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

A histochemical evaluation of the activity of chosen oxido-reductive enzymes of the cardiac muscle connected with the citric acid cycle, glycolysis and pentose shunt in the early experimental alloxan diabetes period in white rats has been carried out. Dehydrogenases: succinate, isocitrate and glucose-6-phosphate indicated a decrease in the enzymatic activity while the lactate dehydrogenase activity did not undergo any change. An increase in the intensity of the histoenzymatic reaction only concerned glutamate dehydrogenase. The presented histoenzymatic evidence of changes in the enzymatic activities may speak for the possibility of an existence of a direct diabetes influence on the cardiac muscle metabolism.
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PMID:Some histochemical observations on the myocardial metabolism in experimental conditions. Part II. 9 52

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Alanine release from skeletal muscle was increased by fasting (65%), cortisone (145%), thyroxine (200%), and diabetes (185%). Glutamine release was decreased by cortisone (37%) and diabetes (23%) but not significantly affected by fasting or thyroxine. Tissue levels of alanine were unchanged but tissue glutamine levels were markedly reduced (30 to 60%) in all treatment groups. Insulin added in vitro did not affect amino acid release even with preparations obtained from diabetic animals. Inhibition of glycolysis with 0.2 mM iodoacetate had no effect on the rate of alanine and glutamine formation in any treatment group. Pyruvate generation was increased by all treatments even in the presence of the inhibitor. Total skeletal muscle alanine, aspartate, and branched chain aminotransferase, glutamate dehydrogenase, and malic enzyme activities were not significantly altered in any treatment groups. The addition of 10 mM aspartate, cysteine, branched chain amino acids, and serine significantly increased alanine formation, whereas the maximal rate of glutamine formation in the presence of stimulating amino acids was reduced in each treatment groups--the most marked effects were noted with cortisone and diabetic preparations. Although accelerated muscle proteolysis is an important factor regulating alanine formation in skeletal muscle, the redirection of carbon flow from glutamine toward alanine formation observed in fasting, cortisone, thyroxine-treated, and diabetic rats, indicates that factors other than proteolysis also participate in the control of amino acid release from muscle.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. III. Dietary and hormonal regulation. 12 73

Eight serum enzyme tests were performed over a three-year period in 1,147 cases of patients with suspected hepatobiliary disease, of whom 580 had identifiable primary disease of the liver or biliary system. Individually, aminotransferase assays did not provide good discrimination among the various categories of hepatobiliary disease, but when expressed as a ratio a useful degree of discrimination was obtained. Isocitrate dehydrogenase, guanase and glutamate dehydrogenase alone were poor discriminants of the various disease categories studied; combination of the latter enzyme with the aminotransferases in various ratios did not achieve worthwhile improvement. Adenosine deaminase was normal in most patients with extrahepatic obstruction and abnormal in most patients with parenchymal hepatic disease, and is potentially a useful test additional to the aminotransferases in routine diagnosis. 5'-Nucleotidase was more sensitive and specific than alkaline phosphatase in diagnosing hepatobiliary disorders. Abnormalities of all these enzymes were encountered in patients who did not have hepatobiliary disease, most frequently among subjects with cancer, diabetes mellitus, and diseases of the respiratory and cardiovascular systems.
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PMID:Serum enzyme tests in diseases of the liver and biliary tree. 69 83

In islets from adult rats injected with streptozocin during the neonatal period, the oxidative and secretory responses to D-glucose are more severely affected than those evoked by L-leucine. A possible explanation for such a preferential defect was sought by comparing the rate of aerobic glycolysis, taken as the sum of D-[3,4-14C]glucose conversion to labeled CO2, pyruvate, and amino acid, with the total glycolytic flux, as judged from the conversion of D-[5-3H]glucose to 3H2O. A preferential impairment of aerobic relative to total glycolysis was found in islets from diabetic rats incubated at either low or high D-glucose concentration. This coincided in islet mitochondria of diabetic rats with a severe decrease in both the basal (no-Ca2+) generation of 3H2O from L-[2-3H]glycerol-3-phosphate and the Ca2(+)-induced increment in [3H]glycerophosphate detritiation. The mitochondria of diabetic rats were also less efficient than those of control animals in generating 14CO2 from [1-14C]-2-ketoglutarate. The diabetes-induced alteration of 2-ketoglutarate dehydrogenase in islet mitochondria was less marked, however, than that of the FAD-linked glycerophosphate dehydrogenase and was not associated with any change in responsiveness to Ca2+. Sonicated islet mitochondria of diabetic rats displayed normal to slightly elevated glutamate dehydrogenase activity. We propose, therefore, that the preferential impairment of the oxidative and secretory responses of islet cells to D-glucose in this experimental model of diabetes may be at least partly attributable to an altered transfer of reducing equivalents into the mitochondria as mediated by the glycerol phosphate shuttle.
Diabetes 1991 Feb
PMID:Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin. 182 72

