8-hydroxy-2--deoxyguanosine and Insulin-Resistance

There is limited evidence whether environmental exposure to perfluorinated compounds (PFCs) affects insulin resistance (IR) and whether vitamin C intake protects against the adverse effect of PFCs. This study was carried out to investigate the effect of PFCs on IR through oxidative stress, and the effects of a 4-week consumption of vitamin C supplement compared placebo on development of IR by PFCs.. For a double-blind, community-based, randomized, placebo-controlled crossover intervention of vitamin C, we assigned 141 elderly subjects to both vitamin C and placebo treatments for 4 weeks. We measured serum levels of PFCs to estimate PFC exposures and urinary levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for oxidative stress. We also measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR.. Perfluorooctane sulfonate (PFOS) and perfluorododecanoic acid (PFDoDA) levels were found to be positively associated with HOMA index at the baseline and after placebo treatment. Risks of IR for the top decile of PFOS and PFDoDA exposures were significantly elevated compared with those with lower PFOS and PFDoDA exposures (both, P < 0.0001). However, the effects of PFOS and PFDoDA on HOMA disappeared after vitamin C supplementation (both, P > 0.30). Furthermore, PFOS and PFDoDA levels were also significantly associated with MDA and 8-OHdG levels, and MDA levels were positively associated with HOMA index.. PFOS and PFDoDA exposures were positively associated with IR and oxidative stress, and vitamin C supplementation protected against the adverse effects of PFOS and PFDoDA on IR.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Ascorbic Acid; Asian People; Biomarkers; Blood Glucose; Caprylates; Cotinine; Creatinine; Cross-Over Studies; Deoxyguanosine; Dietary Supplements; Double-Blind Method; Fluorocarbons; Humans; Insulin; Insulin Resistance; Malondialdehyde; Middle Aged; Oxidative Stress; Republic of Korea

Enhanced oxidative stress-generated nucleoside damage may contribute to the increased cardiovascular disease mortality in patients with bipolar disorder (BD) but the association has never been investigated. We investigated the associations between oxidative stress-generated damage to DNA (8-oxodG) and RNA (8-oxoGuo), respectively, and three measures reflecting cardiovascular risk; namely, the Framingham 30-year risk score of cardiovascular diseases, the metabolic syndrome, and the insulin resistance index in 360 patients newly diagnosed with BD, 102 of their unaffected relatives (UR) and 197 healthy control individuals (HC). In sex- and age-adjusted models, the 30-year cardiovascular risk score increased by 20.8% (CI = 7.4-35.9%, p = 0.002) for every one nM/mM creatinine increase in 8-oxoGuo and by 15.6% (95% CI = 5.8-26.4%, p = 0.001) for every one nM/mM creatinine increase in 8-oxodG, respectively. Further, insulin resistance index increased by 24.1% (95% CI = 6.7-43%, p = 0.005) when 8-oxoGuo increased one nM/mM creatinine. The associations between cardiovascular measures and oxidative nucleoside damage were more pronounced in patients with BD compared with UR, and HC. Metabolic syndrome was not associated with nucleoside damage. Overall, higher oxidative stress-generated nucleoside damage was associated with a higher cardiovascular risk score and a higher degree of insulin resistance index, and having BD impacted the associations. Further, within patients, treatment with psychotropics seemed to enhance the associations between 30-year CVD risk score and insulin resistance index, respectively, and oxidatively stress-generated nucleoside damage. Our findings support enhanced oxidative stress-generated nucleoside damage as a putative pathophysiological mechanism that may mediate the higher cardiovascular risk observed in patients with BD already at the time of diagnosis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Bipolar Disorder; Cardiovascular Diseases; Case-Control Studies; Creatinine; Heart Disease Risk Factors; Humans; Insulin Resistance; Nucleosides; Oxidative Stress; Risk Factors

The link between zinc exposure and glucose metabolism or the development of type 2 diabetes (T2D) is controversial, and underlying mechanisms are unclear. This study aimed to explore the associations of zinc exposure with glucose-insulin homeostasis traits and the long-term effects of zinc on the development of T2D, and further to estimate the potential roles of inflammation and oxidative damage in such relationships. We investigated 3890 urban adults from the Wuhan-Zhuhai cohort, and followed up every three years. Mixed linear model was applied to estimate dose-response associations between urinary zinc and glycemia traits [fasting plasma insulin (FPI), fasting plasma glucose (FPG), insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and β-cell dysfunction (homeostasis model assessment of β-cell function, HOMA-B)], as well as zinc and biomarkers for systemic inflammation (C-reactive protein) and oxidative damage (8-isoprostane and 8-hydroxy-2'-deoxyguanosine). Logistic regression model and Cox regression model were conducted to evaluate the relationships between urinary zinc and prevalence and incidence of T2D, respectively. We further performed mediation analysis to assess the roles of inflammation and oxidative damage biomarkers in above associations. At baseline, we observed significant dose-response relationships of elevated urinary zinc with increased FPI, FPG, HOMA-IR, and T2D prevalence and decreased HOMA-B, and such associations could be strengthened by increased C-reactive protein, 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine. Elevated C-reactive protein significantly mediated 9.09% and 17.67% of the zinc-related FPG and HOMA-IR increments, respectively. In longitudinal analysis, a significantly positive association between urinary zinc and T2D incidence was observed among subjects with persistent high urinary zinc levels when compared with those with persistent low zinc levels. Our results suggested that high levels of zinc exposure adversely affected on glucose-insulin homeostasis and further contributed to increased risk of T2D cross-sectionally and longitudinally. Moreover, inflammatory response might play an important role in zinc-related glucose metabolic disorder.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Blood Glucose; C-Reactive Protein; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Homeostasis; Humans; Inflammation; Insulin; Insulin Resistance; Oxidative Stress; Zinc

