Animals ; Autophagy ; Diabetes Mellitus, Experimental/drug therapy* ; Mice ; Myocardium ; Sitagliptin Phosphate/pharmacology* ; Streptozocin

To evaluate the roles of hyperglycemia and increased plasma FFA level in the development of insulin resistance, we examined the effects of phlorizin and acipimox treatments on tissue sensitivity to insulin in streptozotocin(STZ)-diabetic rats. Insulin sensitivity was assessed with the glucose-insulin clamp technique. Blood glucose concentration was clamped at basal levels of control and diabetic states, and plasma insulin concentrations were clamped at the levels of basal, approximately 60 and approximately 1500 microU/ml. In diabetic rats, the basal blood glucose and plasma FFA levels in the fasting state were elevated, while the plasma insulin concentration was lower than in normal controls. Moreover, diabetic rats became glucose intolerant after intravenous injection of glucose. The metabolic clearance rate(MCR) of glucose showed a decrease of basal and insulin stimulated response in diabetic rats. As results of the glucose-insulin clamp study and intravenous glucose tolerance test, insulin resistance was developed in STZ-diabetic rats. Phlorizin treatment of diabetic rats recovered insulin sensitivity to nearly normal levels and improved glucose tolerance, but had no effect on insulin action in controls. Insulin sensitivity was also improved by acipimox treatment in diabetic rats, but did not reach normal levels. These results show that hyperglycemia is an obvious causative factor of insulin resistance, and increased FFA level may also act on the development of insulin resistance in STZ-diabetic rats.
Animal ; Antilipemic Agents/*pharmacology ; Blood Glucose/analysis ; Diabetes Mellitus, Experimental/*metabolism ; Fatty Acids, Nonesterified/blood ; Female ; *Insulin Resistance ; Phlorhizin/*pharmacology ; Pyrazines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Streptozocin

The present study aimed to evaluate the anti-diabetic property of peanut shell polyphenol extracts (PSPEs). Diabetic rats were oral-administrated with PSPE at doses of 50, 100, and 200 mg/kg body weight (BW) per day for 28 consecutive days, with metformin (Met) as a positive control. The results showed that, similar to the Met treatment, administration of PSPE caused significant decreases in food intake, water intake, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and methane dicarboxylic aldehyde in serum, and significant increases in BW, insulin level, high-density lipoprotein cholesterol, superoxide dismutase, glutathione, and liver glycogen. Further, glucose tolerance was markedly improved in the PSPE-treated diabetic groups. Histopathological results showed that PSPE improved cellular structural and pathological changes in liver, kidney, and pancreatic islets. Collectively, the results indicated that the hypoglycemic effects of PSPE on high-fat diet/streptozotocin (HFD/STZ)-induced diabetes are comparable to Met, though their exact mechanism actions are still under investigation. Therefore, the current study suggests that PSPE could be a potential health-care food supplement in the management of diabetes.
Animals ; Arachis/chemistry* ; Diabetes Mellitus, Experimental/pathology* ; Hypoglycemic Agents/pharmacology* ; Lipids/blood* ; Liver/pathology* ; Male ; Oxidative Stress/drug effects* ; Plant Extracts/pharmacology* ; Polyphenols/pharmacology* ; Rats ; Rats, Wistar ; Streptozocin

OBJECTIVES: To investigate the effects of saffron aqueous extract (SE) on blood glucose, lipid and pancreatic tissue in streptozocin-induced diabetes mice. METHODS: Diabetes mellitus mice were established by intraperitoneal injection of streptozocin (60 mg/kg) for two consecutive days. The 30 well-established diabetes mice were randomly divided into three groups(=10):diabetic mellitus (DM) group, SE treated (SE) group and positive control (metformin hydrochloride, MH) group. Another ten normal mice were selected as normal control (NC) group. The mice in SE and MH groups were intragastrically administered with SE 100 mg/kg or MH 100 mg/kg once a day for 6 weeks, mice in DM and NC were given normal saline. The amount of food-intake, water consumption and body weight were measured weekly, the changes of the indicators including fasting blood glucose (FBG), oral glucose-tolerance test (OGTT), glycated serum protein (GSP), insulin (INS) and blood lipid were determined after 6 weeks of continuous administration. The pathologic changes in the pancreas tissues were detected by HE staining. RESULTS: Compared with the normal control group, the amount of food-intake, water consumption, area under the curve, FBG, GSP, and total cholesterol (TC) were significantly increased, while fasting weight, INS and high density lipoprotein cholesterol (HDL-c) were dramatically decreased in DM group. Compared with DM group, the water consumption, FBG, area under the curve and TC in SE group were starkly declined with a notable elevation of HDL-c and INS. In addition, the biopsy from DM mice showed the structure of pancreas islet was destroyed and reduced, and vascular proliferation with irregular shape. The damaged pancreas was obviously repaired by giving SE. CONCLUSIONS The saffron aqueous extract had efficacy on blood glucose and blood lipids reduction, improvement on damaged pancreas in streptozocininduced diabetic mice, which suggested that saffron could be used for the treatment in diabetes.
Animals ; Blood Glucose ; Crocus ; chemistry ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; Hypoglycemic Agents ; pharmacology ; Insulin ; blood ; Mice ; Plant Extracts ; pharmacology ; Random Allocation ; Streptozocin

OBJECTIVETo observe the changes in the myocardial ultrastructure of diabetic rats and the effect of enalapril treatment.

METHODSMale Wistar rats were divided into 3 groups, namely the control group, diabetic group and enalapril intervention group. Diabetes was induced with peritoneal injection of streptozotocin in the latter 2 groups, and in enalapril group, the rats were treated with enalapril at the daily oral dose of 2 mg/kg for 1, 3 and 5 months after streptozotocin injection. Histological analysis of the left ventricular tissue was performed with transmission electron microscope 1, 3, and 5 months after establishment of diabetes.

