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

Mice deficient in hepatocyte nuclear factor 1alpha (HNF-1alpha) develop Laron dwarfism and non-insulin-dependent diabetes mellitus (Lee et al., 1998). Oxidative stress was present in the diabetic HNF-1alpha-null mice. To understand the mechanism underlying the oxidative stress in HNF-1alpha-null mice, we examined whether HNF-1alpha deficiency affects the integrity of the cellular defense system against oxidative stress. The glutathione level and activities of superoxide dismutase and glutathione reductase in liver and other tissues examined were not affected by HNF-1alpha deficiency. However, activities of cytosolic glutathione peroxidase and catalase, two enzymes responsible for detoxification of hydrogen peroxide within cells, were reduced specifically in liver of HNF-1alpha-null mice. The mRNA and protein levels of hepatic catalase in HNF-1alpha-null mice did not differ from those in normal mice. The loss of hepatic catalase activity in HNF-1alpha-null mice is probably caused by an insufficient heme pool in liver cells, because the mRNA level of ferrochelatase, the enzyme that catalyzes the last step of heme biosynthesis, was significantly reduced in liver, and the daily hemin treatment restored partial catalase activity in liver of HNF-1alpha-null mice. Furthermore, our results of cell transfection and luciferase reporter assay indicated that the mouse ferrochelatase promoter could be trans-activated directly by HNF-1alpha.
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PMID:The role of HNF-1alpha in controlling hepatic catalase activity. 1061 83

Diabetes mellitus and its complications are associated with elevated oxidative stress, leading to much interest in antioxidant compounds as possible therapeutic agents. Two new classes of antioxidant compounds, the pyrrolopyrimidines and the 21-aminosteroids, are known to inhibit lipid peroxidation and other biomolecular oxidation. We hypothesized that in the presence of excess oxidants or the impaired antioxidant defense seen in diabetes mellitus, administration of antioxidants such as these may reverse the effects of diabetes on antioxidant parameters. This study measured the effects of subchronic (14 day) treatment with a pyrrolopyrimidine (PNU-104067F) or a 21-aminosteroid (PNU-74389G) in normal and diabetic Sprague-Dawley rats. Activity levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, concentrations of oxidized and reduced glutathione, and lipid peroxidation were used as measures of antioxidant defense in liver, kidney, heart, and brain tissue. In normal rats, the only effect was a 43% increase in cardiac lipid peroxidation after treatment with PNU-104067F. In diabetic rats, the only reversals of the effects of diabetes were a 30% decrease in hepatic glutathione peroxidase activity after PNU-74389G treatment and a 33% increase in cardiac glutathione disulfide concentration after PNU-104067F treatment. In contrast to these effects, increased cardiac glutathione peroxidase and catalase activities, increased brain glutathione peroxidase activity, increased hepatic lipid peroxidation, decreased hepatic glutathione content, and decreased hepatic catalase activity were seen in diabetic rats, reflecting an exacerbation of the effects of diabetes.
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PMID:Effects of new antioxidant compounds PNU-104067F and PNU-74389G on antioxidant defense in normal and diabetic rats. 1078 96

This study was designed to (1) evaluate retinal lipid peroxidation in early diabetes by the method specific for free malondialdehyde and 4-hydroxyalkenals, (2) identify impaired antioxidative defense mechanisms and (3) assess if enhanced retinal oxidative stress in diabetes is prevented by the potent antioxidant, DL-alpha-lipoic acid. The groups included control and streptozotocin-diabetic rats treated with or without DL-alpha-lipoic acid (100 mg kg(-1) day(-1), i.p., for 6 weeks). All parameters were measured in individual retinae. 4-Hydroxyalkenal concentration was increased in diabetic rats (2.63+/-0.60 vs. 1.44+/-0.30 nmol/mg soluble protein in controls, P<0.01), and this increase was prevented by DL-alpha-lipoic acid (1.20+/-0.88, P<0.01 vs. untreated diabetic group). Malondialdehyde, reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations were similar among the groups. Superoxide dismutase, glutathione peroxidase (GSHPx), glutathione reductase (GSSGRed) and glutathione transferase (GSHTrans) activities were decreased in diabetic rats vs. controls. Quinone reductase was upregulated in diabetic rats, whereas catalase and cytoplasmic NADH oxidase activities were unchanged. DL-alpha-Lipoic acid prevented changes in superoxide dismutase and quinone reductase activities induced by diabetes without affecting the enzymes of glutathione metabolism. In conclusion, accumulation of 4-hydroxyalkenals is an early marker of oxidative stress in the diabetic retina. Increased lipid peroxidation occurs in the absence of GSH depletion, and is prevented by DL-alpha-lipoic acid.
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PMID:Early changes in lipid peroxidation and antioxidative defense in diabetic rat retina: effect of DL-alpha-lipoic acid. 1085 58

