Variation in renal function of type 2 diabetic rats undergoing aerobic exercise / 中国组织工程研究

BACKGROUND:Type 2 diabetes is often accompanied by renal dysfunction.Increasing studies have shown that exercise can alleviate metabolic disorders and renal dysfunction in diabetic patients.However,the specific mechanism underlying the renal protective effect of exercise in patients with type 2 diabetes is rarely reported. OBJECTIVE:To investigate whether aerobic exercise can improve renal function in type 2 diabetic rats by inhibiting transforming growth factor β1/Notch1 pathway. METHODS:Male Sprague-Dawley rats were randomly divided into normal control group and diabetes model group.After successful modeling,they were randomly divided into diabetes control group and diabetes exercise group.Rats in the diabetes exercise group were subjected to an 8-week aerobic exercise.Samples were collected after exercise,and the relevant indexes of glucose and lipid metabolism and renal function were detected by automatic biochemical analyzer and ELISA.The microscopic structure of renal cortex was observed by electron microscope.ELISA and RT-PCR were used to detect the expression of related proteins and genes in rat kidney tissue. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,total cholesterol,and triglyceride levels and insulin resistance index were significantly increased in the diabetic control group(P＜0.05).Aerobic exercise could significantly reduce fasting blood glucose and triglyceride levels(P＜0.05).Compared with the normal control group,the diabetic control group had significantly increased contents of urinary microalbumin,serum urea nitrogen and serum creatinine(P＜0.01),thickened renal basement membrane,mesangial matrix hyperplasia,accompanied by a certain degree of foot process fusion,and obvious lesion of the kidney.Aerobic exercise could significantly down-regulate the overexpressions of urinary microalbumin,serum urea nitrogen and serum creatinine in type 2 diabetic rats(P＜0.01),and significantly improve the pathological changes of the kidney in diabetic rats.Compared with the normal control group,the protein and gene expression levels of transforming growth factor β1,Notch1,Jagged1 and Hes1 in rat kidney tissue were significantly increased in the diabetic control group(P＜0.01).Aerobic exercise had a highly significant inhibitory effect on the overexpression of transforming growth factor β1,Notch1 and Jagged1 proteins and genes(P＜0.01)and also significantly inhibited the overexpression of Hes1 protein(P＜0.05).In conclusion,aerobic exercise can protect renal function and delay the pathological progression of the kidney in diabetic rats,which may be achieved by inhibiting the overexpression of transforming growth factor β1/Notch1 signaling pathway.

Determination of the efficacy of okra seed powder in aqueous solution as a glucose lowering agent compared to acarbose in STZ diabetic rats / The Health Sciences Journal

INTRODUCTION@#Okra is reported to have anti-diabetic effects, but the literature shows conflicting results. The experiment aimed to determine the efficacy of three doses of okra seed powder suspension as a glucose lowering agent on streptozotocin-induced diabetic rats and its cellular effects on the liver and pancreas. @*METHODS@#Twenty-five Sprague Dawley rats that were given streptozotocin 60 mg/kg intraperitoneally were randomly allocated to one of five treatment groups: okra seed powder at 100 mg/kg, 150 mg/kg and 200 mg/kg, acarbose (positive control) and vehicle only (negative control). The treatments were given as a 1.5 mL oral gavage daily for 21 days. Significant differences in blood glucose were determined between treatment groups in terms of relative change from baseline, using One-Way ANOVA with Dunnett’s method with acarbose as the referent group. Repeated measures ANOVA was used to analyze the blood glucose levels across the time point collections (baseline, T1 and T2). Histopathologic changes on the liver and pancreas were described using counts and proportions.@*RESULTS@#Mean blood glucose values increased from baseline to T2 in all treatment groups. Increasing trend was observed only up to T1 in the 150 mg/kg and the 200 mg/kg okra seed treatment groups. Comparing okra treatment groups to acarbose, the percentage increase of mean blood glucose from baseline to T2 was lowest in the 200 mg/kg okra group (p = 0.040). The okra-treated rats had no fatty change and a dose-dependent decrease in cellular degeneration in the liver and none for the 200 mg/ kg treatment group. @*CONCLUSION@#The 200 mg/kg okra suspension has a potential lowering effect on blood glucose and a hepatoprotective effect. A longer period of observation with higher doses of okra suspension is recommended to study these effects further.

