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

Non-enzymic binding of sugars to proteins (glycation) is a common biological phenomenon that is increased in diabetes. Most work has been directed towards structural proteins which may be present for many years and would continue to accumulate sugar residues. As glycation is a non-specific reaction, other proteins such as enzymes will also be susceptible to glycation and could well display altered activity. We investigated the effect of various sugars whose concentrations increase in diabetes in insulin-independent tissues on glutathione reductase, an enzyme that maintains the GSH level in cells. Glucose, glucose 6-phosphate and fructose all displayed a time-dependent inhibition of glutathione reductase activity, suggesting that these sugars glycate this enzyme. Aspirin gave some protection against the loss of activity induced by glucose.
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PMID:Glycation (non-enzymic glycosylation) inactivates glutathione reductase. 144 75

Exposure to hyperglycemia slows the rate of proliferation of cultured human endothelial cells. Recently, it has been reported that glucose may autoxidize generating free radicals which have been hypothesized to delay cell replication time. To test whether oxidative stress has an effect on delaying cell replication time in hyperglycemic conditions, human endothelial cells cultured from umbilical veins were incubated in 5 or 20 mM glucose, either alone or in the presence of one of three different antioxidants: superoxide dismutase (SOD), catalase and glutathione (GSH). Cells grown in medium with 5 mM glucose, with or without antioxidants, yielded similar population doubling times and cell cycle phase distributions. Significantly lower growth parameters were observed in cells grown in medium with 20 mM glucose, without antioxidants. The presence of the antioxidant reverted them to almost normal growth. These data show that high glucose levels may delay endothelial cells replication time through the generation of free radicals, suggesting a possible pathophysiological linkage between the high levels of glucose and the development of microvascular complications of diabetes, possibly suggesting a new therapeutic approach to prevent such complications.
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PMID:Decreased cultured endothelial cell proliferation in high glucose medium is reversed by antioxidants: new insights on the pathophysiological mechanisms of diabetic vascular complications. 148 70

This study reports on the effect of streptozotocin (STZ) induced diabetes on water soluble-SH and -SS, as well as on hepatic glutathione peroxidase (GSH-Px), catalase and superoxide dismutase (SOD) activity and on malondialdehyde (MDA) content. In addition, we determined serum concentrations of glucose, cholesterol, triglycerides and thyroxine, and thyroid weight. To elucidate the possible impact of exogenous iodine on impaired free radical tissue defense mechanisms STZ-diabetic rats were exposed to iodine brine providing for a daily iodide uptake of about 300 micrograms/kg body weight. STZ-exposure caused a decline in thyroid weight (p less than 0.01) and in total serum thyroxine (p less than 0.001), as well as a fall in hepatic catalase (CAT) activity (p less than 0.01) versus control group. Impairment of catalase activity was related to serum glucose level (r = -0.569, p less than 0.01), while hepatic MDA was positively related to serum glucose (r = + 0.5, p less than 0.01). No protective effects of iodine brine were seen with regard to impairment by STZ of antioxidant enzyme status. We conclude that impairment by STZ of antioxidant enzymes may contribute to STZ-dependent experimental diabetes.
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PMID:Alterations of antioxidant tissue defense enzymes and related metabolic parameters in streptozotocin-diabetic rats--effects of iodine treatment. 150 40

Lipid peroxide (LPO) values in blood plasma, along with the glutathione peroxidase (GSH-PX) activity in whole blood and superoxide dismutase (SOD) activity in erythrocytes were determined in 50 patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 33 control subjects. The mean LPO value, SOD activity, LPO/GSH-PX and LPO/SOD ratios in the diabetic patients were significantly higher than those in the control subjects. The increases of LPO value, LPO/GSH-PX and LPO/SOD ratios were more pronounced in diabetics with microangiopathy than in those without microangiopathy. Our results suggest that free radicals may be implicated in the pathogenesis of diabetic microangiopathy.
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PMID:[Relationship between free radicals and diabetic microangiopathy]. 175 51

The present work evaluates some aspects of the redox potential in individuals with insulin-dependent diabetes mellitus (IDDM). The plasma lipid peroxides level and the concentration of glutathione (GSH) were measured. The data obtained revealed a rise in lipoperoxides concentration and a decrease in GSH content suggesting that oxygen derived free radicals may play a role in the pathogenesis of IDDM.
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PMID:Redox changes in insulin-dependent diabetes mellitus. 181 71

