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

Hydroxyl radicals have been implicated in various forms of tissue injury ranging from radiation-induced cell death to alloxan-induced diabetes in animals. Although hydroxyl radicals can be readily generated in vitro, for example by the action of radiation or from the reaction of ferrous (FeII) ions with peroxides, they have not been observed directly in vivo. Their involvement in tissue damage has generally only been inferred from studies with so-called selective radical scavengers. In this paper the validity of such inferences will be briefly discussed in the light of current knowledge about the mechanisms and rates of reactions of hydroxyl radicals with biological compounds.
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PMID:Hydroxyl radicals and biological damage in vitro: what relevance in vivo? 25 61

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

A retrospective study was done in 86 patients on dialysis in order to evaluate the doses of aluminum hydroxide (OH3 Al) received to achieve a better serum phosphate control. Thirty-seven patients were treated with continuous ambulatory peritoneal dialysis (CAPD) divided in 22 diabetics and 15 non-diabetics. Forty-nine patients were treated with hemodialysis (HD), 12 diabetics and 37 non-diabetics. The doses of 1-25 Dihidroxycholecalciferol (1-25 DOH-D3) were similar in all patients. The serum phosphate levels were similar in CAPD and HD patients with smaller doses of OH3 AL in CAPD patients (p less than 0.001). Diabetics on either technique need less OH3 AL in CAPD (CAPD p less than 0.01; HD p less than 0.05) to achieve the same or better control of serum phosphorus than non-diabetics. The overload of glucose on CAPD and the maintained hyperglycemia on diabetes mellitus would shift phosphorus into the cell and could explain these results. Finally, the less needs of aluminum hydroxide on diabetic patients could contribute to their protection against aluminum deposition and its effects.
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PMID:Diabetic patients on CAPD need less aluminum hydroxide as a phosphate binder than non-diabetics. 198 39

The clinical relevance of regular serum aluminium monitoring in dialysis patients was investigated in a multicentre study by 6-monthly determination of the serum aluminium during 4 consecutive years. In a group totalling 1193 patients, a striking decrease of mean serum aluminium was observed the last 2 years of the study. This phenomenon was accompanied by a substantial reduction of the prescribed dose of aluminium hydroxide (Al(OH)3) and its partial replacement by calcium carbonate (CaCO3) and/or magnesium hydroxide (Mg(OH)2). Under this policy serum phosphate control remained satisfactory. In all the centres, water treatment was found to be adequate, yielding dialysate aluminium around 2 micrograms/l. Dialysis patients with clinically overt liver disease showed a significantly greater median serum aluminium concentration than that observed in a control dialysis population. Compared to the latter group, the median serum aluminium concentration of dialysis patients with diabetes mellitus did not differ significantly. Results further indicated that patients with biopsy-proven osteomalacia presented a significantly greater median serum aluminium compared to that of patients without osteomalacia. We demonstrated that a serum aluminium of 60 micrograms/l provides a relatively sensitive (82%) and specific (86%) index for the detection of aluminium-related bone disease (ARBD). Provided the aluminium determinations are performed by a qualified laboratory, serum monitoring in dialysis patients (a) allows the safer use of aluminium-containing phosphate binders, and (b) is of value in the diagnosis of overload/toxicity.
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PMID:Value of serum aluminium monitoring in dialysis patients: a multicentre study. 131 84

