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

Antioxidant status was measured in heart, liver, kidney, lung, and erythrocytes of 2-week streptozotocin-diabetic male Wistar rats exposed to chronic intermittent psychological stress consisting of 1 h of restraint twice daily for 14 days. Diabetes reduced erythrocyte and heart and liver susceptibility to hydrogen peroxide-induced glutathione depletion. Susceptibility to peroxide-induced thiobarbituric acid reactive substance (TBARS) formation increased in erythrocytes, liver, kidney, and lung but decreased in heart. Significant changes also occurred in glutathione levels (increased in heart and decreased in liver) and in the activities of catalase (reduced in liver and kidney), glutathione reductase (elevated in heart and liver), and glutathione peroxidase (decreased in liver and lung), but not Cu,Zn-superoxide dismutase. Stress potentiated diabetes-associated hyperglycemia and attenuated diabetes-induced hyperlipidemia. In addition, the reduction in peroxide-induced glutathione depletion in heart and liver and the increased TBARS formation in kidney and lung were reversed. Similarly, the diabetes-induced induced increase in liver glutathione reductase and decreases in liver and lung glutathione peroxidase activities were abolished by stress. Thus, the relative resistance of antioxidant systems to stress can be modified under pathologic conditions in which antioxidant alterations are present.
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PMID:Alteration of antioxidant status in diabetic rats by chronic exposure to psychological stressors. 857 2

It has been suggested that oxidative stress may play an important role in the pathogenesis of diabetic complications. Hyperglycemia may cause increased production of free radicals, and evidence supports a prominent role for these reactive molecules as mediators of endothelial cell dysfunction in diabetes. It has been demonstrated that active oxygen species induce antioxidant enzyme expression in some tissues, and this phenomenon is considered proof of an existing oxygen-dependent toxicity. In this study, human endothelial cells from umbilical vein, immortalized human endothelial cells, and immortalized human endothelial cells transfected to express high glutathione peroxidase levels were grown in normal and high-glucose conditions. High glucose delayed replication after 7 and 14 days of culture of human endothelial cells, both from umbilical vein and immortalized, while transfected cells were not affected. The activity and the mRNA expression of the antioxidant enzymes CuZn-superoxide-dismutase, Mn-superoxide-dismutase, catalase, and glutathione peroxidase were evaluated after 2, 7, and 14 days of culture. High glucose at days 7 and 14 induced an overexpression of CuZn-superoxide-dismutase, catalase, and glutathione peroxidase in both human endothelial cells from umbilical vein and immortalized human endothelial cells, while in transfected cells it did not. This study demonstrates that high glucose induces an increase in antioxidant enzyme levels in human endothelial cells, suggesting that elevated glucose levels may produce an oxidative stress in the cells.
Diabetes 1996 Apr
PMID:High glucose induces antioxidant enzymes in human endothelial cells in culture. Evidence linking hyperglycemia and oxidative stress. 860 69

Aminoguanidine, nucleophilic hydrazine derivative, has been shown to inhibit diamine oxidase, the formation of advanced glycation endproducts, nitric oxide synthase, and catalase. Prompted by the reports that aminoguanidine also inhibits aldose reductase (AR), we have investigated the effect of aminoguanidine, 1,3-diaminoguanidine, and methylguanidine on AR activity in vitro, and in vivo. In vitro, we have measured the inhibition of AR isolated from bovine lenses; in vivo, we have examined the effect on the galactitol levels in the red blood cells, sciatic nerve, retina, and lens of rats administered the test compounds for 11 days in the drinking water and, for the last 4 days, given access to a 20% galactose diet. Two known, structurally distinct AR inhibitors, tolrestat and compound WAY-121,509, were used as reference. In vitro, at concentrations up to 1.0 mmol/L, none of the tested guanidine derivatives had any effect on AR. As a corollary, in vivo, at doses ranging from 201 to 349 mg/kg/day, none of the guanidine derivatives affected tissular galactitol levels. We conclude that, in short-term galactose-fed rats, at the doses tested, aminoguanidine, 1,3-diaminoguanidine, and methylguanidine do not inhibit AR.
J Diabetes Complications
PMID:Aminoguanidine does not inhibit aldose reductase activity in galactose-fed rats. 863 71

