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)

A peroxidase from yeast that reduces H2O2 with the use of electrons provided by thioredoxin (Trx) together with homologs from a wide variety of species constitute the peroxiredoxin (Prx) family of proteins. Twelve mammalian Prx members have been previously identified in association with various cellular functions apparently unrelated to peroxidase activity. These mammalian proteins have now been divided into three distinct types, Prx I, II, and III, on the basis of their deduced amino acid sequences and immunological reactivity. With the use of recombinant proteins, Prx I, II, and III have now been shown to possess peroxidase activity and to rely on Trx as a source of reducing equivalents. None of the three proteins exhibited peroxidase activity in the presence of glutaredoxin. All three enzymes showed similar kinetic properties: the Vmax was 6-13 micromol/min per mg at 37 degrees C, the Km for Trx was 3-6 microM, and the Km for H2O2 was < 20 microM. Immunoblot analysis of various rat tissues and cultured cells indicated that most cell types contain the three Prx isoforms, the sum of which amounts to approximately 1-10 microg per milligram of soluble protein. Prx I and II are cytosolic proteins, whereas Prx IlI is localized in mitochondria. These results suggest that, together with glutathione peroxidase and catalase, Prx enzymes likely play an important role in eliminating peroxides generated during metabolism as well as during stimulation of cell surface receptors.
Diabetes Res Clin Pract 1999 Sep
PMID:Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin. 1058 61

Hyperglycemia, a well recognized pathogenetic factor of long-term complications in diabetes mellitus, not only generates more reactive oxygen species but also attenuates antioxidative mechanisms through glycation of the scavenging enzymes. Therefore, oxidative stress has been considered to be a common pathogenetic factor of the diabetic complications including nephropathy. A causal relationship between oxidative stress and diabetic nephropathy has been established by observations that (1) lipid peroxides and 8-hydroxydeoxyguanosine, indices of oxidative tissue injury, were increased in the kidneys of diabetic rats with albuminuria; (2) high glucose directly increases oxidative stress in glomerular mesangial cells, a target cell of diabetic nephropathy; (3) oxidative stress induces mRNA expression of TGF-beta1 and fibronectin which are the genes implicated in diabetic glomerular injury, and (4) inhibition of oxidative stress ameliorates all the manifestations associated with diabetic nephropathy. Proposed mechanisms involved in oxidative stress associated with hyperglycemia are glucose autooxidation, the formation of advanced glycosylation end products, and metabolic stress resulting from hyperglycemia. Since the inhibition of protein kinase C (PKC) effectively blocks not only phorbol ester-induced but also high glucose- and H2O2-induced fibronectin production, the activation of PKC under diabetic conditions may also have a modulatory role in oxidative stress-induced renal injury in diabetes mellitus.
Diabetes Res Clin Pract 1999 Sep
PMID:Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C. 1058 67

Hyperglycemia in diabetes induces increased levels of hydrogen peroxide (H2O2), a reactive oxygen species generated by reduced nicotinamide adenine dinucleotide (NADH) oxidase. Nontoxic levels of H2O2 increase endothelial cell permeability. Using a model of non-insulin-dependent diabetes, the BBZ/Wor rat, we investigated retinal levels of H2O2, vascular endothelial growth factor (VEGF) and its receptors, VEGF-R1 and VEGF-R2 by transmission electron microscopy at sites of the blood-retinal barrier (BRB). H2O2 localization was done by the cerium NADH oxidase method, and extravasation of endogenous serum albumin was used to document disruption of the BRB. Higher levels of H2O2 were detected in blood vessels of diabetic (78.7 +/- 4.84%) as compared with vessels from nondiabetic rats (39.0 +/- 4.47%). VEGF immunoreactivity was statistically higher in the inner BRB (24.67 +/- 0.33 colloidal gold particles/63 microm2 vs. 21.52 +/- 0.43 colloidal gold particles/63 microm2, p = .0001) and outer BRB (42.56 +/- 0.45 colloidal gold particles/63 microm2 vs. 15.51 +/- 0.51 colloidal gold particles/63 microm2, p = .0001) of diabetic rats as compared with age matched nondiabetic control rats. VEGF-R1 immunoreactivity was significantly higher in diabetic retinas in both the inner BRB (21.66 +/- 0.75 colloidal gold particles/63 microm2 vs. 12.69 +/- 0.61 colloidal gold particles/63 microm2, p = .0001) and outer BRB (22.76 +/- 2.36 colloidal gold particles/63 microm2 vs. 8.53 +/- 2.67 colloidal gold particles/63 microm2, p = .0013). VEGF-R2 was statistically higher in the inner BRB (8.97 +/- 0.57 colloidal gold particles/63 microm2 versus 7.03 +/- 0.65 colloidal gold particles/63 microm2, p = .0419) but not in the outer BRB (29.42 +/- 1.25 colloidal gold particles/63 microm2 vs. 28.07 +/- 1.42 colloidal gold particles/63 microm2, p = .4889). H2O2 levels correlated with increased VEGF (correlation coefficient = 0.82, p = .001) in this model of nonproliferative diabetic retinopathy. These results support that hyperglycemia is one factor that induces retinal endothelial cells in vivo to increase H2O2 via NADH oxidase and stimulates increases in VEGF resulting in disruption of the BRB.
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PMID:Increased H2O2, vascular endothelial growth factor and receptors in the retina of the BBZ/Wor diabetic rat. 1065 95