Cathodal iontophoresis was used to deliver insulin in 23 alloxan-diabetic, male, New Zealand white rabbits. Currents of 0.2-0.8 mA were used to deliver insulin from reservoirs containing insulin concentrations of 10-500 U/ml in aqueous solution. Regardless of the level of current used, within 1 h of turning the current on, blood glucose levels decreased and serum insulin concentrations increased. Moreover, in most cases, blood glucose levels continued to decrease and serum insulin concentrations continued to increase after the current was turned off, suggesting that iontophoresis could be used to accumulate insulin in the skin and subcutaneous tissues. The amount of insulin that was delivered by iontophoresis could be controlled by the level of current used up to 0.4 mA; increasing the current to 0.8 mA did not deliver more insulin. This may have been due to greater production of hydroxide ions at 0.8 mA, which competed with insulin to carry the current, thus slowing the movement of insulin. The amount of insulin delivered could also be controlled by the amount of insulin available for iontophoresis, i.e., as the insulin reservoir concentration increased, more insulin was delivered at the same current level. Finally, skin preparation was also important in controlling insulin delivery. To deliver enough insulin to reduce blood glucose levels, the stratum corneum had to be disrupted or removed by gentle scraping.
Diabetes 1986 Feb
PMID:Control of blood glucose levels in alloxan-diabetic rabbits by iontophoresis of insulin. 351 Sep 26

The activities of beta-Hydroxy-beta-methylglutaryl CoA reductase (HMG CoA reductase), Acyl CoA: Cholesterol-O-acyltransferase (ACAT) and cholesterol 7 alpha-hydroxylase, the major enzymes involved in cholesterol metabolism, were determined in diabetic and non-diabetic rats after vagotomy and compared with those of sham-operated controls. Hepatic cholesterol levels and serum lipid profiles were also examined. In the non-diabetic animals vagotomy produced a significant increase in HMG CoA reductase (the rate limiting enzyme of cholesterol biosynthesis), and ACAT (the enzyme responsible for intracellular esterification) activities, while the activity of cholesterol 7 alpha-hydroxylase (which catalyses the rate determining step of bile acid biosynthesis) was significantly decreased. These rats had higher levels of free and esterified cholesterol in the liver and serum cholesterol levels were also increased in comparison with sham-operated animals. Vagotomized diabetic rats had similar HMG CoA reductase activity, but significantly reduced ACAT and reduced cholesterol 7 alpha-hydroxylase activity in comparison with sham-operated diabetic rats. There were significant alterations in hepatic and serum cholesterol fractions in both normal and diabetic rats after vagotomy. The results suggest that vagotomy leads to an increased rate of cholesterol synthesis and a decreased rate of cholesterol utilization, thus providing a possible mechanism for excessive cholesterol accumulation. These results are discussed in relation to alterations in cholesterol metabolism found in diabetic autonomic neuropathy.
Diabetes Res 1985 Nov
PMID:Cholesterol metabolism: regulatory effects of the vagus in the normal and diabetic animal. 407

Larger-than-conventional doses of nonsteroidal antiinflammatory drugs (NSAIDs) are known to lower plasma glucose levels. This phenomenon has raised the questions whether or not NSAIDs in conventional dosage can be used for the treatment of hyperglycemia in patients who have non-insulin-dependent diabetes mellitus and whether or not NSAIDs added to preexistent hypoglycemic drug therapy taken orally may lead to unanticipated hypoglycemia. In this study we evaluated aspirin, sodium salicylate and ibuprofen given in conventional dosage to hyperglycemic patients with adult-onset (type II) diabetes. Half the patients were usually treated for hyperglycemia by means of diet only and half with diet plus hypoglycemic drugs given orally. Significant changes in plasma glucose levels were not seen after the administration of a combination drug containing aspirin and magnesium-aluminum hydroxide (Ascriptin, 650 mg three times a day; glucose change = 236+/-30 to 236+/-31 mg per dl) or sodium salicylate (600 mg three times a day; glucose change=284+/-76 to 273+/-84 mg per dl). A statistically significant but small change was seen with the administration of ibuprofen (600 mg three times a day; glucose change=196+/-60 to 179+/-47 mg per dl) but not when giving ibuprofen (300 mg three times a day; glucose change=267+/-78 to 282+/-60 mg per dl). The results of this study indicate that conventional doses of NSAIDs should not be used for treating hyperglycemia and that, since the additive hypoglycemic effect of NSAIDs in conventional doses was minimal or negligible, they can be used safely for other purposes in diabetic patients taking hypoglycemic drugs orally.
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PMID:Effects of nonsteroidal antiinflammatory drugs in conventional dosage on glucose homeostasis in patients with diabetes. 662 82

