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

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.
Diabetes Res Clin Pract 1993 Mar
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

Monocytes from patients with poorly controlled non-insulin-dependent diabetes mellitus (NIDDM) show a decrease in intracellular bactericidal function. To determine whether this reduced bactericidal function is mediated by an impaired oxygen-dependent mechanism, we assayed the production of superoxide (O2-) and hydrogen peroxide (H2O2) by monocytes from poorly controlled NIDDM patients (n = 12), well controlled NIDDM patients (n = 12) and healthy subjects (n = 16). Using phorbol myristate acetate (PMA) as stimulant, the production of O2- by fresh monocytes was significantly decreased in poorly controlled NIDDM patients (231 +/- 30 nmol/mg protein/2-h) as compared with that of well controlled NIDDM patients (430 +/- 81 nmol/mg protein/2-h) and that of healthy subjects (399 +/- 61 nmol/mg protein/2-h), respectively (P < 0.05). Using opsonized zymosan (OZ) as stimulant, the production of O2- by fresh monocytes was also notably decreased in patients with poorly controlled NIDDM (312 +/- 42 nmol/mg protein/2-h) as compared with that of patients with well controlled NIDDM (688 +/- 92 nmol/mg protein/2-h) and that of healthy subjects (539 +/- 96 nmol/mg protein/2-h), respectively (P < 0.05). Poorly controlled NIDDM patients had a significant decrease in the production of H2O2 by monocytes, either stimulated by PMA or OZ, as compared with that of well controlled NIDDM patients and that of healthy subjects, respectively (P < 0.05). Enhancement of the production of O2- and H2O2 occurred in healthy subjects (150% increase) as well as NIDDM patients (170% increase) after a preincubation of monocytes with interferon-gamma (IFN-gamma 100 U/ml) for 48 h. The respiratory burst activity of both fresh and cultured monocytes from well controlled NIDDM patients was not significantly different from that of healthy subjects. This study suggests that both, strict metabolic control and in vitro culture with IFN-gamma may improve the monocyte oxygen-dependent bactericidal mechanism in NIDDM patients.
Diabetes Res Clin Pract 1995 Aug
PMID:Respiratory burst activity of monocytes from patients with non-insulin-dependent diabetes mellitus. 859 99

The Maillard reaction has been implicated in cross-linking and fluorescence formation of collagen exposed to high glucose in vitro. However, several pharmacologic agents, whose action seems unrelated to pathways of nonenzymatic glycation, have been demonstrated to prevent cross-linking in diabetes. To clarify this discrepancy, kinetic changes in glycation, glycoxidation (carboxymethyllysine, CML), and cross-linking (measured as tendon breaking time, TBT) were evaluated in rat tail tendons incubated in 5 and 30 mM glucose in vitro and in tendons implanted in vivo into diabetic rat peritoneal cavity. In vitro, rates were found to be both O2- and glucose-dependent. Tendon preglycation and presence of added 2 mM glycosylamine and Amadori compounds (Amadori product of glucose and propylamine) catalyzed these changes in a primarily O2-dependent manner. In the presence of Amadori compounds, kinetic changes were dramatically increased and were preventable by addition of catalase to the medium. Tendons implanted into diabetic rat peritoneum became more rapidly glycoxidized and cross-linked when implanted at day 30 from diabetes onset (high tissue glycation) compared to day 3 (low tissue glycation) in spite of similar glycation kinetics, suggesting a mechanistic dissociation between glycation, glycoxidation, and cross-linking in diabetes. Indeed, intraperitoneal injection of catalase and other antioxidants dramatically suppressed cross-linking, fluorescence formation, and, to some extent, glycoxidation, without affecting glycation. This study confirms the role of oxidative stress in protein cross-linking by the Maillard reaction in vitro and provides the first evidence for a role of H2O2 in cross-linking in diabetes. Whereas Amadori products are a potent source of H2O2 formation in vitro, their precise contribution to H2O2 generation and the actual role of Maillard reaction products in collagen cross-linking in diabetes requires further investigation.
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PMID:Involvement of hydrogen peroxide in collagen cross-linking by high glucose in vitro and in vivo. 866 99

