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 sensitivities of lipolysis and fatty acid synthesis to dibutyryl-cAMP (dbcAMP), epinephrine, ractopamine and clenbuterol were quantified in vitro using porcine adipocytes. Insulin-stimulated lipogenesis showed a biphasic response to dbcAMP, with increased rates at low concentrations and decreased (55%) rates at higher concentrations of dbcAMP. In the absence of insulin, lipogenesis was inhibited 78% by dbcAMP. In the presence of adenosine deaminase or theophylline, all three beta-adrenergic agonists inhibited basal lipogenesis, but only epinephrine and ractopamine inhibited insulin-stimulated lipogenesis. The relationship between suppressed lipogenesis and enhanced lipolysis in response to dbcAMP and the beta-agonists revealed that 1) basal lipogenesis was more sensitive to inhibition than was the stimulation of lipolysis, 2) sensitivity differences were magnified if adenosine deaminase was present and 3) insulin decreased adipocyte sensitivity to the inhibitory effects of dbcAMP and the beta-adrenergic agonists. These results indicate that the relative sensitivities of lipogenesis and lipolysis to beta-adrenergic stimulation can be modified by adenosine and insulin. Furthermore, adenosine and insulin antagonize beta-adrenergic responses, in part, by cAMP-independent mechanisms.
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PMID:Sensitivity of lipolysis and lipogenesis to dibutyryl-cAMP and beta-adrenergic agonists in swine adipocytes in vitro. 197 May 55

The present study was conducted to determine the influence of dibutyryl-cAMP (dbcAMP), epinephrine, ractopamine and clenbuterol on insulin binding to porcine adipocytes. Dibutyryl-cAMP decreased insulin binding to swine adipocytes by 40 and 20% at 1.8 and 25.8 ng insulin/ml, respectively. Ractopamine and clenbuterol directly reduced insulin binding at the low insulin concentration and decreased binding at high insulin concentrations in the presence of adenosine deaminase. Scatchard analysis suggested that the reduction of insulin binding was due to a decrease in receptor number. Epinephrine alone did not influence insulin binding. In the presence of theophylline, epinephrine decreased binding at both low and high insulin concentrations; however, ractopamine plus theophylline decreased binding only at the low insulin concentration. Clenbuterol did not affect insulin binding in the presence of theophylline. Propranolol blocked the inhibitory effect of epinephrine on insulin binding. These beta-adrenergic agonists can inhibit insulin binding and, thus, antagonize insulin action in swine adipocytes.
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PMID:Decreased insulin binding to porcine adipocytes in vitro by beta-adrenergic agonists. 197 48

1. Insulin increased basal 2-deoxyglucose uptake in isolated swine adipocytes by 75%. In the absence of insulin, isoproterenol did not inhibit basal 2-deoxyglucose transport. 2. Adenosine deaminase plus isoproterenol or theophylline alone reduced insulin effect by 10 and 40%, respectively. Isoproterenol alone or with 2-chloroadenosine did not inhibit insulin effect on glucose transport activity. 3. Insulin effect was inhibited by isoproterenol in the presence of theophylline but not in the presence of adenosine deaminase. 4. These results suggest that catecholamines do not counter-regulate basal and insulin-stimulated glucose transport in swine adipocytes.
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PMID:Effect of insulin and adrenergic agonists on glucose transport of porcine adipocytes. 198 40

We have studied the relationship between insulin activation of insulin-receptor kinase and insulin stimulation of glucose uptake in isolated rat adipocytes. Glucose uptake was half-maximally or maximally stimulated, respectively, when only 4% or 14% of the maximal kinase activity had been reached. To investigate this relationship also under conditions where the insulin effect on activation of receptor kinase was decreased, the adipocytes were exposed to 10 microM-isoprenaline alone or with 5 micrograms of adenosine deaminase/ml. An approx. 30% (isoprenaline) or approx. 50% (isoprenaline + adenosine deaminase) decrease in the insulin effect on receptor kinase activity was found at insulin concentrations between 0.4 and 20 ng/ml, and this could not be explained by decreased insulin binding. The decreased insulin-effect on kinase activity was closely correlated with a loss of insulin-sensitivity of glucose uptake. Moreover, our data indicate that the relation between receptor kinase activity and glucose uptake (expressed as percentage of maximal uptake) remained unchanged. The following conclusions were drawn. (1) If activation of receptor kinase stimulates glucose uptake, only 14% of the maximal kinase activity is sufficient for maximal stimulation. (2) Isoprenaline decreases the coupling efficiency between insulin binding and receptor-kinase activation, this being accompanied by a corresponding decrease in sensitivity of glucose uptake. (3) Our data indicate that the signalling for glucose uptake is closely related to receptor-kinase activity, even when the coupling efficiency between insulin binding and kinase activation is altered. They thus support the hypothesis that receptor-kinase activity reflects the signal which originates from the receptor and which is transduced to the glucose-transport system.
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PMID:The relationship between insulin binding, insulin activation of insulin-receptor tyrosine kinase, and insulin stimulation of glucose uptake in isolated rat adipocytes. Effects of isoprenaline. 201 5

After administration of insulin adenosine deaminase activity was reduced in different skeletal muscle types, the heart and the liver. On the other hand profound reduction in the plasma insulin concentration (streptozotocin diabetes) resulted in elevation of the enzyme activity in the tissues. It is concluded that the local concentration of adenosine may be effected by the concentration of insulin in the plasma.
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PMID:On the role of insulin in regulation of adenosine deaminase activity in rat tissues. 214 55