Nephroprotective and Antihyperlipedemic Activity of Honey in Alloxan Induced Diabetic Wistar Rats

There is increasing evidence to support the health benefits of natural honey. However, its use in the dietary management of diabetes mellitus is still evolving. The present study was aimed at investigating the long-term effects of Nigerian honey of Niger Delta origin on alloxan induced renal and serum lipid dysfunctions in diabetic wistarrats. Four groups of adult male wistarrats were used; 8 rats each. The first group received no honeybut were given salineand served as normal control.Group II werenon-diabetic and received honey solution (50% v/v) at a dose of 10ml/kg body weight/day.Diabetes was induced in groups III and IV by intra-peritonealadministration of 200mg/kg alloxan solution. Group III served as diabetic control. Group IV received a honeysolution. At the end of 56 days, lipid profile and renal function were assessed. Also, atherogenicindex was calculated. Results obtained revealed alloxan induceddiabetic renal dysfunction, as reflected by up-regulated kidney function parameters–urea, creatinine, and a decrease in sodium, and bicarbonate, levels while a non-significant difference between potassiumin diabetic control and diabetic treated. Regardingserum lipid, there was up-regulated total cholesterol, triglyceride, low-densitylipoprotein, atherogenic index and decreased high-densitylipoprotein levels. Therefore, oral administrationof honey diminished the deleterious effects of alloxan-induceddiabetes on renal function and improved lipid profile parameters. We conclude that Niger Delta honey has the potential medicinal properties to protect against alloxan inducedrenal dysfunction and hyperlipedemiain diabetic male wistarrats.

Effects of Shuangdan Mingmu capsule on the expressions of VEGF in the retina of diabetic rat models / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the effects of Shuangdan Mingmu capsule on the expressions of vascular endothelial growth factor-a(VEGF-a), VEGF-b, VEGF-c in the retina of a diabetic rat model. <p>METHODS: Forty male SD rats were divided into Group A(normal group), Group B(model group), Group C(Shuangdan Mingmu group)and Group D(positive control group)10 rats(20 eyes)in each group. A rat model of diabetic retinopathy was established by one-time tail vein injection with STZ(50mg/kg). After modeling for 1wk, the rats were given medicine by gavage. After gavage for 4wk rats were sacrificed, and the expressions of VEGF-a, VEGF-b, VEGF-c in the retina tissues were detected by immunohistochemical method. <p>RESULTS: After gavage for 4wk the average gray values of VEGF-a, VEGF-b and VEGF-c protein in the retina of model group, Shuangdan Mingmu group and positive control group were lower than those of the normal group, and the average optical density were higher than those of the normal group. There was a significant difference between the model group and the normal group(<i>P</i><0.01). The average gray values of VEGF-a, VEGF-b and VEGF-c expression in Shuangdan Mingmu group and positive control group were higher than those in the model group(<i>P</i><0.05)and the average optical density value were lower than those in the model group.(<i>P</i><0.01). <p>CONCLUSION: Shuangdan Mingmu capsule could significantly reduce the expressions of VEGF-a, VEGF-b,VEGF-c in the retina and had a certain protective effect on the retina of rats in the diabetic retinopathy model.

Hypoglycemic and Hypolipidemic Effects of Lycium barbarum Polysaccharide in Diabetic Rats / 中草药·英文版

Objective: To study the antidiabetic effects and the underlying molecular mechanisms of Lycium barbarum polysaccharide (LBP) and its DEAE cellulose elution fraction LBP-IV in diabetic rats induced by high fat diet (HFD) and streptozotocin (STZ). Methods: After ig administration of LBP-IV [50, 100, and 200 mg/(kg·d)] and LBP [100 mg/(kg·d)] once daily for consecutive 4 weeks to diabetic rats, the glucose and lipids in blood, mRNA expression of phosphoenolpyruvate carboxykinase (PEPCK), sterol regulatory element binding-protein-1c (SREBP-1c), and fatty acid synthase (FAS) in liver were determined. Results: Ig administration of LBP and LBP-IV significantly decreased the levels of blood glucose, HbA1c, TC, TG, and LDL-C, as well as the hepatic mRNA expression of PEPCK, SREBP-1c, and FAS, whereas significantly increased the oral glucose tolerance of diabetic rats. Conclusion: The findings suggest that the antidiabetic effects of LBP and LBP-IV are associated with the decreased hepatic mRNA expression of PEPCK, SREBP-1c, and FAS in HFD-STZ induced diabetic rats.

