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)

In the anterogradely perfused rat heart with glucose as fuel, 1 microM isoproterenol (ISO) inhibited the insulin (INS) plus adenosine deaminase (AdoDA) stimulation of ventricular protein synthesis by 72%. ISO (1 microM) alone had no effect on ventricular protein synthesis but inhibited atrial protein synthesis by 20%. The concentration dependence of the ISO inhibition was similar to the stimulation of glucose uptake by ISO. Inhibition could not be overcome by increasing INS concentrations. The effects of ISO were diminished by propranolol and could be partially mimicked by forskolin (FSK) or 8-(4-chlorophenylthio-)adenosine 3',5'-cyclic monophosphate (CPT-cAMP). The stimulation of protein synthesis by noncarbohydrate fuels was antagonized by ISO. Hypoxia (PO2 = 50%) also antagonized the INS stimulation of ventricular protein synthesis but did not affect basal rates. ATP contents were decreased by ISO but not by a PO2 of 50%. Both manipulations increased lactate output. The inhibition of protein synthesis by ISO could possibly be explained by indirect effects of ISO on cardiac "energy status." Furthermore, inhibition may thus represent purely an in vitro phenomenon and may not occur in vivo. However, the possibility that there are more direct effects of ISO on the machinery of protein synthesis has not been excluded. The inhibition of protein synthesis by hypoxia cannot be explained by changes in energy status and may result from intracellular lactoacidosis.
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PMID:Acute inhibition of rat heart protein synthesis in vitro during beta-adrenergic stimulation or hypoxia. 305 5

1. Rates of lipolysis were measured at different concentrations of glucagon in adipocytes prepared from parametrial adipose tissue of fed or starved rats in different reproductive states. All experiments were performed in the presence of a high concentration of adenosine deaminase (1 unit/ml). 2. Maximal rates of lipolysis (elicited by 25 nM-glucagon in each instance) were higher in adipocytes from peak-lactating rats than those from pregnant animals in both the fed and starved states. 3. Of adipocytes from fed animals, those from peak-lactating rats were the most sensitive to glucagon, whereas those from late-pregnant and early-lactating rats were 1-2 orders of magnitude less sensitive. 4. Adipocytes from 24 h-starved rats showed a much smaller stimulation of lipolysis by glucagon, making the assessment of sensitivity difficult. Therefore, rates of lipolysis were also measured in the presence of a maximally anti-lipolytic dose of insulin. The presence of insulin did not alter the relative sensitivities to glucagon of adipocytes from fed animals in different reproductive states, although all dose-response curves were shifted to the right. When lipolysis in adipocytes from starved animals was measured in the presence of insulin, it became evident that starvation for 24 h markedly increased the sensitivity of adipocytes from late-pregnant rats to glucagon, but did not affect that of cells from animals in the other reproductive states. 5. It is concluded that the large changes in sensitivity to glucagon that occurred during the reproductive cycle may enable the modulation of adipose-tissue lipolysis in vivo to satisfy the different metabolic requirements of the animal in the transition from pregnancy to peak lactation.
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PMID:Changes in the sensitivity to glucagon of lipolysis in adipocytes from pregnant and lactating rats. 305 15

1. Adipocytes were isolated from the interscapular brown fat of male rats maintained at 21 degrees C. These animals were controls, streptozotocin-diabetics or 2-day insulin-treated diabetics. 2. With adipocytes from diabetic animals, maximum rates of noradrenaline-stimulated O2 uptake were decreased by 58%, and the Bmax. of [3H]GDP binding to mitochondria was decreased by 55%. Insulin administration reversed both of these changes. 3. Streptozotocin-diabetes increased basal lipolysis in adipocytes incubated with adenosine deaminase (1 unit/ml), decreased the EC50 (concn. giving 50% of maximum effect) for noradrenaline, but did not change the maximum rate of noradrenaline-stimulated lipolysis. Except for some small differences at very low concentrations (10-100 pM), diabetes or insulin treatment did not alter the sensitivity of noradrenaline-stimulated lipolysis or O2 uptake to the inhibitory effect of N6-phenylisopropyladenosine. It is therefore concluded that the lesion(s) in thermogenesis in diabetes are not attributable to any changes in lipolysis. 4. Blood flow through interscapular brown fat, measured by accumulation of [14C]DDT [14C-labelled 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] was increased by 2.3-fold 70 min after a single administration of insulin to diabetic rats. This treatment decreased blood flow through epididymal white fat by 58%. 5. Propranolol treatment of diabetic rats muted the ability of insulin treatment to increase the maximum rate of noradrenaline-stimulated O2 uptake, suggesting that this action of insulin may be a secondary one rather than a direct effect of the hormone on the adipocytes.
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PMID:Factors influencing the altered thermogenic response of rat brown adipose tissue in streptozotocin-diabetes. 327 24

