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

Diabetic patients with hypertriglyceridemia frequently develop atherosclerosis. Because superoxide (O2-) is suspected to play an important role in the initiation of atherosclerosis, we investigated whether an abnormal amount of O2- was produced by circulating mononuclear cells of patients with both diabetes mellitus and hypertriglyceridemia. The rate of production of superoxide dismutase-inhibitable O2- was measured when cells were stimulated by either 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) or by opsonized zymosan (OZ). In addition, the rates of O2- production by mononuclear cells drawn from three other groups (normal, solely diabetic, and solely hypertriglyceridemic) were determined. We found that the rate of O2- production by mononuclear cells from the diabetic hypertriglyceridemic group was significantly higher than that from normal, diabetic, and hypertriglyceridemic groups. When the rates of O2- production by mononuclear cells were plotted against the levels of plasma triglyceride for all individuals tested, they correlated positively (r = .73 in PMA stimulation and r = .79 in OZ stimulation, P less than .01). However, the rate of O2- production did not relate to other parameters, i.e., plasma cholesterol level, hemoglobin A1 level in erythrocytes, and the molar ratio of free cholesterol to phospholipid in mononuclear cells. Thus, we concluded that the observed elevated rate of O2- production in the diabetic hypertriglyceridemic mononuclear cells was a reflection of a hypertriglyceridemic condition and was not unique to the diabetic hypertriglyceridemic condition. Also, O2- may be involved in the pathogenesis of atherosclerosis in diabetic hypertriglyceridemic patients when atherogenic factors specific to diabetes are concomitantly present.
Diabetes 1988 Jun
PMID:Increased superoxide production by mononuclear cells of patients with hypertriglyceridemia and diabetes. 283 56

Amino sugars such as galactosamine are hepatotoxic. It has been verified that toxic hepatitis induced by galactosamine is similar to that of CCl4 poisoning, and that both were inhibited by O2* scavengers. Fructosamine results from the union of glucose with the epsilon-amine of lysine. A test for fructosamine quantification is based on nitroblue tetrazolium (NBT) reduction, in which O2- is involved, the reduction being inhibited in the presence of superoxide dismutase (SOD). Given these facts, we attempted to elucidate if galactosamine and glucosamine reduce NBT and if that reduction is inhibited by SOD. This was confirmed. Subsequently, we incubated aminoacids (glycine, lysine, alanine) with glucose and galactose for 7 days and studied the action of the incubation products on NBT, using amino acids and sugars as controls. We found that NBT reduction increases proportionally to the length of incubation time of glucose/galactose with lysine, but not with other amino acids. Reduction of NBT by the Amadori compounds formed is inhibited by SOD. We suggest that oxygen radical generation by Amadori compounds must be taken into consideration as one cause of damage in diabetes of long duration.
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PMID:Oxygen radical generation by Maillard compounds. 283 94

Several D-sugars were incubated with L-lysine or with L-arginine for 10 days. The resulting compounds are able to reduce nitrobluetetrazolium (NBT). This is prevented by superoxide dismutase (SOD), indicating that the superoxide radical is generated by the resulting Amadori compounds. The formation of superoxide radical in vivo, as a result of nonenzymatic glycosylation of proteins, may be considered to be a contributory factor to the appearance of chronic complications of diabetes.
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PMID:Superoxide radical generation by Amadori compounds. 285 11

Acetyl-homocysteine-thiolactone (CYT) is an organic thio compound that exerts free radical scavenger activity and increases superoxide dismutase (SOD) activity. Administration of 32 mg CYT/kg body wt/day/30 days in rats increased SOD activity in erythrocytes by 126%, and in pancreatic islets by 202%. Treatment affected only the Cu-Zn fraction of the enzyme. Transmission electron microscope observations showed that the damage to the pancreatic beta cells induced by single or multiple subdiabetogenic doses of streptozocin (STZ) (45 mg/kg body wt) was attenuated in animals treated with CYT. This protective effect was not observed with 65 mg of STZ. The experimental results seem to support the hypothesis that pancreatic beta cells are particularly vulnerable to the effect of oxygen radicals and that the cytotoxic effect of STZ is related to free radical-induced peroxidation.
Diabetes 1986 Apr
PMID:Acetyl-homocysteine-thiolactone-induced increase of superoxide dismutase counteracts the effect of subdiabetogenic doses of streptozocin. 293 74