The Maillard reaction has been implicated in cross-linking and fluorescence formation of collagen exposed to high glucose in vitro. However, several pharmacologic agents, whose action seems unrelated to pathways of nonenzymatic glycation, have been demonstrated to prevent cross-linking in diabetes. To clarify this discrepancy, kinetic changes in glycation, glycoxidation (carboxymethyllysine, CML), and cross-linking (measured as tendon breaking time, TBT) were evaluated in rat tail tendons incubated in 5 and 30 mM glucose in vitro and in tendons implanted in vivo into diabetic rat peritoneal cavity. In vitro, rates were found to be both O2- and glucose-dependent. Tendon preglycation and presence of added 2 mM glycosylamine and Amadori compounds (Amadori product of glucose and propylamine) catalyzed these changes in a primarily O2-dependent manner. In the presence of Amadori compounds, kinetic changes were dramatically increased and were preventable by addition of catalase to the medium. Tendons implanted into diabetic rat peritoneum became more rapidly glycoxidized and cross-linked when implanted at day 30 from diabetes onset (high tissue glycation) compared to day 3 (low tissue glycation) in spite of similar glycation kinetics, suggesting a mechanistic dissociation between glycation, glycoxidation, and cross-linking in diabetes. Indeed, intraperitoneal injection of catalase and other antioxidants dramatically suppressed cross-linking, fluorescence formation, and, to some extent, glycoxidation, without affecting glycation. This study confirms the role of oxidative stress in protein cross-linking by the Maillard reaction in vitro and provides the first evidence for a role of H2O2 in cross-linking in diabetes. Whereas Amadori products are a potent source of H2O2 formation in vitro, their precise contribution to H2O2 generation and the actual role of Maillard reaction products in collagen cross-linking in diabetes requires further investigation.
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PMID:Involvement of hydrogen peroxide in collagen cross-linking by high glucose in vitro and in vivo. 866 99

The present work was carried out to examine the role of glycation and transition metal catalysed autoxidation of sugars in glucose-mediated alterations of myofibrillar proteins. Myofibrils were prepared from rat skeletal muscle and incubated with 1) sugar alone 2) sugar and micromolar concentrations of transition metals (Cu2+ or Fe3+) 3) transition metals alone and the control remained without sugar or transition metals. A significant increase in extent of glycation and decrease in ATPase activity of myofibrils incubated under autoxidative conditions were observed over the other three incubations. Reducing agent 2-mercaptoethanol was highly effective in preventing the alterations induced by glucoxidation, compared to EDTA and aminoguanidine, suggesting the involvement of thiol group oxidation in the reduced function of the protein. Free radical scavengers like catalase, benzoic acid and mannitol were also effective in preventing glucose mediated alterations. Although a high concentration of glucose alone has an insignificant effect on myofibrils in vitro, the results from the present work suggest that glucose in combination with transition metals could lead to functional alterations of myofibrils, and this process by generating free radicals may contribute to the overall complications of diabetes and aging.
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PMID:The possible relevance of autoxidative glycosylation in glucose mediated alterations of proteins: an in vitro study on myofibrillar proteins. 871 22

Using a sensitive Northern blot hybridization technique, gene expression of superoxide dismutase (SOD), catalase, and glutathione peroxidase was studied in pancreatic islets and for comparison in various other mouse tissues (liver, kidney, brain, lung, skeletal muscle, heart muscle, adrenal gland, and pituitary gland). Gene expression of the antioxidant enzymes was usually in the range of +/- 50% of that in the liver. Only in pancreatic islets gene expression was substantially lower. The levels of the cytoplasmic Cu/Zn SOD and the mitochondrial Mn SOD gene expression were in the range of 30-40% of those in the liver. Glutathione peroxidase gene expression was 15%, and catalase gene expression was not at all detectable in pancreatic islets. These low levels of antioxidant enzyme gene expression may provide an explanation for the extraordinary sensitivity of pancreatic beta cells towards cytotoxic damage by diabetogenic compounds and during the development of human and animal diabetes.
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PMID:Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. 872 Sep 19

To examine the role of free radicals in diabetic cardiomyopathy, myocardial antioxidants as well as lipid peroxide content were examined in rats made diabetic with a single injection of streptozotocin (65 mg/kg i.v). At 4 wk, the left ventricular peak systolic (LVSP) as well as aortic pressures were depressed in the diabetic group. Hearts from diabetic animals showed about a 100% increase in thiobarbituric acid reactive substances (TBARS), indicating increased lipid peroxidation. This was accompanied by about a 50% decrease in superoxide dismutase (SOD) and 60% decrease in glutathione peroxidase (GSHPx) enzyme activities. Catalase activity in these hearts showed a small but significant increase. Treatment with probucol (10 mg/kg i.p., on alternate days), a known lipid-lowering drug with strong antioxidant properties, was initiated 1 d after the induction of diabetes and was continued for 4 wk. In probucol-treated diabetic animals, LVSP was not different from controls. Probucol treatment caused a small but significant improvement in serum insulin and decrease in glucose levels as well as increased myocardial SOD, GSHPx, and catalase activities with a concomitant decrease in TBARS in the diabetic animals. These data provide evidence that diabetic cardiomyopathy is associated with an antioxidant deficit, and a better cardiac function due to treatment with probucol may be related to the improved insulin levels as well as maintenance of the antioxidant status of the heart.
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PMID:Probucol improves antioxidant activity and modulates development of diabetic cardiomyopathy. 874 20

