 168?hours after 2VO. Cilostazol was administered 1?hour after 2VO, and thereafter at a continuous oral dose of 60?mg/kg per day. Cilostazol reduced the infarct size, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic and B-cell lymphoma 2-associated X protein (Bax)-positive cells, and improved the CBF in control rats. In diabetic rats, cilostazol reduced the infarct size, and the number of TUNEL-positive apoptotic and Bax-positive cells, 96 and 168?hours after 2VO, but did not improve the CBF 4?hours after 2VO. Cilostazol increased the number of B-cell lymphoma 2 (Bcl-2)-positive cells in both strains 48, 96, and 168?hours after 2VO, but did not improve vessel wall thickness or collagen deposits. Cilostazol appeared to limit venous infarcts by improving the penumbral CBF in nondiabetic rats, and inhibited pro-apoptotic changes through Bcl-2 overexpression, without improving the CBF in diabetic rats. PMID:21505475

  10. 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-?1 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-?1 protein expression in the renal tissue. CK improved the pathological changes in the renal tissue, enhanced the antioxidant capacity, reduced the damage of TGF-?1 to renal tissue, and protected the diabetic rats. PMID:25920251

  11. Protection by vanadium, a contemporary treatment approach to both diabetes and focal cerebral ischemia in rats.

    PubMed

    Liu, Zhenquan; Li, Pengtao; Zhao, Dan; Tang, Huiling; Guo, Jianyou

    2012-01-01

    There is now substantial epidemiological evidence that diabetes is a risk factor for cerebrovascular disease. The protection by vanadium from focal cerebral ischemia in diabetic rats was studied in this paper. Rats with streptozotocin-induced diabetes were subjected to middle cerebral artery occlusion followed by 4 weeks of administration of 0.6 mg/ml sodium orthovanadate in drinking water. Vanadium significantly improved the outcome in diabetic rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. Vanadium reduces brain damage in streptozotocin-induced diabetic rats by imitating action of insulin. PMID:21833647

  12. Genetic and environmental influence on diabetic rat embryopathy.

    PubMed

    Ejdesjö, A; Wentzel, P; Eriksson, U J

    2011-03-01

    We assessed genetic and environmental influence on fetal outcome in diabetic rat pregnancy. Crossing normal (N) and manifestly diabetic (MD) Wistar Furth (W) and Sprague-Dawley (L) females with W or L males yielded four different fetal genotypes (WW, LL, WL, and LW) in N or MD rat pregnancies for studies. We also evaluated fetal outcome in litters with enhanced or diminished severity of maternal MD state, denoted MD(+)WL and MD(-)LW. The MDWW litters had less malformations and resorptions (0 and 19%) than the MDLL litters (17 and 30%). The MDWL litters (0 and 8%) were less maldeveloped than the MDLW litters (9 and 22%), whereas the MD(+)WL (3 and 23%) and MD(-)LW (1 and 17%) litters showed increased and decreased dysmorphogenesis (compared with MDWL and MDLW litters). The pregnant MDW rats had lower serum levels of glucose, fructosamine, and branched-chain amino acids than the pregnant MDL rats, whereas the pregnant MD(+)W and MD(-)L rats had levels comparable with those of the MDL and MDW rats, respectively. The 8-iso-PGF2? levels of the malformed MDLW offspring were increased compared with the nonmalformed MDLW offspring. Diabetes decreased fetal heart Ret and increased Bmp-4 gene expression in the MDLW offspring and caused decreased GDNF and Shh expression in the malformed fetal mandible of the MDLW offspring. We conclude that the fetal genome controls the embryonic dysmorphogenesis in diabetic pregnancy by instigating a threshold level for the teratological insult and that the maternal genome controls the teratogenic insult by (dys)regulating the maternal metabolism. PMID:21119026

  13. 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

  14. 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

  15. Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart

    Microsoft Academic Search

    T Hayashi; K Sohmiya; A Ukimura; S Endoh; T Mori; H Shimomura; M Okabe; F Terasaki; Y Kitaura

    2003-01-01

    Background: Cardiac microangiopathy may be involved in the development of heart failure in diabetes mellitus.Objective: To evaluate the effect of angiotensin II receptor blockade on cardiac function and fine structures in diabetes.Methods: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 30), a model of spontaneously developing diabetes mellitus, and their diabetes resistant counterparts (n = 20) were used. At

  16. Increased severity of acute Trypanosoma brucei brucei infection in rats with alloxan-induced diabetes

    E-print Network

    Paris-Sud XI, Université de

    -induced diabetes Ikechukwu Onyebuchi Igbokwea Sani Isaa Umma Kalsum Aliyub Hajja Gana Hamzab Tobias Egbe made diabetic by treatment with alloxan monohydrate (10 % solution, 100 mg/kg body weight). Ten diabetic and ten non-diabetic rats were intraperitoneally infected with the same infective doses

  17. The role of nitric oxide in diabetes-induced changes of morphine tolerance in rats

    Microsoft Academic Search

    Khojasteh Joharchi; Masoumeh Jorjani

    2007-01-01

    Several neuroendocrine complications including diabetes change the morphine antinociception and the development of tolerance to the drug. Morphine antinociception was reduced significantly in morphine tolerant diabetic rats compared to the non-diabetic animals. The exact mechanism of this effect is not known. This study was performed to determine the role of nitric oxide (NO) on morphine tolerance in diabetic state. Nociceptive

  18. Antihyperglycemic and antihyperlipidemic effects of guar gum on streptozotocin-induced diabetes in male rats

    PubMed Central

    Saeed, Samarghandian; Mosa-Al-Reza, Hadjzadeh; Fatemeh, Amin Nya; Saeideh, Davoodi

    2012-01-01

    Background: Herbal medicine is widely used in the treatment of diseases like diabetes mellitus. We investigated the effects of guar gum in diabetic rats for the reduction of the risk of diabetes and cardiovascular disease. Dietary pattern emphasizing foods high in complex carbohydrates and fiber are associated with low blood glucose and cholesterol levels. Materials and Methods: Diet containing 0%, 5%, 10% and 20% (w/w) guar gum was fed to diabetic rats for 28 days. Blood serum glucose, triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol levels, atherogenic index levels, body weights and food intake were monitored at 0, 7.14 and 28 days after induction of diabetes. Results: In spite of the fact that diabetes elevated blood lipids in all rats after 14 days, the guar gum diet significantly decreased the serum concentration of cholesterol, triacylglicerols and LDL-C and atherogenic index. The most significant result in this study was the reduction of blood glucose in diabetic rats treated with the guar gum diet after 28 days versus non- and glibenclamide-treated rats. The gum promoted a general improvement in the condition of the diabetic rats in body weight and food intake in comparison with nontreated rats. Conclusion: The results of this research suggest that guar gum was significantly effective in comparison with glibenclamide in the treatment of hyperlipidemia and hyperglycemia in diabetes rats. Therefore, it may be suggested as a reliable fiber in diabetic regimes in diabetic patients. PMID:22438666

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

    PubMed

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

    2015-08-01

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

  20. Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats.

    PubMed

    Shanmugam, Kondeti Ramudu; Mallikarjuna, Korivi; Kesireddy, Nishanth; Sathyavelu Reddy, Kesireddy

    2011-04-01

    The aim of the present study was to investigate the effect of ginger on oxidative stress markers in the mitochondrial fractions of cerebral cortex (CC), cerebellum (CB), hippocampus (HC) and hypothalamus (HT) of diabetic rats. Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage. A marked decrease in anti-oxidant marker enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH) and increase in malondialdehyde (MDA) was observed in the diabetic rats. Decreased activities of anti-oxidant enzymes in diabetic rats were augmented on oral administration of ginger. Moreover, ginger administration depleted the MDA level, which was earlier increased in the diabetic rats. These results suggest that ginger exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating the MDA levels to the normal levels in the diabetic rats. Thus, ginger may be used as therapeutic agent in preventing complications in diabetic patients. PMID:21184796

  1. 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

  2. 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

  3. Radical scavenging effect of gliclazide in diabetic rats fed with a high cholesterol diet

    Microsoft Academic Search

    MARISTELA LIKA ONOZATO; AKIHIRO TOJO; ATSUO GOTO; TOSHIRO FUJITA

    2004-01-01

    Radical scavenging effect of gliclazide in diabetic rats fed with a high cholesterol diet.BackgroundGliclazide is a sulphonylurea antidiabetic drug with anti-oxidant effect due to its azabicyclo-octyl ring. We hypothesized that gliclazide may have a beneficial effect on diabetic nephropathy via radical scavenging.MethodsStreptozotocin-induced diabetic rats fed a 4% cholesterol diet [high cholesterol-diabetes mellitus (HC-DM)] (N = 12) were treated with gliclazide

  4. Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis

    Microsoft Academic Search

    Muhammed Yusuf; Benny Tan Kwong Huat; A. Hsu; Matthew Whiteman; Madhav Bhatia; Philip K. Moore

    2005-01-01

    This investigation is aimed to determine whether the biosynthesis of H2S, an endogenous vasodilator gas, is altered in the streptozotocin-diabetic rat. Plasma H2S concentration as well as the activity, and expression, of H2S synthesizing enzymes (namely cystathionine-?-lyase (CSE) and cystathionine-?-synthetase (CBS)) were measured in various tissues of non-diabetic, streptozotocin-diabetic and insulin-treated diabetic rats. H2S formation in pancreas and liver was

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. Branched chain amino acid metabolism in the retina of diabetic rats

    Microsoft Academic Search

    R. Frayser; M. G. Buse

    1978-01-01

    Summary  Diabetes is known to produce increased levels of the branched chain amino acids in plasma, heart and muscle as well as increased oxidation of [14C]-leucine by nerves and muscles from rats. Plasma and retinas from streptozotocin diabetic rats had significant elevations in branched chain amino acid levels compared to control. Retinas from diabetic rats have been found to oxidize significantly

  8. The BBZDR\\/Wor Rat Model for Investigating the Complications of Type 2 Diabetes Mellitus

    Microsoft Academic Search

    Rebecca S. Tirabassi; Joan F. Flanagan; Tiangen Wu; Edward H. Kislauskis; Paul J. Birckbichler; Dennis L. Guberski

    Congenic and inbred strains of rats offer researchers invalu- able insight into the etiopathogenesis of diabetes and asso- ciated complications. The inbred Bio-Breeding Zucker diabetic rat (BBZDR)\\/Wor rat strain is a relatively new and emerging model of type 2 diabetes. This strain was created by classical breeding methods used to introgress the defec- tive leptin receptor gene (Leprfa) from insulin-resistant

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

    PubMed

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

    2013-01-01

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

  10. Effect of Nigella sativa fixed and essential oils on antioxidant status, hepatic enzymes, and immunity in streptozotocin induced diabetes mellitus

    PubMed Central

    2014-01-01

    Background Nigella sativa fixed (NSFO) and essential (NSEO) oils have been used to treat diabetes mellitus and its complications. Present study was undertaken to explore and validate these folkloric uses. Methods Sprague dawley rats having streptozotocin (STZ) induced diabetes mellitus were used to assess the role of NSFO and NSEO in the management of diabetes complications. Parameters investigated were antioxidant potential, oxidative stress, and the immunity by in vivo experiments. Results The results indicated that STZ decreased the glutathione contents (25.72%), while NSFO and NSEO increased the trait significantly (P?diabetes complications. Conclusions Overall, results of present study supported the traditional use of N. sativa and its derived products as a treatment for hyperglycemia and allied abnormalities. Moreover, N. sativa fixed and essential oils significantly ameliorate free radicals and improve antioxidant capacity thus reducing the risk of diabetic complications. PMID:24939518

  11. Ginseng modifies the diabetic phenotype and genes associated with diabetes in the male ZDF rat.

    PubMed

    Banz, William J; Iqbal, M J; Bollaert, Michael; Chickris, Nicole; James, Bryce; Higginbotham, D Allan; Peterson, Richard; Murphy, Laura

    2007-10-01

    Asian ginseng (Panax ginseng) and its close relative North American ginseng (Panax quinquefolius) are perennial aromatic herbs that are widely used in Oriental medicine and have been acclaimed to have various health benefits including diabetes treatment. In this study, we compared the effects of a diet containing rosiglitazone to a diet containing ginseng (Panax quinquefolius) in male Zucker diabetic fatty (ZDF) rats. Animals were assigned to one of three diets: control, rosiglitazone (0.1 g/1 kg diet), or ginseng (10 g/1 kg diet). During the 11-week study, body weight, food intake, organ weight, blood glucose, plasma cholesterol, and plasma triglyceride levels were evaluated. Animals treated with rosiglitazone or ginseng exhibited increased body weight (p<0.05) and decreased kidney weight (p<0.05) compared to control animals. The rosiglitazone group demonstrated decreased food intake and plasma triglyceride levels versus the other groups (p<0.05). The ginseng group revealed decreased cholesterol levels relative to the control group (p<0.05). Furthermore, ginseng and rosiglitazone had marked effects on the expression of genes involved in PPAR actions and triglyceride metabolism compared to controls. In conclusion, ginseng modified the diabetic phenotype and genes associated with diabetes in the male ZDF rat. These data are encouraging, and warrant further research to determine the therapeutic value of this medicinal herb in treating human diabetes. PMID:17689944

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

    PubMed Central

    Xie, Kangning; Li, Guoliang

    2014-01-01

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

  13. Antioxidant activity of Cassia fistula (Linn.) flowers in alloxan induced diabetic rats.

    PubMed

    Manonmani, G; Bhavapriya, V; Kalpana, S; Govindasamy, S; Apparanantham, T

    2005-02-10

    Aqueous extract of Cassia fistula (Linn.) flowers (ACF) was screened for its antioxidant effect in alloxan induced diabetic rats. An appreciable decrease in peroxidation products viz thiobarbituric acid reactive substances, conjugated dienes, hydroperoxides was observed in heart tissues of ACF treated diabetic rats. The decreased activities of key antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione in diabetic rats were brought back to near normal range upon ACF treatment. These results suggest that ACF has got promising antioxidative activity in alloxan diabetic rats. PMID:15652272

  14. Antioxidant therapy and streptozotocin-induced diabetes in pregnant rats

    Microsoft Academic Search

    M. Kinalski; A. ?ledziewski; B. Telejko; W. Zarzycki; I. Kinalska

    1999-01-01

    The aim of our study was to analyse the effect of chronic hyperglycaemia on lipid peroxidation and scavenging enzyme activity\\u000a in pregnant animals and their offspring supplemented and not supplemented with vitamin E – a natural antioxidant. Thirty pregnant\\u000a female Wistar rats were used in our experiments. Diabetes was induced on day 7 of pregnancy using a single does of

  15. A new rat model of type 2 diabetes: The fat-fed, streptozotocin-treated rat

    Microsoft Academic Search

    M. J Reed; K Meszaros; L. J Entes; M. D Claypool; J. G Pinkett; T. M Gadbois; G. M Reaven

    2000-01-01

    This study was initiated to develop an animal model of type 2 diabetes in a non-obese, outbred rat strain that replicates the natural history and metabolic characteristics of the human syndrome and is suitable for pharmaceutical research. Male Sprague-Dawley rats (n = 31), 7 weeks old, were fed normal chow (12% of calories as fat), or high-fat diet (40% of

  16. Malondialdehyde and 4-hydroxynonenal adducts are not formed on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) in diabetes.

