Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SR 27388 (N-(2-dimethylaminoethyl)-N-(3-pyridinylmethyl[4-(3,5-di(tert- butyl)-4-hydroxylphenyl)thiazol-2-yl]amine) is a potent and competitive antagonist of the binding of [3H]PAF to its receptor on rabbit platelets exhibiting an equilibrium inhibition constant for PAF binding of 10.5 +/- 1.2 nM (n = 3). SR 27388 potently inhibited PAF-induced aggregation of rabbit platelets in vitro (IC50 = 65 +/- 12 nM) (n = 4). In this respect, SR 27388 was as potent as the triazolothienodiazepine WEB-2086 against PAF-induced aggregation of rabbit platelets and had no effect on the action of other platelet aggregating agents. SR 27388 prevented in a dose-dependent manner the formation of thiobarbituric acid reactive substances during membrane peroxidation (IC50 = 0.7 microM) and inhibited reduction of the stable 1,1-diphenyl-2-picrylhydrazyl radical, indicating that the antioxidant potency of SR 27388 was due to an efficient radical scavenging activity. SR 27388 displayed marked in vitro inhibition of zymosan-induced oxidative burst in human monuclear cells (IC50 = 3 microM). In vivo, SR 27388 protected mice from 100 micrograms/kg PAF-induced death with an ED50 value of 500 micrograms/kg, when given i.v., 5 min before PAF challenge or p.o. (ED50 = 800 micrograms/kg) when given 1 h before PAF administration. Similarly, i.v. or oral doses of SR 27388 afforded in mice complete protection against endotoxin-induced lethality (ED50 values were 250 micrograms/kg and 1.3 mg/kg, respectively). Neither BHT, vitamin E nor catechin exhibited significant protection against PAF- or endotoxin-induced death. In ovalbumin-presensitized rabbits, SR 27388 premixed with the allergen inhibited in a dose-dependent manner allergen-induced oedema formation in the skin (ED50 = 0.1 mumol/site). After an i.v. administration of 10 mg/kg, SR 27388 significantly protected mice against alloxan-induced diabetes. These results show that SR 27388 is a potent and orally active dual PAF receptor antagonist and antioxidant.
 ...
PMID:Biochemical and pharmacological properties of SR 27388, a dual antioxidant and PAF receptor antagonist. 825 76

To determine whether alloxan action is mediated by hydroxyl radicals in vivo, we assayed methane sulfinic acid (MSA), a product of the trapping reaction of dimethyl sulfoxide (DMSO) with hydroxyl radicals. In DMSO-treated rats, the plasma levels of MSA were increased after injection of alloxan (75 mg/kg). This supports the hypothesis that the diabetogenic action of alloxan is mediated by hydroxyl radicals in vivo. The role of cytosolic superoxide dismutase (SOD) in protecting B cells against chemically induced diabetes was studied in rats injected intraperitoneally with diethyldithiocarbamate (DDC). When rats were injected intraperitoneally with DDC (750 mg/kg), the SOD activity at 2.5 h was decreased by 44% in the whole pancreas. The decreased SOD activity was affected by DDC but not by alloxan. Intraperitoneal injection of rats with DDC (750 mg/kg) increased diabetogenic susceptibility to a nondiabetogenic dose of alloxan (20 mg/kg). Subcutaneous injection of vitamin E, prior to administration of both DDC and alloxan, provided partial protection to the rats against the diabetogenic action. These findings suggest that the susceptibility to diabetogenic action of alloxan in B cells is augmented when the cellular SOD activity is inhibited. Thus, cellular SOD may play an important role in the maintenance of B cell function.
Diabetes Res Clin Pract 1993 Jan
PMID:Effect of diethyldithiocarbamate on diabetogenic action of alloxan in rats. 838 78

