OBJECTIVE: To investigate the effects of subcutaneous administration of insulin on insulitis,beta cell apoptosis and diabetes in non-obese diabetic (NOD) mice, and to explore the mechanism of immune tolerance induced by insulin. METHODS: Sixty female NOD mice were randomly divided into insulin group (n=32) and phosphate buffered saline (PBS) group (PBS group, n=28). Insulin was subcutaneously injected with humulin N (60 microL, 6U)+IFA (60 microL) at 4, 12, 20, and 28 weeks respectively, while the PBS group received PBS (60 microL) + IFA (60 microL). Insulitis and beta cell apoptosis of islets were observed at 12 weeks. IL-4 and IFN-gamma in the sera were measured by enzyme linked immunosorbent assay (ELISA). The expression levels of I-Abeta(g7), IL-4, IFN-gamma, IL-1beta, and Fas mRNA of islets were measured by reverse transcription-polymerase chain reaction (RT-PCR) at 12 weeks. RESULTS: The incidences in the insulin group were significantly lower than those in the PBS group (21.4% vs 71.4% at 30 weeks, 28.6% vs 85.7% at 52 weeks, P<0.05). The insulitis scores in the insulin group were lower than those in the PBS group, but there was no statistical significance. Fas expression on islets and apoptotic beta cell rates in the insulin group were lower than those in the PBS group (P<0.05). In the insulin group, serum IL-4 levels were higher, but IFN-gamma levels were lower than those in the PBS group (P<0.05). The levels of I-Abeta g7, IFN-gamma, IL-1beta and Fas mRNA transcription in islets were lower in insulin group, but IL-4 mRNA levels were higher than those in the PBS group (P<0.05). CONCLUSION The specific autoantigen insulin may induce immune tolerance and prevent diabetes in NOD mice, but it can't block the progression of insulitis. Subcutaneous administration of insulin can induce the regulatory T cells, and make Th1 to Th2 cytokine shifts in system and islets, thus preventing the Fas-mediated beta-cell apoptosis and diabetes.
Animals ; Apoptosis ; drug effects ; Diabetes Mellitus, Experimental ; prevention & control ; Diabetes Mellitus, Type 1 ; prevention & control ; Female ; Injections, Subcutaneous ; Insulin ; administration & dosage ; pharmacology ; Islets of Langerhans ; immunology ; pathology ; Mice ; Mice, Inbred NOD ; Pancreatitis ; prevention & control ; Random Allocation

To investigate whether BCG, lymphtoxin (LT) or bee venom (BV) can prevent insulitis and development of diabetes in non-obese diabetic (NOD) mice, we measured the degree of insulitis and incidence of diabetes in 24 ICR and 96 female NOD mice. NOD mice were randomly assigned to control, BCG-, LT-, and BV-treated groups. The BCG was given once at 6 weeks of age, and LT was given in 3 weekly doses from the age of 4 to 10 weeks. The BV was injected in 2 weekly doses from the age of 4 to 10 weeks. Diabetes started in control group at 18 weeks of age, in BCG group at 24 weeks of age, and in LT- or BV-treated group at 23 weeks of age. Cumulative incidences of diabetes at 25 weeks of age in control, BCG-, LT-, and BV-treated NOD mice are 58, 17, 25, and 21%, respectively. Incidence and severity of insulitis were reduced by BCG, LT and BV treatment. In conclusion, these results suggest that BCG, LT or BV treatment in NOD mice at early age inhibit insulitis, onset and cumulative incidence of diabetes.
Adjuvants, Immunologic/pharmacology* ; Age Factors ; Animal ; Bee Venoms/pharmacology* ; Cholesterol/blood ; Diabetes Mellitus/prevention & control* ; Diabetes Mellitus/immunology ; Diabetes Mellitus, Insulin-Dependent/prevention & control* ; Diabetes Mellitus, Insulin-Dependent/immunology ; Disease Models, Animal ; Female ; Islets of Langerhans/pathology* ; Islets of Langerhans/drug effects ; Lymphotoxin/pharmacology* ; Mice ; Mice, Inbred NOD ; Mycobacterium bovis/immunology* ; Triglycerides/blood