    PubMed

    Moore, Caronda J; Shao, Chun Hong; Nagai, Ryoji; Kutty, Shelby; Singh, Jaipaul; Bidasee, Keshore R

    2013-04-01

    Recently, we reported an elevated level of glucose-generated carbonyl adducts on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) in hearts of streptozotocin(STZ)-induced diabetic rats. We also showed these adduct impaired RyR2 and SERCA2 activities, and altered evoked Ca(2+) transients. What is less clear is if lipid-derived malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) also chemically react with and impair RyR2 and SERCA2 activities in diabetes? This study used western blot assays with adduct-specific antibodies and confocal microscopy to assess levels of MDA, 4-HNE, N (?)-carboxy(methyl)lysine (CML), pentosidine, and pyrraline adducts on RyR2 and SERCA2 and evoked intracellular transient Ca(2+) kinetics in myocytes from control, diabetic, and treated-diabetic rats. MDA and 4-HNE adducts were not detected on RyR2 and SERCA2 from either control or 8 weeks diabetic rats with altered evoked Ca(2+) transients. However, CML, pentosidine, and pyrraline adducts were elevated three- to five-fold (p < 0.05). Treating diabetic rats with pyridoxamine (a scavenger of reactive carbonyl species, RCS) or aminoguanidine (a mixed reactive oxygen species-RCS scavenger) reduced CML, pentosidine, and pyrraline adducts on RyR2 and SERCA2 and blunted SR Ca(2+) cycling changes. Treating diabetic rats with the superoxide dismutase mimetic tempol had no impact on MDA and 4-HNE adducts on RyR2 and SERCA2, and on SR Ca(2+) cycling. From these data we conclude that lipid-derived MDA and 4-HNE adducts are not formed on RyR2 and SERCA2 in this model of diabetes, and are therefore unlikely to be directly contributing to the SR Ca(2+) dysregulation. PMID:23354458

  17. Angelica sinensis polysaccharide regulates glucose and lipid metabolism disorder in prediabetic and streptozotocin-induced diabetic mice through the elevation of glycogen levels and reduction of inflammatory factors.

    PubMed

    Wang, Kaiping; Cao, Peng; Shui, Weizhi; Yang, Qiuxiang; Tang, Zhuohong; Zhang, Yu

    2015-03-11

    The present study was designed to evaluate the potential hypoglycemic and hypolipidemic effects of Angelica sinensis polysaccharide (ASP), purified from the fresh roots of Angelica sinensis (AS), in prediabetic and streptozotocin (STZ)-induced diabetic BALB/c mice. It was observed that fasting blood glucose (FBG) levels in both models were reduced after a 4-week oral administration of ASP or metformin, and abnormal fasting serum insulin (FINS) concentrations were ameliorated as well. Moreover, the homeostasis model assessment-insulin resistance (HOMA-IR) index was decreased strikingly and body weight (BW) was reduced significantly in prediabetic mice after treatment with ASP. In addition, ASP also contributed to improving the dyslipidemia conditions. Elevated serum total cholesterol (TC) or triglyceride (TG) concentrations were reduced after treatment with ASP in prediabetic mice or STZ-induced diabetic mice. Meanwhile, hepatic glycogen (HG) and muscle glycogen (MG) concentrations were increased while insulin resistance (IR)-related inflammatory factors IL-6 and TNF-? in serum were reduced in STZ-induced diabetic mice. Histopathological examination indicated that the impaired pancreatic/hepatic tissues or adipose tissues were effectively restored in STZ-induced diabetic mice or prediabetic mice after the ASP treatment. Taken together, these results revealed that ASP efficiently exerted hypoglycemic and hypolipidemic benefits, and its potential effect was associated with the amelioration of IR. ASP can be applied in the prevention and treatment of diabetes. PMID:25630053

  18. Chromium and manganese interactions in streptozocin-diabetic rats

    SciTech Connect

    Davis, M.L.; Jarrett, C.R.; Adeleye, B.O.; Stoecker, B.J. (Oklahoma State Univ., Stillwater (United States))

    1991-03-15

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

  19. Chrysin ameliorates diabetes-associated cognitive deficits in Wistar rats.

    PubMed

    Li, Rui; Zang, Aihua; Zhang, Lei; Zhang, Huiyun; Zhao, Longshan; Qi, Zhonghua; Wang, Hui

    2014-10-01

    Chrysin (CH) is an important natural plant flavonoid and possesses diverse pharmacological activities. Our present investigations aimed to assess the neuroprotection of CH against diabetes-associated cognitive decline (DACD) in a rat model of diabetes and exploring its potential mechanism. Diabetic model was induced by intraperitoneal injection of streptozotocin. Then, they were treated with vehicle or CH by doses of 30 and 100 mg/kg for 26 days. Learning and memory function was evaluated by Morris water maze test. The oxidative indicators [malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH)], NF-?B p65 unit, TNF-?, IL-1?, IL-6 and caspase-3 were measured in cerebral cortex and hippocampus using corresponding commercial kits. The diabetic rats showed marked reductions in body weight, percentage of time spent in target quadrant and number of times of crossing platform, coupled with increases in plasma glucose levels, escape latency, mean path length and oxidative stress (increased MDA level and decreased CAT and SOD as well as reduced GSH), NF-?B p65 unit, TNF-?, IL-1?, IL-6 and caspase-3 in cerebral cortex and hippocampus. Moreover, CH supplement dramatically reversed the corresponding behavioral, biochemical and molecular alterations in diabetes. The alterations of swimming speed among different groups were not observed after CH adminstration. In conclusion, our current work discloses that CH remarkably alleviates DACD and suggests that oxidative stress, inflammation and apoptotic cascades are linked with diabetes-associated cognitive deficits. These findings point toward the therapeutic potential of CH in DACD. PMID:24737349

  20. The role of ghrelin on apoptosis, cell proliferation and oxidant-antioxidant system in the liver of neonatal diabetic rats.

    PubMed

    Koyuturk, Meral; Sacan, Ozlem; Karabulut, Sezin; Turk, Neslihan; Bolkent, Sehnaz; Yanardag, Refiye; Bolkent, Sema

    2015-07-01

    Ghrelin is a multifunctional peptide hormone which stimulates appetite and regulates glucose metabolism and adipogenesis. The purpose of this study was to investigate whether ghrelin has protective effects in the liver of streptozocin (STZ) diabetic rats or not. Wistar-type neonatal rats were divided into four groups: I. Controls, II. Ghrelin administrated controls, III. STZ-diabetic rats, and IV. Ghrelin administrated diabetic rats. On the second day after birth, 100?mg/kg STZ was administered intraperitoneally in a single dose to induce diabetes in rats. 100?µg/kg/day ghrelin was administrated to rats subcutaneously for 4 weeks. Ghrelin administration improved histopathologic changes in STZ-diabetic liver. Obestatin immunoreactivity has been shown in livers of neonatal rats. The immunoreactivity of obestatin increased in diabetic rats and a decline was observed in ghrelin administrated diabetic rats. Caspase 8 and 3 immunoreactivities increased in diabetic rats; however, ghrelin administration differently affected caspases 8 and 3 immunoreactivities. Proliferating cell nuclear antigen immunoreactivities decreased in diabetic rats and in ghrelin administrated diabetic rats. Serum alanine (P?diabetic rats compared to the diabetic rats. Gamma glutamyl transferase activity (P?diabetic rats compared to the diabetic rats. The response of antioxidants including glutathione levels, catalase and superoxide dismutase activities were altered in ghrelin administrated diabetic rats. Our findings indicate that ghrelin administration affects hepatic functions in neonatal diabetic rats and might be considered as a therapeutic agent. PMID:25789445

  1. The role of nitric oxide in diabetes-induced changes of morphine tolerance in rats.

    PubMed

    Joharchi, Khojasteh; Jorjani, Masoumeh

    2007-09-10

    Several neuroendocrine complications including diabetes change the morphine antinociception and the development of tolerance to the drug. Morphine antinociception was reduced significantly in morphine tolerant diabetic rats compared to the non-diabetic animals. The exact mechanism of this effect is not known. This study was performed to determine the role of nitric oxide (NO) on morphine tolerance in diabetic state. Nociceptive responses in alloxan-induced diabetic morphine tolerated rats were measured by the hot-plate test. The urinary nitric oxide level was measured spectrophotometrically with Griess reagent. For the conversion of nitrate to nitrite, vanadium chloride was used. The results showed that experimental diabetes increased morphine analgesia. Conversely, degree of tolerance to morphine was diminished in diabetic state. The urinary nitrite content in diabetic morphine tolerated rats was higher than non-diabetic groups. L-arginine significantly increased the NO production in diabetic morphine tolerated animals, whereas aminoguanidine decreased it. Appropriately, L-arginine increased the latency time of reaction to noxious stimuli in diabetic compared to non-diabetic rats. L-arginine-treated animals also showed more tolerance to morphine analgesia. As expected, aminoguanidine deducted the level of morphine tolerance in diabetic animals. It is suggested that NO has a modulatory role in the effects of diabetes on morphine analgesia and tolerance. PMID:17599829

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

    PubMed

    Prasath, Gopalan Sriram; Subramanian, Sorimuthu Pillai

    2014-10-01

    Chronic hyperglycemia in diabetes is associated with profound changes in lipid and lipoprotein metabolism, with resultant alterations in particle distribution within lipoprotein classes. In the present study, an attempt has been made to explore the antihyperlipidemic effect of fisetin in streptozotocin-induced experimental diabetes in rats. Upon fisetin treatment to diabetic rats, the levels of blood glucose were significantly reduced with an improvement in plasma insulin. The increased levels of lipid contents in serum, hepatic, and renal tissues observed in diabetic rats were normalized upon fisetin administration. Also, the decreased levels of high-density lipoprotein cholesterol, and increased levels of low-density lipoprotein (LDL) and very LDL (VLDL) cholesterol in serum of diabetic rats were normalized. Oil Red O staining established a large number of intracellular lipid droplets accumulation in the diabetic rats. Fisetin treatment exacerbated the degree of lipid accumulation. The results of the present study exemplify the antihyperlipidemic property of the fisetin. PMID:24939606

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

    Microsoft Academic Search

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

    1984-01-01

    Total lymphoid irradiation (TLI) at doses of 2200 rads or greater prevented diabetes in susceptible BB\\/W rats. Two of 29 (7%) treated rats became diabetic compared with 23 of 39 (59%) controls. TLI did not, however, prevent insulitis or thyroiditis in nondiabetic rats, nor did it restore the depressed concanavalin-A responsiveness of BB rat lymphocytes. T-lymphocyte subset proportions were the

  4. Antidiabetic Effects of Corni Fructus Extract in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Li, Qingwang; Gao, Zhengrong; Wang, Lixin

    2012-01-01

    Purpose Diabetes is the leading cause of end-stage renal failure. The present study was undertaken to characterize the effects of Corni Fructus on diabetic nephropathy in streptozotocin-induced diabetic rats and their mechanisms. Materials and Methods Streptozotocin-diabetic rats were orally administrated with Corni Fructus at a dose of 100, 200 or 400 mg/kg body mass for 40 days. Results Corni Fructus-treated diabetic rats showed significant decreases of blood glucose, urinary protein levels and water consumption. Corni Fructus also reduced serum total cholesterol, total triglyceride and low-density lipoprotein cholesterol levels, and showed a tendency of enhancing high-density lipoprotein cholesterol level. Levels of serum albumin and creatinine in diabetic rats were also significantly reduced by Corni Fructus administration at a dose of 200 and 400 mg/kg body mass compared with non-treated diabetic rats. Corni Fructus increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidose (GSH-px) activities in the kidneys of diabetic rats. Furthermore, Corni Fructus treatment enhanced renal peroxisome proliferator-activated receptor-? (PPAR?) expression in diabetic rats. Conclusion These results demonstrated that Corni Fructus may have the potential to protect the animals from diabetic nephropathy by amelioration of oxidative stress and stimulation of PPAR? expression. PMID:22665333

  5. Hypoglycaemic and anti-diabetic activity of stem bark extracts Erythrina indica in normal and alloxan-induced diabetic rats

    PubMed Central

    Yashwant Kumar, A.; Nandakumar, K.; Handral, M.; Talwar, Sahil; Dhayabaran, Daniel

    2010-01-01

    The objective of the study is to investigate the alcoholic (AlcE) and aqueous (AqsE) extracts of stem bark of Erythrina indica (Papilionaceae) for hypoglycaemic effects in normal and diabetic rats. Diabetes was induced in rats by a single dose administration of alloxan (120 mg/kg, i.p.) or by injecting dexamethasone (10 mg/kg, i.p.) for 10 days. In normal rats, AlcE and AqsE had significantly decreased the blood glucose level (BGL) in a dose dependent manner after repeated administration for 7 days. In alloxan-induced diabetic rats, both the extracts decreased blood sugar levels with significant improvement in glucose tolerance and body weight at the end of 1st, 2nd and 3rd week after test extract treatment. In case of dexamethasone induced insulin resistant diabetic rats, repeated administration of AlcE and AqsE inhibited the increase in blood glucose level and improved glucose tolerance induced by dexamethasone as compared to dexamethasone induced diabetic rats. These results suggest that both extracts possess hypoglycaemic activity in normal as well as in diabetic rats. Among AlcE and AqsE, AqsE possesses better hypoglycaemic activity than AlcE in all the models. Preliminary phytochemical investigations revealed that alcoholic extracts contain carbohydrates, alkaloids, flavonoids, saponins, phytosterols, phenolics and tannins. Aqueous extract contains carbohydrates, alkaloids, flavonoids, glycosides, phytosterols and triterpenoids. These phytoconstituents may be responsible for the hypoglycaemic activity of the plant. PMID:23960740

  6. Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.

