The injection of streptozotocin(stz) at a high dose (60 mg/kg) into young male rats produces direct beta cell destruction and leads to insulin dependent diabetes (IDD). In contrast the injection of multiple smal doses of stz (40 mg/Kg/d for 5 days) produce IDD, which resembles type l diabetes in man. The provocative effects of the pertussis vaccine (PV) and cyclosporin(CA) against the development of IDD induced by stz were studied. When PV in a dose of 3.75 X 10(10) microorganism was administered to single or multiple stz treated rats, hyperglycemia still developed and persisted during the experiment. No difference was noted in blood glucose levels, but plasma insulin levels were higher in PV treated rats. When CA (10 mg/kg) was administered daily to single or multiple stz treated rats, hyperglycemia seemed to be lower, but this was not statistically significant, however, plasma insulin levels were higher in CA treated rats. The results of this experiment suggest that PV and CA provide some protection to the beta cells of the pancreas.
Animal ; Blood Glucose/metabolism ; Cyclosporins/pharmacology* ; Diabetes Mellitus, Experimental/prevention & control* ; Diabetes Mellitus, Insulin-Dependent/chemically induced ; Male ; Pertussis Vaccine/pharmacology* ; Rats ; Rats, Inbred Strains

OBJECTIVETo investigate the effect of ursolic acid (UA) on the alloxan-induced kidney injury in diabetic mice and explored its possible mechanisms.

METHODSDiabetes mellitus was induced in male Kunming mice by an injection of alloxan (70 mg/kg, i.v.). After 72 hours, blood glucose levels were detected and mice with blood glucose levels over 13.9 mmol/L were considered as diabetic and selected for further experiment. Thirty mice were randomly divided into three groups: control, diabetic and diabetic + UA(35 mg/kg/d, i.g. continuously for 8 weeks). Blood glucose concentration, organ coefficient of kidney, blood urea nitrogen (BUN), creatinine (Cr) as well as renal tissue levels of superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined. Pathology of the renal tissue was measured by hematoxylin-eosin staining.

RESULTSCompared to the control group, blood glucose, organ coefficient of kidney, BUN and Cr increased significantly. In addition, SOD activities was reduced markedly and levels of MDA and inflammatory factors (TNF-α, IL-6) increased significantly. Renal cells from model group rats showed atrophy and disordered after HE staining and infiltration of inflammatory cells also appeared in renal tissue of the model group. These changes were significantly attenuated in the diabetic group treated with UA.

CONCLUSIONUA can significantly relieve renal damage in mice with diabetic nephropathy induced by alloxan, which might be related to decreased blood glucose level, antioxidation effect and inhibiting the production of inflammatory factors such as TNF-α and IL-6.

Alloxan ; adverse effects ; Animals ; Antioxidants ; metabolism ; Blood Glucose ; Blood Urea Nitrogen ; Creatinine ; metabolism ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetic Nephropathies ; chemically induced ; drug therapy ; Interleukin-6 ; metabolism ; Kidney ; physiopathology ; Male ; Mice ; Superoxide Dismutase ; metabolism ; Triterpenes ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the effects of Qilan Tangzhining capsule on glucose and lipid metabolism in diabetes mellitus and hyperlipemia.

METHODRats were fed with high sugar and fat food for 2 months, then 2% streptozocin (STZ, 30 mg kg(-1)) was injected intraperitoneally to induce hyperglycemia and hyperlipemia. After the model rats were administrated drugs, the blood glucose, the serum lipids, and the histopathology of the liver and pancreas were observed.

RESULTQilan Tangzhining capsule could decrease the FBG and the serum TC, TG, LDL-C, increase HDL-C, and improve the histopathologic injury of the liver and pancreas.

CONCLUSIONQilan Tangzhining capsule can not only adjust the blood glucose and lipid, but also improve the histopathology injury of the liver and pancreas.

Animals ; Astragalus membranaceus ; chemistry ; Blood Glucose ; metabolism ; Capsules ; Diabetes Mellitus, Experimental ; blood ; chemically induced ; complications ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Gynostemma ; chemistry ; Hyperlipidemias ; blood ; complications ; Lipids ; blood ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar

AIMTo evaluate the roles of puerarin in alleviating the STZ-induced lung injury.

