Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of such studies is to identify the hormones that act on the developmental formation of individual urea cycle enzymes, namely argininosuccinate synthetase, argininosuccinate lyase and arginase in the rat fetal liver. The development of argininosuccinate synthetase activity which is completely blocked by the suppression of glucocorticoids in the fetal liver is affected by neither glucagon nor thyroxine. The activity of argininosuccinate lyase which is never changed by the suppression or addition of glucocorticoids, is under the influences of glucagon and thyroxine at a late fetal period and the enzyme activity can be precociously induced in utero by injection of dibutyryl cyclic AMP to fetuses. Cortisol has been shown to precociously stimulate fetal liver arginase activity after an intraperitoneal injection, but the rise in activity at the late fetal period is not completely prevented by suppression of glucocorticoid and it seems that glucagon and thyroxine may also promote its developmental formation just before birth.
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PMID:Hormonal regulation of three urea cycle enzymes in rat fetal liver. 21 56

Parenchymal cells from adult rat liver, cultured in perifused monolayers, increased the levels of urea-cycle enzymes between 15% and 60% in response to glucagon within 24 h. This stimulation was drastically enhanced by the simultaneous presence of dexamethasone, especially in the case of argininosuccinate synthetase and argininosuccinate lyase, which increased nearly threefold. Dexamethasone itself produced only negligible stimulation, but exerted a similar effect on the stimulatory action of glucagon, if it was exclusively present during 6 h prior to the glucagon treatment, suggesting a permissive action of this hormone. The effect of glucagon, particularly in the presence of dexamethasone, was mimicked by dibutyryl adenosine 3':5'-monophosphate, whereas epinephrine was ineffective. All stimulations induced by hormones or dibutyryl adenosine 3':5'-monophosphate were abolished by cycloheximide, suggesting the involvement of protein synthesis in the induction process. Using the usual culture technique with a discontinuous supply of medium no significant effect of glucagon and dexamethasone could be measured. This striking difference between both culture systems indicates that perifusion is the more adequate in vitro system for studies of the regulation of enzyme levels. Possible reasons for the failure of hormonal stimulation of urea-cycle enzymes in normal monolayer culture are discussed.
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PMID:Permissive effect of dexamethasone on glucagon induction of urea-cycle enzymes in perifused primary monolayer cultures of rat hepatocytes. 47 71

All five urea cycle enzymes of rat liver increased in activity 48 h after subcutaneous administration of crystalline zinc glucagon to male rats and remained elevated after 7 days of continuous glucagon infusion. The maximum ratios of enzyme activities over those of controls were 2.0 for carbamyl phosphate synthetase, 1.3 for ornithine transcarbamylase, 2.7 for argininosuccinate synthetase, 3.2 for argininosuccinase, and 2.2 for arginase. Actinomycin D or puromycin prevented these responses to glucagon. The increase in arginase activity after zinc glucagon treatment was matched by an increase in immunoprecipitable enzyme. All five enzymes were induced by physiological plasma levels of glucagon. Tube feeding of casein hydrolysate for 2 days increased all five enzyme activities 1.5- to 2.2-fold and resulted in plasma glucagon levels similar to those required for induction by exogenous glucagon. Thus, glucagon is an inducer of the entire urea cycle in rat liver and plays a role in the induction of the cycle by protein feeding.
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PMID:Induction of urea cycle enzymes of rat liver by glucagon. 63 99

The activity changes of two urea cycle enzymes, argininosuccinate synthetase (ASS) and argininosuccinase (ASL), were followed after corticosteroid and pancreatic hormone treatments in utero and in primary cultured fetal hepatocytes. The ASL activity which was induced by glucagon or by (Bu)2cAMP administration was enhanced by a treatment with streptozotocin for 2 days, although ASS was not changed under these conditions. The activity of both enzymes was enhanced by cortisol administration in utero only in streptozotocin-treated fetuses, suggesting an inhibitory effect of insulin. In cultured fetal hepatocytes, dexamethasone produced a marked increase of the two enzyme activities, which was abolished by the simultaneous addition of insulin. The parallel results obtained with these two experimental models allow one to conclude that the high plasma insulin level in late gestation might repress the development of ASS and ASL activities in utero and antagonize the effect of corticosteroids on these enzyme activities.
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PMID:Effects of pancreatic hormones and glucocorticosteroids on argininosuccinate synthetase and argininosuccinase activities of rat liver during the perinatal period: in vivo and in vitro studies. 301 69