Chile is a mining country, where waste mining is frequently found in the vicinity of inhabited areas. To explore the association between metal exposure and alterations in glucose metabolism, inflammatory status, and oxidative stress in individuals with chronic exposure to metals, a cross-sectional study was performed with 25 volunteers, between 45-65 years old. Inductive coupled plasma mass spectrometry (ICP-MS) was used to measure urinary levels of total arsenic (As) and its metabolites, cooper, nickel, chromium, and lead. Lipid profile, glucose, and insulin were measured in blood, as well as inflammation (interleukin-6, IL-6) and oxidative stress (8-hydroxy-2'deoxyguanosine, 8-OHdG) markers. Increased levels of Low-density lipoprotein, high-density lipoproteins, cholesterol and 8-OHdG, and the index for homeostasis model assessment-insulin resistance (HOMA-IR) were observed in 72%, 60%, and 56% of the volunteers, respectively. Blood-glucose levels were correlated with dimethylarsinic acid (DMA) (R

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Chile; Chronic Disease; Cross-Sectional Studies; Humans; Insulin Resistance; Metals, Heavy; Middle Aged

Sericin could be degraded well into low-molecular-weight sericin (SS) through a novel and environmentally friendly recycling process using an ultrasonically degumming method in Ca(OH)

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Oral; Animal Feed; Animals; Blood Glucose; Body Weight; Bombyx; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Homeostasis; Insulin; Insulin Resistance; Lipids; Liver; Male; Organ Size; Oxidative Stress; Pancreas; Peptides; Rats; Rats, Sprague-Dawley; Sericins

The effect of human exposure to phthalates and consequent contribution to the development of cardiometabolic health problems is unknown. However, oxidative stress has been established as playing an important role in the pathogenesis of cardiometabolic outcomes. In this study, we aimed to explore whether exposure to phthalate metabolites could induce cardiometabolic risk by increasing oxidative stress in a diabetic population from Shanghai. We collected paired blood and urine samples from a total of 300 volunteers, and measured 10 phthalate metabolites in urine and biomarkers of oxidative stress from serum including glucose and lipid levels, and liver and kidney damage. The insulin resistance (IR) risk was assessed by the surrogate indices including homeostasis model assessment-insulin resistance (HOMA-IR) and triglyceride glucose (TyG). We used multivariable linear regression to assess the association between phthalates and these physiological parameters. Mediation and modification analyses were performed to identify the role that oxidative stress played in the underlying mechanisms. The results showed that most of the determined phthalate metabolites were positively associated with HOMA-IR, 8‑hydroxy‑2'‑deoxyguanosine (8-OHDG), and malondialdehyde (MDA). In the mediation analysis, only γ‑glutamiltransferase (GGT) was found to be a significant mediator of the association between phthalates and TyG. In the modification analysis, exposure to phthalates strengthened the association between oxidative stress (MDA and 8-OHDG) and HOMA-IR. Our findings demonstrate that exposure to phthalates might be positively associated with elevated IR and oxidative stress. The direct participation (mediation effect) of GGT might play an important mechanism in promoting IR.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; China; Deoxyguanosine; Diabetes Mellitus; Diabetic Cardiomyopathies; Female; Humans; Insulin Resistance; Liver; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Phthalic Acids; Risk Assessment

8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, has been recently shown to exert anti-inflammatory effects through inhibition of Rac1. Inflammation in adipose tissue is a hallmark of obesity-induced insulin resistance, but the therapeutic potential of 8-OHdG in treatment of metabolic diseases has not been fully elucidated. The aim of this study was to examine the effect of exogenously administered 8-OHdG on adipose tissue and whole body metabolism. In cultured adipocytes, 8-OHdG inhibited adipogenesis and reversed TNFα-induced insulin resistance. In high-fat diet (HFD)-induced obese mice, 8-OHdG administration blunted the rise in body weight and fat mass. The decrease in adipose tissue mass by 8-OHdG was due to reduced adipocyte hypertrophy through induction of adipose triglyceride lipase and inhibition of fatty acid synthase expression. 8-OHdG also inhibited the infiltration of macrophages, resulting in amelioration of adipose tissue inflammation and adipokine dysregulation. Moreover, 8-OHdG administration ameliorated adipocyte as well as systemic insulin sensitivity. Both in vivo and in vitro results showed that 8-OHdG induces AMPK activation and reduces JNK activation in adipocytes. In conclusion, our results show that orally administered 8-OHdG protects against HFD-induced metabolic disorders by regulating adipocyte metabolism.

Topics: 3T3-L1 Cells; 8-Hydroxy-2'-Deoxyguanosine; Adipocytes; Animals; Cell Differentiation; Cells, Cultured; Deoxyguanosine; Diet, High-Fat; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Tumor Necrosis Factor-alpha

