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)

Erythrocyte sodium pump activity, osmotic fragility, and thiol status were measured in genetically hyperglycemic (db/db) mice and compared with their nondiabetic littermates (db/m). The data showed no major differences in these parameters. However, erythrocytes from streptozotocin (Stz)-induced diabetic rats had significantly lower activity of sodium pump and thiols with an almost fourfold increase in osmotic fragility as compared with erythrocytes from nondiabetic rats. Sorbinil (an aldose reductase inhibitor) treatment of Stz-diabetic rats normalized all these lesions, suggesting a key role for polyol pathway. However, sorbitol levels in erythrocytes from db/db and db/m mice were undetectable. The data suggest that in db/db mice, the relative lack of polyol pathway, a potential consumer of NADPH, may provide erythrocytes with optimal NADPH for glutathione reductase system, thus maintaining normal GSH levels even at the height of hyperglycemia. Thus, the genetically hyperglycemic mice may serve as a useful model to study diabetes related complications without involving polyol pathway.
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PMID:Erythrocyte sodium-potassium ATPase activity and thiol metabolism in genetically hyperglycemic mice. 131 May 17

Several components of the erythrocyte-dependent glutathione redox system (reduced glutathione, GSH; oxidized glutathione, GSSG; glutathione peroxidase, GSH-Px; glutathione reductase, GSH-Red) were determined in patients with types I and II diabetes mellitus (DM). All groups studied were male subjects: G1, 20 young healthy individuals (aged 23.7 +/- 4.2 years); G2, 15 young insulin-treated type I DM patients; G3, 20 older insulin-treated type II DM patients; G4, 21 older oral hypoglycemic agent-treated type II DM patients; G5, 28 aged healthy individuals (aged 68.9 +/- 11.5 years). There were no differences between G1 and G2, G3 or G4 regarding erythrocyte GSH, GSSG, and GSH-Red (without FAD) levels. GSH-Px activity was significantly lower in G2 when compared to G1 (15.2 +/- 4.9 vs 20.6 +/- 6.6 IU/g Hb). The GSH-Red and GSH-Px activities and GSH levels were significantly higher in G3 (4.6 +/- 1.7 IU/g Hb, 20.2 +/- 8.7 IU/g Hb and 3.5 +/- 1.3 microM/g Hb) and G4 (5.0 +/- 2.2 IU/g Hb, 16.9 +/- 6.1 IU/g Hb and 5.0 +/- 2.3 microM/g Hb) when compared to G5 (3.4 +/- 0.9 IU/g Hb, 12.0 +/- 3.6 IU/g Hb and 2.3 +/- 0.9 microM/g Hb). The findings suggest that treatment of DM can stimulate the redox activity of red blood cells in aged subjects.
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PMID:Influence of diabetes mellitus on the glutathione redox system of human red blood cells. 134 8

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

Riboflavin excretion with urine in children suffering from diabetes mellitus is found to be significantly higher in comparison with healthy adults, the riboflavin content in the serum being normal. The total riboflavin concentration in erythrocytes is substantially lower and administration of daily-required riboflavin doses does not increase this parameter. FAD-dependent glutathione reductase in erythrocyte hemolysates is approximately 1.5 times higher than that of healthy children and does not depend on the additional intake of polyvitamins. The seeming affinity of the enzyme with exogenous FAD in sick children is almost 40 times lower in comparison with this value in healthy children, that is why the FAD-effect value in diabetes mellitus children does not exceed 1.2. Peculiarities of the riboflavin metabolism at diabetes mellitus and possibility to use the investigated parameters as criteria of vitamin B2 supply are discussed.
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PMID:[Riboflavin metabolism in diabetes mellitus]. 144 66

The metabolism of glutathione and activities of its related enzymes were investigated in erythrocytes from patients with diabetes mellitus. A decrease in the levels of the reduced form of glutathione and an increase in the levels of glutathione disulfide were observed in erythrocytes from diabetics whose fasting plasma glucose was more than 140 mg/dl. The activity of glutathione reductase decreased in diabetics, while that of glutathione peroxidase did no change. ATP-depended outward transport of glutathione disulfide also decreased in diabetics. These data suggest that the increase in the levels of glutathione disulfide in erythrocyte from diabetics is brought about by the decreased transport activity of glutathione disulfide through the erythrocyte membrane together with a decrease in the activity of glutathione reductase. The activity of gamma-glutamylcysteine synthetase was significantly lower in diabetics than in normal controls. Glycated gamma-glutamylcysteine synthetase determined using a boronate affinity column chromatography was higher in diabetics than in normal controls. The rate of glutathione synthesis using (H3)-glycine decreased in diabetics. The decrease is the levels of reduced form of glutathione is erythrocytes of diabetics is thought to be brought about by impaired glutathione synthesis. In order to study the mechanism by which glutathione synthesis is impaired, gamma-glutamylcysteine synthetase was purified from human erythrocytes. The molecular weight of the purified enzyme was 60K. A single band was observed on SDS polyacrylamide gel electrophoresis. When the purified enzyme was incubated with glucose, the enzyme activity decreased dependent on the incubation time. These data suggest that the impaired glutathione synthesis in diabetics is brought by glycation of gamma-glutamylcysteine synthetase. As conclusion, glutathione metabolism is impaired in erythrocytes from diabetics which weaken the defence mechanism against oxidative stress in these patients.
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PMID:[Glutathione metabolism in erythrocytes from patients with diabetes mellitus]. 167 80

