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

Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r = 0.692, P < 0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG < 150 mg/dl), the level increased (P < 0.01) and in poorly controlled patients (FPG > 150 mg/dl), the value decreased (P < 0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG (r = -0.430, P < 0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within +/- 3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.
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PMID:Balneotherapy and platelet glutathione metabolism in type II diabetic patients. 893 70

Cytosolic liver glutathione S-transferase (GST) activity was decreased for CDNB and DCNB as substrates in long term alloxan induced diabetes. Similar to cytosolic, microsomal glutathione S-transferase activity was also decreased for CDNB. In contrast, both microsomal and cytosolic GST activities for ETA as well as cytosolic and microsomal glutathione (GSH) contents were unaffected. The activity of Se-dependent glutathione peroxidase activity, but not nonSe-dependent peroxidase activity was increased in diabetic rats. The results suggest that diabetic state has a different effect on each isoenzyme of hepatic glutathione S-transferase activity. After insulin treatment of diabetic animals the activities of both cytosolic and microsomal GST was not restored and the activity of non Se-GSHPx was significantly lower than the control value.
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PMID:Activity of glutathione-dependent enzymes in long term diabetes. I. Activity of glutathione S-transferase and glutathione peroxidase in the liver of alloxan induced diabetic rats. 896 Feb 50

It is now known that human exposure to certain chemicals e.g. benzene, halocarbons, ketones, nitrosamines, etc. can result in adverse health effects that are often not easily recognised as manifestations of chemical toxicity. These are inflammatory states, such as hepatitis, nephritis, scleroderma, and lupus, due to production of reactive oxygen species (ROS) through activation of cytochrome P4502E1 by the chemical, or by metabolism of the chemical to reactive intermediates and neoantigens which initiate immunotoxic effects. Intracellular glutathione (GSH), vitamins C, E and A protect against this ROS toxicity and inflammation; fasting and consumption of alcohol exacerbate it. Chronic inflammatory states may subsequently develop, including rheumatoid disease, atherosclerosis, diabetes, infertility and birth defects, multiple system organ failure (MSOF), Alzheimer's disease, and cancer.
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PMID:Chemical-induced inflammation and inflammatory diseases. 897 63

Oxygen free radicals (OFRs) have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level measured as thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes viz., [superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px)] in the kidney of streptozotocin induced diabetic rats at various stages of development of diabetes. Sprague Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups each consisting of six rats. Rats in subgroups were studied at weekly intervals (0 to 6 weeks). Blood glucose levels were estimated at the time of sacrifice. TBARS levels and activity of antioxidant enzymes were measured in kidney. The levels of TBARS in the diabetic group increased initially, dropped to baseline level after 2 weeks and then progressively increased at 5th and 6th week (p < 0.05). There was an increase in catalase activity at first week after that it decreased as compared to control group. However, GSH-Px activity in the diabetic group increased after 1 week and then remained at the same level except a small drop in the 2nd week. Total SOD and CuZn-SOD activity increased significantly in diabetic kidney as compared to controls at all time intervals, while Mn-SOD activity showed no change. The present findings suggest that oxidative stress accompanies at early onset of diabetes mellitus and the susceptibility of the kidney to oxidative stress during the early stages may be an important factor in the development of diabetic nephropathy.
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PMID:Antioxidant defense system in diabetic kidney: a time course study. 904 69

This study evaluated the effect of acute intravenous glutathione (GSH) infusion on red blood cell (RBC) sorbitol levels in 21 diabetic subjects and 6 normal controls of similar age and body mass index (Kg/m2). All patients received 1,200 mg of GSH in 500 ml of isotonic saline solution during one-hour intravenous administration. At the end of acute infusion of GSH, sorbitol concentration decreased from 20.90 +/- 1.16 to 16.24 +/- 0.81 nmol/g Hb (p < 0.001) in RBCs of diabetic subjects. No significant changes were observed in controls. These data support the hypothesis that GSH depletion, by reducing glycolytic flux to pyruvate, may enhance the rate of glucose metabolism through the polyol pathway and worsen the metabolic imbalance of diabetic tissues. The administration of exogenous GSH could interrupt this vicious circle.
Diabetes Metab 1997 Feb
PMID:The effect of acute glutathione treatment on sorbitol level in erythrocytes from diabetic patients. 905 67