    PubMed

    Ravidà, Alessandra; Musante, Luca; Kreivi, Marjut; Miinalainen, Ilkka; Byrne, Barry; Saraswat, Mayank; Henry, Michael; Meleady, Paula; Clynes, Martin; Holthofer, Harry

    2015-05-01

    Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. A panel of 12 plant lectins was used in the screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. Our data confirm a substantial link between glycosylation signature and diabetes progression. Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease. PMID:25587705

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

    PubMed

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

    2013-01-01

    The in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP, was induced by a single administration of STZ (55 mg·kg(-1), i.p.). In the drug-treated groups, treatment with bis-1,4-DHP (10 mg·kg(-1)·day(-1)) started one week before diabetes induction; bis-1,4-DHP was dissolved in DMSO (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). Parameters evaluated were body weight, blood glucose, albuminuria, proteinuria, creatinine, urea excretion, kidney's weight / body weight ratio, and kidney perfusion pressure in all rat groups at different times of diabetes (2, 4, 6, and 10 weeks). Kidney weight of diabetic rats significantly increased vs. control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats at different times of diabetes. The ratios % kidney weight / 100 g body weight were different between control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats vs. diabetic rats (P < 0.05). Kidney perfusion pressure was decreased by diabetes, while it was partially recovered by bis-1,4-DHP treatment in response to phenylephrine. Bis-1,4-DHP had a tendency to decrease hyperglycemia vs. diabetic rats, even though glycemia was too high as compared with controls, and it ameliorated albuminuria, creatinine, and urea excretion, suggesting a favorable effect on renal haemodynamics. Bis-1,4-DHP, by inhibiting Ca(2+) entrance, induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction, but does not have significant impact on hyperglycemia. PMID:23823933

  8. ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats

    PubMed Central

    Chen, Xia; Fu, Xiang-Sheng; Li, Chang-Ping; Zhao, Hong-Xian

    2014-01-01

    AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis. METHODS: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4th and 12th week. The ultrastructural changes in gastric smooth muscle cells (SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78 (GRP78), and the ER-specific apoptosis mediator, caspase-12 protein, was determined by immunohistochemistry. RESULTS: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12th wk (40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P < 0.05). Swollen and distended ER with an irregular shape was observed in gastric SMCs in diabetic rats. Apoptosis of gastric SMCs increased in the diabetic rats in addition to increased expression of GRP78 and caspase-12 proteins. CONCLUSION: ER stress and ER stress-mediated apoptosis are activated in gastric SMCs in diabetic rats with gastroparesis. PMID:25009401

  9. 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

  10. Antidiabetic potentials of Momordica charantia and Andrographis paniculata and their effects on estrous cyclicity of alloxan-induced diabetic rats

    Microsoft Academic Search

    B. A. S. Reyes; N. D. Bautista; N. C. Tanquilut; R. V. Anunciado; A. B. Leung; G. C. Sanchez; R. L. Magtoto; P. Castronuevo; H. Tsukamura; K.-I. Maeda

    2006-01-01

    Momordica charantia and Andrographis paniculata are the commonly used herbs by the diabetic patients in Pampanga, Philippines. While the anti-diabetic potential of Momordica charantia is well established in streptozocin- or alloxan-induced diabetic animals, the anti-diabetic potential of Andrographis paniculata in alloxan-induced diabetic rat is not known. Neither the effects of these herbs on estrous cyclicity of alloxan-induced diabetic rats are

  11. A Diet Producing a Low Diabetes Incidence Modifies Immune Abnormalities in Diabetes-Prone BB Rats123

    Microsoft Academic Search

    CATHERINE J. FIELD

    The effect of feeding a diet that produces a high or low incidence of diabetes on immune abnor malities proposed to contribute to the pathogenesis of autoimmune-mediated diabetes was investigated. Di abetes-prone (BBdp) and nondiabetes-prone (BBn) BB rats (21 d) were fed for 21 da non pur ¡fled (high inci dence) or purified (low diabetes incidence) diet. Com pared with

  12. Sodium-Glucose Cotransporter Inhibition Prevents Oxidative Stress in the Kidney of Diabetic Rats

    PubMed Central

    Osorio, Horacio; Coronel, Israel; Arellano, Abraham; Pacheco, Ursino; Bautista, Rocío; Franco, Martha; Escalante, Bruno

    2012-01-01

    The hyperglycemia triggers several chronic diabetic complications mediated by increased oxidative stress that eventually causes diabetic nephropathy. The aim of this study was to examine if the sodium-glucose cotransporter (SGLT2) inhibition prevents the oxidative stress in the kidney of diabetic rats. Methods. The diabetic rat model was established by intraperitoneal injection of streptozotocin (50?mg/kg). The inhibition of SGLT2 was induced by daily subcutaneous administration of phlorizin (0.4?g/kg). Oxidative stress was assessed by catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities and by immunohistochemical analysis of 3-nitrotyrosine (3-NT). Results. Streptozotocin-induced diabetes caused hyperglycemia and lower body weight. The CAT activity decreased in cortex and medulla from diabetic rats; in contrast, the GPx activity increased. Furthermore the 3-NT staining of kidney from diabetic rats increased compared to control rats. The inhibition of SGLT2 decreased hyperglycemia. However, significant diuresis and glucosuria remain in diabetic rats. The phlorizin treatment restores the CAT and GPX activities and decreases 3-NT staining. Conclusion. The inhibition of SGLT2 by phlorizin prevents the hyperglycemia and oxidative stress in kidney of diabetic rats, suggesting a prooxidative mechanism related to SGLT2 activity. PMID:23227274

  13. Caraway and caper: potential anti-hyperglycaemic plants in diabetic rats

    Microsoft Academic Search

    M Eddouks; A Lemhadri; J.-B Michel

    2004-01-01

    The hypoglycaemic effect of aqueous extracts of Carum carvi (CC) and Capparis spinosa L. (CS) fruit were investigated in normal and streptozotocin (STZ) diabetic rats. After a single dose or 14 daily doses, oral administration of the aqueous CC and CS extracts (20mg\\/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (P < 0.001); the blood

  14. Pressure pain precedes development of type 2 disease in Zucker rat model of diabetes

    PubMed Central

    Romanovsky, Dmitry; Walker, James C.; Dobretsov, Maxim

    2008-01-01

    Decreased hind limb pressure pain threshold (PPT) is an early indicator of insulinopenia and neuropathy developing in STZ-rat models of type 1 diabetes and pre-diabetes. To test if pain on pressure is also a hallmark of compensated insulin resistance and type 2 diabetes in this work we measured PPT of Zucker lean (ZL), fatty (ZF) and fatty diabetic rats (ZDF; 8 animals per group). Using clinically accepted cut-off values for diagnosis of human diabetes and pre-diabetes, at 6th week of age (the study entry), all animals maintained random blood glucose within a normal range (< 7.9 mM). Over the following 4 weeks, the random glucose remained normal in lean and ZF rats; it however crossed 11 mM cut-off for the diagnosis of diabetes in all ZDF rats. With no detectable relation to blood glucose levels or changes throughout the study, lean, ZF and ZDF rats maintained respectively highest, intermediate and lowest PPT levels (83 ± 1g, 70 ± 1g and 59 ± 1 g; mean values for all tests per group). Thus in Zucker rat model, type 2 diabetes-associated impairment of nerve function precedes the development of hyperglycemia. Furthermore, since normoglycemic, but displaying decreased PPT, ZF rats were strongly hyperinsulinemic (plasma insulin concentration 30 ± 4 ng/ml vs. 2.4 ± 0.3 ng/ml in lean rats) these data suggest that hyperinsulinemia compensating for glucose metabolism might not restore compromised nerve function. PMID:18790004

  15. Combined effect of probucol and insulin on cataracts of diabetic rats fed a high cholesterol diet

    Microsoft Academic Search

    Masumi Yoshida; Hitoshi Kimura; Kouhei Kyuki; Mikio Ito

    2005-01-01

    We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on cataracts of streptozotocin-induced diabetic rats fed a high cholesterol diet. Each rat was checked for cataracts at 0, 1, 2, 4, 8, 12 and 15 weeks after streptozotocin injection. Cataracts were observed from 8 weeks in untreated hypercholesterolemic and diabetic

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

    Microsoft Academic Search

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

    1985-01-01

    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

  17. The Protective Effect of Cordymin, a Peptide Purified from the Medicinal Mushroom Cordyceps sinensis, on Diabetic Osteopenia in Alloxan-Induced Diabetic Rats.

    PubMed

    Qi, Wei; Zhang, Yang; Yan, Ya-Bo; Lei, Wei; Wu, Zi-Xiang; Liu, Ning; Liu, Shuai; Shi, Lei; Fan, Yong

    2013-01-01

    The aim of this study was to investigate the protective effect of cordymin on diabetic osteopenia in alloxan-induced diabetic rats and the possible mechanisms involved. The diabetic rats received daily intraperitoneal injection with cordymin (20, 50, and 100?mg/kg/day) for 5 weeks. Cordymin could restore the circulating blood glucose, glycosylated hemoglobin (HbA1c), serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), and insulin levels in a dose-dependent manner. Also, the treatment of diabetic rats with cordymin could partially reverse the ? cells death and decrease the total antioxidant status (TAOS) in the diabetic rats. The results may directly and indirectly account for the possible mechanism of the beneficial effect of cordymin on diabetic osteopenia, which was confirmed with the increased bone mineral content (BMC) and bone mineral density (BMD) in diabetic rats (P < 0.05). All those findings indicate that cordymin may play a protective role in diabetic osteoporosis. PMID:24174985

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

    PubMed

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

    2014-03-01

    The use of melatonin, a neurohormone present in plants, represents an exciting approach for the maintenance of optimum health conditions. Melatonin administration ameliorates glucose homeostasis in Zucker diabetic fatty (ZDF) rats. The objective of this study was to investigate the effects of melatonin in diabetes in relation to the levels and regulation of plasma chromium (Cr), vanadium (V), and magnesium (Mg) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. At the age of 6 weeks, ZDF (n = 30) and ZL (n = 30) groups were each subdivided into three groups: control (C) (n = 10), vehicle-treated (V') (n = 10) and melatonin-treated (M) (10 mg kg(-1) per day; n = 10) groups for a 6 week period. After treatment, plasma mineral concentrations were measured by flame (Mg) and electrothermal (Cr and V) atomic absorption spectrometry. No significant differences were found between the C and V' groups (p > 0.05). Plasma Mg levels were significantly lower in C-ZDF vs. C-ZL rats, demonstrating the presence of hypomagnesemia in this diabetes mellitus model. Plasma V and Cr levels were significantly higher in M-ZDF vs. C-ZDF rats. Plasma Mg levels in ZDF rats were not affected by melatonin treatment (p > 0.05). Melatonin administration ameliorates the diabetic status of ZDF rats by enhancing plasma Cr and V concentrations. This appears to be the first report of a beneficial effect of melatonin treatment on plasma Cr and V regulation in ZDF rats. PMID:24441643

  19. Antidiabetic activity of ethanolic extract of Zaleya decandra in alloxan-induced diabetic rats.

    PubMed

    Meenakshi, Periasamy; Bhuvaneshwari, Rajendran; Rathi, Muthaiyan Ahalliya; Thirumoorthi, Lakshmanan; Guravaiah, Dugganaboyana Chinna; Jiji, Muthedath Janardhanan; Gopalakrishnan, Velliyur Kanniappan

    2010-10-01

    Diabetes mellitus is a complex disorder that disturbs the metabolism of carbohydrates, fats, and proteins. Medicinal plants play an important role in the management of diabetes mellitus. The present study was aimed to evaluate the antidiabetic potential of Zaleya decandra roots on alloxan-induced diabetes in rats. Oral administration of ethanolic extract of the root (200 mg/kg body weight/day) for 15 days restored the levels of glucose, cholesterol, triglycerides, total proteins, urea, creatinine, lipid peroxidation level, and antioxidant enzymes significantly in diabetic rats. Histopathological studies showed significant changes like necrosis and degeneration in the liver and pancreas of alloxan-induced diabetic rats. Also these histopathological abnormalities were found to be normalized after treatment with Z. decandra extract. The efficacy of the root extract was found to be equivalent when compared to the standard hypoglycemic drug glibenclamide (1.25 mg/kg body weight/day, orally) in diabetic rats. PMID:19957208

  20. 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.

