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

Diabetes was induced in rats by an injection of streptozotocin (55 mg/kg). Endothelium-dependent relaxations in mesenteric resistance arteries (luminal diameter 210 +/- 20 microns) of control and diabetic rats were compared in myographs. Acetylcholine induced endothelium-dependent relaxations that were mediated by nitric oxide (EDNO). EDNO-mediated relaxations were impaired in diabetic arteries; concentrations of acetylcholine required to produce 50% relaxation (ED50) of activated arteries were 5 nM in control and 13.5 nM in arteries from diabetic rats studied after 6 wk (P < 0.05). The impairment in relaxation worsened with duration of the diabetes; ED50 for acetylcholine increased to 63 and 100 nM in diabetic arteries studied after 16 and 24 wk of diabetes, respectively. NG-nitro-L-arginine produced 5.5- and 16-fold decreases in sensitivity of control and diabetic arteries to acetylcholine. NG-nitro-L-arginine produced at least as much inhibition of acetylcholine relaxations in diabetic arteries, indicating that the impaired relaxation noted in diabetic arteries does not result from decreased production of EDNO. EDNO-mediated relaxations in diabetic arteries were impaired by increased production of endothelium-derived free radicals. Superoxide dismutase, a scavenger of superoxide anion, and dimethylthiourea, a scavenger of hydroxyl radicals, normalized EDNO-mediated relaxations in diabetic arteries. The ED50 values for acetylcholine were 13.5, 5.5, and 4 nM for untreated and SOD- and DMTU-treated diabetic arteries, respectively (P < 0.05 for treated vs. untreated arteries). Superoxide anion and hydroxyl radicals appear to block EDNO-mediated relaxation by inactivating EDNO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: role of free radicals. 816 Aug 18

Low-dose streptozocin-treated (LDS) mice were administered an inhibitor of lipid peroxidation, U-83836-E (a derivative of vitamin E), in order to observe its ability to alter the onset of diabetes. Ten or 20 mg/kg body wt. per day of U-83836-E were given to mice for 7 days and they were killed after 21 days. Results revealed that there was a significant increase in glycaemia in treated groups up to day 14 after which no further increase was noticed. Superoxide dismutase (SOD) assay showed that: (1) the LDS treatment significantly reduces SOD activity when compared with untreated controls (P < 0.005); (2) U-83836-E increases SOD levels (when compared with untreated controls); and (3) U-83836-E counteracts LDS treatment, since SOD activity is significantly higher with respect to that found in LDS-controls (P < 0.05), and SOD levels were significantly higher with respect to that found in Group 2 animals (P < 0.05), but significantly lower with respect to those found in groups 3 and 4 (P < 0.005). Moreover, malondialdehyde (MDA), the end-product of lipoperoxidation, was found at much higher levels in LDS controls than in the other groups and the lowest values were found in U-83836-E controls and in normoglycaemic animals treated with both streptozocin and U-83836-E. Morphological observations demonstrated that islet beta cells were of normal appearance in normoglycaemic animals of the treated groups. In conclusion, the in vivo inhibition of lipid peroxidation by this compound produces a limited but significant prevention of the islet beta cell destruction.
Diabetes Res Clin Pract 1995 Dec
PMID:The vitamin-E derivative U-83836-E in the low-dose streptozocin- treated mouse: effects on diabetes development. 886 55

