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

We studied the effects of dihydroquercetin (3.3.4.5.7-pentahydroxyflavanone, a new Russian patented preparation) on functional activity of polymorphonuclear neutrophils from patients with non-insulin-dependent diabetes mellitus. Flavonoids (quercetin and its derivative dihydroquercetin) dose-dependently suppressed generation of anion radicals and hypochlorous acid and production of malonic dialdehyde during oxidation of neutrophil membranes. Dihydroquercetin decreased activities of protein kinase C and myeloperoxidase in activated polymorphonuclear neutrophils and could bind transition metals (Fe2+). These properties determine the ability of dihydroquercetin to decrease in vitro functional activity of polymorphonuclear neutrophils from patients with non-insulin-dependent diabetes mellitus.
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PMID:Mechanisms underlying diquertin-mediated regulation of neutrophil function in patients with non-insulin-dependent diabetes mellitus. 1527 59

Pathological conditions that predispose to cardiovascular events, such as hypertension, hypercholesterolemia, and diabetes, are associated with oxidative stress. These observations and further data derived from a plethora of investigations provided accumulating evidence that oxidative stress is decisively involved in the pathogenesis of endothelial dysfunction and atherosclerosis. Several enzymes expressed in vascular tissue contribute to production and efficient degradation of reactive oxygen species, and enhanced activity of oxidant enzymes and/or reduced activity of antioxidant enzymes may cause oxidative stress. Various agonists, pathological conditions, and therapeutic interventions lead to modulated expression and function of oxidant and antioxidant enzymes, including NAD(P)H oxidase, endothelial nitric oxide synthase, xanthine oxidase, myeloperoxidase, superoxide dismutases, catalase, thioredoxin reductase, and glutathione peroxidase. Data from numerous studies underline the importance of dysregulated oxidant and antioxidant enzymes for the development and progression of atherosclerotic disease in animal models and humans. Specific pharmacological modulation of key enzymes involved in the propagation of oxidative stress rather than using direct antioxidants may be an approach to reduce oxygen radical load in the vasculature and subsequent disease progression in humans. This review focuses on the modulation of expression and activity of major antioxidant and oxidant enzymes expressed in vascular cells.
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PMID:Modulation of oxidant and antioxidant enzyme expression and function in vascular cells. 1533 34

Vascular non-leukocyte-derived reactive oxygen species (ROS), such as superoxide and hydrogen peroxide (H(2)O(2)), have emerged as important molecules in diabetic endothelial dysfunction. In addition, leukocyte-derived myeloperoxidase (MPO) has been implicated in vascular injury, and its injury response is H(2)O(2) dependent. It is well known that MPO can use leukocyte-derived H(2)O(2); however, it is unknown whether the vascular-bound MPO can use high-glucose-stimulated, vascular non-leukocyte-derived H(2)O(2) to induce diabetic endothelial dysfunction. In the present study, we demonstrated that MPO activity is increased in vessels from diabetic rats. In high-glucose-incubated rat aortas and in carotid arteries from rats with acute hyperglycemia, vascular-bound MPO utilized high-glucose-stimulated H(2)O(2) to amplify the ROS-induced impairment of endothelium-dependent relaxation via reduction of nitric oxide bioavailability. Hypochlorous acid (HOCL)-modified LDL, a specific biomarker for the MPO/HOCL/chlorinating species pathway, was detected in LDL- and MPO-bound vessels with high-glucose-stimulated H(2)O(2). The results suggest that vascular-bound MPO could use high-glucose-stimulated H(2)O(2) to amplify high-glucose-induced injury in the vascular wall. MPO/H(2)O(2)/HOCL/chlorinating species may represent an important pathway in diabetes complications and a new mechanism in phagocyte- and systemic infection-induced exacerbation of diabetic vascular diseases.
Diabetes 2004 Nov
PMID:Leukocyte-derived myeloperoxidase amplifies high-glucose--induced endothelial dysfunction through interaction with high-glucose--stimulated, vascular non--leukocyte-derived reactive oxygen species. 1550 76