Foetal hepatocytes obtained from rats at different stages were cultured in order to investigate the inducibility of the five urea-cycle enzymes by glucagon and dibutyryl cyclic AMP (Bt2cAMP). When 18.5-day-old hepatocytes were cultured for 3 days with 10(-7) M glucagon, the activities of carbamoyl phosphate synthetase (CPS), argininosuccinase (ASL) and arginase were increased by 1.4-, 1.8- and 1.9-fold, respectively, as compared to controls. These effects were mimicked by 10(-4) M Bt2cAMP, but the activities of ornithine transcarbamylase (OTC) and argininosuccinate synthetase (ASS) were never changed by the addition of these compounds. Hepatocytes cultured at earlier stages were not responsive to glucagon unless dexamethasone was added simultaneously, suggesting that this steroid might induce some steps necessary for glucagon action. Bt2cAMP was effective as early as day 16.5 without requiring the presence of steroids. In addition, the effect of the cyclic nucleotide appeared additive or synergistic with that of dexamethasone. The simultaneous addition of actinomycin D did not affect the glucagon-induced increase in enzyme levels, thus suggesting a post-transcriptional effect of the hormone on the foetal enzyme activities. Insulin itself did not have any effect on the basal level of the enzyme activities and had only a moderate inhibitory effect on glucagon-induced ASL activity. This slight effect of insulin is in contrast with the marked inhibitory effect of dexamethasone on this enzyme activity that we described previously.
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PMID:Induction of the five urea-cycle enzymes by glucagon in cultured foetal rat hepatocytes. 332 26

In the present study we examined the in vivo effects of glucocorticosteroids and glucagon on the developmental formation of the individual urea cycle enzymes argininosuccinate synthetase, argininosuccinase, and arginase during the late fetal period. In particular, addition of exogenous glucagon caused a rise in argininosuccinase and arginase activities in the livers of rat fetuses at term but not at earlier stages. Glucagon produced a rise in argininosuccinase activity earlier if fetuses were previously treated with cortisol. When fetuses were deprived of corticosteroid (hypophysectomy in utero), glucagon no longer promoted the argninosuccinase activity, indicating that adrenal glucocorticoids are required for normal enhancement of the enzyme activity by glucagon. Dibutyryl cAMP was still effective in hypophysectomized fetuses. Results obtained by injected combinations of inducers indicated that a glucocorticosteroid-glucagon interaction might be involved in the regulation of argininosuccinate synthetase and argininosuccinase. No synergistic action was found on arginase activity in vivo.
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PMID:Effects of glucocorticosteroids and glucagon on argininosuccinate synthetase, argninosuccinase, and arginase in fetal rat liver. 627 18

Foetal-rat hepatocytes were cultured in primary monolayer culture, and activity changes of argininosuccinate synthetase (ASS, EC 6.3.4.5) and argininosuccinase (ASL, EC 4.3.2.1) were followed under defined hormone conditions. In hormone-free medium, cultured cells maintained the enzyme activities at values equal to those of freshly isolated cells for at least 3 days. Continuous addition of dexamethasone produced the development of the two enzyme activities, but only after the first 20h of culture. Under these conditions, urea production by the foetal hepatocytes was concomitantly increased in the culture medium. Pretreatment with dexamethasone for 20h was sufficient to produce the development of ASL activity within the 2 following days. Introduced alone, glucagon induced an increase of ASL activity, but did not affect the ASS activity. The most powerful stimulation of ASS and ASL could be observed in cultured hepatocytes if glucagon and dexamethasone were added simultaneously or sequentially. These results indicated that the development of the receptor complex for the induction of urea-cycle enzymes appears early before birth and established that glucocorticoids amplify the glucagon stimulation of these enzyme activities during foetal life.
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PMID:Hormonal regulation of two urea-cycle enzymes in cultured foetal hepatocytes. 666 Nov 96