  1. Activation of spinal cannabinoid CB2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.

    PubMed

    Ikeda, H; Ikegami, M; Kai, M; Ohsawa, M; Kamei, J

    2013-10-10

    The role of spinal cannabinoid systems in neuropathic pain of streptozotocin (STZ)-induced diabetic mice was studied. In normal mice, injection of the cannabinoid receptor agonist WIN-55,212-2 (1 and 3?g, i.t.) dose-dependently prolonged the tail-flick latency, whereas there were no changes with the injection of either cannabinoid CB1 (AM 251, 1 ?g, i.t.) or CB2 (AM 630, 4 ?g, i.t.) receptor antagonists. AM 251 (1 ?g, i.t.), but not AM 630 (4 ?g, i.t.), significantly inhibited the prolongation of the tail-flick latency induced by WIN-55,212-2 (3 ?g, i.t.). In STZ-induced diabetic mice, the tail-flick latency was significantly shorter than that in normal mice. A low dose of WIN-55,212-2 (1 ?g, i.t.) significantly recovered the tail-flick latency in STZ-induced diabetic mice. The effect of WIN-55,212-2 (1 ?g, i.t.) in STZ-induced diabetic mice was significantly inhibited by AM 630 (4 ?g, i.t.), but not AM 251 (1 ?g). The selective cannabinoid CB2 receptor agonist L-759,656 (19 and 38 ?g, i.t.) also dose-dependently recovered the tail-flick latency in STZ-induced diabetic mice, and this recovery was inhibited by AM 630 (4 ?g, i.t.). The protein levels of cannabinoid CB1 receptors, CB2 receptors and diacylglycerol lipase ? (DGL-?), the enzyme that synthesizes endocannabinoid 2-arachidonoylglycerol, in the spinal cord were examined using Western blotting. The protein levels of both cannabinoid CB1 and CB2 receptors were increased in STZ-induced diabetic mice, whereas the protein level of DGL-? was significantly decreased. These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain. PMID:23892011

  2. Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus

    PubMed Central

    Kim, Ji-Hye; Kang, Min-Jung; Choi, Ha-Neul; Jeong, Soo-Mi; Lee, Young-Min

    2011-01-01

    The objective of this study was to investigate the hypoglycemic effects of quercetin (QE) in animal models of diabetes mellitus (DM). A starch solution (1 g/kg) with and without QE (100 mg/kg) or acarbose (40 mg/kg) was orally administered to streptozotocin (STZ)-induced diabetic rats after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. To study the effects of chronic feeding of QE, five-week-old db/db mice were fed an AIN-93G diet, a diet containing QE at 0.08%, or a diet containing acarbose at 0.03% for 7 weeks after 1 week of adaptation. Plasma glucose and insulin, blood glycated hemoglobin, and maltase activity of the small intestine were measured. Oral administration of QE (100 mg/kg) or acarbose (40 mg/kg) to STZ-treated rats significantly decreased incremental plasma glucose levels 30-180 min after a single oral dose of starch and the area under the postprandial glucose response, compared with the control group. QE (0.08% of diet) or acarbose (0.03% of diet) offered to db/db mice significantly reduced both plasma glucose and blood glycated hemoglobin compared to controls without significant influence on plasma insulin. Small intestine maltase activities were significantly reduced by consumption of QE or acarbose. Thus, QE could be effective in controlling fasting and postprandial blood glucose levels in animal models of DM. PMID:21556223

  3. Antidiabetic and antihyperlipidaemic effect of alcoholic Syzigium cumini seeds in alloxan induced diabetic albino rats

    Microsoft Academic Search

    P. Stanely Mainzen Prince; N. Kamalakkannan; Venugopal P. Menon

    2004-01-01

    Syzigium cumini, commonly known as ‘jamun’, is widely used in different parts of India for the treatment of diabetes mellitus. The present study was designed to evaluate the antidiabetic and antihyperlipidaemic effect of an alcoholic extract of Syzigium cumini seeds (JSEt) in alloxan diabetic rats. Diabetes was induced by single intraperitoneal injection of alloxan (150mgkg?1 body weight). Oral administration of

  4. Antidiabetic and hypolipidemic effects of Momordica cymbalaria Hook. fruit powder in alloxan-diabetic rats.

    PubMed

    Rao, B K; Kesavulu, M M; Giri, R; Appa Rao, C

    1999-10-01

    This study was undertaken to investigate the effect of Momordica cymbalaria fruit powder on blood glucose and other biochemical parameters in alloxan-induced diabetic rats. The treatment was given for 15 days. After the treatment, a significant reduction was observed in fasting blood glucose levels in the treated diabetic rats, but no hypoglycaemic activity in the treated normal rats. M. cymbalaria treatment showed considerable lowering of serum cholesterol and triglycerides in the treated diabetic group. There was a significant improvement in hepatic glycogen level in treated diabetic rats close to normal level after the treatment with M. cymbalaria. These results suggest that the M. cymbalaria fruit powder possesses antidiabetic and hypolipidemic effects in alloxan-induced diabetic rats. PMID:10616966

  5. Role of thirst and visual barriers in the differential behavior displayed by streptozotocin-treated rats in the elevated plus-maze and the open field test.

    PubMed

    Rebolledo-Solleiro, Daniela; Crespo-Ramírez, Minerva; Roldán-Roldán, Gabriel; Hiriart, Marcia; Pérez de la Mora, Miguel

    2013-08-15

    Conflicting results have been obtained by several groups when studying the effects of streptozotocin (STZ)-treated rats in the elevated plus-maze (EPM). Since thirst is a prominent feature in STZ-induced diabetic-like condition, we studied whether the walls of the closed arms of the EPM, by limiting the search for water in the environment, may contribute to the observed differential behavioral outcomes. The aim of this study was to ascertain whether visual barriers within the EPM have an influence on the behavior of STZ-treated rats in this test of anxiety. A striking similarity between STZ-treated (50 mg/kg, i.p., in two consecutive days) and water deprived rats (72 h) was found in exploratory behavior in the EPM, showing an anxiolytic-like profile. However the anxiolytic response of STZ-treated rats exposed to the EPM shifts into an anxiogenic profile when they are subsequently tested in the open-field test, which unlike the EPM is devoid of visual barriers. Likewise, water deprived rats (72 h) also showed an anxiogenic profile when they were exposed to the open-field test. Our results indicate that experimental outcomes based on EPM observations can be misleading when studying physiological or pathological conditions, e.g. diabetes, in which thirst may increase exploratory behavior. PMID:23948672

  6. Normalization of hyperglycaemia by oral vanadyl sulfate does not reverse diabetes-induced protection against cisplatin nephrotoxicity in streptozotocin-diabetic rats.

    PubMed

    Sarangarajan, R; Cacini, W

    1999-10-01

    Streptozotocin- and galactose-induced diabetic rats are protected against nephrotoxic effects of cisplatin. While the mechanism remains to be defined, protection is associated with a decrease in the accumulation of platinum in renal cortical tissues of streptozotocin-diabetic versus non-diabetic rats. A physiological abnormality common to streptozotocin and galactosemic models of diabetes is hyperglycaemia, suggesting that elevated sugars are involved in mediating protection of diabetic kidney against cisplatin nephrotoxicity. The current study focused on the effect of normalization of hyperglycaemia by vanadyl sulfate trihydrate on the initiation of protection and accumulation of platinum in kidneys of streptozotocin-diabetic rats. Streptozotocin-diabetic rats were treated with 0.75 mg/ml of vanadyl sulfate trihydrate in drinking water to normalize streptozotocin-induced hyperglycaemia. Vanadyl sulfate treatment normalized plasma glucose and glycosylated haemoglobin levels in streptozotocin-diabetic rats to values observed for non-diabetic rats. Intraperitoneal administration of cisplatin (5 mg/kg body weight) increased blood urea nitrogen by a factor >2.5 over baseline in both untreated and vanadyl-treated non-diabetic groups. Cisplatin-induced increases in blood urea nitrogen were 1.6 times baseline in both untreated and vanadyl-treated streptozotocin-diabetic rats. Renal platinum accumulation was significantly lower in streptozotocin-diabetic versus non-diabetic rats regardless of vanadyl sulfate treatment. Renal vanadium levels in all groups of diabetic rats were not significantly different from each other. These results indicate that normalization of plasma glucose levels with vanadyl sulfate in streptozotocin-diabetic rats did not reverse protection of streptozotocin-diabetic kidney against cisplatin nephrotoxicity. PMID:10563515

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

    PubMed Central

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

    2015-01-01

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

  8. Identification of genetic loci involved in diabetes using a rat model of depression

    Microsoft Academic Search

    Leah C. Solberg Woods; Nasim Ahmadiyeh; Amber Baum; Kazuhiro Shimomura; Qian Li; Donald F. Steiner; Fred W. Turek; Joseph S. Takahashi; Gary A. Churchill; Eva E. Redei

    2009-01-01

    While diabetic patients often present with comorbid depression, the underlying mechanisms linking diabetes and depression\\u000a are unknown. The Wistar Kyoto (WKY) rat is a well-known animal model of depression and stress hyperreactivity. In addition,\\u000a the WKY rat is glucose intolerant and likely harbors diabetes susceptibility alleles. We conducted a quantitative trait loci\\u000a (QTL) analysis in the segregating F2 population of

  9. Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats

    Microsoft Academic Search

    Sima Nasri; Mehrdad Roghani; Tourandokht Baluchnejadmojarad; Tahereh Rabani; Mahboubeh Balvardi

    2011-01-01

    Background and objective: Considering the high incidence of cardiovascular disorders in diabetes mellitus and some evidence on the antioxidant and antidiabetic potential of cyanidin-3-glucoside (C3G), this study was conducted to evaluate the possible beneficial effect of C3G administration on vascular reactivity of isolated thoracic aorta in diabetic rats and some of its underlying mechanisms. Materials and methods: Male diabetic rats

  10. Telmisartan improves vascular function and reduces platelet activation in rats with streptozotocin-induced diabetes mellitus

    Microsoft Academic Search

    Andreas Schäfer; Ulrike Flierl; Christian Vogt; Stefanie Menninger; Piet Tas; Georg Ertl; Johann Bauersachs

    2007-01-01

    Diabetes is associated with vascular dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. We investigated whether the angiotensin II antagonist telmisartan improves vascular dysfunction and reduces platelet activation in diabetic rats. Therefore, male Wistar rats were injected with streptozotocin (50mgkg?1 i.v.) to induce insulin-deficient diabetes. Treatment with telmisartan (10mgkg?1day?1) or vehicle was initiated 2 weeks

  11. Polyol Metabolism of Retrograde Axonal Transport in Diabetic Rat Large Optic Nerve Fiber

    Microsoft Academic Search

    Masanori Ino-ue; Lixin Zhang; Hiroaki Naka; Hiroshi Kuriyama; Misao Yamamoto

    PURPOSE. The role of the polyol pathway metabolism in progressive impairment of retrograde axonal transport was evaluated in the optic nerve of rats with streptozotocin-induced diabetes. METHODS. Rats with streptozotocin-induced diabetes received a low (3 mg\\/kg body weight) or high dose (10 mg\\/kg body weight) of oral aldose reductase inhibitor (ARI). At 1 and 3 months after induction of diabetes,

  12. Protection by Vanadium, a Contemporary Treatment Approach to Both Diabetes and Focal Cerebral Ischemia in Rats

    Microsoft Academic Search

    Zhenquan Liu; Pengtao Li; Dan Zhao; Huiling Tang; Jianyou Guo

    There is now substantial epidemiological evidence that diabetes is a risk factor for cerebrovascular disease. The protection\\u000a by vanadium from focal cerebral ischemia in diabetic rats was studied in this paper. Rats with streptozotocin-induced diabetes\\u000a were subjected to middle cerebral artery occlusion followed by 4 weeks of administration of 0.6 mg\\/ml sodium orthovanadate\\u000a in drinking water. Vanadium significantly improved the outcome in

  13. Cardiac Oxidative Stress Is Elevated at the Onset of Dilated Cardiomyopathy in Streptozotocin-Diabetic Rats

    Microsoft Academic Search

    María J. Crespo; Joaquin Zalacaín; Donald C. Dunbar; Nildris Cruz; Lucy Arocho

    2008-01-01

    The association between nitric oxide synthase (eNOS and iNOS) status, oxidative stress, and cardiac function was evaluated in streptozotocin (STZ)-diabetic rats to understand the etiology of diabetic cardiomyopathy. Cardiac function was determined by echocardiography. eNOS and iNOS status and superoxide production were assessed by immunohistochemistry and chemiluminescence, respectively. In STZ-diabetic rats, stroke volume, cardiac output, and left ventricular ejection fraction

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

    PubMed Central

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

    2012-01-01

    Background & objectives: A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Methods: Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. Results: A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. Interpretation & conclusions: The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats. PMID:22771592

  15. Effect of human umbilical cord blood CD34+ progenitor cells transplantation in diabetic mice

    Microsoft Academic Search

    Mona AbdElabry Hasein; Fadia Mostafa Attia; Mohamed Mohy Eldin Awad; Howedya Ahmed Abdelaal; Magady Elbarabary

    Shortage of donor organs spurs research into alternative means of generating ? cells. Stem cells might represent a potential\\u000a source of tissues for cell therapy protocols, and diabetes is a candidate disease that may benefit from cell replacement protocols.\\u000a We examined the effect of transplanted human umbilical cord blood CD34+ cells on some detailed parameters in streptozotocin-\\u000a (STZ) induced diabetic

  16. Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats

    Microsoft Academic Search

    M. M. Mahfouz; F. A. Kummerow

    2005-01-01

    The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and

  17. 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

  18. Alterations in free radical scavenger system profile of type I diabetic rat brain

    Microsoft Academic Search

    Sanjeev Kumar Bhardwaj; Poonam Sharma; Gurcharan Kaur

    1998-01-01

    The activities of the enzymes related to glutathione synthesis, degradation, and functions as well as reactive oxygen scavenging\\u000a enzymes were analyzed in different brain regions, such as cerebral hemisphere, cerebellum, brainstem, thalamus, and hypothalamus\\u000a after 1 and 3 mo of streptozotocin-induced diabetes in rats. Parallel studies were also made in age-matched control rats and\\u000a insulin-treated diabetic rats. The content of

  19. Activation of opioid ?-receptor by loperamide to lower plasma glucose in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    I.-Min Liu; Tzong-Cherng Chi; Yun Chueh Chen; Feng-Hwa Lu; Juei-Tang Cheng

    1999-01-01

    We investigated the effect of loperamide, a selective agonist of opioid ?-receptor, on the plasma glucose in diabetic rats induced by an intravenous injection of streptozotocin (STZ; 60 mg\\/kg). Intravenous injection of loperamide induced a dose-dependent decrease of plasma glucose in fasting STZ-diabetic rats at 30 min later, but did not modify the plasma glucose level in Wistar rats. Plasma

