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

Recently there has been growing interest in studying the differences between different classes of antihypertensive drugs in preventing cardiovascular events in diabetic patients. Hypomagnesemia is common in diabetes mellitus, and correlates to its chronic complications and the associated alteration of the antioxidant enzyme activity. Depletion of reduced glutathione (GSH) in the blood has been demonstrated with myocardial injuries associating hypomagnesemia. A previous study has demonstrated a beneficial effect of metformin hydrochloride (Met), an antihyperglycemic drug, on both magnesium (Mg) and GSH levels in diabetic animals. The purpose of this study was to investigate the effect of oral atenolol, metformin (50 and 60 mg kg[-1] day[-1], respectively) and their combination for 14 days on Mg and GSH levels in blood, liver and heart of diabetic male Wistar rats, as these two parameters have been shown to be altered in diabetics and linked to myocardial ischemic injuries. The results of this investigation showed a state of low levels of Mg and GSH in both blood and liver of the diabetic animals. Treatment with atenolol alone did not change these levels significantly, however administration of metformin or atenolol/metformin increased significantly the GSH levels in both liver and blood, and returned the liver Mg content back to normal values.
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PMID:Influence of atenolol and/or metformin on glutathione and magnesium levels in diabetic rats. 941 50

The effects of acute hyperglycemia on endothelial Ca2+ signaling, formation of endothelium-derived relaxing factor (EDRF) and bioactivity of EDRF were investigated. Hyperglycemia increased 2,5-tert-butyl-1,4-hydrochinone (BHQ)-initiated Ca2+ signaling and EDRF formation in a concentration-dependent manner. The effect of elevated D-glucose on Ca2+/EDRF response could be diminished by co-incubation with the antioxidants vitamin E, probucol, GSH, vitamin C and superoxide dismutase. Convincingly, hyperglycemic conditions yielded an increase in superoxide anion release from endothelial cells and the superoxide anion-generating mixture xanthine oxidase/hypoxanthine mimicked the effect of hyperglycemia on Ca2+/EDRF signaling. Besides an enhanced formation of the vasodilatatory NO compound EDRF, hyperglycemia enhanced NO degradation by endothelial cells and, thus, reduced bioactivity of EDRF. We suggest that vasoactivity during acute hyperglycemia depends on the superoxide anion scavenging properties of the vascular wall. In acute hyperglycemia and early stages of diabetes, radical scavenging capacity may be suitable to protect NO degradation, resulting in an enhanced vasodilation. In contrast, decreased free radical scavenging properties of the vasculature in prolonged hyperglycemia and in later stages of diabetes might promote NO degradation by an overshoot of superoxide anions, resulting in an attenuation of endothelium-dependent vasodilation.
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PMID:Role of superoxide anions in changes of endothelial vasoactive response during acute hyperglycemia. 949 99

Blood samples were analyzed for GSH and GSH redox state in 40 age-related macular degeneration (ARMD) patients (> 60 y), 33 non-ARMD diabetic patients (> 60 years), 27 similarly aged non-ARMD and nondiabetic individuals (> 60 years), and 19 younger individuals (< 60 years) without ARMD or diabetes. Results showed a significantly lower plasma GSH in older individuals (ARMD, diabetes, and controls) than in younger individuals (p < .01). Total GSH (GSHt) obtained following treatment with dithiothreitol was significantly lower only in diabetic cases (p < .05) but also approached significance for ARMD cases (p = .089). Estimation of redox potential indicated that the plasma GSH pool is considerably more oxidized in all of the older groups. Analyses of whole blood GSH showed that GSH was significantly lower in diabetic cases compared to the other groups, but did not reveal any difference associated with age or ARMD. In contrast, GSSG in whole blood was significantly higher in the older groups compared to the younger controls. The results suggest that in studies of age-related pathologies, oxidation of GSH may be a more important parameter than a decline in pool size, while in specific pathologies such as diabetes, both oxidation and a decline in pool size may be important.
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PMID:Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. 958 98