Considerable interest has been focused in recent years on the mechanism of collagen cross-linking by high glucose in vitro and in vivo. Experiments in both diabetic humans and in animals have shown that over time collagen becomes less soluble, less digestible by collagenase, more stable to heat-induced denaturation, and more glycated. In addition, collagen becomes more modified by advanced products of the Maillard reaction, i.e., immunoreactive advanced glycation end products and the glycoxidation markers carboxymethyllysine and pentosidine. Mechanistic studies have shown that collagen cross-linking in vitro can be uncoupled from glycation by the use of antioxidants and chelating agents. Experiments in the authors' laboratory revealed that approximately 50% of carboxymethyllysine formed in vitro originates from pathways other than oxidation of Amadori products, i.e., most likely the oxidation of Schiff base-linked glucose. In addition, the increase in thermal stability of rat tail tendons exposed to high glucose in vitro or in vivo was found to strongly depend on H2O2 formation. The final missing piece of the puzzle is that of the structure of the major cross-link. We speculate that it is a nonfluorescent nonultraviolet active cross-link between two lysine residues, which includes a fragmentation product of glucose linked in a nonreducible bond labile to both strong acids and bases.
Diabetes 1996 Jul
PMID:The mechanism of collagen cross-linking in diabetes: a puzzle nearing resolution. 867 97

It has been reported that oxidative stress is increased in vivo in the diabetic state. Increased oxidative stress is caused not only by accelerated production of oxygen-free radicals but also by decreased scavenging of those molecules. Endothelial cells are extremely sensitive to oxidative stress, resulting in impairments of various endothelial cell function. In this report, we studied the association of intracellular glucose metabolism and oxygen radical scavenging function via the glutathione redox (GR) cycle in cells exposed to high-glucose conditions using cultured human umbilical vein endothelial cells. Glutathione-dependent H2O2 degradation in cells exposed to 33 mmol/l glucose (HG) for 5-7 days was reduced by 48% vs. 5.5 mmol/l glucose (NG). This impairment under the oxidative stress was D-glucose-specific and concentration-dependent and was also associated with a 42% decrease in intracellular NADPH content. Exposure of cells to 200 micromol/l H2O2 stimulated the GR cycle and the pentose phosphate pathway (PPP) at the same time. In the HG condition, activation of PPP was reduced by 50%, which was consistent with a decrease in NADPH content. Inhibition of glycolysis by H2O2 was less marked in HG cells versus NG cells. Activation of polyol pathway in HG cells is not responsible for the decrease in intracellular NADPH content. These results indicate that activation of the PPP and NADPH supply to the GR cycle is impaired in HG cells exposed to H2O2, which may result in increased oxidative stress to endothelial cells.
Diabetes 1996 Jul
PMID:Glycation, oxidative stress, and scavenger activity: glucose metabolism and radical scavenger dysfunction in endothelial cells. 867 1

Several lines of evidence support an atherogenic role for oxidized low-density lipoprotein (LDL). Previous studies have suggested that although Mexican-Americans have an increased rate of diabetes, obesity, elevated triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels, their rates of coronary heart disease (CHD) are similar or possibly lower than in non-Hispanic whites. Mexican-Americans have smaller, denser LDL than non-Hispanic whites. On the basis of this latter observation, we postulated that lipid peroxide (LPO) levels would be increased in Mexican-Americans. We examined the oxidizability of plasma in 50 Mexican-Americans and 50 non-Hispanic whites from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease, at baseline and after coincubation with a metal-independent system (2'2'-azobis-2-amidinopropane hydrochloride [AAPH]) and a metal-dependent system (Fe2+/H2O2) of oxidation. LPO levels were measured by a modified fluorimetric assay. Vitamin E and plasma fatty acid composition were also determined. We found significantly higher LPO levels at baseline and after AAPH coincubation in Mexican-Americans than in non-Hispanic whites (baseline, 2.75 +/- .09 v 2.07 +/- .09 micromol/L, P < .001; post-AAPH, 5.49 +/- .14 v 5.07 +/-. .04 micromol/L, P = .037). However, no significant ethnic differences were seen after coincubation with Fe2+/H2O2. Diabetes and cigarette-smoking were also associated with higher LPO levels. Mexican-Americans also had lower levels of vitamin E (the predominant lipid-soluble antioxidant in plasma) than non-Hispanic whites, although these differences only partially explained the differences in susceptibility to oxidation. Plasma fatty acids were similar in Mexican-Americans and non-Hispanic whites, suggesting only small differences in diet composition. We conclude that LPO levels are higher in Mexican-Americans than in non-Hispanic whites, and that these results are only partially related to differences in vitamin E levels.
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PMID:Plasma oxidizability in Mexican-Americans and non-Hispanic whites. 869 25