The effects of two anti-thrombotic and anti-lipidemic oils, evening primrose oil and fish oil, on glucose and lipid metabolism, prostaglandin (PG) levels and body composition were studied in patients with non-insulin-dependent diabetes. Seven patients were administered 4 g evening primrose oil, 2.4 g sardine oil and 200 mg vitamin E for 4 weeks. Fasting plasma glucose, hemoglobin A1c, total cholesterol, body weight and % body fat mass were significantly decreased after the treatment, and levels of changes in these parameters were not different from 11 patients who did not receive the oils. In the treatment group, concentrations of (e) icosapentaenoic acid (EPA) increased significantly in all the lipoprotein fractions, but dihomo-gamma-linolenic acid (DGLA) increased only in the high-density lipoprotein (HDL) fraction. The treatment decreased urinary 11-dehydro-thromboxane B2 excretion (32.7% decrease, P < 0.05), but did not alter significantly plasma PGE1 or 6-keto-PGF1 alpha levels. The ratio of 6-keto-PGF1 alpha and PGE1 to 11-dehydro-thromboxane B2 increased significantly after the treatment. These results suggest that these oil treatments are useful in improving abnormal lipid and thromboxane (TX)A2 metabolism in diabetic patients.
 ...
PMID:Evening primrose oil and fish oil in non-insulin-dependent-diabetes. 841 6

Increased generation of reactive oxygen species, coupled with impaired endogenous scavenging mechanisms, plays a prominent role in the aetiology of neurovascular abnormalities in experimental diabetes mellitus. We examined the efficacy of the natural anti-oxidants vitamins C, E and beta-carotene in preventing nerve conduction and nutritive blood flow deficits in streptozotocin-diabetic rats. One month of diabetes caused a 19.1% reduction in sciatic motor conduction velocity (p < 0.001). This was approximately prevented 80-90% by high-dose (1000 mg.kg-1.day-1) vitamin E and beta-carotene treatments (p < 0.001). Vitamin C had lesser effects; the maximum protection found for motor conduction velocity was 36% using a dose of 150 mg.kg-1.day-1 (p < 0.001). High dose (500 mg.kg-1.day-1 (p < 0.001). High dose (500 mg.kg-1.day-1) vitamin C had a lesser effect on conduction than intermediate doses. Joint vitamin C and lower dose (500 mg.kg-1.day-1) vitamin E treatment had a predominantly additive preventive effect against nerve dysfunction. Resistance to hypoxic conduction failure for sciatic nerve in vitro was markedly increased by diabetes and this remained relatively unaffected by treatment. Sciatic nutritive endoneurial blood flow, measured using microelectrode polarography and hydrogen clearance, was reduced 46.1% by 1 month of diabetes (p < 0.001). This was prevented to the extent of 87%, 36% and 98% by vitamins E, C and beta-carotene, respectively (p < 0.01). These data emphasize the role of oxidative stress in the development of early neurovascular changes in experimental diabetes and show that naturally available scavengers have a neuroprotective action.
 ...
PMID:Effects of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats. 858 37

Free radicals have been suspected to play a role in the pathogenicity of alcohol-related chronic pancreatitis. The aim of this study was to determine the status of several antioxidant parameters in these patients and examine the factors that are likely to influence them. Thirty-five subjects (23 males and 12 females, mean age 48 +/- 8 years) with disease proven by endoscopic pancreatography and 14 healthy controls (6 males and 8 females, mean age 44 +/- 7 years) were included in the study. Biochemical antioxidant parameters included: selenium, zinc, and copper levels in plasma; glutathione peroxidase in plasma and erythrocytes; plasma malondialdehyde concentrations assessed by thiobarbituric acid reactants; and serum vitamin E and A levels. Selenium and vitamin E oral intake was assessed by a five-day diet analysis. Hemoglobin (130 +/- 16 vs 143 +/- 15 g/liter), vitamin E (8 +/- 5 vs 16 +/- 9 mg/liter), vitamin A (30 +/- 11 vs 49 +/- 12 micrograms/dl), selenium (54 +/- 20 vs 87 +/- 11 micrograms/liter), and plasma glutathione peroxidase (903 +/- 313 vs 1326 +/- 168 units/liter) were significantly lower in patients than in controls (P < 0.05). In contrast, white blood cell count, C-reactive protein, and plasma copper levels were significantly higher in patients than in controls. Cholesterol, triglycerides, iron, ferritin, total proteins, zinc, and malondialdehyde were not different. Vitamin E was lower in patients with steatorrhea, while vitamin A was lower in patients with concomitant diabetes mellitus. Dietary intakes were not different between patients and controls. In conclusion, patients with alcohol-related chronic pancreatitis have low blood levels in many antioxidant factors. Dietary intakes of some of them (selenium and vitamin E) are adequate, however. Such deficiencies are secondary to pancreatic insufficiency and probably to increased requirements related to enhanced oxidative stress.
 ...
PMID:Deficiency in antioxidant factors in patients with alcohol-related chronic pancreatitis. 865 56

