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)

The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with PMA, FMLP, aggregated IgG and phagocytosis were determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). The H2O2 production of PMN after the stimulation was measured using by flow cytometry. The patients were divided into four stages as follows: (1) non-microalbuminuric stage, (2) microalbuminuric stage, (3) proteinuric stage without impairment of renal function (less than 1.2 mg/dl of serum creatinine) and (4) proteinuric stage with impairment of renal function (more than 1.3mg/dl of serum creatinine). The H2O2 production after stimulation with PMA or phagocytosis was significantly higher in patients with NIDDM than normal controls. And also, there is the tendency of an increase in the H2O2 production after stimulation with FMLP or aggregated IgG. This increase of the H2O2 production was observed in all four stages of NIDDM patients after the stimulation, especially in patients with renal failure associated with diabetic nephropathy. These results suggest that reactive oxygen species produced by PMN after stimulation under various conditions may play an important role in the progression and exacerbation of diabetic nephropathy.
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PMID:[The production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with non-insulin dependent diabetes mellitus]. 129 76

The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate (PMA), n-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP), aggregated human IgG, or Staphylococcus aureus was determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). H2O2 production by PMN after stimulation was measured using flow cytometry. Thirty-six patients with NIDDM were divided into four stages as follows: 1) stage I: non-microalbuminuric stage; 2) stage II: microalbuminuric stage; 3) stage III: proteinuric stage without impairment of renal function; and 4) stage IV: proteinuric stage with impairment of renal function. H2O2 production after PMA stimulation in all stages of NIDDM patients was higher than that in healthy controls. This increase of H2O2 production by PMN was particularly observed in stage IV of NIDDM patients after stimulation. Furthermore, H2O2 production in patients in stage IV was higher than that in patients with non-diabetic disease with impairment of renal function. It appears that reactive oxygen species produced by PMN after stimulation under some conditions may play an important role in the progression of diabetic nephropathy.
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PMID:Production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with diabetic nephropathy. 836 Jul 96

Phagocytosis, bactericidal capacity and some selected parameters of oxygen-dependent bactericidal mechanisms were evaluated in 20 patients with type 2 diabetes being in similar (intermediate) state of metabolic control and in 15 healthy individuals. Polymorphonuclear neutrophils (PMNs) from diabetics showed normal ability to phagocytose staphylococci, a decreased Intracellular bacteria killing, the impaired stimulated superoxide anion (O2-) and hydrogen peroxide (H2O2) production and the low intracellular myeloperoxidase activity. The obtained data seem to indicate that the decreased bacterial killing by PMNs isolated from diabetics are partly at least related to an impairment of the oxygen-dependent bactericidal mechanisms. Since none of the diabetic patients suffered from recurrent infection the clinical significance of our finding is still uncertain.
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PMID:Impairment of the oxygen-dependent microbicidal mechanisms of polymorphonuclear neutrophils in patients with type 2 diabetes is not associated with increased susceptibility to infection. 839 18

To evaluate whether granulocyte-colony stimulating factor (G-CSF) improves an impaired production of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients, we studied the effect of G-CSF on myeloperoxidase (MPO) activity and chemiluminescence amplified by a Cypridina luciferin analog (CLA-DCL), which is dependent on O2 generation, and luminol (L-DCL), which is dependent on OCl(-) generation, in response to formyl-methonyl-leucyl-phenylalanine. Both CLA-DCL and L-DCL by neutrophils from the diabetic group (n = 15, HbA(1c) >10%) were significantly decreased (26 and 37%, respectively: P < 0.01) compared with the age-matched normal control group (n = 15), and L-DCL was more sensitive to this inhibition than CLA-DCL (P < 0.05). In both control and diabetic neutrophils, G-CSF significantly enhanced both CLA-DCL (175% in control and 156% in diabetic) and L-DCL (283% in control and 346% in diabetic). In diabetic neutrophils, the enhancing effect of G-CSF on L-DCL was more sensitive than on CLA-DCL (P < 0.001). There was a positive correlation between HbA(1c) and the enhancing effect of G-CSF on L-DCL in diabetic patients (P < 0.05), but not on CLA-DCL. MPO activity was also decreased in the diabetic group (63%, P < 0.05), and G-CSF improved this impaired MPO activity (184%, P < 0.01). Furthermore, there was a positive correlation between HbA(1c) and the improving effect of G-CSF on MPO activity (P < 0.05). Because bacterial infection still accounts for an important cause of morbidity and mortality in diabetic patients, these data suggest that G-CSF may be useful as a drug to prevent the aggravation of bacterial infection by improving neutrophil function, especially through H2O2-MPO-OCl(-) mechanism, in poorly controlled diabetic patients.
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PMID:Effect of granulocyte-colony stimulating factor on generation of oxygen-derived free radicals and myeloperoxidase activity in neutrophils from poorly controlled NIDDM patients. 897 Oct 93

