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

The effect of short term (2-wk) diabetes induced by streptozotocin and starvation (1-wk) on antioxidant enzymes and lipid peroxidation in the liver, kidney and heart of rats was investigated. The activity of mitochondrial oxidative markers was increased in diabetic liver and kidney, while the activity in tissues of starved rats tended to be decreased. Immunoreactive manganese superoxide dismutase was increased only in diabetic liver and was unchanged or decreased in the rest of the tissues. Glutathione peroxidase activity was increased in tissues of diabetic but not starved rats. The changes in copper-zinc superoxide dismutase and catalase in diabetic rats were similar to those in starved rats. In both groups, copper-zinc superoxide dismutase was decreased in liver, while catalase activity was decreased in liver and kidney, and increased in heart. The lipid peroxide level was increased in diabetic kidney and in the heart of starved rats, and decreased in the rest of the tissues. Insulin treatment in diabetic rats and refeeding in starved rats restored most of the abnormalities toward normal. These results suggest that accelerated mitochondrial oxidative metabolism not accompanied by induction of manganes superoxide dismutase results in oxidative injury in the hypertrophied kidney at an early stage of diabetes and possibly contributes to the development of nephropathy. Peroxidative myocardial damage in starved rat appears to be mediated by a catabolic process.
Diabetes Res 1989 Oct
PMID:Antioxidant enzyme status and lipid peroxidation in various tissues of diabetic and starved rats. 256 53

Although inherited forms of phagocyte defects affect a small proportion of the general population, their clinical course can be altered dramatically by a physician's awareness of these diseases and modifications of the approach to and treatment of affected patients. The most common syndromes are chronic granulomatous disease of childhood (CGD), the Chediak-Higashi syndrome (CHS), the hyperimmunoglobulin-E-recurrent infection (Job's) syndrome (HIE), and myeloperoxidase (MPO) deficiency. CGD patients have defects in the oxidative metabolism involved in killing catalase-positive organisms. CHS patients have giant granules defective in fusing with phagosomes and subsequent killing of ingested organisms. HIE patients have abnormal chemotaxis and elevated IgE levels and are susceptible to skin infections with Staphylococcus aureus and recurrent sinopulmonary infections. MPO-deficient patients often go undetected since they rarely have recurrent infections unless they have a concomitant disease such as diabetes mellitus. Patients with a recently described syndrome, C3bi receptor deficiency, have recurrent bacterial infections and persistent leukocytosis, and their neutrophils have abnormal adherence and phagocytosis. The absence of specific granules is a more rare entity but these patients also have recurrent infections thought to be secondary to a chemotactic defect and a minor abnormality of microbial killing exhibited by their neutrophils. This review will focus on the clinical presentation and management of these patients.
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PMID:Phagocyte defects. 294 Nov 93

Superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase were assayed in the erythrocytes of a diabetic population on various treatment regimens (diet, oral therapy, and insulin), to investigate any relationships between their activities and diabetes markers (serum glucose, lipids, and fructosamine, as well as glycated haemoglobin). In the group of patients as a whole, there was significant negative correlation of SOD, but not of the other two enzymes with glycated haemoglobin and fructosamine. Specifically, there was a lower activity of the enzyme in the poorly-controlled patients. It is concluded that SOD in particular is potentially an additional marker for long-term diabetic pathophysiology.
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PMID:Correlates of diabetes markers with erythrocytic enzymes decomposing reactive oxygen species. 321 26

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9-12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status. Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.
Diabetes 1987 Sep
PMID:Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment. 330 71

Tissue antioxidant status in insulin-dependent spontaneously diabetic BB Wistar rats (ISDBB), diabetes-prone nondiabetic littermates (NDLM), and weight-matched non-BB control Wistar rats was investigated in pancreas, heart, and liver, as well as kidney. Pancreatic activities of CuZn-superoxide dismutase and glutathione reductase (GSSG-RD) were higher in ISDBB rats, while catalase (CAT) activities were elevated in both ISDBB and their NDLM compared with control animals. On the other hand, pancreatic reduced glutathione (GSH) levels were decreased in both ISDBB and NDLM rats. Cardiac tissues of ISDBB rats had higher activities of CAT and GSSG-RD and elevated levels of GSH compared with weight-matched control rats. Hepatic GSH levels in both ISDBB and their NDLM were lower than those of control rats. ISDBB rats showed higher renal activities of glutathione peroxidase compared with control rats. Our results demonstrate the presence of alterations in tissue antioxidant status in BB Wistar rats (both diabetic BB rats and their diabetes-prone nondiabetic littermates). The fact that most of the enzyme changes present in BB rats with overt diabetes paralleled those we have previously reported in rats with uncontrolled streptozotocin-induced diabetes and the fact that the latter alterations were corrected with insulin therapy suggest that the alterations in diabetic BB rats were probably related to suboptimal insulin therapy. The significance of the alterations in antioxidant status seen in the nondiabetic BB animals is as yet unknown.
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PMID:Alterations in tissue antioxidant systems in the spontaneously diabetic (BB Wistar) rat. 332 63