Pharmacological Effect of α-Glucosidase Inhibitor Voglibose in a Novel Obese Diabetic Model.

Aim: This study was conducted to investigate the preventive or therapeutic effect of α- glucosidase inhibitor voglibose in a new model rat, Spontaneously Diabetic Torii-Leprfa (SDT fatty) rat, which is a novel type 2 diabetic rat showing obesity, hyperglycemia and hyperlipidemia from a young age. Place and Duration of Study: Niigata University and JT Central Pharmaceutical Research Institute, between January and August 2011. Methodology: The present study was designed to the preventive and therapeutic effect of voglibose by administering (0.3, 1 mg/kg) voglibose as a dietary admixture to SDT fatty rats from 5 to 11 and 14 to 20 weeks of age, respectively. Results: In the examination of preventive effect, the obtained biochemical results show that voglibose decrease glucose level significantly in dose-dependent manner within 5-11 weeks of age. In voglibose-treated rats at 11 weeks of age, the histopathological pancreatic changes, such as vacuolation and irregular boundaries in islets, were improved. On the other hand, in the examination of therapeutic effect, voglibose improved the hyperglycemia only at a dose of 1 mg/kg within 16-20 weeks of age. Conclusion: Voglibose showed both preventive and therapeutic effects for diabetes in female SDT fatty rats. The SDT fatty rat is a useful model for development of anti-diabetic agents.

Effects of Huanglian Jiedu Decoction on Blood Glucose, Abdominal Aortic Morphology and HIF-1α in Type 2 Diabetic Rats / 中国中医药信息杂志

Objective To observe effects of Huanglian Jiedu Decoction on fasting blood glucose (FBG), fasting insulin (FINS), abdominal aortic morphology and expression of HIF-1α in the abdominal aorta in rats with type 2 diabetes. Methods The rat model of type 2 diabetes was established by intravenous injection of streptozotocin and feeding with high sugar and high fat diet. Rats were randomly divided into blank group, model group, control group and treatment group. The blank group and model group were given normal saline by gavage, the control group was given metformin, and the treatment group was given Huanglian Jiedu Decoction. Six weeks later, the levels of FBG and FINS were determined. Immunohistochemical method was used to determine the expression of HIF-1α in abdominal aorta and HE staining method to observe the changes of abdominal aortic morphology. Results Compared with model group and control group, abdominal aorta of HIF-1α and FBG level of treatment group were significantly decreased (P <0.01), FINS significantly increased (P <0.01), and abdominal aortic endothelial cell injury was significantly improved. Conclusion Huanglian Jiedu Decoction has a protective effect on the injury of vascular endothelium, and its mechanism may be related with inhibiting the expression of HIF-1α.

Study on vascular endothelial growth factor and its receptor in the vitreous of diabetic rats / Estudio del factor de crecimiento endotelial vascular y su receptor en el humor vítreo de ratas diabéticas

OBJECTIVE: To investigate the vitreous level of vascular endothelial growth factor (VEGF) and kinase insert domain-containing receptor (KDR) in diabetic rats, and to explore the role of VEGF and KDR in diabetic retinopathy. METHODS: Eighty-four adult Wistar rats were randomly divided into two groups. Fifty-eight rats in group A were injected intraperitoneally with streptozotocin to induce diabetes and 20 rats in group B were injected with physiological saline. Blood glucose meter was used to detect the blood glucose level at 72 hours after injection; blood glucose level >16.67 mmol/L was considered to be successful modelling. Blood glucose level was assayed and body mass was measured on the same modelling day, one week, two weeks and four weeks after modelling. Four weeks after modelling, the vitreous was taken and the VEGF and KDR levels were detected by enzyme-linked immunosorbent assay (ELISA). The eyeballs were fixed with paraform and embedded by petrolin for haematoxylin and eosin (H & E) staining. RESULTS: Forty-two rats survived and 16 rats died in group A. No rats died in group B. The blood glucose at one week, two weeks and four weeks between the two groups had statistical differences (p < 0.05). The weight at one week and two weeks between the two groups was not different but there was statistical difference at four weeks between the two groups (p < 0.01). The ELISA results showed that the VEGF and KDR levels were 0.276 ± 0.026 ng/mL and 2.936 ± 0.295 ng/mL in group A, 0.231 ± 0.021 ng/mL and 2.394 ± 0.227 ng/mL in group B, respectively. The VEGF and KDR levels of group A were higher than those of group B (p < 0.05). CONCLUSIONS: The changes of VEGF and KDR levels in the vitreous of diabetic rats were related to the early retinopathy induced by diabetes.

