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)

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

Levels of lipid peroxidation in liver, kidney, brain and blood, liver glutathione (GSH) and several enzymes in liver tissue associated with antioxidant defence mechanism, namely Catalase (EC: 1.11.1.6), GSH reductase (EC:1.6.4.2) and GSH-S-transferase (EC: 2.5.1.18), were investigated in streptozotocin-induced diabetic rats. The single intraperitoneal injection of streptozotocin (65 mg/kg) caused a four-, eight- and seven-fold increase in lipid peroxidation in brain, liver and kidney, respectively. A decline in GSH levels both in blood (two-fold) and liver (16%) compared with normal counterparts was also observed. A marginal increase in catalase activity, a 20% decrease in GSH reductase and an increase of GSH-S-transferase activity was also found in this experimental diabetic condition. These results suggest experimental diabetes, induced by streptozotocin, can produce biochemical changes not only in pancreas but also in liver, kidney and brain tissue.
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PMID:Lipid peroxidation, glutathione levels and changes in glutathione-related enzyme activities in streptozotocin-induced diabetic rats. 820 Jun 86

The effect of sodium metavanadate (NaVO3) consumption on trace element metabolism, components of the antioxidant defense system and lipid oxidative damage were studied in control (CON) and streptozotocin-induced diabetic (DIAB) rats. Ten days after injection, CON and DIAB rats received either 0 mM NaVO3/80 mM NaCl (0 group) or 1.2 mM NaVO3/80 mM NaCl (1.2V group) in their drinking water. DIAB groups had higher food and fluid intakes than the CON groups; vanadium (V) groups had lower food and fluid intakes than the saline groups. Vanadium therapy lowered plasma glucose concentrations of DIAB rats. The following parameters were similar among the groups: plasma Zn, Cu and Fe concentrations, plasma ceruloplasmin activity, liver Zn, Cu, Mn and Fe concentrations, kidney Mn and Fe concentrations, liver non-Se-dependent glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Red) and Mn-SOD activities, liver reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations and kidney non-Se-dependent GSH-Px activity. Kidney Zn and Cu concentrations were higher in DIAB rats than in CON rats. The CON-1.2V and DIAB-1.2V groups had V accumulation in the liver and kidney. Liver CuZn-SOD and Se-dependent GSH-Px and kidney CuZn-SOD and GSH-Red activities were lower in DIAB rats compared to CON rats; kidney Mn-SOD and kidney Se-dependent GSH-Px activities were higher in DIAB rats than CON rats. Vanadium treatment did not cause significant alterations in the antioxidant defense system; however, tissue vanadium concentrations were positively correlated to TBARS production. These results show that diabetes caused significant alterations in the antioxidant defense system and that V therapy was associated with a marked deterioration in health of both control and diabetic rats.
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PMID:Vanadium treatment of diabetic Sprague-Dawley rats results in tissue vanadium accumulation and pro-oxidant effects. 824 40

In 35 children of 9-13 years old with insulin-dependent diabetes mellitus distinct alterations in metabolism of vitamin B2 were detected, which were manifested as elevated rate of riboflavin excretion with urine and a decrease in the vitamin content in erythrocytes, as 1.5-fold increase in activity of erythrocyte glutathione reductase and augmented affinity of erythrocyte glutathione reductase to exogenous FAD. Alterations in metabolism of riboflavin did not involve the vitamin deficiency as shown by analysis of vitamins B6 and PP (4-pyridoxic acid and I-methyl nicotinamide, respectively) excretion with urine as well as by study of the coenzymes content in blood of healthy and sick children with various rates of riboflavin consumption. Rates of 4-pyridoxic acid and I-methyl nicotinamide excretion with urine were similar both in healthy children of 9-13 years and in children of this age with diabetes mellitus. The data obtained suggest that rates of riboflavin consumption in patients with diabetes mellitus differed from those of healthy persons; these reasons should be taken into consideration in evaluation of vitamins B2 consumption in patients with diabetes mellitus.
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PMID:[Metabolism of riboflavin and B group vitamins functionally bound to it in insulin-dependent diabetes mellitus]. 827 39

To study the effect of vanadium (V) intake on blood glucose lowering, tissue V concentrations, glutathione reductase (GR) activity, and plasma trace metal concentrations, streptozotocin(STZ)-diabetic rats were treated with vanadyl sulfate (VS) (0.5-1.2 g/l in the drinking water) for up to 12 weeks. Kidney and plasma V concentrations were positively correlated with V intake. Kidney GR activities were not affected by VS treatment nor were plasma cobalt, molybdenum, manganese or lithium concentrations. Individual V intakes were dependent upon severity of diabetes, with more hyperglycemic rats consuming greater quantities of VS solution. A diminished effect on glucose lowering of VS above 1 g/l was noted.
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PMID:Studies of vanadyl sulfate as a glucose-lowering agent in STZ-diabetic rats. 828 Jan 74