Cell-cell interactions are important in intravascular inflammation. Neutrophils and monocytes adhere to the vascular endothelium and release mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and reactive oxygen species. Red blood cells (RBC) from patients with malaria, sickle cell anemia, and diabetes also adhere to endothelial cells. The objectives of this investigation were to develop a bovine system of RBC adhesion to endothelial cells and to begin to investigate the mechanisms involved in the RBC adhesion. We show that 51Cr-RBC adhere to bovine pulmonary artery endothelial cells (BPAEC) after stimulation of both cell types with endotoxin (ETX; 50 micrograms/ml). RBC adhesion to BPAEC depended on the ETX concentration and the presence of divalent cations. TNF-alpha, IL-1 beta, and antioxidants (superoxide dismutase; catalase; and dimethyl sulfoxide) all induced RBC adhesion to BPAEC. Phosphatidylserine, which has been implicated in adhesion of sickle cells and aged RBC to endothelium, reduced RBC adhesion to BPAEC, whether ETX-treated or not. In conclusion, ETX, proinflammatory cytokines and, surprisingly, antioxidants increase RBC adherence to BPAEC monolayers. RBC adhesion to endothelium is decreased by phosphatidylserine.
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PMID:Endotoxin-induced adhesion of red blood cells to pulmonary artery endothelial cells. 877 24

1. This study was conducted on 467 cases of non-insulin-dependent diabetes mellitus and 180 healthy controls. Lipid peroxidation products in plasma and erythrocytes were assayed as thiobarbituric acid reactive substances, along with the erythrocyte antioxidant enzymes, namely superoxide dismutase, catalase and glutathione peroxidase. In addition, scavenger vitamins A, C and E and reduced glutathione levels in blood were also measured. 2. Lipid peroxidation was significantly raised within the first 2 years of diagnosis, and superoxide dismutase, catalase, reduced glutathione and vitamins C and E were significantly lowered. 3. These changes were correlated with the duration of the disease and were of a higher magnitude with the development of complications. 4. The results suggest that the antioxidant deficiency and excessive peroxide-mediated damage may appear early on in non-insulin-dependent diabetes mellitus, before the development of secondary complications.
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PMID:Antioxidant status and lipid peroxidation in type II diabetes mellitus with and without complications. 877 31

Maternal diabetes during pregnancy is associated with an increased rate of congenital malformations in the offspring. The exact molecular etiology of the disturbed embryogenesis is unknown, but an involvement of radical oxygen species in the teratological process has been suggested. Oxidative damage presupposes an imbalance between the activity of the free oxygen radicals and the antioxidant defence mechanisms on the cellular level. The aim of the present study was to investigate if maternal diabetes in vivo, or high glucose in vitro alters the expression of the free oxygen radical scavenging enzymes superoxide dismutase (CuZnSOD and MnSOD), catalase and glutathione peroxidase in rat embryos during late organogenesis. We studied offspring of normal and diabetic rats on gestational days 11 and 12, and also evaluated day-11 embryos after a 48 hour culture period in 10 mM or 50 mM glucose concentration. Both maternal diabetes and high glucose culture caused growth retardation and increased rate of congenital malformations in the embryos. The CuZnSOD and MnSOD enzymes were expressed on gestational day 11 and both CuZnSOD, MnSOD and catalase were expressed on day 12 with increased concentrations of MnSOD transcripts when challenged by a diabetic milieu. There was a good correlation between mRNA, protein, and activity levels, suggesting that the regulation of these enzymes occurs primarily at the pretranslational level. Maternal diabetes in vivo and high glucose concentration in vitro induced increased MnSOD expression, concomitant with increased total SOD activity, and a tentative decrease in catalase expression and activity in the embryos. These findings support the notion of enhanced oxidative stress in the embryo as an etiologic agent in diabetic teratogenesis.
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PMID:Altered levels of scavenging enzymes in embryos subjected to a diabetic environment. 880 88


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