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

Stable compensation of diabetes mellitus, including normolipidemia, underlies the therapy of diabetic angiopathies. Mevacor represents a nonactive lactone form of a certain hydroxy acid, a potent inhibitor of endogenous synthesis of cholesterol, conducive to blood cholesterol reduction. The aim of the present study was the assessment of the efficacy of this drug in therapy of patients with diabetes mellitus. Ten patients were administered mevacor in a dose of 20 mg for a month. Such therapy was conducive to a significant reduction of the levels of cholesterol, LNP cholesterol, triglycerides, and cholesterol/LVP ratio. It also promoted a reduction of the content of lipid peroxidation products in the blood, these products being an active factor of vessel destruction. The levels of hydroperoxides, blood serum and red cell malonic dialdehyde, and superoxide dismutase were also reduced. These results necessitate addition of mevacor to a complex of therapy for diabetes to normalize lipid metabolism.
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PMID:[Use of the lipolytic drug mevacor in the treatment of patients with diabetes mellitus]. 130 47

The defense system of aortic endothelial cells against oxidative stress was studied in alloxan-induced diabetic rabbits, and the effect of insulin on the antioxidant activities was estimated. Endothelial cells were prepared from 10 diabetic rabbits, 18 diabetic rabbits treated with insulin, and 10 age-matched controls after 17 days of diabetes. These cells were used for the estimation of glutathione (GSH) levels and its related enzyme activities. The antioxidant activities in these endothelial cells from diabetic rabbits were compared with those from control subjects. The concentration of GSH decreased in diabetic rabbits (1.6 +/- 0.2 nmol/mg protein [mean +/- SD] v 3.7 +/- 0.6 nmol/mg protein). Decreases in the activities of Cu, Zn-superoxide dismutase (Cu,Zn-SOD) (62.7 +/- 11.0 U/mg protein v 172.9 +/- 20.2 U/mg protein), catalase (7.6 +/- 2.1 U/mg protein v 12.3 +/- 3.2 U/mg protein), and GSH peroxidase (134.0 +/- 27.0 mU/mg protein v 179.1 +/- 26.2 mU/mg protein) were observed. The activities of other GSH-related enzymes such as GSH S-transferase or GSH reductase did not change in endothelial cells from diabetic rabbits. Most of these antioxidant activities were prevented when diabetic rabbits were treated with insulin (1 to 2 U/kg/d). These antioxidant activities were also determined in the diabetic liver and kidney. Similar decreases in the cellular defense activities and prevention of the decrease in activities by insulin were observed in the diabetic liver, while these antioxidant enzyme activities in the kidney were resistant to diabetic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of insulin on impaired antioxidant activities in aortic endothelial cells from diabetic rabbits. 140 92

Alloxan induces diabetes in laboratory animals through the destruction of the endocrine pancreatic B cells. The mechanism of alloxan toxicity is still obscure. This study was conducted to investigate the effects of superoxide dismutase (SOD) or reduced nicotinamide adenine dinucleotide (NADPH) treatment on the B cells in isolated rat islets prior to alloxan treatment. Islets were treated with SOD (1000 U) or 0.1 mM NADPH for 10 min followed by alloxan treatment (0.18 mg) for 5 min. Insulin secretion was studied in samples incubated for 60 min in media supplemented with glucose (1.8 mg/ml). Morphological examinations were conducted on fixed samples after the alloxan treatment. SOD significantly protected the islets from the cytotoxic effect of alloxan. Although alloxan decreased insulin secretion to 35% of the control, SOD increased this level to 73% of the control values. NADPH did not provide any protection to the islets. Insulin secretion from islets treated with NADPH and alloxan was not different from that after alloxan treatment alone. Morphological changes were observed in the islets treated with alloxan alone or alloxan in the presence of NADPH. Islets exhibited multiple cellular necrosis, marked degranulation and extensive vesiculation of the endoplasmic reticulum and Golgi complex. Mitochondrial enlargement with disrupted cristae and mitochondrial ruptures were prominent. However, islets treated with SOD and alloxan were similar to the control except for the enlarged mitochondria. The increased insulin secretion from islets treated with SOD and alloxan reinforces the free radical hypothesis of alloxan toxicity. The markedly enlarged mitochondria was one of the targets through which alloxan destroyed the B cells.
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PMID:Protection of B cells against the effect of alloxan. 145 47

