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)

The concentrations of Cu and Zn were determined in the plasma, granulocytes and mononuclear cells of 26 patients with diabetes mellitus and 26 age and sex-matched controls. In addition, Cu was measured in both washed and unwashed red blood cells, and Cu,Zn-superoxide dismutase (SOD) activity measured in washed red blood cells. Cu and Zn were determined by Zeeman-effect graphite furnace atomic absorption spectrometry following separation of plasma and red blood cells, and the white blood cell fractions (granulocytes and mononuclear cells) by density gradient centrifugation. There were no significant differences in any of the matching factors, or lipid profiles, between the groups. Plasma Zn was reduced by 17% in diabetics, compared with the controls (P = 0.0001). Neither the plasma nor the red blood cell Cu concentrations were significantly different. Of the white blood cell fractions, only mononuclear cell Cu was significantly different (30% lower in diabetics P = 0.0035, The red blood SOD activity was reduced in diabetics by over 12%, but this difference was non-significant (P = 0.0872). There was a significant negative correlation between washed red blood cell Cu and the duration of diabetes (r = -0.613, P = 0.0069). In conclusion, the copper and zinc status of these diabetic patients was reduced, providing further evidence of a role for these antioxidant trace elements in this disease.
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PMID:Plasma, granulocyte and mononuclear cell copper and zinc in patients with diabetes mellitus. 774 Dec 48

Experiments were performed to determine the influence of endogenous nitric oxide (NO) on basal arteriolar diameter in kidneys from diabetic rats and to evaluate the role of superoxide anions as modulators of NO activity under these conditions. Male Sprague-Dawley rats were injected with streptozotocin (STZ, 65 mg/kg i.v.) and received insulin via ip osmotic minipumps (3 U/kg per day). Sham rats received vehicle treatments. Videomicroscopy was used, in conjunction with the in vitro blood-perfused juxtamedullary nephron technique, to visualize renal afferent and efferent arterioles 2 wk after the onset of diabetes. Baseline afferent arteriolar inside diameter was greater in STZ (32 +/- 2 microns) than in sham rats (24 +/- 2 microns). Efferent arteriolar diameter did not differ between STZ (24 +/- 2 microns) and sham rats (21 +/- 1 microns). In kidneys from sham rats, N omega-nitro-L-arginine (L-NNA, an NO synthase inhibitor) decreased arteriolar diameters in a concentration-dependent manner, with 100 microM L-NNA significantly reducing both afferent (13 +/- 2%) and efferent (11 +/- 1%) diameters. In kidneys from STZ rats, 100 microM L-NNA reduced afferent and efferent diameters by only 3 +/- 1 and 4 +/- 1%, respectively, indicating a suppressed arteriolar influence of NO. In STZ kidneys treated with superoxide dismutase (SOD, 150 U/mL), afferent and efferent arteriolar L-NNA responses were restored to levels comparable to those of SOD-treated and untreated sham kidneys. These observations suggest that suppressed SOD activity reduces the tonic influence of NO on renal arterioles during the early stage of diabetes mellitus, perhaps through allowing the accumulation of NO-scavenging superoxide anions.
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PMID:Superoxide dismutase restores the influence of nitric oxide on renal arterioles in diabetes mellitus. 775 88

Cytokines are a group of regulatory and immunomodulatory proteins involved in a number of physiological processes. Various disease states are believed to involve alteration of normal cytokine activity, including insulin-dependent diabetes mellitus, an autoimmune disease in which insulin secreting beta cells within pancreatic islets of Langerhans are selectively destroyed. Glucose-induced insulin secretion is inhibited by the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 and tumour necrosis factor alpha (TNF) when combined with IL-1 beta in cultured rat islets, by IL-1 beta, TNF and interferon gamma in mouse islets, and by combined treatment of IL-1 beta, TNF and interferon gamma in human islets. Continued cytokine treatment in many cases leads to destruction of some, if not all, islet cells. A key factor in the inhibitory effect of IL-1 beta and TNF in rat islets is the generation of nitric oxide which inactivates enzymes such as aconitase and ribonucleotide reductase by formation of iron-nitrosyl complexes. This in turn may lead to reduced oxidation of glucose and synthesis of ATP and DNA respectively. The causes of cytokine-induced beta cell death are less well defined, but important factors may be nitric oxide-mediated DNA damage, depletion of NAD levels and toxic effects of oxygen free radicals and eicosanoids generated in addition to nitric oxide. Potentially important defence and repair responses induced by IL-1 beta treatment of rat islets are formation of heat shock protein, haem oxygenase, and superoxide dismutase. Other protective responses may be induction of cytokines and cytokine receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines, nitric oxide and insulin secreting cells. 775 73

