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:3.5.4.17 (adenosine deaminase)
5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The maximal activities of 5'-nucleotidase, adenosine deaminase and adenosine kinase were measured in quadriceps or soleus muscle from animals in which the sensitivity to insulin was changed. Most conditions caused no effect on the activities but exercise-training increased the activity of adenosine deaminase and cold exposure increased the activity of 5'-nucleotidase in soleus muscle: in addition, ageing decreased markedly the activities of all three enzymes in both muscles. When the activities are based on mg protein they are much higher in both white and brown adipose tissue than in muscle, suggesting that changes in adenosine concentration may be important in changing insulin sensitivity in adipose tissue whereas changes in adenosine receptor number may be more important in muscle.
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PMID:Maximal activities of enzymes involved in adenosine metabolism in muscle and adipose tissue of rats under conditions of variations in insulin sensitivity. 298 53

Glucose transport as assessed by the uptake rate of 3-O-methylglucose was stimulated in isolated rat fat cells by preincubation with isoprenaline or orciprenaline. The effect was apparently mediated by beta 1-receptors, since (1) it was abolished by propranolol, (2) it closely paralleled the stimulation of lipolysis, and (3) isoprenaline was 10(2) times more potent that orciprenaline. Isoprenaline enhanced the effect of submaximal insulin concentrations as well as the basal transport rate but failed to increase the maximal effect of insulin. The stimulatory effect of isoprenaline was antagonized by adenosine deaminase which removes adenosine spontaneously released from the cells, and by bordetella toxin (IAP) which blocks the inhibitory coupling component of adenylate cyclase. Moreover, bordetella toxin uncovered an inhibitory effect of isoprenaline on insulin stimulated glucose transport. There was no apparent correlation between the effects on glucose transport and the response of cellular cyclic AMP levels to the agents investigated. It is suggested that a step in the coupling of beta-receptors and adenylate cyclase, but not total cellular cyclic AMP levels, may mediate stimulatory as well as inhibitory effects of catecholamines on glucose transport in the adipocyte.
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PMID:Dual effect of isoprenaline on glucose transport and response to insulin in isolated adipocytes. 298 32

The adenosine-sensitive cyclic AMP phosphodiesterase of rat adipocytes was found to reside in the same subcellular fraction as the enzyme sensitive to insulin. There were several similarities between the action of adenosine and that of insulin on the enzyme. The action of adenosine on the phosphodiesterase is probably like that of insulin, both being receptor-mediated, although different sites or different receptors could be involved. Adenosine analogues with intact ribose but a modified purine moiety elicited a response similar to that of adenosine. Added Ca2+ was also not a requirement for the action of adenosine. The action of adenosine was not synergistic with that of insulin, neither was adenosine essential for insulin action. Insulin stimulated the enzyme even at low cell concentrations and in the presence of adenosine deaminase. Adenosine, however, enhanced the effect of insulin, but only at insulin concentrations that produced submaximal effects. Thus the mechanisms of action could be similar or related. The time-course effect of a suboptimal concentration of insulin was transitory, like that of adenosine, and was influenced by the presence of adenosine, whereas that of a maximally effective concentration of insulin was sustained for at least 20 min and was not affected by the presence of adenosine. Isoprenaline enhanced phosphodiesterase activity stimulated by optimal concentrations of either adenosine or insulin, suggesting that their effects were mediated through different mechanisms of action.
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PMID:The action of adenosine in relation to that of insulin on the low-Km cyclic AMP phosphodiesterase in rat adipocytes. 298 6

The effects of adenosine deaminase and of pertussis toxin on hormonal regulation of lipolysis were investigated in isolated human fat cells. Adenosine deaminase (1.6 micrograms/ml) caused a two-to threefold increase in cyclic AMP, which was associated with an increase in glycerol release averaging 150-200% above basal levels. Clonidine, N6-phenylisopropyladenosine, prostaglandin E2, and insulin caused a dose-dependent inhibition of glycerol release in the presence of adenosine deaminase. Pretreatment of adipocytes with pertussis toxin (5 micrograms/ml) for 180 min resulted in a five- to sevenfold increase in cyclic AMP. Glycerol release was almost maximal and isoproterenol caused either no further increase or only a marginal additional increase of lipolysis after pretreatment with pertussis toxin, whereas cyclic AMP levels were 500 times higher than in controls. The effects of antilipolytic agents known to affect lipolysis by inhibition of adenylate cyclase activity, i.e., clonidine, N6-phenylisopropyladenosine, and prostaglandin E2, were impaired. In contrast, the antilipolytic action of insulin was preserved in adipocytes pretreated with pertussis toxin. As in controls, the peptide hormone had no detectable effect on cyclic AMP after pertussis toxin treatment. The findings support the view that the antilipolytic effect of insulin does not require adenylate cyclase or phosphodiesterase action. In addition, the results demonstrate that, upon relief of endogenous inhibition, human fat cell lipolysis proceeds at considerable (adenosine deaminase) or almost maximal (pertussis toxin) rates. A certain degree of inhibition, therefore, appears to be necessary for human fat cell lipolysis to be susceptible for hormonal activation.
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PMID:Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms. 299 84

