PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 microL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and gamma-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.
Agmatine/*therapeutic use ; Alzheimer Disease/*chemically induced/*drug therapy ; Animals ; Cognition Disorders/*chemically induced/*drug therapy ; Disease Models, Animal ; Male ; Rats ; Streptozocin/*toxicity

BACKGROUNDBerberine is one of the main constituents of Coptidis rhizoma (CR) and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy (DN).

METHODSMale Wistar rats were divided into three groups: normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin (STZ). Glomerular area, glomerular volume, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Cr) and urine protein for 24 hours (UP24h) were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) in serum, activity of aldose reductase (AR) and the expression of AR mRNA and protein in kidney were detected by different methods.

RESULTSThe results showed that oral administration of berberine (200 mg x kg(-1) x d(-1)) significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group (P < 0.05). Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group (P < 0.05). AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group (P < 0.05).

CONCLUSIONThese results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.

Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Berberine ; pharmacology ; therapeutic use ; Diabetes Mellitus, Experimental ; complications ; Diabetic Nephropathies ; drug therapy ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Wistar ; Streptozocin

BACKGROUNDDiabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 (GHRP-6), increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.

METHODSA diabetic guinea pig model was produced by intraperitoneal (i.p.) injection of streptozotocin (STZ, 280 mg/kg). Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 (10 - 100 microg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor (GHS-R) antagonist, D-Lys(3)-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 (100 microg/kg) was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 (0.01 - 10 micromol/L) on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction (RT-PCR).

RESULTSWe established a guinea pig model of delayed gastric emptying. Ghrelin (20, 50, or 100 microg/kg) and GHRP-6 (20, 50, or 100 microg/kg) accelerated gastric emptying in diabetic guinea pigs with gastroparesis (n = 6, P < 0.05). In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 (100 microg/kg) failed to accelerate gastric emptying (n = 6, P < 0.05). D-Lys(3)-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist (n = 6, P < 0.05). Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs (n = 6, P < 0.05). RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.

CONCLUSIONSGhrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.

Animals ; Diabetes Mellitus, Experimental ; complications ; Female ; Gastric Emptying ; drug effects ; Gastroparesis ; drug therapy ; physiopathology ; Ghrelin ; therapeutic use ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Oligopeptides ; therapeutic use ; Receptors, Ghrelin ; analysis ; Streptozocin

OBJECTIVETo investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy (LVH) in type 2 diabetic rats.

METHODSType 2 diabetic mellitus (DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy (LVH) by ultrasound examination, and randomly assigned into three groups: untreated (DM-LVH, n=7), treated with insulin (DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3 (DM-LVH+VD, n=6). Healthy male rats were used as the controls group (n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later.

RESULTSIn the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group (P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased (all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group (P<0.05), whereas the other parameters were significantly decreased (all P<0.05).

CONCLUSION1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.

Animals ; Blood Glucose ; analysis ; Calcitriol ; therapeutic use ; Diabetes Mellitus, Experimental ; blood ; complications ; Diabetes Mellitus, Type 2 ; blood ; complications ; Hypertrophy, Left Ventricular ; prevention & control ; Insulin ; blood ; Male ; Rats ; Rats, Wistar ; Receptors, Calcitriol ; analysis ; Streptozocin

OBJECTIVETo investigate the effects of Chlorophytum borivilianum (CB) on sexual dysfunction, loss of body weight, and lack of libido in hyperglycemic rats induced with streptozotocin or alloxan.

METHODSWistar strain male albino rats were divided into five groups of six animals each: the control group (2% polyvinylpyrollidone solution), the streptozotocin control group (50 mg/kg), the alloxan control group (100 mg/kg), the streptozotocin + CB treated group (200 mg/kg), and the alloxan + CB treated group (200 mg/kg). Only after confirming the induction of diabetes, the animals of test groups were treated with CB. The sexual behavior of male rats of in presence of female rat in a special cage was recorded. The effects of induced diabetes in control groups and on simultaneous extract treatment in CB treated groups were tested for sexual parameters. The parameters evaluated included mount, ejaculation, and intromission latencies/frequencies, hesitation time, and penile erection index. Parallel to this, using a separate set of similarly treated animals, the influence of diabetes and CB treatment on anabolism and weight of secondary sexual organs were determined on day 0 and day 28 of the treatment.

RESULTSCB extract treatment ameliorated the diabetes-induced dysfunction at 200 mg/kg dose. There was very low weight loss (P<0.05) in CB-treated animals as compared to the diabetic control. There was a very high latency time (P<0.05) in the diabetic animals, whereas the latency time was very low in CB-treated animals. Mount, intromission, and ejaculation frequencies were very high (P<0.01) in CB-treated animals, while streptozotocin and alloxan groups animals had a very significantly lower sexual behavior (P<0.05) compared to the normo-glycemic control group animals.