Free radical-mediated damage to vascular cells may be involved in the pathogenesis of diabetic vasculopathy. The aim of this study was to compare the extent of glucose-induced oxidative stress in both vascular smooth muscle cells (VSMCs) and pericytes and the effect on antioxidant enzyme gene expression and activities. Porcine aortic VSMC and retinal pericytes were cultured in either 5 or 25 mmol/l glucose for 10 days. Intracellular malondialdehyde (MDA) was measured as a marker of peroxidative damage, and mRNA expression of CuZn-SOD, MnSOD, catalase, and glutathione peroxidase (GPX) were measured by Northern analysis. Glutathione (GSH) was also measured. There was a significant increase in MDA in VSMCs in 25 mmol/l glucose (1.34 +/- 0.11 vs. 1.88 +/- 0.24 nmol/mg protein, 5 vs. 25 mmol/l D-glucose, mean +/- SE, n = 15, P < 0.01), but not in pericytes (0.38 +/- 0.05 vs. 0.37 +/- 0.05 nmol/mg protein, n = 11). There was a significant decrease in GSH in both cell types (VSMC, 1.40 +/- 0.13 vs. 0.69 +/- 0.12 nmol/mg protein, n = 15, P < 0.001; pericytes, 1.97 +/- 0.17 vs. 0.94 +/- 0.16 nmol/mg protein, n = 11, P < 0.001). mRNA expression of CuZnSOD and MnSOD was increased only in VSMCs (by 58.5 +/- 8.1 and 41.0 +/- 6.9%, respectively, n = 8, P < 0.01). CuZnSOD protein was increased by approximately 120% (P < 0.00001). None of the antioxidant enzyme activities was altered between 5 and 25 mmol/l glucose in either cell type. Both MnSOD activities and GSH concentrations were higher in pericytes compared with VSMC under basal (5 mmol/l) conditions (P < 0.05 and P < 0.02, respectively). These results demonstrate glucose-induced reduction of GSH in both cells, but only in VSMC is there evidence of oxidant damage in the form of lipid peroxidation, implying significant differences in intracellular responses to glucose between contractile cells in the macro- and microvasculature.
Diabetes 1998 May
PMID:Glucose-induced oxidative stress in vascular contractile cells: comparison of aortic smooth muscle cells and retinal pericytes. 958 53

Oxidative stress has been proposed as a possible pathogenic factor for diabetic complications. It is relevant in determining cell replicative capacity and life span, and in vitro antioxidant treatment is able to reverse the impaired proliferative activity of different cell types. It was recently demonstrated that cultured skin fibroblasts from insulin-dependent diabetic patients with nephropathy age prematurely and have a shorter life cell cycle. To test whether the growth phenotype of cells from patients with diabetic nephropathy was related to a lack of protection from oxidative stress, the effect of reduced glutathione (GSH) on cultured skin fibroblasts from 13 insulin-dependent diabetes mellitus (IDDM) patients with nephropathy (DN), 10 IDDM patients without kidney disease (D), and 10 nondiabetic control subjects (C), in normal (5 mM) glucose (NG) and high (22 mM) glucose (HG) medium was studied. After 6 to 8 passages, fibroblasts from DN showed impaired growth both in NG (mean +/- SD fold increase over baseline counts in DN 1.17 +/- 0.6 versus D 1.7 +/- 0.5 versus C 1.95 +/- 0.8; P = 0.04 by ANOVA) and in HG (mean +/- SD fold increase over baseline counts DN 1.16 +/- 0.41 versus D 1.89 +/- 0.66 versus C 2.24 +/- 0.9; P = 0.003 by ANOVA). GSH prevented the growth abnormalities of cells from DN restoring it to values similar to that of the other two groups (mean +/- SD fold increase over baseline counts NG +/- GSH: DN 1.68 +/- 0.9 versus D 1.78 +/- 0.49 versus C 1.99 +/- 0.7, P = 0.6; and in HG + GSH: DN 1.66 +/- 0.69 versus D 1.87 +/- 0.75 versus C 2.2 +/- 0.9, P = 0.3). Growth rates were not affected by the addition of GSH in fibroblasts from D and C. The treatment of fibroblasts from D and C with the inhibitor of the gamma-glutamylcysteine synthetase activity, L-buthionine-S,R-sulfoximine, resulted in growth impairment, and the addition to the culture medium of another antioxidant, superoxide dismutase, corrected the growth abnormalities in fibroblasts from DN. The impaired growth of cultured fibroblasts from IDDM patients with nephropathy is prevented by GSH and superoxide dismutase and is independent of prevailing glucose concentrations. This suggests that oxidative stress is an important mechanism of intrinsic cell dysfunction in these patients.
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PMID:Glutathione reverses the growth abnormalities of skin fibroblasts from insulin-dependent diabetic patients with nephropathy. 962 Dec 89

Effects of taurine supplementation on lipid peroxide formation and the activities of glutathione (GSH) dependent enzymes in diabetic model mice were investigated. Type I diabetes mellitus was induced by injecting alloxan to ICR mice while type II diabetes mellitus was produced by high calorie diet feeding to genetically hyperglycemic KK mice. Taurine was given in drinking water at the level of 5% (w/v) for seven days. The malondialdehyde (MDA) levels of liver and the islets of type I diabetes were significantly increased compared to the control group but the levels were significantly decreased by taurine supplementation. In the type II diabetic model, the concentrations of MDA were not changed by taurine treatment. The activity of hepatic and islet GSH-peroxidase (GPX) was increased in the type I diabetic group, but in type II animals it was decreased. Hepatic GPX activity of both type I and II diabetics was not altered by taurine supplementation but was increased in the islets of the type II animals. No effect on the activity of GSH S-transferase (GST) was observed in both types of diabetes (I and II) following taurine supplementation. These results suggest that taurine supplementation protects type I diabetic mice from lipid peroxide formation.
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PMID:Effect of taurine supplementation on the lipid peroxide formation and the activities of glutathione-related enzymes in the liver and islet of type I and II diabetic model mice. 963 20