Nutrition labels are helpful for chronic disease management in patients requiring balanced nutritional intake. This study aimed to investigate the association between the use of nutrition labels and chronic diseases (hypertension, diabetes mellitus, and hyperlipidemia) by using the 2008-2009 Korea National Health and Nutrition Examination Survey data. A total of 10,695 individuals aged 20 and over was included in the analysis. Using multiple logistic regressions, there was no difference in nutrition label use between the chronic disease and normal groups (men with hypertension OR, 0.97; 95% CI, 0.75-1.27; women with hypertension OR, 0.83; 95% CI, 0.67-1.03; men with diabetes OR, 0.70; 95% CI, 0.45-1.08; women with diabetes OR, 1.13; 95% CI, 0.84-1.53; men with hyperlipidemia OR, 0.85; 95% CI, 0.59-1.23; women with hyperlipidemia OR, 1.14; 95% CI, 0.91-1.44). In hyperlipidemia patients, awareness (OR, 1.55; 95% CI, 1.03-2.35) and control (OR, 2.19; 95% CI, 2.32-3.63) of disease were related to nutrition label use; however, no significant associations were found for the hypertension and diabetes mellitus patients. Considering the importance of dietary habits in the management of chronic diseases, an improvement in nutrition label use by patients with these diseases is required.
Adult ; Aged ; Chronic Disease ; Demography ; Diabetes Mellitus/pathology/*prevention & control ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Hyperlipidemias/pathology/*prevention & control ; Hypertension/pathology/*prevention & control ; Logistic Models ; Male ; Middle Aged ; *Nutrition Surveys ; Nutritive Value ; Odds Ratio ; Republic of Korea

BACKGROUNDControlling plasma glucose levels, blood pressure and lipid levels is proven to reduce the risk of vascular complications in patients with type 2 diabetes mellitus. This has prompted intensive multitherapy targeted at several macrovascular risk factors. Carotid intima-media thickness (cIMT) is a reliable measure of early atherosclerosis. We sought to determine whether a 6-month intensive mutiltherapy program resulted in better goal attainment than usual care and its effect on the development of cIMT among patients with newly diagnosed type 2 diabetes mellitus.

METHODSThe study randomly assigned 220 patients with newly diagnosed type 2 diabetes mellitus to intensive or traditional therapy groups. The clinical parameters, such as fasting plasma glucose, total cholesterol, triglyceride, blood pressure, body weight and insulin were assessed at the baseline and after the 6-month therapy. cIMT of the patients was also obtained.

RESULTSThe average levels of fasting plasma glucose, hemoglobin A1c, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the intensive group were significantly lower than those in the control group at the end of 6-month treatment. By 6 months, a higher proportion of patients in the intensive therapy group than in the control group attained goals for fasting plasma glucose (FPG), TC, LDL-C and hemoglobin A1c. With intensive multherapy the level of carotid intima-media thickness in the intensive therapy group was lower than that in the control group ((0.88 +/- 0.26) mm vs (0.96 +/- 0.22) mm, P < 0.01).

CONCLUSIONSThe evidence from this clinical trial demonstrates that intensive glucose, lipid and blood pressure control in patients with newly diagnosed type 2 diabetes is associated with diabetic macrovascular benefits. Intensive multitherapy allows more patients to achieve aims of control and may reduce macrovascular complications and delay disease progression.

Arteriosclerosis ; prevention & control ; Carotid Arteries ; pathology ; Diabetes Complications ; prevention & control ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Therapy, Combination ; Humans ; Hypoglycemic Agents ; administration & dosage ; Middle Aged ; Prospective Studies ; Tunica Intima ; pathology

OBJECTIVETo evaluate the aldose reductase inhibitory (ARI) activity of different fractions of Hybanthus enneaspermus for potential use in diabetic cataract.

