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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate whether increased levels of reactive oxygen species (ROS) are involved in the pathogenesis of essential hypertension (EH) and non-insulin-dependent diabetes mellitus (NIDDM), both resting and stimulated levels of intracellular ROS were measured in lymphocytes from patients with EH (n = 10), NIDDM (n = 16) and age-matched healthy individuals (control subjects, n = 19). ROS was monitored with the dye, dihydrorhodamine-123 (DHR; 1 micromol/L) in the presence or absence of superoxide dismutase (superoxide scavenger), sodium azide (singlet oxygen/hydrogen peroxide scavenger), genistein (tyrosine kinase inhibitor), or bisindolylmaleimide (protein kinase C inhibitor). Simultaneous monitoring of cytosolic [Ca2+]i was done with fura-2. Resting ROS levels were significantly higher in NIDDM (4.71+/-0.25 nmol/10(6) cells; mean +/- SEM, P<.05) compared with EH (4.03+/-0.22 nmol/10(6) cells) or controls (4.05+/-0.15 nmol/10(6) cells). The formyl-Met-Leu-Phenylalanine-(fMLP)-induced ROS generation was significantly higher in NIDDM (21.92+/-2.23 nmol/10(6) cells; P<.05) compared with EH (14.58+/-1.90 nmol/10(6) cells) or control (16.06+/-1.22 nmol/10(6) cells). The fMLP-induced ROS increase was significantly reduced in the presence of sodium azide in all groups (P<.01) but was largely unaffected in the presence of SOD. Genistein and bisindolylmaleimide significantly inhibited the fMLP-induced ROS in all groups. The fMLP-induced [Ca2+]i increase was significantly higher in NIDDM (71+/-12 nmol/L, P <.01) compared with EH (42+/-4 nmol/L) and control subjects (35+/-3 nmol/L). Phytohemagglutinin was more effective in increasing [Ca2+]i than ROS. It is concluded that ROS may play a role in the metabolic syndrome of NIDDM but not in EH.
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PMID:Reactive oxygen species in essential hypertension and non-insulin-dependent diabetes mellitus. 1061 78

The metabolic syndrome, Type II (non-insulin-dependent) diabetes and obesity are associated with endothelial dysfunction and increased plasma concentrations of NEFAs (non-esterified fatty acids; free fatty acids). The present study was undertaken to define the inhibitory effects of saturated NEFAs on EDR (endothelium-dependent relaxation). Experiments were performed in rings of rabbit aorta to establish (i) dose-response relationships, (ii) the effect of chain length, (iii) the effect of the presence of double bonds, (iv) reversibility and time course of inhibition, and (v) the effect on nitric oxide production. Aortic rings were incubated (1 h) with NEFA-albumin complexes derived from lauric (C(12:0)), myristic (C(14:0)), palmitic (C(16:0)), stearic (C(18:0)) and linolenic (C(18:3)) acids. EDR induced by acetylcholine (0.1-10 mumol/l) was measured after pre-contraction with noradrenaline. Inhibition of EDR was dose-dependent (0.5-2 mmol/l NEFA), and the greatest inhibition (51%) was observed with stearic acid (2 mmol/l). Lauric acid had the smallest inhibitory effect. The inhibitory effects were always reversible and were evident after 15 min of incubation. Linolenic acid caused a significantly lower inhibition of EDR than stearic acid. SOD (superoxide dismutase) restored the inhibitory effect caused by NEFAs, suggesting the involvement of ROS (reactive oxygen species) in removing nitric oxide. The nitric oxide concentration measured after exposure of the rings to acetylcholine was lower after incubation with NEFAs than with Krebs buffer alone. This finding is consistent with removal of nitric oxide by ROS. This claim was supported by the demonstration of increased concentrations of nitrated tyrosine in the rings incubated with NEFAs.
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PMID:Effect of fatty acids on endothelium-dependent relaxation in the rabbit aorta. 1652 62