METHODSDM model was established by streptozotocin (STZ) intraperitoneal injection to study the injury mechanisms of the lung. SD rats were divided randomly into control group (C group), diabetes group (DM group), diabetes + puerarin group (DM + Pur group). The blood glucose and weight were observed and recorded before and the 20 th, 40 th, 60 thd after administration of saline, STS, STZ+ Pur. Contents of NO and malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were measured in lung tissues. Light microscope (LM), transmission electron microscope (TEM) and immunohistochemical analysis were also used.

RESULTS(1) Compared with control group, the contents of NO and MDA were increased significantly (P < 0.01), while the activity of SOD reduced (P < 0.05). Compared with DM group, treatment with puerarin inhibited the increase of NO level (P < 0.01), and MDA content began to decline from 40 days after the model was established (P < 0.01), and inhibited the decrease of SOD activity induced by DM (P < 0.01). (2) LM and TEM results showed that alveolar and capillary basement membrane became thick, the number of tiny villus decreased markedly, the quantity of osmiophilic multilamellar body reduced remarkably, hyperplasia was shown in collgen fibre. Puerarin could alleviate above injuries induced by DM. (3) Immunohistochemical staining results showed that mild brown positive stain of NT could be seen in protoplasm of lung tissues. STZ administration induced the expression of NT in the protoplasm of cells, and led to stronger positive signals of NT than that of control group. Treatment with puerarin weakened the positive stain of NT.

CONCLUSION(1) DM induced by STZ leads to a significant and sustained increase in blood glucose and obvious lung injury, which may be associated with the overproduction of free radicals. (2) The pathway of NO/ONOO- is one of the injury mechanisms of the lung tissues cells. (3) Puerarin suppresses the expression of NT and elevates the activity of SOD. Thereby, resulting in the reduces of the production of free radicals, which may be one of the mechanisms of its anti-oxidative-injuries.

Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Isoflavones ; pharmacology ; Lung ; metabolism ; pathology ; Lung Injury ; chemically induced ; Malondialdehyde ; analysis ; Nitric Oxide ; analysis ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the hypoglycemic effect of the total flavonoids in Leucaena seeds(TF).

METHODExperimental observation was performed by using various diabetic mice induced by alloxan, adrenalin, etc.

RESULTTF could significantly lower the blood glucose levels in Alloxan model mice, adrenalin model mice and hyperglycemic mice, while had no hypoglycemic effect on the normal mice.

CONCLUSIONThe total flavonoids in Leucaena seeds has hypoglycemic effect in diabetic model mice.

Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; blood ; Epinephrine ; Fabaceae ; chemistry ; Flavonoids ; isolation & purification ; pharmacology ; Hyperglycemia ; blood ; chemically induced ; Hypoglycemic Agents ; isolation & purification ; pharmacology ; Male ; Mice ; Plants, Medicinal ; chemistry ; Seeds ; chemistry

Objective To establish a Daphnia model of alloxan-induced diabetes. Methods Daphnia were exposed to three different concentrations of alloxan (3, 5, and 10 mmol/L) for 30 minutes. Blood glucose and survival rate were recorded for 72 hours after alloxan insult. Sequence analysis and phylogenetic inference for glucose transporters (GLUT) were clustered with the maximum-likelihood method. Using reverse transcription and quantitative polymerase chain reaction techniques, we investigated the transcriptional changes of GLUT at 12 hours after alloxan (5 mmol/L) exposure. Results Compared with control, 3 mmol/L, and 5 mmol/L as well as 10 mmol/L alloxan initially induced transient blood glucose decline by 15% for 2 hours and 12 hours respectively. In Daphnia with 5 and 10 mmol/L alloxan, their blood glucose was persistently raised by about 150% since after 24-hour insult. Survival rate of Daphnia exposure to alloxan with concentrations of 3, 5, and 10 mmol/L were 90%, 75%, and 25% respectively. We predicted seven GLUT genes in the Daphnia genome and successfully amplified them using real-time polymerase chain reaction. Two of seven GLUT transcripts were down-regulated in Daphnia with 5 mmol/L alloxan-induced diabetes. Conclusion Alloxan-induced diabetes model was successfully established in the Daphnia pulex, suggesting diabetes-relevant experiments can be conducted using Daphnia.
Alloxan ; Animals ; Blood Glucose ; analysis ; Daphnia ; Diabetes Mellitus, Experimental ; chemically induced ; physiopathology ; Disease Models, Animal ; Gene Expression Regulation ; Glucose Transport Proteins, Facilitative ; genetics ; metabolism ; Likelihood Functions ; Phylogeny ; Real-Time Polymerase Chain Reaction