METHODSTotal phenol and flavonoid content of different fractions was determined. ARI activity of different fractions in rat lens was investigated in vitro.

RESULTSThe results showed significant level of phenolic and flavonoid content in ethyl acetate fraction [total phenol (212.15±0.79 mg/g), total flavonoid (39.11±2.27 mg/g)] and aqueous fraction [total phenol (140.62±0.57 mg/g), total flavonoid (26.07±1.49 mg/g)] as compared with the chloroform fraction [total phenol (68.56±0.51 mg/g), total flavonoid (13.41±0.82 mg/g)] and petrolium ether fraction [total phenol (36.68±0.43 mg/g), total flavonoid (11.55±1.06 mg/g)]. There was a significant difference in the ARI activity of each fraction, and it was found to be the highest in ethyl acetate fraction [IC50 (49.26±1.76 µg/mL)] followed by aqueous extract [IC50 (70.83±2.82 µg/mL)] and it was least in the petroleum ether fraction [IC50 (118.89±0.71 µg/mL)]. Chloroform fraction showed moderate activity [IC50 (98.52±1.80 µg/mL)].

CONCLUSIONSDifferent fractions showed significanct amount of ARI activity, where in ethyl acetate fraction it was found to be maximum which may be due to its high phenolic and flavonoid content. The extract after further evaluation may be used in the treatment of diabetic cataract.

Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Cataract ; drug therapy ; prevention & control ; Diabetes Complications ; drug therapy ; prevention & control ; Diabetes Mellitus ; pathology ; Flavonoids ; analysis ; Lens, Crystalline ; enzymology ; Phenols ; analysis ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Violaceae ; metabolism

AIMTo investigate the effects of ramipril on myocardial ischemia/reperfusion injury in diabetic rats, and to explore its mechanism according to the observation on myocardial ultrastructure.

METHODSStreptozotocin induced diabetic rats were divided randomly into three groups (n = 16): ischemia/reperfusion (I/R), ischemic preconditioning (IPC) and ramipril (RAM) group. Rats in RAM group were administered by RAM(1 mg x kg(-1) x d(-1)) orally for 4 weeks, the others were administered by normal saline. Then all rats were subjected to myocardial ischemia/ reperfusion injury. Rats in IPC group were preconditioned before ischemia. The ECG and the infarct size were examined. The changes of myocardial morphology were examined by light and electron microscopes.

RESULTSCompared with I/R group, the elevation of ST segment and the incidence of ventricular tachycardia and ventricular fibrillation during ischemia were significantly decreased, the infarct size at the end of reperfusion was remarkably reduced, the myocardial morphology were significantly improved, special structure of myofilaments and mitochondria remained clearly, blood vessels were unobstructed, injury of endothelium were decreased in PC and RAM groups.

CONCLUSIONRamipril administered for 4 weeks induces myocardial protection in diabetic rats, which is similar to that of IPC. The mechanism may be involved in protection of cardiocytes and mitochondria, and improvement of endothelial function.

Animals ; Cardiotonic Agents ; pharmacology ; Diabetes Mellitus, Experimental ; complications ; Ischemic Preconditioning, Myocardial ; methods ; Myocardial Reperfusion Injury ; pathology ; prevention & control ; Myocardium ; ultrastructure ; Ramipril ; pharmacology ; Rats

OBJECTIVETo investigate the effects of Liuweidihuang pills (LP) on visceral fat deposition in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

METHODSForty male OLETF rats were randomly divided into LP group and control group (n=20 per group), and 10 male Long-evans Tokushima Otsuka (LETO) rats were used as normal controls. The rats in LP group were given LP(2.4 mg/kg) daily by intragastric administration since the age of 8 weeks, and those in the other two groups were given water of the same volume by intragastric administration. Blood glucose of all the rats was determined by oral glucose tolerance test (OGTT) and visceral fat deposition examined after the rats were sacrificed.