In rats with diabetes induced by streptozotocin (STZ), we studied the reactivity of the aorta in response to vasoconstrictor and vasorelaxant agents, changes in conduction velocity in the sciatic nerve, and glutathion (GSH) content in the gastric mucosa as well as the occurrence of spontaneous gastric lesions. STZ-induced diabetes was found to be accompanied by endothelial injury, exhibited by diminished endothelium-dependent relaxation and by increased noradrenaline- and H2O2-induced contraction. Conduction velocity in the nerves from STZ-treated animals was significantly lower compared to that in nerves from control animals. Moreover, gastric hyperaemia, occasional gastric lesions, and a significant depletion of GSH in the gastric mucosa were observed in STZ-treated rats. Our experiments confirmed the suitability of Wistar rats for the model of STZ-induced diabetes.
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PMID:Streptozotocin diabetes-induced changes in aorta, peripheral nerves and stomach of Wistar rats. 1070 34

Time and dose-dependency of the effects of estrogens (17-beta estradiol, estrone) and non-estrogenic steroids (progesterone, dexamethasone and methylprednisolone) on the toxicity of hydrogen peroxide were examined in mouse hippocampal HT22 cells. Hydrogen peroxide, an important intermediate of various disease-relevant oxidative stressors, induced cell death in HT22 cells in extracellular concentrations between 0.5 and 1.5 mM in a dose-dependent manner (EC50=0.95 mM). Regarding the underlying mechanisms of toxicity, incubation with hydrogen peroxide did not induce lipid peroxidation in living HT22 cells under these conditions. After preincubation with estrogens and non-estrogenic steroids for 22 hours, estrogen compounds protected the cells against hydrogen peroxide toxicity. Estrogens showed a maximal protective effect at 60-70% of hydrogen peroxide toxicity which diminished at higher and lower concentrations of the toxic challenge. Dose-dependency studies of estrogens revealed that concentrations of 1 microM already exerted a significant cytoprotective effect. Co- and postincubation with 17-beta estradiol and estrone also resulted in significant cell protection even if the estrogens were added 30 min after the initiation of the challenge with hydrogen peroxide. In contrast, preincubation with other steroids like progesterone, a physiological gonadal steroid, dexamethasone, a synthetic glucocorticoid and methylprednisolone, a glucocorticoid with radical scavenging properties, did not protect the cells against hydrogen peroxide toxicity but resulted in a dose-related decrease of HT22 cell survival in the course of the toxic challenge.
Exp Clin Endocrinol Diabetes 2000
PMID:Characterization of the neuroprotective effects of estrogens on hydrogen peroxide-induced cell death in hippocampal HT22 cells: time and dose-dependency. 1082 19