The aim of the present study is to investigate the effects of sequoyitol (Seq) on expression of eNOS and NOX4 in aortas of type 2 diabetic rats. Type 2 diabetic rats induced by high fat and high sugar diet and low dose of streptozotocin (STZ, 35 mg x kg(-1)) and were administered Seq (12.5, 25 and 50 mg x kg(-1) x d(-1)) for 6 weeks. The fasting blood glucose (FBG) and body weight were tested. Acetylcholine (Ach) induced endothelium-dependent relaxation and sodium nitroprusside (SNP) induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Aortic morphological change was observed with HE staining. The level of serum insulin was measured by radioimmunoassay. The total antioxidative capacity (T-AOC), malondialdehyde (MDA) and NO levels in aortas were determined according to the manufacturer's instructions. In addition, the expressions of eNOS and NOX4 in aortas were measured by immunohistochemisty, real-time PCR or Western blotting. The results showed that Seq significantly decreased FBG and insulin resistance, and improved aortic endothelium-dependent vasorelaxation function. The expressions of NOX4 and MDA content were obviously decreased, while the expression of eNOS, the levels of NO and T-AOC increased significantly in aortas of diabetic rats with Seq treatment. In conclusion, Seq protects against aortic endothelial dysfunction of type 2 diabetic rats through down-regulating expression of NOX4 and up-regulating eNOS expression.
Animals ; Aorta ; metabolism ; pathology ; Blood Glucose ; metabolism ; Body Weight ; Diabetes Mellitus, Experimental ; chemically induced ; metabolism ; physiopathology ; Diabetes Mellitus, Type 2 ; chemically induced ; metabolism ; physiopathology ; Hypoglycemic Agents ; pharmacology ; Inositol ; analogs & derivatives ; pharmacology ; Insulin ; blood ; Insulin Resistance ; Male ; Malondialdehyde ; metabolism ; NADPH Oxidase 4 ; NADPH Oxidases ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Oxidation-Reduction ; drug effects ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Vasodilation ; drug effects

The aim of this study is to investigate the therapeutic effect of RegIII-proinsulin-pBudCE4.1 plasmid on streptozotocin (STZ)-induced type 1 diabetes mellitus and its underlying mechanisms. The model of type 1 diabetes mellitus was established by intraperitoneal injections of STZ (40 mg kg(-1)) to Balb/c mice for five consecutive days. Then, ten type 1 diabetic mice were intramuscularly injected with 100 microg RegIII-proinsulin-pBudCE4.1 plasmid for 4 weeks (one time/week) and the blood glucose levels were monitored every week; whereas another ten diabetic mice served as negative control group were injected with pBudCE4.1 vector at the same dose. Normal control and model control mice were treated with normal saline at identical volume under the same way. Western blotting, MTT assay, ELISA, HE staining and Tunel assay were applied to explore the underlying mechanisms. Results showed that RegIII-proinsulin-pBudCE4.1 plasmid ameliorated the hyperglycemia symptoms in diabetic mouse remarkably. It induced an immunological tolerance state in type 1 diabetic mice by inhibiting the proliferation of splenic lymphocytes and recovering Th1/Th2 balance evidenced by MTT and ELISA analysis. Furthermore, it elevated insulin concentration in the serum of type 1 diabetic mice and promoted the regeneration of beta cells supported by the results of HE staining and Tunel assay. In conclusion, RegIII-proinsulin-pBudCE4.1 plasmid possesses powerful anti-diabetic ability, which may be involved in the inducing of immunological tolerance and enhancing beta cells recovery.
Animals ; Apoptosis ; Blood Glucose ; metabolism ; Cell Proliferation ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; therapy ; Diabetes Mellitus, Type 1 ; chemically induced ; metabolism ; pathology ; therapy ; Genetic Therapy ; Hyperglycemia ; therapy ; Injections, Intramuscular ; Insulin ; blood ; Islets of Langerhans ; cytology ; Male ; Mice ; Mice, Inbred BALB C ; Plasmids ; Proinsulin ; genetics ; metabolism ; therapeutic use ; Proteins ; genetics ; metabolism ; therapeutic use ; Streptozocin ; T-Lymphocytes ; cytology ; Th1-Th2 Balance