RESULTSOLETF rats had obviously greater amount of visceral fat than LETO rats (P<0.05) and administration of LP ameliorated the increment of visceral fat deposition in this type 2 diabetic model, producing significant effect at the age of 40 weeks (P<0.01).

CONCLUSIONLP may effectively decrease visceral fat deposition in OLETF rats.

Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Intra-Abdominal Fat ; drug effects ; pathology ; Male ; Obesity ; pathology ; prevention & control ; Phytotherapy ; Random Allocation ; Rats ; Rats, Inbred OLETF

OBJECTIVETo investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats.

METHODSThirty Sprague-dawley female rats were randomly divided into three groups (n = 10 each), "control group" with intraperitoneal saline injection, "diabetic group" with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao group" with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 (TSP-1) expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy.

RESULTSBefore diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group.

CONCLUSIONOur results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP-1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; pathology ; Diabetic Nephropathies ; metabolism ; pathology ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Kidney ; drug effects ; metabolism ; pathology ; ultrastructure ; Lamiaceae ; chemistry ; Rats ; Rats, Sprague-Dawley ; Thrombospondin 1 ; metabolism

This study examined the potential roles of astragalus and angiotensin II type 2 receptor (AT2) in rats with streptozotocin (STZ)-induced diabetic cardiomyopathy. Of 52 female 4-week-old Wistar rats treated with high glucose and lipid diet to induce insulin resistance, 7 treated with sodium citrate buffer (pH=4.5) served as controls (con1) and the other 45 were treated by intraperitoneal injection (ip) of STZ to induce type 2 diabetes. After 20 weeks, the maximal velocity decrease of pressure per second in left ventricle within the period of isovolumic relaxation (-dp/dtmax) was detected by inserting cannula through right carotid artery. Of the 45 rats, 24 with -dp/dtmax < or = 700 mmHg/s (1 mmHg=0.133 kPa) developing diabetic cardiomyopathy were grouped as follows: 7 treated with double distilled H2O (ip) were included in control group 2 (con2); other 8 treated with AT2 agonist (CGP42112A, ip) were included in experimental group1 (exp); 9 treated with astragalus (po) constituted experimental group 2 (exp2). All injections lasted 4 weeks (qd) and the heart weight (HW) was recorded. Cardiomyocyte apoptosis index (CAI), mRNA of AT2 and Bcl-2 as well as AT2 and Bcl-2 protein values in cardiomyocytes were also measured. Our results showed that -dp/dtmax in exp1, exp2 and con2 were much lower than those in con1 (P<0.01). CAI and AT2 in both mRNA and protein in con1 were lower than those in the other three groups (P<0.01). The three parameters above were higher in exp1 but less in exp2 than those in con2, respectively (P<0.01). The three parameters and HW in exp1 were much higher than those in exp2 (P<0.01). Changes of Bcl-2 were opposite to those of AT2. Our results suggested that high expression of AT2 might accelerate the apoptosis of cardiomyocytes in diabetic rats and play an important role in precipitating diabetic cardiomyopathy and astragalus protects diabetic rats from developing cardiomyopathy by downregulating AT2.
Animals ; Apoptosis ; drug effects ; Astragalus membranaceus ; chemistry ; Cardiomyopathies ; etiology ; pathology ; prevention & control ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Myocytes, Cardiac ; pathology ; Phytotherapy ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 2 ; biosynthesis ; genetics

Adolescent ; Adult ; Aged ; Body Fat Distribution ; Body Mass Index ; Diabetes Mellitus, Type 2 ; complications ; Fatty Liver ; etiology ; pathology ; prevention & control ; Female ; Humans ; Intra-Abdominal Fat ; metabolism ; pathology ; Male ; Middle Aged ; Obesity ; complications ; Risk Factors ; Severity of Illness Index ; Young Adult