1. Soleus, extensor digitorum longus (EDL) or hemi-diaphragm muscles of the rat were incubated in the presence of insulin and rates of the processes of glycolysis and glycogen synthesis were measured. 2. The concentrations of insulin required to cause half-maximal stimulation of glycolysis in both soleus and EDL preparations were significantly decreased by the presence of adenosine deaminase in the medium. 3. Adenosine deaminase increased the sensitivity of the process of hexose transport to insulin (in an identical manner to the change in sensitivity of glycolysis) in the EDL preparation. 4. None of the adenosine mediated effects on insulin-stimulated rates of glycolysis were observed in the hemi-diaphragm preparation or on the rates of glycogen synthesis in any of the three muscle preparations. 5. Therefore, changes in the adenosine system in skeletal muscle influence insulin sensitivity regardless of fibre type composition of the muscle.
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PMID:Effects of adenosine deaminase on the sensitivity of glucose transport, glycolysis and glycogen synthesis to insulin in muscles of the rat. 327 78

1. The relationship between the activity of adenosine metabolizing enzymes 5'nucleotidase (5'N), adenosine kinase (A.K.) and adenosine deaminase (A.D.) with basal and insulin-stimulated glucose transport in isolated fat cells from young and old animals was studied at 08:00 and 16:00 hr. 2. In cells from young animals a larger insulin-stimulation of glucose transport was observed at 16:00 hr than at 08:00 hr. Also at 16:00 hr small changes in 5'N, A.K. and A.D. activities suggest a decrease in adenosine formation. 3. In the cells from old animals no effect of insulin was observed at any time, while a 3-5-fold increase in 5'N indicated a predominance of adenosine formation at both times studied. 4. An inverse relationship was observed in the changes of adenosine metabolism and insulin action.
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PMID:Effect of age and day time on the adenosine modulation of basal and insulin-stimulated glucose transport in rat adipocytes. 328 66

Myocardial adenosine (ADO) has long been regarded as a regulator of coronary blood flow. In other tissues, such as adipose and skeletal muscle, much attention has focused on the role of ADO as a metabolic regulator of the actions of insulin. In the present study, we determined the effect of ADO infusion on insulin-stimulated myocardial glucose uptake (MGU). Mongrel dogs of either sex were instrumented to obtain arterial-coronary sinus differences for glucose, lactate, and oxygen. These were multiplied by circumflex artery blood flow (Q) to obtain uptake values. Measurements were made before and during hyperinsulinemic (4 U/min)-euglycemic clamp (clamp) with intracoronary infusions of saline, ADO, adenosine deaminase (ADA), or nitroprusside (NP). During clamp, MGU increased from a basal value of 3.0 +/- 0.8 mg/min (mean +/- SE) to 5.53 +/- 0.8 mg/min. Adenosine infusion potentiated this response, raising MGU further to 9.02 +/- 1.1 mg/min while not significantly affecting lactate or oxygen uptakes. Infusion of ADA confirmed the specificity of the response by blocking the metabolic effect of exogenously infused ADO. When NP was infused, Q increased significantly without altering MGU, indicating that the metabolic response to ADO was independent of the changes it caused in Q. A dose-response relationship existed between ADO and insulin-stimulated MGU. The metabolic response to ADO was more sensitive than the vasodilator response. It is concluded that ADO acts as a regulator of insulin in heart. This metabolic regulation occurs independent of changes in coronary blood flow.
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PMID:Adenosine potentiates insulin-stimulated myocardial glucose uptake in vivo. 328 95

The influence of prolonged energy restriction (1250 kJ for 4 weeks) on insulin's antilipolytic action was investigated in abdominal adipocytes of obese subjects. An attempt was made to discriminate between dietary influences per se and indirect influences caused by changes in the concentration or action of adenosine. Prolonged energy restriction resulted in about a 3.5-fold increase in basal lipolytic rate which was associated with a corresponding increase in maximal response to insulin. Both these effects could be mimicked by adenosine deaminase (1.6 micrograms/ml) which increased glycerol release of adipocytes from fed donors to levels normally seen during starvation suggesting that the improvement of lipolytic responsiveness to insulin during energy restriction was an apparent one only, due to the fact that glycerol release was increased. To identify dietary influences that selectively affect insulin action the effects of insulin were compared with those of other antilipolytic agents in the presence of adenosine deaminase. Maximally effective concentrations of prostaglandin E2, clonidine and N6-phenylisopropyladenosine almost completely suppressed glycerol release before and during starvation. The extent of inhibition produced by these latter compounds was therefore related to basal activity by the same linear relationship in all experimental settings. By contrast insulin only partially depressed glycerol release and the relationships between basal activity and response to maximal concentrations of insulin were significantly different before and during starvation (P less than or equal to 0.01) in the presence of adenosine deaminase indicating that starvation selectively influences insulin action via mechanisms that are unrelated to the effects of other antilipolytic compounds. It is concluded that the main effect of energy restriction on insulin's antilipolytic action is an apparent one which is secondary increased lipolytic activity. Direct dietary effects on insulin action became apparent upon removal of endogenous adenosine. These tend to limit the maximal response to insulin and may be due to changes at the post-binding level but could also reflect an intrinsic property of insulin's antilipolytic action.
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PMID:Antilipolytic action of insulin in abdominal adipocytes of obese subjects before and during energy restriction. Influence of adenosine deaminase. 330 11