Free radicals are thought to be involved in the pathogenesis of many disease states such as diabetes, cataractogenesis, cancer, and aging. Involvement of free radicals in most of these disorders, especially diabetic cataractogenesis, however, is derived from indirect evidence only. The purpose of this study was to directly detect the free radicals generated in lens homogenate incubated under hyperglycemic conditions. We investigated the generation of free radicals in lens homogenates incubated with 5.5 or 50 mM glucose containing the spin trap 5,5'-dimethyl 1-pyroline-N-oxide. The spin adducts were identified by electron spin resonance (ESR) spectroscopy and modulation of the levels of the spin adducts was achieved by including various antioxidants and metal chelators. Increased ESR signals were observed in the homogenates incubated with 50 mM glucose compared to those incubated with 5.5 mM glucose. The results show that the principal spin adduct has hyperfine splitting constants of a(N) = 1.41 +/- 0.01 mt and a(N) = 2.02 +/- 0.02 mt, indicating that these signals are due to carbon-centered free radicals. Superoxide dismutase, catalase, Trolox, and diethylenetriamine pentaacetic acid inhibited the signals while EDTA enhanced them. Based upon the results obtained by the inclusion of various modulators, it is concluded that the generation of the free radicals is mediated by a metal-derived Fenton type reaction.
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PMID:Glucose-dependent formation of free radical species in lens homogenate. 890 97

Streptozotocin induces severe and irreversible hyperglycaemia in experimental animals. The effect of oral administration of D-400 (1 gm/kg/day), a herbomineral formulation on streptozotocin induced-diabetes was studied in rats. Liver glycogen content was assayed biochemically on 2,4 and 8 weeks after D-400 treatment. Superoxide dismutase(SOD) activity of pancreatic islet cells was assessed on 8th week of D-400 treatment. The microscopic structure of pancreas and liver were examined in both control and treated animals. D-400 treatment showed progressive and significant increase in liver glycogen at 2,4 and 8 weeks respectively. Streptozotocin induced a decrease in pancreatic islet cell superoxide dismutase which was reversed by D-400 treatment for a period of 8 weeks. The free radical scavenging activity of D-400 may be attributed to shilajeet, one of its important ingredient. Streptozotocin induced histopathological changes in pancreas and liver was also partially reversed by D-400. The findings indicate that D-400 helps in improving the glycogen stores in the liver and prevents the streptozotocin induced damage through free radicals by increasing the islet cell superoxide dismutase activity.
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PMID:Effect of D-400, a herbomineral formulation on liver glycogen content and microscopic structure of pancreas and liver in streptozotocin induced diabetes in rats. 905 47

The goal of this study was to test the hypothesis that administration of superoxide dismutase restores nitric oxide synthase-mediated dilatation of the basilar artery during diabetes mellitus. We measured the diameter of the basilar artery in vivo in nondiabetic and diabetic rats (streptozotocin; 50-60 mg/kg i.p.) in response to nitric oxide synthase-dependent agonists (acetylcholine and bradykinin) and a nitric oxide synthase-independent agonist (nitroglycerin) before and during application of superoxide dismutase. Topical application of acetylcholine (1.0 and 10 microM) and bradykinin (1.0 and 10 microM) produced dose-related dilatation of the basilar artery in nondiabetic and diabetic rats. However, the magnitude of vasodilation produced by acetylcholine and bradykinin was significantly less in diabetic rats. Topical application of nitroglycerin (0.1 and 1.0 microM) produced similar dose-related dilatation of the basilar artery in nondiabetic and diabetic rats. Treatment with superoxide dismutase (150 U/ml) did not alter baseline diameter of the basilar artery in nondiabetic and diabetic rats. However, topical application of superoxide dismutase partially restored nitric oxide synthase-dependent dilatation of the basilar artery in diabetic rats towards that observed in nondiabetic rats. Superoxide dismutase did not alter dilatation of the basilar artery in nondiabetic rats. These findings suggest that impaired nitric oxide synthase-dependent dilatation of the basilar artery during diabetes mellitus may be related, in part, to enhanced release of oxygen-derived free radicals.
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PMID:Superoxide dismutase partially restores impaired dilatation of the basilar artery during diabetes mellitus. 923 36

