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

The role of oxidative/reductive balance derangement in the pathogenesis of diabetic microangiopathy has often been discussed in the last few years. Therefore, we decided to evaluate the influence of intensive insulin therapy on selected indicators of free radical production. The levels of plasma hydrogen peroxide (H2O2) and serum malonyldialdehyde (MDA) were estimated in 15 patients with Type 1 and 15 with Type 2 diabetes before and after 2 weeks of intensive treatment. The initial H2O2 and MDA levels in all cases were significantly higher than in controls. After 2 weeks of treatment, the values for both estimated parameters were significantly lower; however, they were still higher than in the control group. Our results seem to confirm the previous suggestions concerning the relation between metabolic disturbances and oxidative stress in diabetic patients.
Diabetes Res Clin Pract 1995 Mar
PMID:Metabolic control quality and free radical activity in diabetic patients. 755 1

To explore the mechanisms of inhibition of insulin secretion in pancreatic beta-cells by oxygen free radicals, we studied the effects of H2O2 on membrane currents using the patch-clamp technique. Exposure of beta-cells to H2O2 (> or = 30 mumol/l) increased the activity of ATP-sensitive potassium (K+ATP) channels without changing the single channel conductance in cell-attached membrane patches. Action currents observed during superfusion of 11.1 mmol/l glucose were suppressed. In inside-out membrane patches, the activity of K+ATP channels was not influenced by H2O2. In conventional whole-cell clamp experiments using a pipette solution containing 3 mmol/l ATP, H2O2 did not influence the membrane currents. However, H2O2 did activate the K+ATP channel current in perforated whole-cell clamp configurations. The increased K+ATP channel current was reversed by subsequent exposure to 11.1 mmol/l 2-ketoisocaproic acid. In cell-attached membrane patches, the K+ATP channel current evoked by exposure to 30 mumol/l H2O2 was inhibited by exposure to 11.1 mmol/l glyceraldehyde, whereas the channel was again activated by exposure to 0.3 mmol/l H2O2. Subsequent superfusion of 11.1 mmol/l 2-ketoisocaproic acid inhibited the channel; this effect was counteracted by exposure to 10 mmol/l H2O2. Transient inhibition of K+ATP channels with provocation of action potentials was observed after washout of 100 mumol/l H2O2 during superfusion of 2.8 or 11.1 mmol/l glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Aug
PMID:Involvement of ATP-sensitive K+ channels in free radical-mediated inhibition of insulin secretion in rat pancreatic beta-cells. 762 91

Diabetic complications are believed to arise, in part, through an increase in oxidative stress. We characterized antioxidant status in vascular tissue in untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) were measured. Sprague-Dawley rats with streptozotocin-induced diabetes were killed after 8 weeks of untreated hyperglycemia and compared with age-matched controls. Eight weeks of untreated diabetes resulted in a significant increase of tissue catalase in aorta, iliac artery, and femoral artery as compared with controls. No significant changes in either superoxide dismutase or glutathione peroxidase were observed in aorta, iliac artery, or femoral artery of diabetic animals. This increase in catalase in diabetic vascular tissue suggests increased oxidative stress due to chronic exposure to H2O2 in vivo. To assess the impact of islet transplantation on oxidative stress in vascular tissue, inbred Lewis strain rats were rendered diabetic with streptozotocin. After 8 weeks of untreated diabetes, rats received an intraportal islet isograft and were monitored for 4 subsequent weeks of euglycemia. Islet transplantation improved weight gain and normalized blood glucose and total glycosylated hemoglobin. While catalase was significantly increased in aorta and iliac artery at 8 and 12 weeks of diabetes, vascular catalase was restored to normal by islet transplantation. These data suggest that islet transplantation is an effective treatment strategy to minimize increased oxidative stress in diabetic vasculature.
Diabetes 1995 Aug
PMID:Peroxidative stress in diabetic blood vessels. Reversal by pancreatic islet transplantation. 762 92

Using a precise technique for measuring authentic plasma lipid hydroperoxides (ROOHs), we show that individuals with non-insulin-dependent diabetes mellitus (NIDDM) have higher levels of ROOH than do control subjects. ROOHs were measured by the ferrous oxidation with xylenol orange assay coupled with the selective ROOH reductant triphenylphosphine. Formation of the ferric xylenol orange complex was determined at 560 nm and calibrated against H2O2. For 22 individuals with NIDDM, a concentration of 9.04 +/- 4.3 mumol/l (mean +/- SD) ROOH was recorded. This concentration was higher (P < 0.0005 by separate-variance t test) than that of plasma ROOHs from control subjects (3.76 +/- 2.48 mumol/l). There was no difference between concentrations of plasma malondialdehyde measured as thiobarbituric acid-reactive material (TBARM) in NIDDM or control subjects (1.00 +/- 0.70 vs. 1.21 +/- 0.62 mumol/l, respectively; P > 0.1). A trend to lower vitamin E levels in the NIDDM group (9.03 +/- 3.31 vs. 10.31 +/- 5.02 micrograms/ml in control subjects) failed to achieve significance at the 95% confidence level. Plasma ROOHs in the diabetic group did not correlate with total plasma cholesterol, triglyceride, fasting glucose, HbA1, vitamin E, or TBARM levels. These data indicate that measurement of authentic ROOHs shows NIDDM to be associated with oxidative stress, which may be unrelated to abnormalities in lipid metabolism and glycemic control.
Diabetes 1995 Sep
PMID:Elevated levels of authentic plasma hydroperoxides in NIDDM. 765 28