Previously, we have demonstrated that chronic consumption of a high-fat, high-refined sugar (HFS) diet results in metabolic syndrome which is marked by obesity, insulin resistance, hyperlipidemia, and hypertension in Fischer rats. Metabolic syndrome in this model is associated with oxidative stress, avid nitric oxide (NO) inactivation by reactive oxygen species (ROS), diminished NO bioavailability, and dysregulation of NO synthase isotypes. Although occurrence of oxidative stress and its impact on NO metabolism are well established, the molecular source(s) of ROS in this model is unknown. In an attempt to explore this issue, we measured protein expressions of the key ROS-producing enzyme, NAD(P)H oxidase, and the main antioxidant enzymes, superoxide dismutase (CuZn SOD and Mn SOD), catalase, glutathione peroxidase (GPX), and heme oxygenase-2 (HO-2), in the kidney and aorta of Fischer rats fed an HFS or low-fat, complex-carbohydrate diet for 7 months. In addition, plasma lipid peroxidation product (malondialdehyde) as well as endothelium-dependent and -independent vasorelaxation (aorta rings) was determined. The results showed a significant upregulation of gp91(phox) subunit of NAD(P)H oxidase and downregulations of SOD isoforms, GPX, and HO-2 in the kidney and aorta of the HFS-fed animals. This was associated with increased plasma malondialdehyde concentration and impaired vasodilatory response to acetylcholine, but not the NO donor, Na nitroprusside. The latter findings confirm the presence of oxidative stress and endothelial dysfunction in the HFS-fed rats. Oxidative stress and endothelial dysfunction in the diet-induced metabolic syndrome are accompanied by upregulation of NAD(P)H oxidase, pointing to increased ROS production capacity, and downregulation of SOD isoforms, GPX, and HO-2, the key enzymes in the antioxidant defense system.
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PMID:Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome. 1678 66

Insulin Resistance along with endothelial dysfunction give rise to a constellation of syndromes designated as IRS/MBS metabolic syndrome. Endothelial dysfunction starts early in life much before the development of structural atherosclerosis. Recent insights into vascular biology enable us to understand the molecular mechanisms underlying endothelial dysfunction, and the scope and need for prevention of "pre-clinical" coronary atherosclerosis through lifestyle modification; diet, exercise and stress management. Diminished production of nitric oxide (NO) and/or increased inactivation of NO through oxidative stress (reactive oxygen species ROS and reactive nitrogen species (RNS) are the basis of endothelial dysfunction hence increasing the bioavailability of NO and decreasing its inactivation is the aim of prevention and reversal of endothelial dysfunction. Insulin regulates constitutive NOS gene expression in endothelial cells in vivo; vasodilation is an important component of Insulin-stimulated whole body glucose uptake. Successful strategies are: PPAR alpha and gamma agonists which increase NO production in endothelium; anti-oxidants such as vit. E and C; supplementation with L-arginine, tetrahydrobiopterin-BH4 or sepiapterin (precursor of BH4), SOD mimetic tempol, statins which apart from lowering cholesterol improve NO production, selective beta1 adrenoreceptor antagonists such as nebivolol; suppression of angiotensin-mediated endothelin production by ACE inhibitors and ATR blockers; CB1 receptor blockers, PKCb inhibitors, nitric oxide donors (glyceryl trinitrate and isosorbide dinitrate), dietary supplements of EPA/DHA and regular physical exercise and control of mental stress.
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PMID:Causation, prevention and reversal of vascular endothelial dysfunction. 1805 38

