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)

Fas-associated death domain protein (FADD)/MORT1 is a 23-kDa cytoplasmic protein containing a C-terminal death domain that interacts with the intracellular death domain of the Fas transmembrane receptor. Cross-linking of Fas mediates apoptosis in a variety of cells, primarily peripheral T lymphocytes, for which this pathway plays a major role in mature lymphocyte homeostasis. We report the characterization of the human FADD gene, which spans approximately 3.6 kb and contains two exons (286 and 341 bp) separated by a 2.0-kb intron. FADD was mapped to chromosome 11q13.3 by the independent techniques of PCR screening of somatic cell hybrid mapping panels and fluorescence in situ hybridization. In addition FADD was shown by fluorescence in situ hybridization to be amplified along with other 11q13.3 genes previously studied in the breast cancer cell line MDA-MB-134-VI, raising the possibility that overexpression of mutant FADD could contribute to poor prognosis and increased invasiveness of tumors. Its known role in apoptosis has made FADD a candidate susceptibility gene for autoimmune lymphoproliferative syndrome. Now that it has been colocalized in 11q13.3 with IDDM4, a diabetes susceptibility locus, alterations in FADD should also be considered as potential contributors to insulin-dependent familial diabetes. Elucidation of the map position and gene structure of FADD will make possible linkage and mutation analysis to study the role of this gene in human diseases.
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PMID:Genomic structure and mapping of human FADD, an intracellular mediator of lymphocyte apoptosis. 895 95

Experiments on rats with experimental streptosotocin-induced diabetes have shown intensification of the lipid peroxidation processes and reduction of activity of antioxidant defensive enzymes. The content of G-SH and glutathione peroxidase activity has decreased in comparison with the normal rate by 69% and 28%, respectively. Glutathione reductase activity has risen by 20%. Activity of the antioxidant enzymes (superoxide dismutase, catalase) has reduced and the amount of the final product of lipid peroxidation, MDA has increased. Injection of nicotinamide to diabetic rats (200 mg/1 kg of weight) for 14 days normalized activity of the antioxidant enzyme system and the content of the lipid peroxidation products.
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PMID:[The effect of nicotinamide on the enzymatic activity of the antioxidant defense in experimental diabetes]. 900 53

Many antioxidants have been found in spices and herbs, and some of them are well known as strong scavengers of active oxygen radicals. We have isolated active products, which markedly inhibited the formation of malondialdehyde (MDA from 2-deoxyribose and the hydroxylation of benzoate with the hydroxyl radical, from methanol extracts of allspice and clove. Pimentol from allspice, and biflorin and its isomer, abbreviated as clove3, from clove were identified as the active principles. These revealed strong activity as hydroxyl radical scavengers at a concentration of 2.0 microM. The antioxidative activities in an in vitro model system involving the rabbit erythrocyte membrane ghost were as strong as those of alpha-tocopherol at 200 microM. Such advanced glycation end products (AGE) as pentosidine are biomarkers of diabetes mellitus, and active oxygens have been suggested to be involved in the formation of AGE. The above-mentioned free radical scavengers effectively inhibited the formation of pentosidine in a model system of N alpha-t-butoxycarbonyl-fructoselysine and N alpha-t-butoxycarbonyl-arginine.
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PMID:Spice constituents scavenging free radicals and inhibiting pentosidine formation in a model system. 905 63

The actions of S2-receptor antagonist naftidrofuril (Duzodril-retard, Byk Gulden, FRG) on both basal and thrombin-induced levels of malondialdehyde in platelets as well as platelet aggregability in patients with insulin-dependent diabetes mellitus with or without angiopathies were studied. Significant decrease in the basal level of MDA was observed after treatment and the effect was more profound in patients without vascular complications. The treatment with Duzodril-retard at daily dose of 200 mg during 40 days was not shown to decrease in platelet hyperfunction in response to the inductors: ADP, 1 and 5 microM; adrenaline, 1 microM; collagen, 4 mu/ml; ristomycin, 0.9 and 1.2 mg/ml; and thrombin 0.5 U/ml). The reduction of hyperreactivity of platelets in response to adrenaline in patients without angiopathies was found out during treatment with Duzodril-retard. This could be referred as positive sign for prognosis because of decrease in sensitivity of platelets to adrenaline may lead to corresponding decrease in reactivity to ADP during long-term usage of naftidrofuril. Platelets of the patients were shown to be hypersensitive to ADP at maximal extent. The decrease in the sensitivity of platelets to large concentrations of ristomycin was found, the fact which may serve as an evident for some normalization of functional activity of platelets as well endothelin-platelet interactions in patients without vasal complications. Thus, Duzodril-retard has an activity as angio-protector in most degree at the cases when vasal disturbances are not clinically significant yet.
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PMID:[Possibility of regulating platelet aggregation ability with the S2-receptor blocker, naftidrofuril, in patients with insulin-dependent diabetes mellitus]. 925 23

