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

Production of the superoxide radical anion O2-. and the nitric oxide radical NO-. by granulocytes was studied in 14 patients with type 2 diabetes without nephropathy, 21 patients with type 2 diabetes and diabetic nephropathy, and 19 healthy subjects, both without and after stimulation with opsonized zymosan. O2-. production by both resting and stimulated granulocytes was increased in type 2 diabetes patients without nephropathy but decreased in type 2 diabetes patients with nephropathy, compared with healthy subjects. NO. generation was highly augmented in type 2 diabetes patients without nephropathy by both resting and stimulated cells; values for type 2 diabetes patients with nephropathy were intermediate between the type 2 diabetes patients without nephropathy and the healthy subjects. These data point to granulocytes as one of possible sources of oxidative stress in type 2 diabetes.
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PMID:Production of superoxide and nitric oxide by granulocytes in non-insulin-dependent diabetic patients with and without diabetic nephropathy. 1069 Jun 52

Endothelial dysfunction has been proposed as an early manifestation of atherosclerosis. The risk for atherosclerosis is increased in patients with diabetes mellitus, but the mechanism of the increased risk in these patients remains to be elucidated. Emerging evidence suggests that postprandial hyperglycaemia and hyperlipidemia are important risk factors in the development of atherosclerosis in patients with diabetes. Using a high-resolution ultrasound technique, we evaluated the acute effects of oral glucose loading on endothelium-dependent flow-mediated dilation (EFMD) and endothelium-independent flow-mediated dilation (EIFMD) of the brachial artery in 11 men (mean age: 59 +/- 5 years) with type 2 diabetes without chronic complications of diabetes. During these examinations, changes in the level of superoxide anion formation in the neutrophils were also measured. In addition, to investigate the relationship between acute hypertriglyceridemia and EFMD, we assessed the effects of high- and low-fat meals on EFMD of the brachial artery in 12 healthy volunteers. EFMD was diminished after glucose loading (13.2% +/- 6.4%, 7.3% +/- 3.3%*, 12.8% +/- 5.6%, in fasting and at 1 and 2 hours, respectively; *P<0.001 vs fasting). Superoxide anion formation by neutrophils (expressed as 10(-7) nmol/10(6) cells/30 min) was increased after glucose loading (4.7 +/- 2.8 and 6.2 +/- 2.2, in fasting and at one hour, respectively; P<0.05). EIFMD and triglyceride concentrations were not significantly affected by glucose loading. EFMD was also decreased by high-fat feeding (13.1% +/- 4.3%, 7.7% +/- 3.7%*, 7.3% +/- 2.2%*, basal, 2 hours, and 4 hours, respectively; *P<0.01 vs basal). These decreases were reversed by vitamin E treatment. These results show that acute hyperglycaemia induced by 75 gm oral glucose intake and acute hypertriglyceridemia induced by high-fat feeding are implicated in endothelial dysfunction. In addition, these results suggest that chronic and repeated hyperglycaemia and hypertriglyceridemia may play important roles in the development and progression of vascular complications in diabetes, probably through increased oxidative stress.
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PMID:Endothelial dysfunction: its relationship with acute hyperglycaemia and hyperlipidemia. 1216 9

Oxygen free radicals have been implicated in beta-cell dysfunction and apoptosis associated with type 1 and type 2 diabetes mellitus. The roles of free radicals in diabetes have thus far been defined indirectly by monitoring oxidative tissue damage and the effects of antioxidants, free radical scavengers, and overexpression of superoxide dismutase. We employed the superoxide-mediated oxidation of hydroethidine to ethidium to dynamically and directly assess the relative rates of mitochondrial superoxide anion generation in isolated islets in response to glucose stimulation. Superoxide content of isolated islets increased in response to glucose stimulation. We next compared the oxyradical levels in Zucker lean control and Zucker diabetic fatty rat islets by digital imaging microfluorometry. The superoxide content of Zucker diabetic fatty islets was significantly higher than Zucker lean control islets under resting conditions, relatively insensitive to elevated glucose concentrations, and correlated temporally with a decrease in glucose-induced hyperpolarization of the mitochondrial membrane. Importantly, superoxide levels were elevated in islets from young, pre-diabetic Zucker diabetic fatty animals. Overproduction of superoxide was associated with perturbed mitochondrial morphology and may contribute to abnormal glucose signaling found in the Zucker diabetic fatty model of type 2 diabetes mellitus.
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PMID:Visualizing superoxide production in normal and diabetic rat islets of Langerhans. 1251 70

