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

Previous studies from our laboratory have demonstrated the presence of complex alterations in the activities of antioxidant enzymes in various tissues of rats with streptozotocin (STZ)-induced diabetes. In the present investigation, it is shown that rats made diabetic with alloxan (ALX), an agent differing from STZ both chemically and in its mechanism of diabetogenesis, show virtually identical tissue antioxidant enzyme changes which, as is the case with STZ, are preventable by insulin treatment. The finding that the patterns of antioxidant enzyme alterations in chemically-induced diabetes are independent of the diabetogenic agent used and the presence of similar abnormalities in tissues of spontaneously diabetic (BB) Wistar rats (particularly when diabetic control is less than optimal) suggest that the changes observed are a characteristic feature of the uncontrolled diabetic state and that these may be responsible for (or predispose to) the development of secondary complications in clinical diabetes. Comparative studies involving red cells of diabetic rats and human diabetics revealed a number of common changes, namely an increase in glutathione reductase activity, a decreased susceptibility to oxidative glutathione depletion (which was related to the presence of hyperglycemia) and an increased production of malondialdehyde (an indirect index of lipid peroxidation) in response to in vitro challenge with hydrogen peroxide. In the diabetic patients, the extent of this increase in susceptibility of red cell lipids to oxidation paralleled the severity of diabetic complications. Our results suggest that increased (or uncontrolled) oxidative activity may play an important role in the pathogenesis of complications associated with the chronic diabetic state.
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PMID:Antioxidant enzyme alterations in experimental and clinical diabetes. 323 Dec 24

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

Riboflavin nutritional status was assessed on the basis of activity coefficients of glutathione reductase in erythrocyte hemolysates of normal and streptozotocin-diabetic rats. Activity coefficient values higher than 1.3 were regarded as evidence of riboflavin deficiency. All diabetic animals were found to be riboflavin-deficient, with activity coefficient values of 1.47-2.11. Treatment of diabetic rats with either insulin or riboflavin returned their activity coefficients to normal. Rats fed a restricted diet had normal activity coefficient values. The erythrocyte glutathione reductase activity was significantly lower in diabetic rats, and the augmentation of enzyme activity in the presence of flavin-adenine dinucleotide (FAD) was 72% compared to 16% in normal rats. Hepatic activities of glutathione reductase and succinate dehydrogenase, both FAD-containing enzymes, were significantly lower in diabetic than in normal rats. Like activity coefficient values, all enzyme activities were normalized after insulin or riboflavin treatments. These data suggest that insulin and riboflavin enhance the synthesis of erythrocyte and hepatic FAD. The results of the present study suggest that experimental diabetes causes riboflavin deficiency, which in turn decreases erythrocyte and hepatic flavoprotein enzyme activities. These changes can be corrected for by either insulin or riboflavin. The pathogenesis of riboflavin deficiency in diabetes mellitus is not clearly understood. The data of the present study provide evidence in addition to the previous findings of an increased prevalence of riboflavin deficiency in genetically diabetic KK mice.
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PMID:Riboflavin nutritional status and flavoprotein enzymes in streptozotocin-diabetic rats. 351 4

It has been established that the pyrogallol autoxidation method for the estimation of the activity of superoxide dismutase (SOD) (EC 1.15.1.1) is superior in precision and sensitivity to a superoxide-generating method (NADH/phenazine methosulfate linked to nitroblue tetrazolium reduction). Reference intervals were established in an urban population in the Far East for SOD activity in erythrocytes using the pyrogallol method, and for glutathione peroxidase (GSH-Px) (EC 1.11.1.9) activity in erythrocytes using a standard glutathione reductase-linked method. On this basis, erythrocyte SOD activities were significantly (P less than 0.05) depressed in cases of visceral cancer, acute myocardial infarct, congestive heart failure, respiratory failure, chronic renal failure, and diabetes mellitus, but within the reference interval in cases of lung cancer and asthma. Erythrocyte GSH-Px activity was significantly (P less than 0.05) depressed in cases of diabetes mellitus and chronic renal failure but elevated in respiratory failure and asthma. GSH-Px and SOD activities were well correlated in patients but not in the reference population.
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PMID:Superoxide dismutase and glutathione peroxidase activities in erythrocytes as indices of oxygen loading in disease: a survey of one hundred cases. 366

The activities of hexokinase, glucose-6-phosphate dehydrogenase, hydroxyacyl-CoA-dehydrogenase, adenylate kinase and glutathione reductase were determined in the aorta of rats made diabetics with streptozotocin for over two weeks and in noninjected controls. Adenosinetriphosphate (ATP) and total adenine nucleotide content were also measured. Glutathione reductase activity was not significantly changed in the diabetic aorta whereas the activities of glucose-6-phosphate dehydrogenase, hydroxyacyl-CoA-dehydrogenase and adenylate kinase were all increased. Hexokinase activity was significantly decreased in diabetic rat aorta. When measured after incubation in vitro for 2 h with 5.6 mmol/l glucose, the ATP-concentration was reduced in the diabetic aorta while the total concentration of adenine nucleotides was unchanged. Insulin treatment started three days after induction of diabetes with streptozotocin and continued for twelve days restored the growth rate of the rats but their glucose metabolism was not completely normalized. After insulin treatment no significant differences between diabetic and normal rats were found in the aortic activities of glucose-6-phosphate dehydrogenase, hydroxyacyl-CoA-dehydrogenase, adenylate kinase or in the ATP content.
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PMID:Influence of diabetes on enzyme activities in rat aorta. 626 26