Tissue culture for one or seven days of pancreatic islets isolated from 21-day old fetal rats was found to be associated with a marked increase in the oxidation of L-(U-14C) glutamine by intact islets and in the activity of both alanine-glutamate and aspartate-glutamate transaminases as well as glutamate dehydrogenase in islet homogenates. This coincided with an increase in the relative amount of mitochondrial DNA. The activities of glucose-phosphorylating enzymes (hexokinase and glucokinase), glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase were less markedly increased during the culture period than those of enzymes involved in amino acid catabolism and located, in part at least, in mitochondria. The combined data suggest that the functional maturation of fetal islets during the culture period is associated with and may be attributable to a preferential maturation of their mitochondria.
Diabetes Res 1990 Apr
PMID:Maturation of fetal rat islet cells in vitro during tissue culture is associated with increased mitochondrial function. 213 6

The beta-cell is unique because its major agonists, i.e., insulin secretagogues, undergo metabolism instead of interacting with a receptor. This perspectives presents the hypothesis that the first part of a metabolic signal of a secretagogue is specific to the secretagogue and the beta-cell and can be envisioned as proximal. The second part, which occurs after transduction to more universal signaling mechanisms, is viewed as distal. Distal signaling and exocytosis in the beta-cell operate the same as in other cells. Aerobic glycolysis is required for glucose-induced insulin release. Because glyceraldehyde, which enters metabolism at the triose phosphates in the glycolytic pathway, is a potent insulin secretagogue but pyruvate, which is metabolized in the mitochondrion, is not an insulin secretagogue, the proximal signal for glucose-induced insulin release originates with an interaction between the central part of the glycolytic pathway and mitochondrial metabolism. The proximal message in leucine-induced insulin release originates with leucine allosterically activating glutamate dehydrogenase, which activates endogenous glutamate metabolism, and by the metabolism of leucine itself. The methyl ester of succinate is a potent experimental insulin secretagogue. It is puzzling why the glucose signal requires the interplay of glycolysis and mitochondrial metabolism, whereas the signals from leucine and succinate originate entirely from within the mitochondrion. Leucine-induced insulin release is suppressed and glucose-induced insulin release is activated in islets cultured at a high concentration of glucose. Conversely, leucine-induced insulin release is activated and glucose-induced insulin release is suppressed in islets cultured at low glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Dec
PMID:Elusive proximal signals of beta-cells for insulin secretion. 224 73

The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
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PMID:Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta. 266 6

This study provides explanation for conflicting evidence in the literature relating to changes in mitochondrial function and metabolic parameters during chemically induced diabetes. Diabetes of 3 days' duration (early ketosis) did not alter heart, kidney, or liver mitochondrial respiratory rates with glutamate or succinate even though serum glucose and triglycerides were elevated. Diabetes of 5 weeks' duration did not alter kidney or liver mitochondrial function in the fed adult rat although weight gain was depressed. The amount of kidney mitochondrial protein isolated per gram of tissue was increased by 30% in the diabetic. This increase was reversed by insulin treatment as were the other biochemical modalities measured. Superimposition of a 24-hr fast resulted in enhanced gluconeogenesis as measured by an animal weight loss of 17% within 24 hr (liver weight loss, 21%) and an elevation of serum urea nitrogen by 180% compared to fasted control. Respiratory rates of diabetic kidney mitochondria with glutamate were unaffected in the fasted animal whereas diabetic liver mitochondrial respiratory rates during succinate oxidation were reduced by 43%. Respiratory control was unchanged in the fasted diabetic rat. All the observed changes were reversed by insulin. Variation in the serum and liver metabolic indices (urea nitrogen, creatinine, glycerol, free fatty acids, free amino acids, triglycerides, and glucose) and liver mitochondrial responses to 7 weeks of chemically induced diabetes was affected by the rat strain, Sprague-Dawley versus Sherman, and rat weight, 72 g versus 222 g. Liver mitochondrial respirations in fed Sherman rats were not depressed by diabetes. Both rat strains had elevated liver free fatty acids and glutamate dehydrogenase activity in the diabetic state. Serum leucine, isoleucine, and valine were more elevated and serum lysine and arginine were more depressed in the diabetic Sprague-Dawley rat than in the Sherman rat. Conjectures on these results are presented in the text.
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PMID:Metabolic and mitochondrial disturbances in streptozotocin-treated Sprague-Dawley and Sherman rats. 293 62