Hyperglycemia, a major cause of vascular complications in diabetes, has been shown to activate the diacylglycerol (DAG)-protein kinase C (PKC) pathway in vascular tissues. We have found that D-alpha-tocopherol (vitamin E) treatment reversed the adverse effects of hyperglycemia both in vitro and in vivo. In aortic smooth muscle cells (ASMCs), the PKC specific activity from the membranous fraction and total DAG were increased by 31 +/- 4% (P < 0.05) and 50 +/- 7% (P < 0.05), respectively, when the glucose levels were changed from 5.5 to 22 mmol/l. D-alpha-tocopherol prevented the glucose-stimulated increases in DAG level and PKC activity as well as the amount of PKC beta II isoform in ASMCs cultured with elevated glucose levels. Comparing streptozotocin-induced diabetic rats after 2 weeks of disease to controls, specific membranous PKC activities and total DAG levels were increased in aorta (162%, P < 0.05; 60%, P < 0.05). Intraperitoneal injection of D-alpha-tocopherol (40 mg/kg) every other day resulted in a significant decrease of the elevated membranous PKC specific activity and total DAG levels in parallel with a significant increase of D-alpha-tocopherol content in the aorta. These findings suggested that D-alpha-tocopherol can prevent the activation of PKC in the vascular cells and aorta induced by hyperglycemia by normalizing the elevated levels of DAG.
Diabetes 1996 Jul
PMID:Vitamin E normalizes diacylglycerol-protein kinase C activation induced by hyperglycemia in rat vascular tissues. 867 76

The relationship between cataract extraction and diet was considered in a case-control study conducted in northern Italy. A total of 207 patients who had cataract extraction and 706 control subjects in a hospital for acute, nonneoplastic, nonoculistic, nondigestive tract diseases were interviewed during their hospital stay. Odds ratios (ORs) and their 95% confidence intervals (CIs), according to the intake of alcohol, coffee, tea, and cola, and frequency of intake of 34 food items and 8 micronutrients were derived from multiple logistic regression equations, including terms for age, sex, education, smoking status, body mass index, diabetes, and total calorie intake. Alcohol, coffee, decaffeinated coffee, tea, and cola intakes were not associated with cataract extraction. Among food items, reduced ORs for cataract extraction (highest tertile of intake compared to the lowest), with a significant inverse trend in risk, were found for intake of meat (OR 0.6, 95% CI 0.4 to 0.9), cheese (OR 0.7, 95% CI 0.5 to 1.0), cruciferae (OR 0.5, 95% CI 0.3 to 0.8), spinach (OR 0.6, 95% CI 0.4 to 0.9), tomatoes (OR 0.5, 95% CI 0.4 to 0.8), peppers (OR 0.7, 95% CI 0.4 to 1.1), citrus fruit (OR 0.5, 95% CI 0.2 to 1.3), and melon (OR 0.5, 95% CI 0.4 to 0.8). A significant increase in risk was found for the highest intake of butter (OR 2.8, 95% CI 1.2 to 6.4), total fat (OR 1.8, 95% CI 1.2 to 2.8), and salt (OR 2.4, 95% CI 1.4 to 4.0) compared to the lowest, and for consumption of oil other than olive oil (OR 1.6, 95% CI 1.1 to 2.2). Among micronutrients, lower ORs for cataract extraction (highest quintile of intake compared to the lowest) were found for intake of calcium (OR 0.5, 95% CI 0.3 to 0.8), folic acid (OR 0.4, 95% CI 0.2 to 0.7), and vitamin E (OR 0.5, 95% CI 0.3 to 1.0), while estimated intakes of methionine, retinol, beta-carotene, and vitamins A, C, and D were not associated. Thus, this study indicates that diet plays a considerable role in the risk of cataract extraction in this Italian population, with a protective action played by some vegetables, fruit, calcium, folic acid,and vitamin E, and an increased risk associated with elevated salt and fat intake.
 ...
PMID:Food and nutrient intake and risk of cataract. 868 Jun 24