To explore influence of carbohydrates/fat proportions, dietary ingredients on telomere length shortening, oxidative stress and inflammation in a Chinese population with different glucose tolerance status.. Five hundred and fifty-six Chinese subjects without diabetes history underwent a 75 g, 2 h Oral Glucose Tolerance Test (OGTT). Subjects with diabetes (n = 159), pre-diabetes (n = 197), and normal glucose tolerance (n = 200) were screened. Dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood leukocyte telomere length (LTL) was assessed using a real-time PCR assay. Blood lipid profile, levels of the oxidative stress indicators superoxide dismutase (SOD), glutathione reductase (GR), 8-oxo-2'-deoxyguanosine (8-oxo-dG) and inflammation indicators tumor necrosis factor (TNF-ɑ), interleukine-6 (IL-6) were measured. Levels of HbA1c, plasma glucose, insulin, and C peptide were also determined. Measurements were taken at 0 min, 30 min, 60 min, and 120 min after 75 g OGTT. Insulin sensitivity was evaluated by HOMA-IR. Basal insulin secretion index (HOMA-β), early phase disposition index (DI30) and total phase disposition index (DI120) indicate insulin levels at different phases of insulin secretion.. In patients with newly diagnosed diabetes, LTL adjusted by age was longer in HbA1c < 7 % group (log (LTL):1.93 ± 0.25) than in HbA1c ≥ 7 % group (log (LTL):1.82 ± 0.29). LTL was not associated with daily energy intake, diet fat, carbohydrates and protein proportions. Multiple linear regression analysis indicated that legumes, nuts, fish and seaweeds were protective factors for LTL shortening, and sweetened carbonated beverage was a risk factor for LTL shortening ( legumes: β = 0.105, p = 0.018; nuts: β = 0.110, p = 0.011; fish: β = 0.118, p = 0.007; seaweeds: β = 0.116, p = 0.009; sweetened carbonated beverage: β = -0.120, p = 0.004 ). Daily energy intake was positively associated with TNF-ɑ, IL-6 (TNF-ɑ: r = 0.125, p = 0.006;IL-6: r = 0.092, p =0.04). Fat, carbohydrate proportions were positively associated with TNF-ɑ (fat: r = 0.119, p = 0.008 ; carbohydrate: r = 0.094, p = 0.043). Seaweeds and dairy intake were negatively associated with 8-oxo-dG (seaweed: r = -0.496, p = 0.001;dairy: r = -0.246, p = 0.046 ), vegetables and fruits were positively associated with GR ( vegetables: r = 0.101, p = 0.034;fruits: r = 0.125, p = 0.045). Cereal, meat were positively associated with TNF-ɑ ( cereal: r = 0.091, p = 0.048 ; meat: r = 0.405, p = 0.009).. Diabetes patients with better plasma glucose (HbA1c < 7 %) had longer LTL, LTL could reflect plasma glucose status in diabetes patients. LTL were probably not influenced by diet carbohydrates/fat proportions but was associated with diet ingredients. Diet ingredients significantly impacted on markers of inflammation and oxidative stress, which probably had an effect on LTL.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Asian People; Biomarkers; Blood Glucose; China; Cross-Sectional Studies; Deoxyguanosine; Diet; Female; Glucose Intolerance; Glutathione Reductase; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leukocytes; Male; Middle Aged; Nutrition Surveys; Oxidative Stress; Superoxide Dismutase; Telomere; Tumor Necrosis Factor-alpha

Urinary markers of nucleic acid oxidation may be useful biomarkers in diabetes. It has been demonstrated that T2DM patients have an increased level of oxidative DNA damage; however, it is unclear whether increased DNA damage may be related to a greater degree of inflammation and insulin resistance. Thus, the aim of this present study was to investigate the relation of the impact of oxidative DNA damage, assessed by urinary 8-OHdG, on the levels of inflammatory cytokines, as well as insulin resistance. In addition, we also investigated the diagnostic ability of urinary 8-OHdG in the identification of microvascular complications in T2DM.A case-control study, enrolling 22 healthy controls and 54 subjects with T2DM, was performed to evaluate the relation between oxidative DNA damage and interleukin-6 (IL-6), IL-1,tumor necrosis factor-alpha (TNF-α), IL-10, and Homeostasis Model Assessment (HOMA-IR) index. T2DM patients presented higher urinary 8-OHdG, IL-6, IL-1, TNF-α levels and HOMA-IR, and lower IL-10 levels than control subjects. Moreover, urinary 8-OHdG levels were significantly higher in the group T2DM with microvascular complications when compared to the without complications. The areas under the curve for urinary 8-OHdG and urinary albumin were, respectively, 0.836 (P<0.001) and 0.786 (P=0.002). Thus, urinary 8-OHdG has a slightly higher ability to discriminate microvascular complications in T2DM compared with urinary albumin. It was also demonstrated that T2DM patients with higher median of urinary 8-OHdG had significantly elevated levels of IL-6, TNF-α and HOMA-IR, and decreased IL-10 levels. Our findings showed that T2DM patients with higher urinary 8-OHdG levels showed a greater inflammatory degree and higher insulin resistance. It is possible to speculate that T2DM patients present a cascade of events as increasing metabolic abnormalities such as insulin resistance and inflammatory activation, as well as increased ROS generation factors that may contribute directly to greater oxidative DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Case-Control Studies; Cytokines; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; DNA Damage; Female; Humans; Insulin Resistance; Linear Models; Male; Microvessels; Middle Aged; Oxidative Stress; ROC Curve

The goal of this study is to investigate the association between oxidative stress and telomere length shortening in the comorbid depression and diabetes. Therefore, 71 patients with newly diagnosed type 2 diabetes (T2D) and 52 subjects with normal glycemic level (control, Ctrl) were enrolled. Depressive status was identified with the Depression Subscale of Hospital Anxiety and Depression Scale (HADS-D). Leukocyte telomere length ratio (T/S ratio) was determined with quantitative PCR. Oxidative stress status was evaluated with 8-hydroxy-desoxyguanosine (8-OHdG) assay kit. Some other biochemical blood testing was also performed. The data showed that T2D patients had higher proportion of depression evaluated by the HADS-D (x(2) = 4.196, P = 0.041). T/S ratio was significantly negatively correlated with 8-OHdG, HADS-D, age, HbA1c, FPG, and HOMA-IR. In addition, HADS-D was significantly positively correlated with HbA1c, FPG, HOMA-IR, and 8-OHdG. Both HADS-D and 8-OHdG were the major independent predictors for T/S ratio. This study indicates that oxidative stress contributes to both telomere length shortening and depression development in newly diagnosed type 2 diabetic patients, while in depression status, some other mechanisms besides oxidative stress may also affect the telomere length.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Age Factors; Aged; Blood Glucose; Deoxyguanosine; Depression; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Leukocytes; Male; Middle Aged; Oxidative Stress; Telomere; Telomere Shortening

Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes.. LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls.. Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Benzofurans; C-Reactive Protein; Chemokine CCL2; Deoxyguanosine; Depsides; Diabetic Retinopathy; Glucose; Glucose Intolerance; Insulin Resistance; Male; Obesity; Rats; Rats, Long-Evans; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Alloxan generates hydrogen peroxide in the body, and a small amount of alloxan administered to acatalasemic mice results in diabetes. D-α-Tocopherol (vitamin E) is an antioxidant which helps prevent excess oxidation in the body. In this study, we examined the effect of vitamin E on diabetes caused by alloxan administration in mice.. Mice were maintained on a vitamin E-deprived diet and supplemented diet, respectively, for 14 weeks. Alloxan was then intraperitoneally administered, and blood glucose, glucose tolerance and the insulin level in mouse blood were examined.. Hyperglycemia was observed in the mice maintained on the vitamin E-deprived diet. The incidence of hyperglycemia in the mice maintained on the vitamin E-deprived diet was significantly higher than that in the mice maintained on the supplemented diet. The abnormal glucose metabolism caused by alloxan administration was ameliorated by the vitamin E-supplemented diet.. It is deduced that vitamin E can prevent a decrease of insulin concentration in the blood in this mouse model.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Oral; Alloxan; alpha-Tocopherol; Animals; Antioxidants; Biomarkers; Blood Glucose; C-Peptide; Catalase; Deoxyguanosine; Diabetes Mellitus, Experimental; Glucose Tolerance Test; Hyperglycemia; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C3H; Oxidative Stress; Pancreas

Insulin resistance is one of the feature of obesity. Fetuin A is inhibitor of insulin receptor which belongs the family of receptor tyrosine kinase. It has been observed that fetuin-null mice are resistant to diet-induced obesity and they exhibit increased insulin sensitivity. Increased production of reactive oxygen species is suggested to be associated with insulin resistance. Attacks of reactive oxygen species to DNA results in base oxidation. Among the oxidized bases, 8-hydroxydeoxyguanosine is predominant lesion with pro-mutagenic potential. In the present study; measurement of serum levels of fetuin A and 8-hydroxydeoxyguanosine in obese subjects (n=46) and healthy controls (n=22), and examination of the relations between these parameters and insulin resistance have been purposed. Blood samples were taken form morbidly obese subjects after a 12 h fasting. Serum levels of fetuin A and 8-hydroxydeoxyguanosine were measured by ELISA. Statistical analysis was performed by Mann Whitney U test and correlations were examined by Spearman correlation coefficient. Serum levels of total cholesterol, HDL, LDL, VLDL, triglycerides, free T3, free T4, fasting glucose, c-peptide and %HbA1c in the obese group were found to be different from those in the control group. Serum level of fetuin A was found to be higher, 8-hydroxydeoxyguanosine level was found to be lower in the morbid obese group than those in the control group. Fetuin A was found to be positively correlated with HOMA-IR (r:0,40, P<0.05) and negatively correlated with 8-hydroxydeoxyguanosine (r:-0,52, P<0.01). No significant association was determined between body mass index and measured parameters. In conclusion, serum level of fetuin A is high in morbidly obese subjects and is negatively associated with 8-hydroxydeoxyguanosine level in peripheral circulation. Fetuin A may be a promising link between insulin resistance and obesity as well its comorbidities.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; alpha-2-HS-Glycoprotein; Animals; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Deoxyguanosine; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Mice; Middle Aged; Obesity, Morbid; Triglycerides

Increasing evidence showed that telomere length was shorter in age-related diseases, but the mechanism of this phenomenon is still unclear.. To determine whether telomere shortening occurs in Type 1 diabetes (T1D) and Type 2 diabetes (T2D), and explore the effect of antioxidant status on the telomere length.. T2D patients (no.=62), T1D patients (no.=34), and non-diabetic subjects used as control (CTL) (no.=40) were included in this study. Leukocyte telomere length ratio (T/S ratio) was measured using a quantitative PCR and analyzed. Antioxidant status was estimated by human 8-hydroxy-desoxyguanosine quantization. Other biomarkers, such as fasting plasma glucose, fasting insulin, glycated hemoglobin (HbA1c) and lipid profile were also measured.. Compared with CTL group [T/S ratio (mean ± SD), 2.39 ± 0.55], leukocyte telomere length was significantly shorter in T2D group (1.67 ± 0.50) and T1D group (1.77 ± 0.50). 8-OHdG that indicated oxidative stress was significantly higher in T2D (2.99 ± 0.85 ng/ml) and T1D (2.03 ± 0.92 ng/ml) group than in CTL group (0.90 ± 0.46 ng/ml). T/S ratio was significantly negatively correlated with age, waist circumference, waist-to-hip ratio, diastolic blood pressure, fasting plasma glucose, HbA1c, homeostasis model assessment of insulin resistance and 8- OHdG in the whole population. 8-OHdG was independent risk factor for telomere shortening in both T1D (p=0.018) and T2D group (p=0.022).. In our study, shorter telomere length and increased oxidative stress were observed in both T1D and T2D. Older people with central obesity, hyperglycemia, insulin resistance and severe antioxidant status tended to have shorter telomere length. In addition, 8- OHdG was an independent predictor for telomere length for both T1D and T2D patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Deoxyguanosine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leukocytes; Male; Middle Aged; Oxidative Stress; Telomere

