Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, the antioxidative properties of repaglinide were examined in tissues of alloxan-induced diabetic rabbits. Glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and protein carbonyl groups (PCG) were measured after 4 and 8 weeks treatment with repaglinide (0.3 mg/kg daily). In liver, diabetic versus control values (mean +/- S.E.M., p<0.05) for GSH-Px were 181.0 +/- 5.4 mU/mg protein versus 203.1 +/- 1.9 mU/mg protein and 187.4 +/- 6.6 mU/mg protein versus 240.9 +/- 18.8 mU/mg protein. The respective values for GSH were 33.7 +/- 0.4 nmol/mg protein versus 49.0 +/- 1.6 nmol/mg protein and 37.7 +/- 1.0 nmol/mg protein versus 41.2 +/- 0.7 nmol/mg protein. In diabetic kidney, GSSG-R activity (20.6 +/- 1.6 mU/mg protein versus 32.4 +/- 1.5 mU/mg protein and 23.6 +/- 0.6 mU/mg protein versus 36.3 +/- 0.3 mU/mg protein) and GSH level (16.6 +/- 0.5 nmol/mg protein versus 23.2 +/- 0.9 nmol/mg protein and 17.9 +/- 0.5 nmol/mg protein versus 23.2 +/- 0.6 nmol/mg protein) were reduced compared to control. PCG level was elevated in diabetic liver (0.58 +/- 0.02 nmol/mg protein versus 0.16 +/- 0.03 nmol/mg protein at 4 weeks and 0.64 +/- 0.04 nmol/mg protein versus 0.16 +/- 0.03 nmol/mg protein at 8 weeks) and in diabetic kidney (0.32 +/- 0.03 nmol/mg protein versus 0.11 +/- 0.02 nmol/mg protein and 0.35 +/- 0.03 nmol/mg protein versus 0.16 +/- 0.03 nmol/mg protein). Repaglinide did not affect the glucose level but reduced to some extent the oxidative stress enhanced by chronic hyperglycemia. In diabetic kidney, it restored to control values GSSG-R activity (45.4 +/- 2.0 mU/mg protein at 4 weeks and 41.1 +/- 0.07 mU/mg protein at 8 weeks), GSH level (27.0 +/- 0.8 and 26.8 +/- 0.9 nmol/mg protein), and partly PCG level (0.17 +/- 0.02 nmol/mg protein at 8 weeks). The treatment partly affected GSH-Px activity (262.7 +/- 17.6 mU/mg protein) and GSH level (40.4 +/- 1.4 nmol/mg protein) in diabetic liver. This study shows that repaglinide produces measurable antioxidative effects at therapeutic dose.
Diabetes Res Clin Pract 2005 May
PMID:Effects of repaglinide on oxidative stress in tissues of diabetic rabbits. 1586 Feb 35

