Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of alloxan-induced diabetes on CuZn- and Mn-superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities, as well as the content of thiobarbituric acid reactive substances (TBARs) were examined in rat lymphoid organs (mesenteric lymph nodes (MLN), thymus and spleen) and, for comparison, red and white muscle fibres. The capacity for generation of reduced equivalents was also evaluated by measuring the activities of glucose-6-phosphate dehydrogenase (pentose-phosphate pathway-cytosol) and citrate synthase (Krebs cycle-mitochondria). Diabetes raised the capacity for the generation of reducing equivalents in the lymphoid organs: in the mitochondria of the thymus and spleen and in the cytosol of the mesenteric lymph nodes and thymus. In muscles, diabetes reduced CuZn-SOD activity in soleus and raised the activity in gastrocnemius, and depressed the activities of catalase in soleus and of glutathione peroxidase in both soleus and gastrocnemius. In relation to the lymphoid organs, the spleen showed a decrease in the antioxidant enzyme activities (except for glutathione peroxidase), whereas the thymus showed an increased level (except for Mn-SOD), and the MLN presented a reduction in Mn-SOD and catalase activities and an increase in GPX activity caused by diabetes. The content of TBARs in the tissues followed the changes in GPX activity inversely: i.e. a decrease in the lymphoid organs (except in the spleen) and an increase in the muscles of diabetic rats compared with the control group. All these changes found in diabetic rats were reversed by insulin treatment and were not modified by the normalization of glycaemia.
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PMID:Superoxide dismutase, catalase and glutathione peroxidase activities in the lymphoid organs of diabetic rats. 796 75

Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30-300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy.
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PMID:Evidence of oxidant injury and tubular damage in early diabetic nephropathy. 798 55

Extracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein that is the major SOD isozyme in extracellular fluids. It has previously been shown that EC-SOD levels in sera from healthy persons are clearly divided into two discontinuous groups: a lower group (named Group I, below 120 ng/ml) and a higher group (Group II, above 400 ng/ml). The family studies have shown that the high EC-SOD level in healthy persons is genetically transmitted. We report here on the EC-SOD levels in the sera of patients with various diseases. The EC-SOD levels were distinctly higher in patients with renal diseases and moderately higher in liver diseases and diabetes than those in normal healthy persons. In cerebrovascular diseases, heart diseases and acute digestive diseases, significant differences of EC-SOD were not observed. In patients with renal diseases, the increase of EC-SOD was accompanied by the lack of renal function. Serum EC-SOD in Group I healthy persons is known to be heterogeneous with regard to heparin affinity and can be separated into three fractions: A without affinity, B with weak affinity and C with relatively strong heparin affinity, whereas the EC-SOD in Group II is mainly one fraction of C-type. Also in the case of hemodialysis patients, serum EC-SOD in Group I or Group I' (approximately 120-400 ng/ml) was divided into three fractions. EC-SOD in Group II showed two different profiles on heparin-Sepharose column chromatographies: one consisted mainly of EC-SOD C and the other consisted of EC-SOD A and C. It is probable that the high serum EC-SOD level in hemodialysis patients was due to two possible factors: the genetic transmitted factor and unknown pathophysiological factor(s).
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PMID:Quantitative and qualitative changes of extracellular-superoxide dismutase in patients with various diseases. 798 42

An activity of erythrocyte SOD, HBA1C levels and FA activity have been determined in 17 patients with diabetes mellitus type I and 15 healthy subjects. It was found that the treatment of diabetes mellitus has no effect on the SOD activity.
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PMID:[Effect of diabetes mellitus therapy on activity of erythrocyte superoxide dismutase]. 800 69

