Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of blood glutathione (GSH) were measured in 26 type II diabetes mellitus patients compared to 36 controls. Total blood GSH did not differ significantly between the two groups (mean +/- s.d., 8.0 +/- 1.5 vs. 7.7 +/- 1.3 mmol/g Hb, respectively); however reduced GSH was lowered in diabetes mellitus (5.0 +/- 1.0 vs. 5.8 +/- 1.0 mmol/gHb; P = 0.01), whereas oxidized GSH was increased (0.4 +/- 0.2 vs. 0.2 +/- 0.1 mmol/gHb; P = 0.001). Urinary excretion of 5-oxoproline was excessive in the diabetic patients (14.5 +/- 9.9 vs. 3.8 +/- 1.4 mmol/24 h; P = 0.004), and was positively correlated with levels of glycosylated haemoglobin (r = 0.69; P less than 0.01).
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PMID:Excessive excretion of 5-oxoproline and decreased levels of blood glutathione in type II diabetes mellitus. 208 14

The inhibition of lipid peroxidation of erythrocyte membranes by glutathione-dependent protection was studied in patients with non-insulin dependent diabetes mellitus. Incubation of red cells from diabetics with 1.5 mM t-butyl hydroperoxide resulted in a lipid peroxidation increase greater than that of normal controls. Glutathione-dependent and glutathione-independent protection against oxidative damage was examined using an artificial system, in which erythrocyte ghosts were incubated with t-butyl peroxide and dialysed hemolysate in the presence or the absence of 2 mM glutathione. The glutathione-dependent protection of hemolysate from diabetics was approximately 70% of that from normal controls. The results suggest that decrease in glutathione-dependent protection against lipid peroxidation, along with decrease in glutathione levels, increases oxidative damage in erythrocyte membranes taken from diabetic patients.
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PMID:Decrease of the inhibition of lipid peroxidation by glutathione-dependent system in erythrocytes of non-insulin dependent diabetics. 270 43

In the present study, leukocyte lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and serum and leukocyte vitamin C levels of patients with type II diabetes mellitus and healthy controls were investigated. Patients consisted of 53 cases (23 male, 30 female) aged 35-75 years and controls of 34 subjects (15 male, 19 female) aged 34-66 years. Leukocyte lipid peroxidation of diabetics was significantly increased (P < 0.05) whereas vitamin C level was decreased (P < 0.05) compared to those of controls. There was no significant difference in the other parameters. Also, there was no correlation between the above parameters and HbA1c and glucose levels. Our results show that leukocytes of diabetics are affected by oxidative stress which might be a reason for decreased microbicidal activity.
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PMID:Leukocyte lipid peroxidation, superoxide dismutase, glutathione peroxidase and serum and leukocyte vitamin C levels of patients with type II diabetes mellitus. 871 39

A total of 105 subjects with impaired glucose tolerance were classified into two groups, 51 subjects with plasma glucose > 11.1 mmol l-1 in one of the blood samplings during OGTT, but at 2 h being less than < 11.1 mmol l-1 were classified as early hyperglycaemics. Fifty-four cases were classified as true IGT, with fasting plasma glucose < 7.8 mmol l-1 and post plasma glucose level between 7.8 and 11.1 mmol l-1. Age and sex matched groups of normals (healthy adults) and NIDDM cases without symptomatic secondary complications were also included in the study. Lipid peroxidation (LPO) product in plasma, erythrocyte, and erythrocyte cell membrane were found to be significantly elevated (p < 0.001) in IGT, early hyperglycaemia and diabetes mellitus while glycosylated haemoglobin was also higher. Antioxidant enzymes superoxide dismutase and catalase were significantly lower in red blood cells obtained from IGT and early hyperglycaemic groups. They were closer to the levels showed in NIDDM confirming that antioxidant deficiency is already present in subjects classified as impaired glucose tolerant. Among the antioxidant scavengers, reduced glutathione (GSH) and ascorbic acid are reduced by 15% and 20% in IGT and NIDDM, respectively. We conclude that antioxidant status is poor in both IGT and NIDDM, suggesting an overlap of frank diabetic state in those classified as IGT. It is possible that antioxidant therapy might retard progression from IGT to NIDDM.
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PMID:Abnormal antioxidant status in impaired glucose tolerance and non-insulin-dependent diabetes mellitus. 886 45

ICAM-1 is one of the most important intercellular adhesion molecules involved in atherogenesis. Previous studies reported increased circulating ICAM-1 plasma levels in NIDDM patients with or without vascular complications. It has been suggested that an acute increase of plasma glucose may produce an oxidative stress in man, and in vitro studies have demonstrated that high glucose and free radicals induce cellular expression of ICAM-1. In this study, three different experiments were performed in nine NIDDM patients and in seven matched healthy controls: oral glucose tolerance test, antioxidant glutathione i.v. administration for two h, oral glucose tolerance test plus glutathione i.v. administration. Blood samples were drawn at -15 min and every 30 min from 0 to 180 min. During the oral glucose tolerance test, circulating ICAM-1 plasma levels significantly increased in both diabetic and normal subjects. Glutathione administration during the oral glucose tolerance test abolished this phenomenon. Glutathione administered alone significantly decreased circulating ICAM-1 plasma levels in diabetic patients, while no effect was observed in the normal subjects. These data suggest that hyperglycemia may induce an increase of circulating ICAM-1 plasma levels through an oxidative stress, and that the antioxidant glutathione counterbalances this effect. These data support the hypothesis of a causal relationship linking hyperglycemia, oxidative stress and atherogenesis in diabetes mellitus.
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PMID:Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus: the possible role of oxidative stress. 956 57