Body iron status has been implicated in atherosclerotic cardiovascular disease. The main hypothesis was that high iron status was associated with increased oxidation of LDL. The associations of serum ferritin (a marker of iron status) and dietary iron intake with the susceptibility of LDL to in vitro oxidation (lag phase) and autoantibodies against MDA-modified LDL (two markers of oxidation stress) were examined among 281 men and 192 women with a mean age of 59 years (S.D. = 5) who participated in the Atherosclerosis Risk in Communities (ARIC) Study visit 2 in 1990 through 1992. Lag phase duration and the autoantibodies against MDA-modified LDL were weakly correlated with each other (r = 0.19, P = 0.001 in men; r = 0.15, P = 0.03 in women). In linear regression analysis adjusting for age, field center, blood storage time, and carotid atherosclerosis case-control status, there was no association between ferritin level and the lag-phase, or between ferritin level and autoantibodies against MDA-modified LDL in either sex. Further adjustment for traditional cardiovascular risk factors (smoking, vitamin supplement use, body mass index, LDL cholesterol, hypertension and diabetes) did not alter these null results. Ferritin was significantly and positively correlated with body mass index in both sexes (r = 0.21 among men and r = 0.22 among women) and with the waist-to-hip ratio among women (r = 0.26). In addition, among women, ferritin was positively correlated with orosomucoid (r = 0.24) and with sialic acid (r = 0.19). Dietary iron was not associated with the parameters of LDL oxidation or with ferritin level. These findings do not support a role of body iron stores in promoting oxidation of LDL.
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PMID:Lack of association between ferritin level and measures of LDL oxidation: the ARIC study. Atherosclerosis Risk in Communities. 969 7

We have studied the effect of the administration of two doses of melatonin (melatonin 100 and melatonin 200 microg/kg bw) on diabetes and oxidative stress experimentally induced by the injection of streptozotocin (STZ) in female Wistar rats. STZ was injected as a single dose (60 mg/kg i.p. in buffered citrate solution, pH 4.0) and melatonin (melatonin 100, 100 microg/kg/day i.p.; melatonin 200, 200 microg/kg/day i.p.) beginning 3 days before diabetes induction and continuing until the end of the study (8 weeks). The parameters analysed to evaluate oxidative stress and the diabetic state were a) for oxidative stress, changes of lipoperoxides (i.e., malondialdehyde, MDA) in plasma and erythrocytes and the changes in reduced glutathione (GSH) in erythrocytes and b) for diabetes, changes in glycemia, lipids (triglycerides: TG; total cholesterol: TC; HDL-cholesterol, HDL-c), percentage of glycosylated hemoglobin (Hb%), and plasma fructosamine. The injection of STZ caused significant increases in the levels of glycemia, percentage of glycosylated hemoglobin, fructosamine, cholesterol, triglycerides, and lipoperoxides in plasma and erythrocytes, whereas it decreased the levels of HDL-c and the GSH content in erythrocytes. The melatonin 100 dose reduced significantly all these increases, except the percentage of glycosylated hemoglobin. With regard to the decreases of plasma HDL-c and GSH content in erythrocytes, this melatonin dose returned them to normal levels. The melatonin 200 dose produced similar changes, though the effects were especially noticeable in the decrease of glycemia (55% vs. diabetes), percentage of hemoglobin (P < 0.001 vs diabetes), and fructosamine (31% vs. diabetes). This dose also reversed the decreases of HDL-c and GSH in erythrocytes. Both doses of melatonin caused significant reduction of the percentage of glycosylated hemoglobin in those groups that were non-diabetic. These illustrate the protective effect of melatonin against oxidative stress and the severity of diabetes induced by STZ. In particular, this study confirms two facts: 1) the powerful antioxidant action of this pineal indole and 2) the importance of the severity of oxidative stress to maintain hyperglycemia and protein glycosylation, two pathogenetic cornerstones indicative of diabetic complications. Melatonin reduces remarkably the degree of lipoperoxidation, hyperglycemia, and protein glycosylation, which gives hope to a promising perspective of this product, together with other biological antioxidants, in the treatment of diabetic complications where oxidative stress, either in a high or in a low degree, is present.
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PMID:Oxidative stress in diabetic rats induced by streptozotocin: protective effects of melatonin. 975 30