  20. Dietary Plant Materials and Development of Diabetes in the BB Rat

    Microsoft Academic Search

    JAFAR HOORFAR; SER W. SCOTT; HEATHER E. CLOÃœTIER

    The present study was designed to ex amine further the impact of individual plant protein sources found in a diabetogenic, cereal-based, rodent laboratory diet, NIH-07 (open formula, nonpurified rat and mouse diet (positive control)), on the development of diabetes. Diabetes-prone BB rats that were pan- T(OX19+)-lymphopenic were fed a low diabetogenic diet during gestation and lactation. Progeny of these rats

  1. Hydrolysed Casein Diet Protects BB Rats from Developing Diabetes by Promoting Islet Neogenesis

    Microsoft Academic Search

    Gen-Sheng Wang; Heidi Gruber; Peter Smyth; Olga Pulido; Lawrence Rosenberg; William Duguid; Fraser W Scott

    2000-01-01

    Feeding diabetes-prone BioBreeding (BBdp) rats a hydrolysed-casein (HC)-based semi-purified diet results in two-to-three-fold fewer diabetes cases compared with feeding cereal-based diets such as NIH-07 (NIH). We showed previously that young NIH-fed BBdp rats had decreased islet area at a time when classic insulitis was minimal. Rats fed an HC diet maintained near normal islet area followed 3–4 weeks later by

  2. Protective effect of vanadyl sulfate on the pancreas of streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Sema Bolkent; Sehnaz Bolkent; Refiye Yanardag; Sevim Tunali

    2005-01-01

    The aim of this study is to examine from a biochemical and histological perspective, whether vanadium has a protective effect on the pancreas of diabetic rats. Male, 6–6.5 months old, Swiss albino rats were divided into four groups. Group I: control (intact) animals (n=13). Group II: control rats given vanadyl sulfate (n=5). Group III: streptozotocin-induced diabetic animals (n=11). Group IV:

  3. 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

  4. The influence of gender, diabetes, and acetaldehyde on the intrinsic contractile properties of isolated rat myocardium

    Microsoft Academic Search

    Ricardo A. Brown; Marci J. Anthony; Pauline Petrovski; Jun Ren

    2001-01-01

    Diabetes is associated with ventricular dysfunction. Ethanol consumption increases the risk of cardiovascular disease among\\u000a diabetics. Acetaldehyde (ACA), the main ethanol metabolite, depresses cardiac contraction and contributes to ethanol-induced\\u000a cardiac dysfunction. This study examined the influence of gender and diabetes on ACA-induced myocardial dysfunction. Adult\\u000a male and female rats were made diabetic with streptozotocin (55 mg\\/kg). Left ventricular papillary muscles

  5. Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats.

    PubMed

    Suresh Babu, P; Srinivasan, K

    1998-04-01

    Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT, alkaline and acid phosphatases. The integrity of kidney was assessed by measuring the activities of several key enzymes of the renal tissue: glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate metabolism), aldose reductase and sorbitol dehydrogenase (polyol pathway), transaminases, ATPases and membrane PUFA/SFA ratio (membrane integrity). Data on enzymuria, albuminuria, activity of kidney ATPases and fatty acid composition of renal membranes in diabetic condition suggested that dietary curcumin brought about significant beneficial modulation of the progression of renal lesions in diabetes. These findings were also corroborated by histological examination of kidney sections. It is inferred that this beneficial ameliorating influence of dietary curcumin on diabetic nephropathy is possibly mediated through its ability to lower blood cholesterol levels. PMID:9562245

  6. Perturbation in kidney lipid metabolic profiles in diabetic rats with reference to alcoholic oxidative stress.

    PubMed

    Shanmugam, K R; Ramakrishna, C H; Mallikarjuna, K; Reddy, K Sathyavelu

    2009-07-01

    Diabetes is a major threat to global public health, and the number of diabetic patients is rapidly increasing worldwide. Evidence suggests that oxidative stress is involved in the pathophysiology of diabetic complications and alcoholic diseases. The aim of this study is to find out the impact of alcohol on lipid metabolic profiles in kidney tissue under streptozotocin induced diabetic condition. No study has been reported so far on the effect of alcohol on diabetic condition and also with reference to lipid metabolic profiles. Hence, the present study has been designed to elucidate the impact of alcoholism on diabetic condition. Male wistar strain albino rats were randomly divided into four groups: control (saline treated) NC, alcohol-treated (At), diabetic control (DC), and alcohol-treated diabetic rats (D+At). In alcohol-treated diabetic rats, we observed high levels of MDA, total cholesterol, triglycerides, phospholipids and also high levels of blood glucose than other groups. Moreover, degenerative changes of renal cells in alcohol-treated diabetic group were maximized by administration of alcohol as evinced by histopathological examination. This study suggests that alcohol consumption could be an aggravation factor which contributes for the formation of free radicals in diabetic condition. Therefore, consumption of alcohol during diabetic condition is harmful. PMID:20436729

  7. Effects of silymarin on the pharmacokinetics of atorvastatin in diabetic rats.

    PubMed

    Malekinejad, Hassan; Rokhsartalab-Azar, Shirin; Hassani-Dizaj, Sepideh; Alizadeh-Fanalou, Shahin; Rezabakhsh, Aysa; Amniattalab, Amir

    2014-12-01

    The effect of silymarin (SMN) on the pharmacokinetics of atorvastatin in diabetic rats was evaluated. Male Wistar rats were assigned into two major groups and then sub-grouped according to the purposes of the study. The first major group was subdivided into three groups (n = 6) including control, non-treated diabetic and SMN-treated diabetic animals. In the first major group, metabolism of testosterone by the hepatic microsomes was studied. The second major group also was divided to three groups including atorvastatin-treated non-diabetic, atorvastatin-treated diabetic and diabetic animals which received both atorvastatin and SMN. To study the pharmacokinetics of atorvastatin, serum samples were collected at 0, 3, 6, 12 and 24 h after the atorvastatin administration. Pharmacokinetic parameters were calculated using non-compartmental model. Streptozotocin-induced diabetes resulted in a remarkable induction of testosterone hydroxylation as the V max for 6?-hydroxytestosterone production in the diabetic rats (77.3 ± 8.6 pM/min/mg) was significantly higher than that in the control animals (45.9 ± 5.9 pM/min/mg). Moreover, SMN-treated animals showed a significant (P < 0.05) reduction of V max (59.4 ± 6.1 pM/min/mg). Diabetes resulted in a significant reduction of AUC (control 6.98 ± 0.58 vs diabetic rats 4.35 ± 0.24 h mg/ml) and C max values (control 0.52 ± 0.03 vs diabetic group 0.33 ± 0.01 ?g/ml), while the SMN-received group showed remarkable recovery of diabetes-reduced values of AUC and C max. These findings indicated that diabetes resulted in a significant up-regulation of microsomal enzyme activities. Moreover, as SMN could significantly regulate the enzyme activities and consequently the atorvastatin pharmacokinetics in diabetic rats, its regulative effect in a combination therapy is concluded. PMID:24346850

  8. Cobalt-Protoporphyrin Improves Heart Function by Blunting Oxidative Stress and Restoring NO Synthase Equilibrium in an Animal Model of Experimental Diabetes

    PubMed Central

    Cao, Jian; Vecoli, Cecilia; Neglia, Danilo; Tavazzi, Barbara; Lazzarino, Giuseppe; Novelli, Michela; Masiello, Pellegrino; Wang, Yu-tang; Puri, Nitin; Paolocci, Nazareno; L’Abbate, Antonio; Abraham, Nader G.

    2012-01-01

    Myocardial dysfunction and coronary macro/microvascular alterations are the hallmarks of diabetic cardiomyopathy and are ascribed to increased oxidative stress and altered nitric oxide synthase (NOS) activity. We hypothesize that pre-treatment by cobalt-protoporphyrin IX (CoPP) ameliorates both myocardial function and coronary circulation in streptozotocin (STZ)-induced diabetic rats. Isolated hearts from diabetic rats in Langendorff configuration displayed lower left ventricular function and higher coronary resistance (CR) compared to hearts from control animals. CoPP treatment of diabetic animals (0.3?mg/100?g body weight i.p., once a week for 3?weeks) significantly increased all the contractile/relaxation indexes (p?diabetic animals, as indicated by the significant (p?diabetic heart. Furthermore, after CoPP treatment, a rise in malonyl-CoA as well as a decrease in acetyl-CoA was observed in diabetic hearts. In this experimental model of diabetic cardiomyopathy, CoPP treatment improved both cardiac function and coronary flow by blunting oxidative stress, restoring eNOS/iNOS expression balance and increasing HO-1 levels, thereby favoring improvement in both endothelial function and insulin sensitivity. PMID:22675305

  9. Taurine reverses neurological and neurovascular deficits in Zucker diabetic fatty rats.

    PubMed

    Li, Fei; Abatan, Omorodola I; Kim, Howard; Burnett, Diana; Larkin, Dennis; Obrosova, Irina G; Stevens, Martin J

    2006-06-01

    Increased oxidative stress is implicated in the pathogenesis of diabetic peripheral neuropathy (DPN). However, the efficacy of antioxidant therapy on DPN complicating type 2 diabetes remains unexplored. We therefore determined the ability of the antioxidant taurine to reverse deficits of hind limb sciatic motor and digital sensory nerve conduction velocity (NCV), nerve blood flow (NBF), and sensory thresholds in hyperglycemic Zucker diabetic fatty (ZDF) rats. Experimental groups comprised lean nondiabetic (ND), ND treated with taurine (ND + T), untreated ZDF diabetic (D), and D rats treated with taurine (D + T). Compared to ND rats, 23%, 15% and 56% deficits of motor NCV, sensory NCV and NBF, respectively as well as thermal and mechanical hyperalgesia were reversed by taurine. An 84% deficit of dorsal root ganglion neuron calcitonin gene-related peptide in D rats was prevented by taurine. In summary, the antioxidant taurine reverses neurological and neurovascular deficits in experimental type 2 diabetes. PMID:16624563

  10. 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

  11. Cardiovasc Res. Author manuscript Type 2 diabetes severely impairs structural and functional adaptation of rat

    E-print Network

    Paris-Sud XI, Université de

    and functional adaptation of rat resistance arteries to chronic changes in blood flow Belin De Chantem leè Eric J diabetic fatty rats (ZDF) would present an impaired flow-induced remodeling in resistance artery. Aim lean (LZ) and ZDF rats, to chronic changes in blood flow. Methods Two mesenteric resistance arteries

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

    SciTech Connect

    Thompson, K.H.; Lee, M. (Univ., of British Columbia, Vancouver (Canada))

    1991-03-15

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

  13. Arginine rich coconut kernel protein modulates diabetes in alloxan treated rats.

    PubMed

    Salil, G; Nevin, K G; Rajamohan, T

    2011-01-15

    Diabetes mellitus is a syndrome characterized by the loss of glucose homeostasis due to several reasons. In spite of the presence of known anti-diabetic medicines in the pharmaceutical market, remedies from natural resources are used with success to treat this disease. The present study was undertaken to investigate the effect of coconut kernel protein (CKP) on alloxan induced diabetes in Sprague-Dawley rats. Diabetes was induced by injecting a single dose of alloxan (150mg/kg body weight) intraperitoneally. After inducing diabetes, purified CKP isolated from dried coconut kernel was administered to rats along with a semi synthetic diet for 45 days. After the experimental period, serum glucose, insulin, activities of different key enzymes involved in glucose metabolism, liver glycogen levels and the histopathology of the pancreas were evaluated. The amount of individual amino acids of CKP was also determined using HPLC. Results showed that CKP has significant amount of arginine. CKP feeding attenuated the increase in the glucose and insulin levels in diabetic rats. Glycogen levels in the liver and the activities of carbohydrate metabolizing enzymes in the serum of treated diabetic rats were reverted back to the normal levels compared to that of control. Histopathology revealed that CKP feeding reduced the diabetes related pancreatic damage in treated rats compared to the control. These results clearly demonstrated the potent anti-diabetic activity of CKP which may be probably due to its effect on pancreatic ? cell regeneration through arginine. PMID:21050842

  14. Irbesartan Ameliorates Diabetic Nephropathy by Reducing the Expression of Connective Tissue Growth Factor and Alpha-Smooth-Muscle Actin in the Tubulointerstitium of Diabetic Rats

    Microsoft Academic Search

    Xiaojun Ren; Guangju Guan; Gang Liu; Gaohong Liu

    2009-01-01

    The effect of irbesartan on the expression of connective tissue growth factor (CTGF) and ?-smooth-muscle actin (?-SMA) in the renal tubulointerstitium of diabetic rats was investigated in our study. Diabetes was induced in male Wistar rats by intraperitoneal administration of streptozotocin (STZ), 60 mg·kg–1 body weight. The rats were then randomized to a diabetic group (DM) and an irbesartan therapy

  15. Pioglitazone reverses down-regulation of cardiac PPAR{gamma} expression in Zucker diabetic fatty rats

    SciTech Connect

    Pelzer, Theo [Department of Medicine, University of Wuerzburg (Germany)]. E-mail: pelzer_t@klinik.uni-wuerzburg.de; Jazbutyte, Virginija [Department of Medicine, University of Wuerzburg (Germany); Arias-Loza, Paula Anahi [Department of Medicine, University of Wuerzburg (Germany); Segerer, Stephan [Department of Medicine, University of Wuerzburg (Germany); Lichtenwald, Margit [Department of Medicine, University of Wuerzburg (Germany); Law, Marilyn P. [Department of Nuclear Medicine, University Hospital, Muenster (Germany); Schaefers, Michael [Department of Nuclear Medicine, University Hospital, Muenster (Germany); Ertl, Georg [Department of Medicine, University of Wuerzburg (Germany); Neyses, Ludwig [Division of Cardiology University of Manchester (United Kingdom)

    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.