The sensitivity to the diabetogenic action of triphenyltin hydroxide (TPTOH) was investigated in 5 species of experimental animals. A single oral administration of TPTOH produced marked hyperglycemia and triglyceridemia in rabbits and hamsters, but no evidence of diabetes was found in mice, rats and guinea-pigs. No morphological abnormality was observed in islet tissue from TPTOH-treated hamsters.
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PMID:Species difference in sensitivity to the diabetogenic action of triphenyltin hydroxide. 671 70

Hydroxyl radicals (.OH) may contribute to beta cell death. Because iron catalyzes .OH production, we examined whether administration of a novel, long-acting iron chelator, hydroxyethyl starch-deferoxamine (HES-DFO) could prevent diabetes in spontaneously diabetic biobreeding (BB) rats. In our colony, a peripheral lymphocyte count (PBLC) < 4200 mm3 has an 88% positive predictive value for onset of diabetes mellitus (DM). Rats with PBLC < 4200 mm3 were randomized at 6 weeks of age to receive 50 mg/kg of HES-DFO (a high molecular weight hydroxyethyl starch-conjugated derivative of deferoxamine) or equimolar hydroxyethyl starch (HES) alone given intraperitoneally three times weekly until DM or 120 days of age. Administration of HES significantly decreased the incidence of IDDM to 57% as compared with the incidence of 87% in the lymphopenic unmanipulated BB rats in the colony (p < 0.01). Administration of HES-DFO further significantly decreased the incidence of IDDM to 31% as compared with the lymphopenic unmanipulated rats (p < 0.01). When analyzed by sex, 3 of 17 (18%) HES-DFO-treated males developed DM, versus 10 of 17 (58%) of HES-treated males (p < 0.05, chi square); 8 of 19 (42%) of HES-DFO-treated females developed DM, versus 11 of 20 (55%) HES-treated females (p = NS). There were no differences between the groups in (1) mean time of onset of DM, (2) serum iron levels at study entry and completion, (3) weekly hematocrits, (4) total lymphocyte counts; and (5) weekly weight gains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydroxyethyl starch deferoxamine, a novel iron chelator, delays diabetes in BB rats. 751 76

Production of hydroxyl radicals was examined in the diabetic rats induced by streptozotocin to prove its involvement to the pathogenesis of diabetes. Hydroxyl radicals generated in plasma, heart muscle, liver and brain of the hyperglycemic rats were quantitatively assayed by trapping hydroxyl radicals with salicylic acid as 2,3- and 2,5-dihydroxybenzoic acid. The concentrations of 2,3- and 2,5-dihydroxybenzoic acid were significantly increased in all the tissues of the diabetic rats. In the brain and heart muscle of the diabetic rats, the increase of 2,3-dihydroxybenzoic acid was more manifest than that of 2,5-dihydroxybenzoic acid, while in liver 2,5-dihydroxybenzoic acid increased markedly. All the values of 2,3-dihydroxybenzoic acid detected in the tissues of the diabetic rats were quite higher than those in control. Hydroxyl radical production and blood glucose concentration were depended almost linearly on the amount of streptozotocin injected to rats up to 60 mg/kg body weight. It was suggested that 2,3-dihydroxybenzoic acid was produced from hydroxyl radicals themselves, while 2,5-dihydroxybenzoic acid was produced by hydroxylation of salicylic acid not only with hydroxyl radicals, but also by enzymatic reaction of microsomal cytochrome-P450. Hydroxyl radical formation may account for some pathological process especially in the heart muscle and brain.
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PMID:Hydroxyl radical formation in diabetic rats induced by streptozotocin. 773 53


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