Metformin (1,1-dimethylbiguanide) is an antihyperglycaemic drug used to normalize glucose concentrations in type 2 diabetes. Furthermore, antioxidant benefits have been reported in diabetic patients treated with metformin. This work was aimed at studying the scavenging capacity of this drug against reactive oxygen species (ROS) like *OH and (O2*-)-free radicals. ROS were produced by gamma radiolysis of water. The irradiated solutions of metformin were analyzed by UV/visible absorption spectrophotometry. It has been shown that hydroxyl free radicals react with metformin in a concentration-dependent way. The maximum scavenging activity was obtained for concentrations of metformin > or = 200 micromol.L(-1), under our experimental conditions. An estimated value of 10(7) L.mol(-1).s(-1) has been determined for the second order rate constant k(*OH + metformin). Superoxide free radicals and hydrogen peroxide do not initiate any oxidation on metformin in our in vitro experiments.
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PMID:Radical-induced oxidation of metformin. 1560 61

Oxidative stress has been implicated in pancreatic beta-cell damage, insulin resistance and vascular function in diabetic patients and the dysfunction of antioxidant enzymes may be associated with the pathogenesis of diabetes. Extracellular superoxide dismutase (EC-SOD) is found in the extracellular matrix of tissues and the major scavenger of superoxide radical. To investigate the role of genetic variability for the pathogenesis of type 2 diabetes, we scanned the protein coding exon and flanking introns of EC-SOD gene for mutation in Japanese type 2 diabetic patients. We identified two missense mutations, Ala40Thr (GCG-->ACG) and Arg213Gly (CGG-->GGG), and a silent mutation, Leu53Leu (CTG-->TTG). For one of these variants, the Ala40Thr polymorphism, the frequency of Thr allele and the number of subjects with Thr allele (Ala/Thr+Thr/Thr) were higher in type 2 diabetic patients (n=205) than those in non-diabetic subjects (n=220) (33.2% versus 24.1%, p=0.003 and 55.6% versus 42.7%, p=0.008, respectively). The patients with Thr allele also showed earlier age at diagnosis of diabetes (42.2+/-7.8 years versus 44.4+/-6.9 years, p=0.037) and higher prevalence of hypertension (53.5% versus 38.5%, p=0.032) than those without the allele. Insulin sensitivity, furthermore, was evaluated in 71 type 2 diabetic patients with short insulin tolerance test (SITT). The patients with Thr allele showed lower insulin sensitivity (Kitt value of SITT) than those without the allele (1.78+/-0.78%/min versus 2.33+/-1.02%/min, p=0.012), although no significant differences in other clinical and biochemical characteristics were observed between two groups. These results suggest that the genetic variant of EC-SOD gene is associated with insulin resistance and the susceptibility to type 2 diabetes.
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PMID:Extracellular superoxide dismutase gene polymorphism is associated with insulin resistance and the susceptibility to type 2 diabetes. 1599 Jan 93

Oxidative stress is suggested to have an important role in the development of complications in diabetes. Because ozone therapy can activate the antioxidant system, influencing the level of glycemia and some markers of endothelial cell damage, the aim of this study was to investigate the therapeutic efficacy of ozone in the treatment of patients with type 2 diabetes and diabetic feet and to compare ozone with antibiotic therapy. A randomized controlled clinical trial was performed with 101 patients divided into two groups: one (n = 52) treated with ozone (local and rectal insufflation of the gas) and the other (n = 49) treated with topical and systemic antibiotics. The efficacy of the treatments was evaluated by comparing the glycemic index, the area and perimeter of the lesions and biochemical markers of oxidative stress and endothelial damage in both groups after 20 days of treatment. Ozone treatment improved glycemic control, prevented oxidative stress, normalized levels of organic peroxides, and activated superoxide dismutase. The pharmacodynamic effect of ozone in the treatment of patients with neuroinfectious diabetic foot can be ascribed to the possibility of it being a superoxide scavenger. Superoxide is considered a link between the four metabolic routes associated with diabetes pathology and its complications. Furthermore, the healing of the lesions improved, resulting in fewer amputations than in control group. There were no side effects. These results show that medical ozone treatment could be an alternative therapy in the treatment of diabetes and its complications.
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PMID:Therapeutic efficacy of ozone in patients with diabetic foot. 1619 34

Diabetes mellitus type 2 (T2DM) is a worldwide pandemic disease. T2DM and hypertension (HT) are closely related and classified as non-communicable diseases. These conditions represent as part of metabolic syndrome. Ageing is an independent risk factor of both diseases. Accumulation of reactive oxygen species (ROS) or imbalance of ROS and antioxidant system, which cause endothelial dysfunction (ED) through depletion of nitric oxide (NO), is likely to be the main risk factor in ageing, T2DM and HT. The organ that is rich in capillary blood supply like the islets of Langerhans and renal glomeruli, is theoretically prone to ED after long exposure to accumulation of various oxidants derived from dietary products, such as superoxide radical (O2-), hydroxyl radical (OH), malondialdehyde (MDA) and peroxynitrite (ONOO-), a potent long lived oxidant and cytotoxic. Preventive measures to correct imbalance of oxidant and antioxidation pathways and the sequential effects should be implemented since birth or childhood period by ways of proper diet, exercise, adequate supply of natural antioxidants and lifestyle modifications.
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PMID:Implications of microcirculation-research based information on prevention and treatment of diabetes mellitus type 2: a perspective. 1654 16