Using diabetes mellitus as a model of oxidative damage, this study investigated whether subacute treatment (10 mg/kg/day, intraperitoneally for 14 days) with the compound piperine would protect against diabetes-induced oxidative stress in 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione (GSH and GSSG, respectively) content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Piperine treatment of normal rats enhanced hepatic GSSG concentration by 100% and decreased renal GSH concentration by 35% and renal glutathione reductase activity by 25% when compared to normal controls. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with piperine reversed the diabetic effects on GSSG concentration in brain, on renal glutathione peroxidase and superoxide dismutase activities, and on cardiac glutathione reductase activity and lipid peroxidation. Piperine treatment did not reverse the effects of diabetes on hepatic GSH concentrations, lipid peroxidation, or glutathione peroxidase or catalase activities; on renal superoxide dismutase activity; or on cardiac glutathione peroxidase or catalase activities. These data indicate that subacute treatment with piperine for 14 days is only partially effective as an antioxidant therapy in diabetes.
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PMID:Effects of piperine on antioxidant pathways in tissues from normal and streptozotocin-induced diabetic rats. 1108 86

Increased oxidative stress is believed to be an important factor in the development of diabetic complications. In this study, the effect of diabetes on the susceptibility of synaptosomes to oxidative stress, induced by the oxidizing system ascorbate/Fe2+, on the activity of antioxidant enzymes and on the levels of glutathione and vitamin E was investigated. Synaptosomes were isolated from brain of 29-weeks-old Goto-Kakizaki (GK) rats, a model of non-insulin dependent diabetes mellitus and from normal Wistar rats. Synaptosomes isolated from GK rats displayed a lower susceptibility to lipid peroxidation, as assessed by quantifying thiobarbituric acid reactive substances (TBARS), than normal rats (5.33 +/- 0.79 and 7.58 +/- 0.7 nmol TBARS/mg protein, respectively). In the absence of oxidants, no significant differences were found between the levels of peroxidation in synaptosomes of diabetic or control rats. Superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase activities were unaltered in the brain of diabetic rats. There were no statistically significant differences in fatty acid composition of total lipids and reduced glutathione levels in synaptosomes of diabetic and control rats. The decreased susceptibility to membrane lipid peroxidation of diabetic rats synaptosomes correlated with a 1.3-fold increase in synaptosomal vitamin E levels. Vitamin E levels in plasma were also higher in diabetic rats (21.32 micromol/l) as compared to normal rats (15.13 micromol/l). We conclude that the increased resistance to lipid peroxidation in GK rat brain synaptosomes may be due to the increased vitamin E content, suggesting that diabetic animals might develop enhanced defense systems against brain oxidative stress.
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PMID:Synaptosomes isolated from Goto-Kakizaki diabetic rat brain exhibit increased resistance to oxidative stress: role of vitamin E. 1112 43

Coenzyme Q10 is an endogenous lipid soluble antioxidant. Because oxidant stress may exacerbate some complications of diabetes mellitus, this study investigated the effects of subacute treatment with exogenous coenzyme Q10 (10 mg/kg/day, i.p. for 14 days) on tissue antioxidant defenses in 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione contents, and activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. All tissues from diabetic animals exhibited increased oxidative stress and disturbances in antioxidant defense when compared with normal controls. Treatment with the lipophilic compound coenzyme Q10 reversed diabetic effects on hepatic glutathione peroxidase activity, on renal superoxide dismutase activity, on cardiac lipid peroxidation, and on oxidized glutathione concentration in brain. However, treatment with coenzyme Q10 also exacerbated the increase in cardiac catalase activity, which was already elevated by diabetes, further decreased hepatic glutathione reductase activity, augmented the increase in hepatic lipid peroxidation, and further increased glutathione peroxidase activity in the heart and brain of diabetic animals. Subacute dosing with coenzyme Q10 ameliorated some of the diabetes-induced changes in oxidative stress. However, exacerbation of several diabetes-related effects was also observed.
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PMID:Effects of coenzyme Q10 treatment on antioxidant pathways in normal and streptozotocin-induced diabetic rats. 1117 Mar 14

In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin-induced diabetic Sprague-Dawley rats (30 days after streptozotocin induction). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense.
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PMID:Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic rats. 1142 24