Incubation of normal erythrocytes with 10 mM H2O2 has caused a loss of deformability. This loss of deformability was correlated with the extent of malonyldialdehyde, MDA (an indicator of lipid peroxidation) and alanine production (an indicator of protein degradation). The susceptibility of erythrocytes from 21 non-insulin-dependent diabetes mellitus (NIDDM) and 18 hemodialysis patients, 21 cigarette smokers and 25 healthy controls to in vitro oxidative stress with H2O2 has been measured as MDA production. Besides this, their erythrocytes reduced glutathione (GSH; an antioxidant) level has also been determined, but before exposure to H2O2. Erythrocytes from NIDDM and hemodialysis patients have shown significant increase in MDA production and a significantly low GSH level, compared to healthy controls. In cigarette smokers, although the GSH level was significantly low, but there was no significant difference in MDA production, compared to healthy controls. The low GSH level in NIDDM and hemodialysis patients, and smokers indicates that their erythrocytes were exposed to oxidative stress (an increase in free radical load) in vivo, resulting in an overconsumption and/or decreased production of GSH. The increased susceptibility to oxidative stress along with the decrease in some antioxidants (e.g., GSH) may explain the significant increase in MDA production in NIDDM and hemodialysis patients. But in cigarette smokers, the increased susceptibility to oxidative stress is probably not sufficient to cause a significant increase in MDA production. The results may also indicate an increased susceptibility to the loss of erythrocyte deformability in NIDDM and hemodialysis patients compared to healthy controls.
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PMID:Susceptibility of erythrocytes from non-insulin-dependent diabetes mellitus and hemodialysis patients, cigarette smokers and normal subjects to in vitro oxidative stress and loss of deformability. 1097 10

The main purpose of this study was to investigate the effect of free radicals and experimental diabetes on cytosolic creatine kinase activity in rat heart, muscle and brain. Hydrogen peroxide decreased creatine kinase activity in a dose dependent manner which was reversed by catalase. Xanthine/xanthine oxidase, which produces superoxide anion, lowered the creatine kinase activity in the same manner whose effect was protected by superoxide dismutase. N-acetylcysteine and dithiothreitol also significantly ameliorated the effect of Xanthine/xanthine oxidase and hydrogen peroxide. Experimental diabetes of twenty-one days (induced by alloxan), also caused a similar decrease in the activity of creatine kinase. This led us to the conclusion that the decrease in creatine kinase activity during diabetes could be due to the production of reactive oxygen species. The free radical effect could be on the sulfhydryl groups of the enzyme at the active sites, since addition of sulfhydryl groups like N-acetylcysteine and dithiothreitol showed a significant reversal effect.
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PMID:Effects of free radicals on cytosolic creatine kinase activities and protection by antioxidant enzymes and sulfhydryl compounds. 1097 54

Both chronic hyperglycemia and ischemia/reperfusion (IR) cause an imbalance in the oxidative state of tissues. Normoglycemic and streptozotocin (STZ)-diabetic rats were subjected to bilateral carotid artery occlusion for 30 min followed by reperfusion for 60 min. Rats had either been treated with dehydroepiandrosterone (DHEA) for 7, 14, or 21 days (2 or 4 mg/day per rat) or left untreated. Oxidative state, antioxidant balance, and membrane integrity were evaluated in isolated synaptosomes. IR increased the levels of reactive species and worsened the synaptic function, affecting membrane Na/K-ATPase activity and lactate dehydrogenase release in all rats. The oxidative imbalance was much severer when transient IR was induced in STZ-diabetic rats. DHEA treatment restored H2O2, hydroxyl radical, and reactive oxygen species to close to control levels in normoglycemic rats and significantly reduced the level of all reactive species in STZ-diabetic rats. Moreover, DHEA treatment counteracted the detrimental effect of IR on membrane integrity and function: the increase of lactate dehydrogenase release and the drop in Na/K-ATPase activity were significantly prevented in both normoglycemic and STZ-diabetic rats. The results confirm that DHEA, an adrenal steroid that is synthesized de novo by brain neurons and astrocytes, possesses a multitargeted antioxidant effect. They also show that DHEA treatment is effective in preventing both derangement of the oxidative state and neuronal damage induced by IR in experimental diabetes.
Diabetes 2000 Nov
PMID:Dehydroepiandrosterone prevents oxidative injury induced by transient ischemia/reperfusion in the brain of diabetic rats. 1107 61