Exposure to hyperglycemia slows the rate of proliferation of cultured human endothelial cells. Recently, it has been reported that glucose may autoxidize generating free radicals which have been hypothesized to delay cell replication time. To test whether oxidative stress has an effect on delaying cell replication time in hyperglycemic conditions, human endothelial cells cultured from umbilical veins were incubated in 5 or 20 mM glucose, either alone or in the presence of one of three different antioxidants: superoxide dismutase (SOD), catalase and glutathione (GSH). Cells grown in medium with 5 mM glucose, with or without antioxidants, yielded similar population doubling times and cell cycle phase distributions. Significantly lower growth parameters were observed in cells grown in medium with 20 mM glucose, without antioxidants. The presence of the antioxidant reverted them to almost normal growth. These data show that high glucose levels may delay endothelial cells replication time through the generation of free radicals, suggesting a possible pathophysiological linkage between the high levels of glucose and the development of microvascular complications of diabetes, possibly suggesting a new therapeutic approach to prevent such complications.
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PMID:Decreased cultured endothelial cell proliferation in high glucose medium is reversed by antioxidants: new insights on the pathophysiological mechanisms of diabetic vascular complications. 148 70

We propose new hypotheses for the mechanisms of streptozotocin (STZ) and alloxan inducing experimental diabetes in animals. STZ is transported into pancreatic beta cells through glucose transporter in the cell membranes and attacks mitochondria. Mitochondrial ATP generation is inhibited and the resulting high concentration of intracellular ADP causes its degradation providing hypoxanthine, a substrate of xanthine oxidase (XOD) whose activity is intrinsically very high in beta cells. Then, XOD-catalyzing reaction is proceeded as proved by increased formation of uric acid and O2- radicals are produced, but beta cells are inefficient to scavenge these radicals because of their extremely low activity of superoxide dismutase. On the other hand, STZ directly activates XOD and enhances O2- generation. Consequently, pancreatic beta cells are dually suffered from O2- radicals or probably hydroxyl radicals derived from the former when exposed to STZ. Allopurinol, an inhibitor of XOD, can protect animals from the diabetogenic effect of STZ. In pancreatic beta cells, alloxan anion radicals are generated from alloxan probably mediated by the action of microsomal cytochrome P-450 system. These radicals have long half-life and directly damage DNA in vitro. The widely accepted hypothesis that the cause of alloxan-induced diabetes is attributable to O2- radicals formed from alloxan is excluded, because alloxan itself shows a very potent scavenging effect to O2- radicals. Therefore alloxan anion radicals seem to be directly related to the incidence of diabetes by alloxan.
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PMID:[New hypotheses for the mechanisms of streptozotocin and alloxan inducing diabetes mellitus]. 148 45

This study reports on the effect of streptozotocin (STZ) induced diabetes on water soluble-SH and -SS, as well as on hepatic glutathione peroxidase (GSH-Px), catalase and superoxide dismutase (SOD) activity and on malondialdehyde (MDA) content. In addition, we determined serum concentrations of glucose, cholesterol, triglycerides and thyroxine, and thyroid weight. To elucidate the possible impact of exogenous iodine on impaired free radical tissue defense mechanisms STZ-diabetic rats were exposed to iodine brine providing for a daily iodide uptake of about 300 micrograms/kg body weight. STZ-exposure caused a decline in thyroid weight (p less than 0.01) and in total serum thyroxine (p less than 0.001), as well as a fall in hepatic catalase (CAT) activity (p less than 0.01) versus control group. Impairment of catalase activity was related to serum glucose level (r = -0.569, p less than 0.01), while hepatic MDA was positively related to serum glucose (r = + 0.5, p less than 0.01). No protective effects of iodine brine were seen with regard to impairment by STZ of antioxidant enzyme status. We conclude that impairment by STZ of antioxidant enzymes may contribute to STZ-dependent experimental diabetes.
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PMID:Alterations of antioxidant tissue defense enzymes and related metabolic parameters in streptozotocin-diabetic rats--effects of iodine treatment. 150 40