The effects of glucose concentration on D-glucose oxidation and reduced nicotinamide adenine dinucleotide phosphate (NADPH) supply were studied during exposure of cultured human umbilical vein endothelial cells to hydrogen peroxide (H2O2). The activation of glucose oxidation via the pentose phosphate pathway (PPP), induced by exposure of cells to 200 mumol/l H2O2 for 1 h, was reduced by 50% (P < 0.01) in cells cultured for 5-7 days in 33 mmol/l D-glucose (HG) versus those cultured in 5.5 mmol/l D-glucose without (NG) or with (HR) 27.5 mmol/l D-raffinose. The intracellular NADPH content in HG cells, but not in NG or HR cells, was decreased by 42% (P < 0.01) by exposing cells to 200 mumol/l H2O2. The decrease in NADPH was dependent on D-glucose concentration in the medium and was prevented in glutathione (GSH)-depleted cells. The latter observation suggests that the decrease in NADPH is associated with activation of the GSH redox cycle. In the presence of 200 mumol/l H2O2, lactate release into the medium, NADH/NAD ratio, and phosphofructokinase activity in HG cells were 56, 53, and 68% greater, respectively, than in the NG group, which indicates that inhibition of glycolysis by H2O2 is less marked in the HG group compared with NG group. These results indicate that activation of the PPP was impaired in endothelial cells cultured under conditions of high-glucose and oxidative stress, resulting in a decreased supply of NADPH to various NADPH-dependent pathways, including the GSH redox cycle.
Diabetes 1995 May
PMID:Impaired activation of glucose oxidation and NADPH supply in human endothelial cells exposed to H2O2 in high-glucose medium. 772 9

The preventive effect of antioxidant on the islet cell destruction in NOD mice was studied. Oral administration of probucol prevented the development of cyclophosphamide induced diabetes in NOD mice (incidence of diabetes; probucol: 0/10 vs. control: 9/15) As in vitro studies, the effects of probucol on the generation of H2O2 in the content of H2O2 in islet cells co-cultured with M phi were measured. Intracellular oxidation of 2'7'-dichlorofluorescin by H2O2 was analyzed by flow cytometry. The probucol-treated M phi induced less marked increase of H2O2 in islet cells in comparison with control M phi. The generation of H2O2 by M phi in islet cells from treated mice was less marked than that in controls. These results suggest that the preventive effect of probucol may be mediated by protection of islet cells from oxidative stress induced by M phi.
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PMID:Antioxidant, probucol, can inhibit the generation of hydrogen peroxide in islet cells induced by macrophages and prevent islet cell destruction in NOD mice. 773 89

Low-density lipoproteins (LDL) oxidized by oxygen radicals are a potent atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor, and could induce foam cell transformation. Post-translational nonenzymatic glycosylation of low density lipoprotein (LDL) occurs in vivo in diabetic patients. Glycosylated LDL (glcLDL) is degraded by macrophages in part by the classic LDL-receptor and in part by the scavenger receptor. This latter mechanism may contribute to the formation of foam cells and acceleration of atherosclerosis in diabetes mellitus. Oxygen free radicals (ORs) could induce LDL peroxidation and subsequent formation of foam cells. Glycosylation may alter protein conformation. A free radical is any chemical species that has an unpaired electron. This property renders it highly chemically reactive. When a radical reacts with a non radical another free radical is generated. This characteristic enables radicals to trigger chain reactions. Oxygen radicals are: superoxide anion (.O2-), hydroxyl radical (.OH) and hydrogen peroxide (H2O2). Thus, the aim of this study was to investigate whether glcLDL are susceptible to peroxidative modification by ORs. GlcLDL was prepared incubating LDL with 40 mM glucose in sterile phosphate-buffer-EDTA 1 mM for 10 days at 37 degrees C. Control LDL (cLDL) was similarly incubated with buffer but without glucose. After this preparation both forms of LDL were oxidized by CuSO4 (15 microM for 20 hours at 37 degrees C) or by xanthine/xanthine oxidase (X:2 mM/XO: 100 mU for 20 hours at 37 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The peroxidation of human glycosylated low-density lipoproteins is mediated by the superoxide radical: the protective effects of superoxide dismutase]. 808 16