Increased endogenous generation of advanced glycation endproducts (AGEs) contributes importantly to the vascular complications of diabetes, in part owing to activation of the pro-inflammatory RAGE receptor. However, AGE-altered oligopeptides with RAGE-activating potential can also be absorbed from the diet, and indeed make a significant contribution to the plasma and tissue pool of AGEs; this contribution is especially prominent when compromised renal function impairs renal clearance of AGEs. Perhaps surprisingly, foods rich in both protein and fat, and cooked at high heat, tend to be the richest dietary sources of AGEs, whereas low-fat carbohydrate-rich foods tend to be relatively low in AGEs. Conceivably, this reflects the fact that the so-called "AGEs" in the diet are generated primarily, not by glycation reactions, but by interactions between oxidized lipids and protein; such reactions are known to give rise to certain prominent AGEs, such as epsilonN-carboxymethyl-lysine and methylglyoxal. Although roasted nuts and fried or broiled tofu are relatively high in AGEs, low-fat plant-derived foods, including boiled or baked beans, typically are low in AGEs. Thus, a low-AGE content may contribute to the many benefits conferred to diabetics by a genuinely low-fat vegan diet. Nonetheless, the plasma AGE content of healthy vegetarians has been reported to be higher than that of omnivores - suggesting that something about vegetarian diets may promote endogenous AGE production. Some researchers have proposed that the relatively high-fructose content of vegetarian diets may explain this phenomenon, but there so far is no clinical evidence that normal intakes of fructose have an important impact on AGE production. An alternative or additional possibility is that the relatively poor taurine status of vegetarians up-regulates the physiological role of myeloperoxidase-derived oxidants in the generation of AGEs - in which case, taurine supplementation might be expected to suppress elevated AGE production in vegetarians. Thus, a taurine supplemented low-fat vegan diet may be recommended as a strategy for minimizing AGE-mediated complications in diabetics and in patients with renal failure.
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PMID:The low-AGE content of low-fat vegan diets could benefit diabetics - though concurrent taurine supplementation may be needed to minimize endogenous AGE production. 1560 76

Growing evidence indicates that oxidative modification of low-density lipoprotein (LDL) is increased in diabetes mellitus; however, the mechanism(s) of this phenomenon is still unclear. gamma-Glutamyl semialdehyde (gammaGSA) is a product of hemin (Fe(3+)-protoporphyrin IX)-catalyzed oxidation of apolipoprotein B-100 (apoB- 100) proline and arginine residues. On reduction, gammaGSA forms 5-hydroxy-2-aminovaleric acid (HAVA). This report describes the application of sensitive HAVA assay, to characterize gammaGSA formation in LDL under normo- and hyperglycemic conditions, both in vitro and in vivo. In vitro studies revealed that apoB-100 proline and arginine residues are not oxidized to HAVA by HOCl or the myeloperoxidase/hydrogen peroxide (H(2)O(2)) oxidation system. Cu(2+), Cu(2+)/H(2)O(2), and Fe(2+) induced only minor HAVA formation. In contrast, the hemin oxidation system appeared reactive toward LDL apoB-100 proline and arginine residues. The resulting significant HAVA formation was specifically inhibited by a redox-inert ferric iron chelator. Glucose further enhanced hemin-induced increase in relative electrophoretic mobility of LDL and apoB-100 HAVAformation. In vivo we observed elevated concentrations of HAVA in LDL apoB-100 in patients with impaired glucose tolerance and with manifest diabetes mellitus. In conclusion, glucose promotes iron-mediated oxidation of apoB- 100 proline and arginine residues via a superoxide-dependent mechanism, thus rendering the LDL particles more atherogenic. The findings (a) identify a potential mechanism of enhanced atherogenesis in subjects with diabetes mellitus and (b) support the value of HAVA as a specific marker of LDL apoB-100 oxidation. Antioxid. Redox Signal. 7, 1507-1512.
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PMID:Glucose-induced enhancement of hemin-catalyzed LDL oxidation in vitro and in vivo. 1635 14

Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.
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PMID:Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health. 1641 45

Polymorphonuclear neutrophils and inflammatory process play a key role in the development of late diabetic vascular complications. Antineutrophil-cytoplasmic autoantibodies (ANCA) are considered important serological markers for vasculitis. The aim of study was the assessment of prevalence ANCA in type 1 diabetic patients and evaluation of the relationship between ANCA and diabetic microangiopathy. 94 type 1 diabetic subjects, 47 male and 47 female, aged 30.7 +/- 9.6 years, with mean duration of diabetes 9.5 +/- 6.8 years and HbA1c 7.9 +/- 1.3% were included to this study. ANCA were detected by the indirect immunofluorescence test and the specificity was evaluated by ELISA test. The significantly positive result of ANCA was noticed in 11 subjects (12%), anti-myeloperoxidase (anti-MPO) in 9 and anti-proteinase 3 (anti-Pr-3c) in 2 subjects. It was not observed any differences in sex, parameters of metabolic control, duration of diabetes, C-reactive protein levels and diabetic retinopathy and nephropathy between group with ANCA and without ANCA (p>0.05). Moreover, we did not notice relationship between ANCA and the risk of late diabetic complications (retinopathy: OR 1.64; 95% CI 0.46-5.82, p = 0.52 and nephropathy: OR 0.16; 95% CI 0.02-1.35, p = 0.10). The obtained results do not fully confirm hypothesis that ANCA are connected with the development of diabetic microangiopathy.
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PMID:[Assessment of antineutrophil-cytoplasmic autoantibodies (ANCA) in type 1 diabetic patients]. 1645 44

