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)

We investigated the possible involvement of thyroid hormones and lipid peroxidation in the antidiabetic potential of rosiglitazone (a peroxisome proliferator-activated receptors gamma-agonist) on corticosteroid-induced type 2 diabetes mellitus. Rosiglitazone was administered to dexamethasone-induced hyperglycaemic male mice and the alterations in serum concentrations of thyroid hormones insulin, total cholesterol, triglycerides and fasting glucose were studied. Simultaneously changes in lipid peroxidation, reduced glutathione (GSH) content, superoxide dismutase and catalase activities in renal and cardiac tissues (which are commonly affected in diabetes mellitus), were also investigated. Administration of dexamethasone (1.0 mg/kg/day intramuscularly for 28 days) caused hyperglycaemia with a parallel increase in serum insulin, total cholesterol, triglycerides and tissue lipid peroxidation with a decrease in serum levels of both the thyroid hormones (triiodothyronine, T(3) and thyroxine, T(4)) and in the activity of associated tissue antioxidants such as superoxide, catalase and glutathione. However, rosiglitazone administration (3.2 mg/kg/day orally for 21 days) along with an equivalent amount of dexamethasone reverted most of these changes, including a marked inhibition of tissue lipid peroxidation and an increase in the serum levels of both thyroid hormones. The present findings reveal that the test drug ameliorates corticosteroid-induced type 2 diabetes mellitus through an increase in serum thyroid hormone concentrations and inhibition in tissue lipid peroxidation.
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PMID:Amelioration of corticosteroid-induced type 2 diabetes mellitus by rosiglitazone is possibly mediated through stimulation of thyroid function and inhibition of tissue lipid peroxidation in mice. 1769 37

This study aimed to investigate the interrelationship of plasma lipid profile, lipid peroxidation, and erythrocyte antioxidative defense in patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Plasma levels of total cholesterol, triglycerides, and lipid peroxides and the activities of copper, zinc superoxide dismutase (CuZnSOD), catalase, glutathione peroxidase (GSH-Px), as well as the amount of glutathione in erythrocytes, were determined in IDDM, NIDDM, and nondiabetic control subjects. Additionally, morphology of erythrocytes in all subjects was examined. Plasma levels of total cholesterol and triglycerides were significantly increased in NIDDM compared with controls. Also, the lipid peroxide level was higher in NIDDM than in either control or IDDM subjects. CuZnSOD activity in erythrocytes was elevated in NIDDM patients compared with the control. In NIDDM patients, more extensive erythrocyte spherocytosis and echinocytosis compared with both control and IDDM subjects were observed. In contrast with the IDDM group, the observed abnormality in lipid metabolism in NIDDM patients is closely associated with increased lipid peroxidation, changes in antioxidative defense, and erythrocyte morphology.
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PMID:Interrelationship of antioxidative status, lipid peroxidation, and lipid profile in insulin-dependent and non-insulin-dependent diabetic patients. 1806

In this paper, the antidiabetic effects of cysteinyl metformin (CM), a newly synthesized agent, were investigated to evaluate the hypoglycemic/hypolipidemic effects by measuring blood glucose, triglyceride and insulin levels in CM- and metformin-treated diabetic rats. Two diabetic models were used: (1) an alloxan-induced model in which diabetes was produced by alloxan (200 mg/kg, i.p.), then rats were treated with CM (300, 100 and 33 mg/kg) for 14 days; (2) a streptozocin-induced model in which diabetes was produced by streptozocin (30 mg/kg, i.p.) and a sustained high lipid diet, then rats were treated with CM for 8 weeks. The hypoglycemic effect of CM exceeded that of metformin while the hypolipidemic effect was similar. In addition, CM increased the blood insulin level of the alloxan-induced experimental animals (which had an insulin deficiency), but reduced the insulin level of the streptozocin-induced animals (which had an insulin excess), suggesting that CM improves pancreatic beta-cell function. The effects of CM, metformin and cysteine on the antioxidant defense system in alloxan-induced rats were also studied. The serum malondialdehyde (MDA) level was determined to provide evidence for lipid peroxidation, All the groups of animals given CM, metformin and cysteine exhibited less severe oxidative stress than the diabetic group. Then, several key antioxidants such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and the pancreatic exocrine enzyme amylase (AMS) were measured. CM restored the activity of all these agents to nearly normal values while metformin and cysteine merely restored the activity of SOD. At the end of our study, the animals were sacrificed by decapitation and the liver, kidney and pancreas were weighed to allow investigation of organ edema. The results obtained showed that CM corrected the organ edema of the diabetic rats. All these findings suggested that CM has a protective effect on the antioxidant defense system and beta-cell dysfunction in alloxan-induced diabetic rats. All these results suggest that CM is a potential candidate for the future treatment of both type 1 and type 2 diabetes.
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PMID:The antidiabetic effects of cysteinyl metformin, a newly synthesized agent, in alloxan- and streptozocin-induced diabetic rats. 1837 84

