Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biologic actions of vasoactive intestinal polypeptide (VIP) on insulin binding, glucose uptake and utilization, and on lipolysis were studied. At concentrations between 10(-10) and 10(-7) mol/l VIP influenced neither glucose uptake nor glucose incorporation into lipids under basal and insulin-stimulated conditions. This effect was independent of the presence of adenosine deaminase in the incubation medium. At 10(-8) mol/l VIP increased insulin binding affinity slightly but not significantly, shifting the ID-50 from 12.4 ng/ml to 10.3 ng/ml, without any change in receptor number. However, VIP showed a marked dose-dependent lipolytic activity with the lowest effective concentration at 10(-9) mol/l. At 10(-6) mol/l glycerol release increased 7.3-fold as compared to basal lipolysis. In conclusion, VIP did not affect adipose tissue metabolism at physiologic concentrations. In the rare Verner-Morrison syndrome, however, the potent lipolytic activity of VIP may contribute to the metabolic disturbances observed.
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PMID:Effect of vasoactive intestinal polypeptide (VIP) on glucose and lipid metabolism of isolated rat adipocytes. 342 Mar 1

The regulation of the glucose transport system by catecholamines and insulin has been studied in isolated rat cardiomyocytes. In the basal state, 1-isoproterenol exhibited a biphasic concentration-dependent regulation of 3-O-methylglucose transport. At low concentrations (less than 10 nM), isoproterenol induced a maximal inhibition of 65-70% of the basal rates, while at higher concentrations (greater than 10 nM) a 25-70% stimulation of transport was observed. In the presence of adenosine deaminase, the inhibition of isoproterenol at low doses was attenuated. No effect of adenosine deaminase was observed on the stimulation of transport at high doses of isoproterenol. The inhibitory effect of isoproterenol returned when N6-phenylisopropyladenosine (a non-metabolizable analog of adenosine) was included along with adenosine deaminase. Dibutyryl cAMP and forskolin both inhibited basal transport rates. In the presence of maximally stimulating concentrations of insulin, cardiomyocyte 3-O-methylglucose transport was generally elevated 200-300% above basal levels. In the presence of isoproterenol, insulin stimulation was inhibited at both high and low concentrations of catecholamine, with maximum inhibition occurring at the lowest concentrations tested. When cells were incubated with both adenosine deaminase and isoproterenol, the inhibition of the insulin response was greater at all concentrations of catecholamine and was almost completely blocked at isoproterenol concentrations of 10 nM or less. Dibutyryl cAMP inhibited the insulin response to within 10% of basal transport levels, while forskolin completely inhibited all transport activity in the presence of insulin. These results suggest that catecholamines regulate basal and insulin-stimulated glucose transport via both cAMP-dependent and cAMP-independent mechanisms and that this regulation is modulated in the presence of extracellular adenosine.
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PMID:Interactions of insulin, catecholamines and adenosine in the regulation of glucose transport in isolated rat cardiac myocytes. 351 11

In the anterogradely perfused rat heart, physiological concentrations of insulin stimulated the rates and efficiencies of protein synthesis in both ventricles and atria. Half-maximal stimulation of ventricular protein synthesis was obtained at about 35 microU/ml. Glucose uptake and lactate release were also stimulated over this range of insulin concentrations. Adenosine deaminase increased protein synthesis rates in ventricles and atria in the presence of submaximally stimulating insulin concentrations (40 microU/ml) but had no effect in the absence of insulin or in the presence of maximally stimulating concentrations. The insulin sensitivities of glucose uptake and lactate release were also increased by adenosine deaminase. Adenosine may be a modulator of insulin sensitivity in the heart.
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PMID:Stimulation of protein synthesis, glucose uptake and lactate output by insulin and adenosine deaminase in the rat heart. 351 83

