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)

Serum levels of total cholesterol, triglycerides, lipoproteins, lipid peroxides (TBARS) and erythrocyte antioxidant enzyme activities were measured in 105 non insulin dependent diabetic patients, among whom 38 had microvascular complications (MVC) of diabetes. All the diabetic patients had higher concentrations of glycated hemoglobin (HbA1) compared to controls (10.51 +/- 2.42% vs 6.31 +/- 0.85% P <0.001). Significant increase of serum triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) and a significant decrease of high density lipoprotein cholesterol (HDL-C) were observed in the diabetic patients compared to controls (TG: 2.31 +/- 0.9 mmol/l vs 1.53 +/- 0.48 mmol/l P <0. 001; TC: 5.94 +/- 1.4 mmol/l vs 4.3 +/- 0.85 mmol/l P <0.001; LDL-C: 3.96 +/- 1.33 mmol/l vs 2.39 +/- 0.8 mmol/l P <0.001; VLDL-C: 0.46 +/- 0.2 mmol/l vs 0.3 +/- 0.09 mmol/l P <0.001; HDL-C: 0.81 +/- 0.24 mmol/l vs 1.04 +/- 0.18 mmol/l P <0.001). Significantly increased levels of serum TBARS were observed in diabetic patients compared to those in controls (TBARS: 6.7 +/- 1.5 mmol/l vs 5.14 +/- 0.61 mmol/l P <0.001). Erythrocyte catalase (CAT) activity was increased and Glutathione peroxidase (GPx) activity was decreased in diabetic patients compared to controls, but no significant change in Superoxide dismutase (SOD) activity was observed in diabetic patients (CAT: 104.94 +/- 37.1 KU/g Hb vs 85.8 +/- 23.6 KU/g Hb, P <0.01; GPx: 30 +/- 9.7 U/g Hb/min vs 40.84 +/- 12.3 U/g Hb/min, P <0. 001; SOD: 2.4 +/- 1.2 U/mg Hb/min vs 2.55 +/- 0.84 U/mg Hb/min, P=NS). In comparison with the diabetic group without MVC, the diabetic group with MVC had decreased GPx and SOD activities, while no difference was observed between these two groups regarding CAT activity (GPx: 25.32 +/- 8.4 U/g Hb/min vs 34.5 +/- 8.8 U/g Hb/min, P <0.001; SOD: 1.83 +/- 0.53 U/mg Hb/min vs 2.84 +/- 1.4 U/mg Hb/min, P<0.001; CAT: 106.3 +/- 39.9 KU/g Hb vs 103 +/- 34.9 KU/g Hb, P =NS). TBARS concentrations were significantly increased in the group with MVC compared to the group without these complications, indicating a positive relationship between TBARS and MVC of diabetes (7.05 +/- 1.23 mmol/l vs 6.3 +/- 1.02 mmol/l, P <0.001). Serum triglycerides, LDL and VLDL cholesterol concentration were significantly higher in diabetics with MVC than in diabetics without the complications (TG: 2.7 +/- 0.98 mmol/l vs 2.13 +/- 0.82 mmol/l, P<0.01; LDL - C: 4.45 +/- 1.3 mmol/l vs 3.67 +/- 1.3 mmol/l, P <0. 02; VLDL-C: 0.53 +/- 0.19 mmol/l vs 0.43 +/- 0.16 mmol/l, P <0.01), and the serum levels of TC in the group with MVC showed a positive correlation with their lipid peroxide levels (r =0.368, P <0.001). The increase in TBARS and the decreased GPx and SOD activities in diabetics with MVC in this study indicate that these factors may contribute to the occurrence of micro vascular complications in NIDDM patients.
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PMID:Lipid peroxidation and antioxidant enzyme levels in type 2 diabetics with microvascular complications. 1111 18

Metformin reduces blood glucose levels predominantly by inhibiting hepatic gluconeogenesis, although it also may enhance insulin receptor number or activity. The full effects of metformin are still poorly understood. In this study the effects of metformin on plasma xanthine oxidase (XO) activity, thiobarbituric acid-reactive substance (TBARS), lactate and fructosamine concentration as well as erythrocyte antioxidant enzyme activities were investigated in 46 patients with type 2 diabetes mellitus. All parameters were measured simultaneously just before metformin therapy (T0), 1 month (T1) and 2 months (T2) later. Results were compared with placebo and control group. We noted significant decrease in XO activity and in TBARS concentration (p<0.001) during monotherapy with metformin vs. placebo and T0 group. A significant correlation was observed between the activity of XO and the concentration of fructosamine (p<0.001). Erythrocyte glutathione peroxidase showed significantly lower activity in T2 group in comparison with T0 group (p<0.01). It is known that diabetic patients produce more TBARS as a result of enhanced free radical generation the source of which may also be the large amounts of XO produced following the conversion of xanthine dehydrogenase in hypoxic diabetic tissues. Thus, our results indirectly suggest that metformin can reduce toxic tissue damage through the inhibition on XO activity.
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PMID:Monotherapy with metformin: does it improve hypoxia in type 2 diabetic patients? 1160 79

Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, a process that is termed glucose toxicity. Our perspective about glucose toxicity as it pertains to the pancreatic beta-cell is that the characteristic decreases in insulin synthesis and secretion are caused by decreased insulin gene expression. The responsible metabolic lesion appears to involve a posttranscriptional defect in pancreas duodenum homeobox-1 (PDX-1) mRNA maturation. PDX-1 is a critically important transcription factor for the insulin promoter, is absent in glucotoxic islets, and, when transfected into glucotoxic beta-cells, improves insulin promoter activity. Because reactive oxygen species are produced via oxidative phosphorylation during anaerobic glycolysis, via the Schiff reaction during glycation, via glucose autoxidation, and via hexosamine metabolism under supraphysiological glucose concentrations, we hypothesize that chronic oxidative stress is an important mechanism for glucose toxicity. Support for this hypothesis is found in the observations that high glucose concentrations increase intraislet peroxide levels, that islets contain very low levels of antioxidant enzyme activities, and that adenoviral overexpression of antioxidant enzymes in vitro in islets, as well as exogenous treatment with antioxidants in vivo in animals, protect the islet from the toxic effects of excessive glucose levels. Clinically, consideration of antioxidants as adjunct therapy in type 2 diabetes is warranted because of the many reports of elevated markers of oxidative stress in patients with this disease, which is characterized by imperfect management of glycemia, consequent chronic hyperglycemia, and relentless deterioration of beta-cell function.
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PMID:Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. 1260 96

The relentless decline in beta-cell function frequently observed in type 2 diabetic patients, despite optimal drug management, has variously been attributed to glucose toxicity and lipotoxicity. The former theory posits hyperglycemia, an outcome of the disease, as a secondary force that further damages beta-cells. The latter theory suggests that the often-associated defect of hyperlipidemia is a primary cause of beta-cell dysfunction. We review evidence that patients with type 2 diabetes continually undergo oxidative stress, that elevated glucose concentrations increase levels of reactive oxygen species in beta-cells, that islets have intrinsically low antioxidant enzyme defenses, that antioxidant drugs and overexpression of antioxidant enzymes protect beta-cells from glucose toxicity, and that lipotoxicity, to the extent it can be attributable to hyperlipidemia, occurs only in the context of preexisting hyperglycemia, whereas glucose toxicity can occur in the absence of hyperlipidemia.
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PMID:Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. 1474 76

To determine the effects of chromium (Cr) supplementations on oxidative stress of type 2 diabetes and euglycemic (EU) subjects, adult having HbA(1C) values of <6.0% (EU), 6.8-8.5% (mildly hyperglycemic, MH), and >8.5% (severely hyperglycemic, SH) were supplemented for 6 months with 1000 microg/day of Cr (as Cr yeast) or with a placebo. In the beginning, the levels of the plasma Cr in the MH and SH groups were 25-30% lower than those of the EU subjects. The values of thiobarbituric acid reactive substances (TBARS) and total antioxidative status (TAS) of the MH and SH groups were significantly higher than those of the EU ones. Following supplementations, the levels of plasma TBARS in the Cr groups of MH and SH groups were significantly decreased (the inverse was found in the EU) and showed no significant changes in the placebo group. The levels of plasma TAS in the Cr groups of EU and MH were significantly decreased (the inverse was found in the SH) and showed no significant changes in the placebo group. No significant difference was found in the antioxidant enzyme (superoxide dismutase, glutathione peroxidase, catalase) activities during supplementations. These data suggest that Cr supplementation was an effective treatment strategy to minimize increased oxidative stress in type 2 diabetes mellitus patients whose HbA(1C) level was >8.5%, and the Cr in EU groups might act as a prooxidant.
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PMID:Antioxidant effects of chromium supplementation with type 2 diabetes mellitus and euglycemic subjects. 1499 50

