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

Non-enzymic binding of sugars to proteins (glycation) is a common biological phenomenon that is increased in diabetes. Most work has been directed towards structural proteins which may be present for many years and would continue to accumulate sugar residues. As glycation is a non-specific reaction, other proteins such as enzymes will also be susceptible to glycation and could well display altered activity. We investigated the effect of various sugars whose concentrations increase in diabetes in insulin-independent tissues on glutathione reductase, an enzyme that maintains the GSH level in cells. Glucose, glucose 6-phosphate and fructose all displayed a time-dependent inhibition of glutathione reductase activity, suggesting that these sugars glycate this enzyme. Aspirin gave some protection against the loss of activity induced by glucose.
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PMID:Glycation (non-enzymic glycosylation) inactivates glutathione reductase. 144 75

To clarify the therapeutic effects of several traditional Chinese medicines to improve disorders of carbohydrate, lipid and mineral metabolism, spontaneously diabetic rats (WBN/Kob) were treated with Vit. D2, 1 x 10(5) I.U./kg b.w./day, for 4 days, and then fed a hyperlipidemic diet containing traditional Chinese medicines for 6 weeks. The following results were obtained: 1) In the diabetic rats, the 3 traditional Chinese medicines further decreased the blood glucose level at 120 min after glucose loading in the glucose tolerance test. 2) The drugs increased the inorganic phosphate in the liver and normalized mineral metabolic disorder. 3) Hachimi-zio-gan decreased the cholesterol content in the kidney, and Sho-saiko-to decreased the cholesterol content in the elastin fraction (elastin-cholesterol) of the kidney. Such experimental results suggest that traditional Chinese medicines may be effective against the pathological conditions of diabetes mellitus that involve disorders of lipid and mineral metabolism.
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PMID:[Effects of traditional Chinese medicines (dai-saiko-to, sho-saiko-to and hachimi-zio-gan) on spontaneously diabetic rat (WBN/Kob) with experimentally induced lipid and mineral disorders]. 144 86

A procedure for the assay of methylglyoxal in biological systems is described, together with sample storage, sample processing procedures, and statistical evaluation. Specimen data are presented. Methylglyoxal was assayed by derivatization with 1,2-diamino-4,5-dimethoxybenzene and high-performance liquid chromatography (HPLC) of the resulting quinoxaline, 6,7-dimethoxy-2-methylquinoxaline, with spectrophotometric or fluorescence detection. Derivatization, solid-phase extraction, and HPLC were performed under acid conditions to prevent the spontaneous formation of methylglyoxal from glyceraldehyde 3-phosphate and dihydroxyacetone phosphate during the assay. The limits of detection in the biological matrix were 45 pmol (absorbance detection) and 10 pmol (fluorimetric detection), the recovery was 58%, and the intra- and interbatch coefficients of variance were 7.7 and 30.0%, respectively. The concentration of methylglyoxal in whole blood from normal healthy human individuals was (mean +/- SE, nM) 256 +/- 92 (n = 12) and that from diabetic patients was 479 +/- 49 (n = 55), showing a significant increase in diabetes mellitus (P < 0.01; Mann-Whitney U test). Sample processing under acidic conditions was essential to avoid interferences. Previous estimates of the concentration of methylglyoxal in biological samples require re-evaluation.
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PMID:The assay of methylglyoxal in biological systems by derivatization with 1,2-diamino-4,5-dimethoxybenzene. 145 30

Diabetes mellitus is the most frequent chronic disease associated with secondary magnesium deficit. Hypomagnesaemia is a central feature of the deficit, which is often reported in experimental and clinical forms of the disease. In diabetic rats as in man, plasma magnesium concentrations may correlate inversely with the degree of hyperglycaemia. The duration of the disease also appears to be relevant. The hypomagnesaemia of diabetes might be expected to affect intracellular concentrations of the ion. However, although some animal and clinical studies have reported subnormal magnesium concentrations in blood cells, bone, and soft tissues of diabetics, the relationship between plasma magnesium concentration and intracellular level of the ion is inconsistent. Clinical studies have speculated on a potential link between the magnesium deficit of diabetes and several diabetic complications, including cardiovascular problems and retinopathy. Recent experimental studies are largely supportive of such a link; myocardial disorders associated with magnesium deficiency have been reported in diabetic mice and rabbits. It is possible that a common mechanism involving magnesium may be responsible for some of the diverse complications of diabetes. The aetiology of hypomagnesaemia in diabetes is complex. Nevertheless, plasma magnesium concentrations are ultimately determined by four processes: intake, gastrointestinal absorption, redistribution within body pools, and urinary excretion. This review considers in turn the potential role of each of these processes in the development of diabetic hypomagnesaemia. Both experimental and clinical studies suggest that hypermagnesiuria may be the major factor involved. Recent animal studies have described a specific renal tubular magnesium defect in diabetes, which, together with the osmotic diuresis, is responsible for large magnesium losses. The precise cause of the defect is unknown, but it may relate to the prolonged hyperglycaemia, insulinopenia, disturbance of phosphate metabolism, or other hormonal changes which characterize the disease.
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PMID:New experimental data on the relationship between diabetes mellitus and magnesium. 146 58