OBJETIVO: Investigar el nivel vítreo del factor de crecimiento endotelial vascular (FCEV) y receptor con dominio inserto-quinasa (KDR) en ratas diabéticas, y explorar el papel de FCEV y KDR en la retinopatía diabética. MÉTODOS: Ochenta y cuatro ratas adultas Wistar fueron divididas aleatoriamente en dos grupos. A cincuenta y ocho ratas en el grupo A se les inyectó estreptozotocinapor vía intraperitonealpara inducir diabetes, mientras que a 20 ratas en el grupo B se les inyectó una solución salina fisiológica. Se usó un medidor de glucosa en sangre para detectar el nivel de glucosa en sangre a las 72 horas después de la inyección. Un nivel de glucosa en sangre > 16.67 mmol/L se consideró como un modelo exitoso. Se analizó el nivel de glucosa en sangre, y se midió la masa corporal en el mismo día del modelado, y una semana, dos semanas, y cuatro semanas después del modelado. Cuatro semanas después del modelado, se tomó el humor vítreo, y los niveles de FCEV y KDR fueron detectados mediante ensayo por inmunoabsorción ligado a enzimas (ELISA). Los globos oculares fueron fijados con para formaldehido e incrustados por petrolin para tinción (H & E) hematoxilina-eosina. RESULTADOS: Cuarenta y dos ratas sobrevivieron y 16 ratas murieron en el grupo A. Ninguna de las ratas en el grupo B murió. La glucosa en la sangre a la semana, las dos semanas, y las cuatro semanas entre los dos grupos tuvo diferencias estadísticas (p < 0.05). El peso a la semana y a las dos semanas entre los dos grupos no fue diferente, pero hubo diferencia estadística a las cuatro semanas entre los dos grupos (p < 0.01). Los resultados de ELISA mostraron que los niveles de FCEV y KDR fueron 0.276 ± 0.026 ng/mLy 2.936 ± 0.295 ng/mL en el grupo A, 0.231 ± 0.021 ng/mL y 2.394 ± 0.227 ng/mL en el grupo B, respectivamente. Los niveles de FCEV y KDR del grupo A fueron superiores a los del grupo B (p < 0.05). CONCLUSIONES: Los cambios de nivel FCEV y KDR en el humor vítreo de las ratas diabéticas estaban asociados con la retinopatía temprana inducida por diabetes.

Differential effects of treadmill exercise on cyclooxygenase-2 in the rat hippocampus at early and chronic stages of diabetes / 한국실험동물학회지

Cyclooxygenase-2 (COX-2) is believed to be a multifunctional neural modulator that affects synaptic plasticity in the hippocampus. In the present study, we investigated the differential effects of treadmill exercise on COX-2 immunoreactivity in the dentate gyrus in early and chronic diabetic stages in Zucker diabetic fatty (ZDF) rats and lean control (ZLC) rats. To this end, ZLC and ZDF rats at 6 or 23 weeks of age were put on a treadmill with or without running for 1 h/day for 5 consecutive days at 16-22 m/min for 5 weeks or 12-16 m/min for 7 weeks, respectively. Treadmill exercise in prediabetic and chronic diabetic rats significantly reduced blood glucose levels. In particular, exercise in the prediabetic rat blocked the onset of diabetes. COX-2 immunoreactivity was mainly detected in the granule cell layer of the dentate gyrus and stratum pyramidale of the CA3 region in all groups. COX-2 immunoreactivity was significantly increased in these regions of ZLC and ZDF rats after treadmill exercise in the early diabetic stage. However, COX-2 immunoreactivity was not changed in these regions in ZDF rats after treadmill exercise in the chronic stage. These results suggest that treadmill exercise in diabetic animals in the chronic stage has limited ability to cause plasticity in the dentate gyrus.