CONCLUSIONCB can significantly ameliorate diabetes-induced sexual dysfunction. Polysaccharide and saponin-rich aqueous extract appears to have the most suitable effects on diabetes and its associated effects on sexual functionality.

Alloxan ; Animals ; Asparagaceae ; Blood Glucose ; analysis ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; complications ; drug therapy ; Female ; Male ; Nitric Oxide ; physiology ; Plant Extracts ; therapeutic use ; Rats ; Rats, Wistar ; Sexual Behavior, Animal ; drug effects ; Streptozocin

BACKGROUNDOxidative stress has been implicated in the onset and progression of diabetes. Tongxinluo is a traditional Chinese medicine with potent antioxidant properties. The aim of this study was to test the hypothesis that pretreatment with Tongxinluo has similar effects as melatonin on preventing hyperglycemia and beta-cell damage in a rat model of streptozotocin (STZ)-induced diabetes.

METHODSForty male Sprague Dawley rats were randomly assigned to four groups (n = 10 each): normal control (NC) group; STZ group (70 mg/kg, i.p.); Tongxinluo (1.0 g×kg(-1)×d(-1)) pretreated (TXL + STZ) group and melatonin (200 µg×kg(-1)×d(-1)) pretreated (MLT + STZ) group. Tongxinluo and melatonin were administered by gavage beginning 8 days before STZ injection and continuing until the end of the study (15 days after STZ administration). Blood glucose levels and body weights, malondialdehyde (MDA), and reduced glutathione (GSH) levels were measured, and immunofluorescence studies were performed in all of the groups.

RESULTSPretreatment with Tongxinluo, as with melatonin, attenuated severe hyperglycemia and weight loss induced by STZ. In pancreatic homogenates, MDA levels were significantly lower and GSH levels were significantly higher in Tongxinluo pretreated group and in melatonin pretreated group than those in STZ group. Values of insulin staining were significantly improved in Tongxinluo pretreated group and in melatonin pretreated group as compared with those in STZ group.

CONCLUSIONSTongxinluo, as melatonin, prevented hyperglycemia and beta-cell destruction induced by STZ in rats through reducing oxidative stress in pancreatic tissues. Tongxinluo may provide an alternative therapy for the prevention and treatment of diabetes.

Animals ; Blood Glucose ; analysis ; Body Weight ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Fluorescent Antibody Technique ; Hyperglycemia ; drug therapy ; Male ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Streptozocin

BACKGROUNDThe effects of triterpenic acid from Prunella vulgaris L. (TAP) on diabetes and its mechanism are uncertain. The aim of this study was to investigate the effects of TAP on antihyperglycemic, antioxidant, and pancreas-protective in streptozotozin (STZ)-diabetic rats.

METHODSThe diabetic model was produced by injection of 60 mg/kg STZ. Blood was drawn from the tail vein of rats after 72 hours. Rats with blood glucose ≥ 16.7 mmol/L were considered diabetic. Diabetic rats were randomly divided into four groups: (1) Diabetes rat (STZ), (2) Diabetic rats treated with 50 mg/kg of triterpenic acid from Prunella vulgaris L (STZ + TAP50), (3) Diabetic rats treated with 100 mg/kg TAP (STZ + TAP100), and (4) Diabetic rats treated with 200 mg/kg TAP (STZ + TAP200). Normal rats (n = 10) acted as the control group (NC). TAP was administered by the intragastric route once each day for six weeks. Body weight and the concentration of blood glucose (BG) were measured after three and six weeks. Fructosamine (FMN), malondialdehyde (MDA), and nitric oxide (NO), and the activities of nitric oxide synthase (NOS) and superoxide dismutase (SOD) in serum were determined after six weeks using commercially available kits following the manufacturer's instructions. Pathologic changes in pancreatic β-cells were also investigated by microscopic examination after hematoxylin-eosin (HE) staining. The level of SOD mRNA in pancreatic β-cells was measured by polymerase chain reaction (PCR).

RESULTSThe levels of BG, FMN, NO, and MDA and the activities of NOS in serum in the four diabetes groups were significantly increased compared with the control group (P < 0.01). The activity of SOD in serum and the body weight was significantly decreased compared with the control group (P < 0.01). After administration of TAP to diabetic rats for six weeks, the body weight and the levels of BG, FMN, MDA, NO and the activity of NOS in serum decreased significantly compared with the STZ group in a dose-dependent manner. The activity of SOD in serum and body weight increased significantly compared with the STZ group in a dose-dependent manner. In addition, diabetic rats showed a significant decrease in SOD mRNA expression in pancreatic β cells. However, these changes were reversed by TAP. Histopathological examination also showed the protective effect of TAP on pancreatic β cells.