"Urtica pilulifera has been traditionally used in Egyptian system as an herbal remedy to be a diuretic, antiasthmatic, anti-inflammatory, hypoglycemic, hemostatic, antidandruff and astringent". To evaluate the potential effects of ethyl acetate (EA), chloroform (CHLOR) and hexane (HEXA) extracts of Urtica piluliferaas oral anti-diabetic agents as well as to evaluate their possible anti-oxidant and anti-inflammatory effects in type 2 diabetic rat model.. Type 2 diabetes was induced by a high fat diet and low dose streptozotocin (STZ). Diabetic adult male albino rats were allocated into groups and treated according to the following schedule; Pioglitazone HCL (PIO), EA, CHLOR and HEXA extracts of Urtica pilulifera at two doses of 250 and 500 mg/kg were used. In addition, a normal control group and a diabetic control one were used for comparison. Blood glucose, insulin resistance, antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as C-reactive protein and tumor necrosis factor-α levels were evaluated.. EA and CHLOR extracts of Urtica pilulifera exhibited a significant hypoglycemia associated with antioxidant and anti-inflammatory effects in diabetic rats; however, HEXA extract showed no beneficial effect. These activities are responsible, at least partly, for improvements that have been seen in hyperglycemia and insulin resistance of diabetic rats.. Our results encourage the traditional use of Urtica pilulifera extract as an antioxidant and anti-inflammatory agent as an additional therapy of diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blood Proteins; Blood Urea Nitrogen; Creatinine; Deoxyguanosine; Diabetes Mellitus, Experimental; Hypoglycemic Agents; Inflammation Mediators; Insulin; Insulin Resistance; Lipid Metabolism; Liver; Male; Oxidative Stress; Pancreas; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Urticaceae

To correlate changes between VEGF expression with systemic and retinal oxidative stress and inflammation in rodent models of obesity induced insulin resistance and diabetes.. Retinal VEGF mRNA and protein levels were assessed by RT-PCR and VEGF ELISA, respectively. Urinary 8-hydroxydeoxyguanosine (8-OHdG), blood levels of C-reactive protein (CRP), malondialdehyde (MDA), and CD11b/c positive cell ratio were used as systemic inflammatory markers. Retinal expression of Nox2, Nox4, and p47phox mRNA levels were measured as oxidative stress markers. TNF-α, inter-cellular adhesion molecule-1 (ICAM-1), IL1β, and activation of nuclear factor κB (NF-κB) were used as retinal inflammatory markers.. Retinal VEGF mRNA and protein expression increased in Zucker diabetic fatty (ZDF(fa/fa)) rats and streptozotosin (STZ) induced diabetic Sprague-Dawley rats, after two months of disease, but not in Zucker fatty (ZF) rats. Systemic markers of oxidative stress and inflammation were elevated in insulin resistant and diabetic rats. Some oxidative stress and inflammatory markers (TNF-α, IL-6, ICAM-1, and IL1-β) were upregulated in the retina of ZDF(fa/fa) and STZ diabetic rats after 4 months of disease. In contrast, activation of NF-κB in the retina was observed in high fat fed nondiabetic and diabetic cis-NF-κB(EGFP) mice, ZF, ZDF(fa/fa), and STZ-induced diabetic rats.. Only persistent hyperglycemia and diabetes increased retinal VEGF expression. Some markers of inflammation and oxidative stress were elevated in the retina and systemic circulation of obese and insulin resistant rodents with and without diabetes. Induction of VEGF and its associated retinal pathologies by diabetes requires chronic hyperglycemia and factors in addition to inflammation and oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; C-Reactive Protein; CD11b Antigen; CD11c Antigen; Deoxyguanosine; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Inflammation; Insulin Resistance; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; NF-kappa B; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Rats, Zucker; Retina; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stress, Physiological; Vascular Endothelial Growth Factor A

Resveratrol (RSV) has anti-inflammatory and anti-oxidant actions which may contribute to its cardiovascular protective effects. We examined whether RSV has any beneficial effects on pancreatic islets in db/db mice, an animal model of type 2 diabetes. The db/db and db/dm mice (non-diabetic control) were treated with (db-RSV) or without RSV (db-control) (20 mg/kg daily) for 12 weeks. After performing an intraperitoneal glucose tolerance test and insulin tolerance test, mice were sacrificed, the pancreas was weighed, pancreatic β-cell mass was quantified by point count method, and the amount of islet fibrosis was determined. 8-Hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, was determined in 24 h urine and pancreatic islets. RSV treatment significantly improved glucose tolerance at 2 hrs in db/db mice (P = 0.036), but not in db/dm mice (P = 0.623). This was associated with a significant increase in both pancreas weight (P = 0.011) and β-cell mass (P = 0.016). Islet fibrosis was much less in RSV-treated mice (P = 0.048). RSV treatment also decreased urinary 8-OHdG levels (P = 0.03) and the percentage of islet nuclei that were positive for 8-OHdG immunostaining (P = 0.019). We conclude that RSV treatment improves glucose tolerance, attenuates β-cell loss, and reduces oxidative stress in type 2 diabetes. These findings suggest that RSV may have a therapeutic implication in the prevention and management of diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Blood Glucose; Deoxyguanosine; Diabetes Mellitus, Type 2; Disease Models, Animal; Fibrosis; Glucose Tolerance Test; Immunohistochemistry; Insulin; Insulin Resistance; Islets of Langerhans; Male; Mice; Organ Size; Oxidative Stress; Resveratrol; Stilbenes