Acetonemia is generally associated with the ketogenic states of fasting and diabetes. Disulfiram (DS), an inhibitor of aldehyde dehydrogenase (AlDH) that is used as an alcohol deterrent drug, is also known to elevate blood acetone in humans, but in the absence of a commensurate increase in its metabolic precursor, acetoacetate. We reexamined the effects of DS and other AlDH inhibitors on circulating ketone body levels in male rats of Sprague-Dawley descent and again demonstrated a 6- and 16-fold increase in blood acetone along with normal levels of acetoacetate at 6 and 24 hr after DS. Pargyline, another inhibitor of AlDH, maintained normal blood acetone levels in the presence of reduced acetoacetate levels. A third inhibitor of AlDH, cyanamide, administered to fasted and nonfasted rats, elevated blood acetone levels 10-fold over controls, with, however, a commensurate 5- and 7-fold increase in blood acetoacetate levels. The threshold values for the cyanamide-induced elevation of blood acetone and acetoacetate were equivalent, i.e. approximately 0.25 mmol/kg body weight (i.p.). The elevation of acetoacetate and the inhibition of hepatic catalase activity by cyanamide are not mechanistically linked, since 3-amino-1,2,4-triazole, another inhibitor of catalase, elevated blood acetone but not acetoacetate levels. These findings suggest that DS-induced acetonemia is due to inhibition of acetone metabolism, whereas enhanced acetone formation through acetoacetate contributes significantly to cyanamide-induced acetonemia.
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PMID:Acute effects of the aldehyde dehydrogenase inhibitors, disulfiram, pargyline and cyanamide, on circulating ketone body levels in the rat. 334 79

Rats with streptozotocin-induced diabetes mellitus (DM) are resistant to aminoglycoside (AG) nephrotoxicity presumably because of defective transport and accumulation of drug by proximal tubular cells. To test this hypothesis we injected DM rats with saline or with gentamicin, 100, 200, and 400 mg/kg per day for 6 days, to determine if the renal cortical concentration of gentamicin could be raised to toxic levels. Nephrotoxicity was assessed by monitoring for evidence of accelerated lipid peroxidation in the renal cortex, for elevation of the serum creatinine concentration, and for evidence of proximal tubular cell injury and necrosis by light and electron microscopy. At 100 mg/kg per day renal cortical gentamicin was 454 +/- 85 micrograms/g. Except for an increase in renal cortical phospholipids these rats manifested no evidence of accelerated lipid peroxidation or elevation of serum creatinine. At 200 mg/kg per day renal cortical gentamicin rose to 636 +/- 20 micrograms/g. These rats manifested mild functional and morphological evidence of toxicity. At 400 mg/kg renal cortical gentamicin rose to 741 +/- 43 micrograms/g. These rats developed severe nephrotoxic injury as manifested by a marked increase of lipid peroxidation evident by an increase of malondialdehyde from a control level of 0.48 +/- 0.02 to 1.72 +/- 0.12 nmole/mg protein, a shift from unsaturated to saturated fatty acids esterified in renal cortical phospholipids, depression of superoxide dismutase and catalase, and a shift from reduced to oxidized glutathione. The serum creatinine rose from a baseline level of 0.24 +/- 0.01 to 0.46 +/- 0.05 mg/dl. Light and electron microscopy revealed enlarged lysosomes distended with typical myeloid bodies and extensive proximal tubular cell necrosis. These observations provide compelling evidence in support of the view that the resistance of DM rats to AG nephrotoxicity is causally linked to the low rate of drug uptake by renal proximal tubular cells. When the renal cortical concentration reaches a critical level, it elicits a pattern of toxic injury indistinguishable from that of nondiabetic rats. Thus, there is nothing inherent to the diabetic state that prevents AGs from causing their usual adverse effects on the metabolism of renal proximal tubular cells once they gain access in sufficient quantity into these cells.
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PMID:Induction of nephrotoxicity by high doses of gentamicin in diabetic rats. 342 18