  16. 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

  17. Effects on the bones of vanadyl acetylacetonate by oral administration: a comparison study in diabetic rats.

    PubMed

    Zhang, Shuang-Qing; Chen, Guo-Hua; Lu, Wan-Liang; Zhang, Qiang

    2007-01-01

    Oral delivery, rather than parenteral administration, would be beneficial for treating diabetic mellitus owing to the need for a long-term regimen. The objectives of this study were to evaluate oral delivery tolerance and the effects on the bone of accumulated vanadium following the long-term administration of vanadyl acetylacetonate (VAC). Normal and diabetic rats were intragastrically administered VAC at a dose of 3 mg vanadium/kg body weight once daily for 35 consecutive days. VAC did not cause any obvious signs of diarrhea, any changes in kidney or liver, or deaths in any group. The phosphate levels in the bone were slightly increased, and the calcium levels in the bone were not obviously changed as compared with those of the rat group not receiving VAC. After administration of VAC, the decreased ultimate strength, trabecular thickness, mineral apposition rate, and plasma osteocalcin in diabetic rats were either improved or normalized, but reduced bone mineral density (BMD) in diabetic rats was not improved. None of the parameters evaluated in normal rats were altered. The results indicate that the oral VAC is tolerated and benefits the diabetic osteopathy of rats, but seems not to influence the bone of normal rats. They also suggest that VAC improves diabetes-related bone disorders, primarily by improving the diabetic state. PMID:17704994

  18. Regenerative Therapeutic Potential of Adipose Stromal Cells in Early Stage Diabetic Retinopathy

    PubMed Central

    Rajashekhar, Gangaraju; Ramadan, Ahmed; Abburi, Chandrika; Callaghan, Breedge; Traktuev, Dmitry O.; Evans-Molina, Carmella; Maturi, Raj; Harris, Alon; Kern, Timothy S.; March, Keith L.

    2014-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved “b” wave amplitude (as measured by electroretinogram) within 1–3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration. PMID:24416262

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

    PubMed

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

    2012-08-01

    Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease (ESRD) as the burden of diabetes increases worldwide. To find improved intervention strategies for this disease, it is necessary to investigate the molecular mechanisms involved. To obtain more insight into processes that lead to DN, mRNA expression profiles of diabetic and normal glomeruli from rat kidneys were compared. Rats were divided into a control group and a DN group randomly. The DN group was injected with streptozotocin. Fasting blood glucose (FBG) and weight were measured monthly. On the 12th week, blood samples were collected and analyzed for plasma creatinine and blood urea nitrogen (BUN). Glomeruli were isolated and Illumina Rat Ref-12 V1.0 Expression Beadchip gene array was performed. Quantitative realtime polymerase chain reaction (Q-RT-PCR) was used to confirm the results of gene array for a selected number of genes. We found FBG, 24-h urinary albumin, serum creatinine and BUN were significantly increased, while urinary creatinine and body weight were significantly decreased in the DN group. Glomeruli from the DN group had 624 genes with differential expression. DAVID (Database for Annotation, Visualization and integrated Discovery) analysis showed that the three most enriched terms were 'cytosol' (GO:0005829), 'translational elongation' (GO:0006414) and 'mitochondion' (GO:0005739). Those genes could be mapped to eight pathways. The most common type of enriched pathway was related to 'extracellular matrix (ECM)-receptor interaction'. Other pathways included those for 'ribosome', 'focal adhesion', 'oxidative phosphorylation', 'transforming growth factor (TGF)-beta signaling pathway', 'Parkinson's disease', 'Alzheimer's disease' and 'renin-angiotensin system'. Q-RT-PCR verified that Atp5b (F1-ATPase beta subunit), Col1a1 (collagen type 1 alpha 1), Cox6c (cytochrome c oxidase subunit VIc), Ndufs3 (NADH dehydrogenase [ubiquinone] Fe-S protein 3) and Tgfb1 (transforming growth factor ?1) were significantly up-regulated in the DN group. The expressions of NDUFS3 and TGF-?1 in DN rats were increased. Our findings suggested that the oxidative phosphorylation pathway, ECM-receptor interaction, TGF-? pathway and renin-angiotensin system may be involved in the development of DN. PMID:22903132

  20. 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

  1. Effect of hypocholesterolemia on cholesterol synthesis in small intestine of diabetic rats

    SciTech Connect

    Feingold, K.R.; Moser, A.H.

    1987-11-01

    Studies by our and other laboratories have demonstrated that cholesterol synthesis is increased in the small intestine of insulinopenic diabetic animals. In normal animals, many factors have been shown to regulate cholesterol synthesis in the small intestine, including changes in plasma cholesterol levels. The purpose of this study was to determine the effect of lowering plasma cholesterol levels on small intestine cholesterol synthesis in streptozocin-induced diabetic rats. In diabetic rats, 4-aminopyrazolo(3,4-d)pyrimidine (4-APP)-induced hypocholesterolemia (plasma cholesterol levels less than 20 mg/dl) resulted in a 2.5-fold increase in small intestine cholesterol synthesis, which was most marked in the distal small intestine, decreasing proximally. In the distal small intestine the incorporation of /sup 3/H/sub 2/O into cholesterol was 0.28 +/- 0.04 mumol.h-1.g-1 in diabetic rats versus 1.60 +/- 0.38 in diabetic rats administered 4-APP (P less than .01). This stimulation of cholesterol synthesis occurred in the upper villus, middle villus, and crypt cells isolated from the middle intestine of the 4-APP-treated diabetic animals. In agreement with these observations, functional hypocholesterolemia due to Triton WR-1339 administration also stimulated cholesterol synthesis 2.5-fold in the small intestine of normal and diabetic animals. In the distal small intestine, cholesterol synthesis was 0.43 +/- 0.10 mumol.h-1.g-1 in the diabetic rats versus 1.08 +/- 0.21 in diabetic rats treated with Triton WR-1339 (P less than .05). In both the 4-APP and Triton WR-1339 experiments, the response of the diabetic rats was similar to that observed in normal rats.

  2. 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

  3. Polyopes lancifolia Extract, a Potent ?-Glucosidase Inhibitor, Alleviates Postprandial Hyperglycemia in Diabetic Mice

    PubMed Central

    Min, Seong Won; Han, Ji Sook

    2014-01-01

    This study was designed to investigate the inhibitory effects of Polyopes lancifolia extract (PLE) on ?-glucosidase activity, ?-amylase activitiy, and postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. The results of this study revealed a marked inhibitory effect of PLE on ?-glucosidase and ?-amylase activities. The IC50s of PLE against ?-glucosidase and ?-amylase were 0.20 mg/mL and 0.35 mg/mL, respectively. PLE was a more effective inhibitor of ?-glucosidase and ?-amylase activities than acarbose, the positive control. The postprandial blood glucose levels of STZ-induced diabetic mice were significantly lower in the PLE treated group than in the control group. Moreover, PLE administration was associated with a decreased area under the curve for the glucose response in diabetic mice. These results indicate that PLE may be a potent inhibitor of ?-glucosidase and ?-amylase activities and may suppress postprandial hyperglycemia. PMID:24772403

  4. Tempol Prevents Altered K+ Channel Regulation of Afferent Arteriolar Tone in Diabetic Rat Kidney

    PubMed Central

    Troncoso Brindeiro, Carmen M.; Lane, Pascale H.; Carmines, Pamela K.

    2012-01-01

    Experiments were performed to test the hypothesis that oxidative stress underlies the enhanced tonic dilator impact of inward-rectifier K+ (KIR) channels on renal afferent arterioles of rats with streptozotocin-induced diabetes. Sham and diabetic rats were left untreated or provided tempol in their drinking water for 26±1 days, after which afferent arteriolar lumen diameter and its responsiveness to K+ channel blockade were measured using the in vitro blood-perfused juxtamedullary nephron technique. Afferent diameter averaged 19.4±0.8 ?m in sham rats and 24.4±0.8 ?m in diabetic rats (P<0.05). The decrease in diameter evoked by Ba2+ (KIR channel blocker) was 3-times greater in diabetic rats than in sham rats. Glibenclamide (KATP channel blocker) and tertiapin-Q (Kir1.1/Kir3.x channel blocker) decreased afferent diameter in diabetic rats, but had no effect on arterioles from sham rats. Chronic tempol treatment prevented diabetes-induced increases in both renal vascular dihydroethidium staining and baseline afferent arteriolar diameter. Moreover, tempol prevented the exaggeration of afferent arteriolar responses to Ba2+, tertiapin-Q, and glibenclamide otherwise evident in diabetic rats. Preglomerular microvascular smooth muscle cells expressed mRNA encoding Kir1.1, Kir2.1 and Kir6.1. Neither diabetes nor tempol altered Kir1.1, Kir2.1, Kir6.1 or SUR2B protein levels in renal cortical microvessels. To the extent that the effects of tempol reflect its antioxidant actions, our observations indicate that oxidative stress contributes to the exaggerated impact of Kir1.1, Kir2.1 and KATP channels on afferent arteriolar tone during diabetes and that this phenomenon involves post-translational modulation of channel function. PMID:22252401

  5. Systemic Administration of Multipotent Mesenchymal Stromal Cells Reverts Hyperglycemia and Prevents Nephropathy in Type 1 Diabetic Mice

    Microsoft Academic Search

    Fernando E. Ezquer; Marcelo E. Ezquer; Daniela B. Parrau; Daniel Carpio; Alejandro J. Yañez; Paulette A. Conget

    2008-01-01

    Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 diabetes C57BL\\/6 mice, we tested whether a single intravenous dose

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

    SciTech Connect

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

    1984-06-01

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

  7. Infection With Viruses From Several Families Triggers Autoimmune Diabetes in LEW.1WR1 Rats

    PubMed Central

    Tirabassi, Rebecca S.; Guberski, Dennis L.; Blankenhorn, Elizabeth P.; Leif, Jean H.; Woda, Bruce A.; Liu, Zhijun; Winans, Donald; Greiner, Dale L.; Mordes, John P.

    2010-01-01

    OBJECTIVE The contribution of antecedent viral infection to the development of type 1 diabetes in humans is controversial. Using a newer rat model of the disease, we sought to 1) identify viruses capable of modulating diabetes penetrance, 2) identify conditions that increase or decrease the diabetogenicity of infection, and 3) determine whether maternal immunization would prevent diabetes. RESEARCH DESIGN AND METHODS About 2% of LEW.1WR1 rats develop spontaneous autoimmune diabetes, but disease penetrance is much higher if weanling rats are exposed to environmental perturbants including Kilham rat virus (KRV). We compared KRV with other viruses for diabetogenic activity. RESULTS Both KRV and rat cytomegalovirus (RCMV) induced diabetes in up to 60% of LEW.1WR1 rats, whereas H-1, vaccinia, and Coxsackie B4 viruses did not. Simultaneous inoculation of KRV and RCMV induced diabetes in 100% of animals. Pretreatment of rats with an activator of innate immunity increased the diabetogenicity of KRV but not RCMV and was associated with a moderate rate of diabetes after Coxsackie B4 and vaccinia virus infection. Inoculation of LEW.1WR1 dams with both KRV and RCMV prior to pregnancy protected weanling progeny from virus-induced diabetes in a virus-specific manner. CONCLUSIONS Exposure to viruses can affect the penetrance of autoimmune diabetes in genetically susceptible animals. The diabetogenicity of infection is virus specific and is modified by immunomodulation prior to inoculation. Maternal immunization protects weanlings from virus-induced diabetes, suggesting that modification of immune responses to infection could provide a means of preventing islet autoimmunity. PMID:19794063

  8. Altered synthesis of some secretory proteins in pancreatic lobules isolated from streptozotocin-induced diabetic rats

    SciTech Connect

    Duan, R.D.; Erlanson-Albertsson, C. (Univ. of Lund (Sweden))

    1990-03-01

    The in vitro incorporation of (35S)cysteine into lipase, colipase, amylase, procarboxypeptidase A and B, and the serine proteases and total proteins was studied in pancreatic lobules isolated from normal and diabetic rats with or without insulin treatment. The incorporation of (35S)cysteine into total proteins was 65% greater in pancreatic lobules from diabetic animals than from normal rats. The increased incorporation was partly reversed by insulin treatment (2 U/100 g/day for 5 days) of diabetic rats. The relative rates of biosynthesis for amylase and the procarboxypeptidases in diabetic pancreatic lobules were decreased by 75 and 25%, respectively, after 1 h of incubation, while those for lipase, colipase, and the serine proteases were increased by 90, 85, and 35%, respectively. The absolute rates of synthesis for these enzymes changed in the same direction as the relative rates in diabetic lobules, except that for the procarboxypeptidases, which did not change. The changed rates of biosynthesis for the pancreatic enzymes were reversed by insulin treatment of the diabetic rats. Kinetic studies showed that the incorporation of (35S)cysteine into amylase, lipase, and colipase was linear until up to 2 h of incubation in normal pancreatic lobules, while in the diabetic lobules the incorporation into lipase and colipase was accelerated, reaching a plateau level already after 1 h of incubation. It is concluded that the biosynthesis of pancreatic secretory proteins in diabetic rats is greatly changed both in terms of quantity and kinetics.

  9. Clodronate changes neurobiological effects of pulsed magnetic field on diabetic rats with peripheral neuropathy.

    PubMed

    Mert, Tufan; Ocal, Is?l; Guzel, A Irfan; Gunay, Ismail

    2013-09-01

    Several studies have reported that pulsed magnetic fields (PMFs) can be a choice of therapy for diabetic peripheral neuropathy. However, the exact underlying mechanism of PMF is still not known. The purpose of this study was, therefore, to investigate the effects of clodronate encapsulated with liposome, a specific agent depleting macrophage, on PMF-treated streptozotocin-induced type I diabetic rats with peripheral neuropathy. Effects of PMF, liposome-encapsulated clodronate (LEC) or their combined treatments were investigated in diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels, serum insulin level, and body mass. In diabetic rats, PMF exhibited a decrease in the blood glucose levels but did not change the serum insulin level. Both mechanical thresholds and thermal latencies of diabetic rats enhanced throughout the PMF treatment. During the PMF treatment, the administration of LEC suppressed the PMF-induced decrease in blood glucose level, PMF-induced increase in mechanical threshold and thermal latencies in diabetic animals. In addition, PMF reduced the LEC-induced increase in insulin levels of diabetic rats. Findings demonstrated that although effects of both PMF alone and LEC alone on diabetic animals are mostly positive, LEC may remove the therapeutic efficacies of PMF in combined treatment. PMID:23323995

  10. Hepatic glucose production from L-alanine is absent in perfused liver of diabetic rats.

    PubMed

    Ferraz, M; Brunaldi, K; Oliveira, C E; Bazotte, R B

    1997-02-01

    The effects of L-alanine on hepatic glucose production in diabetic rats and the corresponding controls was investigated. Diabetes was obtained with an injection iv of streptozotocin (STZ) or alloxan. Livers from diabetic and control rats after 24 hours of fasting were perfused in situ and glucose production from L-alanine and several gluconeogenic substrates were measured. Hepatic gluconeogenesis from L-alanine was absent in rats with diabetes induced by STZ or alloxan. STZ-diabetic rats also shown this metabolic change when the period of diabetes was prolonged. It was concluded that this effect may be partly at least, the consequence of an increased NADH/NAD+ ratio in the diabetic rat liver, which indicates that the cytosolic redox potential is favorable to pyruvate conversion to L-lactate but not to glucose. However, considering that glucose production from pyruvate, L-lactate, glycerol and sorbitol was not affected by the diabetic condition, the rate of conversion of L-alanine to pyruvate can contribute to the lack of gluconeogenesis when this amino acid was employed as a substrate. PMID:9090751

  11. 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

  12. Cerebrovascular responsiveness to NG-nitro-L-arginine methyl ester in spontaneously diabetic rats.

    PubMed Central

    Fouyas, I. P.; Kelly, P. A.; Ritchie, I. M.; Whittle, I. R.