Progressive β-cell dysfunction and loss of β-cell mass are fundamental pathogenic features of type 2 diabetes. To examine if anti-diabetic reagents, such as insulin, pioglitazone (pio), and alogliptin (alo), have protective effects on β-cell mass and function in vivo, we treated obese diabetic db/db mice with these reagents.. Male db/db mice were treated with a chow including pio, alo, or both of them from 8 to 16 weeks of age. Insulin glargine (gla) was daily injected subcutaneously during the same period.. At 16 weeks of age, untreated db/db mice revealed marked increase of HbA1c level, whereas those treated with pio, pio+alo, or insulin revealed the almost same HbA1c levels as non-diabetic db/m mice. Islet mass evaluated by direct counting in the whole pancreas and insulin content in isolated islets were preserved in pio, pio+alo and gla groups compared with untreated or alo groups, and there was no difference among pio, pio+alo and gla groups. To precisely evaluate islet β-cell functions, islet perifusion analysis was performed. In pio, pio+alo and gla groups, biphasic insulin secretion was preserved compared with untreated or alo groups. In particular, pio+alo as well as gla therapy preserved almost normal insulin secretion, although pio therapy improved partially. To examine the mechanism how these reagents exerted beneficial effects on β-cells, we evaluated expression levels of various factors which are potentially important for β-cell functions by real-time RT-PCR and immunohistochemistry. The results showed that expression levels of MafA and GLP-1 receptor were markedly decreased in untreated and alo groups, but not in pio, pio+alo and gla groups.. Combination therapy with pio and alo almost completely normalized β-cell functions in vivo, which was comparable with gla treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Body Weight; Deoxyguanosine; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Insulin, Long-Acting; Maf Transcription Factors, Large; Mice; Mice, Inbred C57BL; Pioglitazone; Piperidines; Receptors, Glucagon; Thiazolidinediones; Triglycerides; Uracil

Several studies have shown increased oxidative stress in patients with pre-diabetes and newly diagnosed Type 2 diabetes mellitus (T2DM). It has been proposed that oxidative stress initiates insulin resistance in genetically predisposed individuals. The aim of this study was to evaluate the markers of oxidative stress in the offspring of patients with T2DM.. We examined 60 lean normoglycemic offspring of Type 2 diabetics, and 52 age, sex and body mass index matched subjects without family history of T2DM as controls. Anthropometric, biochemical and carotid intima media thickness (IMT) measurements and oral glucose tolerance test (OGTT) were performed. Erythrocyte superoxide dismutase and glutathione peroxidase activities, serum nitric oxide, plasma total sulfhydryl (tSH) groups, plasma total antioxidant status, plasma malondialdehyde and serum 8-hydroxydeoxy-guanosine (8-OHdG) levels were compared between 2 groups.. 2 groups were similar for the measurements of anthropometric, blood pressure, lipids, fasting glucose, HOMA-IR and carotid IMT. Glucose levels during OGTT were significantly higher in the offspring of Type 2 diabetics than controls (p=0.035). The offspring of Type 2 diabetics showed a significant increase in serum 8-OHdG level (p=0.005) and plasma tSH groups (p=0.032) when compared to the controls. Significant differences were not obtained in other oxidative stress marker levels between 2 groups.. Main finding of our study was the presence of increased oxidative DNA damage in lean normoglycemic offspring of Type 2 diabetic patients. There is a need for further clinical studies in order to explain whether oxidative stress is present in genetically predisposed subjects and induces the insulin resistance.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Blood Glucose; Body Mass Index; Deoxyguanosine; Diabetes Mellitus, Type 2; DNA Damage; Family Health; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Oxidative Stress; Parents; Prediabetic State; Sulfhydryl Compounds; Thinness; Young Adult

Type 2 diabetes is a heterogeneous metabolic disease characterized by insulin resistance and β-cell dysfunction leading to hyperglycaemia and dyslipidaemia. Dietary intervention seems to improve some of these cellular complications, namely insulin resistance. Our aim was to evaluate the effects of dietary restriction on systemic and skeletal muscle oxidative stress and insulin resistance in normal Wistar rats and Goto-Kakizaki (GK) rats, a non-obese type 2 diabetic animal model. Four-month-old normal and diabetic rats were separated in four groups. One group of each strain was maintained with ad libitum standard diet, and the other group was submitted to a dietary restriction (50% of control animals daily food intake), during 2 months. Metabolic profile, insulin resistance indexes and muscle lipids were determined. Oxidative stress parameters were also measured at systemic and muscle levels: protein carbonyl, 8-hydroxy-2'-deoxyguanosine and free 8-isoprostane. Dietary restriction improved lipid profile in both strains and urinary free 8-isoprostane and plasma carbonyl compounds in diabetic rats. An improvement of muscle triglycerides accumulation and 8-isoprostane concentration and a reduction of insulin resistance were also observed in GK rats. Our data show that dietary restriction ameliorates systemic and skeletal muscle oxidative stress state in type 2 diabetes, which is associated with improved insulin resistance.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Cholesterol; Deoxyguanosine; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Dinoprost; Eating; Insulin Resistance; Male; Muscle, Skeletal; Oxidative Stress; Protein Carbonylation; Rats; Rats, Inbred OLETF; Rats, Wistar; Triglycerides

Oxidative stress is involved in the development and progression of diabetic nephropathy (DN). Because Trigonella foenum graecum has been reported to have antidiabetic and antioxidative effects, we hypothesized that T foenum graecum seed aqueous extract (TE) restores the kidney function of diabetic rats via its antioxidant activity. Rats were fed diets enriched with sucrose (50%, wt/wt), lard (30%, wt/wt), and cholesterol (2.5%, wt/wt) for 8 weeks to induce insulin resistance. After a DN model was induced by streptozotocin, the rats were administered a low (440 mg/kg), medium (870 mg/kg), or high (1740 mg/kg) dose of TE by oral intragastric intubation for 6 weeks. In TE-treated DN rats, blood glucose, kidney/body weight ratio, serum creatinine, blood urea nitrogen, 24-hour content of urinary protein, and creatinine clearance were significantly decreased compared with nontreated DN rats. Diabetic rats showed decreased activities of superoxide dismutase and catalase, increased concentrations of malondialdehyde in the serum and kidney, and increased levels of 8-hydroxy-2'-deoxyguanosine in urine and renal cortex DNA. Treatment with TE restored the altered parameters in a dose-dependent manner. Furthermore, all of the ultramorphologic abnormalities in the kidney of diabetic rats, including the uneven thickening of the glomerular base membrane, were markedly ameliorated by TE treatment. We conclude that TE confers protection against functional and morphologic injuries in the kidneys of diabetic rats by increasing activities of antioxidants and inhibiting accumulation of oxidized DNA in the kidney, suggesting a potential drug for the prevention and therapy of DN.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Biomarkers; Blood Glucose; Blood Urea Nitrogen; Body Weight; Catalase; Creatinine; Deoxyguanosine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diet; DNA; Dose-Response Relationship, Drug; Hypoglycemic Agents; Insulin Resistance; Kidney; Male; Malondialdehyde; Organ Size; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds; Superoxide Dismutase; Trigonella