Several lines of evidence support an atherogenic role for oxidized low-density lipoprotein (LDL). Previous studies have suggested that although Mexican-Americans have an increased rate of diabetes, obesity, elevated triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels, their rates of coronary heart disease (CHD) are similar or possibly lower than in non-Hispanic whites. Mexican-Americans have smaller, denser LDL than non-Hispanic whites. On the basis of this latter observation, we postulated that lipid peroxide (LPO) levels would be increased in Mexican-Americans. We examined the oxidizability of plasma in 50 Mexican-Americans and 50 non-Hispanic whites from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease, at baseline and after coincubation with a metal-independent system (2'2'-azobis-2-amidinopropane hydrochloride [AAPH]) and a metal-dependent system (Fe2+/H2O2) of oxidation. LPO levels were measured by a modified fluorimetric assay. Vitamin E and plasma fatty acid composition were also determined. We found significantly higher LPO levels at baseline and after AAPH coincubation in Mexican-Americans than in non-Hispanic whites (baseline, 2.75 +/- .09 v 2.07 +/- .09 micromol/L, P < .001; post-AAPH, 5.49 +/- .14 v 5.07 +/-. .04 micromol/L, P = .037). However, no significant ethnic differences were seen after coincubation with Fe2+/H2O2. Diabetes and cigarette-smoking were also associated with higher LPO levels. Mexican-Americans also had lower levels of vitamin E (the predominant lipid-soluble antioxidant in plasma) than non-Hispanic whites, although these differences only partially explained the differences in susceptibility to oxidation. Plasma fatty acids were similar in Mexican-Americans and non-Hispanic whites, suggesting only small differences in diet composition. We conclude that LPO levels are higher in Mexican-Americans than in non-Hispanic whites, and that these results are only partially related to differences in vitamin E levels.
 ...
PMID:Plasma oxidizability in Mexican-Americans and non-Hispanic whites. 869 25

Among many factors, elevated lipids and lipid peroxide levels in blood are major risk factors in the development of cardiovascular disease in diabetic patients. This study has examined whether oral supplementation of vitamin E, an antioxidant, has any effect on blood lipid peroxidation products (LP) and lipid profile of diabetic patients. Thirty-five diabetics(D) were supplemented with DL-alpha-tocopherol (E) capsule (orally, 100 IU/d) or placebo (P) for three months in double-blind clinical trials. Plasma E was analyzed by HPLC and LP by the thiobarbituric acid-reactivity; serum lipids by auto-analyzer. Data were analyzed using paired t-test and Wilcoxon Signed Rank Test. Vitamin E supplementation significantly lowered LP and lipid levels in diabetic patients; there were no differences in these parameters after P supplementation. There were no differences in the duration of diabetes and ages of D between P- and E- supplemented groups. This study suggests that vitamin E supplementation significantly lowers blood LP and lipid levels in diabetic patients.
 ...
PMID:The effect of modest vitamin E supplementation on lipid peroxidation products and other cardiovascular risk factors in diabetic patients. 872

Undernutrition, overnutrition and malnutrition, in addition to several other environmental insults have been claimed to play roles in the etiopathogenesis of insulin-dependent and -independent diabetes. These factors are known to alter the beta-cell function and disturb its homeostasis, i.e. qualitative and quantitative changes in its activity. This can lead to disturbed glucose homeostasis and thereby diabetes. It is possible to stop this vicious cycle and reduce the incidence of diabetes by restoring the homeostasis of beta-cell function through proper diabetes management and maintainance of an appropriate dietary milieu. It has been suggested that beta-cell dysfunction or death occurs by oxyradical mediated processes. Adequate stimulation of beta cells through high carbohydrate and fibre intake, and reduced oxidative tone by caloric restriction (low protein and saturated fat), supplementation with antioxidants (vitamin E and D) and polyunsaturated essential fatty acids may prevent loss or even restore the beta-cell activity from environmental diabetogenic insults.
 ...
PMID:Dietary management of pancreatic beta-cell homeostasis and control of diabetes. 873 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>