Hyperglycemia causes the autoxidation of glucose, glycation of proteins, and the activation of polyol metabolism. These changes accelerate generation of reactive oxygen species (ROS) and increases in oxidative chemical modification of lipids, DNA, and proteins in various tissues. Oxidative stress may play an important role in the development of complications in diabetes such as lens cataracts, nephropathy, and neuropathy. Glycation reactions, especially Maillard reactions, occur in vivo as well as in vitro and are associated with the chronic complications of diabetes mellitus and aging and age-related diseases by increases in oxidative chemical modification of lipids, DNA, and proteins. In particular, long-lived proteins such as lens crystallines, collagens, and hemoglobin may react with reducing sugars to form advanced glycation end products (AGEs). Recently, we found a novel type of AGE, named MRX, and we found that MRX is a good biomarker for detecting oxidative stress produced during Maillard reaction. We also examined in detail the role of lipid peroxidation reaction in hyperglycemia and found that hexanoyl modification formed by the reaction of oxidized lipids and proteins must be important for oxidative stress. Detailed analyses of the formation mechanism of hexanoyl lysine (HEL) moiety in proteins were conducted, and excretion of HEL into urine was quantified by using LC/MS/MS. Macrophages and neutrophils play an important role in oxidative stress during hyperglycemia, and we determined that oxidatively modified tyrosines are a good biomarker for formation of oxidative stress at an early stage. Immunochemical analyses by application of monoclonal antibodies specific to lipid hydroperoxide-modified proteins produced by polyunsaturated fatty acids including docosahexaenoic acid (DHA) in oxidative stress caused by hyperglycemia were conducted, and the relationship between glycation and lipid peroxidation reactions both by chemical and immunochemical approaches are discussed. Recently, we put much more focus on dietary antioxidants for prevention of diabetic complications. Curcuminoids, the main yellow pigments in Curcuma longa (turmeric), have been used widely and for a long time in the treatment of sprain and inflammation in indigenous medicine. Curcumin is the main component of turmeric, and two minor components are also present as the curcuminoids. Curcuminoids possess antioxidant activity. Protective effects of curcumin (U1) and one of its major metabolites, tetrahydrocurcumin (THU1), have been examined for development of diabetic cataract in 25% galactose-fed SD rats. Through detailed examination of protective mechanisms of THU1, it was found that THU1 showed that scavenger ROS not only formed during hyperglycemia, but also induced antioxidative enzymes including detoxification enzymes such as glutathine S-transferase. THU1 also showed significant increase of glutathione concentration in the cultured rat lens. Glutathione (gamma-glutamylcysteinyl glycine [GSH]) is thought to be an important factor in cellular function and defense against oxidative stress, and we found that dietary GSH suppresses oxidative stress in vivo in prevention of diabetic complications such as diabetic nephropathy and neuropathy.
 ...
PMID:Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. 1603 65

In the present study, we investigated the antioxidant status in diabetes mellitus, related or not to alcohol consumption. A total of 38 type 1, 48 type 2 and 42 alcohol-related diabetic patients were selected. Total antioxidant status was assessed through the oxygen radical absorbance capacity of the plasma and the determination of enzymatic and non-enzymatic antioxidant molecules. Serum triglycerides, total cholesterol and HDL-cholesterol concentrations were determined and the lipid peroxydation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) assay. Plasma total antioxidant capacity was more decreased in alcohol-related diabetes than that in type 1 and type 2 diabetes, regardless of the complications (retinopathy and renal failure). Plasma vitamin E concentrations were significantly decreased whereas those of vitamin C increased in all of the diabetic patients compared to the controls, irrespective to the complications. In addition, superoxide dismutase and glutathione peroxidase activities were reduced in all the patients (type 1, type 2 and alcohol-related), irrespective to the complications. Glutathione reductase activity was diminished in type 1 and alcohol-related, but not in type 2, diabetic patients. Glutathione (GSH) concentrations significantly decreased in all diabetic patients with a significant decrease in alcohol-related diabetic patients. Excessive alcohol consumption appears as an oxidative aggravating factor in diabetes mellitus. Besides, alcohol-related diabetes highly resembles to type 1 diabetes as far as the antioxidant parameters are concerned.
 ...
PMID:Antioxidant status in alcohol-related diabetes mellitus in Beninese subjects. 1637 21

Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction involving auto-reactive T-cells, pro-inflammatory cytokines, reactive oxygen species (ROS) and loss of insulin. Monozygotic twin studies show a 20-60% concordance with T1D indicating there may be an environmental component to the disease. Glutathione (GSH) is the major endogenous antioxidant produced by the cell. GSH participates directly in the neutralization of free radicals and plays a role in the immune response. Glutathione-s-transferases (GSTs) conjugate GSH to free-radicals or xenobiotics. GST activity depletes GSH levels and may either detoxify or enhance the toxicity of a compound. Glutathione-s-transferase mu 1 (GSTM1) and glutathione-s-transferase theta 1 (GSTT1) have polymorphic homozygous deletion (null) genotypes resulting in complete absence of enzyme activity. GSTM1 and GSTT1 null genotypes in Caucasian populations have frequencies of approximately 40-60% and 15-20%, respectively. GST null genotypes have been associated with susceptibility to cancer and protection against chronic pancreatitis. The aim of this study was to investigate associations with GSTM1 and GSTT1 polymorphisms in a group T1D patients and control subjects 0-35 years old who participated in the Combined Swedish Childhood Diabetes Registry and Diabetes Incidence Study (1986-1988). Results show that the presence of the GSTM1 and not the null genotype (OR, 2.13 95% CI, 1.23-3.70, p-value, 0.007, Bonferroni corrected p-value, 0.035) may be a susceptibility factor in T1D 14-20 years old. These results suggest that the GSTM1 null genotype is associated with T1D protection and T1D age-at-onset and that susceptibility to T1D may involve GST conjugation.
 ...
PMID:Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset. 1639 Aug 10