With moderate training (30-60 min daily at 70-80% of VO2 max, 3-5 times weekly), the trained muscles display a 40-50% increase in the content of mitochondrial oxidative enzymes. Concomitantly, the total number of muscle capillaries may increase by 50%, whereas the content of glycolytic enzymes is not, or only marginally, affected. The oxidative enzyme increase, which occurs over 6-8 wk, is lost in 4-6 wk if training is stopped. This loss occurs faster than the decrease in muscle capillarization and in the whole-body VO2 max. Trained muscles of athletes have 3-4 times higher oxidative enzyme levels and two- to threefold more capillaries per muscle fiber than untrained muscle. Extensive endurance training results in an enhanced percentage of slow-twitch fibers, but the time course of this change is not known. More extensive changes are observed in chronically stimulated rabbit muscle. In this case, enzymes of oxidation display large increases (6- to 12-fold), whereas there is a decrease of 70-90% in enzymes of glycolysis, glycogenolysis, gluconeogenesis, and high-energy phosphate transfer. There is a normal training response in mitochondrial enzyme activities in individuals with insulin-dependent and non-insulin-dependent diabetes, but the ability to form new skeletal muscle capillaries in response to physical training may be deficient in insulin-dependent diabetes. Training-induced changes in the metabolic character of skeletal muscle leads to an increased reliance on fat metabolism during exercise, with a lowered blood lactate concentration and a sparing of muscle glycogen.
Diabetes Care 1992 Nov
PMID:Effects of physical training on the metabolism of skeletal muscle. 146 4

The effect of chemically-induced diabetes on the handling of phosphate (Pi) by rat jejunal enterocytes has been investigated in the presence of a Na- or a choline-gradient. Pi uptake was significantly increased in both gradients. The Pi efflux rate constants for enterocytes from diabetic rats were similar to those of control rats. The effect of diabetes on both the protein and alkaline phosphatase isoenzymes of the rat small intestinal brush-border membranes was examined using SDS-PAGE. The patterns given by membranes from rats 14 days after the induction of diabetes were no different from those of controls.
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PMID:Effect of streptozotocin-induced diabetes on the handling of phosphate by the rat small intestine. 147 66

Measurements have been made of the activities of the enzymes of the de novo and salvage pathways of pyrimidine synthesis (carbamoyl phosphate synthetase II (glutamine) (EC 6.3.5.5); dihydroorotate dehydrogenase (EC 1.3.99.11); the overall activity of Complex II (orotate phosphoribosyl pyrophosphate transferase (EC 2.4.2.10) and orotidine 5-phosphate decarboxylase (EC 4.1.1.23); uracil phosphoribosyltransferase (EC 2.4.2.9)) in the mammary gland of rats at different stages of the lactation cycle and the effects of diabetes on the activity of these enzymes in lactation have been studied. From a consideration of the changes in enzyme activities and the changes in the tissue concentration of phosphoribosyl pyrophosphate, an activator of the de novo pathway and substrate for both the de novo and salvage routes, it is concluded that the de novo pathway is the major route of pyrimidine synthesis in mammary tissue. Diabetes decreases the activity of the enzymes of the de novo pathway; the effects are particularly marked for Complex II. The present results on pyrimidine synthesis are compared to the pattern for purine synthesis previously published.
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PMID:Pyrimidine nucleotide synthesis in the rat mammary gland: changes in the lactation cycle and effects of diabetes. 147 92