Because some complications of diabetes mellitus may result from oxidative damage, we investigated the effects of subacute treatment (10mg/kg/day, intraperitoneal [ip], for 14 days) with the antioxidant isoeugenol on the oxidant defense system in normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free radical-detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with isoeugenol reversed diabetic effects on hepatic glutathione peroxidase activity and on oxidized glutathione concentration in brain. Treatment with the lipophilic compound isoeugenol also decreased lipid peroxidation in both liver and heart of normal animals and decreased hepatic oxidized glutathione content in both normal and diabetic rats. Some effects of isoeugenol treatment, such as decreased activity of hepatic superoxide dismutase and glutathione reductase in diabetic rats, were unrelated to the oxidative effects of diabetes. In heart of diabetic animals, isoeugenol treatment resulted in an exacerbation of already elevated activities of catalase. These results indicate that isoeugenol therapy may not reverse diabetic oxidative stress in an overall sense.
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PMID:Effects of isoeugenol on oxidative stress pathways in normal and streptozotocin-induced diabetic rats. 1142 26

Elevation of glucose concentration in diabetes may induce generation of oxygen free radicals such as superoxide (O2*-) and hydroxyl (*OH). The aim of the present study was to investigate the effect of the oxidative stress on the activities of blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and aldose reductase, the levels of reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances; TBARS) and plasma levels of insulin-like growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in type 2 (non-insulin-dependent diabetes) patients and in healthy controls. Blood SOD, CAT, GSH-Px and GSSG-R were lower in type 2 diabetic patients compared with the the control group. Blood aldose reductase activity was elevated in patients with type 2 diabetes compared with the control group. GSH was decreased while TBARS concentration was increased in red blood cells (RBC) and leukocytes from the patients with type 2 diabetes mellitus in comparison to the control group. The mean values of plasma LH, FSH and testosterone were decreased, whereas the mean plasma IGF-1 concentration was increased in type 2 diabetes compared with controls. These findings support the hypothesis that hyperglycemia enhances the activity of the polyol pathway and impairs the antioxidant status, particularly glutathione redox cycle, resulting in poorer defense against oxidative stress. In addition, decreased circulating testosterone and gonadotropin levels may reflect the oxidative stress exerted by diabetes.
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PMID:Oxidative stress and male IGF-1, gonadotropin and related hormones in diabetic patients. 1152 8

Oxidative stress is involved in both the pathogenesis and complications of diabetes. ACE inhibitors can slow the progression of cardiac and renal impairments related to diabetes. The effect of enalapril treatment on oxidative stress and tissue injury was studied in hearts, kidneys, and livers from streptozotocin-induced diabetic rats. Twenty-four rats were divided into the following groups: streptozotocin (65 mg/kg, single intraperitoneal dose), streptozotocin+enalapril (20 mg enalapril/L drinking water), and control (intraperitoneal saline). Seven months after streptozotocin injection, organs were studied by light microscopy and collagen III immunolabeling. Tissue lesions and collagen labeling were graded by a semiquantitative score (0 to 4). Total glutathione content, glutathione redox status (reduced/oxidized glutathione), antioxidant enzyme activities, protein-associated sulfhydryls, thiobarbituric acid-reactive substances, and fluorescent chromolipids were determined in tissue homogenates. Glycemia was higher in both the streptozotocin and streptozotocin+enalapril groups relative to the control group. In the streptozotocin group, creatinine clearance and body weight were lower, and systolic blood pressure and urinary albumin excretion were higher than in the streptozotocin+enalapril and control groups. Heart, kidney, and liver lesion/labeling scores were significantly higher in the streptozotocin group compared with the streptozotocin+enalapril and control groups. Kidney and liver total glutathione was lower in the streptozotocin group relative to the control group (P<0.05). Enalapril treatment significantly attenuated the reduction of total glutathione. In the heart, kidney, and liver, both glutathione and proteins were relatively more oxidized in the streptozotocin group relative to the control group (P<0.05). Protein and glutathione oxidation were attenuated in the streptozotocin+enalapril group in the 3 tissues studied (P<0.05). Enalapril treatment attenuated the oxidation of lipids in the heart and kidney (P<0.05). Tissue fibrosis scores were inversely correlated with (1) both total glutathione and reduced/oxidized glutathione in heart, kidney, and liver and (2) glutathione reductase activity in the kidney. These results suggest that in streptozotocin-induced diabetic rats, the protective action of enalapril might be mediated, at least in part, by its effect on tissue oxidant/antioxidant status.
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PMID:Enalapril attenuates oxidative stress in diabetic rats. 1171 10


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