Echocardiographic valuation of left ventricular diastolic function and the dynamic observation of ultrastructure and argyrophilic fiber in dabetic rats / 中国综合临床

Objective To explore the relationship between left ventricular diastolic function and the dynamic changes of myocardial ultrastructure and argyrophilic fiber in diabetic rats on the different periods of lesions(week 4,12 and 24).Methods The diabetes mellitus(DM)in healthy male Sprague-Dawley rats was induced by a single injection of streptozotocin(STZ,Sigma)into intraperitoneal at a dose of 65 mg/kg body weight.The left ventricular diastolic function was measured by Color Doppler Flow Imaging-Pulsed Wave(CDFIPW)and Doppler Tissue Imaging(DTI)echocardiography.Heart tissue at the apex was obtained rapidly for transmission electron microscope study.Argyrophilic staining was used in the study of argyrophilic fiber volume fraction(APFVF)in heart interstitial tissue.Results Diastolic dysfunction of left ventricle was detected in STZinduced diabetic rats by CDFI-PW(E/A ＜ 1)at week 4,and progressed gradually.Pseudonormal filling (E/A ＞ 1)was found in diabetic rats at week 24,which could be identified by DTI(Ea/Aa ＜ 1).Diastolic function of normal rats was not impaired(E/A ＞ 1 and Ea/Aa ＞ 1).Transmission electron microscopy revealed a spectrum of subcellular remodeling in myocardium which was characterized by myofibril content decrease,disorganization,mitochondrial degeneration,sarcoplasmic reticulum,structural disorder.Compared with the control group,APFVF in myocardium was increased significantly in diabetic rats(P ＜ 0.05).Conclusion The diastolic dysfunction in STZ-induced diabetic rats correlates with damage of ultrastructure and increase of myocardial argyrophilic fiber.

Anti-hyperglycemic and anti-oxidative effect of aqueous extract of Momordica charantia pulp and Trigonella foenum graecum seed in alloxan-induced diabetic rats.

Diabetes is an oxidative stress disorder and oxidative damage to tissues such as heart, kidney, liver and other organs may be a contributory factor to several diabetic complications. Momordica charantia (family: Cucurbitaceae) and Trigonella foenum graecum (family: Fabaceae) are used traditionally in Indian folk medicine to manage diabetes mellitus. In the present study, the anti-hyperglycemic and anti-oxidative potential of aqueous extracts of M. charantia pulp and seed powder of T. foenum graecum were assessed in alloxan (150 mg/kg body weight) induced diabetic rats. Alloxan treatment to the rats could induce diabetes as the fasting blood glucose (FBG) levels were >280 mg/dl. Treatment of diabetic rats for 30 days with M. charantia and T. foenum graecum could significantly (p<0.001) improve the FBG levels to near normal glucose levels. Antioxidant activities (superoxide dismutase, catalase, reduced glutathione content and glutathione-s-transferase) and lipid peroxidation levels were measured in heart, kidney and liver tissues of normal, diabetic and experimental animals (diabetics + treatment). TBARS levels were significantly (p<0.001) higher and anti-oxidative activities were found low in diabetic group, as compared to the control group. Significant (p<0.001) improvement in both the TBARS levels and antioxidant activities were observed when M. charantia and T. foenum graecum were given to diabetic rats. Our results clearly demonstrate that M. charantia and T. foenum graecum are not only useful in controlling the blood glucose levels, but also have antioxidant potential to protect vital organs such as heart and kidney against damage caused due to diabetes induced oxidative stress.

Effect of sulodexide on islet β-cell function in streptozocin induced diabetic rats / 中国综合临床