The specific activities of superoxide dismutase, catalase, and glutathione S-transferase (mu subtype) were significantly lower in the brains of mice with type II diabetes than in the brains of control mice. On the other hand, the specific activity of glutathione peroxidase was unaltered. The concentration of vitamin E, but not that of total glutathione and ascorbate, was increased in the brains of the type II diabetic mice. The relative amount of polyunsaturated fatty acids (as determined with soybean lipoxygenase) was increased in whole brains and crude synaptosomal membranes of the type II diabetic mice. Endogenous levels of thiobarbituric acid-positive material were decreased in both whole brain homogenates and crude synaptosomal membranes of the db/db mice. Susceptibility of lipids within whole brain homogenates and crude synaptosomal membranes of mice with type II diabetes to peroxidation with iron/ascorbate was also markedly decreased compared with that of controls. Vitamin E is known to quench lipid peroxidation. Therefore, decreased lipid peroxidation in the type II mouse brain may be due to increased vitamin E content.
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PMID:Antioxidant defense systems in the brains of type II diabetic mice. 779 Aug 73

Vascular complications such as atheroma, hypertension and macroangiopathy are the leading causes of morbidity and mortality in diabetic patients. Epidemiological and clinical data linking hyperinsulinaemia to both hypertension and atherosclerosis are inconsistent. Hyperglycaemia is the distinguishing feature of diabetes and it seems a likely candidate for the poor cardiovascular outlook of diabetic patients. High blood glucose levels cause selective impairment of endothelium-dependent relaxation and delay cell replication time of cultured human endothelial cells. These effects of hyperglycaemia are reversed by a number of antioxidants, including superoxide dismutase, catalase and glutathione. Impaired endothelium-dependent vasodilation has been reported both in Type 1 and Type 2 diabetic patient. The evidence for a role of oxygen-derived free radicals in the pathogenesis of vascular diabetic complications can be summarized as follows: 1) glucose can auto-oxidize generating oxygen derived free radicals; 2) elevated levels of oxygen derived free radicals are found in red blood cells, plasma and retina of diabetic animals and patients, and correlate with metabolic control; 3) endogenous antioxidants are all decreased in diabetic tissues and blood; and 4) treatment with different antioxidants may improve many of the metabolic abnormalities reported to occur in diabetic patients. The use of antioxidants to reduce the risk of coronary heart disease in diabetes should await the results of randomized trials with these drugs in the primary and secondary prevention of coronary disease.
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PMID:Medical hypothesis: cardiovascular complications of diabetes mellitus-from glucose to insulin and back. 785 91

Free radicals are produced in the body as by products of normal metabolism and as a result of exposure to radiation and some environmental pollutants. Because they are highly reactive, they can damage cellular components and are implicated in a variety of diseases. Free radicals are normally neutralized by efficient systems in the body that include the antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and the nutrient-derived antioxidant small molecules (vitamin E, vitamin C, carotenes, flavonoids, glutathione, uric acid, and taurine). In healthy individuals, a delicate balance exists between free radicals and antioxidants. In some pathologic conditions such as diabetes, and in critically ill patients, oxidative stress causes the level of antioxidants to fall below normal. Antioxidant supplements for such conditions are expected to be of benefit. As a preventive measure against certain diseases, the best approach for healthy individuals is to regularly consume adequate amounts of antioxidant-rich foods, eg, fruits and vegetables.
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PMID:Role of antioxidants in health maintenance. 789 13

