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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines the possibility that polymorphonuclear leukocyte activation, which can cause endothelial injury, may contribute to the capillary closure of diabetic retinopathy. To examine diabetes-related alterations in polymorphonuclear leukocyte activation, we compared the production of superoxide radical by these cells from normal and from diabetic cats that were maintained hyperglycemic. Polymorphonuclear leukocytes isolated from five diabetic and five normal cats were stimulated with 10 ng ml-1 phorbol myristate acetate, and the maximum rate of their superoxide radical production was measured spectrophotometrically. Stimulated polymorphonuclear leukocytes from diabetic cats generated more superoxide radical, at significantly higher rates, than did those from normals (3.32 +/- 0.33 and 2.50 +/- 0.41 nmol O2- min-1 10(-6) cells, respectively; P < 0.02). While addition of insulin or glucagon did not alter stimulated polymorphonuclear leukocyte radical production, glucose in high concentration did mildly impair its production in both groups. The exaggerated respiratory burst of polymorphonuclear leukocytes in diabetes could contribute to microvascular injury in the retina as well as in other tissues.
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PMID:Enhanced superoxide radical production by stimulated polymorphonuclear leukocytes in a cat model of diabetes. 133 85

In order to make a systematic study of the effect of Coptis chinensis on free radicals, the authors used the method that the drug and the brain homogenate of rat were mixed and incubated to investigate the effect of Coptis on lipid peroxidation. The result showed that the malondialdehyde (MDA) product of rat brain homogenate inhibited by 5% Coptis was significantly different from control (P < 0.001). On the basis of the above-mentioned results, the effect of Coptis on lipid peroxidation and diabetes of rats induced by alloxan was investigated. The result showed: (1) The MDA product of both pancreas and liver homogenate in Coptis group was significantly less than that in control and alloxan group (P < 0.01, P < 0.05). (2) Superoxide dismutases (SODs) in erythrocytes activity was the same for all groups (P > 0.50). (3) The blood catalase (CAT) activity in alloxan group markedly decreased compared with control group (P < 0.05), but no significant change between Coptis and alloxan group (P > 0.05). (4) The value of serum glucose in alloxan group was significantly increased in comparing with control group (P < 0.05). There was a trend to decrease the value of serum glucose in Coptis group compared with alloxan group, but no significant difference between two groups (P > 0.05). The experiment indicated that there was very strong inhibitory effect of Coptis to the lipid peroxidation in vitro and in vivo. Coptis could protect rat from diabetes inducing by alloxan and that probably was due to the fact that Coptis was able to inhibit alloxan inducing free radicals.
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PMID:[The effect of Coptis chinensis on lipid peroxidation and antioxidases activity in rats]. 139 95

The most common form of neuropathy associated with diabetes mellitus is distal symmetric sensorimotor polyneuropathy, often accompanied by autonomic neuropathy. This disorder is characterized by striking atrophy and loss of myelinated and unmyelinated fibers accompanied by Wallerian degeneration, segmental, and paranodal demyelination and blunted nerve fiber regeneration. In both humans and laboratory animals, this progressive nerve fiber damage and loss parallels the degree and/or duration of hyperglycemia. Several metabolic mechanisms have been proposed to explain the relationship between the extent and severity of hyperglycemia and the development of diabetic neuropathy. One mechanism, activation of the polyol pathway by glucose via AR, is a prominent metabolic feature of diabetic rat peripheral nerve, where it promotes sorbitol and fructose accumulation, myo-inositol depletion, and slowing of nerve conduction by alteration of neural Na(+)-K(+)-ATPase activity or perturbation of normal physiological osmoregulatory mechanisms. ARIs, which normalize nerve myo-inositol and nerve conduction slowing, are currently the focus of clinical trials. Other specific metabolic abnormalities that may play a role in the pathogenesis of diabetic neuropathy include abnormal lipid or amino acid metabolism, superoxide radical formation, protein glycation, or potential blunting of normal neurotrophic responses. Metabolic dysfunction in diabetic nerve is accompanied by vascular insufficiency and nerve hypoxia that may contribute to nerve fiber loss and damage. Although major questions about the pathogenesis of diabetic neuropathy remain unanswered and require further intense investigation, significant recent progress is pushing us into the future and likely constitutes only the first of many therapies directed against one or more elements of the complex pathogenetic process responsible for diabetic neuropathy.
Diabetes Care 1992 Dec
PMID:Complications: neuropathy, pathogenetic considerations. 146 45

