Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gamma-tocopherol (gammaT) is one of the major forms of vitamin E consumed in the diet. Previous reports have suggested increased levels of nitrated gamma-tocopherol (5-NO2-gammaT) in smokers and individuals with conditions associated with elevated nitrative stress. The monitoring of 5-NO2-gammaT and its possible metabolite(s) may be a useful marker of reactive nitrogen species generation in vivo. The major pathway for the metabolism of gammaT is the cytochrome P450 dependent oxidation to its water-soluble metabolite gamma-CEHC, which is excreted in urine. In order to determine if 5-NO2-gammaT could be metabolised via the same route and detected in urine we developed a sensitive gas chromatography-mass spectrometry assay for 5-NO2-gamma-CEHC. 5-NO2-gamma-CEHC was synthesised and its structure confirmed by proton nuclear magnetic resonance and mass spectrometry. While gamma-CEHC was abundant in urine from healthy volunteers, as well as patients with coronary heart disease and type 2 diabetes, 5-NO2-gamma-CEHC was undetectable (limit of detection of 5 nM). To understand this observation we examined the uptake and metabolism of gammaT and 5-NO2-gammaT by HepG2 cells. gammaT was readily incorporated into cells and metabolised to gamma-CEHC over a period of 48 hours. In contrast, 5-NO2-gammaT was poorly incorporated into HepG2 cells and not metabolised to 5-NO2-gamma-CEHC over the same time period. We conclude that nitration of gammaT prevents its incorporation into liver cells and therefore its metabolism to the water-soluble metabolite. Whether 5-NO2-gammaT could be metabolised via other pathways in vivo requires further investigation.
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PMID:Nitration of gamma-tocopherol prevents its oxidative metabolism by HepG2 cells. 1604 20

Low-grade inflammation, enhanced oxidant stress and lipid peroxidation have been shown in association with increased cardiovascular risk associated with cardiovascular events. It has been hypothesized that the low-grade inflammatory state characterizing metabolic disorders such as obesity, hypercholesterolemia, type 2 diabetes mellitus and homozygous homocystinuria may be the primary trigger of thromboxane-dependent platelet activation mediated, at least in part, through enhanced lipid peroxidation. Interestingly, as the clinical course of systemic lupus erythematosus (SLE), in particular in the presence of antiphospholipid antibodies, may be complicated by vascular disease, several mechanisms contributing to vascular complications have been documented also in this setting, including enhanced lipid peroxidation and thromboxane biosynthesis. Although epidemiological studies show an inverse relationship between antioxidant vitamin intake and cardiovascular disease, several clinical trials have obtained conflicting results on the effects of vitamin E on the risk of cardiovascular events. The availability of analytical tools for measuring F2-isoprostane biosynthesis in man has improved our understanding of the interplay between lipid peroxidation and low-grade inflammation. The use of F2-isoprostane as a biochemical end-point for dose-finding studies may allow reassessing the adequacy of vitamin supplementation in different clinical settings.
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PMID:Oxidant stress, inflammation and atherogenesis. 1621 83

In the present study, we investigated the antioxidant status in diabetes mellitus, related or not to alcohol consumption. A total of 38 type 1, 48 type 2 and 42 alcohol-related diabetic patients were selected. Total antioxidant status was assessed through the oxygen radical absorbance capacity of the plasma and the determination of enzymatic and non-enzymatic antioxidant molecules. Serum triglycerides, total cholesterol and HDL-cholesterol concentrations were determined and the lipid peroxydation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) assay. Plasma total antioxidant capacity was more decreased in alcohol-related diabetes than that in type 1 and type 2 diabetes, regardless of the complications (retinopathy and renal failure). Plasma vitamin E concentrations were significantly decreased whereas those of vitamin C increased in all of the diabetic patients compared to the controls, irrespective to the complications. In addition, superoxide dismutase and glutathione peroxidase activities were reduced in all the patients (type 1, type 2 and alcohol-related), irrespective to the complications. Glutathione reductase activity was diminished in type 1 and alcohol-related, but not in type 2, diabetic patients. Glutathione (GSH) concentrations significantly decreased in all diabetic patients with a significant decrease in alcohol-related diabetic patients. Excessive alcohol consumption appears as an oxidative aggravating factor in diabetes mellitus. Besides, alcohol-related diabetes highly resembles to type 1 diabetes as far as the antioxidant parameters are concerned.
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PMID:Antioxidant status in alcohol-related diabetes mellitus in Beninese subjects. 1637 21