Objective To study the effects of sulodexide on islet B-cell function in streptozocin induced di-abetic rats. Methods Sprague-Dawley(SD) rats were randomly divided into normal control group (group C), dia-betic group without treatment(group D), and suledexide treatment group(group S), a single dose of streptozotocin were abdominally injected to establish the diabetic rat models. Each animal in sulodexide treated group was addition-ally fed with sulodexide of 10 mg/(kg·d) for 12 weeks,while the remained group (group C and D) were given normal water in the same period. After 12 weeks of treatment, fasting plasma glucose(FPG),fasting plasma insulin (FINS), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C), serum creatinine rates (SCr) and alanine aminotransferase (ALT) were measured. Insulin sensitivity index(ISI) and insulin resistant index (HOMA-IR) were calculated. Results After 12 weeks, the levels of TG, LDL-C and ALT had no significant difference between group D and group S, but were higher than those in group C (P <0.05);There were no significant difference of SCr levels among the three groups. Compared with the group C, APTT, PT, TT and ISI in group D and S were significantly decreased, HOMA-IR were significantly increased (P < 0.05). APTT, PT, TT and ISI in group S had significantly increased compared with that in group D, HOMA-IR was significantly decreased in group S compared with that in group D (P < 0.01). Conclusions Sulodexide can reduce insulin resistant, improve hypercoagulability and insulin sensitiv-ity in streptozocin induced diabetic rats. The effects to blood lipid, liver and renal functions in diabetic rats are not obvious.

Effects of Various Mulberry Products on the Blood Glucose and Lipid Status of Streptozotocin-induced Diabetic Rats

The study aim was to investigate the effects of three types of mulberry products on the blood glucose and lipid statuses and peroxidative state under diabetic condition. The three types were mulberry liquor prepared by adding 30% ethanol to the crushed fresh fruit, mulberry wine and vinegar by fermentation. For diet experiment the mulberry liquor (M-Liquor), wine (M-Wine), and vinegar (M-Vinegar) were prepared as powders by freeze-drying of the respective product and were added to the diet at the level of 1% and mulberry fruit powder (M-Powder) at the level of 5%. Sprague-Dawley female rats weighing 150 +/- 10 g were randomly assigned to one normal group, and five diabetic groups induced by one intraperitoneal injection of streptozotocin (STZ) at the level of 50 mg/kg. The normal and diabetic control (DM-Control) groups were fed diet without the mulberry products. During twenty-one days of experimental diet, blood glucose was maintained at a low level in the M-Liquor group compared with the DM-Control group. However, serum insulin level was higher in both M-Liquor and M-Vinegar groups after the experimental diet period. Serum levels of total cholesterol and triglyceride (TG) were lower in M-Liquor but HDL-/total cholesterol ratios were higher in the four M groups. The TG liver level was lower in M-Powder and M-Vinegar groups but the cholesterol level was lower in M-Powder than in the DM-Control group. Serum levels of thiobarbituric acid reactive substances were not different among the groups but the liver levels of these substances were lower in the four M groups than in DM-Control. Serum GOT and GPT levels were not changed by the mulberry products. These results indicated that mulberry liquor is the most effective among the four mulberry products for normalizing blood glucose and lipid status and that all the mulberry products were effective in enhancing antioxidant defense in the diabetic state.

Relationship between Expression of p75 Gene and Apoptosis of Cerebrum Cells in Type 2 Diabetic Rats / 中国康复理论与实践

@#Objective To study the relationship between expression of p75 gene and apoptosis of cerebrum cells in type 2 diabetic rats.Methods Ten type 2 diabetic rats and ten natural rats were used to test the expression of brain p75 mRNA by RT-PCR technique, and the apoptosis of cerebrum cells was measured by agarose gel electrophoresis (AGA).Results The expression of brain p75 mRNA and apoptosis of cerebrum cells in type 2 diabetic rats were higher than that of the natural group.Conclusion The apoptosis of cerebrum cells in type 2 diabetic rats increases, and it is positively correlated with the expression of brain p75 gene mRNA.

Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium (KATP) channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of KATP channels, insulin receptor beta-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that KATP-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on KATP channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