This study examined the effect of streptozotocin-induced diabetes on biliary reduced glutathione (GSH) efflux. Biliary GSH efflux was measured before and after acivicin, an irreversible inhibitor of gamma-glutamyl transpeptidase (GGT). One week after streptozotocin treatment, liver GGT activity doubled in diabetic rats but was inhibited by approximately 90% after acivicin to levels comparable to controls. Despite maximal GGT inhibition, biliary GSH efflux in untreated diabetic rats decreased progressively to approximately 10% of control levels by week 4 and was partially restored by insulin. The mechanism for the decrease in biliary GSH efflux was not increased paracellular permeability. GSH transport kinetics, ATP-stimulated taurocholate, and oxidized glutathione (GSSG) transport in canalicular liver plasma membrane prepared from diabetic and control rats were similar. Inhibition of protein kinase C (PKC) with high-dose H-7 increased biliary GSH efflux in diabetic animals to near control basal levels. In conclusion, streptozotocin-induced diabetic rats exhibit a progressive impairment in biliary GSH transport. One of the responsible mechanisms is heightened PKC tone in diabetic animals.
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PMID:Progressive defect in biliary GSH secretion in streptozotocin-induced diabetic rats. 912 63

It is postulated that glutathione acting as a free oxygen radical scavenger may protect beta-cells from cytokine-mediated cytotoxicity in insulin-dependent diabetes. In this study the effect of glutathione in preventing the cytotoxic damage mediated by tumor necrosis factor-a in vitro towards a human beta-cell line (CM insulinoma) was investigated. CM cells were exposed in vitro to tumor necrosis factor-alpha, tumor necrosis factor-alpha plus glutathione or glutathione alone at different concentrations. The resulting cytotoxicity was measured using a colorimetric assay. Glutathione significantly reduced the cytotoxicity mediated by tumor necrosis factor-alpha in a dose-dependent fashion (P < 0.001). These results suggest a protective effect of glutathione on beta-cell cytotoxicity induced by tumor necrosis factor-alpha and encourage the use of glutathione in trials aimed at reducing the beta-cell damage occurring in insulin-dependent diabetes.
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PMID:Glutathione protects a human insulinoma cell line from tumor necrosis factor-alpha-mediated cytotoxicity. 914 26

Diabetes mellitus is associated with hypertension. An antihypertensive effect of the antioxidant glutathione has been recently demonstrated. It has been suggested that hyperglycemia may contribute to the pathophysiology of hypertension in diabetes by generating an oxidative stress. In this study, three different tests were performed in ten hypertensive and ten nonhypertensive diabetic subjects: (1) an oral glucose tolerance test, (2) glutathione i.v. administration (1 g/m2 bolus + 1 g/m2 in 2 h), and (3) oral glucose tolerance test + glutathione administration. At -15', 0', 30', 60', 90', 120', and 180' systolic and diastolic blood pressure, plasma glucose, and insulin were measured. Variations in plasma glucose and insulin levels were not different during each test in the two groups of patients and in test (1) compared to (3). Glutathione administration reduced systolic and diastolic blood pressure in both hypertensive and nonhypertensive diabetic subjects from 30' to 120'. This phenomenon was abolished as glycemia increased after oral glucose loading. In hypertensive, but not in nonhypertensive diabetic subjects, a significant increase of systolic and diastolic blood pressure was observed at 90' and 120' of the oral glucose tolerance test (p < 0.01). These data show that hyperglycemia can counteract the hypotensive effects of the antioxidant glutathione, suggesting that glucose may impair arterial relaxation by producing free radicals. Also, it appears that hypertension in diabetic patients is aggravated by high glucose plasma levels.
J Diabetes Complications
PMID:Hyperglycemia counterbalances the antihypertensive effect of glutathione in diabetic patients: evidence linking hypertension and glycemia through the oxidative stress in diabetes mellitus. 920 3