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

Several studies suggest that nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to cardiovascular mortality. Furthermore, NO synthesis is impaired in glutathione (GSH)-depleted human umbilical vein endothelial cells and GSH is reduced in patients with type 2 diabetes mellitus (T2DM). We tested the hypothesis that treatment with GSH may improve platelet constitutive NO sinthase (cNOS) activity in patients with T2DM. Fifteen patients with T2DM underwent a treatment with GSH 600 mg/day i.m. for 10 days. With respect to the basal values on the 10th day of treatment, the red blood cell GSH concentration and platelets cNOS increased (1.4+/-0.1 vs 1.9+/-0.1 micromol/10(10) RBC, p<0.001 and 0.7+/-0.1 vs 2.9+/-0.2 fmol x min(-1) x 10(-9) PLTs, p<0.001, respectively) and the plasma PAI-1 levels diminished (81.4+/-3.7 vs 68.7+/-4.0 ng/ml, p<0.002). A negative correlation between the cNOS and the PAI-1 was found on the basal values. After a wash-out of 30 days the values of red blood cell GSH concentration, platelet cNOS activity and PAI-1 Ag returned to the basal levels. These data suggest that the administration of GSH, in patients with T2DM, is able to improve platelet cNOS activity together with a reduction of PAI-1.
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PMID:Administration of glutathione in patients with type 2 diabetes mellitus increases the platelet constitutive nitric oxide synthase activity and reduces PAI-1. 1122 30

The high level of glucose in blood for a long duration is the main cause of the development of retinopathy. So yearly screening of patients newly diagnosed with NIDDM diabetes is recommended because rare cases of treatable diabetic retinopathy have occurred early in one course of NIDDM diabetes. Hyperglycaemia leads to non-enzymatic glycosylation of proteins and HbA1C was found increased. Antioxidants such as GSH and SOD level is found decreased in retinopathy conditions due to the higher lipid peroxidation, which is evident from high MDA and DC values. So it can be clearly stated that increase in the free radical by hyperglycaemia, lipid peroxidation and advanced glycosylation endproducts along with decreased antioxidants are the causative agents for the development of retinopathy.
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PMID:Lipid peroxidation and diabetic retinopathy. 1148 66

Elevation of glucose concentration in diabetes may induce generation of oxygen free radicals such as superoxide (O2*-) and hydroxyl (*OH). The aim of the present study was to investigate the effect of the oxidative stress on the activities of blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and aldose reductase, the levels of reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances; TBARS) and plasma levels of insulin-like growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in type 2 (non-insulin-dependent diabetes) patients and in healthy controls. Blood SOD, CAT, GSH-Px and GSSG-R were lower in type 2 diabetic patients compared with the the control group. Blood aldose reductase activity was elevated in patients with type 2 diabetes compared with the control group. GSH was decreased while TBARS concentration was increased in red blood cells (RBC) and leukocytes from the patients with type 2 diabetes mellitus in comparison to the control group. The mean values of plasma LH, FSH and testosterone were decreased, whereas the mean plasma IGF-1 concentration was increased in type 2 diabetes compared with controls. These findings support the hypothesis that hyperglycemia enhances the activity of the polyol pathway and impairs the antioxidant status, particularly glutathione redox cycle, resulting in poorer defense against oxidative stress. In addition, decreased circulating testosterone and gonadotropin levels may reflect the oxidative stress exerted by diabetes.
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PMID:Oxidative stress and male IGF-1, gonadotropin and related hormones in diabetic patients. 1152 8

The cytotoxic side effects of anti-neoplastic drugs are increased in patients with either type 1 or type 2 diabetes mellitus by a mechanism that is not clearly defined. We report that the circulating glucose metabolite, methylglyoxal (MGO), enhances cisplatin-induced apoptosis by activating protein kinase Cdelta (PKCdelta). We found that treatment of myeloma cells with the antioxidant N-acetylcysteine completely blocked cisplatin-dependent intracellular GSH oxidation, reactive oxygen species (ROS) generation, poly(ADP-ribose) polymerase cleavage, and apoptosis. Importantly, co-treatment of cells with the reactive carbonyl MGO and cisplatin increased apoptosis by 90% over the expected additive effect of combined MGO and cisplatin treatment. This same synergism was also observed when ROS generation was examined. MGO and cisplatin increased PKCdelta activity by 4-fold, and this effect was blocked by the PKCdelta inhibitor rottlerin but not by NAC. Furthermore, rottlerin blocked combined MGO and cisplatin-induced ROS generation and apoptosis. Finally, MGO and cisplatin induced c-Abl activation and c-Abl:PKCdelta association. Rottlerin blocked c-Abl activation, but the c-Abl inhibitor STI-571 increased MGO and cisplatin-induced apoptosis by 50%. Taken together these data indicate that MGO synergistically enhances cisplatin-induced apoptosis through activation of PKCdelta and that PKCdelta is critical to both cell death and cell survival pathways. These findings suggest that in the patient with diabetes mellitus heightened oxidative stress can enhance the cytotoxicity of agents that induce DNA damage.
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PMID:Methylglyoxal enhances cisplatin-induced cytotoxicity by activating protein kinase Cdelta. 1170 30


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