Glutathione and the related enzymes belong to the defence system protecting the eye against chemical and oxidative stress. This review focuses on GSH and two key enzymes, glutathione reductase and glucose-6-phosphate dehydrogenase in lens, cornea, and retina. Lens contains a high concentration of reduced glutathione, which maintains the thiol groups in the reduced form. These contribute to lens complete transparency as well as to the transparent and refractive properties of the mammalian cornea, which are essential for proper image formation on the retina. In cornea, gluthatione also plays an important role in maintaining normal hydration level, and in protecting cellular membrane integrity. In retina, glutathione is distributed in the different types of retinal cells. Intracellular enzyme, glutathione reductase, involved in reducing the oxidized glutathione has been found at highest activity in human and primate lenses, as compared to other species. Besides the enzymes directly involved in maintaining the normal redox status of the cell, glucose-6-phosphate dehydrogenase which catalyzes the first reaction of the pentose phosphate pathway, plays a key role in protection of the eye against reactive oxygen species. Cornea has a high activity of the pentose phosphate pathway and glucose-6-phosphate dehydrogenase activity. Glycation, the non-enzymic reaction between a free amino group in proteins and a reducing sugar, slowly inactivates gluthathione-related and other enzymes. In addition, glutathione can be also glycated. The presence of glutathione, and of the related enzymes has been also reported in other parts of the eye, such as ciliary body and trabecular meshwork, suggesting that the same enzyme systems are present in all tissues of the eye to generate NADPH and to maintain gluthatione in the reduced form. Changes of glutathione and related enzymes activity in lens, cornea, retina and other eye tissues, occur with ageing, cataract, diabetes, irradiation and administration of some drugs.
 ...
PMID:Glutathione-related enzymes and the eye. 1642 Oct 14

Both experimental and clinical studies suggests that oxidative stress plays an important role in the pathogenesis of diabetes mellitus type 1 and type 2. Hyperglycaemia leads to free radical generation and causes neural degeneration. In the present study we investigated the possible neuroprotective effect of mexiletine against streptozotocin-induced hyperglycaemia in the rat brain and spinal cord. 30 adult male Wistar rats were divided into three groups: control, diabetic, and diabetic-mexiletine treated group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Mexiletine (50 mg/kg) was injected intraperitoneally every day for six weeks. After 6 weeks the brain, brain stem and cervical spinal cord of the rats were removed and the hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical analysis (the level of Malondialdehide [MDA], Nitric Oxide [NO], Reduced Glutathione [GSH], and Xanthine Oxidase [XO] activity). MDA, XO and NO levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group increased significantly, when compared with control and mexiletine groups (P < 0.05). GSH levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group decreased significantly when compared with control and mexiletine groups (P < 0.05). This study demonstrates that mexiletine protects the neuronal tissue against the diabetic oxidative damage.
 ...
PMID:Neuroprotective effect of mexiletine in the central nervous system of diabetic rats. 1654 Nov 98

Patients with beta-thalassemia (thal) major are subject to peroxidative tissue injury by iron overload. Glutathione S-transferases work as antioxidants, and their activity is determined genetically. In this study, we used multiplex polymerase chain reaction (m-PCR) to analyze polymorphisms of two endogenous antioxidant agents, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), and to determine their roles in 41 patients with beta-thal major. Our results showed that the GSTM1 and GSTT1 null genotypes were not associated with any incidence of endocrine dysfunction (including diabetes mellitus, hypogonadism, hypothyroidism, and growth hormone deficiency), liver function, or impaired left ventricular ejection fraction (LVEF). The GSTM1 null genotype, but not the GSTT1 null genotype, was associated with a decreased signal intensity ratio on cardiac magnetic resonance imaging (MRI). Our results suggest that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition in patients with beta-thal major.
 ...
PMID:Glutathione S-transferase M1 gene polymorphisms are associated with cardiac iron deposition in patients with beta-thalassemia major. 1679 50