A total of 154 patients with type-I insulin-nondependent diabetes mellitus were examined together with 222 patients presenting with type-II insulin-nondependent diabetes mellitus. In glycemia of up to 6.66 mmol/l the level of blood plasma cholesterol was (5.40 +/- 0.02) mmol/l; with 7.77 mmol/l it came up to (6.33 +/- 0.02) mmol/l. Correlation has been shown to exist between fast glycemia and decline in the HDLP levels of cholesterol and rise in the atherogenicity factor. The content of MDA in plasma, LDLP + VLDLP, erythrocytes appeared to be related to the content of glycosylated hemoglobin. The author arrives at a conclusion that decompensation of DM is the most important factor of atherogenesis, attainment of a stable compensation is an essential condition of prevention of atherosclerosis further development in DM patients.
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PMID:[The atherogenesis characteristics of diabetic patients]. 1042 99

This study examines the effect of high glucose levels on the markers of oxidative stress, phosphatidylserine (PS) externalization, and induction of coagulation by high-glucose-treated red blood cells (RBCs). Washed normal RBCs were suspended to 15% hematocrit in phosphate-buffered saline and incubated with different concentrations of glucose for 24 hours in a shaking water bath at 37 degrees C. This treatment caused depletion of vitamin E and accumulation of vitamin E-quinone and malondialdehyde ([MDA] an end product of lipid peroxidation), externalization of PS in the membrane bilayer, and induction of coagulation by RBCs. Pretreatment of RBCs with N-acetylcysteine (NAC) and vitamin E reduced membrane lipid peroxidation, PS externalization, and the tendency of high-glucose-treated RBCs to clot plasma. This study provides further evidence for the increased oxidative stress in RBCs exposed to high glucose levels. In addition, it suggests a role for membrane lipid peroxidation in the PS externalization in the membrane bilayer and in the induction of clotting by RBCs exposed to hyperglycemia. It also suggests that certain antioxidants can decrease cellular damage and restore certain cellular functions in diabetes.
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PMID:Effect of vitamin E and N-acetylcysteine on phosphatidylserine externalization and induction of coagulation by high-glucose-treated human erythrocytes. 1045 57

By-products of lipoperoxidation reactions may be associated with the genesis or the progression of several diseases as arteriosclerosis, diabetes and cancer, among many others. Acrolein, at first a widely distributed environmental pollutant, is currently known as a compound capable of being generated as a result of metabolic reactions within biological systems, highly toxic and the most electrophilic of the alpha, beta-unsaturated aldehydes formed during lipoperoxidation. In the present study: 1. The separation of acrolein and malondialdehyde was achieved at alkaline pH with the use of high voltage capillary electrophoresis in uncoated fused-silica capillaries. 2. It was demonstrated how the oxidation of fatty acids (arachidonic/linoleic) with ozone generates, in dose-dependent form, acrolein as one of the by-products of the lipoperoxidation process. The oxidation of open human erythrocyte membranes with ozone also generated acrolein. 3. After aldolic condensation, aldol-acrolein derivative has a positive reaction with 2-thiobarbituric acid (TBA) and shows a maximum absorption at 498 nm. This novel characteristic is used in its identification after the separation of the by-products. 4. It is possible to suggest that in the classic reaction of the denominated thiobarbituric acid reactive substances (TBARS), when used as an indicator of the degree of peroxidation in biological systems, a portion of acrolein could be present but dwarfed by the TBA-MDA adduct.
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PMID:Identification of acrolein from the ozone oxidation of unsaturated fatty acids. 1060 92

Incubation of normal erythrocytes with 10 mM H2O2 has caused a loss of deformability. This loss of deformability was correlated with the extent of malonyldialdehyde, MDA (an indicator of lipid peroxidation) and alanine production (an indicator of protein degradation). The susceptibility of erythrocytes from 21 non-insulin-dependent diabetes mellitus (NIDDM) and 18 hemodialysis patients, 21 cigarette smokers and 25 healthy controls to in vitro oxidative stress with H2O2 has been measured as MDA production. Besides this, their erythrocytes reduced glutathione (GSH; an antioxidant) level has also been determined, but before exposure to H2O2. Erythrocytes from NIDDM and hemodialysis patients have shown significant increase in MDA production and a significantly low GSH level, compared to healthy controls. In cigarette smokers, although the GSH level was significantly low, but there was no significant difference in MDA production, compared to healthy controls. The low GSH level in NIDDM and hemodialysis patients, and smokers indicates that their erythrocytes were exposed to oxidative stress (an increase in free radical load) in vivo, resulting in an overconsumption and/or decreased production of GSH. The increased susceptibility to oxidative stress along with the decrease in some antioxidants (e.g., GSH) may explain the significant increase in MDA production in NIDDM and hemodialysis patients. But in cigarette smokers, the increased susceptibility to oxidative stress is probably not sufficient to cause a significant increase in MDA production. The results may also indicate an increased susceptibility to the loss of erythrocyte deformability in NIDDM and hemodialysis patients compared to healthy controls.
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PMID:Susceptibility of erythrocytes from non-insulin-dependent diabetes mellitus and hemodialysis patients, cigarette smokers and normal subjects to in vitro oxidative stress and loss of deformability. 1097 10


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