This study was carried out to determine the relationships between blood trace metal concentrations and the clinical status of patients with cerebrovascular disease, gastric cancer and diabetes mellitus. The concentrations of blood trace metals were determined by flameless atomic absorption spectrophotometry. The concentrations were compared to clinical parameters such as blood biochemical parameters, CBC, etc. The contribution of blood trace elements to these three diseases and the possibilities for prophylaxis of these three diseases are discussed. The results obtained were as follow: 1. Patients with cerebrovascular disease showed generally lower concentrations than normal subjects, while the gender difference of the blood metal concentrations showed a pattern similar to that of normal subjects. In some combination, significant correlations were observed between blood metal concentrations and clinical biochemical parameters. 2. As the stage of gastric cancer advanced, blood copper concentrations increased. In all gastric cancer patients the blood copper concentration had a positive correlation with platelet counts, CEA and LDH, and a negative correlation with hemoglobin concentrations, hematocrit value and catalase. Plasma copper concentrations had a significant positive correlation with catalase. Corpuscular zinc concentrations had a significant positive correlation with platelet counts, CEA, ALP and LDH, and a significant negative correlation with hemoglobin concentration and GSH-Px. Corpuscular manganese concentrations had a significant positive correlation with CEA and LDH. 3. The blood copper concentration of patients with diabetes mellitus showed a distribution pattern similar to that of healthy subjects. Therefore, copper is not considered to be an important factor in diabetes mellitus. Diabetic patients treated by insulin injection showed increased blood zinc concentrations. Chromium, which is contained in GTF (glucose tolerance factor), showed lower blood concentrations in patients with severe complications, such as retinopathy or nephropathy. Therefore, it appears that chromium plays an important role in advancing diabetes mellitus.
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PMID:[Studies on the relationships between blood trace metal concentrations and the clinical status of patients with cerebrovascular disease, gastric cancer and diabetes mellitus]. 344 33

Previous experiments on alloxan diabetogenicity suggest that alloxan increases the permeability of B-cell plasma membranes by generation of noxious free radicals. Whether the radicals are generated intra- or extracellularly has however been disputed. To test if extracellularly generated free radicals could decrease trypan blue exclusion of dispersed islet cells, a radical-generating solution of xanthine oxidase/hypoxanthine was employed. The solution increased dye uptake by cells in the cell suspension. Superoxide dismutase and catalase but not scavengers of hydroxyl radicals protected against the increase in dye uptake. Both L- and D-glucose protected the cells from injury. It is concluded that extracellularly generated free radicals induce damage to the plasma membrane of islet cells. The result strengthens the hypothesis of plasma membrane damage by extracellularly generated free radicals as the primary event in alloxan diabetogenicity and may provide a link for explanation of damage caused by islet inflammation in juvenile diabetes.
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PMID:Effect of extracellularly generated free radicals on the plasma membrane permeability of isolated pancreatic B-cells. 351 30

There is increasing evidence that islet beta cells may be susceptible to redox insult, and that this susceptibility may contribute to the pathogenesis of experimental models of diabetes mellitus. We investigated the effect of vitamin E deficiency, selenium deficiency, and combined deficiency on islet function and free radical scavenging systems. The tissue levels of glutathione peroxidase, catalase, and immunoreactive superoxide dismutases were measured in four groups of rats (i.e., controls and those with vitamin E, selenium, and combined deficiency). Glucose tolerance tests were performed for each animal before sacrifice. Superoxide dismutase concentrations in liver, heart, and skeletal muscle were within 20% of the control levels in all groups. However, the manganosuperoxide dismutase concentrations in islets were significantly lower than control levels in response to vitamin E, selenium, and combined deficiency. Combined deficiency appeared to have an additive effect. In contrast, cuprozinc superoxide dismutase concentration in islets was higher in the deficient groups than in controls. Insulin secretory reserve was decreased in each of the three deficient groups. This decrease was reflected as glucose intolerance only in the group with combined deficiency. Glutathione peroxidase activity was markedly decreased in selenium-deficient animals in all tissues studied. Catalase activity did not change significantly among groups in any tissue studied. Islets had the lowest glutathione peroxidase and cuprozinc and total superoxide dismutase levels among tissues studied.
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PMID:Effect of vitamin E deficiency and selenium deficiency on insulin secretory reserve and free radical scavenging systems in islets: decrease of islet manganosuperoxide dismutase. 351 3


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