The aim of the present study was to determine the time course of changes in oxidant/antioxidant status, as well as serum glucose, insulin, leptin and lipid levels, liver adipose tissue and muscle lipid and protein contents, in cafeteria-diet-fed dams during gestation and lactation, and in their offspring throughout adulthood. Food intake was also evaluated. The cafeteria diet induced a significant increase in maternal body and relative adipose tissue weights, daily energy intake, and plasma glucose, insulin, leptin and lipid levels at parturition (day 0) and at the end of lactation (day 21). Plasma total antioxidant status [ORAC (oxygen radical absorbance capacity)], erythrocyte catalase and SOD (superoxide dismutase) activities were lower, whereas plasma hydroperoxide and carbonyl protein levels were higher in cafeteria-diet-fed mothers compared with control mothers at days 0 and 21. Pups from cafeteria-diet-fed dams, both males and females, also had consistently higher body and relative adipose tissue weights, and plasma glucose, insulin, leptin, triacylglycerol (triglyceride) and cholesterol levels at birth (day 0), weaning (day 21) and 3 months of age (day 90). These offspring had significantly lower ORAC and catalase activity, and higher plasma hydroperoxide and carbonyl protein levels and SOD activity at birth, at days 21 and 90 compared with control offspring. In conclusion, excessive maternal fat and energy intake can play an important role in the development of metabolic disorders in the offspring. Maternal oxidative stress may be among the responsible factors. Fetal oxidative stress may present an additional confounding influence and probably contributes to additional disorders, aggravating features of the metabolic syndrome. An improvement in maternal oxidant/antioxidant status during pregnancy and lactation, with adequate nutrition, could have beneficial effects on the progeny.
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PMID:Time course of changes in serum oxidant/antioxidant status in overfed obese rats and their offspring. 1898 2

This study is to evaluate beta cell function and investigate the mechanism of impaired pancreatic islet beta cell function in monosodium glutamate (MSG) obese rat with insulin resistance, an animal model of metabolic syndrome. Insulin tolerance test was used to screen MSG obese rats with insulin resistance. Blood concentrations of glucose, triglyceride, total cholesterol and insulin were determined. Beta cell function was assessed with hyperglycemic clamp technique. The morphological alterations in pancreas and changes of islet beta cell mass were evaluated by hematoxylin-eosin (HE) and Gomori aldehyde fuchsin staining. Lipid, oxidative stress relevant factors, nitric oxide (NO) level and activity of ATPase in pancreas and pancreatic mitochondrial were tested. The MSG obese rats with insulin resistance could be validated as a typical metabolic syndrome animal model possessing increased fasting plasma triglycerides and insulin (P < 0. 001), markedly decreased weight indices of pancreas and impaired glucose-stimulated insulin secretion. Hematoxylin-eosin (HE) and Gomori aldehyde fuchsin staining showed increased adipocytes and fibroplasia deposition in pancreas and reduced beta cell mass. The increased contents of triglyceride and NO level, the decreased SOD levels and activities of total ATPase (P < 0.001), Na+-K+-ATPase (P < 0.001) and Ca2+-Mg2+-ATPase (P < 0.01) were observed in pancreas and its mitochondria versus normal rat. The study demonstrates that accumulation of lipids in pancreas could lead to increased systemic indicators of inflammation, such as NO, which may influence the activities of several kinds of ATPase in cell membranes and interfere the ion transport, substance metabolism and energy production in pancreas. Finally the MSG obese rats characterized with metabolic syndrome displayed an impairment of beta cell function.
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PMID:[A preliminary study on the mechanism of impaired beta cell function in monosodium glutamate obese rat with insulin resistance]. 1923 28

Previous evidence supports the concept that increased oxidative stress may play an important role in MetS (metabolic syndrome)-related manifestations. Dietary fat quality has been proposed to be critical in oxidative stress and the pathogenesis of the MetS. In the present study, we investigated whether oxidative stress parameters are affected by diets with different fat quantity and quality during the postprandial state in subjects with the MetS. Patients were randomly assigned to one of four isoenergetic diets distinct in fat quantity and quality for 12 weeks: a high-saturated-fatty-acid (HSFA) diet, a high-mono-unsaturated-fatty-acid (HMUFA) diet and two low-fat/high-complex carbohydrate diets [supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acid (LFHCC n-3) or with 1 g/day of sunflower oil high in oleic acid (LFHCC) as placebo]. The HMUFA diet enhanced postprandial GSH (reduced glutathione) levels and the GSH/GSSH (oxidized glutathione) ratio, compared with the other three diets. In addition, after the HMUFA-rich diet postprandial lipid peroxide levels, protein carbonyl concentrations, SOD (superoxide dismutase) activity and plasma H2O2 levels were lower compared with subjects adhering to the HSFA-rich diet. Both LFHCC diets had an intermediate effect relative to the HMUFA and HSFA diets. In conclusion, our data support the notion that the HMUFA diet improves postprandial oxidative stress in patients with the MetS. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with mono-unsaturated dietary fat, particularly in subjects with the MetS.
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PMID:Postprandial oxidative stress is modified by dietary fat: evidence from a human intervention study. 2042 May 79