To determine whether increased oxidative stress in diabetes mellitus is due to an impaired free-radical scavenger function in endothelial cells, GSH-dependent H2O2 degradation in human umbilical vein endothelial cells was studied. The GSH-dependent, NaN3-uninhibitable H2O2-degradation in endothelial cells was reduced by 48% (p < 0.001) when the cells were exposed to 33 mmol/l D-glucose vs 5.5 mmol/l D-glucose. This impairment was dependent not only on the D-glucose concentration in the medium but also on D-glucose specific metabolism, since neither 27.5 mmol/l L-glucose nor 27.5 mmol/l D-raffinose had any effect on the peroxide degradation activity. Activation of the glutathione redox cycle by H2O2 in cells exposed to high glucose concentrations was attenuated as compared with 5.5 mmol/l D-glucose because of: 1) a 42% decrease (p < 0.001) in intracellular NADPH content, and 2) a 34% reduction (p < 0.01) in glutathione release into the media. This results in an accumulation of GSSG in the cells following exposure to H2O2. Both H2O2-evoked 51Cr-release and H2O2-induced endothelial cell damage were significantly (p < 0.01) greater in the 33 mmol/l D-glucose group than in the 5.5 mmol/l D-glucose group. These results indicate that the abnormal glutathione redox cycle observed in endothelial cells is induced by high glucose concentrations in the medium, resulting in an impairment of reduced GSH-dependent H2O2-degradation. These abnormalities may associate with the increased cellular damage following an exogenous exposure to H2O2.
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PMID:Abnormal glutathione metabolism and increased cytotoxicity caused by H2O2 in human umbilical vein endothelial cells cultured in high glucose medium. 817 40

Reactive oxygen species such as superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxy radical (OH) possess potent oxygen toxicity to cells. Superoxide dismutases (SODs) are metalloenzymes that are essential for dismutation of O2- to H2O2 and O2. SODs are important initial components in the cellular defense against oxygen toxicity since O2- can react with H2O2 to generate single oxygen and hydroxy radicals, which are even more reactive and cytotoxic than O2- or H2O2. In mammalian tissues three superoxide dismutases (SODs) designated Cu,Zn-SOD, Mn-SOD and extracellular SOD exist. These enzymes play an important role in the antioxidant defense system against superoxide anion (O2-) generated in vivo and may be involved in various pathophysiological processes including inflammation, cancer diabetes, aging and ischemia. (1) The role of superoxide anion in ovulation and luteal function was investigated the localization of Cu, Zn-SOD and Mn-SOD in rat and human ovary by immunohistochemical methods. Cu,Zn-SOD was present in granulosa cells of mature Graafian follicles and growing follicles and Mn-SOD was present in luteal cells of the corpus luteum in rat. (2) To investigate the relationship between active oxygen radical-scavenge system and ovulatory mechanism in human. Mn-SOD was found in granulosa cells and theca cells of mature follicles, luteal cells of corpus luteum and epithelial cells of fallopian tubes. Cu,Zn-SOD was localized in theca cells of mature follicles, margin of corpus luteum and epithelial cells of tubal isthmus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Oxygen radicals-superoxide dismutase system and reproduction medicine]. 837 Oct 13

Glucose metabolism and respiratory burst were studied in vitro in resident peritoneal macrophages from non-diabetes-prone BB, spontaneously diabetic BB, diabetes-prone BB, and STZ-induced diabetic BBn rats, in the presence or absence of phorbol myristate acetate plus ionomycin. Glycolysis and pentose phosphate pathway activity were increased in BBd compared with BBn cells. PMA plus IONO did not influence glycolysis in BBn macrophages and slightly decreased it in BBd macrophages. In contrast, PMA plus IONO increased the pentose phosphate pathway activity in BBn and BBd macrophages with a much greater increase in BBd cells. The release of O2- was greater in BBd than BBn cells; PMA plus IONO also induced a much greater release of O2- in BBd cells. H2O2 release was undetectable in unstimulated BBn cells, and stimulation by PMA plus IONO caused a small incremental release. In contrast, the release of H2O2 was measurable in unstimulated cells and further increased by 50% in BBd cells with PMA-plus-IONO stimulation. The release of O2- and H2O2 was increased in macrophages from 75-day-old BBdp rats but not in 50-day-old BBdp rats, compared with age-matched BBn rats. No differences were observed in either glucose metabolism or release of O2- and H2O2 between BBn and STZ-BBn cells in the absence or presence of PMA plus IONO. These data suggest that enhanced oxidative metabolism in BBd macrophages is unlikely to be attributable to diabetes per se.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Apr
PMID:Enhanced glucose metabolism and respiratory burst in peritoneal macrophages from spontaneously diabetic BB rats. 838 32


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