Gene expression of transforming growth factor-β2 in retina of diabetic rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To detect the gene expression of TGF-β2 in retinas of diabetic rats at different stages, to observe and analyze the effect of TGF-β2 on the retinas of diabetic rats, to explore the role of TGF-β2 in pathogenesis of diabetic retinopathy (DR), and to provide experiment data and experience for further clinic studies.METHODS: Sprague-Dawley (SD) rats were used and retinas were dissected. The total RNA was isolated from which the first strand of cDNA was prepared. Diabetes mellitus was induced by a single intraperitoneal injection of 60mg/kg streptozotocin (STZ) and the rats were held without insulin treatment until sacrifice. Besides, agematched rats treated with saline were used as controls. Tail vein blood glucose was measured after 2 days and rats were considered hyperglycemic if blood glucose reading>16.7mmol/L. Animals with blood glucose level<16.7mmol/L were excluded from the study. The rats were killed at the 4th, 8th, 12th, 16th, 20th and 24th week respectively after hyperglycemic models were established. The retinas were separated and preserved in liquid nitrogen. The expressions of TGF-β2 gene mRNA were detected by reverse transcription PCR (RT-PCR).RESULTS: The RNA of rat retina was integrative enough to be used to further carry out PCR analysis. Compared with control groups, the expression of TGF-β2 mRNA in retinas of diabetic rats was up-regulated at the 4th week, but there was no statistical difference (P>0.05); it was down-regulated at the 8th week, and there was statistical difference (P<0.05); it was also down-regulated at the 12th week, and there was statistical difference (P<0.05); at the 16th week there was no statistical difference (P>0.05); it was up-regulated at the 20th week, but there was no statistical difference (P>0.05); it continued to be up-regulated at the 24th week, and there was statistical difference (P<0.05).CONCLUSION: Since the expression of TGF-β2 mRNA in retinas of diabetic rats was down-regulated at the 8th week and 12th week statistically, up-regulated at the 24th week statistically, it has obviously shown that TGF-β2 was down-and up-regulated through the period of DR. That is, its changes are diphasic with time. It may confirm that TGF-β2, with the characteristic of diphasic regulation, played an important role in DR. It is necessary to study it furthermore.

Effects of soybean isoflavone extract on the plasma lipid profiles and antioxidant enzyme activity in streptozotocin-induced diabetic rats

The present study evaluated the effects of various dosages of soybean isoflavone extract on lipid profiles, lipid peroxidation and antioxidant activities in streptozotocin-induced diabetic rats. The one normal control group was fed an AIN-76-based experimental diet and four diabetic groups were fed the same diet, supplemented with four different levels of soybean isoflavone extract for seven weeks. The daily dosages of pure isoflavone for four diabetic groups were set to be 0 mg (diabetic control), 0.5 mg (ISO-I), 3.0 mg (ISO-II) and 30.0 mg (ISO-III) per kilogram of body weight, respectively. The plasma total cholesterol levels and the TBA-reactive substances contents in the liver and kidney were significantly lowered in ISO-II and ISO-III groups compared to those in the diabetic control group. The levels of plasma HDL-cholesterol, plasma vitamin A and hepatic superoxide dismutase were significantly increased in those two groups compared with the diabetic control group. The present study demonstrated the possibility that the diets supplemented with 3.0 mg and 30.0 mg of soybean isoflavone extract may have beneficial effects on the plasma lipids, tissue lipid peroxidation and partly on antioxidant system in diabetic animals and there were no significant differences between the ISO-II and ISO-III groups. The results suggest that the effective daily dosage level of isoflavone for improving lipid metabolism in diabetic rats may be above 3.0 mg per kilogram body weight.

Leukocyte-endothelial cell interaction is attenuated by low-intensity exercise training and vitamin C supplementation in diabetic rats.

Objective: To determine the effects of vitamin C supplementation and low-intensity exercise training on diabetesinduced endothelial dysfunction. Methods: Male Spraque-Dawley rats were randomly divided into five groups: control (Con), diabetes (DM) (streptozotocin; 50 mg/kg BW, i.v.), diabetes with supplemented vitamin C (DM+Vit.C; 1 g/L mixed in drinking water), diabetes with low-intensity exercise-trained (DM+Ex; running 5 times/week with 13-15 m/min velocity for 30 minutes) and diabetes with supplemented vitamin C and exercisetrained (DM+Vit.C+Ex) groups. The number of leukocyte-endothelial cell (EC) interactions in mesenteric postcapillary venules was monitored using intravital fluorescence videomicroscopy. Liver malondialdehyde (MDA) level, an indicator for oxidative stress, was determined by using the thiobarbituric acid reaction. Results: At 24 weeks, the plasma vitamin C level was significantly increased (p<0.05) in DM+Vit.C and DM+Vit.C+Ex rats when compared with DM rats. DM+Ex and DM+Vit.C+Ex rats had lower triglyceride levels and heart weights when compared with DM rats (P<0.05). Mean arterial pressures were significantly decreased in all treatment groups. DM rats had significantly higher malondialdehyde (MDA) levels and lower activities of superoxide dismutase (SOD) than Con. The number of adherent leukocytes and levels of MDA were significantly lower in DM+Vit.C, DM+Ex and DM+Vit.C+Ex than those of DM rats. Conclusion: The increased leukocyte-EC adherence in diabetic rats is significantly related to increased ROS, based on lower MDA levels. Vitamin C supplementation and regular low-intensity exercise training can prevent these deleterious effects, including hypertension, cardiac hypertrophy, hypertriglyceridemia, and leukocyte-EC adherence. Vitamin C supplementation combined with low-intensity exercise training is highly effective in preventing diabetic cardiovascular complications.

