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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma vitamin A, C and E levels and erythrocyte antioxidant enzyme activities were investigated in type I and type II diabetic subjects with and without complications, i.e., hypertension, coronary artery disease and renal failure. Reverse phase HPLC was used to quantify vitamin A and E levels. We observed that the vitamin C levels were not significantly different between control and diabetic subjects. However, vitamin A and E levels were significantly lower in type I and type II diabetic subjects compared to controls. Superoxide dismutase (SOD) activity was significantly lower in type II, but not in type I, diabetic patients compared to controls. Interestingly, glutathione reductase and peroxidase activities were diminished in type I, but not in type II, diabetic subjects as compared to controls. Catalase activity was lower in both types of diabetic patients in comparison with their respective controls. Altogether these results suggest that diabetes mellitus may be associated with altered antioxidant status regardless to various complications.
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PMID:Antioxidant status and levels of different vitamins determined by high performance liquid chromatography in diabetic subjects with multiple complications. 1287 Jun 98

Concentration of lipid peroxidation products and antioxidant enzyme activities in rat brain and erythrocytes and the effects of nicotinamide and nicotinoyl-GABA administration on these parameters were estimated on 21st day of streptozotocin-induced diabetes. It was demonstrated more then two-fold diabetes-induced accumulation of conjugated dienes and malondialdehyde in tissues studied. Superoxide dismutase and glutathione reductase activities of both brain homogenate and erythrocytes as well as catalase and glutathione peroxidase activities of brain homogenate were shown to decrease significantly in diabetic rats, meanwhile, catalase activity of erythrocytes was increased and glutathione peroxidase unchanged. So the correlation between changes in enzymatic antioxidant system in brain and erythocytes failed to be found. Alterations observed were virtually prevented by the course of nicotinamide and nicotinoyl-GABA treatment. The results suggested that the suppression of antioxidant system could be primary biochemical disturbance in diabetic neuropathy progression. It was shown that the antioxidant efficacy of nicotinoyl-GABA is lower than that of nicotinamide. It was suggested that the mechanism of antioxidant action of nicotinamide and its structural analogue consists of both scavenging of lipid peroxides and NAD biosynthesis that leads to activation and normalization of altered energy and lipid metabolism.
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PMID:[Oxidative stress correction by nicotinamide and nicotynol-GABA in diabetic neuropathy]. 1291 62

Paraoxonase (PON1) is an antioxidant enzyme closely associated with high-density lipoproteins. Low PON1 has been shown in oxidative stress-associated processes such as dyslipidemia, diabetes mellitus, advancing age, and smoking. Indeed, oxidative stress is related to the degree of insulin resistance, a key component of the metabolic syndrome. Therefore, the possible relationship between PON1 activity and the metabolic syndrome was investigated. From 1364 randomly recruited subjects, 285 were found to have the metabolic syndrome, according to the guidelines published by the National Cholesterol Education Program, Adult Treatment Panel III. PON1 activity, lipid peroxides, and PON1 codon 192 genotypes, which strongly modulate PON1 activity, were determined. Serum PON1 activity levels were found to be significantly lower, and lipid peroxide concentrations significantly higher, in subjects with the metabolic syndrome compared with unaffected subjects (P = 0.033 and < 0.001, respectively). Study subjects showed a significant decreasing trend in PON1 activity levels and a significant increasing trend in lipid peroxide concentrations, with the increase in the number of metabolic disturbances. No differences in the prevalence of PON1 codon 192 genotypes were found among the categories of metabolic abnormalities. In conclusion, a greater degree of severity of the metabolic syndrome is associated with a progressively worse antioxidant/oxidant balance, which is consistent with increased oxidative stress and lower antioxidant PON1 enzymatic capacity.
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PMID:Antioxidant paraoxonase 1 activity in the metabolic syndrome. 1460 83

In this study, the effects of L-carnitine treatment on lipids, lipid peroxidation of plasma, reactivity and antioxidant enzyme activity of aorta were evaluated in streptozotocin (STZ)-diabetic rats. Treatment with L-carnitine (0.6 g kg(-1) daily, i.p.) was started 8 weeks after the induction of diabetes and continued for 2 weeks. Diabetes was induced by a single injection of streptozotocin (45 mg kg(-1), i.p.). Plasma cholesterol, triglyceride and thiobarbituric acid reactive substance (TBARS) levels and blood glucose levels were significantly increased, although free carnitine levels were markedly decreased in diabetic rats. L-Carnitine treatment completely normalized plasma cholesterol, triglyceride, free carnitine and TBARS levels but partially restored blood glucose levels of diabetic rats. STZ-diabetes caused a significant reduction in the endothelium-dependent relaxation response to acetylcholine (ACh). In diabetic aorta, TBARS levels and catalase (CAT) activity were significantly increased but glutathione peroxidase (GSH-Px) activity was unchanged. Treatment of diabetic rats with L-carnitine resulted in partial restoration of the endothelium-dependent relaxation response to ACh and completely normalized the oxidant/antioxidant state. These results suggested that the beneficial effects of L-carnitine treatment partially improve vascular reactivity and antioxidant property beyond its reduction of plasma lipids and it may have an important therapeutic approach in the treatment of diabetic vascular complications.
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PMID:Effects of L-carnitine treatment on oxidant/antioxidant state and vascular reactivity of streptozotocin-diabetic rat aorta. 1460 21