In patients with diabetes mellitus, the processes of lipid peroxidation are activated and the system of antioxidants is disturbed (the content of reduced glutathione and red cell glutathione reductase is lowered and red cell glutathione peroxidase activity is heightened). At the same time the patients demonstrate high concentration of sterols bound by fibrinogen, a considerable lowering of cholesterol content in high density lipoproteins having an antiiatrogenic action. The alterations found underlie the development of atherosclerosis and coronary heart disease.
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PMID:[Interrelation of diabetes mellitus, atherosclerosis and ischemic heart disease]. 652 67

Reduced glutathione (GSH) and activity of GSH related enzymes play a key role in defence against oxygen free radicals, whose production is, as known, raised in patients affected by diabetes mellitus, and at the same time they may contribute to the process of platelet aggregation. The purpose of this study was to evaluate GSH levels and activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-Red), glutathione transferase (GSH-Tr), glucose-6-phosphate-dehydrogenase (G6PDH), and thioltransferase (TT) in platelets of insulin-dependent diabetic patients in fair metabolic control (mean glycated haemoglobin: 6.5%), as related to presence of retinopathy, neuropathy or nephropathy and to platelet aggregation by arachidonic acid (AA) in vitro. Mean effective dose (ED50) of AA was on average significantly lower in the group of insulin-dependent diabetic patients (0.41 +/- 0.02 mM (SEM), n = 46) as compared with that of control subjects strictly matched for age, sex and weight (0.77 +/- 0.02, n = 51; P = 0.0001). Mean platelet GSH as well as the activity of GSH related enzymes expressed as geometric mean (95% confidence intervals) were similar in diabetic patients and in controls, except for GSSG-Red whose activity was significantly higher in diabetic subjects (28.5 (14.4-57.5) mU 10(-9) platelets vs. 20.3 (8.7-56) mU 10(-9) platelets; P = 0.01). In the diabetic group TT was reduced when compared with healthy controls (3.8 (0.9-12.2) mU 10(-9) platelets vs. 6 (1.6-26.1) mU 10(-9) platelets; P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutathione, glutathione utilizing enzymes and thioltransferase in platelets of insulin-dependent diabetic patients: relation with platelet aggregation and with microangiopatic complications. 749 40

Arylsulfonylamino acids, displaying a wide range of inhibitory activities versus rat lens aldose reductase (RLAR), were analyzed for enzyme selectivity in several test systems. These RLAR inhibitors were found not to produce significant inhibition of genetically-linked reductases (aldehyde reductase, ALR), catalytically similar reductases (Pachysolen tannophilus xylose reductase, PTXR), functionally distinct oxidoreductases (glutathione reductase, GR, lactate dehydrogenase, LDH, and gamma-transaminase, GABA-T), and thymidylate synthase (TS). These data suggest that aldose reductase differs significantly from other oxidoreductases in its inhibitor binding domain(s). Furthermore, the aldose reductase selectivity demonstrated by the arylsulfonylamino acids suggests that these compounds may not inhibit other key metabolic transformations in various cell types and that they may function as selective probes for studies of the relationship between aldose reductase mediated biochemical changes and the pathologies of chronic diabetes.
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PMID:Enzyme selectivity analyses of arylsulfonylamino acid aldose reductase inhibitors. 750 72

Male weanling rats were fed diets containing either adequate (6.2 mg/kg) or deficient (0.82 mg/kg) quantities of copper for 35 days. Six rats from each group (n = 12) were then injected with streptozotocin to induce diabetes. Rats were killed after a further 16 days and tissues removed for the analysis of the copper level and antioxidant enzyme activities. Diabetes resulted in increased cardiac catalase, glutathione S-transferase (GST), copper-zinc superoxide dismutase and manganese superoxide dismutase activities. Renal catalase levels were decreased in diabetes, while glucose-6-phosphate dehydrogenase activity (G6PDH) was increased. Diabetes significantly decreased the activities of hepatic GST and G6PDH. The combination of diabetes and copper deficiency resulted in increased levels of hepatic GST, glutathione peroxidase and glutathione reductase. Hepatic and renal tissue copper levels were also increased in diabetes, apparently improving copper status in the copper-deficient rats. Alterations of antioxidant enzyme activities in diabetes were suggestive of increased oxidant stress, especially in cardiac tissue.
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PMID:Effects of copper deficiency and experimental diabetes on tissue antioxidant enzyme levels in rats. 771 Feb 61


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