This is a report investigating the methylglyoxal (MG) bypass in animals, by which D-lactate is produced from triosephosphate via MG. Rats were made diabetic using streptozotocin or starved for 72 h. D-Lactate and various metabolites related to it, such as L-lactate, pyruvate, methylglyoxal, glucose, and inorganic phosphate, were measured in the blood plasma, liver, and skeletal muscle of the rats. Diabetic and starved rats had significantly higher levels of D-lactate in plasma, liver, and skeletal muscle compared with the control group. In contrast, pyruvate levels in plasma, liver, and skeletal muscle was markedly lower than normal in diabetic and starved rats. L-Lactate level lowered markedly in plasma, liver, and skeletal muscle of starved rats and elevated in liver of diabetic rats. Differences between plasma L-lactate level for diabetes and control were not significant. MG level was significantly elevated in plasma and depressed in livers and muscles of starved rats as well as livers of diabetic rats. Hepatic glycerol content was markedly increased in those states. Enzyme activities related to D- and L-lactate, such as pyruvate kinase, phosphofructokinase, aldolase, and glyoxalase I, were measured in the livers of these rats. Pyruvate kinase activity decreased in these states, but other enzyme activities showed no significant changes. D-Lactate was much more excreted than L-lactate in the urine of diabetic and fasted rats compared with normal rats.
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PMID:Concentrations of D-lactate and its related metabolic intermediates in liver, blood, and muscle of diabetic and starved rats. 148 Aug 18

This study determined whether exercise training in rats would prevent the accumulation of lipids and depressed glucose utilization found in hearts from diabetic rats. Diabetes was induced by intravenous streptozotocin (60 mg/kg). Trained diabetic rats were run on a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk. Training of diabetic rats had no effect on glycemic control but decreased plasma lipids. In vivo myocardial long-chain acylcarnitine, acyl-CoA, and high-energy phosphate levels were similar in sedentary control, sedentary diabetic, and trained diabetic groups. The levels of myocardial triacylglycerol were similar in sedentary control and diabetic rats but decreased in trained diabetic rats. Hearts were perfused with buffer containing diabetic concentrations of glucose (22 mM) and palmitate (1.2 mM). D-[U-14C] glucose oxidation rates (14CO2 production) were depressed in hearts from sedentary diabetic rats relative to sedentary control rats. Hearts from trained diabetic rats exhibited increased glucose oxidation relative to those of sedentary diabetic rats, but this improvement was below that of the sedentary control rats. [9,10(-3)H]palmitate oxidation rates (3H2O production) were identical in all three groups. These findings suggest that exercise training resulted in a partial normalization of myocardial glucose utilization in diabetic rats.
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PMID:Metabolic effects of treadmill exercise training on the diabetic heart. 150 79

To clarify whether glomerular hyperfiltration or disturbances in renal tubular function may be early markers of the later development of nephropathy a follow-up study was performed in 34 young Type 1 diabetic patients, who had originally been investigated 12 years previously. The initial median age was 14 (range 7-18) years and median diabetes duration 7 (2-14) years. At initial examination only one of the 34 diabetic patients exhibited increased urinary albumin excretion rate. The median glomerular filtration rate was increased (136 vs 107 ml min-1 1.73 m-2; p less than 0.0001) and median threshold concentration of phosphate per litre of glomerular filtrate was decreased (1.27 vs 1.76 mmol l-1; p less than 0.0001) in the diabetic group as compared to that of 28 healthy children. At follow-up 17 patients showed increased urinary albumin excretion rate and the median glomerular filtration rate in this group was significantly lower than that of 17 patients with normal urinary albumin excretion rate (108 vs 125 ml min-1 1.73 m-2; p less than 0.05). However, no relationships were found between the increased urinary albumin excretion (incipient and/or overt diabetic nephropathy) at follow-up to either the initial glomerular filtration rate (134 vs 137 ml min-1 1.73 m-2; p greater than 0.05) or to renal tubular function assessed from urinary excretion rate of beta 2-microglobulin (0.059 vs 0.069 microgram min-1; p greater than 0.05) and the renal threshold concentration of phosphate per litre of glomerular filtrate (1.29 vs 1.22 mmol l-1; p greater than 0.05).
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PMID:Does increased glomerular filtration rate or disturbed tubular function early in the course of childhood type 1 diabetes predict the development of nephropathy? 151 70


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