The counterregulatory action of catecholamines on insulin-stimulated glucose transport and its relation to glucose transporter phosphorylation were studied in isolated rat adipose cells. Plasma membranes exhibiting reduced glucose transport activity were prepared as described previously (Joost, H. G., Weber, T. M., Cushman, S. W., and Simpson, I. A. (1986) J. Biol. Chem. 261, 10033-10036) from cells treated with insulin, and subsequently with isoproterenol and adenosine deaminase. In these membranes, transporter affinity for cytochalasin B binding was significantly reduced (KD = 133.5 +/- 14 versus 89.8 +/- 11 nM, means +/- S.E.) with no change in number of sites or immunoreactivity of the transporter on Western blots. Reconstituted plasma membrane transport was significantly lower with isoproterenol treatment (0.50 +/- 0.12 versus 0.97 +/- 0.27 nmol/mg protein/10 s). In contrast, transport activity reconstituted from corresponding intracellular transporters (from low density microsomes) was unchanged (5.4 +/- 2.2 versus 6.9 +/- 1.2 nmol/mg protein/10 s). Thus, the intrinsic activity change of the transporter produced by catecholamines appears to reflect a structural modification that is confined to the plasma membrane and not recycled into the intracellular compartment. In cells equilibrated with [32P]phosphate, neither insulin nor isoproterenol induced [32P]phosphate incorporation into the glucose transporter immunoprecipitated from plasma membranes. Conversely, phorbol 12-myristate 13-acetate stimulated significant incorporation of [32P]phosphate into the glucose transporter in insulin-stimulated cells without any change in plasma membrane transport activity or transporter concentration. Thus, the phosphorylation state of the glucose transporter does not seem to be involved in either signaling transporter translocation or triggering changes in transporter intrinsic activity.
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PMID:Activity and phosphorylation state of glucose transporters in plasma membranes from insulin-, isoproterenol-, and phorbol ester-treated rat adipose cells. 330 53

Weight-maintaining fat-rich, "prudent," carbohydrate-rich, as well as energy-restricted diets (300 kcal/d) were fed in succession for 7 d to 12 healthy males of ideal body weight under metabolic ward conditions. At the end of each period isolated fat cells were prepared from subcutaneous abdominal adipose tissue and incubated in vitro in the absence or presence of adenosine deaminase, either alone or in combination with various lipolytic or antilipolytic hormones and agents. Variations in total energy intake and dietary composition had characteristic and specific effects on fat cell lipolysis in vitro. High carbohydrate and prudent diets resulted in low rates of nonstimulated glycerol release and impaired insulin action in the presence of adenosine deaminase (320 mU/ml). High-fat and energy restricted diets were characterized by high rates of nonstimulated glycerol release. Sensitivity of antilipolysis to insulin and prostaglandin E2 was 10 to 200 times lower respectively on energy-restricted than on fat-rich diets. The effects of alpha 2- and beta-adrenergic catecholamines and of N6-phenylisopropyladenosine were not affected by the preceding diets.
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PMID:Influences of variation in total energy intake and dietary composition on regulation of fat cell lipolysis in ideal-weight subjects. 330 2

Glucose is an important fuel for rat brown adipose tissue in vivo and its utilization is highly sensitive to insulin. In this study, the different glucose metabolic pathways and their regulation by insulin and norepinephrine were examined in isolated rat brown adipocytes, using [6-14C]glucose as a tracer. Glucose utilization was stimulated for insulin concentrations in the range of 40-1000 microU/ml. Furthermore, the addition of adenosine deaminase (200 mU/ml) or adenosine (10 microM) did not alter insulin sensitivity of glucose metabolism. The major effect of insulin (1 mU/ml) was a respective 7-fold and 5-fold stimulation of lipogenesis and lactate synthesis, whereas glucose oxidation remained very low. The 5-fold stimulation of total glucose metabolism by 1 mU/ml of insulin was accompanied by an 8-fold increase in glucose transport. In the presence of norepinephrine (8 microM), total glucose metabolism was increased 2-fold. This was linked to a 7-fold increase of glucose oxidation, whereas lipogenesis was greatly inhibited (by 72%). In addition, norepinephrine alone did not modify glucose transport. The addition of insulin to adipocytes incubated with norepinephrine, induced a potentiation of glucose oxidation, while lipogenesis remained very low. In conclusion, in the presence of insulin and norepinephrine glucose is a oxidative substrate for brown adipose tissue. However the quantitative importance of glucose as oxidative fuel remains to be determined.
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PMID:Effects of insulin and norepinephrine on glucose transport and metabolism in rat brown adipocytes. Potentiation by insulin of norepinephrine-induced glucose oxidation. 331 19


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