Recent studies have suggested that the fetal dysmorphogenesis in diabetic pregnancies is associated with an increase in embryonic oxygen-free radicals. This excess of oxygen-free radicals may result from either overproduction or decreased clearance by the enzymatic scavenging mechanism. However, there are no in vivo data on the activity of embryonic oxygen-free radical scavenging enzymes. The purpose of the current study is to investigate whether this increase in embryonic oxygen-free radicals is the result of a change in the activity of the fetal oxygen-free radical scavenging/antioxidant enzymes during pregnancy complicated by maternal diabetes in an in vivo rat model. Thirty-six Sprague-Dawley rats were randomly assigned to one of two study groups: nondiabetic control and an untreated diabetic group. On day 12, fetuses were examined for crown-rump lengths, somite numbers, and external anomalies. The activity of fetal oxygen-free radical scavenging enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), were determined. The untreated diabetic group of rats had a significantly higher mean blood glucose level than that of the nondiabetic controls and also a significantly lower weight gain, higher resorption rate, smaller embryonic size with lower total protein content, and a approximately 6-fold increase in the rate of fetal neural tube defects compared to the nondiabetic controls. Superoxide dismutase activity was significantly reduced in the embryos with neural tube defects regardless of maternal diabetic status (2.25 +/- 0.83 vs. 1.17 +/- 0.04 u/mg protein; P < 0.05). Glutathione peroxidase and catalase activity were significantly reduced in malformed versus normal-formed embryos of nondiabetic mothers (GPX-2.68 +/- 1.15 vs. 4.46 +/- 1.12 mu/mg protein, CAT -1.67 +/- 0.53 vs 2.49 +/- 0.61 u/mg protein respectively; P < 0.01). However, overall catalase activity was increased in embryos of diabetic mothers as compared to controls. Two-way analysis of variance identified fetal malformations as the variance associated with reduced fetal SOD activity, whereas maternal diabetes was associated with the increase in fetal catalase activity. Neither neural tube defect nor maternal diabetes was found to be the variable affecting fetal GPX activity, Fetal oxygen-free radical scavenging enzymes respond differently to the adverse environment created by maternal diabetes during pregnancy. Defects in embryonic SOD and catalase activity, regardless of maternal diabetic status, may reduce the ability of the fetus to clear free oxygen radicals, thereby exposing it to an increased oxidative load that may cause fetal dysmorphogenesis. The diabetic state of the mothers did not decrease embryonic activity of any of the scavenging enzymes. Therefore, although excess oxidative load, as observed in diabetes, may cause tissue injury and embryopathy, the mechanism does not appear to be a diabetes-induced reduction in the action of the scavenging enzymes.
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PMID:Free radical scavenging enzymes in fetal dysmorphogenesis among offspring of diabetic rats. 948 43

This study was conducted on type 2 non-insulin-dependent diabetes mellitus (NIDDM) cases and healthy blood donors. Lipid peroxidation (LP) products in plasma and red blood cell (RBC) hemolysates were estimated as total thiobarbituric acid reactive substances (TTBARS). The plasma and hemolysate reduced and oxidized glutathione (GSH and GSSG) levels are compared. In the hemolysates the antioxidant enzymes namely superoxide dismutase (SOD), glutathione peroxidase (GPx-ase), glutathione reductase (GR-ase) and catalase (C-ase) are also compared. The RBC filtration characteristics are determined and compared with controls: 1. LP and GSH in diabetic plasma were significantly higher, but in the hemolysate the GSH raised but the LP was significantly lower in diabetics than in healthy controls. 2. Superoxide dismutase and C-ase were significantly higher in NIDDM hemolysate. Contrary the GPx-ase activity was significantly lower in diabetics. 3. The diabetic RBCs filtration characteristics are changed in respects significantly namely the Fi was lower, the Tc and CR were higher. It means higher rigidity and oxidative damage of the membrane of diabetic RBCs.
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PMID:Pro-, antioxidant and rheologic studies in the blood of type 2 diabetic patients. 970 4