    1996-01-01

    1. There is evidence that endothelial dysfunction is associated with diabetes mellitus. The purpose of the present study was to assess local cerebral blood flow (LCBF) and cerebrovascular responsiveness to the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in spontaneously diabetic insulin-dependent BioBred (BB) rats. 2. Diabetic rats, and non-diabetic controls, were treated with L-NAME (30 mg kg-1, i.v.) or saline, 20 min prior to the measurement of LCBF by the fully quantitative [14C]-iodoantipyrine autoradiographic technique. 3. There were no significant differences in physiological parameters (blood pH, PCO2, and PO2, rectal temperature, arterial blood pressure, or plasma glucose) between any of the groups of rats, and no difference in either the extent or the temporal characteristics of the hypertensive response to L-NAME between diabetic and non-diabetic rats. 4. In diabetic rats, a global reduction in basal LCBF was observed, although significant reductions (between -20 and -30%) were found in only 5 (mainly subcortical) out of the 13 brain regions measured. Following L-NAME injection, significant reductions in LCBF (between -20 and -40%) were found in the non-diabetic animals. In diabetic animals treated with L-NAME, a significant reduction in LCBF was measured only in the hypothalamus (-33%). 5. The cerebrovascular response to acute L-NAME is attenuated in spontaneously diabetic insulin-dependent BB rats. This would be consistent with the endothelial dysfunction in cerebral vessels, known to be associated with diabetes mellitus and it is possible that a loss of NO-induced dilator tone, amongst other factors, may underlie the observed reductions of basal LCBF in these animals. PMID:8735622

  13. Effect of glycation of albumin on its renal clearance in normal and diabetic rats

    SciTech Connect

    Layton, G.J.; Jerums, G.

    1988-03-01

    Two independent techniques have been used to study the renal clearances of nonenzymatically glycated albumin and nonglycated albumin in normal and streptozotocin-induced diabetic rats, 16 to 24 weeks after the onset of diabetes. In the first technique, serum and urinary endogenous glycated and nonglycated albumin were separated using m-aminophenylboronate affinity chromatography and subsequently quantified by radioimmunoassay. Endogenous glycated albumin was cleared approximately twofold faster than nonglycated albumin in normal and diabetic rats. However, no difference was observed in the glycated albumin/nonglycated albumin clearance ratios (Cga/Calb) in normal and diabetic rats, respectively (2.18 +/- 0.39 vs 1.83 +/- 0.22, P greater than 0.05). The second technique measured the renal clearance of injected 125I-labelled glycated albumin and 125I-labelled albumin. The endogenous results were supported by the finding that 125I-labelled glycated albumin was cleared more rapidly than 125I-labelled albumin in normal (P less than 0.01) and diabetic (P less than 0.05) rats. The Cga/Calb ratio calculated for the radiolabelled albumins was 1.4 and 2.0 in normal and diabetic rats, respectively. This evidence suggests that nonenzymatic glycation of albumin increases its renal clearance to a similar degree in normal and diabetic rats.

  14. 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

  15. Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    William C. S. Cho; Wai-Shing Chung; Sally K. W. Lee; Albert W. N. Leung; Christopher H. K. Cheng; Kevin K. M. Yue

    2006-01-01

    Diabetes mellitus is characterized by hyperglycemia and complications affecting the eye, kidney, nerve and blood vessel. We have previously demonstrated the occurrence of oxidative stress of streptozotocin-induced diabetic rats, preceded by a depletion in the tissue level of glutathione. In this study, when diabetic rats were treated with ginsenoside Re of Panax ginseng C.A. Meyer, there was a significant reduction

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

    PubMed

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

    2009-08-01

    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

  17. 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

  18. 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

  19. Neuroprotective Effects of Rutin in Streptozotocin-Induced Diabetic Rat Retina.

    PubMed

    Ola, Mohammad Shamsul; Ahmed, Mohammed M; Ahmad, Rehan; Abuohashish, Hatem M; Al-Rejaie, Salim S; Alhomida, Abdullah S

    2015-06-01

    Diabetic retinopathy is widely recognized as a neurodegenerative disease of the eye. Increased oxidative stress has been considered the central factor in damaging neural retina in diabetes. Flavonoids, being powerful antioxidants, play protective roles in several oxidative stress-mediated neurodegenerative diseases. In this study, we analyzed the neuroprotective effects of a potential flavonoid, rutin, in the diabetic rat retina. Diabetes was induced in male Wistar rats by single injection of streptozotocin (65 mg/kg). In age-matched control (non-diabetic) and 1 week of diabetic rats, rutin (100 mg/kg/day) was orally administered and continued for 5 weeks. In another group of diabetic rats, only saline was supplemented. After treatments, retinas from all the groups were isolated and analyzed for potential neurotrophic factors and apoptotic and oxidative stress markers using biochemical and immunoblotting techniques. Our results indicate that rutin possesses antidiabetic activity, as blood glucose level decreased and insulin level increased in diabetic rats. In the diabetic retina, rutin supplementation enhanced the reduced levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glutathione (GSH) (P?diabetic retina. These results suggest the effectiveness of rutin in ameliorating the levels of neuroprotective factors in diabetic retina. Therefore, rutin might be a potential flavonoid that can prevent the retinal damage and subsequently the development of diabetic retinopathy. PMID:25929832

  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. (University Hospital, Zurich (Switzerland))

    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. Hypoglycaemic effects of alcoholic root extract of Borassus flabellifer (Linn.) in normal and diabetic rats.

    PubMed

    Debnath, Titas; Radhakrishnan, Rajesh; Murugananthan, Gopal; Talwar, Sahil; K, Nandakumar

    2013-07-01

    The objective of the study was to investigate the alcoholic (ALEBF) extract of B. flabellifer for their hypoglycaemic effects in normal and diabetic rats. Diabetes was induced in rats by single dose administration of alloxan (120 mg/kg, i.p.) or by injecting dexamethasone (10 mg/kg, i.p.) for 10 days. In normal rats, ALEBF (100, 200 and 400 mg/kg) had significantly decreased the blood glucose level in a dose dependent manner after repeated administration for 7 days. In alloxan induced diabetic rats, extract (ALEBF) had decreased blood sugar level and improved glucose tolerance in alloxan induced diabetic rats at the end of 1st, 2nd , 3rd and 4th week after test extract treatment. However, the insulin levels of extract treated group did not significantly change after 28 days treatment with the extract. It did not alter the insulin levels. In alloxan model, repeated dose administration of ALEBF had showed significant increase in body weight, prevention of elimination of sugar in urine and reduced the mortality rate induced by alloxan. In dexamethasone induced insulin resistance diabetic rats, repeated administration of ALEBF inhibited the increase in blood glucose level, improved glucose tolerance and reduced the insulin levels as compared dexamethasone induced diabetic rats. PMID:23811441

  2. Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. Possible mediation by glucose

    SciTech Connect

    Craven, P.A.; DeRubertis, F.R.

    1989-05-01

    Glomerular inositol content and the turnover of polyphosphoinositides was reduced by 58% in 1-2 wk streptozotocin diabetic rats. Addition of inositol to the incubation medium increased polyphosphoinositide turnover in glomeruli from diabetic rats to control values. Despite the reduction in inositol content and polyphosphoinositide turnover, protein kinase C was activated in glomeruli from diabetic rats, as assessed by an increase in the percentage of enzyme activity associated with the particulate cell fraction. Total protein kinase C activity was not different between glomeruli from control and diabetic rats. Treatment of diabetic rats with insulin to achieve near euglycemia prevented the increase in particulate protein kinase C. Moreover, incubation of glomeruli from control rats with glucose (100-1,000 mg/dl) resulted in a progressive increase in labeled diacylglycerol production and in the percentage of protein kinase C activity which was associated with the particulate fraction. These results support a role for hyperglycemia per se in the enhanced state of activation of protein kinase C seen in glomeruli from diabetic rats. Glucose did not appear to increase diacylglycerol by stimulating inositol phospholipid hydrolysis in glomeruli. Other pathways for diacylglycerol production, including de novo synthesis and phospholipase C mediated hydrolysis of phosphatidylcholine or phosphatidyl-inositol-glycan are not excluded.

  3. Reduction of diabetes incidence of BB Wistar rats by early prophylactic insulin treatment of diabetes-prone animals

    Microsoft Academic Search

    C. F. Gotfredsen; K. Buschard; E. K. Frandsen

    1985-01-01

    Summary  A group of 36 diabetes-prone BB Wistar rats were given prophylactic insulin treatment with heat-treated bovine ultralente insulin (15 IU · kg–1 · day–1) from 50 to 142 days of age. The incidence of Type 1 (insulin-dependent) diabetes at the end of the treatment period was compared to that of 36 control animals given insulin only from the first day

  4. Evaluation of buspirone on streptozotocin induced type 1 diabetes and its associated complications.

    PubMed

    Raghunathan, Suchi; Tank, Pratik; Bhadada, Shraddha; Patel, Bhoomika

    2014-01-01

    We have evaluated the effect of buspirone (1.5?mg/kg/day, p.o.) type 1 diabetes induced cardiovascular complications induced by streptozotocin (STZ, 45?mg/kg, i.v.) in Wistar rats. Various biochemical, cardiovascular, and hemodynamic parameters were measured at the end of 8 weeks of treatment. STZ produced significant hyperglycaemia, hypoinsulinemia, and dyslipidemia, which was prevented by buspirone treatment. STZ produced increase in serum creatinine, urea, lactate dehydrogenase, creatinine kinase, and C-reactive protein levels and treatment with buspirone produced reduction in these levels. STZ produced increase in cardiac and LV hypertrophy index, LV/RV ratio, and LV collagen, which were decreased by buspirone treatment. Buspirone also prevented STZ induced hemodynamic alterations and oxidative stress. These results were further supported by histopathological studies in which buspirone showed marked reduction in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that buspirone is beneficial as an antidiabetic agent in type 1 diabetes mellitus and also prevents its cardiac complications. PMID:24563867

  5. Evaluation of Buspirone on Streptozotocin Induced Type 1 Diabetes and Its Associated Complications

    PubMed Central

    Raghunathan, Suchi; Bhadada, Shraddha

    2014-01-01

    We have evaluated the effect of buspirone (1.5?mg/kg/day, p.o.) type 1 diabetes induced cardiovascular complications induced by streptozotocin (STZ, 45?mg/kg, i.v.) in Wistar rats. Various biochemical, cardiovascular, and hemodynamic parameters were measured at the end of 8 weeks of treatment. STZ produced significant hyperglycaemia, hypoinsulinemia, and dyslipidemia, which was prevented by buspirone treatment. STZ produced increase in serum creatinine, urea, lactate dehydrogenase, creatinine kinase, and C-reactive protein levels and treatment with buspirone produced reduction in these levels. STZ produced increase in cardiac and LV hypertrophy index, LV/RV ratio, and LV collagen, which were decreased by buspirone treatment. Buspirone also prevented STZ induced hemodynamic alterations and oxidative stress. These results were further supported by histopathological studies in which buspirone showed marked reduction in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that buspirone is beneficial as an antidiabetic agent in type 1 diabetes mellitus and also prevents its cardiac complications. PMID:24563867

  6. Antidiabetic and antihyperlipidaemic effect of alcoholic Syzigium cumini seeds in alloxan induced diabetic albino rats.