All the living molecules appear to suffer from the deleterious effects of aging, but the primary mechanisms of this inexorable evolution are still unknown. In the case of proteins, two major types of chemical reactions participate in the aging phenomena: 1) structural transformations induced by the addition of radicals by enzymic or non-enzymic reactions, 2) proteolytic cleavages. Among the reactions of the first group, the nonenzymatic glycation is the more generalized, not only in diabetic patients but also in non diabetic subjects. This glycation depends on the probabilities of encounters between circulating glucose molecules and free amino groups existing either at the N-terminal end of the polypeptide chains or on the lysyl side chains. These reactions are more frequent in the extracellular spaces and connective tissues because glucose circulates freely in these spaces, because the level of glucose is better controlled inside the cells (and even lower in diabetes mellitus), and finally because the proteins of these regions, such as the collagens, fibronectin and elastin, are relatively long lived, even if their life-span is really shorter than it was precedently believed. The binding of sugar residues to protein amino groups determines frequent modifications of structure that often make the molecule inactive. For instance, when a glucose unit binds to a lysyl radical located in the active center of an enzyme, it suppresses the activity of this enzyme. More generally, in the case of the connective tissue proteins that participate in complex supramolecular assemblies, the presence of additional radicals on some ponctual locations may interfere with the correct association of molecules. This is particularly true for basement membranes whose structure is impaired in diabetes. Glycation might also introduce abnormal cross-links between polypeptides or modify the antigenic power of some proteins and explain the formation of autoantibodies. Another property of glycated proteins is their reaction with oxygen leading to the formation of superoxide. The binding of a reducing sugar on an amino function is followed by an Amadori rearrangement that forms a ketol group. Ketols groups have the property to transmit electrons to molecular oxygen, and to forming superoxide radicals. Superoxide is capable of degrading only one protein: collagen, but it is also able to transform itself into hydrogen peroxide and hydroxyl radicals, which are far more toxic than O2-. The result of the formation of these oxygen free radicals from glycated proteins is the initiation of the degradation of several types of proteins, like the collagens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Aging mechanisms of proteins]. 165 Dec 60

Incubation of corneal collagen type I with glucose in the presence of transition metal ions (copper, iron) results in the formation of collagen aggregates insoluble in 6 M urea, and in 2% sodium dodecyl sulfate + 5% beta-mercaptoethanol. The reaction is mediated by hydrogen peroxide and transition metals since it is inhibited by catalase and by the chelating agent diethylenetriaminepentaacetic acid. Comparative studies showed that copper is more efficient than iron and that the reaction proceeds more rapidly with ribose than with glucose. The data support a mechanism involving transition metal ion catalyzed autoxidation of glucose (and possibly of Amadori products) with generation of superoxide radical. Superoxide dismutation produces hydrogen peroxide, which then generates hydroxyl radicals in the presence of transition metal ions (Fenton reaction). Hydroxyl radical attack is known to lead to cross-linking, which is enhanced in glycated proteins. The experimental data presented are consistent with in vivo alteration of collagen properties during normal aging and with the acceleration of similar changes in diabetes mellitus.
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PMID:The role of nonenzymatic glycosylation, transition metals, and free radicals in the formation of collagen aggregates. 189 43

Bactericidal ability of alveolar macrophages is depressed in rats with diabetes mellitus. To define the mechanism of this abnormality, we measured the parameters of respiratory burst in alveolar macrophages, peripheral blood monocytes, and neutrophils of rats 8 wk after the induction of diabetes by streptozocin. Superoxide anion (O2-.) generation during basal conditions and after stimulation with phorbol myristate acetate (PMA) was measured as superoxide dismutase-inhibitable cytochrome c reduction. NADPH, the principal substrate for NADPH-oxidase-dependent O2-. generation, was measured in the alveolar macrophages and quick-frozen lungs by the enzyme-cycling method. O2-. generation after PMA was significantly lower in the alveolar macrophages of diabetics than in the controls (14.4 +/- 2.0 nmol.10(6) cells-1.20 min-1 vs. 26.2 +/- 1.9, P less than 0.05). Conversely the peripheral blood monocytes of diabetics demonstrated an enhanced O2-. production after PMA stimulation. There was no significant difference in the neutrophil O2-.-generation between the groups. The alveolar macrophage NADPH (control 0.44 +/- 0.15 nmol/10(6) cells vs. diabetic 0.21 +/- 0.04, P less than 0.05) and lung tissue NADPH levels (control 81.4 +/- 16.3 nmol/g dry wt vs. diabetic 35.8 +/- 20.5, P less than 0.05) were significantly lower in the diabetics than in the controls. These data indicate that the O2-.-generating capacity of alveolar macrophages is markedly depressed in diabetes, whereas their precursors, monocytes, are primed to generate O2-. with PMA stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Respiratory burst in alveolar macrophages of diabetic rats. 216 35