Tolbutamide (TOLB) is a sulfonylurea used to treat non-insulin-dependent diabetes mellitus and is a suspected teratogen. However, it is not possible to discriminate between potential teratogenic effects of TOLB and malformations produced by either drug-induced hypoglycemia or the diabetic state itself. We examined the direct effect of TOLB on rat embryos cultured in a rodent whole embryo culture system. CD strain rat embryos were cultured for 48 h beginning on day 9 of gestation (plug day = day 0). Tolbutamide was added at various concentrations (90-3,600 microM). At the end of culture, viable embryos were examined for morphological score, number of somite pairs, crown-rump and head lengths, and DNA and protein content. Tolbutamide produced dose-related decreases in all endpoints at concentrations (2,250-3,600 microM) which are two to four times the human therapeutic concentration. Sera from TOLB-treated rats were adjusted to contain equal concentrations of glucose and insulin and then used for embryo culture. Serum from TOLB-treated rats had no observable effect on embryonic development. The mechanism for the embryotoxic effect of TOLB is unknown; however, the drug was previously demonstrated to alter activity of purified yeast glutathione reductase (GR). Because GR may be important for normal embryonic development, the effect of TOLB on this enzyme activity in cultured rat embryos was evaluated. Tolbutamide (2,700 microM) reduced embryonic GR activity by 35-57%. These results indicate that TOLB has a direct embryotoxic effect at levels 2 to 4 times the usual therapeutic serum concentrations on developing rodent embryos which may be mediated by GR inhibition.
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PMID:The effect of tolbutamide on rat embryonic development in vitro. 835 47

In vivo effects of vanadate on the antioxidant status of control and alloxan diabetic rats liver were examined. The increased oxidative stress during diabetes caused a decline in the activities of glutathione peroxidase (GPx), catalase (CAT), CuZn superoxide dismutase (CuZn-SOD) and Mn-superoxide dismutase (Mn-SOD) in the liver. Reduced glutathione (GSH) was also depleted, but the level of oxidized glutathione and glutathione reductase activity remained unchanged in the livers of diabetic rats. Vanadate treatment of diabetic rats (0.6 mg/mL in drinking water) resulted in almost complete restoration of GPx and Mn-SOD but caused only a partial restoration of CuZn-SOD. However, CAT and GSH were found to be lowered further in vanadate-treated diabetic rats as compared to untreated diabetic rat. Similar decreases in CAT and GSH levels were also observed in the vanadate-treated controls. These results suggest that vanadate, an insulin-mimetic agent, effectively normalized hyperglycemia, but unlike insulin, could not completely restore the altered endogenous defence mechanisms in diabetic liver.
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PMID:Impaired antioxidant status in diabetic rat liver. Effect of vanadate. 844 52

The susceptibility of mitochondria from liver and kidney of diabetic and normal rats to in vitro oxidative damage was assessed. Mitochondria were isolated from diabetic rats 4 weeks after streptozotocin injection and from age-matched, normal rats. Liver mitochondria from diabetic rats were less susceptible to oxidative damage (induced by Fe3+/adenosine 5'-diphosphate (ADP) xanthine/xanthine oxidase), as assessed by the formation of thiobarbituric acid reacting substances (TBARS) and sulfhydryl loss, than were mitochondria from normal rats. The decreased susceptibility of liver mitochondria from diabetic rats to oxidative damage correlated with a sevenfold increase in mitochondrial alpha-tocopherol levels. Activities of the antioxidant enzymes, glutathione reductase, glutathione peroxidase, and superoxide dismutase, were lower in liver mitochondria from diabetic compared to normal rats. Manipulation of dietary alpha-tocopherol, to counteract the increased intake of alpha-tocopherol due to diabetes-associated polyphagia, failed to lower liver mitochondrial alpha-tocopherol to the levels found in normal rats. Mitochondria from kidney of diabetic rats were equally as susceptible to in vitro oxidative damage as kidney mitochondria from normal rats. They had increased levels of superoxide dismutase and glutathione peroxidase but identical levels of alpha-tocopherol compared to mitochondria from normal rats. Dietary manipulation of alpha-tocopherol had no effect on kidney mitochondrial levels of the nutrient.
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PMID:Decreased susceptibility of liver mitochondria from diabetic rats to oxidative damage and associated increase in alpha-tocopherol. 845 24

Abnormal plasma ascorbic acid (AA) and dehydroascorbic acid (DHAA) levels observed in diabetes may be correlated to a deficiency in the recycling of AA. Ascorbic acid and DHAA levels are altered in diabetic liver in the present study. In addition, a coupling of the hexose monophosphate (HMP) shunt by way of NADPH to glutathione reductase and subsequent DHAA reduction is demonstrated. Ascorbic acid production was assayed directly and by way of the HMPS pathway. Results indicate that AA production from DHAA via the HMPS pathway occurs, and is significantly decreased in diabetic liver. Glucose-6-phosphate dehydrogenase (G6PDH) activity is shown to be decreased in diabetic liver. Since G6PDH is essential in providing NADPH for the reduction of glutathione required for subsequent DHAA reduction, its decreased activity is consistent with altered levels of AA and DHAA observed in diabetic tissues.
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PMID:Enzymatic basis for altered ascorbic acid and dehydroascorbic acid levels in diabetes. 846 10


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