RESULTSOnset of myocardial damages was observed 1 month after the development of diabetes in the rats with gradual time-dependent exacerbation. Enalapril treatment could partially reverse the myocardial destruction in the diabetic rats.

CONCLUSIONEnalapril intervention may improve the ultrastructural pathology of the myocardium in diabetic rats, which is suggestive of the action mechanisms of angiotensin-converting enzyme inhibitors in myocardium preservation.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Diabetes Mellitus, Experimental ; drug therapy ; pathology ; Enalapril ; pharmacology ; Male ; Myocardium ; ultrastructure ; Rats ; Rats, Wistar ; Streptozocin

OBJECTIVETo investigate the protective effect and mechanism of curcumin derivatives B06 on myocardium from type 2 diabetic rats.

METHODSThirty-five male SD rats were randomly divided into 5 groups, normal control group (NC group), high fat group (HF group), high fat treatment group (FT group), diabetes mellitus group (DM group) and diabetes treatment group (DT group) (n = 7). The late four groups were fed with high fat food, after four weeks of high fat feeding, the rats from DM group and DT group were injected with low dosage of streptozocin intraperitoneally to induce diabetes mellitus, FT group and DT group were gavaged with curcumin derivatives B06 at the dosage of 0.2 mg/kg x d. The blood glucose and lipid were detected biochemically, blood insulin was assayed by ELISA and the insulin resistance index was calculated, the morphology of myocardium was observed by light and transmission electron microscopy, the protein expression of AMP-activated protein kinase alpha (AMPKalpha) and phosphorylated AMP-activated protein kinase alpha (p-AMPKalpha) in myocardium were tested by Western blot.

RESULTSThe level of blood glucose, lipid, insulin and the insulin resistance index were increased in HF group and DM group, but they were decreased after the treatment with B06. The expression of AMPKalpha and p-AMPKalpha were decreased, but they became increased after the treatment of B06. There were increased collagen fibers in interstitium and expansion of mitochondria in cytoplasm of myocardium from DM group, but they were ameliorated in B06 treatment group.

CONCLUSIONIt is suggested that B06 may relieve the damage of myocardium from type 2 diabetic rats and the increased expression of AMPKalpha and p-AMPKalpha may be involved in it.

AMP-Activated Protein Kinases ; metabolism ; Animals ; Blood Glucose ; Curcumin ; pharmacology ; Diabetes Mellitus, Experimental ; physiopathology ; Heart ; drug effects ; Insulin Resistance ; Male ; Myocardium ; pathology ; Rats ; Rats, Sprague-Dawley ; Streptozocin

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

OBJECTIVE: To investigate the therapeutic effects of puerarin on rats with type 2 diabetes mellitus (T2DM). METHODS: T2DM models were established by high fat and high glucose feeding combined with a one-time intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Then the rats were randomly divided into normal group, model group, metformin group (MET, 40 mg/kg), puerarin low-dose group, medium-dose group and high-dose group (40, 80, 160 mg/kg), n=10. After the model was successfully established, rats were treated with corresponding drug intervention by intragastrical administration for 4 weeks. The body weight and fasting blood glucose (FBG) were measured per week, and blood samples were collected 24 h after the last administration, and serum levels of blood glucose, serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholestrol (HDL-C), serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine (SCr), and blood uric acid (UA) were measured. RESULTS: As compared with normal group, the body weight was decreased after 4 weeks-intervention in the model group, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were all increased,while HDL-C level was decreased (P＜0.05). As compared with model group,the body weight was increased after 4 weeks-intervention in metformin group and puerarin groups, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were decreased (P＜0.01); meanwhile, HDL-C level was increased significantly (P＜0.05). CONCLUSION Puerarin can reduce the weight loss of T2DM rats, decrease the blood lipid and blood glucose levels of T2DM rats, which can be used to control T2DM.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Isoflavones ; pharmacology ; Lipids ; blood ; Random Allocation ; Rats ; Streptozocin ; Weight Loss

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.
Mice ; Animals ; Diabetes Mellitus, Type 2/genetics* ; Streptozocin/pharmacology* ; Diet, High-Fat/adverse effects* ; Proteomics ; Inflammation ; TOR Serine-Threonine Kinases ; Autophagy ; Mammals

OBJECTIVETo study the effects of Meilian Xiaoke capsule (a traditional Chinese medicinal preparation) combined with metformin for protecting islet cells and lowering blood glucose in diabetic rats.

METHODSRat models with type 2 diabetes, established by high-fat and high-glucose diet combined with streptozotocin (STZ) injection, were treated with a low dose of metformin, Meilian Xiaoke capsule, or both for 4 weeks by gavage. Blood glucose level was tested in the rats, and islet pathologies and changes in islet β cell number after the treatment were observed with HE staining and aldehyde fuchsin staining, respectively.

RESULTSTreatment with metformin or Meilian Xiaoke capsule alone for 2 or 4 weeks did not produce significant improvement of blood glucose in the diabetic rats. Their combined treatment for 4 weeks resulted in significantly lowered blood glucose level and improved glucose tolerance with also obviously increased islet β cell number and lessened islet pathologies.

CONCLUSIONSMeilian Xiaoke capsule and metformin show a synergistic effect to significantly enhance the therapeutic effect in rats with type 2 diabetes.

Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Synergism ; Drugs, Chinese Herbal ; pharmacology ; Hypoglycemic Agents ; pharmacology ; Insulin-Secreting Cells ; pathology ; Metformin ; pharmacology ; Rats ; Streptozocin