Silymarin is a free-radical scavenger and a membrane stabilizer which prevents lipoperoxidation and its associated cell damage in some experimental models. It has been proposed that lipid peroxidation caused by free radicals may be involved in alloxan-induced diabetes mellitus. Alloxan elicits pancreatic lipid peroxidation which precedes the appearance of hyperglycemia in mice. We studied the effects of silymarin on rat pancreas, the effect of this flavonoid on pancreatic, hepatic and blood glutathione (GSH) together with the pancreatic malondialdehyde concentrations in response to alloxan. On its own, silymarin increases pancreatic and blood GSH without changes in either hepatic GSH or in blood glucose. Silymarin prevents the increase in lipid peroxidation produced by alloxan. It also blunts the sustained increment in plasma glucose induced by alloxan. We suggest that silymarin has a protective effect on the pancreatic damage in experimental diabetes mellitus. This may be related to its antioxidative properties and to the increase in concentrations of plasma and pancreatic glutathione.
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PMID:Prevention of alloxan-induced diabetes mellitus in the rat by silymarin. 966 80

Syzigium cumini, commonly known as 'jamun', is widely used in Indian folk medicine for the treatment of diabetes mellitus. Oral administration of 2.5 and 5.0 g/kg body weight of the aqueous extract of the seed for 6 weeks resulted in a significant reduction in blood glucose and an increase in total haemoglobin, but in the case of 7.5 g/kg body weight the effect was not significant. It also prevents decrease in body weight. The aqueous extract also resulted in decreased free radical formation in tissues studied. Thus the study shows that Jamun seed extract (JSEt) has hypoglycaemic action. The decrease in thiobarbituric acid reactive substances (TBARS) and increase in reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) clearly show the antioxidant property of the JSEt. The effect of JSEt was most prominently seen in the case of animals given 5.0 g/kg body weight. JSEt was more effective than glibenclamide.
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PMID:Hypoglycaemic activity of Syzigium cumini seeds: effect on lipid peroxidation in alloxan diabetic rats. 968 76

IDDM results from the destruction of pancreatic beta-cells by autoreactive T-cells that appear to avoid deletion early in development, possibly due to improper interaction with antigen-presenting cells (APCs) resident in the thymus or periphery. In the nonobese diabetic (NOD) mouse, there exists a defect in APC function characterized by its failure to fully mature upon stimulation. The NOD mouse thus provides an excellent model for the investigation of APC dysfunction and development and how these relate to the incidence of autoimmune diabetes. We initiated studies of APC function in the NOD mouse with respect to antigen processing and presentation, using a well-characterized antigen hen egg lysozyme (HEL) and comparing it with the closely related, major histocompatibility complex (MHC) (I-Ag7) identical, diabetes-resistant mouse strain NOR. Proliferation assays comparing NOD and NOR HEL-specific T-cells demonstrated that the T-cell proliferation response of the NOD mouse to both native and denatured forms of the antigen is lower than that of NOR. When crisscross proliferation experiments were conducted using purified T-cells and irradiated spleen cells as APCs from both strains, the results demonstrated that the defect in proliferation resided in the APC compartment of activation. The levels of intracellular glutathione (GSH) were compared in splenic macrophages from NOD and NOR mice; it was found that on antigenic stimulation, NOR macrophages produced significantly more intracellular GSH than did NOD macrophages, even under hyperglycemic (50 mmol/l glucose) conditions. The lower amount of GSH seen in the NOD may result in less efficient processing of antigen, and subsequently, lower levels of T-cell activation.
Diabetes 1998 Aug
PMID:Splenic macrophages from the NOD mouse are defective in the ability to present antigen. 970 19

In our present work we attempt to clarify the pro-, antioxidant status (redox status) of blood and the red blood cell (RBC) filtration changes in type 1 (insulin dependent diabetes mellitus = IDDM) diabetic patients, broadening our biochemical knowledge about the mechanism of disease. Further on we try to apply our observations in therapy. Our studies on enzymes and the pro- and antioxidant status in type 1 diabetes are closely related to earlier works. Our studies on antioxidants have been extended deeper on redox conditions for example on the reduced and oxidized glutathione (GSH and GSSG) and glutathione reductase activity. The properties and changes of antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase and catalase) as well as lipid peroxidation (LP) have been studied earlier without selecting the different type of human diabetics. At the same time the red blood cell filtration characteristics are compared also with normal values. The results of our studies confirmed the earlier findings that human diabetes is accompanied by a strong oxidative predominance (oxidative stress) in blood.
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PMID:Pro-, antioxidant and filtration changes in the blood of type 1 diabetic patients. 970 3


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