Activities of superoxide dismutase and glutathione peroxidase were measured in 60 children aged 5 to 15 with insulin-dependent diabetes of various degrees of compensation and duration. Measurements of glutathione peroxidase were found to be the most informative marker of the status of antioxidant defense system.
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PMID:[Activities of antioxidant defense enzymes in children with insulin-dependent diabetes mellitus]. 789 50

Free radicals have been implicated in beta-cell destruction. pancreatic antioxidant enzymatic defenses provide significant endogenous protection from these highly cytotoxic effector molecules. In our colony of BB rats, the reliability of peripheral blood lymphocyte count (PBLC) as a predictor of diabetes onset was assessed in 99 male and 110 female BB rats. In rats with a PBLC < 4,200 mm3, 90% of males and 86% of females developed diabetes by 120 days of age and are designated "lymphopenic" or BBL. Rats with a PBLC > 4,200 mm3 have a much lower incidence of insulin-dependent diabetes mellitus (IDDM) and are designated "nonlymphopenic" or BBNL. In separate cohorts of normoglycemic (prediabetic) BBL rats (high risk for developing diabetes) and BBNL rats (low risk for developing diabetes), the activities of pancreatic cytosolic antioxidant enzymes, copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), and glutathione peroxidase (GPX) were determined. Alterations in CuZnSOD and CAT were noted in BBL males only as compared to BBNL males and BBL and BBNL females. CuZnSOD and CAT activities were significantly lower in BBL males. GPX showed a similar trend. The changes in pancreatic antioxidant enzymes precede overt hyperglycemia in male rats at risk for development of diabetes and may result in increased beta-cell vulnerability to oxygen-derived free radical destruction.
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PMID:Pancreatic antioxidant enzyme activity in normoglycemic diabetic prone BB rats. 789 60

A growing body of evidence suggests that active oxygen is an important participant in the destruction of the pancreatic beta cell, which, in turn, leads to type I or insulin-dependent diabetes mellitus. Consequently, genetic factors predisposing susceptibility to insulin-dependent diabetes mellitus may include those that determine active oxygen metabolism. A direct test of this hypothesis is provided by a transgenic model for increased activity of Cu/Zn superoxide dismutase (EC 1.15.1.1), a principal radical scavenging enzyme. Here we demonstrate that elevated levels of this enzyme provided by a Cu/Zn superoxide dismutase transgene enhance the tolerance of pancreatic beta cells to oxidative stress-induced diabetogenesis. These results show that this transgenic approach holds promise for revealing the role of reactive oxygen in autoimmune models of diabetogenesis as well as in other models of disease pathology in which active oxygen has been implicated.
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PMID:Transgenic copper/zinc superoxide dismutase modulates susceptibility to type I diabetes. 793 25

Pancreatic superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities were measured during the development of diabetes in diabetes-prone BB rats (BBdp) prior to insulin dependence. The pancreata from seven to eight BBdp rats of each sex were examined at ages 5, 7, 10, and 18 weeks and compared with age-matched control BB rats (BBc). At Week 18, BBdp rats had moderate to high insulitis but normal levels of blood glucose and insulin. Pancreatic CuZnSOD activity in BBdp rats was two times higher than the activity seen in BBc rats at age 5-10 weeks but then declined to the same level as seen in BBc rats at 18 weeks of age. MnSOD activity increased over time in the BBdp rats but remained very low in BBc rats. These changes in CuZnSOD and MnSOD activity resulted in BBdp rats having twice the pancreatic total SOD activity compared with BBc rats (P < 0.0001). Total GSHPx activity was significantly reduced in the pancreata from both male and female BBdp rats compared with their respective controls (P < 0.01 and P < 0.0001, respectively). The lower total GSHPx activity was due to reduced selenium-dependent GSHPx (SeGSHPx) activity. Erythrocyte and plasma activity of these enzymes was not different between rats with or without insulitis, indicating that differences in enzyme activities were confined to the pancreas. Thus, changes in pancreatic antioxidant enzyme activities occur prior to the development of diabetes symptoms in BBdp rats and may be related to the destruction of the pancreatic B cells and ultimate development of diabetes.
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PMID:Changes in pancreatic glutathione peroxidase and superoxide dismutase activities in the prediabetic diabetes-prone BB rat. 793 51


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