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)

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

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

The adenosine analogues 5'-(N-ethyl) carboxamidoadenosine (NECA) and N6-(phenylisopropyl) adenosine (R-PIA) were shown to differ in their effect on the plasma level of free fatty acids (FFA), glucose and lactate in pigs representing low (Ada 0) and high (Ada A) red cell adenosine deaminase activity. At the same dosage range (0.001-0.005 mg/kg) R-PIA produced a much stronger suppression of the FFA level than NECA, indicating that A1 adenosine receptors predominate in porcine adipose tissue. Pretreatment with 8-phenyltheophylline completely abolished the antilipolytic effect of both adenosine analogues. NECA in contrast to R-PIA elevated the blood glucose concentration, suggesting that A2 adenosine receptors are involved in the stimulation of glycogenolysis. This effect of NECA was not altered by a beta-adrenoceptor blockade providing evidence for a direct effect of adenosine on glycogenolysis. Whereas the changes in plasma FFA following NECA administration were of similar magnitude in Ada A and Ada 0 pigs, the changes in the blood glucose concentration were different in these two groups of pigs.
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PMID:Adenosine deaminase and porcine meat quality. II. Effects of adenosine analogues on plasma free fatty acids, glucose and lactate in pigs representing high and low adenosine deaminase red cell activity. 226 May 6

When fragments of rat or human adipose tissue, or isolated adipocytes, are incubated with [14C]glucose in vitro, [14C]diacylglycerol accumulates rapidly: it comprises 20-50% of newly synthesized (14C-labeled) acylglycerols, compared to less than 1% diacylglycerol accumulated in the bulk lipid store in vivo. The experiments reported in this study were performed to test the possibility that agents that influence the rate of lipolysis might differentially affect the accumulation of di- and triacylglycerol in human adipose tissue, and perhaps account for the discrepancy between the early labeling and the later accumulation of diacyglycerol. Fragments of gluteal subcutaneous adipose tissue obtained from obese men and women were incubated with isoproterenol, epinephrine plus yohimbine, adenosine deaminase, or dibutyryl 3',5'-cyclic adenosine monophosphate to stimulate lipolysis. Tissue fragments were also incubated with clonidine, adenosine, or insulin to inhibit lipolysis. No agent had any effect on the rate of accumulation of newly synthesized triacylglycerol. The effects of these agents on the rate of lipolysis were negatively correlated with their effects on accumulation of newly synthesized diacylglycerol. Newly synthesized diacylglycerol may be preferentially hydrolyzed by hormone sensitive lipase. This increased susceptibility to lipolytic stimulation, compared to newly synthesized triacylglycerol, may account for the minute accumulation of diacylglycerol in adipose tissue in vivo.
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PMID:Lipolytic effects on diacylglycerol accumulation in human adipose tissue in vitro. 228 Jan 78

Adenosine has been shown in vitro to be a potent antilipolytic agent and an inhibitor of insulin-stimulated glucose utilization in skeletal muscle. To test whether endogenously produced adenosine (e.g., from ATP hydrolysis) shares these deleterious effects on substrate mobilization and utilization and thus limits maximum thermogenesis in vivo, adenosine deaminase (converts adenosine to inosine) was given to rats 15 min before cold exposure. Significant (P less than 0.05) increases in thermogenesis were observed under both well-fed (100 units/kg ip) and food-rationed (200 units/kg ip) states. Significant (P less than 0.05) increases in thermogenesis and cold resistance were also observed after pretreatment with selective adenosine receptor antagonists [8-cyclopentyltheophylline (1 microgram/kg ip) greater than 1,3-dipropyl-8-p-sulfophenylxanthine (1.25 mg/kg ip) greater than aminophylline (18.7 mg/kg ip)], indicating an A1-receptor-mediated effect. These results indicate that endogenously released adenosine can indeed attenuate the thermogenic capacity in severe cold and that adenosine antagonists, especially those selective for A1-receptor, are useful in improving cold resistance under varying nutritional states.
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PMID:Enhancement of maximal thermogenesis by reducing endogenous adenosine activity in the rat. 231 70

In summary, this study characterized the biphasic inhibition of fat cell glucose transport by the lipolytic agents caffeine and theophylline. Like the lipolytic drug forskolin, both methylxanthines produced an immediate inhibition of glucose transport that was not seen with 8-phenyltheophylline, a pure adenosine receptor antagonist. The immediate inhibition was therefore not mediated by the adenosine receptor antagonism but seems to be due to a direct interaction with the hexose transporter. This conclusion is supported by the immediate onset of the inhibition and additionally by the interference of theophylline and caffeine with the binding of cytochalasin B, a ligand of the glucose transporter that binds to an intracellular site of the transporter molecule. In addition, a second, delayed inhibitory effect of theophylline and caffeine on glucose transport was observed. This portion shared many aspects of the inhibitory effect of lipolytic hormones. It developed over a period of about 5 min and was antagonized by the simultaneous addition of the antilipolytic hormone PGE2. This component of transport inhibition could be attributed to the antagonistic effect of methylxanthines at the fat cell A1-adenosine receptor since it was also seen with 8-phenyltheophylline. This conclusion is further supported by data showing that the removal of endogenous adenosine with adenosine deaminase resulted in a comparable 25-30% inhibition of insulin-stimulated glucose transport. In addition, the time course of glucose transport inhibition by the subsequent addition of adenosine deaminase is similar to that of the delayed portion of the inhibition seen with theophylline and caffeine. Both treatments produced their maximal inhibition after 5 min. In conclusion, the methylxanthines theophylline and caffeine inhibit glucose transport by a combination of two different modes of action. The immediate major component is mediated via a direct interaction with the hexose transporter whereas the delayed component involves adenosine receptor antagonism and thereby the interaction with G-proteins.
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PMID:Methylxanthines inhibit glucose transport in rat adipocytes by two independent mechanisms. 239 Jan 12