We examined the responses of basilar arteries taken from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model. Both the nitric oxide (NO)-mediated relaxation and the cyclic 3',5'-guanosine monophosphate (cGMP) production elicited by acetylcholine (ACh) were much weaker in OLETF rats than in age-matched control Long Evans Tokushima Otsuka (LETO) rats. The contraction induced by an NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine (L-NNA)] was weaker in the OLETF group. In that group, application of apocynin, an NAD(P)H oxidase inhibitor, normalized (i) ACh-induced relaxation, (ii) L-NNA-induced contraction, and (iii) ACh-induced cGMP production to the LETO levels. Superoxide anion production was greater in basilar arteries from OLETF rats than in those from LETO rats. The protein expression of gp91(phox), an NAD(P)H oxidase subunit, was upregulated in the OLETF arteries (versus LETO ones). These results suggest that the existence of endothelial dysfunction in basilar arteries in type 2 diabetes is related to increased oxidative stress mediated via NAD(P)H oxidase. Possibly, an impairment of NO-dependent relaxation responses and a basal impairment of NO signaling may be responsible for the increased risk of adverse cerebrovascular events in type 2 diabetes.
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PMID:Vascular NAD(P)H oxidase mediates endothelial dysfunction in basilar arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats. 1683 40

Superoxide, which mitochondria mainly produce in vascular endothelial cells, plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. Accordingly, mitochondrial functional differences are thought to be one of the most important factors for the risk of myocardial infarction among various individuals. In the present study, we surveyed mitochondrial haplogroups associated with myocardial infarction in Japanese subjects. The study population comprised 2,137 unrelated Japanese individuals, including 1,181 subjects with a first myocardial infarction (920 males, 261 females) and the control subjects (522 males, 434 females). Twenty-eight mitochondrial single nucleotide polymorphisms of 12 major mitochondrial haplogroups (A, B, D4, D5, F, G1, G2, M7a, M7b, M7c, N9a, and N9b) were determined by use of 28-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes. After adjustment for age, sex, body mass index, and prevalence of smoking, hypertension, hypercholesterolemia, and type 2 diabetes, a significantly (P = 0.0019) lower prevalence of haplogroup N9b was detected in subjects with myocardial infarction than in the controls. Especially, the prevalence of this haplogroup was significantly lower (P = 0.0007) in the male subjects with the disease than in the male controls. In contrast, there were trends towards higher prevalence of the disease in haplogroup G1 for males (P < 0.05). No significant haplogroup-related associations were detected for females. Our data suggest that haplogroup N9b confers resistance against myocardial infarction in Japanese males.
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PMID:Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese males. 1703 20

Angiotensin II (Ang II) is able to induce free radical generation in neutrophils, which is more elevated in neutrophils of patients with hypercholesterolemia (HC). In addition, the signal processing through angiotensin I (Ang I) receptors is altered. In present study, we compared the Ang II-triggered free radical generation of neutrophils obtained from patients with relatively isolated forms of metabolic syndrome (MS) with membrane-bound cholesterol content and membrane fluidity. We determined the enhancement of Ang II-induced superoxide anion and leukotriene C(4) (LTC(4)) generation, membrane fluidity and cell-bound cholesterol content of neutrophils obtained from 12 control subjects, 11 patients with obesity (Ob), 10 patients with type 2 diabetes mellitus (t2-DM) and 12 patients with HC. The alteration of signal processing was studied after preincubation with different inhibiting drugs. Superoxide anion, LTC(4) production and membrane rigidity were increased in the following order: control < Ob < t2-DM < HC. Both Ang II-induced superoxide anion and LTC(4) generation were decreased in control cells by pertussis toxin and fluvastatin (Flu), whereas in each patient group, mepacrin, verapamil and Flu were effective, suggesting alterations in signal pathways, which may be attributed to isoprenylation. The enhancement of superoxide anion and LTC(4) generation correlated significantly with membrane rigidity, independently from the experimental groups and membrane-bound cholesterol content. Membrane rigidity of neutrophils, obtained from patients with MS, plays a role in Ang II-induced free radical generation independent of intracellular cholesterol homeostasis.
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PMID:The association between angiotensin II-induced free radical generation and membrane fluidity in neutrophils of patients with metabolic syndrome. 1754 12


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