Morbidity and mortality in patients with diabetes is mainly driven by its vascular manifestations. The underlying pathophysiology of diabetes is centrally linked to increased generation of reactive oxygen species, namely superoxide and hydrogen peroxide. Superoxide, generated upon uncoupling of the mitochondrial respiratory chain, oxidizes endothelial-derived nitric oxide and thus impairs endothelial function. Superoxide-derived hydrogen peroxide is the principal substrate for leukocyte-derived peroxidases, in particular myeloperoxidase, which associates with endothelial cells and has been shown to catalytically oxidize nitric oxide in vivo. Superoxide also promotes synthesis of advanced glycation endproducts, which also exert potent proatherogenic properties. Moreover, superoxide and hydrogen peroxide activate the redox-sensitive transcription factors NF-kappaB and thus mediates expression of proinflammatory proteins like adhesion molecules. Herein some the most recent discoveries in the pathophysiology of diabetic vasculopathy are reviewed.
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PMID:[Current concepts of diabetic atherogenesis]. 1659 35

Oxidative stress plays a critical role in the pathogenesis of cardiovascular disease and diabetes. Studies in vascular cells and experimental animals have demonstrated that the angiotensin type-1 receptor (AT1R) contributes to formation of reactive oxygen species by activating nicotinamide-adenine dinucleotide phosphate oxidases, but the relevance of this pathway to human heart disease has not been established. Here we demonstrate that a polymorphism in the AT1R gene (A1166C), linked to increased receptor activity, is associated with elevated levels of oxidative stress markers in heart failure patients but not in healthy controls. Plasma protein carbonyls (PCs), a marker of oxidative protein modification, were 10-fold higher in heart-failure patients compared with controls [geometric means and 95% CIs for patients, 75 (57 to 100) pmol/mg; controls, 5 (4 to 7) pmol/mg; P<0.001]. Moreover, levels of PCs were 50-fold higher in patients homozygous for the polymorphism (CC) than in controls and significantly higher than the AA and AC genotype patient groups [CC: 273 (135-550); AC: 59 (35-98); AA: 65 (40-106) pmol/mg; P<0.001]. Levels of myeloperoxidase were also modestly increased in heart-failure patients [51 (46-57) ng/mL] compared with controls [37 (32-44) ng/mL; P<0.001], but were especially elevated in patients with a CC genotype [CC: 72 (58-89); AC: 52 (44-61); AA: 39 (34-46) ng/mL; P<0.001]. The AT1R genotype was demonstrated to be an independent predictor of both PCs and myeloperoxidase levels in heart-failure patients. These findings suggest that oxidative stress in human heart failure is regulated via angiotensin signaling and may involve the nicotinamide dinucleotide oxidase pathway.
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PMID:Angiotensin type-1 receptor A1166C gene polymorphism correlates with oxidative stress levels in human heart failure. 1665 60

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, not only improves insulin resistance in patients with type II diabetes but also exerts a broad spectrum protective effects in variable animal models of neurologic or cardiovascular diseases. We studied the effect of rosiglitazone on angiogenesis and neurological recovery after focal cerebral ischemia. Rosiglitazone (3 mg/kg or 0.3 mg/kg, p.o.) was administered for 7 days prior to and 3 days after the induction of focal ischemia (total 10 days) in adult rats. The rosiglitazone-treated group showed the enhanced neurologic improvement, the reduced infarction volume compared to the ischemia-vehicle group with dose dependency, and the reduced hemispheric atrophy. Rosiglitazone treatment reduced TUNEL(+)/activated caspase-3(+) cells, MPO(+)/Ox-42(+) inflammatory cell infiltrations, caspase-3 activity, and Bax(+) cells, as compared to the ischemia-vehicle group. The vascular surface area, the vascular branch points, the vascular length, and the number of BrdU(+) endothelial cells were significantly increased in the rosiglitazone group compared with the ischemia-vehicle group. Rosiglitazone increased eNOS expression around the ischemic margin with downregulation of FasL. Here, we show that rosiglitazone treatment enhances angiogenesis and functional recovery with dose-dependent induction of ischemic tolerance.
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PMID:Peroxisome proliferator-activated receptor-gamma-agonist, rosiglitazone, promotes angiogenesis after focal cerebral ischemia. 1669 56


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