The inhibition of insulin-stimulated glucose transport by lipolytic agents was studied in isolated rat adipose cells. Two different mechanisms for the inhibition of glucose transport by lipolytic hormones and agents were distinguished by use of the antilipolytic agent prostaglandin E2 (PGE2). The inhibition of glucose transport induced by lipolytic hormones such as glucagon, catecholamines or ACTH in the presence of adenosine deaminase was antagonized by PGE2. In contrast, inhibition of hexose transport by alkylxanthines was only partially (20-30%) attenuated by PGE2, although the eicosanoid had antagonized cyclic AMP accumulation and stimulation of lipolysis in response to all tested lipolytic agents. The inhibition of glucose transport by IBMX was immediate, whereas the lipolytic hormones (isoprenaline and ACTH) exhibited a latency of 2-3 min. In addition, the inhibition induced by the lypolytic hormones disappeared after cooling of the cells to 22 degrees C, at which temperature IBMX was still inhibitory. Thus, the PGE2-sensitive component of the effect of lipolytic agents on glucose transport appears to be mediated by adenylate cyclase or its subunits Ns/Ni. The PGE2-insensitive effect of alkylxanthines probably reflects a direct interaction of the agents with a regulatory site at the transporter or a related protein.
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PMID:Prostaglandin E2 differentiates between two forms of glucose transport inhibition by lipolytic agents. 244 31

Crude preparations of histones had insulin-like actions in isolated adipocytes. This activity was attributed to the arginine-rich histones, H3 and H4. The metabolic effects of purified H3 and H4 on isolated adipocytes were similar to those of insulin in a number of respects. Like insulin, H3 and H4 stimulated the incorporation of both glucose and pyruvate in isolated cells and stimulated intercellular oxidation of glucose; in contrast, the lipolytic agents ACTH and isoproterenol actually inhibited the incorporation of pyruvate into adipocytes. In contrast to the effects of the lipolytic hormones, the effects of H3 and H4, like insulin, were not blocked by the presence of adenosine deaminase in the medium. The same concentrations of phenylarsine oxide were required to inhibit the stimulation of glucose incorporation whether by insulin or by histones. Furthermore, the addition of H4 or insulin to isolated adipocytes resulted in the increased phosphorylation of 17 kDa phosphoproteins as detected by two-dimensional electrophoresis. The insulin-like effect of the active histones was specific to their structure. Lysine-rich histones (H1, H2A and H2B), various polycations, and proteolytic fragments of purified H3 or H4 were all inactive. It is unknown whether this phenomenon might imply a physiological function for such endogenous molecules; however, a comparison of the detailed effects of insulin and histones might be informative in terms of common intracellular transduction systems.
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PMID:Insulin-like effects of histones H3 and H4 on isolated rat adipocytes. 254 Aug 34

Backfat was obtained at slaughter from market weight hogs to study the acute effects of clenbuterol (CB), ractopamine (RAC) or epinephrine (EPI), in the presence and absence of theophylline (THEO) or adenosine deaminase (ADA), on rates of lipolysis and fatty acid synthesis in vitro. Only EPI increased lipolytic rate in the absence of THEO or ADA. In the presence of THEO or ADA, RAC and CB were lipolytic, although CB had a lower maximal response. With THEO present, RAC and EPI increased lipolysis with a similar potency and responsiveness. Lipolytic responses from all agonists were prevented by propranolol. Insulin stimulated glucose incorporation into fatty acids 50 to 100%; stimulated rates were not influenced by any agonist, either alone or in the presence of ADA. When THEO was present, EPI and RAC inhibited fatty acid synthesis approximately 50%. Clenbuterol was not inhibitory under any conditions. Results indicate that, under appropriate conditions, beta-adrenergic agents increase lipolysis and decrease lipogenesis in porcine adipocytes. Combined evidence suggests that lipolysis is more sensitive to beta-adrenergic stimulation than is insulin-stimulated lipogenesis. Finally, RAC and CB possess only partial agonist activity relative to EPI, CB being least active.
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PMID:Acute effects of beta-adrenergic agonists on porcine adipocyte metabolism in vitro. 257 68

Regulation of hormone action with aging has been extensively studied; adipocytes provide an interesting model for some of these questions. We have compared the ability of insulin to stimulate glucose uptake and suppress lipolysis in adipocytes isolated from two month and twelve month-old rats. The ability of insulin to stimulate maximal glucose transport was decreased in adipocytes from the older rats (P less than 0.001); as well, insulin's EC50 was also higher (P less than 0.01) in these cells. Furthermore, these defects were present when insulin-stimulated glucose transport was measured in the presence or absence of adenosine deaminase which metabolizes endogenously released adenosine. Endogenously released adenosine is a stimulator of glucose transport and an inhibitor of lipolysis. Maximal suppression of isoproterenol-induced lipolysis by insulin was similar when adipocytes isolated from the two age groups were incubated in the absence of adenosine deaminase. However, maximal insulin-mediated suppression of lipolysis was found to be significantly decreased (P less than 0.001) in adipocytes isolated from older rats when the experiments were done in the presence of adenosine deaminase; also, insulin's EC50 was increased in these cells under these conditions (P less than 0.001). These results emphasize the importance of the adenosine receptor in modulating the response of isolated adipocytes to insulin, particularly for lipolysis, and document the presence of age-associated defects in insulin regulation of both glucose transport and lipolysis.
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PMID:Impaired insulin-mediated inhibition of lipolysis and glucose transport with aging. 266 94


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