Non-enzymatic glycation of reactive amino groups in model proteins increased the rate of free radical production at physiologic pH by nearly fifty-fold over non-glycated protein. Superoxide generation was confirmed by electron paramagnetic resonance measurements with the spin-trap phenyl-t-butyl-nitrone. Both Schiff base and Amadori glycation products were found to generate free radicals in a ratio of 1:1.5. Free radicals generated by glycated protein increased peroxidation of membranes of linoleic/arachidonic acid vesicles nearly 2-fold over control, suggesting that the increased glycation of proteins in diabetes may accelerate vascular wall lipid oxidative modification.
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PMID:Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes. 217 95

Superoxide dismutases (SOD) and their changes in diabetes, aging, ischemia and cancer were studied, Cu, Zn-SOD undergoes glycation reaction in vitro and in vivo and loses its activity by formation of Amadori compounds. Two lysine residues of Cu, Zn-SOD, Lys-122 and Lys-128 are primary glycated sites which are located on the surface of the molecule. The sites are also located on the active site liganding loop which plays a major role in the activity. The glycated Cu, Zn-SOD increased in the red cells of diabetic patients, especially those with diabetic complications. Mn-SOD appears in the serum of patients with acute myocardial infarction in a biphasic manner. The enzyme appears in sera 16 hr and 108 hr after the attack as determined by ELISA. The Mn-SOD levels are also increased in the serum of patients with epithelial ovarian cancer and it is a good marker for detecting and monitoring this cancer. Mn-SOD may play an important role in the ischemic and cancer tissues.
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PMID:[Superoxide dismutases: significances in aging, diabetes, ischemia and cancer]. 223 47

Several D-sugars were incubated with L-lysine or with L-arginine for 10 days. The resulting compounds are able to reduce nitrobluetetrazolium (NBT). This is prevented by superoxide dismutase (SOD), indicating that the superoxide radical is generated by the resulting Amadori compounds. The formation of superoxide radical in vivo, as a result of nonenzymatic glycosylation of proteins, may be considered to be a contributory factor to the appearance of chronic complications of diabetes.
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PMID:Superoxide radical generation by Amadori compounds. 285 11

Leukocyte dysfunction may contribute to infection in the elderly diabetic. Leukocyte oxidative metabolism assessed by chemiluminescence, correlates with microbicidal activity, and may be impaired with hyperglycaemia and ageing. The leukocyte chemiluminescence response to zymosan +/- luminol was assessed in 12 healthy controls (3M, 9F), aged 69 +/- 5 (mean +/- SD) years and in 23 non-insulin dependent diabetics, aged 68 +/- 5 years, before and after improving glycaemic control with sulphonylureas, when the glycosylated haemoglobin fell from 11.2 +/- 2.3 to 7.9 +/- 1.4% (p less than 0.001). The onset of maximal chemiluminescence with zymosan was similar in controls and diabetics, although the actual counts after improved glycaemic control were less in diabetic patients at all time points than initially (p range less than 0.025-less than 0.001) or when compared to the controls (p range less than 0.05-less than 0.005). Following luminal enhancement the onset and magnitude of maximum chemiluminescence was similar in all groups although an increase early response was observed in diabetics initially. We suggest that sulphonylureas may modify chemiluminescence by suppressing superoxide radical generation. Hyperglycaemic elderly non-insulin dependent diabetics may have subtle disturbances of the leukocyte oxidative burst but in general behave in a similar fashion to healthy elderly controls.
Diabetes Res 1988 Oct
PMID:Leukocyte microbicidal activity assessed by chemiluminescence in elderly non-insulin dependent diabetes mellitus. 324 29


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