Several lines of evidence have suggested that oxidative stress plays an important role for the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, by using immunohistochemical staining of liver biopsy samples, we measured hepatic 7,8-dihydro-8-oxo-2' deoxyguanosine (8-oxodG), a DNA base-modified product generated by hydroxyl radicals, of 38 NASH patients and compared with 24 simple steatosis and 10 healthy subjects. Relation of hepatic 8-oxodG with clinical, biochemical, and histologic variables and changes after iron reduction therapy (phlebotomy plus iron-restricted diet) were also examined. Hepatic 8-oxodG levels were significantly higher in NASH compared with simple steatosis (17.5 versus 2.0 8-oxodG-positive cells/10(5) microm(2); P < 0.0001). 8-oxodG was significantly related to iron overload condition, glucose-insulin metabolic abnormality, and severities of hepatic steatosis in NASH patients. Logistic regression analysis also showed that hepatic iron deposit and insulin resistance were independent variables associated with elevated hepatic 8-oxodG. After the iron reduction therapy, hepatic 8-oxodG levels were significantly decreased (from 20.7 to 13.8 positive cells/10(5) microm(2); P < 0.01) with concomitant reductions of serum transaminase levels in NASH patients. In conclusion, iron overload may play an important role in the pathogenesis of NASH by generating oxidative DNA damage and iron reduction therapy may reduce hepatocellular carcinoma incidence in patients with NASH.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Analysis of Variance; Carcinoma, Hepatocellular; Case-Control Studies; Deoxyguanosine; DNA Damage; Fatty Liver; Female; Humans; Insulin Resistance; Iron Overload; Liver Function Tests; Liver Neoplasms; Logistic Models; Male; Middle Aged; Oxidative Stress; Severity of Illness Index; Statistics, Nonparametric

We examined whether or not epigallocatechin-3-gallate (EGCG) improves liver injury of nonalcoholic steatohepatitis (NASH) model mice expressing nuclear sterol regulatory element-binding protein 1c (nSREBP-1c) in adipose tissue. nSREBP-1c transgenic C57BL6 mice aged 30 weeks were divided into group 1 (no treatment), group 2 (ascorbic acid alone), group 3 (ascorbic acid and 0.05% EGCG), and group 4 (ascorbic acid and 0.1% EGCG). At 42 weeks, we performed measurement of liver weight to body weight, biochemical assays, morphometry of liver specimens, immunohistochemistry for 8-hydro-2'-deoxyguanosine (8-OhdG), and Western blotting for insulin and TNF-alpha signalings. Ratio of liver weight to body weight in the high dose EGCG-treated group (group 4) was significantly lower than those of groups 1 and 2 (p<0.05 and <0.01, respectively). Blood ALT, glucose, total cholesterol, and triglyceride levels of group 4 were significantly low compared with those of the EGCG-non-treated group (groups 1 and 2) (p<0.05, respectively). The degrees of steatosis, inflammation, ballooning hepatocytes and Mallory-Denk bodies in group 4 significantly improved compared with those in other groups (p<0.05, respectively). The 8-OhdG immunolocalization in liver tissues of the group 4 obviously decreased compared with those of groups 2 and 3. For Western blotting, the expressions of insulin receptor substrate-1 (IRS-1) and phosphorylated IRS-1 (pIRS-1) in liver tissues of group 4 increased compared with those of groups 2 and 3. On the other hand, the expressions of pAkt, pIKKbeta and pNF-kappaB decreased compared with those of groups 2 and 3. From these results, EGCG reduces inflammation, insulin resistance and oxidative stress, and suppresses liver injury in nSREBP-1c transgenic mice.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adipose Tissue; Animals; Catechin; Deoxyguanosine; Fatty Liver; Insulin Receptor Substrate Proteins; Insulin Resistance; Liver; Mice; Mice, Transgenic; Sterol Regulatory Element Binding Protein 1

Oxidative stress is associated with atherosclerosis. Familial combined hyperlipidemia (FCH) is considered as a human model of primary dyslipidemia and atherosclerosis frequently associated with insulin resistance (IR), but there are few data on its possible relation to oxidative stress. The objective of this study was to evaluate oxidative stress status using different markers in subjects with FCH assessing its possible correlation with anthropometric parameters and IR. This was a cross-sectional study. A cohort of 40 FCH patients (20 with IR (HOMA>or=3.2) and 20 without IR (HOMA<3.2)), and 20 healthy volunteers were included, all of them non-diabetic, normotensive and non-smokers. We measured lipid profile, glucose and insulin levels in plasma, HOMA, and representative indicators of oxidative stress such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), reduced glutathione (GSH), oxidized glutathione (GSSG) and GSSG/GSH ratio in mononuclear cells. All parameters were determined at basal conditions with standard methodology in the three groups. All FCH subjects showed an increased status of oxidative stress compared to the control group. When the impact of IR was investigated, significant differences between groups were observed in terms of increased levels of 8-oxo-dG, GSSG and GSSG/GSH ratio in FCH subjects with IR indicating higher levels of oxidative stress in these patients. Correlation studies showed that 8-oxo-dG and GSSG/GSH ratio are independently related to IR with odds ratio of 3.5 and 7.4, respectively. We conclude that FCH is related to oxidative stress, especially in the presence of IR.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Atherosclerosis; Deoxyguanosine; Female; Glutathione; Glutathione Disulfide; Humans; Hyperlipidemia, Familial Combined; Insulin Resistance; Lipids; Male; Middle Aged; Oxidative Stress

Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone and is a new clinically available class of agents for improving of insulin resistance in both animals and humans with type 2 diabetes. These studies aimed to determine whether long-term treatment with a long-acting GLP-1 analog, exendin-4, delayed the progression of diabetes. Male db/db mice and db/m mice at 8 wk of age were treated with exendin-4 for 8 wk, whereas the control db/db mice received only vehicle. Urinary albumin excretion was significantly decreased in db/db mice that were treated with 1 nmol/kg exendin-4 compared with those in db/db mice that were treated with 0.5 nmol/kg exendin-4 and control db/db mice (P < 0.005). Intraperitoneal glucose tolerance test was improved in db/db mice that were treated with 1 nmol/kg exendin-4 compared with other groups (P < 0.05). Despite this, fasting blood glucose, glycated hemoglobin, and creatinine concentrations were not significantly different among db/db mice. Renal histology studies further demonstrated that glomerular hypertrophy, mesangial matrix expansion, TGF-beta1 expression, and type IV collagen accumulation and associated glomerular lipid accumulation were significantly decreased in db/db mice that were treated with 1 nmol/kg exendin-4. Furthermore, there were fewer infiltrating inflammatory cells and apoptotic cells in the glomeruli of db/db mice that were treated with 1 nmol/kg exendin-4 compared with those in the other groups accompanied by an increase in the renal immunoreactivity of peroxisome proliferator-activated receptor alpha and GLP-1 receptor-positive cells and a decrease in 24-h urinary 8-hydroxy-deoxyguanosine levels (P < 0.01, respectively) along with decreases in lipid content. Taken together, exendin-4 treatment seems to ameliorate diabetic nephropathy together with improvement of the metabolic anomalies. These results suggest that exendin-4 could provide a therapeutic role in diabetic nephropathy that results from type 2 diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Caspase 3; Creatinine; Deoxyguanosine; Diabetic Nephropathies; Exenatide; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Insulin Resistance; Kidney; Lipids; Male; Mice; Mice, Inbred C57BL; Peptides; PPAR alpha; Receptors, Glucagon; Systole; Transforming Growth Factor beta1; Venoms

To evaluate the association between the C242T polymorphism of the p22 phox gene, an essential component of NAD(P)H oxidase in the vasculature, with intima-media thickness (IMT) of the carotid artery and risk factors for atherosclerosis in type 2 diabetic subjects.. C242T polymorphism of the p22 phox gene was detected by polymerase chain reaction-restriction fragment-length polymorphism in 200 Japanese type 2 diabetic subjects and 215 nondiabetic subjects. We examined the association with this mutation and carotid atherosclerosis as well as the patients' clinical characteristics and the level of 8-hydroxy-2'deoxyguanosine (8-OHdG) as an index of oxidative DNA damage.. The diabetic subjects with the TC+TT genotypes displayed a significantly lower average IMT (1.13 +/- 0.31 vs. 1.31 +/- 0.34 mm; P = 0.0099) and a not significantly lower serum 8-OHdG level than those with the CC genotype, despite no difference in the risk factors. Stepwise multiple regression analysis showed that the risk factors for increased IMT in the diabetic subjects were systolic blood pressure (P = 0.0042) and p22 phox CC genotype (P = 0.0151). In nondiabetic subjects, the average IMT of the TC+TT group was not different from that of the CC group (0.85 +/- 0.14 vs. 0.94 +/- 0.30 mm, P = 0.417). Fasting plasma insulin concentration (41.4 +/- 15.6 vs. 64.2 +/- 59.4 pmol/l, P = 0.0098) and insulin resistance index of homeostasis model assessment (HOMA-R) (1.58 +/- 0.66 vs. 2.60 +/- 2.56, P = 0.0066) were significantly lower in the TC+TT group than in the CC group.. These results show that the C242T mutation in the p22 phox gene is associated with progression of asymptomatic atherosclerosis in the subjects with type 2 diabetes and is also associated with insulin resistance in nondiabetic subjects.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Asian People; Carotid Arteries; Carotid Artery Diseases; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Insulin; Insulin Resistance; Japan; Male; Membrane Transport Proteins; Middle Aged; NADPH Dehydrogenase; NADPH Oxidases; Phosphoproteins; Polymorphism, Genetic; Risk Factors; Tunica Intima; Tunica Media; Ultrasonography

Over the years, several lines of evidence have emerged supporting the role of oxidative stress in the development of diabetic complications. This could involve the increase in the production of reactive oxygen species and the decrease in antioxidative defense systems. Modulation of the level of intracellular reactive oxygen species is likely to affect the intracellular redox homeostasis, which is crucial for numerous biological events such as the transcriptional activation of genes. In this work we studied the binding of the redox transcription factors Sp1 and NF-kappaB extracted from kidney and liver of streptozotocin diabetic (STZ) and fructose-fed rats using electrophoretic mobility shift (EMSA) assay. In addition, the level in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) was assessed within DNA by high performance liquid chromatography with electrochemical detection (HPLC-EC). A decrease in the affinity of Sp1 to DNA was observed in the kidney of STZ rats and fructose-fed rats (15% +/- 8.3 and 54% +/- 6.9, respectively, versus control group set to 100%). This was also found to occur to a lower extent, in the liver. Interestingly, higher levels of 8-oxodGuo, a biomarker of DNA oxidation, were measured in the kidney of diabetic rats. Therefore, the modification in the binding efficiency of Sp1 or NF-kappaB could be related to reactive oxygen species-mediated DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Chromatography, High Pressure Liquid; Deoxyguanosine; Diabetes Mellitus, Experimental; Diet; DNA; Fructose; Insulin Resistance; Kidney; Liver; Male; NF-kappa B; Oxidation-Reduction; Rats; Rats, Wistar; Reactive Oxygen Species; Sp1 Transcription Factor