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

Tests were carried out on the influence of alloxan-induced diabetes mellitus on the metabolism and the ultrastructure of ovaries of juvenile rats. The diabetes mellitus caused the following changes in the metabolism: reduction in the concentration of ATP and NADPH, increase in the lactate/pyruvate quotient to above 40, reduction in the ATP/ADP quotient to below 1, reduction in the level of activity of the hydrogen-conveying enzymes G-6-P-dehydrogenase, isocitrate dehydrogenase and malate dehydrogenase, increase in the level of activity of the alkaline phosphatase, reduction of the protein content. Ultrastructure: almost complete disappearance of the rough endoplasmic reticulum, shrinkage of the mitochondria, reduction of the cristae and condensation of the matrix. The smooth endoplasmic reticulum remains unchanged, the extent of the Golgi-complex is reduced. Easy removal of the lipid deposits.
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PMID:Metabolism and ultrastructure in ovaries of alloxan-diabetic juvenile rats. 0 67

In adrenalectomized rats the effect of i.v. injection of glucose and ATP on insulin changes in external jugular vein was determined in normal and alloxan diabetic animals. In another set of experiments the direct effect of ATP on insulin secretion was investigated. Glucose and ATP were injected in the carotid artery and the blood samples were withdrawn from the portal vein. In these experiments there was immediate and excessive production of insulin release in the portal vein after ATP injection in the carotid artery. In alloxan diabetic rats, despite the high blood glucose levels, the plasma insulin was low and did not respond to glucose stimulation. ATP could increase the sensitivity of the diabetic rats to glucose. The possible role of purinergic nerves in insulin secretion is discussed. It is concluded that multiple innervation of the islets by purinergic, cholinergic and adrenergic nerves, regulate insulin secretion. It is suggested that: 1. Purinergic nerve stimulation is more specific for insulin secretion. 2. ATP is considered the principal transmitter released from purinergic nerves causing insulin secretion. 3. The insulin stimulatory effect normally produced by glucose is through purinergic nerves. 4. It could be possible that one of the causes of diabetes is a defect in the purinergic innervation of the islet cells thus the sensitivity of the islets to glucose is decreased.
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PMID:The purinergic nerve hypothesis and insulin secretion. 4 35

It has been suggested that the hyperglucagonemia observed in diabetic animals and man may be due to an impairment of glucose uptake and metabolism by the alpha-cells resulting in a decreased production of ATP. To test this hypothesis glucose, ATP, glucagon, and insulin were measured in pancreatic islets of normal and alloxan or streptozotocin diabetic rats. Two experimental approaches were used. In the first, the pancreas was perfused in vitro for assessing insulin and glucagon release due to 10 mM amino acids with and without 5 mM glucose. These perfusions were performed in the presence and absence of insulin. After perfusion, the pancreas was frozen and processed for analysis of islet glucose, ATP, insulin, and glucagon content. The second approach was to investigate the islet sucrose, urea, and glucose spaces together with ATP, insulin, and glucagon content in vivo in normal and in insulin-treated and untreated streptozotocin diabetic rats. Perfusion of the pancreas in vitro with 5 mM glucose resulted in higher glucose content of normal islets than in alloxan and streptozotocin diabetic islets. Similarly in the in vivo studies, the intracellular glucose space of the streptozotocin diabetic islets was 30% the value found in normals. In the in vivo experiments, despite the relatively small intracellular glucose space of alpha-cell islets, the ATP content of these islets was only 15-20% lower than the ATP content of normal islets. In the in vitro experiments, perfusion with glucose resulted in ATP contents of alpha-cell islets and of normal mixed alpha-beta-cell islets which were indistinguishable. However, the ATP content of alpha-cell islets was maintained for prolonged periods in the absence of glucose in contrast to mixed islets, composed primarily of beta-cells, in which the ATP level decreased by 45% when glucose-free medium was perfused for sustained periods. Finally, insulin infused in high concentrations or administered to the diabetic animal had no effect on the glucose spaces or the ATP contents of normal or alpha-cell islets. It can be calculated that in vivo the intracellular glucose level of islets from streptozotocin treated rats is approximately 15 mM. Since in normals an extracellular glucose concentration of this magnitude inhibits stimulated glucagon release completely, it would seem unlikely that a lack of intracellular glucose is the cause of the apparent glucose "blindness" of the alpha-cells in diabetes. In fact, in perfusion studies as little as 2.5 mM free intracellular glucose was sufficient to suppress glucagon secretion from diabetic alpha-cells. The results of the ATP measurements clearly eliminate a possible energy deficit of diabetic alpha-cells as cause of the apparent glucose resistance of alpha-cells.
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PMID:Glucose and ATP levels in pancreatic islet tissue of normal and diabetic rats. 13 53

The proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart was decreased by alloxan-diabetes or by perfusion with media containing acetate, n-octanoate or palmitate. The total activity of the dehydrogenase was unchanged. 2. Pyruvate (5 or 25mM) or dichloroacetate (1mM) increased the proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart, presumably by inhibiting the pyruvate dehydrogenase kinase reaction. Alloxan-diabetes markedly decreased the proportion of active dehydrogenase in hearts perfused with pyruvate or dichloroacetate. 3. The total activity of pyruvate dehydrogenase in mitochondria prepared from rat heart was unchanged by diabetes. Incubation of mitochondria with 2-oxo-glutarate plus malate increased ATP and NADH concentrations and decreased the proportion of active pyruvate dehydrogenase. The decrease in active dehydrogenase was somewhat greater in mitochondria prepared from hearts of diabetic rats than in those from hearts of non-diabetic rats. Pyruvate (0.1-10 mM) or dichloroacetate (4-50 muM) increased the proportion of active dehydrogenase in isolated mitochondria presumably by inhibition of the pyruvate dehydrogenase kinase reaction. They were much less effective in mitochondria from the hearts of diabetic rats than in those of non-diabetic rats. 4. The matrix water space was increased in preparations of mitochondria from hearts of diabetic rats. Dichloroacetate was concentrated in the matrix water of mitochondria of non-diabetic rats (approx. 16-fold at 10 muM); mitochondria from hearts of diabetic rats concentrated dichloroacetate less effectively. 5. The pyruvate dehydrogenase phosphate phosphatase activity of rat hearts and of rat heart mitochondria (approx. 1-2 munit/unit of pyruvate dehydrogenase) was not affected by diabetes. 6. The rate of oxidation of [1-14C]pyruvate by rat heart mitochondria (6.85 nmol/min per mg of protein with 50 muM-pyruvate) was approx. 46% of the Vmax. value of extracted pyruvate dehydrogenase (active form). Palmitoyl-L-carnitine, which increased the ratio of [acetyl-CoA]/[CoA] 16-fold, inhibited oxidation of pyruvate by about 90% without changing the proportion of active pyruvate dehydrogenase.
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PMID:Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide. 18 Sep 74

Numerous general metabolic systems are disturbed in association with psoriasis: the frequency of diabetes mellitus and of hyperuricaemia, lipid disturbances and a decrease in folates as a result of their excessive consumption by the skin. Cutaneous metabolism is also altered. Numerous compounds are formed in excess from glucose: amino acids, fatty acids and sterols, lactic acid--the formation of which persists in the corneal layer, ribose and ribulose--synthesised as a result of glucose-6-phosphate-dehydrogenase hyperactivity (role of the increased catabolism of dehydro-epi-androsterone) and uronic acids. The accumulation of glycogen is probably due to excessive synthesis and impaired breakdown. These abnormalities may exist to a lesser extent in healthy skin. In the corneal layer there are lipid vacuoles visible under the electron microscope. Lipogenesis is increased. The same may apply to lipolysis (blood NEFA are increased). Esterification of cholesterol is decreased. The utilisation of ATP by cell membranes is probably diminished (low ATP ase activity). The absence of formation of keratohyaline is due to persistence of the repression which normally prevents it in the mucus body. Renewal of collagen appears increased. The synthesis of DNA is increased in the lesions and neighbouring areas. It is possible that these various abnormalities are dependent upon modifications in the regulator systems of cyclic AMP and GMP, variations in which are however discussed.
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PMID:[The biochemistry of psoriasis]. 18 76