Glutathione S-transferases protect cells against exogenous and endogenous oxidative stress. Type 2 diabetes is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This study investigated whether GSTA1*A/*B and GSTP1Ile105Val polymorphisms could affect the risk for type 2 diabetes. A cross-sectional case-control analysis included 468 (326 men and 142 women) Japanese participants in a health screening program. The prevalence of type 2 diabetes was 11.3% (63 subjects: 52 male and 11 female). The frequency of GSTA1*B allele carriers was higher in diabetes than in non-diabetes, though the difference was not statistically significant (adjusted OR, 1.8; 95% CI, 0.9-3.4). The risk among the GSTA1*B allele carriers was significantly increased by current-smoking status (adjusted OR, 3.7; 95% CI, 1.1-12.7; vs. never-smoking non-carriers), whereas the smoking status was not an independent risk factor. The GSTP1 genotype alone or in combination with the smoking status did not affect the risk for diabetes. This is the first report to show that the GSTA1*B allele is a potential risk factor for smoking-related type 2 diabetes.
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PMID:Glutathione S-transferase A1 polymorphism as a risk factor for smoking-related type 2 diabetes among Japanese. 1843 May 27

The possible contribution of early changes in lipid composition, function, and antioxidant status of abdominal adipose tissue (AAT) induced by a fructose-rich diet (FRD) to the development of insulin resistance (IR) and oxidative stress (OS) was studied. Wistar rats were fed with a commercial diet with (FRD) or without 10% fructose in the drinking water for 3 weeks. The glucose (G), triglyceride (TG), and insulin (I) plasma levels, and the activity of antioxidant enzymes, lyposoluble antioxidants, total glutathione (GSH), lipid peroxidation as TBARS, fatty acid (FA) composition of AAT-TG as well as their release by incubated pieces of AAT were measured. Rats fed with a FRD have significantly higher plasma levels of G, TG, and I. Their AAT showed a marked increase in content and ratios of saturated to monounsaturated and polyunsaturated FAs, TBARS, and catalase, GSH-transferase and GSH-reductase, together with a decrease in superoxide dismutase and GSH-peroxidase activity, and total GSH, alpha-tocopherol, beta-carotene and lycopene content. Incubated AAT from FRD released in vitro higher amount of free fatty acids (FFAs) with higher ratios of saturated to monounsaturated and polyunsaturated FAs. Our data suggest that FRD induced an early prooxidative state and metabolic dysfunction in AAT that would favor the overall development of IR and OS and further development of pancreatic beta-cell failure; therefore, its early control would represent an appropriate strategy to prevent alterations such as the development of type 2 diabetes.
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PMID:Abdominal adipose tissue: early metabolic dysfunction associated to insulin resistance and oxidative stress induced by an unbalanced diet. 1862 97