Free radical activity may contribute to atherosclerotic lesions which in diabetic subjects may frequently lead to vascular complications. It is known that oxidative stress is associated to diabetes. Protein glycation and glucose oxidation could be possible source of free radicals. 28 non insulin dependent diabetic subjects (NIDDM) were examined. 20 healthy subjects matched for age, sex and for the presence of hypertension and hyperlipidemia were also studied. Hydrogen peroxide, measured by intracellular levels of the fluorescent 2,7-dichloro-fluorescein (DCF), was considered as indicative parameter of free radical production. The results showed that in resting platelets the basal level of hydrogen peroxide was significantly higher in diabetic subjects than in controls. Moreover, after stimulation with thrombin, collagen, phorbol myristate acetate (PMA) and platelet activating factor (PAF), platelets of diabetic subjects generated significantly higher amounts of hydrogen peroxide than controls. Moreover, platelet aggregation induced by adenosine 5'-diphosphate (ADP) and plasma beta TG levels were higher in diabetics than in controls. In diabetic patients platelet free radical production and functional activity are increased and therefore could play a role in the elevated thrombotic risk described in diabetes.
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PMID:Hyperactivity and increased hydrogen peroxide formation in platelets of NIDDM patients. 917 36

We examined the effects of high-fructose (FR) feeding on the development of diabetic complications in the lens and the kidney of streptozotocin (STZ)-diabetic rats. Male Wistar Furth rats were treated with one of two doses of STZ (HIGH STZ, 55 mg/kg body weight; MOD STZ, 35 mg/kg body weight) or vehicle alone (SHAM) and were then assigned to a control (CNTL) or 400 g FR/kg diet for 12 weeks. At the end of the study, body weight, plasma glucose and insulin concentrations differed among STZ groups (HIGH v. MOD v. SHAM, P < 0.001) but did not differ due to diet. Plasma FR concentrations were significantly higher in FR-fed v. CNTL-fed groups (P < 0.0001) and in HIGH-STZ groups v. MOD-STZ and SHAM groups (P < 0.0004 and P < 0.0001 respectively). Focal length variability of the lens, a quantitative measure of cataract formation, was increased in the HIGH STZ, FR group compared with the HIGH STZ, CNTL group (P < 0.01). The concentration of H2O2 in kidney microsomes was significantly higher in HIGH STZ, FR rats v. HIGH STZ, CNTL rats (P < 0.01). Micro-albuminuria was not observed in any of the groups examined, and there was no evidence of extensive histological damage in the kidney from any rats. Under conditions of severe hyperglycaemia, high FR intake promotes the development of cataracts in the lens of the eye, and results in increased concentrations of substances indicative of oxidative stress in the kidney. Although FR has been suggested as a carbohydrate source for diabetics, a high FR diet coupled with hyperglycaemia produces effects that may promote some of the complications associated with diabetes.
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PMID:High-fructose feeding of streptozotocin-diabetic rats is associated with increased cataract formation and increased oxidative stress in the kidney. 1110 29

Oxidative stress is induced under diabetic conditions and possibly causes various forms of tissue damage in patients with diabetes. Recently, it has become aware that susceptibility of pancreatic beta-cells to oxidative stress contributes to the progressive deterioration of beta-cell function in type 2 diabetes. A hypoglycemic sulfonylurea, gliclazide, is known to be a general free radical scavenger and its beneficial effects on diabetic complications have been documented. In the present study, we investigated whether gliclazide could protect pancreatic beta-cells from oxidative damage. One hundred and fifty microM hydrogen peroxide reduced viability of mouse MIN6 beta-cells to 29.3%. Addition of 2 microM gliclazide protected MIN6 cells from the cell death induced by H(2)O(2) to 55.9%. Glibenclamide, another widely used sulfonylurea, had no significant effects even at 10 microM. Nuclear chromatin staining analysis revealed that the preserved viability by gliclazide was due to inhibition of apoptosis. Hydrogen peroxide-induced expression of an anti-oxidative gene heme oxygenase-1 and stress genes A20 and p21(CIP1/WAF1), whose induction was suppressed by gliclazide. These results suggest that gliclazide reduces oxidative stress of beta-cells by H(2)O(2) probably due to its radical scavenging activity. Gliclazide may be effective in preventing beta-cells from the toxic action of reactive oxygen species in diabetes.
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PMID:Gliclazide protects pancreatic beta-cells from damage by hydrogen peroxide. 1264 74