Changes in the levels of lipid peroxides and antioxidant enzymes were studied in male albino rats with experimental diabetes mellitus. Diabetes was induced by single subcutaneous injection of alloxan (19 mg/100 g body weight). The concentration of malondialdehyde (MDA) showed an increase both in the liver (P less than 0.01) and kidney (0 less than 0.05), while in the heart, there was a decrease (P less than 0.01), as compared to control values. A similar pattern of change was observed in the level of hydroperoxides in the liver and heart. The conjugated dienes showed an elevation during diabetes in all tissues (P less than 0.01). Glutathione levels in heart (P less than 0.01) and kidney were found to be decreased (P less than 0.05) while the liver showed an elevation during long-term diabetes (P less than 0.01). Serum ceruloplasmin showed an increase (P less than 0.05) in diabetes. Antioxidant enzymes superoxide dismutase and catalase decreased in all tissues (P less than 0.01) while the activity of glutathione s-transferase increased in heart, but no change in other tissues. The studies thus show that lipid peroxidation is activated in liver and kidney while heart tissues show some resistance towards lipid peroxidation.
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PMID:Peroxidative changes in experimental diabetes mellitus. 151 41

Studies were carried out on the metabolism of lipid peroxides and antioxidative enzymes during diabetes and diabetes superimposed with myocardial infarction. Diabetes was induced using alloxan and myocardial infarction was induced by isoproterenol. In the case of diabetic animals there was a decrease in the levels of lipid peroxides in the heart while in the case of diabetes associated with myocardial infarction it was slightly elevated. The activity of superoxide dismutase and catalase showed a decrease in both the groups. Glutathione showed a fall in the case of diabetes and diabetes associated with myocardial infarction while taurine in heart and ceruloplasmin in the serum was elevated. Histopathological changes in the heart tissue showed some focal changes in the case of both diabetes and diabetes associated with myocardial infarction, but the degree of necrosis was much less than in the case of myocardial infarction.
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PMID:Changes in levels of lipid peroxides and activity of superoxide dismutase and catalase in diabetes associated with myocardial infarction. 152 61

In vitro studies have demonstrated that gliclazide has free radical scavenging and antiplatelet activities. To assess this clinically, we studied gliclazide in a blinded, randomized, glibenclamide-controlled trial in 30 type II diabetic patients with retinopathy. All patients had been taking glibenclamide for more than 12 months before being randomized to receive either an equipotent dose of gliclazide or to continue on glibenclamide. Diabetic control was not modified. The patients were well matched at randomization (mean age, 58 years; duration of diabetes, 8 years; 20 males; mean hemoglobin A1 [HbA1], 8.6%) and their degree of diabetic control was not altered during the trial. Free radical activity was assessed as oxidative status by plasma thiols (PSH), lipid peroxides (MDA-LM), and red blood cell superoxide dismutase activity (SOD). Platelet aggregation in whole blood to collagen (Plt-ag) was used as the measure of platelet reactivity. There were no differences between these measurements at baseline. At 3 months, the oxidative status and platelet aggregation in the gliclazide group had improved significantly compared with baseline and had also showed significant differences in all parameters when compared with the glibenclamide group. Therefore, comparing gliclazide with glibenclamide-treated patients at 3 months, we found: PSH, 458 +/- 38 versus 414 +/- 34 mumol/L, P less than .004; MDA-LM, 7.0 +/- 0.6 versus 8.3 +/- 0.8 mumol/L, P less than .0002; SOD, 152 +/- 36 versus 123 +/- 15 micrograms/mL, P less than .016; Plt-ag, 50.8 +/- 24 versus 72.3% +/- 15%, P less than .006. These changes were maintained at 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of gliclazide on platelet reactivity and free radicals in type II diabetic patients: clinical assessment. 157 14

Our previous study indicated that erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn-SOD) undergoes glycation and inactivation in vivo (1) and in vitro (2). The aim of the present study was to assess glycated Cu,Zn-SOD in patients with insulin-dependent diabetes mellitus. Glycated Cu,Zn-SOD, which binds to a boronic acid affinity column, was measured by the enzyme-linked immunosorbent assay. The percentage of the glycated form in 25 insulin-dependent diabetic children was 40.2 +/- 8.2%; this was significantly higher than that in the normal controls (P less than 0.01). The specific activity of the glycated form in the diabetic children was 163,000 +/- 33,000 IU/mg Cu,Zn-SOD protein, significantly lower than that in controls (P less than 0.01). These data indicate that glycated and less active Cu,Zn-SOD is increased in erythrocytes of patients with insulin-dependent diabetes mellitus.
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PMID:Increased glycated Cu,Zn-superoxide dismutase levels in erythrocytes of patients with insulin-dependent diabetis mellitus. 159 80


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