Exposing micro-dissected pancreatic islets of non-inbred ob/ob mice to 2-5 mM-alloxan for 10 min decreased the ability of the islets to accumulate Rb+. Rb+ accumulation in pieces of exocrine pancreas was unaffected by alloxan. When islets were treated with alloxan in the presence of 2-20 mM-D-glucose, the Rb+-accumulating ability was protected in a dose-dependent manner. The protective action of D-glucose was reproduced with 3-O-methyl-D-glucose but not with L-glucose or D-mannoheptulose; mannoheptulose prevented D-glucose from exerting its protective action. The inhibition of Rb+ accumulation was due to a decreased inward pumping, since alloxan did not affect Rb+ efflux from pre-loaded islets. The inhibitory effect of alloxan had a latency of about 1 min, as revealed by experiments with dispersed islet cells in suspension. Alloxan-treated islets showed only a marginal decrease in ATP and no change in glucose 6-phosphate concentration. Although alloxan slightly decreased the hydrolysis of ATP in a subcellular fraction enriched in plasma membranes, this effect could not be attributed to a ouabain-sensitive adenosine triphosphatase. The plasma membranes exhibited a K+-activated hydrolysis of p-nitrophenyl phosphate; this enzyme activity too was insensitive to alloxan. Glucose may protect the univalent-cation pump by preventing permeation of alloxan via a path coupled to the hexose-transport system. Inhibition of the pump may be fundamental to the induction of alloxan-diabetes.
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PMID:Alloxan cytotoxicity in vitro. Inhibition of rubidium ion pumping in pancreatic beta-cells. 19 15

Experiments with rats were set up to study the interaction of hormones with Na+, K+-ATP-ase and Ca2+-ATP-ase of the sarcoplasmatic reticulum fragments and with pyruvate-dehydrogenase of the myocardial mitochondria in healthy rats and the ones with alloxan diabetes. Insulin was found to activate, while epinephrine and c-AMP to inhibit Na+, K+-ATP-ase. The Ca2+-ATP-ase is activated with epinephrine and c-AMP. In alloxan diabetes Na+, K+-ATP-ase is inhibited and Ca2+-ATP-ase and pyruvate-dehydrogenase--activated.
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PMID:[Effect of insulin, adrenaline and cyclic adenosine monophosphate on the activity of transport adenosine triphosphatases and pyruvate dehydrogenase of the rat myocardium under normal conditions and in insular insufficiency]. 19 87

1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. 2. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH][NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 micrometer-palmitotoyl-L-carnitine and in 250 micrometer-2-oxoglutarate +50 micrometer-L-malate. 4. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. 5. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyruvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/NAD+ or acetyl-CoA/CoA.
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PMID:Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A. 19 89

In the paper the author is concerned with the histochemical estimation of the metabolic adaptation of the heart muscle of albino rats during an early experimental alloxan diabetes. It has been found that the state of experimentally produced insulin deficiency directly influences metabolism of the heart muscle and the changes observed in the histochemical reactions prove this. An increase in the intensity of histochemical reactions concerns the PAS-positive reaction and the reactions to the NADH and NADPH tetrazole reductase activities. Alkaline phosphatase shows a decrease in the enzymatic activity, whose nature is transitional and reversible with regard to cytochrome oxidase and ATP-ase. The histochemical picture of metabolic changes depends on the duration time of experimental diabetes.
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PMID:Some histochemical observations on the myocardial metabolism in experimental conditions. Part I. 21 83

In perfused livers of rats fasted for 24 h, glucagon (5 x 10(-10) M) significantly elevated tissue and perfusate levels of cyclic AMP and caused a twofold increase in glucose formation from lactate. Chlorpropamide (0.8 x 10(-3) M) consistently blocked these effects. Measurements of metabolic intermediates suggest that chlorpropamide may inhibit gluconeogenesis by antagonizing the action of glucagon on the phosphoenolpyruvate cycle. In the experiments described, chlorpropamide did not lower hepatic ATP concentration or energy charge, and exerted its effects at perfusate concentrations comparable to serum concentrations reported in patients on maintenance doses of the drug.
Diabetes 1979 Jul
PMID:Hepatic effects of chlorpropamide: inhibition of glucagon-stimulated gluconeogenesis in perfused livers of fasted rats. 22 Dec 98


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