Glutathione S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. In the present study, we investigated the GSTM1, GSTT1 and GSTP1 gene polymorphisms in diabetic patients and healthy individuals and searched whether polymorphisms in GST genes are associated with diabetes mellitus (DM) in the Turkish population. The study population consisted of 98 unrelated healthy individuals and 98 patients with DM. Genotyping of GSTM1, GSTT1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument. Patients had a higher frequency of the GSTM1 null genotype than the control group (Odds ratios, OR = 3.7; 95% confidence intervals, CI = 2.05-6.70). However, there was no significant difference in the frequencies of the GSTT1 and GSTP1 gene polymorphisms between the patients and control group. The combined analysis of these three GST genotypes showed a further DM risk increase (OR = 5.7, 95% CI = 1.51-31.07). This is the first study to determine the association of diabetes with GST gene polymorphism in the Turkish population. These results show that GSTM1 null genotype may play a significant role in the aetiopathogeneses of DM and the GSTM1 gene may be a useful marker in the prediction of DM susceptibility of the Turkish population.
 ...
PMID:Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus. 1692 13

This study investigated the effect of an acute bout of exercise (>85% VO2Max) on biochemical, hemodynamic and oxidative stress variables in sedentary and physically active subjects with type 2 diabetes (T2D). Blood measurements were taken before and after a treadmill test on 12 sedentary non-diabetes subjects (ND), 12 sedentary type 2 diabetes (T2S) and 9 physically active T2D subjects (T2DA). T2DS subjects before and after the treadmill test showed a higher plasma glucose (123.2 +/- 19.0 mg/dL versus 108.9 +/- 16.8 mg/dL, p < 0.001), HbA1C (8.7 +/- 2.4% versus 7.3 +/- 1.2%, p < 0.001) and body fat% (21.3 +/- 5.7% versus 34.6 +/- 4.5%, p < 0.001) than T2DA subjects. T2DA had higher VO2Max (37.7 +/- 3.5 versus 29.5 +/- 3.2, p < 0.05), time on treadmill (22.3 +/- 2.1 min versus 16.1 +/- 2.1 min, p < 0.05), hemoglobin (17.9 +/- 0.9 g/dL, p < 0.05) and lower blood pressure levels in comparison to ND and T2DS subjects. Thiobarbituric acid substances (TBARS) in T2DS were higher than in T2DA subjects (0.27 +/- 0.1 nmol/mL versus 0.21 +/- 0.1 nmol/mL, p < 0.05). Glutathione (GSH) levels were similar among the groups. Physically active type 2 diabetes subjects had a more favorable biochemical, hemodynamic and oxidative stress profile than sedentary subjects. The coexistence of a poor cardiopulmonary performance and high oxidative stress environment can determine a profile of high risk for serious cardiovascular events in patients with diabetes.
Diabetes Res Clin Pract 2007 Mar
PMID:Hemodynamic and oxidative stress profile after exercise in type 2 diabetes. 1694 48

Free radical-induced lipid peroxidation has been associated with numerous disease processes including diabetes mellitus. Glutathione-S-transferase (GST) catalyses the conjugation of glutathione with a variety of organic peroxides to form more water-soluble compounds. Glucose-6-phosphate dehydrogenase (G6PDH) is essential to control intracellular reductive potential by increasing glutathione intracellular levels, which in turn decrease the amount of reactive oxygen species. Glyburide decreases glucose production and enhances insulin action in liver. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the liver tissue of diabetic rat. We investigated the activities of GST and G6PDH in the liver of both control and streptozotocin-induced diabetic rats. Forty male albino rats were included in this study. Liver GST and G6PDH activities decreased significantly in five-week diabetic rats (p<0.001 and p<0.001 respectively) compared to controls and glyburide therapy restored these activities (p<0.001 for GST and p<0.001 for G6PDH). Elevations of hepatic antioxidant enzymes with glyburide administration suggest that glyburide may directly alter hepatic enzyme activities.
 ...
PMID:The effect of the sulfonylurea glyburide on glutathione-S-transferase and glucose-6-phosphate dehydrogenase in streptozotocin-induced diabetic rat liver. 1721 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>