The relentless decline in beta-cell function frequently observed in type 2 diabetic patients, despite optimal drug management, has variously been attributed to glucose toxicity and lipotoxicity. The former theory posits hyperglycemia, an outcome of the disease, as a secondary force that further damages beta-cells. The latter theory suggests that the often-associated defect of hyperlipidemia is a primary cause of beta-cell dysfunction. We review evidence that patients with type 2 diabetes continually undergo oxidative stress, that elevated glucose concentrations increase levels of reactive oxygen species in beta-cells, that islets have intrinsically low antioxidant enzyme defenses, that antioxidant drugs and overexpression of antioxidant enzymes protect beta-cells from glucose toxicity, and that lipotoxicity, to the extent it can be attributable to hyperlipidemia, occurs only in the context of preexisting hyperglycemia, whereas glucose toxicity can occur in the absence of hyperlipidemia.
Diabetes 2004 Feb
PMID:Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. 1474 76

Recent evidence suggests that impaired antioxidant status is involved in oxidative stress associated with diabetes. The main antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). The aim of the present investigation was to evaluate the activities and protein expression of these antioxidant enzymes in streptozotocin-induced diabetes. Furthermore, the effects of insulin and antioxidant therapy alone and in combination were studied. Male Sprague-Dawley rats were rendered diabetic by streptozotocin administration and randomly assigned to untreated, insulin-treated, antioxidant (vitamin E and C)-treated and insulin plus antioxidant-treated groups. Normal rats fed either a regular diet or the antioxidant (vitamin E and C)-rich diet served as controls. The animals were observed for 4 weeks. Diabetic animals showed marked weight loss, decreased activities of Cu Zn SOD and CAT and normal GPX activity. Additionally, the expression of all antioxidant enzyme proteins was decreased in the diabetic rats compared to the untreated controls. Insulin therapy prevented weight loss and normalized the activities and protein expression of all antioxidant enzymes. Antioxidant therapy in the diabetic rats normalized Cu Zn SOD and GPX protein expression. Combined therapy with insulin and antioxidants normalized all measured antioxidant enzyme protein expression and activities. Thus diabetes-associated reductions in antioxidant enzymes can be ameliorated by insulin and/or antioxidant therapy.
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PMID:Dysregulation of hepatic superoxide dismutase, catalase and glutathione peroxidase in diabetes: response to insulin and antioxidant therapies. 1500 Feb 96

It has been proposed that low activities of antioxidant enzymes in pancreatic beta cells may increase their susceptibility to autoimmune attack. We have therefore used the spontaneously diabetic BB/S rat model of type 1 diabetes to compare islet catalase and superoxide dismutase activities in diabetes-prone and diabetes-resistant animals. In parallel studies, we employed the RINm5F beta cell line as a model system (previously validated) to investigate whether regulation of antioxidant enzyme activity by inflammatory mediators (cytokines, nitric oxide) occurs at the gene or protein expression level. Diabetes-prone rat islets had high insulin content at the age used (58-65 days) but showed increased amounts of DNA damage when subjected to cytokine or hydrogen peroxide treatments. There was clear evidence of oxidative damage in freshly isolated rat islets from diabetes-prone animals and significantly lower catalase and superoxide dismutase activities than in islets from age-matched diabetes-resistant BB/S and control Wistar rats. The mRNA expression of antioxidant enzymes in islets from diabetes-prone and diabetes-resistant BB/S rats and in RINm5F cells, treated with a combination of cytokines or a nitric oxide donor, DETA-NO, was analysed semi-quantitatively by real time PCR. The mRNA expression of catalase was lower, whereas MnSOD expression was higher, in diabetes-prone compared to diabetes-resistant BB/S rat islets, suggesting regulation at the level of gene expression as well as of the activities of these enzymes in diabetes. The protein expression of catalase, CuZnSOD and MnSOD was assessed by Western blotting and found to be unchanged in DETA-NO treated cells. Protein expression of MnSOD was increased by cytokines in RINm5F cells whereas the expression of CuZnSOD was slightly decreased and the level of catalase protein was unchanged. We conclude that there are some changes, mostly upregulation, in protein expression but no decreases in the mRNA expression of catalase, CuZnSOD or MnSOD enzymes in beta cells treated with either cytokines or DETA-NO. The lower antioxidant enzyme activities observed in islets from diabetes-prone BB/S rats could be a factor in the development of disease and in susceptibility to DNA damage in vitro and could reflect islet alterations prior to immune attack or inherent differences in the islets of diabetes-prone animals, but are not likely to result from cytokine or nitric oxide exposure in vivo at that stage.
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PMID:Antioxidant enzyme activity and mRNA expression in the islets of Langerhans from the BB/S rat model of type 1 diabetes and an insulin-producing cell line. 1500 13