The protective roles of metallothionein (MT) in streptozotocin (STZ)-induced pancreatic damage were investigated using zinc (Zn) as the inducer of MT synthesis in rats. Diabetes was produced in a group of Sprague Dawley rats by a single injection of STZ. In another group of rats, to induce the synthesis of MT, Zn was injected subcutaneously about 12 h before injection of STZ. Rats were sacrificed at about 30 h, 3 and 6 weeks after administration of STZ. The plasma glucose levels in STZ and Zn+STZ group increased significantly in 30 h, 3 and 6 weeks compared with the control group, but the level of glucose in Zn+STZ group was lower than that in the STZ group. Both Zn and MT levels increased in pancreas, liver, and kidney of rats injected with Zn or Zn+STZ. The induction of MT synthesis in pancreas of Zn-injected rats was also demonstrated by Western Blot analysis. Lipid peroxidation induced by STZ was inhibited significantly by pretreatment with Zn. Injection of STZ decreased the activities of superoxide dismutase (SOD) in plasma, liver and pancreas, but injection of Zn had no effect on the activities of SOD. The results support that pretreatment with Zn can partially prevent the development of diabetes induced by STZ injection and it may be related to the effects of MT as a scavenger for the oxygen free radicals.
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PMID:Protective effects of metallothionein on streptozotocin-induced diabetes in rats. 801 48

Oxidized lipoproteins may be important in the pathogenesis of atherosclerosis. Because diabetic subjects are particularly prone to vascular disease, and glucose autoxidation and protein glycation generate reactive oxygen species, we explored the role of glucose in lipoprotein oxidation. Glucose enhanced low density lipoprotein (LDL) oxidation at concentrations seen in the diabetic state. Conjugated dienes, thiobarbituric acid reactive substances, electrophoretic mobility, and degradation by macrophages were increased when LDL was modified in the presence of glucose. In contrast, free lysine groups and fibroblast degradation were reduced. Although loss of reactive lysine groups could be due to either oxidative modification or nonenzymatic glycation of apolipoprotein B-100, inhibition of lipid peroxidation by the metal chelator, diethylenetriamine pentaacetic acid, blocked the changes in free lysines. Thus, glycation of lysine residues is unlikely to account for the alterations in macrophage and fibroblast uptake of LDL modified in the presence of glucose. Glucose-mediated enhancement of LDL oxidation was partially blocked by superoxide dismutase and nearly completely inhibited by butylated hydroxytoluene. These findings indicate that glucose enhances LDL lipid peroxidation by an oxidative pathway involving superoxide and raise the possibility that the chronic hyperglycemia of diabetes accelerates lipoprotein oxidation, thereby promoting diabetic vascular disease.
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PMID:Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway. 804 Mar 32

A decrease in superoxide dismutase (SOD), the first cellular defence against free radicals, occurs at about the same time as the activation of macrophages within the islets of low-dose streptozocin (LDS)-treated mice. Furthermore, a decrease in the total islet capillary area also has been shown to occur by 10 days after the first streptozocin (STZ) injection and this decline in capillary area is concomitant with the activation of macrophages as is the fall in SOD. Intracellular levels of SOD have been shown to increase after administration of acetyl-homocysteine-thiolactone (citiolone); therefore, the aim of the present study was to observe any relationship between the citiolone-induced increase in SOD levels and islet microvasculature area during LDS-induced diabetes. C57BL6/J male mice were pretreated with daily intramuscular injections of 50 mg citiolone/kg body wt. for 30 days and were then rendered diabetic with 45 mg STZ/kg body wt. given for 5 days; citiolone was given until the animals were killed (days 6, 11 and 18 after the first STZ injection). Further animals were used as non-diabetic and diabetic (STZ-only) controls. The results show that LDS-treated animals when given citiolone: (1) were generally normoglycaemic; (2) had SOD levels that were higher than those of STZ-only control animals; (3) had an islet capillary area that was larger than that of LDS-treated mice. Therefore, the administration of a free radical scavenger, namely citiolone, is able partly to counteract and delay the reduction of islet vascular area and oedema formation in LDS-treated mice.
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PMID:An increase in superoxide dismutase counteracts islet vascular alterations in low-dose streptozocin-treated mice. 805 21