Glucagon, a potent inducer of urea cycle enzymes, was administered subcutaneously, at a dose of 0.5 mg once a day, for 7 days to two citrullinemic patients. During this period, plasma NH3 levels in case 1 decreased significantly (P < 0.05 compared to levels before administration) and daily urinary excretion of urea N increased significantly (P < 0.05). For 1 week after the cessation of administration, the daily urinary excretion of urea N was significantly higher than the level before administration (P < 0.05), the plasma citrulline level during glucagon administration was lower than that before administration. In case 2, glucagon administration also decreased the plasma NH3 level (although the decrease was not statistically significant), and significantly increased daily urinary excretion of urea N (P < 0.05 compared to levels before administration). For 1 week after the cessation of glucagon administration the plasma citrulline level was significantly lower than that before administration (P < 0.05). These results indicate that glucagon significantly increases the urinary excretion of urea in the late onset form of argininosuccinate synthetase deficiency and that it may also decrease plasma NH3 levels in some patients with the deficiency.
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PMID:Effects of glucagon on urinary excretion of urea and on plasma ammonia level in argininosuccinate synthetase deficiency. 819 93

Induction of the mRNAs of the five urea cycle enzymes by glucagon and dexamethasone was studied in cultured rat hepatocytes to define mechanisms which coordinate the increases in the enzyme activities by these hormones. The transcription rate for arginase mRNA increased 9-fold in 7 h, the mRNA level 90-fold in 28 h, and the arginase activity 1.5-fold at 48 h, suggesting that induction is due primarily to stabilization of mRNA. Arginase mRNA induction was minimal with either hormone alone, combined hormones were synergistic, and cycloheximide pretreatment did not prevent the rise in mRNA levels. Carbamyl phosphate synthetase mRNA levels responded synergistically to the combined hormones and peaked 240-fold above controls at 24 h although activity only increased 1.4-fold at 48 h. Argininosuccinate lyase and synthetase mRNAs were induced by an increased transcriptional rate, were not induced by single hormones, responded synergistically to combined hormones, and showed a partial blockage of mRNA induction by cycloheximide. The ornithine transcarbamylase mRNA level was not increased by these hormones although activity increased 1.3-fold, suggesting stabilization of the enzyme. Thus glucagon and dexamethasone induce the urea cycle enzymes by three different mechanisms: transcriptional control of mRNA in argininosuccinate synthetase and lyase, stabilization of mRNA in carbamyl phosphate synthetase and arginase, and protein stabilization of ornithine transcarbamylase.
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PMID:Coordinate induction of the urea cycle enzymes by glucagon and dexamethasone is accomplished by three different mechanisms. 846 Sep 37

Expression of the hepatic gene for argininosuccinate synthase (ASS), one of the key enzymes of the urea cycle, was analysed during the perinatal period in the rat. To this end, the amount of specific mRNA was measured in the liver at various stages of development and in cultured foetal hepatocytes maintained in different hormonal conditions. The ASS mRNA was first detected in 15.5-day foetuses and its level increased concomitantly with a rise in the enzyme activity, suggesting that the appearance of the ASS activity reflects the turning on of specific gene transcription. This was demonstrated by run-on assay which showed an enhanced rate of transcription of the ASS gene during the perinatal period. When foetal hepatocytes were cultured with dexamethasone, a dose-dependent increase in ASS mRNA was measured, which was completely abolished by actinomycin D addition. The transcription rate of the gene was increased about twofold in the presence of the steroid, as measured by nuclear run-on assay. This transcriptional action could additionally require a protein factor since it could be inhibited by the simultaneous addition of puromycin. Insulin or glucagon respectively repressed or enhanced the dexamethasone-induced accumulation of ASS mRNA when added simultaneously with the steroid for 24 h. This developmental regulation of the ASS mRNA by glucocorticoids, insulin and glucagon could account for the modulation of the enzyme activity previously observed in vivo and in vitro in the foetal liver.
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PMID:Regulation of argininosuccinate synthetase mRNA level in rat foetal hepatocytes. 939 12


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