The reduction of oxygen by the ene-diol tautomer of simple monosaccharides produces hydrogen peroxide and alpha-oxoaldehydes. This process, termed monosaccharide autoxidation, occurs at physiological pH and temperature and may contribute to the development of several pathological processes. Enolization of the monosaccharide to an ene-diol tautomer is a prerequisite for the reaction of the monosaccharides with oxygen. The reaction kinetics suggest a two step process: the enolization of the monosaccharide to the ene-diol followed by the reaction of the ene-diol with oxygen. Free-radical reactive intermediates are formed by the reaction of the ene-diol with oxygen: superoxide, semidione, and 1-hydroxyalkyl radicals are formed under physiological conditions (hydroxyl radicals are also detected at high pH). The autoxidation of monosaccharides stimulates the oxidation of oxyhemoglobin in erythrocytes, producing methemoglobin and hydrogen peroxide, and the oxidation of reduced pyridine nucleotides NAD(P)H to the oxidized congener NAD(P)+ and enzymatically inactive nucleotide. This stimulates oxidative metabolism (via the hexose monophosphate shunt) and alpha-oxoaldehyde metabolism (via the glyoxalase system) in erythrocytes in vitro. The oxidative challenge is relatively mild even with very high concentrations (50 mM) of monosaccharide. However, crosslinking of membrane proteins by alpha-oxoaldehydes is enhanced; this effect may exacerbate ageing and decrease the lifetime of erythrocytes in circulation. In vivo, the autoxidation of monosaccharides is expected to be a chronic oxidative process occurring in biological tissue which utilises simple monosaccharides, e.g., in glycolysis and gluconeogenesis. Monosaccharide autoxidation is suggested to be a determinant in the control of cellular mitosis and ageing, providing physiological substrates for the glyoxalase system, and may contribute to the chronic disease processes associated with diabetes mellitus and the smoking of tobacco.
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PMID:Monosaccharide autoxidation in health and disease. 300 96

Glucose dehydrogenase (GDH), one of the recently discovered NAD(P)+-independent 'quinoprotein' class of oxidoreductase enzymes, was purified from Acinetobacter calcoaceticus LMD 79.41 and immobilised on a 1,1'-dimethylferrocene-modified graphite foil electrode. The second-order rate constant (ks) for the transfer of electrons between GDH and ferrocenemonocarboxylic acid (FMCA) in a homogeneous system, determined using direct current (DC) cyclic voltammetry, was found to be 9.4 x 10(6) litres mol-1 s-1. This value of ks for GDH was more than 40 times greater than that for the flavoprotein glucose oxidase (GOD) under identical conditions. Such high catalytic activities were also observed when GDH was immobilised in the presence of an insoluble ferrocene derivative; a biosensor based on GDH was found to produce more than twice the current density of similar GOD-based electrodes. The steady-state current produced by the GDH-based electrode was limited by the enzymic reaction since methods which increased the enzyme loadings elevated the upper limit of glucose detection from 5 mM to 15 mM. The temperature, pH, stability and response characteristics of the GDH-based glucose sensor illustrate its potential usefulness for a variety of practical applications. In particular, the high catalytic activity and oxygen insensitivity of this biosensor make it suitable for in vivo blood glucose monitoring in the management of diabetes.
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PMID:Quinoprotein glucose dehydrogenase and its application in an amperometric glucose sensor. 345 51


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