Oxidative biotransformation of xenobiotics and endogenous substances involves glutathione in reduced form as an integral component through two mechanisms: glutathione peroxidase catalysing the reduction of hydrogen peroxide and organic hydroperoxides, and glutathione-S-transferases catalysing the conjugation of oxygenated derivatives with glutathione. We studied glutathione and glutathione-related enzyme activities in haemolysed venous blood samples from 49 healthy children and from 11 children with diabetes mellitus, 10 children with rheumatoid arthritis, seven children with active coeliac disease, and seven children with acute lymphoblastic leukaemia. Among the healthy children glutathione content and the activities of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were unrelated to sex; age-dependent differences were also minor. The patients with diabetes mellitus had decreased activity of glutathione reductase. The patients with acute lymphoblastic leukaemia had increased activity of both glutathione peroxidase and glutathione-S-transferase, possibly reflecting an adaptive response to free-radicals. The patients with active coeliac disease had control levels of all measured parameters of glutathione-related reactions indicating, since we earlier found decreased activities of glutathione peroxidase in intestinal mucosa of celiacs, that blood may not always reflect tissue-specific changes.
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PMID:Glutathione and glutathione-metabolizing enzymes in the erythrocytes of healthy children and in children with insulin-dependent diabetes mellitus, juvenile rheumatoid arthritis, coeliac disease and acute lymphoblastic leukaemia. 204 16

Superoxide dismutase, glutathione peroxidase and glutathione reductase activities were measured in erythrocytes of 214 young patients with insulin-dependent diabetes and 37 healthy subjects with similar age and sex distribution. The diabetic patients were divided into groups and subgroups according to sex, age, duration of disease, existence of diabetes complications and family history of atherogenic risks. Data analysis was performed by comparing enzyme activities in subgroups according to the degree of diabetes control and the plasmatic level of various lipid fractions. Results showed that superoxide dismutase, glutathione peroxidase and glutathione reductase activities in young diabetic patients were similar to those in controls, except for patients with retinopathy, whose glutathione peroxidase activity was decreased. This last finding might suggest that there is a relationship between the development of diabetic microvascular complications and the accumulation of free radicals and peroxide lipids.
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PMID:[Antioxidant enzymes in insulin-dependent diabetes in the child and adolescent]. 208 81

Glutathione peroxidase and glutathione reductase activities were measured in erythrocytes from control, diabetic and insulin-treated diabetic rats. A significant decrease in the activity of glutathione peroxidase and an increase in the glutathione reductase activity were found with increase in the time of diabetes which may result in the alteration in the activity of the pentose phosphate pathway by the modulation of the levels of NADPH. Insulin administration reverses the change in the activity of glutathione peroxidase but does not reverse the glutathione reductase activity during diabetes. The overall changes may be due to changes in the levels of insulin, triiodothyronine and thyroxine.
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PMID:Changes in erythrocyte glutathione peroxidase and glutathione reductase in alloxan diabetes. 224 98

The metabolism of glutathione and activities of its related enzymes were studied in erythrocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM). A decrease in the levels of the reduced form of glutathione and an increase in the levels of glutathione disulfide were found in erythrocytes of diabetics. To elucidate these changes in the levels of glutathione, synthetic and degradative processes were studied. The activity of gamma-glutamylcysteine synthetase was significantly lower in diabetics than in normal controls. The activity of glutathione synthetase of each group was the same. The rate of outward transport of glutathione disulfide in diabetics decreased to approximately 70% of that of normal controls. The activity of glutathione reductase decreased in diabetics. These data suggest that the decrease in the levels of reduced form of glutathione in erythrocytes of diabetics is brought about by impaired glutathione synthesis and that the increase in the levels of glutathione disulfide is brought about by the decreased transport activity of glutathione disulfide through the erythrocyte membrane together with a decrease in the activity of glutathione reductase. These data also suggest that the impairment of glutathione metabolism weakens the defense mechanism against oxidative stress in erythrocytes of diabetics.
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PMID:Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. 256 61

Depletion of lens glutathione (GSH) occurs quickly and drastically following induction of diabetes or galactosemia in rats as well as in lens culture. The explanation for this dramatic loss of GSH has been investigated by many laboratories but the solution has been elusive. There are several possible causes for the change in the reducing power of the lens under hyperglycemia. (a) The enzyme glutathione reductase which reduces oxidized glutathione to GSH is inhibited. (b) The cofactor NADPH which both the aldose reductase of polyol pathway and glutathione reductase require becomes depleted under hyperglycemia to the point that there is an insufficient amount for glutathione reduction. (c) Membrane permeability is increased, due to osmotic-induced lens hydration. We explored all the above possibilities in the mechanism of GSH depletion and studied the effect of aldose reductase inhibitor (ARI) on osmotic change. We found that under hyperglycemic condition, there was no change in the enzyme glutathione reductase activity. There was an initial drop in NADPH level but there was sufficient remaining for glutathione reductase use. Both NADPH and glutathione depletion could be prevented completely by ARI. In addition, ARI could also prevent any hyperglycemic-induced abnormal transport and leakage of amino acids. We have therefore concluded that only the decreased membrane transport of amino acids which are needed for glutathione biosynthesis and the simultaneous loss of GSH through leaky membrane as initiated by the polyol pathway can be responsible for the drastic GSH depletion.
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PMID:Glutathione depletion in the lens of galactosemic and diabetic rats. 313 35


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