We aimed to investigate whether metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes. This study analyzed the effect of metformin on oxidative stress markers (thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA) and carbonyl groups), hydrogen peroxide (H(2)O(2)) levels, non-enzymatic antioxidant defenses [reduced (GSH) and oxidized (GSSG) glutathione and vitamin E] and enzymatic antioxidant defenses [glutathione peroxidase (GPx), glutathione reductase (GRed) and manganese superoxide dismutase (MnSOD)] in brain homogenates of diabetic GK rats, a model of type 2 diabetes. For this purpose we compared brain homogenates obtained from untreated GK rats versus GK rats treated with metformin during a period of 4 weeks. Brain homogenates obtained from Wistar rats were used as control. The MDA levels, GPx and GRed activities are significantly higher in untreated GK rats, while TBARS levels, carbonyl groups, glutathione content and vitamin E levels remain statistically unchanged when compared with control rats. In contrast, MnSOD activity and the levels of H(2)O(2) are significantly decreased in untreated GK rats when compared with control animals. However, metformin treatment normalized the majority of the parameters altered by diabetes. We observed that metformin, besides its antihyperglycemic action, induces a significant decrease in TBARS and MDA levels, GPx and GRed activities and a significant increase in GSH levels and MnSOD activity. These results indicate that metformin protects against diabetes-associated oxidative stress suggesting that metformin could be an effective neuroprotective agent.
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PMID:Metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes. 1867 48

Troglitazone (TGZ) was developed for the treatment of type 2 diabetes but was withdrawn from the market due to hepatotoxicity. The formation of reactive metabolites has been associated with the observed hepatotoxicity. Such reactive metabolites have been proposed to be formed via three different mechanisms. One of the proposed mechanisms involves the oxidation of the chromane moiety of TGZ to a reactive o-quinone methide. The two other mechanisms involve metabolic activation of the thiazolidinedione moiety of TGZ. In the present study, it is shown that electrochemical oxidations can be used to generate a reactive metabolite of TGZ, which can be trapped by GSH or N-acetylcysteine. From incubations of TGZ with rat and human liver microsomes in the presence of either GSH or N-acetylcysteine, it was shown that similar conjugates were formed in vitro as formed from electrochemical oxidations of TGZ. One- and two-dimensional NMR studies of the troglitazone- S-( N-acetyl)cysteine conjugate revealed that N-acetylcysteine was attached to a benzylic carbon in the chromane moiety, showing that the conjugate was formed via a reaction between the o-quinone methide of TGZ and N-acetylcysteine. From electrochemical oxidations of rosiglitazone, pioglitazone, and ciglitazone in the presence of GSH, no GSH conjugates could be identified. These three compounds all contain a thiazolidinedione moiety. In conclusion, it has been shown that the primary reactive metabolite of TGZ formed from electrochemical oxidation was the o-quinone methide, and this metabolite was similar to what was observed to be the primary reaction product in human and rat liver microsomes.
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PMID:Electrochemical oxidation of troglitazone: identification and characterization of the major reactive metabolite in liver microsomes. 1878 55

An investigation was made to evaluate the role of Anethum graveolens L. (dill) leaf extract in the regulation of corticosteroid-induced type 2 diabetes mellitus in female rats. In dexamethasone-treated animals (1 mg/kg for 22 days) an increase in serum concentration of insulin and glucose and in hepatic lipid peroxidation (LPO) was observed. However, there was a decrease in serum concentration of thyroid hormones and in the endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in liver. In animals treated with an equivalent amount of dexamethasone for a similar period (22 days) when received the leaf extract (100 mg/kg b.wt/d.) for last 15 days a decrease in the concentration of both serum glucose and insulin was observed, indicating the potential of the plant extract in the regulation of corticosteroid-induced diabetes. Dexamethasone-induced alterations in the levels of thyroid hormones as well as in hepatic LPO, SOD, CAT and GSH were also reversed by the plant extract.
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PMID:The effect of Anethum graveolens L. (dill) on corticosteroid induced diabetes mellitus: involvement of thyroid hormones. 1881 8