Ribonuclease inhibitor (RI) is an acidic cytosolic glycoprotein with molecular weight of about 50 kDa, which contains 32 cysteine residues. It is possibly that RI may have antioxidant effect by thiol-disulfide exchange reaction. We studied the effects of RI over-expression on the rat glial cell line C6 injured with H2O2. The transfected C6 cells with RI cDNA (C6') had higher viability, less LDH leakage and MDA contents, but more GSH contents compare that in the control C6 cells. In transfected C6 cells, the activities of CAT and GST were higher than that in the control C6 cells. Without H202 stress, the activities of CAT and GST in the C6' cells were 1.73 and 3.62 times that in the control C6 cells, respectively; With 1.00 mmol/L H2O2 stress, the activities of CATand GSTin the C6' cells were 3.38 and 2.11 times that in the C6 cells, respectively. These results suggest that the over-expression RI has antioxidant activity and it is able to protect cells from per-oxidative injuries. Moreover, we investigated whether RI has a protective role against mouse hepatic damage in vivo. The mice pretreated with different doses of human RI were injected by CC14. The results show that the SOD activities of therapy groups were significantly higher than that of the control group (p < 0.01), while the contents of MOD and activities of ALT and AST in blood were remarkably lower than that of the control group (p < 0.01). Pathological examination shows that the degree of damage was alleviated with RI therapy. These results suggest that RI has the protective role against mouse hepatic damage induced by CC14. The anti-oxidative effects of RI may play an important role in cell protection from per-oxidative injuries.
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PMID:The antioxidant effects of ribonuclease inhibitor. 1470 97

Glucose toxicity to pancreatic beta-cells is defined as irreversible beta-cell damage, including apoptosis, caused by chronic exposure to high glucose levels in type 2 diabetes. Oxidative stress is an important mechanism for glucose toxicity to pancreatic beta-cells. Reducing sugars produce reactive oxygen species through autoxidation and protein glycosylation. 2-Deoxy-d-ribose (dRib) is a reducing sugar with high reactivity. We investigated whether cAMP-stimulating agents could protect beta-cells from dRib-induced oxidative damage. HIT-T15 cells were cultured with various concentrations of dRib for 24 h. We measured cell survival, intracellular cAMP and H2O2 levels, and apoptosis. dRib decreased cell survival in a dose- and time-dependent manner and markedly increased intracellular H2O2 levels and apoptosis. N-Acetyl-l-cysteine decreased dRib-induced rises in intracellular H2O2 and apoptosis to control levels. Forskolin, IBMX, and dbcAMP markedly elevated intracellular cAMP levels and significantly attenuated dRib-induced cytotoxicity and apoptosis, but had no influence on the dRib-induced rise in intracellular H2O2 levels. These results demonstrate that dRib produced oxidative stress and apoptosis in pancreatic beta-cells and that elevated intracellular cAMP levels reduced dRib-induced damage, independent of reactive oxygen species metabolism.
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PMID:Elevated cAMP level attenuates 2-deoxy-d-ribose-induced oxidative damage in pancreatic beta-cells. 1591 Jul 37

Protein tyrosine phosphatase activity depends on a catalytic thiolate group on an acidic cysteine residue that is sensitive to reactive oxygen species. Representative of this family of enzymes is protein tyrosine phosphatase 1B (PTP1B), a major target for type 2 diabetes therapy. PTP1B is sensitive to hydrogen peroxide (H2O2) in vitro and in cells. It is also sensitive to glutathionylation by glutathione disulfide (GSSG). The sensitivity of PTP1B to the redox state of its environment was partially characterized in vitro by examination of phosphatase activity in the presence of various concentrations of glutathione (GSH) and GSSG. Enzyme sensitivity to glutathionylation was dependent on the amount of available thiol groups and increased as GSH concentration was increased. The half-inhibitory concentration for H2O2 was much less than that of GSSG in the presence of low concentrations of GSH, indicating that reaction with H2O2 is much more likely than is glutathionylation by GSSG. PTP1B and a related oxidant-sensitive phosphatase, PTEN, were also sensitive to the lipid peroxidation by-product 4-hydroxynonenal. Furthermore, PTP1B was inhibited by cytochrome c and microperoxidase. Taken together, these data suggest that not only H2O2, but also a variety of redox-active metabolites and hemes can oxidatively inactivate PTPs with potentially profound implications for signal transduction.
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PMID:Sensitivity of protein tyrosine phosphatase activity to the redox environment, cytochrome C, and microperoxidase. 1599 63


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