Depletion of cellular antioxidant defense mechanisms and the generation of oxygen free radicals by advanced glycation end products (AGEs) have been proposed to play a major role in the pathogenesis of diabetic vascular complications. Here we demonstrate that incubation of cultured bovine aortic endothelial cells (BAECs) with AGE albumin (500 nmol/l) resulted in the impairment of reduced glutathione (GSH) and ascorbic acid levels. As a consequence, increased cellular oxidative stress led to the activation of the transcription factor NF-kappaB and thus promoted the upregulation of various NF-kappaB-controlled genes, including endothelial tissue factor. Supplementation of the cellular antioxidative defense with the natural occurring antioxidant alpha-lipoic acid before AGE albumin induction completely prevented the AGE albumin-dependent depletion of reduced glutathione and ascorbic acid. Electrophoretic mobility shift assays (EMSAs) revealed that AGE albumin-mediated NF-kappaB activation was also reduced in a time- and dose-dependent manner as long as alpha-lipoic acid was added at least 30 min before AGE albumin stimulation. Inhibition was not due to physical interactions with protein DNA binding, since alpha-lipoic acid, directly included into the binding reaction, did not prevent binding activity of recombinant NF-kappaB. Western blots further demonstrated that alpha-lipoic acid inhibited the release and translocation of NF-kappaB from the cytoplasm into the nucleus. As a consequence, alpha-lipoic acid reduced AGE albumin-induced NF-kappaB mediated transcription and expression of endothelial genes relevant in diabetes, such as tissue factor and endothelin-1. Thus, supplementation of cellular antioxidative defense mechanisms by extracellularly administered alpha-lipoic acid reduces AGE albumin-induced endothelial dysfunction in vitro.
Diabetes 1997 Sep
PMID:Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. 928 50

The current study aimed to evaluate whether nicotinamide adenine dinucleotide phosphate (NADPH) alteration in erythrocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM) is responsible for the impaired glutathione (GSH) redox status, and to assess if short-term inhibition of the polyol pathway normalizes NADPH levels and GSH redox status via an amelioration of the NADPH/total NADP (tNADP) ratio. For this purpose, erythrocyte NADPH and GSH levels were measured in 18 NIDDM patients at baseline and then after 1 week of random double-blind assignment to treatment with either tolrestat (an aldose reductase inhibitor, 200 mg daily) (n = 12) or placebo (n = 6). A group of 16 healthy volunteers served as the control. In the basal condition, mean GSH (P < .0001) and NADPH (P < .0001) levels and NADPH/tNADP (P < .0001) and GSH/ glutathione disulfide (GSSG) (P < .005) ratios were lower in NIDDM patients than in control subjects. Tolrestat treatment increased GSH levels (P < .05 v placebo and baseline) and the NADPH/tNADP ratio (P < .05 v placebo and baseline). Interestingly, tolrestat-induced changes in GSH and NADPH levels and in GSH/GSSG and NADPH/tNADP ratios were significant only in patients who showed a decreased NADPH/tNADP ratio at baseline (n = 8). In these latter patients, we also found a direct correlation between percentage increments in GSH levels and NADPH/tNADP ratios after tolrestat treatment (r = .71, P < .05). In conclusion, our findings support the hypothesis that polyol pathway activation decreases NADPH and GSH levels. Accordingly, short-term inhibition of this enzymatic route increased both the GSH level and the NADPH/tNADP ratio. These changes were observable only in the subgroup of patients with an abnormal NADPH/tNADP ratio at baseline. Polyol pathway inhibition could be useful for decreasing oxidative stress in NIDDM.
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PMID:Polyol pathway activation and glutathione redox status in non-insulin-dependent diabetic patients. 932 6


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