Several studies have shown impairment of endothelium-dependent relaxations as well as increased release of vasoconstrictor prostanoids in arteries from diabetic animals and humans. This impairment is restored towards normal by prostaglandin (PG) H2/thromboxane A2 receptor blockade or superoxide dismutase, indicating that the PGH2 and/or superoxide anion (O2-.) generated contributes to the abnormality. Of particular note is that PGH2 impairs endothelium-dependent relaxations and causes contractions by a mechanism that involves generation of O2-. in the endothelium. The effects of elevated glucose are exacerbated by increased aldose reductase activity leading to depletion of NADPH and generation of reactive oxidants. Because NADPH is required for generation of nitric oxide from L-arginine, the depletion of NADPH leads to reduced nitric oxide formation. In a manner similar to that observed with elevated glucose, oxygen-derived free radicals or activation of protein kinase C also cause impairment of endothelium-dependent relaxations, smooth muscle contractions, and release constrictor prostanoids, indicating that a common mechanism for the impairment of endothelial cell function may be operative in diabetes. In this review the cumulative effects of oxidative stress on diabetic endothelial cell dysfunction, together with the complex interrelationship of cyclooxygenase catalysis, protein kinase C activity, and flux through the polyol pathway, are considered.
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PMID:Free radicals in diabetic endothelial cell dysfunction. 806 1

Diabetic human patients and laboratory animals show abnormalities which can be observed also in enhanced lipid peroxidation (LPO) induced in vitro. It seemed to be necessary to demonstrate the presence of these processes also in dogs with experimentally induced alloxan diabetes. In a 5-day experiment, five 1 to 5-year-old dogs of mixed sex were examined. Blood samples were taken before the intravenous administration of 60 mg alloxan/kg body mass and then daily for a period of 5 days. After the administration of alloxan, the dogs became depressed and lost their appetite. Their urine contained varying concentrations of glucose detectable with a test strip. As compared to the physiological values, blood glucose concentration increased considerably throughout. Alanine aminotransferase (ALT) enzyme activity underwent an 8-fold increase by the 24th hour; subsequently, it remained practically unaltered. The malonyldialdehyde (MDA) concentration of red blood cell (RBC) haemolysate also rose with respect to the basal values. Glutathione-peroxidase (GSH-Px) activity increased only transiently, up to the second day of the experiment; subsequently, its activity dropped below the basal values. Similar changes were found in catalase activity, while the activity changes of superoxide dismutase (SOD) were identical in tendency to the above ones; in fact, it hardly showed any alterations. Besides the severe pancreatic and liver damage caused by alloxan, increased MDA production in the RBC haemolysate indicated enhanced peroxidation of polyunsaturated fatty acids, i.e. intensification of the LPO processes. The increase of GSH-Px and catalase activity, followed by their decrease was suggestive of changes in the enzymatic defence mechanism acting against free radicals.
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PMID:Changes of lipid peroxidation parameters in dogs with alloxan diabetes. 806 47

The aim of our research was elucidation of a relationship between red cell membrane lipid peroxidation (LPO) and antioxidant defense enzymes, on the one hand, and the age, disease duration, and presence of vascular complications in patients with type I diabetes mellitus, on the other. The possibility of correcting red cell peroxide status with human insulin preparations was investigated. Red cell membrane LPO was found increased more than twofold and antioxidant defense enzymes activities virtually unchanged vs. controls in 16 patients with diabetes aged 20 to 43. These characteristics of red cell peroxidation status do not depend on patients' age, disease standing, or presence of vascular complications. A twelve-week therapy with biosynthetic insulin resulted in complete normalization of LPO processes in patients with angiopathies aged under 35 and with disease standing of less than 10 years. In diabetics with angiopathies aged over 35 and disease standing of more than 10 years red cell MDA level reduced under the effect of therapy with human insulin preparations but was still increased vs. that in healthy donors by 1.5 times. Red cell GP and SOD activities reduced in the course of insulin therapy in all the examined groups of diabetics. Catalase activity increased by approximately 50% in patients with angiopathies, those aged over 35, and a disease standing of more than 10 years under the effect of insulin. In the rest groups of patients catalase activity did not differ from its initial level. Our results permit us recommending besides human insulin preparations antioxidant therapy for patients with vascular complications, those aged over 35, and a disease standing of more than 10 years.
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PMID:[Effect of biosynthetic insulin on lipid peroxidation in erythrocyte membranes in patients with type I diabetes mellitus]. 807 92


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