Non enzymatic glycation could be involved in the early impairment of Na+/K+ ATPase that occurs in sciatic nerve of diabetic rats. In fact, decrease of Na+/K+ ATPase activity is one of the first alterations showed in experimental diabetic neuropathy. In this respect, it is known that in the presence of transition metals under physiological conditions, glucose can autoxidize yielding hydrogen peroxide (H2O2) and free radical intermediates, which, in turn, inhibit the cation pump. Our experiments were designed to determine if glucose autoxidation has any relevance in the early steps of Na+/K+ ATPase experimental glycation. Compared experiments with and without the sodium borohydride (NaBH4) reduction step demonstrated that incubation of brain Na+/K+ ATPase with glucose 6-phosphate (G 6-P) and trace metals induced a significant decrease in enzyme activity dramatically enhanced by addition of copper (Cu2+). A concomitant production of H2O2 was noticed. The presence of diethylenetriaminepentaacetic acid (DTPA), a strong metal chelator, completely prevented Na+/K+ ATPase impairment and hydrogen-peroxide formation. No gross structural and conformational alterations of the enzyme can be demonstrated by intrinsic and extrinsic fluorescence measurements. Our results suggest that during the exposure of brain NA+/K+ ATPase to glucose 6-phosphate in vitro (experimental glycation), the decrease in activity can be correlated, at lease in the early phases, to metal-catalyzed production of oxidative species, such as H2O2, through the glucose autoxidation process, and not to glucose attachment to the enzyme. Since plasma hydroperoxides and copper appear to be elevated in diabetic patients with complications, our data suggest a critical role for oxidative reactions in the pathophysiology of the chronic complications of diabetes like neuropathy.
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PMID:NA+/K+ ATPase impairment and experimental glycation: the role of glucose autoxidation. 873 42

This study examined the effects of glycocorticoids, insulin, thyroxine, and epinephrine upon the activities of CuZn- and Mn-superoxide dismutases (SOD), catalase, and glutathione peroxidase (GPX) and upon hydrogen peroxide production in rat macrophages obtained from the intraperitoneal cavity. The experiments were performed in vivo under conditions causing hormonal dysfunctions: adrenal demedullation, dexamethasone treatment, thyroidectomy, administration of L-tri-iodothyronine (T3) and L-thyroxine (T4), and diabetes. Macrophages were also cultured for 24 hr in the presence of dexamethasone, thyroid hormones, and insulin as to evaluate possible interferences caused in vivo by changes in other hormones. The results indicated that these hormones do control the activities of the antioxidant enzymes and hydrogen peroxide production both in vivo and in vitro. Insulin increased the activities of CuZn-SOD, catalase, and GPX and reduced that of Mn-SOD. Thyroid hormones raised the activities of CuZn- and Mn-SOD and decreased that of GPX, whereas glucocorticoids reduced both Mn-SOD and GPX. The removal of the adrenal medulla caused a decrease of Mn-SOD and GPX activities in the macrophages. Hydrogen peroxide production was increased by insulin and reduced by thyroid hormones and glucocorticoids. The changes in antioxidant enzyme activities caused by these hormones in macrophages may indicate important mechanisms for the establishment of impaired immune function in endocrine pathologies.
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PMID:Hormonal regulation of superoxide dismutase, catalase, and glutathione peroxidase activities in rat macrophages. 884 37