This triple-blind, placebo-controlled clinical trial was conducted to determine the effect of the vitamin E on fasting blood sugar (FBS), serum insulin, and glycated hemoglobin (GHb) in type 11 diabetic patients (NIDDM). A total of 100 patients, with no complications, aged 20-60 years old were chosen from those consulting the Isfahan Social Security Service Diabetes Clinic and divided randomly into two treated and placebo groups, and matched for age, sex, level of education, and occupation. The treated and placebo groups were given vitamin E tablets (200 IU/day) and placebo respectively. Serum vitamin E, total cholesterol (TC), triglycerides (TG), FBS, insulin, and GHb were measured at the beginning and at the end of the study (a period of 27 weeks); FBS, GHb and insulin levels were also determined several times during the period. Blood lipids and FBS were measured using the ELAN 2000 autoanalyzer at the Isfahan Cardiovascular Research Center, while for measuring insulin the enzyme-linked immunosorbent assay (ELISA) method was used; GHb was determined calorimetrically (thiobarbituric acid), and for vitamin E measurements the Hansen and Warwick method was used, by which the vitamin E was determined fluorometrically. The findings of this study show no effect of vitamin E supplementation in the patients: GHb did not change appreciably, FBS was reduced nonsignificantly (-4.3% in the treated group vs. -14.0% in the placebo group, p < 0.05). In the case of insulin, no increase was seen; instead, a decrease was observed (slightly more than 17% in the two groups, p = 0.15). No changes were observed in the levels of blood lipids. It was concluded that a daily vitamin E supplement of 200 IU for a period of 27 weeks does not affect insulin, GHb, or FBS in type II diabetic patients. However, since this antioxidant vitamin is beneficial in other ways in these patients, it would seem justified to recommend its use. Certainly, more extensive research is necessary to draw definite conclusions.
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PMID:Long term effects of oral vitamin E supplement in type II diabetic patients. 1647 66

Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases. A striking exception is probucol, which retards atherosclerosis in carotid arteries and restenosis of coronary arteries after angioplasty. Because probucol has in vitro cellular-protective effects independent of inhibiting lipid oxidation, we investigated the mode of action of probucol in vivo. We used three models of vascular disease: apolipoprotein E-deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Unexpectedly, we observed that the phenol moieties of probucol were insufficient, whereas its sulphur atoms were required for protection. Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation. These processes were mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the molecular target of probucol. They indicate 2-electron rather than radical (1-electron) oxidants as important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.
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PMID:Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging. 1660 77

Type 2 diabetes mellitus shares risk factors for and has shown a positive association with colorectal cancer. Anthropometric measures (height, weight, and body mass index (weight (kg)/height (m)(2)) and metabolic abnormalities associated with insulin resistance syndrome (IRS) (abnormalities in measured blood pressure, high density lipoprotein (HDL) cholesterol, and total cholesterol) were prospectively evaluated for associations with incident colon (n = 227), rectal (n = 183), and colorectal (n = 410) cancers diagnosed between 1985 and 2002 in 28,983 Finnish male smokers from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. In comparison with the lowest quintile, the highest quintile of body mass index was significantly associated with colorectal cancer (hazard ratio (HR) = 1.70, 95% confidence interval (CI): 1.01, 2.85; p-trend = 0.01), particularly colon cancer. Subjects with a cluster of three IRS-related conditions (hypertension, body mass index >/=25 kg/m(2), and HDL cholesterol level <40 mg/dl (<1.55 mmol/liter)), compared with those with fewer conditions, had a significantly increased risk of colorectal cancer (HR = 1.40, 95% CI: 1.12, 1.74), particularly colon cancer (HR = 1.58, 95% CI: 1.18, 2.10), but not rectal cancer. These results support the hypothesis that the significant association observed between IRS-defining metabolic abnormalities and colorectal cancer is determined primarily by adiposity.
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PMID:A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers. 1687 36

Succinic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic tool in the treatment of non-insulin dependent diabetes mellitus. The aim of this study was to investigate the effect of EMS on oxidative stress in a streptozotocin (STZ)-nicotinamide induced type 2 diabetic model. The EMS was injected intraperitoneally at 8 micro mol/g body weight for 30 days. Plasma glucose, plasma insulin, thiobarbituricacid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), reduced glutathione (GSH), glutathione-S-transferase (GST), and vitamins C and E were assayed in liver and kidney. Treatment with EMS and metformin to diabetic rats resulted in a significant reduction in plasma glucose, TBARS, and hydroperoxides. In addition, the treated groups also showed a significant increase in the activities of plasma insulin, SOD, CAT, GPx, GST, GSH, vitamin C, and vitamin E in liver and kidney of STZ-nicotinamide-induced diabetic rats. Our result suggest that non glucidic nutrient, such as EMS as a potent antidiabetic, may optimalize antiperoxidative and antioxidants status by restoring the biochemical alterations found in STZ-nicotinamide-induced type 2 diabetes.
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PMID:Succinic acid monoethyl ester prevents oxidative stress in streptozotocin-nicotinamide-induced type2 diabetic rats. 1691 Mar 16