Patients with tumors secreting vasoactive intestinal peptide (VIP) often develop hyperglycemia and glucose intolerance. Although VIP has been reported to increase glucose output by the liver, the concentration required for this effect greatly exceeds that observed clinically. We therefore investigated the effects of VIP on insulin-stimulated glucose transport in isolated adipocytes. Inhibition of insulin action was observed at a concentration of 1 ng/ml VIP with half-maximal inhibition at approximately 20 ng/ml. 125I-VIP bound to specific high-affinity sites on the adipocytes. Fifty percent inhibition of binding occurred at a concentration of unlabeled VIP of approximately 10 ng/ml and was not affected by insulin, glucagon, or growth hormone. As we have observed previously with glucagon and catecholamines, inhibition of insulin action by VIP was observed only when accumulation of adenosine in the incubation medium was prevented by addition of adenosine deaminase. Under these conditions VIP markedly increased cellular cAMP levels. A good correlation was observed among VIP binding, inhibition of insulin-stimulated glucose transport, and cellular concentrations of cAMP. The results suggest that inhibition of insulin action in adipose tissue contributes to the hyperglycemic effect of VIP. Together, with our published findings on glucagon and catecholamines, these results support the hypothesis that counterregulatory hormones inhibit insulin action by increasing cellular concentrations of cAMP.
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PMID:Vasoactive intestinal peptide inhibits insulin-stimulated glucose transport in rat adipocytes. 300 79

The effects of adenosine on glycogen metabolism have been studied in isolated fat-pads from epididymal adipose tissue. Adenosine caused a sustained short-term increase in the incorporation of [U-14C]glucose into glycogen, as well as a stimulation of both basal and insulin-induced [1-14C]glucose oxidation. Adenosine produced changes also in the activity of glycogen synthase and phosphorylase, these effects being apparent only when glucose was present in the incubation medium. The addition of adenosine prevented the depressed synthesis of glycogen observed in the presence of dibutyryl cyclic AMP. In the presence of adenosine deaminase, the stimulation by insulin of glycogen synthesis was markedly decreased. The results suggest that adenosine may have a regulatory role on glycogen synthesis by facilitating the glucose transport.
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PMID:Short-term stimulation by adenosine of basal and insulin-induced glycogen synthesis in rat adipose tissue. 300 88

This paper examines the modulation of insulin-stimulated glucose transport activity in rat adipose cells by ligands for receptors (R) that mediate stimulation (Rs; lipolytic) or inhibition (Ri; antilipolytic) of adenylate cyclase. The changes in glucose transport activity and cAMP, as assessed by 3-O-methylglucose uptake and (-/+) cAMP-dependent protein kinase (A-kinase) activity ratios, respectively, were monitored under conditions that maintain steady-state A-kinase activity ratios (Honnor, R. C., Dhillon, G. S., and Londos, C. (1985) J. Biol. Chem. 260, 15122-15129). Removal of endogenous adenosine with adenosine deaminase decreased insulin-stimulated glucose transport activity by approximately 30%, which was prevented or restored with Ri agonists such as phenylisopropyladenosine, nicotinic acid, and prostaglandin E1. These changes in transport activity were not accompanied by changes in A-kinase activity ratios, indicating that Ri-mediated effects on transport are independent of cAMP changes. Addition of an Rs ligand, isoproterenol, in the presence of adenosine increased kinase activity but did not change glucose transport activity. Conversely, upon removal of adenosine, addition of Rs ligands such as isoproterenol, adrenocorticotropic hormone, or glucagon strongly inhibited transport (approximately 50%) and stimulated kinase activity. However, subsequent addition of phenylisopropyladenosine nearly restored transport activity without alteration of A-kinase activity. These data and additional kinetic experiments suggest that Rs-mediated glucose transport modulations are also independent of cAMP. The interchangeability of ligands for both Rs and Ri receptors in modulating transport activity suggests that these cAMP-independent effects are mediated by the stimulatory (Ns) and inhibitory (Ni) guanyl nucleotide-binding regulatory proteins of adenylate cyclase. All Rs-and Ri-induced changes in transport activity occurred without a change in glucose transporter distribution, as assessed by D-glucose-inhibitable cytochalasin B binding, suggesting that Rs and Ri ligands modulate the intrinsic activity of the glucose transporter present in the plasma membrane.
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PMID:Regulation of insulin-stimulated glucose transport in the isolated rat adipocyte. cAMP-independent effects of lipolytic and antilipolytic agents. 302 4