We evaluated the effects of granulocyte colony-stimulating factors (G-CSF), granulocyte-macrophage colony-stimulating factors (GM-CSF) and phorbol myristate acetate (PMA) on H2O2 production in purified neutrophils from patients with diabetes mellitus (DM), using flow cytometry. Twenty-two age-matched male subjects were selected: 11 were normal volunteers and the remainder had DM. No significant differences in intracellular H2O2 production per 60 min was observed in the "resting' neutrophils from DM patients (37.2 +/- 20.4 A.U.) compared with those from normal volunteers (24.9 +/- 8.4 A.U.). The PMA-stimulated neutrophils from normal volunteers generated approximately 4-fold increases in H2O2 per 60 min compared with those from DM patients. Under similar culture conditions, G-CSF caused 1.6-fold increases of H2O2 in neutrophils from normal volunteers compared with those of DM patients. Increases after GM-CSF stimulation were 2-fold higher in volunteer neutrophils compared with those from DM patients. The levels of G-CSF- or GM-CSF-stimulated H2O2 production in neutrophils from DM patients were low and were little different from non-stimulated resting cells. These data showed that H2O2 production in neutrophils induced by PMA is impaired in patients with DM, and neither G-CSF nor GM-CSF enhances its production.
Diabetes Res Clin Pract 1996 Jul
PMID:Reduced hydrogen peroxide production in neutrophils from patients with diabetes. 887 67

We address the question whether oxygen metabolism of polymorphonuclear neutrophils (PMN) is influenced by disease duration in patients with insulin-dependent diabetes mellitus (IDDM). PMN were isolated from patients with IDDM of various durations and from healthy controls. We measured PMN production of superoxide anions (O2-) by cytochrome c reduction (see Babior, B.M. et al. (1973) J. Clin. Invest. 52, 741-746) and PMN production of hydrogen peroxide (H2O2) by phenol red oxygenation (see Pick, E. (1980) J. Immunol. Methods 38, 161-169) in three groups of IDDM patients subdivided according to disease duration (group A: IDDM less that 10 years; group B: IDDM of 10-15 years; group C: IDDM of more than 15 years) and in control healthy subjects (group H). Unstimulated O2- production in all IDDM patients was not statistically different from control values (A: 4.3 +/- 0.4 nmol/10(6) PMN per 30 min, nmol/10(6) PMN per 30 min; C: 4.9 +/- 0.9 nmol/10(6) PMN per 30 min; and H: 3.5 +/- 0.2 nmol/10(6) PMN per 30 min, respectively). In contrast, stimulated O2- production was significantly lower in both patients with 10-15 years, and patients with more than 15 years, duration of IDDM than in controls (B: 25.7 +/- 2.5 nmol/10(6) PMN per 30 min; C: 21.1 +/- 3.4 nmol/10(6) PMN per 30 min and H: 42.2 +/- 1.1 nmol/10(6) PMN per 30 min, respectively) correlating with disease duration (r = -0.44, P < 0.033). The stimulated O2- production in patients with less than 10 years duration of IDDM (A: 35.7 +/- 1.9 nmol/10(6) PMN per 30 min) was slightly lower than in controls. H2O2 production of unstimulated PMN (A: 4.0 +/- 0.5 nmol/10(6) PMN per 30 min; B: 4.4 +/- 0.8 nmol/10(6) PMN per 30 min and C: 4.4 +/-1.0 nmol/10(6) PMN per 30 min, respectively) was much higher than those in controls. In contrast, stimulated H2O2 production did not differ statistically from the value noticed in healthy subjects. The results obtained might indicate that production of H2O2 by unstimulated cells is increased in diabetic patients while generation of O2- by stimulated neutrophils is markedly impaired, suggesting that toxic oxygen species production might be influenced by disease duration.
Diabetes Res Clin Pract 1996 Aug
PMID:The influence of insulin-dependent diabetes mellitus (IDDM) duration on superoxide anion and hydrogen peroxide production by polymorphonuclear neutrophils. 892 34


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