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disease whose hallmark is the accumulation of large-droplet fat in hepatocytes. This metabolic disorder occurs mainly in overweight or obese individuals. The disease mechanism involves hyperinsulinemia and hepatic insulin resistance, not ethanol abuse. NAFLD may be the hepatic manifestation of the "metabolic syndrome" classically associated with type 2 diabetes mellitus and cardiovascular disease. NAFLD ranges from simple steatosis, which is the least rapidly progressing disorder, to nonalcoholic steatohepatitis to cirrhosis, which can evolve to chronic liver failure. The high prevalence of NAFLD in children has been recognized only in the past 5 to 10 years, as rates of childhood obesity have soared. Accordingly, the best strategies for diagnosis and treatment of childhood NAFLD are a work in progress and remain controversial. Weight reduction through a healthy diet and regular medium-intensity exercise is the mainstay of current treatment. Few research data are available to guide pharmacologic therapy. Certain points regarding management of childhood NAFLD require emphasis: It is a serious liver disease that requires detailed clinical investigation. Other liver diseases causing fatty liver and/or abnormal liver tests, notably Wilson disease and chronic viral hepatitis, need to be excluded. Liver biopsy can provide critical diagnostic and staging information. Associated genetic or endocrine disorders need to be identified. Treatment should begin with a low-glycemic index diet that provides adequate nutrients but is low in harmful fats and eliminates foods causing postprandial hyperglycemia. Initially, this can target two to three problem foods so that it is easy for the adolescent to follow. Regular exercise suited to the capabilities and interests of the teenager should be added to the daily routine. Where possible, a team approach, including a dietician and psychologist, should be utilized, as adolescents do better in a supportive atmosphere. Optimal drug treatment requires further research: current front-runners are vitamin E and metformin. The roles of drugs that alter appetite and bariatric surgery for adolescents with NAFLD have not been determined.
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PMID:Nonalcoholic Fatty Liver Disease (NAFLD): Approach in the Adolescent Patient. 1694 68

We directly assessed the efficacy of vitamin E supplements for primary prevention of type 2 diabetes among apparently healthy women in the Women's Health Study randomized trial. Between 1992 and 2004, 38,716 apparently healthy U.S. women aged >or=45 years and free of diabetes, cancer, and cardiovascular disease were in two randomly assigned intervention groups and received 600 IU of vitamin E (alpha-tocopherol, n = 19,347) or placebo (n = 19,369) on alternate days. During a median 10-year follow-up, there were 827 cases of incident type 2 diabetes in the vitamin E group and 869 in the placebo group, a nonsignificant 5% risk reduction (relative risk [RR] 0.95 [95% CI 0.87-1.05], P = 0.31). There was no evidence that diabetes risk factors including age, BMI, postmenopausal hormone use, multivitamin use, physical activity, alcohol intake, and smoking status modified the effect of vitamin E on the risk of type 2 diabetes. In a sensitivity analysis taking compliance into account, women in the vitamin E group had an RR of 0.93 (95% CI 0.83-1.04) (P = 0.21) compared with those randomized to placebo. In this large trial with 10-year follow-up, alternate-day doses of 600 IU vitamin E provided no significant benefit for type 2 diabetes in initially healthy women.
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PMID:Vitamin E and risk of type 2 diabetes in the women's health study randomized controlled trial. 1700 53

Dietary epidemiological studies indicate correlations between the consumption of red meat and/or processed meat and cancer of the colon, rectum, stomach, pancreas, bladder, endometrium and ovaries, prostate, breast and lung, heart disease, rheumatoid arthritis, type 2 diabetes and Alzheimer's disease. The correlation of all these major diseases with dietary red meat indicates the presence of factors in red meat that damage biological components. This hypothesis will focus on the biochemistry of heme compounds and their oxidative processes. Raw red meat contains high levels of oxymyoglobin and deoxymyoglobin and oxyhemoglobin and deoxyhemoglobin and cytochromes in muscle and other tissues. Cooked and processed meat contain hemichromes and hemochromes. After being eaten heme proteins are hydrolyzed to amino acids and peptides and the heme group which is coordinated with strong ligands. The iron of heme coordinates to the sulfur, nitrogen or oxygen of amino acids and peptides and other biological components. The coordinated heme groups are absorbed and transported by the blood to every organ and tissue. Free and coordinated heme preferentially catalyze oxidative reactions. Heme catalyzed oxidations can damage lipids, proteins, DNA and other nucleic acids and various components of biological systems. Heme catalysis with hydroperoxide intermediates can initiate further oxidations some of which would result in oxidative chain reactions. Biochemical and tissue free radical damage caused by heme catalyzed oxidations is similar to that resulting from ionizing radiation. Oxidative biochemical damage is widespread in diseases. It is apparent that decreasing the amount of dietary red meat will limit the level of oxidative catalysts in the tissues of the body. Increasing consumption of vegetables and fruits elevates the levels of antioxidative components, for example, selenium, vitamin E, vitamin C, lycopene, cysteine-glutathione and various phytochemicals. These detrimental processes of heme catalysis of oxidative damage hypothesized here are not well recognized. More investigative studies in this field need to be done.
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PMID:Heme of consumed red meat can act as a catalyst of oxidative damage and could initiate colon, breast and prostate cancers, heart disease and other diseases. 1704 17


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