OBJECTIVETo observe the the protective effection of polysaccharides-2b of mudan cortex of Paeonia suffruticosa andr (PSM2b) on diabetic cataract.

METHODThe animal model of diabetic cataract in rats was induced by streptozotocin (STZ) and freund's adjuvant complete (CFA). The initial opacity occurrence time in lens was investigated with cranny lamp, and opacity degree of lens was compared too. The activities of glutathione peroxidase (GSH-pX), superoxide dismutase (SOD), catalase (CAT), the content of malonaldehyde (MDA) in serum and lens were detected. At the same time, the activities of Na(+) -K(+) -ATPase, the content of macromolecular weight protein and infusibility protein in lens were detected too.

RESULTThe results examinated by cranny lamp showed that PSM2b could significantly postpone the occurrence and alleviate opacity degree of lens. Compared with model group, every treatment group of PSM2b could lower the level of MDA, high and middle dose groups could increase the levels of SOD, GSH-pX, CAT in serum and lens in evidence, and enhance the activity of Na(+) -K(+) -ATPase. These indexes present favorable positive correlation between dose and effect.

CONCLUSIONAll these results demonstrated that PSM2b had apparently protective effection on diabetic cataract in rats.

Animals ; Catalase ; blood ; metabolism ; Cataract ; etiology ; metabolism ; prevention & control ; Diabetes Mellitus, Experimental ; blood ; chemically induced ; complications ; Glutathione Peroxidase ; blood ; metabolism ; Lens, Crystalline ; drug effects ; metabolism ; pathology ; Male ; Malondialdehyde ; blood ; metabolism ; Paeonia ; chemistry ; Phytotherapy ; Plant Bark ; chemistry ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Streptozocin ; Superoxide Dismutase ; blood ; metabolism

This study is to observe the effects of sequoyitol on the expression of NADPH oxidase subunits p22 phox and p47 phox in rats with type 2 diabetic liver diseases. The model of high fat and high sugar diet as well as intraperitoneal injection of small dose of streptozotocin (STZ, 35 mg x kg(-1)) induced diabetic rat liver disease was used. After sequoyitol (50, 25 and 12.5 mg x kg(-1)) was administrated for 6 weeks, the contents of blood glucose (BG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), NO and insulin (Ins) were measured, liver p22 phox and p47 phox mRNA content was determined with real-time PCR and the expression of p22 phox and p47 phox protein was examined by Western blotting. In addition, pathological changes in liver were observed with HE staining. Sequoyitol could reduce the content of fasting blood glucose, ALT, AST, Ins and H2O2, restore insulin sensitive index (ISI) and weight, elevate liver tissue T-AOC and NO content, reduce the NADPH oxidase subunit liver tissue p22 phox and p47 phox mRNA and protein expression, as well as ameliorate liver pathologic lesions. The results showed that sequoyitol can ease the type 2 diabetic rat liver oxidative stress by lowering NADPH oxidase expression.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; chemically induced ; metabolism ; Hydrogen Peroxide ; metabolism ; Hypoglycemic Agents ; pharmacology ; Inositol ; analogs & derivatives ; pharmacology ; Insulin ; blood ; Liver ; metabolism ; pathology ; Liver Diseases ; metabolism ; Male ; NADPH Oxidases ; genetics ; metabolism ; Nitric Oxide ; metabolism ; Oxidation-Reduction ; drug effects ; Oxidative Stress ; drug effects ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Streptozocin