The effect of the instillation of gamma-glutamylcysteinylethyl ester (gamma-GCE), which has been reported to function as a precursor of glutathione, on cataract formation was examined in rats in which diabetes had been induced by Streptozotocin (STZ). Three days after i.p. treatment with 50 mg/kg body weight of STZ, male Wistar rats aged 6 weeks received instillations of gamma-GCE in solution or liposomes prepared with dipalmitoylphosphatidylcholine (DPPC) for a period of 9 weeks. Cataract formation and development were observed by use of a cataract camera every week. After 9 weeks' observation, the lenses were enucleated and the content of the lens GSH was measured. Instillation of gamma-GCE in solution or liposomes to STZ-diabetic rats not only inhibited cataract formation but also kept lens GSH level almost at the control level. In addition, the inhibitory effect of the instillation of gamma-GCE in liposome was stronger than that of gamma-GCE in solution. The present results indicate that the administration of gamma-GCE in solution or in liposomes inhibits diabetic cataract formation, possibly by preventing lens GSH depletion.
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PMID:[The inhibitory effect of gamma-glutamylcysteinylethyl ester (gamma-GCE) instillation on experimental diabetic cataract formation in rats]. 183 18

Levels of blood glutathione (GSH) were measured in 26 type II diabetes mellitus patients compared to 36 controls. Total blood GSH did not differ significantly between the two groups (mean +/- s.d., 8.0 +/- 1.5 vs. 7.7 +/- 1.3 mmol/g Hb, respectively); however reduced GSH was lowered in diabetes mellitus (5.0 +/- 1.0 vs. 5.8 +/- 1.0 mmol/gHb; P = 0.01), whereas oxidized GSH was increased (0.4 +/- 0.2 vs. 0.2 +/- 0.1 mmol/gHb; P = 0.001). Urinary excretion of 5-oxoproline was excessive in the diabetic patients (14.5 +/- 9.9 vs. 3.8 +/- 1.4 mmol/24 h; P = 0.004), and was positively correlated with levels of glycosylated haemoglobin (r = 0.69; P less than 0.01).
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PMID:Excessive excretion of 5-oxoproline and decreased levels of blood glutathione in type II diabetes mellitus. 208 14

Disease diagnosis, age, sex, and selected hematologic variables were evaluated retrospectively in a population of feline patients with high number of circulating Heinz bodies. By comparing these cats with a control population and results of additional hematologic investigation on a subsample of the cats, we tested the hypotheses that endogenous Heinz body formation is increased in specific disease states and that endogenous Heinz bodies may contribute to anemia. There was strong correlation between diabetes mellitus, hyperthyroidism, and lymphoma and Heinz body formation. Diabetic cats, in particular, consistently had marked Heinz body formation. These diseases together accounted for nearly 40% of cats with Heinz body formation, but for less than 12% of cats of the control group. The PCV of cats with Heinz bodies (29.77 +/- 9.32%) was significantly (P less than 0.001) lower than that of control cats (35.33 +/- 8.08%). Polychromasia and punctate reticulocyte number were slightly increased in cats with Heinz body formation and correlated significantly (P less than 0.001) with PCV. A subsample of 13 of the cats had significant (P less than 0.006) inverse correlation between Heinz body percentage and erythrocyte reduced glutathione (GSH) concentration. Mean GSH concentration was significantly lower in cats with Heinz bodies, compared with that in a random cat population (5.28 +/- 1.67 mumol/g of hemoglobin vs 7.06 +/- 2.10 mumol/g of hemoglobin), in which GSH values followed normal distribution. Cats with Heinz body formation were older, and were more likely to be spayed.
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PMID:Relation of endogenous Heinz bodies to disease and anemia in cats: 120 cases (1978-1987). 270 16

Transglutaminase activity in rat islet homogenates was increased after preincubation of the islets at high glucose concentration, and severely decreased after preincubation in the presence of either 1,2-bis(2-chloroethyl)-1-nitrosurea or 2-cyclohexene-1-one. The stimulatory action of glucose was still observed when the islets were preincubated in the absence or extracellular Ca2+. The enzymic activity was decreased by NAD+ or NADP+ but not NADH or NADPH, and inhibited by GSSG more than by GSH. These findings suggest that the glucose-induced activation of transglutaminase may be related to induction of a more reduced redox state with subsequent change in thiol-disulfide balance.
Diabetes Res 1986 Mar
PMID:Glucose-induced activation of transglutaminase in pancreatic islets. 287 59

Decreased glutathione levels in the ocular lens have been invoked as a possible cause for the decreased lenticular Na+-K+-ATPase in diabetes because both are corrected by aldose reductase inhibitors, and the Na+-K+-ATPase is known to be susceptible to oxidation inactivation. Because an analogous Na+-K+-ATPase defect that is prevented by aldose reductase inhibitors has been described in diabetic peripheral nerve, we examined the effect of streptozocin (STZ) diabetes and aldose reductase inhibition on reduced (GSH) and oxidized (GSSG) glutathione levels in crude homogenates of rat sciatic nerve. Neither GSSG nor GSH levels were altered by 2 or 8 wk of untreated diabetes or by aldose reductase inhibition. Because the defect in Na+-K+-ATPase is fully expressed by 4 wk of STZ diabetes, we conclude that altered glutathione redox state plays no detectable role in the pathogenesis of this defect in diabetic peripheral nerve.
Diabetes 1986 Nov
PMID:Glutathione redox state is not the link between polyol pathway activity and myo-inositol-related Na+-K+-ATPase defect in experimental diabetic neuropathy. 301 9


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