Oxidative stress is implicated in the pathogenesis and complications of type 2 diabetes mellitus (NIDDM). Glycoxidation may damage the enzymes that synthesise glutathione (GSH), an endogenous intracellular antioxidant. Erythrocytes (RBCs) taken from NIDDM subjects, and non-diabetic controls, were GSH-depleted using 1-chloro-2,4-dinitrobenzene, incubated in a solution containing GSH-rebuilding substrates, and sampled for GSH using a 5,5'-gamma-dithiobis-(2-nitrobenzoic acid)/enzymatic recycling procedure. NIDDM subjects, on average, had the same GSH concentration and synthesising ability as non-diabetic controls, indicating normal function of the synthesis enzymes. A positive correlation between synthesis and concentration of GSH seen in non-diabetic controls did not exist in NIDDM, due to their putatively larger oxidative load. The results, to the best of our knowledge, provide the first evidence that, despite a higher oxidative load, intact RBCs from NIDDM subjects are able to synthesise GSH normally. It is hypothesised that increased rates of GSH synthesis would maintain a normal steady-state GSH concentration.
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PMID:Glutathione synthesis by red blood cells in type 2 diabetes mellitus. 1901 68

This study compares the lipid peroxidation marker urinary thiobarbituric acid reactive substances (TBARS) and antioxidants including plasma alpha-tocopherol (vitamin E), plasma (P-GSH-Px) and erythrocyte glutathione peroxidase (E-GSH-Px) activities, and plasma selenium levels in two groups of type 2 diabetic subjects (both n=20) with a disease duration of < or =2 (GP1) and 4-6 years (GP2), and non-diabetic age and gender-matched control subjects (CG, n=20). The mean (standard deviation [SD]) age of the groups was similar at 41(10) years. Fasting blood and midstream urine samples were obtained from diabetic and non-diabetic subjects attending the diabetic clinic and HbAlc, fructosamine, urine TBARS, total antioxidant (TAS) levels, P-GSH-Px, E-GSHPx and plasma selenium and vitamin E concentrations were measured. HbA1c (%) and fructosamine levels in the GP1 and GP2 diabetic subjects and the controls were 5.75 (0.67), 11.43 (2.01) and 4.33 (0.47), and 3.09 (0.57), 6.09 (1.15) and 1.67 (0.31), respectively (GP1 vs. GP2, GP1 vs. GC and GP2 vs. CG, all P < 0.001). Elevated urinary TBARS (micromol/mmol urinary creatinine) in the GP1, GP2 and GC groups were 2.47 (0.37), 3.73 (0.93) and 1.18 (0.24), respectively (GP1 vs. GP2, GP1 vs. GC and GP2 vs. CG, all P < 0.001). A significant correlation between HbA1c and TBARS was also noted (r2 = 0.894, P < 0.001) but only in the GP2 subjects. TAS levels were only decreased in the GP2 group compared to control values (0.59 [0.18] vs. 1.74 [0.21], P < 0.001). Plasma vitamin E concentrations (micromol/L) of 34.11 (3.31), 9.57 (2.20) and 39.01 (2.91) were observed in the GP1, GP2 and GC groups, respectively (GP1 vs. CG, P < 0.05 and GP1 vs. GP2 and GP vs. CG, both P < 0.001). E-GSH-Px (U/g Hb) and P-GSH-Px (U/L) activities in GP1, GP2 and CG groups were also decreased at 57.04 (4.31), 24.0 (8.94) and 67.6 (4.29), and 6.16 (1.56), 2.67 (0.47) and 8.72 (0.31), respectively (E-GSH-Px: CG vs. GP1, P < 0.01, CG vs. GP2 and GP1 vs. GP2, both P < 0.001; P-GSH-Px: CG vs. GP1, CG vs. GP2 and GP1 vs. GP2, all P < 0.001). Plasma selenium levels (miromol/L) were only significantly decreased in GP2 compared to both GP1 and CG values (0.49 [0.29] vs. 1.67 [0.80] vs. 1.79 [0.26], both P < 0.001). These observations support the suggestion that chronic hyperglycaemia can influence the generation of free radicals, which may lead ultimately to increased lipid peroxidation and depletion of antioxidants, and thereby enhanced oxidative stress in subjects with type 2 diabetes mellitus.
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PMID:The relationship between chronic glycaemic control and oxidative stress in type 2 diabetes mellitus. 1905 8


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