Oxidative stress is produced under diabetic conditions and is likely involved in progression of pancreatic beta-cell dysfunction found in diabetes. Possibly caused by low levels of antioxidant enzyme expressions, pancreatic beta-cells are vulnerable to oxidative stress. When beta-cell-derived HIT-T15 cells or isolated rat islets were exposed to oxidative stress, insulin gene expression was markedly decreased. To investigate the significance of oxidative stress in the progression of pancreatic beta-cell dysfunction in type 2 diabetes, we evaluated the effects of antioxidants in diabetic C57BL/KsJ-db/db mice. According to an intraperitoneal glucose tolerance test, the treatment with antioxidants retained glucose-stimulated insulin secretion and moderately decreased blood glucose levels. Histological analyses of the pancreata revealed that the beta-cell mass was significantly larger in the mice treated with the antioxidants, and the antioxidant treatment suppressed apoptosis in beta-cells without changing the rate of beta-cell proliferation. The antioxidant treatment also preserved the amounts of insulin content and insulin mRNA, making the extent of insulin degranulation less evident. As possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. Under diabetic conditions, JNK is activated by oxidative stress and involved in the suppression of insulin gene expression. This JNK effect appears to be mediated in part by nucleocytoplasmic translocation of PDX-1, which is also downstream of JNK activation. Taken together, oxidative stress and consequent activation of the JNK pathway are involved in progression of beta-cell dysfunction found in diabetes. Antioxidants may serve as a novel mechanism-based therapy for type 2 diabetes.
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PMID:Role of oxidative stress in pancreatic beta-cell dysfunction. 1512 94

We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.
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PMID:Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. 1518 Oct 35

Insulin resistance, a hallmark of type 2 diabetes, is associated with oxidative stress. However, the role of reactive oxygen species or specific antioxidant enzymes in its development has not been tested under physiological conditions. The objective of our study was to investigate the impact of overexpression of glutathione peroxidase 1 (GPX1), an intracellular selenoprotein that reduces hydrogen peroxide (H(2)O(2)) in vivo, on glucose metabolism and insulin function. The GPX1-overexpressing (OE) and WT male mice (n = 80) were fed a selenium-adequate diet (0.4 mg/kg) from 8 to 24 weeks of age. Compared with the WT, the OE mice developed (P < 0.05) hyperglycemia (117 vs. 149 mg/dl), hyperinsulinemia (419 vs. 1,350 pg/ml), and elevated plasma leptin (5 vs. 16 ng/ml) at 24 weeks of age. Meanwhile, these mice were heavier (37 vs. 27 g, P < 0.001) and fatter (37% vs. 17% fat, P < 0.01) than the WT mice. At 30-60 min after an insulin challenge, the OE mice had 25% less (P < 0.05) of a decrease in blood glucose than the WT mice. Their insulin resistance was associated with a 30-70% reduction (P < 0.05) in the insulin-stimulated phosphorylations of insulin receptor (beta-subunit) in liver and Akt (Ser(473) and Thr(308)) in liver and soleus muscle. Here we report the development of insulin resistance in mammals with elevated expression of an antioxidant enzyme and suggest that increased GPX1 activity may interfere with insulin function by overquenching intracellular reactive oxygen species required for insulin sensitizing.
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PMID:Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase. 1518 68

Pregnancy is susceptible to oxidative stress and antioxidant defenses can be altered in response to elevated levels of oxidative stress. Limited data in gestational diabetes mellitus (GDM) suggest that products of lipid peroxidation may be increased and antioxidant enzyme activities decreased, although the results have been inconsistent. As in type 2 diabetes mellitus (T2DM), glycemic levels in patients with GDM correlate with concentrations of lipid peroxides. The effects of supplementation with antioxidants or antioxidant-rich food in T2DM are controversial. Whether or not increased antioxidant intake can reduce the complications of GDM in both mother and fetus has not been explored.
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PMID:Oxidative stress: changes in pregnancy and with gestational diabetes mellitus. 1603 80

Oxidative stress is induced under diabetic conditions through various pathways, including the electron transport chain in mitochondria and the nonenzymatic glycosylation reaction, and is likely involved in progression of pancreatic beta-cell dysfunction developing in diabetes. beta-Cells are vulnerable to oxidative stress, possibly due to low levels of antioxidant enzyme expression. When oxidative stress was induced in vitro in beta cells, the insulin gene promoter activity and mRNA levels were suppressed, accompanied by the reduced activity of pancreatic and duodenal homeobox factor-1 (PDX-1) (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene. The suppression of oxidative stress by a potent antioxidant, N-acetyl-l-cysteine or probucol, led to the recovery of insulin biosynthesis and PDX-1 expression in nuclei and improved glucose tolerance in animal models for type 2 diabetes. As a possible cause of this, we recently found that PDX-1 was translocated from the nucleus to the cytoplasm in response to oxidative stress. Furthermore, the addition of a dominant-negative form of c-Jun N-terminal kinase (JNK) inhibited the oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating the phenomenon. Taken together, the oxidative stress-mediated activation of the JNK pathway leads to nucleocytoplasmic translocation of PDX-1 and thus is likely involved in the progression of beta-cell dysfunction found in diabetes.
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PMID:Oxidative stress and pancreatic beta-cell dysfunction. 1628 Jun 46


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