We examined the effects of high-fructose (FR) feeding on the development of diabetic complications in the lens and the kidney of streptozotocin (STZ)-diabetic rats. Male Wistar Furth rats were treated with one of two doses of STZ (HIGH STZ, 55 mg/kg body weight; MOD STZ, 35 mg/kg body weight) or vehicle alone (SHAM) and were then assigned to a control (CNTL) or 400 g FR/kg diet for 12 weeks. At the end of the study, body weight, plasma glucose and insulin concentrations differed among STZ groups (HIGH v. MOD v. SHAM, P < 0.001) but did not differ due to diet. Plasma FR concentrations were significantly higher in FR-fed v. CNTL-fed groups (P < 0.0001) and in HIGH-STZ groups v. MOD-STZ and SHAM groups (P < 0.0004 and P < 0.0001 respectively). Focal length variability of the lens, a quantitative measure of cataract formation, was increased in the HIGH STZ, FR group compared with the HIGH STZ, CNTL group (P < 0.01). The concentration of H2O2 in kidney microsomes was significantly higher in HIGH STZ, FR rats v. HIGH STZ, CNTL rats (P < 0.01). Micro-albuminuria was not observed in any of the groups examined, and there was no evidence of extensive histological damage in the kidney from any rats. Under conditions of severe hyperglycaemia, high FR intake promotes the development of cataracts in the lens of the eye, and results in increased concentrations of substances indicative of oxidative stress in the kidney. Although FR has been suggested as a carbohydrate source for diabetics, a high FR diet coupled with hyperglycaemia produces effects that may promote some of the complications associated with diabetes.
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PMID:High-fructose feeding of streptozotocin-diabetic rats is associated with increased cataract formation and increased oxidative stress in the kidney. 1110 29

Many clinical and experimental studies have established the beneficial effect of kinins in hypertension, heart failure and ischaemia-reperfusion syndrome, but little attention has been given to the role of kinins in hyperglycaemic conditions. The purpose of the present study was to determine the influence of bradykinin on the levels of glucose, insulin, malondialdehyde and hydrogen peroxide, as well as antioxidative enzyme activity in rats with streptozotocin (STZ)-induced acute hyperglycaemia. In STZ-induced hyperglycaemic rats the levels of glucose, hydrogen peroxide and malondialdehyde were increased by 256% (from 6.0+/-0.3 to 21.4+/-1.3 mmol/l, P<0.001), 33% (from 1.9+/-0.1 to 5.6+/-0.3 mmol H(2)O(2)/ml, P<0.001) and 19% (from 3.7+/-0.3 to 4.9+/-0.2 nmol/l, P<0.001) respectively. The activity of superoxide dismutase, catalase and glutathione peroxidase and the level of insulin were decreased by 46% (from 1367+/-73 to 737+/-59 U/g Hb, P<0.001), 36% (from 2.3+/-0.3 to 1.4+/-0.1 U Bergmayera/g Hb, P<0.001), 31% (from 236+/-19 to 163+/-24 U/g Hb, P<0.001) and 91% (from 47.5+/-1.7 to 2.4+/-0.5 mU/l, P<0.001) respectively in rats treated with streptozotocin. The administration of bradykinin caused the decrease in glucose, hydrogen peroxide and malondi-aldehyde levels by 38% (from 21.4+/-1.3 to 13.3+/-1.0 mmol/l, P<0.001), 37% (from 5.6+/-0.3 to 4.3+/-0.2 mmol H2O2/ml, P<0.001), 39% (from 4.9+/-0.2 to 3.0+/-0.2 nmol/l, P<0.001) respectively and the increase in insulin level and superoxide dismutase, catalase and glutathione peroxidase activity by 62% (from 2.4+/-0.5 to 4.0+/-0.4 mU/l, P<0.001), 23% (from 736.8+/-58.5 to 906.7+/-47.8 U/g Hb, P<0.001), 23% (from 1.4+/-0.1 to 1.9+/-0.1 U Bergmayera/g Hb, P<0.01) and 19% (from 163.1+/-23.6 to 202.3+/-11.7 U/g Hb, P<0.001) respectively in rats with hyperglycaemia. Thus, bradykinin is able to reduce oxidative stress in hyperglycaemic conditions.
Diabetes Res Clin Pract 2001 Feb
PMID:The effect of bradykinin on the oxidative state of rats with acute hyperglycaemia. 1116 87


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