Diabetes produced spontaneously in the BB rat is similar to that observed in multiple low dose streptozocin-induced diabetes, both being characterized histologically by a lympho-monocytic infiltrate in the pancreatic islets (insulitis). Recent studies indicated that streptozocin acts through peroxidative patterns sensitive to superoxide dismutase (SOD) activity. We therefore conducted a time-course study to evaluate if SOD activity in the islets of Langerhans is related to the onset of diabetes in BB rats with varying degree of diabetes. It was found that SOD activity does not change with age nor with the onset of diabetes. However SOD activity in the islets of BB rats was significantly lower than in the control Wistars. This lower SOD activity may be a proneness factor that favors the development of the diabetic syndrome.
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PMID:Superoxide dismutase activity in the BB rat: a dynamic time-course study. 305 4

The activity of aortic glutathione peroxidase, a selenium-dependent enzyme, significantly decreased in rats 4 and 8 months after the injection of streptozotocin (STZ). Catalase activity was shown to occur at low levels in rat aorta and was not influenced by the diabetic state. Superoxide dismutase activity was less than detectable. The activity of selenium-dependent glutathione peroxidase in kidney, but not in lung and liver, increased in diabetic rats. Catalase and superoxide dismutase activities in the kidney were not altered. The plasma lipid peroxide value increased in diabetic rats. The selenium content in plasma of diabetic rats increased markedly while the increase in plasma glutathione peroxidase activities was insignificant. The observed abnormalities in plasma of STZ rats were improved by insulin treatment. The defects in glutathione peroxidase in the diabetic rat aorta were restored by insulin treatment. These results may suggest that the capacity of the antioxidative defense system in the aorta decreased in the diabetic state, and this may help clarify the mechanism of the pathogenesis of endothelial dysfunction associated with diabetes.
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PMID:Alterations of the plasma selenium concentrations and the activities of tissue peroxide metabolism enzymes in streptozotocin-induced diabetic rats. 321 28

Human erythrocytes contain glycosylated and nonglycosylated Cu-Zn-superoxide dismutases which can be separated by boronate affinity chromatography. The percentage of the glycosylated form is significantly increased in the erythrocytes of the patients with diabetes as compared to normal erythrocytes. The nonglycosylated Cu-Zn-superoxide dismutase, which was washed through the boronate column, was glycosylated in vitro upon exposure to radioactive or nonradioactive D-glucose. Incorporation of D-glucose into the protein was observed, and with increase in glycosylation, the enzymatic activity decreased, indicating that the glycosylation of the enzyme led to low active form. The sites of glycosylation of the superoxide dismutase were identified by amino acid analysis after reverse-phase high performance liquid chromatography of the trypsin-treated peptides.
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PMID:[Biochemical study on nonenzymatic glycosylation of human erythrocyte Cu-Zn-superoxide dismutase]. 324 72

B-cells have previously been shown to be very susceptible to damage induced by superoxide radicals, and protection against such damage has been achieved both in vitro and in vivo with superoxide dismutase. During maturation, db/db mice develop diabetes and accumulation of potentially superoxide radical-producing leucocytes can be demonstrated in the islets during the process. To test for the possibility that superoxide radical-induced damage contributes to the development of diabetes, db/db mice were given daily ip injections of 200 mg/kg polyethylene glycol-substituted CuZn superoxide dismutase. No effect of the treatment could be demonstrated.
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PMID:No effect of superoxide dismutase on spontaneous development of diabetes in db/db mice. 328 95

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9-12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status. Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.
Diabetes 1987 Sep
PMID:Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment. 330 71

Tissue antioxidant status in insulin-dependent spontaneously diabetic BB Wistar rats (ISDBB), diabetes-prone nondiabetic littermates (NDLM), and weight-matched non-BB control Wistar rats was investigated in pancreas, heart, and liver, as well as kidney. Pancreatic activities of CuZn-superoxide dismutase and glutathione reductase (GSSG-RD) were higher in ISDBB rats, while catalase (CAT) activities were elevated in both ISDBB and their NDLM compared with control animals. On the other hand, pancreatic reduced glutathione (GSH) levels were decreased in both ISDBB and NDLM rats. Cardiac tissues of ISDBB rats had higher activities of CAT and GSSG-RD and elevated levels of GSH compared with weight-matched control rats. Hepatic GSH levels in both ISDBB and their NDLM were lower than those of control rats. ISDBB rats showed higher renal activities of glutathione peroxidase compared with control rats. Our results demonstrate the presence of alterations in tissue antioxidant status in BB Wistar rats (both diabetic BB rats and their diabetes-prone nondiabetic littermates). The fact that most of the enzyme changes present in BB rats with overt diabetes paralleled those we have previously reported in rats with uncontrolled streptozotocin-induced diabetes and the fact that the latter alterations were corrected with insulin therapy suggest that the alterations in diabetic BB rats were probably related to suboptimal insulin therapy. The significance of the alterations in antioxidant status seen in the nondiabetic BB animals is as yet unknown.
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PMID:Alterations in tissue antioxidant systems in the spontaneously diabetic (BB Wistar) rat. 332 63


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