CONCLUSIONSTriterpenic acid from Prunella vulgaris L. has an anti-diabetic effect, by controlling blood glucose and antioxidants, and has a protective effect on the pancreas.

Animals ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Insulin-Secreting Cells ; drug effects ; pathology ; Male ; Prunella ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Superoxide Dismutase ; genetics ; Triterpenes ; therapeutic use

OBJECTIVETo study the effects of different compatibility proportion of Jiaotai pills on treating type 2 diabetes mellitus (T2DM) in rats.

METHODThe model of type 2 diabetes mellitus in rats was established by injecting streptozotocin from tail vein and feeding with high fat and high caloric diet. Diabetic rats were randomly divided into model group, Jiaotai pill 1 group (Coptidis Rhizoma-cinnamon 2: 1), Jiaotai pill 2 group (Coptidis Rhizoma-cinnamon 4: 1), Jiaotai pill 3 group (Coptidis Rhizoma-cinnamon 10: 1) and metformin group. Rats in different treatment groups were given by corresponding therapy from gastric tube. Meanwhile normal control group was another set. Body weight, oral glucose tolerance test (OGTT), blood lipid level including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), plasma levels of free fatty acid (FFA) and adiponectin, plasma liver enzymes activity(ALT, AST, AKP, gamma-GT) and pathological results of liver tissue were determined after eight weeks.

RESULTBody weight, fasting plasma glucose (FPG), postpradial plasma glucose at one hour (PG-1 h), postpradial blood glucose at two hour (PG-2 h), plasma levels of TC, TG, LDL-C, FFA and liver enzymes activity were all increased in rats of model group compared with those in normal control group. Plasma levels of HDL-C and adiponectin were decreased in model group (P < 0.01). Fatty degeneration of hepatocytes was apparent in liver tissues in rats of model group. Compared with model group results of OGTT, blood lipid levels and liver enzymes activity were improved while levels of HDL-C and adiponectin were increased in rats of different treatment groups (P < 0.05 or P < 0.01). Meanwhile fatty degeneration of hepatocytes was improved in liver tissues in rats of different treatment groups. Compared with metformin group, plasma level of HDL-C was elevated while AKP and gamma-GT were decreased significantly in rats of Jiaotai pill 1 group (P < 0.05), gamma-GT level was decreased significantly in rats of Jiaotai pill 2 group (P < 0.05), AST, AKP and gamma-GT levels were decreased significantly in rats of Jiaotai pill 3 group (P < 0.05). Compared with Jiaotai Pill 1 group, plasma levels of HDL-C was decreased while AKP levels was elevated significantly in rats of Jiaotai pill 2 group, but HDL-C was decreased in rats of Jiaotai pill 3 group (P < 0.05).

CONCLUSIONIt is suggested that different compatibility proportion of Jiaotai pills are effective on treating type 2 diabetes mellitus in rats. The effect of Jiaotai pill 1 group is better than that of other therapy groups.

Animals ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Acids, Nonesterified ; blood ; Lipids ; blood ; Male ; Medicine, Chinese Traditional ; Rats ; Streptozocin

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

The objective of this study is to fully investigate the therapeutic effect and mechanisms of action of Gegen Qinlian decoction (GD) on type 2 diabetes mellitus (type 2 DM). A rat model of type 2 DM was established with the combination of high-fat diet and multiple low doses of streptozotocin (STZ). Biochemical indicators related to glucose metabolism disorders, insulin resistance, oxidative stress were observed. The type 2 DM rats were administrated with GD for 80 days, the above-mentioned indexes were detected. The results indicated that the hepatic glycogen synthesis level was promoted, fasting blood glucose level and fasting blood insulin level were significantly reduced, insulin sensitivity index was significantly improved; the level of superoxide dismutase (SOD) was increased and the level of malondialdehyde (MDA) was reduced; pathologic morphology of pancreas and kidney was ameliorated in the GD group. It was indicated that the therapeutic mechanisms of action of GD on type 2 DM might be related to its effect of ameliorating glucose metabolism disorders, relieving insulin resistance, increasing the tissues' sensitivity to insulin, improving the antioxidative ability of living system, GD has therapeutic effect on type 2 DM and protective effects against damaged pancreatic function.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Female ; Glycogen ; metabolism ; Hypoglycemic Agents ; isolation & purification ; pharmacology ; therapeutic use ; Insulin ; blood ; Insulin Resistance ; Kidney ; pathology ; Liver ; metabolism ; Male ; Malondialdehyde ; metabolism ; Pancreas ; pathology ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Superoxide Dismutase ; metabolism