Effects of Mulberry Juice and Cake powders on Blood Glucose and Lipid Lowering and Erythrocytic Antioxidative Enzyme Activities in Streptozotocin -Induced Diabetic Rats

The aim of this study was to investigate the effects of mulberry juice and cake powder on blood glucose and lipid status along with intestinal disaccharidase and erythrocyte antioxidative enzyme system in streptozotocin (STZ )-induced diabetic rats. Sprague-Dawley male rats weighing 100 +/- 10 g were randomly assigned to one normal group, and eight STZ-induced diabetic groups: control diet group without mulberry juice and cake powders (DM-C ), three mulberry juice powder groups (0.5%:DM-0.5J, 1%:DM-1J, 2%:DM-2J )and four mulberry cake powder groups (0.25%:DM-0.25C, 0.5%:DM-0.5C, 1%:DM-1C, 2%:DM-2C ). After three-week feeding of each experimental diet, diabetes was induced by intravenous injection of 50 mg/kg body weight of STZ in sodium citrate buffer (pH 4.3 )via tail vein of eight DM groups. Rats were sacrificed at the 9th day of diabetic states. Level of blood glucose was 505 mg/dl in DM-C group but it was 28% and 39% lower in mulberry juice and cake powder fed groups, respectively, than the DM-C group. Activities of maltase, sucrase and lactase in proximal part of small intestine were significantly lower in the mulberry juice and cake powder groups by 42~47% than those of DM-C group. Erythrocytic superoxide dismutase, glutathione peroxidase and catalase activities were significantly reduced by STZ but increased close to normal levels along with less accumulation of thiobarbituric acid reactive substances (TBARS ). Serum levels of triglyceride and total cholesterol and HDL-cholesterol by STZ-DM were reduced and increased respectively, to the normal levels by the mulberry juice and cake powder. Except the levels of TBARS, the effects on the other measure-ments by the various dietary levels of mulberry juice and cake powder were almost same and the effect of the cake powder was most significant at the lowest level. These results indicate that mulberry juice and cake powders have considerable hypoglycemic effect and strengthening antioxidant defense systems at the low levels in diabetic state and may be able to reduce diabetic complications.

Soybean isoflavone extract improves glucose tolerance and raises the survival rate in streptozotocin-induced diabetic rats

The present study evaluated the effect of various dosages of soybean isoflavone extract on body weight changes, glucose tolerance and liver function in streptozotocin-induced diabetic rats. One group of normal rats (normal control) was fed an AIN-76-based experimental diet and four groups of diabetic rats were fed the same diet supplemented with four different levels of soybean isoflavone extract for seven weeks. The daily dosages of pure isoflavone for four diabetic groups were set to be 0 mg (diabetic control), 0.5 mg (ISO-I), 3.0 mg (ISO-II) and 30.0 mg (ISO-III) per kilogram of body weight, respectively. The daily consumption of isoflavone at the level of 3.0mg per kilogram of body weight resulted in the suppression of body weight loss and increased the survival rate of diabetic animals one and half times compared to that of the diabetic control group. Blood glucose levels in a fasting state and after the oral administration of glucose were significantly lower in the ISO-II group during the oral glucose tolerance test. The ISO-II group showed a tendency to elongate the gastrointestinal transit time. The activity of serum aminotransferases, indicator of liver function, was not negatively affected by any intake level of isoflavone. The present study demonstrated that the soybean isoflavone extract may be beneficial to diabetic animals by improving their glucose tolerance and suppressing weight loss without incurring hepatotoxicity at the daily dosage of 3.0 mg per kg of body weight.