We have investigated the effects of adenosine on the stimulation of glucose oxidation and lipogenesis by oxytocin and insulin in rat epididymal adipocytes. The addition of adenosine deaminase (1 U/ml) to the assay medium reduced the maximal oxytocin response (glucose oxidation and lipogenesis) to between 25 and 50% of the maximum response in control cells. The maximal response to insulin was not appreciably affected under these conditions. The addition of adenosine (10 or 30 microM) increased the cell sensitivity to oxytocin by elevating the maximum rate of oxytocin-stimulated glucose metabolism. Adenosine also increased the cell sensitivity to insulin by decreasing its ED50. A change in ED50, however, was observed only when control or adenosine-treated cells were compared to adenosine deaminase-treated cells; but not when control and adenosine-treated cells were compared. On its own, adenosine also caused an appreciable increase in both glucose oxidation and lipogenesis (ED50 approximately equal to 3 microM adenosine). The difference in the effect of adenosine on oxytocin action, compared with the effect on insulin action, points to differences in the mechanisms by which insulin and oxytocin stimulate glucose metabolism in adipocytes.
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PMID:Adenosine modulation of fat cell responsiveness to insulin and oxytocin. 354 88

Endogenous adenosine enhances the insulin sensitivity of isolated rat adipocytes. We studied whether this effect was related to an ability of adenosine to alter the activation of insulin receptor kinase by insulin. It was found that depletion of endogenous adenosine by adenosine deaminase treatment decreases insulin's ability to activate the receptor kinase at submaximal insulin concentrations. This occurred without changes in insulin binding. At 4 ng/ml insulin, adenosine deaminase decreased insulin activation of insulin receptor kinase by 25%, a reduction that equalled the effect of adenosine deaminase on insulin stimulation of 2-deoxyglucose transport. The effects of adenosine deaminase on both insulin activation of insulin receptor kinase and insulin stimulation of 2-deoxyglucose transport were reversed by the addition of N6-phenylisopropyl-adenosine, a nonhydrolyzable adenosine analog. Our data are consistent with the view that adenosine modulates the coupling of insulin binding to biological actions of insulin at or before the level of activation of insulin receptor kinase.
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PMID:Adenosine modulates insulin activation of insulin receptor kinase in intact rat adipocytes. 355 35

The replenishment of lipid reserves of adipocytes following the removal of litters from lactating rats is associated with a 3-fold decrease in both the response of lipolysis to noradrenaline and the maximum rate of lipolysis (measured in the presence of noradrenaline plus adenosine deaminase); these adaptations do not appear to result from the changes in serum prolactin and insulin concentrations that occur on litter removal.
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PMID:Lipolysis in rat adipocytes during recovery from lactation. Response to noradrenaline and adenosine. 370 44

The effect of glucose on lipolytic regulation was studied in isolated human adipocytes. Glucose enhanced adipocyte glycerol release in the presence and absence of the beta-adrenergic agent ritodrine by 150-200% of control rates. The glucose effect was maximal at just greater than 1 mM glucose and could not be attributed to prevention of a time-dependent decline in lipolysis. Glucose not only increased lipolytic stimulation at each of several concentrations of ritodrine but also enhanced the sensitivity to stimulation at low concentrations of the agent. Ritodrine-stimulated lipolysis was inhibited by insulin by 50-60%; although glucose increased absolute rates of lipolysis, it did not affect the relative inhibition of lipolysis by insulin or the sensitivity to the hormone. In investigating a possible cause of the glucose effect on lipolysis, it was found that the addition of adenosine deaminase increased lipolytic rates in the absence of glucose and blunted the relative stimulation of lipolysis by glucose, the latter implicating extracellular adenosine in the mechanism of the glucose effect.
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PMID:Potentiation by glucose of lipolytic responsiveness of human adipocytes. 372 Oct 62