The effect of superoxide dismutase, catalase, metal-chelating agents and hydroxyl radical scavengers on the toxicity of alloxan to isolated ob/ob mouse pancreatic islets in vitro has been compared with the reported ability of such substances to protect against alloxan diabetes in vivo. Superoxide dismutase and catalase protected beta-cells of isolated pancreatic islets against alloxan cytotoxicity, as did the hydroxyl radical scavengers dimethyl sulfoxide (DMSO) and butanol. However, 1,3-dimethylurea and thiourea, that are recognised as effective hydroxyl radical scavengers and that protect animals against the diabetogenic effects of alloxan, were without effect. Similarly, desferrioxamine, that inhibits hydroxyl radical formation from alloxan in chemically defined systems, did not protect against alloxan toxicity. Diethylenetriamine pentaacetic acid, which does not inhibit hydroxyl radical formation from alloxan, also gave no significant protection. The results indicate a role for superoxide radical and hydrogen peroxide in the mechanism of toxicity of alloxan but do not support the involvement of the hydroxyl radical in this process. Alternative explanations must be sought for the ability of hydroxyl radical scavengers and metal-chelating agents to protect against alloxan toxicity in vivo.
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PMID:Effect of superoxide dismutase, catalase, chelating agents, and free radical scavengers on the toxicity of alloxan to isolated pancreatic islets in vitro. 1038 Dec 3

The respiratory function and the antioxidant capacity of liver mitochondrial preparations isolated from Goto-Kakizaki non-insulin dependent diabetic rats and from Wistar control rats, with the age of 6 months, were compared. It was found that Goto-Kakizaki mitochondrial preparations presented a higher coupling between oxidative and phosphorylative systems, compared to non-diabetic preparations. Goto-Kakizaki mitochondria presented a lower susceptibility to lipid peroxidation induced by ADP/Fe2+, as evaluated by the formation of thiobarbituric acid substances. The decreased susceptibility to peroxidation in diabetic rats was correlated with an increase in mitochondrial vitamin E (alpha-tocopherol) content and GSH/GSSG ratio. Moreover, the glutathione reductase activity was significantly increased, whereas the glutathione peroxidase was decreased. Superoxide dismutase activity was unchanged in diabetic rats. Fatty acid analyses showed that the content in polyunsaturated fatty acids of Goto-Kakizaki mitochondrial membranes was significantly higher compared to controls. These results indicate that the lower susceptibility to lipid peroxidation of mitochondria from diabetic rats was related to their antioxidant defense systems, and may correspond to an adaptative response of the cells against oxidative stress in the early phase of diabetes.
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PMID:Decreased susceptibility to lipid peroxidation of Goto-Kakizaki rats: relationship to mitochondrial antioxidant capacity. 1049 69

Experiments were performed to test the hypothesis that the impact of endogenous nitric oxide (NO) on ANG II-induced renal arteriolar constriction is reduced in rats with insulin-dependent diabetes mellitus (65 mg/kg streptozotocin; STZ). Arteriolar diameter responses to exogenous ANG II were quantified before and during NO synthase inhibition (100 microM N(omega)-nitro-L-arginine; L-NNA) by using the in vitro blood-perfused juxtamedullary nephron technique. Afferent arteriolar lumen diameter averaged 20.7 +/- 2.0 micrometer in Sham kidneys and 25.9 +/- 1.3 micrometer in STZ kidneys (P < 0.05). Efferent arteriolar diameter did not differ between Sham and STZ rats. In kidneys from Sham rats, afferent and efferent arteriolar responses to ANG II (0.1-10.0 nM) were exaggerated significantly by L-NNA. L-NNA also augmented efferent arteriolar ANG II responses in kidneys from STZ rats (high-glucose bath) but did not alter ANG II responses in afferent arterioles from STZ rats. L-NNA also accentuated efferent, but not afferent, arteriolar ANG II responses in STZ kidneys during acute restoration of bath glucose to normal levels. Superoxide dismutase (150 U/ml) restored the ability of L-NNA to allow exaggerated afferent arteriolar responses to ANG II in kidneys from STZ rats. These observations indicate that superoxide anion suppresses the modulatory influence of endogenous NO on ANG II-induced afferent arteriolar constriction in diabetes mellitus.
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PMID:Superoxide anion curbs nitric oxide modulation of afferent arteriolar ANG II responsiveness in diabetes mellitus. 1066 34


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