The effects of cold exposure (7 days, 5 degrees C) and cold acclimation (21 days, 5 degrees C) on the regulation of lipolysis were investigated in adipocytes isolated from epididymal fat pads of rats. Catecholamines stimulated lipolysis in an affinity sequence typical of the beta 1-adrenoceptor subtype: one-half maximum velocity (1/2 Vmax) isoproterenol (35 nM) much greater than 1/2 Vmax norepinephrine (150 nM) approximately 1/2 Vmax epinephrine (200 nM). Cold exposure markedly decreased the sensitivity (1/2 Vmax) and the responsiveness (Vmax) of the adipocytes to the lipolytic action of catecholamines. Addition of adenosine deaminase to fat cells isolated from cold-exposed rats did not normalize the lipolytic activity, suggesting that extracellular adenosine was not responsible for the obtunded lipolysis. This effect of cold exposure was transient as the lipolytic response to catecholamines was normal in fully cold-acclimated animals. Remarkably, the responsiveness of adipocytes to the lipolytic action of glucagon (200 nM) and adrenocorticotropic hormone (ACTH, 1 microM) progressively increased during cold acclimation. Adipocyte lipolytic response to dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and theophylline was normal in cold-exposed rats, indicating that the lipolytic defect resides at an early step in the lipolytic cascade (pre-cAMP). On the other hand, the antilipolytic effect of insulin on norepinephrine-induced lipolysis significantly decreased during cold acclimation, particularly at physiological levels of insulin (nanomolar level). These results demonstrate that the transient decrease in the lipolytic action of catecholamines observed during cold acclimation is compensated by 1) an increased responsiveness of adipocytes to glucagon and ACTH and 2) by a decreased effectiveness of insulin to induce antilipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in adipocyte response to lipolytic hormones during cold acclimation. 215 29

1. Ovine adipocytes were isolated in the presence of adenosine to minimize cell damage and were incubated at a low cell concentration. 2. Insulin sensitivity of lipid metabolism was retained. 3. Insulin inhibited basal lipolysis by 61% and isoproterenol- and adenosine deaminase-stimulated lipolysis by 84%. 4. Insulin increased glucose conversion to cell lipid by 3-fold.
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PMID:Sensitivity of freshly isolated ovine adipocytes to inhibition of lipolysis by insulin. 219 71

Incubation of rat adipocytes with 1 microM glucagon plus adenosine deaminase (5 micrograms/ml) inhibited maximally insulin-stimulated 3-O-methyl-D-glucose (MeGlc) transport by approximately 70%, concomitant with 30% and 55% decreases in insulin binding and cellular ATP, respectively. In contrast, under conditions where cellular ATP levels are well preserved (i.e. high albumin concentration in the medium), the inhibition of transport was reduced to about 30%, but that of insulin binding was not. Because depletion of the cellular ATP level by more than 60% by metabolic inhibitors induced 40% or more inhibition of insulin-stimulated MeGlc transport, the greater inhibition of the transport with the low albumin concentration appears to be caused in part by the secondary effect of ATP loss. The relationship between the amount of cell-bound insulin and hormone-stimulated transport activity showed that glucagon does not modulate insulin action at the step of insulin binding to its receptors. Furthermore, glucagon suppressed insulin-stimulated MeGlc transport, mainly through an attenuation of the hormone-induced increase in maximum velocity. The data show that glucagon modulates the process of signal transduction of insulin action. However, the possibility that glucagon directly modulates the process of translocation or the intrinsic activity of the glucose transporters cannot be eliminated.
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PMID:Glucagon inhibits insulin activation of glucose transport in rat adipocytes mainly through a postbinding process. 220 31

The age-related declines in the antilipolytic and lipogenic actions of insulin were studied in adipocytes from rats aged 2, 6, 12, and 24 months. Since adenosine modulates insulin action, its concentration was controlled by treatment of adipocytes with adenosine deaminase and addition of the non-metabolizable adenosine analog, N6-[(R)-(-)1-methyl-2-phenethyl] adenosine (PIA). Inhibition of isoproterenol-stimulated lipolysis by PIA increased significantly by 6 months of age. Decreasing the concentration of PIA rendered the adipocytes from the 6-, 12-, and 24-mo-old rats less sensitive to the antilipolytic effect of insulin. Basal and insulin-stimulated lipogenesis decreased with aging. PIA increased insulin-stimulated lipogenesis at 0.2 ng/ml insulin only in the 2-month-old rats. PIA reduced insulin-stimulated lipogenesis at higher insulin doses in the oldest rats. These results suggest that aging causes quantitative declines in maximal lipolysis and basal and maximal lipogenesis. Maturation may cause a decline in sensitivity to insulin, but adenosine in sufficient concentration reverses the acquired resistance to the antilipolytic effect of insulin.
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PMID:Effects of age and adenosine in the modulation of insulin action on rat adipocyte metabolism. 220 45

Rat soleus muscle strips cultured for 24 h in medium 199 were well preserved in terms of electron microscopy; ATP and creatine phosphate concentrations; rates of glucose utilization, glycogen and protein synthesis, and effects of insulin thereon. Culture led to modest changes in fluid spaces and intracellular (K+); increased basal glucose utilization up to two-fold; had no effect on the maximum response to insulin; and had no effect on sensitivity to insulin except in the presence of adenosine deaminase. Thus in vitro neither denervation nor absence of insulin had any marked effects in 24 h to decrease responses to insulin.
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PMID:Long term culture of rat soleus muscle in vitro. Its effects on glucose utilization and insulin sensitivity. 222 70


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