ACTH, isoprenaline, forskolin, and dibutyryl cyclic AMP prevented insulin from stimulating adipocyte pyruvate dehydrogenase in the presence of adenosine deaminase. Antagonism was reversed by N6-phenylisopropyladenosine as well as oxytocin. The stimulatory effects of insulin, adenosine and oxytocin on adipocyte pyruvate dehydrogenase appear to be through (a) mechanism(s) which is (are) similar or related.
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PMID:Adenosine and oxytocin reverse antagonism of cyclic AMP elevating agents to insulin activation of adipocyte pyruvate dehydrogenase. 303 Aug 21

The effect of insulin and factors which have insulin-like activity on the kinetic parameters of 3-O-methyl-D-glucose (MeGlc) transport in rat adipocytes were assessed. Carrier-mediated uptake of MeGlc was estimated by the difference in the amounts of [14C]MeGlc and L-[3H]glucose taken up in cells under equilibrium exchange conditions at 37 degrees C. The Km and Vmax values in basal cells were 17.4 mM and 0.24 nmol/10(6) cells/s, respectively. Removal of endogenous adenosine by adenosine deaminase resulted in a 26% decrease in the basal rate due to a slight increase in the Km (19.6 mM) and a decrease in the Vmax value (0.20 nmol/10(6) cells/s). The maximum concentration (10 nM) of insulin decreased the Km to approximately one-half of the basal (7.1 mM) concomitant with an 8.5-fold increase in the Vmax value (2.04 nmol/10(6) cells/s). Submaximal concentrations (50 and 150 pM) of insulin, N6-phenylisopropyladenosine (1 microM), mechanical agitation of cells by centrifugal force (160 x g), low temperature (15 degrees C), 12-O-tetradecanoylphorbol-13-acetate (1 microM), and hydrogen peroxide (10 mM) all decreased the basal Km value to a range of 13.5-7.3 mM, concomitant with a 1.7-7.4-fold increase in the Vmax. A possible explanation for the alterations in the kinetic parameters may be that insulin and other factors cause the translocation of the mobile low-Km glucose transporters from an intracellular site to the cell surface, where the stationary high-Km transporters are located. Thus, when the Km and Vmax values of the hypothetical high-Km transporters were assumed to be 20 mM and 0.20 nmol/10(6) cells/s, respectively, and the Km of the low-Km transporters was assumed to be 7 mM, the theoretical Km decreased from 20 to 7.5 mM as the Vmax of the low-Km transporters increased from near 0 to 2.0 nmol/10(6) cells/s. The relation between empirical Km and Vmax values as affected by several agents and conditions followed closely the relation predicted by the above two-transporter model.
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PMID:Reassessment of the translocation hypothesis by kinetic studies on hexose transport in isolated rat adipocytes. 304 14

Adipocytes incubated with adenosine deaminase (ADA) showed: (1) increased amounts of fatty acids in the medium; (2) increased glucose incorporation into acylglycerol glycerol; (3) decreased glucose incorporation into acylglycerol fatty acids; (4) a co-ordinate decrease in the sensitivity of lipolysis and glucose incorporation into acylglycerol to insulin; (5) similar effects on glucose incorporations in perifused and normal incubations. The decrease in fatty acid synthesis by perfusion was found to be dependent on the presence of insulin or fatty acids, and independent of the effects of ADA. The significance of the effects of perifusion, ADA and insulin are discussed in relation to effects of fatty acids.
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PMID:The response of adipocyte glucose metabolism and fatty acid release to adenosine deaminase, insulin and perifusion. Investigation of intermediary metabolism by perifusion. 304 1


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