The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant enzyme genes (CuZn-SOD, CAT, GPX1, GSR, GSS and TXN) were measured in mononuclear cells of controls (n = 20) and patients (n = 90) by assessing mRNA levels. Activity of some of these antioxidant enzymes was also tested. An increase in OS and pro-oxidant gene mRNA values was observed in patients compared to controls. The hypertensive group showed not only the highest OS values, but also the highest pro-oxidant activation compared to those observed in the other groups. In addition, in HT a significantly reduced antioxidant activity and mRNA induction of antioxidant genes were found when compared to controls and the other groups. In FH and FCH, the activation of pro-oxidant enzymes was also higher and antioxidant ones lower than in the control group, although it did not reach the values obtained in hypertensives. The thioredoxin system was more activated in patients as compared to controls, and the highest levels were in hypertensives. The increased oxidative status in the presence of cardiovascular risk factors is a consequence of both the activation of pro-oxidant mechanisms and the reduction of the antioxidant ones. The altered response of the main cytoplasmic antioxidant systems largely contributes to OS despite the apparent attempt of the thioredoxin system to control it.
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PMID:Different impacts of cardiovascular risk factors on oxidative stress. 2201 50

Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas control group (Con) animals were fed 65% cornstarch (Research Diet, USA). Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared to Con group. Administration of metformin or resveratrol significantly (p<0.05) normalized all the altered metabolic parameters. However, a marked insulin sensitizing action was only observed in the Dia+Resv group. Similarly, while metformin administration failed to normalize the increased TBARS levels and decreased SOD activity, resveratrol showed a more promising effect of all oxidative stress parameters measured in the present study. Attenuation of hepatic oxidative stress in fructose-fed rat liver after resveratrol administration was associated with significant (p<0.05) increase in nuclear level of NRF2 compared with other groups. The present study demonstrates that resveratrol is more effective than metformin in improving insulin sensitivity, and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.
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PMID:Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats. 2262 69

In type 2 diabetes, the relationship between antioxidants and insuline-like trace elements is very complex during oxidative stress, being mediated by hyperglycemia, dyslipidemia and inflammation. We investigated the antioxidant status, particularly Mn and Cr on the diabetes metabolic control, and their interaction with the metabolic syndrome (MS) parameters. The study was undertaken on 278 Algerian diabetic subjects who were divided in 2 groups according to glycated hemoglobin (HbA(1c)) <7% or >7% value, attesting for a good or poor metabolic control of diabetes, respectively. The MS was defined according to NCEP-ATPIII. Insulin resistance was evaluated by HOMA-IR model. The plasma manganese concentrations was significantly increased in both diabetics groups, independently of metabolic control. However, chromium (Cr) seems to play a determinant action in metabolic control, as shown by better values of insulin resistance (HOMA-IR) and HbA(1c). The selenium status was positively correlated with glutathion peroxidase activity. Copper and zinc plasma levels in the diabetic patients were similar to those of control subjects. In conclusion, our results suggest that Mn play a crucial role in antioxidant capacity and we hypothesize that antioxidant defense is preserved in the cytosol (superoxide dismutase Cu/Zn -SOD), whereas it is impaired in mitochondria (Mn-SOD), which makes this cell organelle a true therapeutic target in diabetes.
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PMID:[Preliminary evaluation of the antioxidant trace elements in an Algerian patient with type 2 diabetes: special role of manganese and chromium]. 2320 12


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