Recent data indicate that the oxidative stress plays an important role in the pathogenesis of diabetes and its complications such as retinopathy, nephropathy and accelerated atherosclerosis. In diabetic retinopathy, it was demonstrated a selective loss of pericytes accompanied by capillary basement membrane thickening, increased permeability and neovascularization. This study was designed to investigate the role of diabetic conditions such as high glucose, AGE-Lysine, and angiotensin II in the modulation of antioxidant enzymes activities, glutathione level and reactive oxygen species (ROS) production in pericytes. The activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) was measured spectrophotometrically. The production of ROS was detected by spectrofluorimetry and fluorescence microscopy after loading the cells with 2'-7' dichlorofluoresceine diacetate; as positive control H2O2 was used. Intracellular calcium was determined using Fura 2 AM assay. The results showed that the cells cultured in high glucose alone, do not exhibit major changes in the antioxidant enzyme activities. The presence of AGE-Lys or Ang II induced the increase of SOD activity. Their combination decreased significantly GPx activity and GSH level. A three times increase in ROS production and a significant impairment of intracellular calcium homeostasis was detected in cells cultured in the presence of the three pro-diabetic agents used. In conclusion, our data indicate that diabetic conditions induce in pericytes: (i) an increase of ROS and SOD activity, (ii) a decrease in GPx activity and GSH level, (iii) a major perturbation of the intracellular calcium homeostasis. The data may explain the structural and functional abnormalities of pericytes characteristic for diabetic retinopathy.
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PMID:Changes in oxidative balance in rat pericytes exposed to diabetic conditions. 1509 Feb 67

In the present study we investigated the effects of simvastatin treatment on lipid metabolism and peroxidation, antioxidant enzyme activities and ultrastructure of the diabetic rat myocardium. Diabetes was induced by single injection of streptozotocin (45 mg/kg i.p.). Eight weeks after induction of diabetes, a subgroup of control and of diabetic rats was treated with simvastatin for 4 weeks (10 mg/kg/day, orally). Blood glucose, plasma cholesterol and triacylglycerol, as well as levels of cardiac thiobarbituric acid reactive substances (TBARS) were significantly increased in diabetic rats. The activities of antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GSHPx), were also elevated in the diabetic myocardium. Treatment with simvastatin markedly reduced serum triacylglycerol and cholesterol, and partially controlled hyperglycemia in diabetic animals. The increased activation of antioxidant enzymes and the excess of lipid peroxidation measured by TBARS were completely reversed by simvastatin treatment. Diabetic rats displayed ultrastructural ischemia-like alterations of cardiomyocytes and capillaries, which support oxidative stress-induced tissue remodelling. In the diabetic myocardium simvastatin treatment partly attenuated angiopathic and atherogenic processes, detected by electron microscopy. These results suggest that simvastatin, known as a lipid-lowering drug, may positively affect diabetes induced cardiovascular complications via reducing risks of atherosclerotic pathological processes, such as imbalance between oxidant and antioxidant state.
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PMID:Effects of simvastatin treatment on oxidant/antioxidant state and ultrastructure of diabetic rat myocardium. 1511 25

Oxidative stress is produced under diabetic conditions and is likely involved in progression of pancreatic beta-cell dysfunction found in diabetes. Possibly caused by low levels of antioxidant enzyme expressions, pancreatic beta-cells are vulnerable to oxidative stress. When beta-cell-derived HIT-T15 cells or isolated rat islets were exposed to oxidative stress, insulin gene expression was markedly decreased. To investigate the significance of oxidative stress in the progression of pancreatic beta-cell dysfunction in type 2 diabetes, we evaluated the effects of antioxidants in diabetic C57BL/KsJ-db/db mice. According to an intraperitoneal glucose tolerance test, the treatment with antioxidants retained glucose-stimulated insulin secretion and moderately decreased blood glucose levels. Histological analyses of the pancreata revealed that the beta-cell mass was significantly larger in the mice treated with the antioxidants, and the antioxidant treatment suppressed apoptosis in beta-cells without changing the rate of beta-cell proliferation. The antioxidant treatment also preserved the amounts of insulin content and insulin mRNA, making the extent of insulin degranulation less evident. As possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. Under diabetic conditions, JNK is activated by oxidative stress and involved in the suppression of insulin gene expression. This JNK effect appears to be mediated in part by nucleocytoplasmic translocation of PDX-1, which is also downstream of JNK activation. Taken together, oxidative stress and consequent activation of the JNK pathway are involved in progression of beta-cell dysfunction found in diabetes. Antioxidants may serve as a novel mechanism-based therapy for type 2 diabetes.
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PMID:Role of oxidative stress in pancreatic beta-cell dysfunction. 1512 94


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