The steady-state relationship between the activation state of cAMP-dependent protein kinase (A-kinase) and lipolysis has been defined quantitatively. A-kinase activation was assessed by measuring the ( +/- cAMP) activity ratio in adipocyte extracts, and lipolysis was determined by measuring glycerol release from cells. Both processes were stimulated either by incubating cells in a ligand-free environment achieved with adenosine deaminase or by addition of lipolytic hormones. A response spectrum was obtained with a variety of adenylate cyclase stimulators and inhibitors, both receptor- and nonreceptor-mediated. Regardless of the ligands used to manipulate adipocyte activity, lipolysis varied from nil to maximal as the A-kinase activity ratio varied from approximately 0.05 to 0.3-0.35. These data provide a quantitative description of the steady-state relationship between A-kinase activity and lipolysis and indicate that the various lipolytic and antilipolytic agents tested act on the lipolytic process exclusively by altering adenylate cyclase activity and, thus, cellular cAMP concentrations. The data reveal also that transient "peaking" of cAMP, as measured by A-kinase activity ratios, is not an inherent feature of adipocyte metabolism. Moreover, the concentration requirements for lipolytic hormone action are critically dependent on the ambient concentration of antilipolytic agents, and t concentration requirements for antilipolytic agents are dependent on the extent to which cells are stimulated. The data in this paper provide the basis for assessing the relationship between A-kinase activity ratio and lipolysis in the presence of insulin (Londos, C., Honnor, R. C., and Dhillon, G. S. (1985) J. Biol. Chem. 260, 15139-15145).
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PMID:cAMP-dependent protein kinase and lipolysis in rat adipocytes. II. Definition of steady-state relationship with lipolytic and antilipolytic modulators. 387 23

2-Deoxyglucose uptake (3 min) and 3-O-methylglucose transport (2 s) was measured in rat adipocytes preincubated with 5 microM epinephrine plus adenosine deaminase as described by Green (Green, A. (1983) FEBS Lett. 152, 261-264). 2-Deoxyglucose uptake was about 95% depressed in insulin-treated, but not in 'basal', cells preincubated with epinephrine plus adenosine deaminase for 60 min in broad agreement with Green's report. However, this depression was caused by a decrease in sugar phosphorylation rather than transport. In similarly incubated cells, transport of 3-O-methylglucose, a sugar analogue not phosphorylated in the adipocytes, was not affected by catecholamine plus adenosine deaminase. However, a decrease in transport of about 60% was observed both in the absence and the presence of insulin when the albumin concentration was high enough and the cell concentration low enough to prevent accumulation of free fatty acids in the medium. In addition, the insulin sensitivity with regard to hexose transport was markedly reduced. Transport was approximately doubled in cells incubated with 5 microM epinephrine in the absence of adenosine deaminase. Thus, epinephrine at a high concentration stimulates hexose transport in the absence of adenosine deaminase (presence of adenosine) whereas it inhibits both basal and insulin-stimulated transport in the presence of adenosine deaminase (absence of adenosine).
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PMID:The effect of catecholamines and adenosine deaminase on the glucose transport system in rat adipocytes. 389 Sep 59

The relationship between cAMP-dependent protein kinase (A-kinase) activity ratios and lipolysis in the presence of insulin was compared to the standard relationship between these two parameters established with a variety of adenylate cyclase modulators (Honnor, R. C., Dhillon, G., and Londos, C. (1985) J. Biol. Chem. 260, 15130-15138). Three phases of insulin action were observed. First, when tested in control cells exhibiting A-kinase activity ratios up to approximately 0.25, insulin inhibition of lipolysis could be accounted for by the decrease in A-kinase activity. Second, in cells exhibiting A-kinase activity ratios greater than 0.3, the decrease in kinase activity by insulin did not account for the decrease in lipolysis. Finally, as the A-kinase activity ratio approached 0.6 the insulin effect on lipolysis was lost. The data suggest that protein phosphatase activation accounts for the cAMP-independent insulin action. Moreover, the insulin effect not accounted for by a decrease in A-kinase activity appears to be elicited only upon elevation of A-kinase activity. The method by which cells were stimulated determined the IC50 for insulin inhibition of: 1) A-kinase activity ratios, 2) lipolysis explained by the decrease in A-kinase activity ratios, and 3) lipolysis not explained by a decrease in A-kinase activity ratios. For all three parameters, cells stimulated by lipolytic hormones were approximately 5 times more sensitive to insulin than cells stimulated by incubation in a ligand-free environment achieved with adenosine deaminase; insulin IC50 values were approximately 120 and 600 pM, respectively. Such data establish a link between insulin actions in modifying cAMP concentrations and in modifying events apparently independent of changes in cAMP. It is proposed that the receptors and regulatory components associated with adipocyte adenylate cyclase are associated also with components of the insulin response system separate from cyclase.
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PMID:cAMP-dependent protein kinase and lipolysis in rat adipocytes. III. Multiple modes of insulin regulation of lipolysis and regulation of insulin responses by adenylate cyclase regulators. 390 91


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