    PubMed

    Prince, P Stanely Mainzen; Kamalakkannan, N; Menon, Venugopal P

    2004-04-01

    Syzigium cumini, commonly known as 'jamun', is widely used in different parts of India for the treatment of diabetes mellitus. The present study was designed to evaluate the antidiabetic and antihyperlipidaemic effect of an alcoholic extract of Syzigium cumini seeds (JSEt) in alloxan diabetic rats. Diabetes was induced by single intraperitoneal injection of alloxan (150 mg kg(-1) body weight). Oral administration of alcoholic JSEt to diabetic rats at a dose of 100 mg kg(-1) body weight resulted in a significant reduction in blood glucose and urine sugar and lipids in serum and tissues in alloxan diabetic rats. The extract also increases total haemoglobin. The extract brought back all the parameters to normal levels. The effect of alcoholic JSEt was similar to that of insulin. Thus, our investigation clearly shows that alcoholic JSEt has both antidiabetic and antihyperlipidaemic effects. PMID:15120440

  7. Evaluation of antidiabetic effect of Momordica cymbalaria fruit in alloxan-diabetic rats.

    PubMed

    Kameswararao, B; Kesavulu, M M; Apparao, C

    2003-02-01

    The oral treatment with the aqueous extract of Momordica cymbalaria fruit (MC) (0.5 g/kg) for 6 weeks showed a significant antihyperglycemic as well as antihyperlipidemic effects in the alloxan-induced diabetic rats. PMID:12628387

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

    PubMed Central

    Hajizadeh, Mohammad Reza; Eftekhar, Ebrahim; Zal, Fatemeh; Jafarian, Aida; Mostafavi-Pour, Zohreh

    2014-01-01

    Background: It has been proposed that oxidative stress may contribute to the development of testicular abnormalities in diabetes. Morus alba leaf extract (MAE) has hypoglycemic and antioxidant properties. We, therefore, explored the impact of the administration of MAE on steroidogenesis in diabetic rats. Methods: To address this hypothesis, we measured the serum level of glucose, insulin, and free testosterone (Ts) as well as oxidative stress parameters (including glutathione peroxidase, glutathione reductase, total antioxidant capacity, and malondialdehyde) in the testis of control, untreated and MAE-treated (1 g/day/kg) diabetic rats. In order to determine the likely mechanism of MAE action on Ts levels, we analyzed the quantitative mRNA expression level of the two key steroidogenic proteins, namely steroid acute regulatory protein (StAR) and P450 cholesterol side-chain cleavage enzyme (P450scc), by real-time PCR. Results: The MAE-treated diabetic rats had significantly decreased glucose levels and on the other hand increased insulin and free Ts levels than the untreated diabetic rats. In addition, the administration of MAE to the diabetic rats restored the oxidative stress parameters toward control. Induction of diabetes decreased testicular StAR mRNA expression by 66% and MAE treatment enhanced mRNA expression to the same level of the control group. However, the expression of P540scc was not significantly decreased in the diabetic group as compared to the control group. Conclusion: Our findings indicated that MAE significantly increased Ts production in the diabetic rats, probably through the induction of StAR mRNA expression levels. Administration of MAE to experimental models of diabetes can effectively attenuate oxidative stress-mediated testosterone depletion. PMID:24644381

  9. Treadmill exercise ameliorates apoptotic cell death in the retinas of diabetic rats.

    PubMed

    Kim, Dae-Young; Jung, Sun-Young; Kim, Chang-Ju; Sung, Yun-Hee; Kim, Jae-Deung

    2013-06-01

    Apoptotic neuronal cell death in the retina is a hallmark of diabetic retinopathy. Exercise has been recommended for the alleviation of symptoms in patients with diabetes. In the present study, the effect of treadmill exercise on apoptosis in the retinas of diabetic rats was investigated. Diabetes was induced by intraperitoneal injection of streptozotocin. The rats in the exercise groups ran on a treadmill for 30 min/day, 5 times a week, over the course of 6 weeks. In this study, the terminal deoxynucleotidyl transferase?mediated dUTP nick?end labeling (TUNEL) assay, immunohistochemistry staining of caspase?3 and western blot analysis for Bax, Bcl?2 and phosphorylated protein kinase B (p?Akt) in the retinas of diabetic rats were performed. The results demonstrated that the number of TUNEL? and caspase?3?positive cells was increased in the retinas of diabetic rats, whereas treadmill exercise decreased these numbers. In addition, the expression of the pro?apoptotic protein Bax and the anti?apoptotic protein Bcl?2 was enhanced in the retinas of diabetic rats. Treadmill exercise suppressed Bax and enhanced Bcl?2 levels. The expression of the cell survival factor, p?Akt, was decreased in the retinas of diabetic rats and treadmill exercise increased the expression of p?Akt. The results of the present study demonstrated that treadmill exercise ameliorated diabetes?induced apoptosis in retinal cells by enhancing p?Akt levels in the retina. Treadmill exercise represents an effective strategy to delay or prevent the onset of ocular complications in diabetic patients. PMID:23620139

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

    PubMed

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

    2014-06-01

    Compound K (CK) is a final metabolite of panaxadiol ginsenosides from Panax ginseng. Although anti-diabetic activity of CK has been reported in recent years, the molecular mechanism of CK in the treatment of diabetes mellitus remains unclear. In the present investigation, we established a rat model of type 2 diabetes mellitus (T2DM) with insulin resistance using high-fat diet (HFD) and streptozotocin (STZ), and attempted to verify more details and exact mechanisms in the treatment of T2DM. CK was administered orally at three doses [300, 100 and 30 mg/kg bodyweight (b.w.)] to the diabetic rats. Bodyweight, food-intake, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity (ISI), total glycerin (TG), total cholesterol (TC), as well as oral glucose tolerance test (OGTT) were evaluated in normal and diabetic rats. According to our results, CK could improve bodyweight and food-intake of diabetic rats. CK exhibited dose-dependent reduction of FBG, TG and TC of diabetic rats. CK treatment also enhanced FINS and ISI. Meanwhile, the glucose tolerance observed in the present study was improved significantly by CK. It is concluded from the results that CK may have improving effects on hyperglycemia and insulin resistance of diabetic rats. Furthermore, research showed that CK could promote the expression of InsR, IRS1, PI3Kp85, pAkt and Glut4 in skeletal muscle tissue of diabetic rats. These results indicate that the hypoglycemic activity of CK is mediated by improvement of insulin sensitivity, which is closely related to PI3K/Akt signaling pathway. PMID:24613802

  11. Studies on hypoglycaemic effects of polyherbal preparation in streptozotocin-induced diabetic male albino rats.

    PubMed

    Ismail Khan, A; Yuvaraj, S; Suthagar, E; Parthasarathy, C; Balasubramanian, K

    2009-11-01

    Many traditional treatments have been recommended in the alternative system of medicine for diabetes mellitus. However, the mode of action of most of the herbals used has not been defined. It has been reported that sex hormones are important regulators of insulin-mediated events in skeletal muscles. In view of this, a novel herbal preparation containing antidiabetic and aphrodisiac plants was used in the present study. Adult male albino rats were divided into following groups after induction of diabetes. Rats were given an intraperitoneal (i.p.) injection of streptozotocin (STZ), at a dose of 65 mg/kg body weight after overnight fasting, to induce diabetic state with blood glucose levels >250 mg/dL. Group 1-Control rats treated with single i.p. injection of vehicle, Group 2-Rats treated with polyherbal preparation (PHP; 500 mg/kg body weight by oral intubation, morning and evening for 30 days), Group 3-STZ-diabetic rats treated orally with equal volumes of vehicle (water) alone and Group 4-STZ-diabetic rats treated with PHP after 10 days of diabetic induction. STZ-diabetes decreased the body weight, serum insulin level and glucose oxidation in liver and skeletal muscles but increased the fasting blood glucose level. After polyherbal treatment, body weight and glucose oxidation were completely restored to control level while serum insulin level was restored partially and the glucose tolerance was significantly improved. There was a significant decrease in total haemoglobin (Hb) level of diabetic rats when compared to control but polyherbal treatment significantly improved the same. However, the other parameters studied (red blood cell [RBC], white blood corpuscle [WBC], packed cell volume [PCV], mean corpuscular volume [MCV] and mean corpuscular haemoglobin [MCH]) were unaltered. In conclusion, the anti-diabetic properties of PHP appear to be mediated through pancreatic beta-cell regeneration, resulting in maintenance of optimal blood glucose and its oxidation in liver and skeletal muscles. PMID:19755436

  12. Application of Isoproterenol Inhibits Diabetic-Like Changes in the Rat Retina

    PubMed Central

    Jiang, Youde; Walker, Robert J.; Kern, Timothy S.; Steinle, Jena J.

    2014-01-01

    Diabetic retinopathy is the leading cause of blindness to working-age adults. We have recently shown that surgical removal or genetic manipulations to eliminate sympathetic neurotransmission produces many of the retinal changes similar to rodent diabetic retinopathy with normal glucose levels. We hypothesized that application of a beta-adrenergic receptor agonist, isoproterenol, could reach the retina to elicit normal cellular signaling and inhibit the functional and morphological markers of early stage diabetic retinopathy in the rat. Rats were made diabetic by injection of 60mg/kg streptozotocin. Within 3 days of diabetes-induction, rats were placed into 1 of 3 groups (control, diabetes, or diabetic + isoproterenol). Dose and time course studies were done for isoproterenol using a PKA ELISA and CREB analyses. Once the optimal dose and time course were established, electrical activity of the retina was analyzed by electroretinogram each month for the 8-month study. Western blotting was done for insulin receptor signaling and Akt and ELISA analyses for TNF? concentration and cleavage of caspase 3 at 2- and 8-months of diabetes. Diabetes-induced degeneration of neural cells and retinal thickness were assessed at 2 months, while degenerate capillaries were quantitated at 8 months of treatment. Daily application of 50mM isoproterenol was effective in inhibiting the diabetes-induced loss of a- and b-wave and oscillatory potential amplitudes in the electroretinogram. Isoproterenol blocked the increase in TNF? and apoptosis in the diabetic retina. The numbers of degenerate capillaries were also reduced in the treated + diabetes retina. These data strongly suggest that loss of beta-adrenergic receptor signaling may be a key factors in early stage diabetic retinopathy. Resolution of this loss of adrenergic receptor signaling can inhibit some of the hallmarks of diabetic retinopathy in the retina. PMID:20493839

  13. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

    PubMed Central

    Hernández-Fonseca, Juan P.; Rincón, Jaimar; Pedreañez, Adriana; Viera, Ninoska; Arcaya, José L.; Carrizo, Edgardo; Mosquera, Jesús

    2009-01-01

    Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral. PMID:19812703

  14. Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine

    Microsoft Academic Search

    M. Sagara; J. Satoh; R. Wada; S. Yagihashi; K. Takahashi; M. Fukuzawa; G. Muto; Y. Muto; T. Toyota

    1996-01-01

    Summary  N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC

  15. Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats

    Microsoft Academic Search

    P Pushparaj; C. H Tan; B. K. H Tan

    2000-01-01

    The present study was designed to investigate the hypoglycemic and hypolipidemic activities of an ethanolic extract of Averrhoa bilimbi Linn. leaves (Oxalidaceae, Common name: Bilimbi) in streptozotocin (STZ)-diabetic rats. The optimal hypoglycemic dose (125 mg kg?1) was determined by performing the oral glucose tolerance test (OGTT) in both normal and STZ-diabetic rats. To investigate the effect of repeated administration of

  16. Polaprezinc Exerts a Salutary Effect on Impaired Healing of Acute Gastric Lesions in Diabetic Rats

    Microsoft Academic Search

    Roman P. Korolkiewicz; Akinobu Fujita; Koichi Seto; Keizo Suzuki; Koji Takeuchi

    2000-01-01

    We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of polaprezinc [N-(3-aminopropionyl)-l-histidinato zinc] on these lesions. Studies were performed on rats injected intraperitoneally with streptozotocin (STZ, 70 mg\\/kg) five weeks prior to experiments. Diabetic rats had blood glucose levels (BGLs) higher than 350 mg\\/100 ml. Randomly chosen animals were

  17. Amelioration of Diabetic Nephropathy in OLETF Rats by Prostaglandin I2 Analog, Beraprost Sodium

    Microsoft Academic Search

    Maho Watanabe; Hitoshi Nakashima; Shizue Mochizuki; Yasuhiro Abe; Atsunori Ishimura; Kenji Ito; Takao Fukushima; Katsuhisa Miyake; Satoru Ogahara; Takao Saito

    2009-01-01

    Background: Strict control of blood glucose and blood pressure levels sometimes fails to delay the development of diabetic nephropathy, and an effective therapy is not yet available. The present study aimed to examine whether the prostaglandin I2 analog beraprost sodium (BPS) ameliorates diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Method: Fifty-week-old OLETF rats were divided into three groups

  18. Blocking ?V?3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats

    PubMed Central

    Maile, Laura A.; Gollahon, Katherine; Wai, Christine; Busby, Walker; Clemmons, David

    2014-01-01

    This study determined if blocking ligand occupancy of the ?V?3 integrin could inhibit the pathophysiologic changes that occur in the early stages of diabetic nephropathy (DN). Diabetic rats were treated with either vehicle or a monoclonal antibody that binds the ?3 subunit of the ?V?3 integrin. After 4 weeks of diabetes the urinary albumin to creatinine ratio (UACR) increased in both diabetic animals that subsequently received vehicle and in the animals that subsequently received the anti-?3 antibody compared with control nondiabetic rats. After 8 weeks of treatment the UACR continued to rise in the vehicle-treated rats; however it returned to levels comparable to control nondiabetic rats in rats treated with the anti-?3 antibody. Treatment with the antibody prevented the increase of several profibrotic proteins that have been implicated in the development of DN. Diabetes was associated with an increase in phosphorylation of the ?3 subunit in kidney homogenates from diabetic animals, but this was prevented by the antibody treatment. This study demonstrates that, when administered after establishment of early pathophysiologic changes in renal function, the anti-?3 antibody reversed the effects of diabetes normalizing albuminuria and profibrotic proteins in the kidney to the levels observed in nondiabetic control animals. PMID:25389530

  19. Impaired mitochondrial metabolism and protein synthesis in streptozotocin diabetic rat hepatocytes

    SciTech Connect

    Memon, R.A.; Bessman, S.P.; Mohan, C. (Univ. of Southern California, Los Angeles (United States))

    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.

  20. Green Tea (Camellia sinensis) Supplementation to Diabetic Rats Improves Serum and Hepatic Oxidative Stress Markers

    PubMed Central

    Haidari, Fatemeh; Omidian, Kosar; Rafiei, Hossein; Zarei, Mehdi; Mohamad Shahi, Majid

    2013-01-01

    Diabetes is one of the most common metabolic disorders and is interrelated to oxidative stress-induced diseases. According to the role of dietary antioxidants in control and prevention of diabetes, this study was aimed to evaluate the effect of green tea extract on serum glucose levels and serum and hepatic total antioxidant capacity (TAC) and lipid (MDA) in diabetic rats. Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (55 mg/Kg). Alcoholic extract of green tea (100, 200 mg/Kg) was given by oral gavage to normal and diabetic rats for 4 weeks. Finally, serum glucose and serum and hepatic levels of MDA and TAC were measured and analyzed statistically. Data showed that green tea extract at dose of 200 mg/Kg significantly decreased the serum glucose levels, serum and hepatic MDA concentration and increased the total antioxidant capacity in diabetic rats (p < 0.05). Green tea supplementation also increased hepatic TAC in normal rats (p < 0.05). The antihyperglycemic and antioxidative