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)

DL-alpha-Methyltryptophan (alphaMeTrp), a synthetic analogue of tryptophan, has been found to be a potent inducer of hepatic tyrosine aminotransferase activity in the adrenalectomized rat. alphaMeTrp is inactive in vitro. Unlike the action of other known inducers (tryptophan, hydrocortisone, adenosine cyclic 3:5-monophosphate, and glucagon), maximal stimulation of enzyme activity occurs only 16 to 30 hours after alphaMeTrp administration and the activity is still elevated at 96 hours. Only the L isomer of alphaMeTrp is active, and addition of a hydroxyl group to position 5 of the indole ring renders an inactive compound. The induction can be prevented by actinomycin D or cycloheximide but not galactosamine. Administration of alphaMeTrp together with hydrocortisone produced an additive stimulation of enzyme activity. alphaMeTrp given along with glucagon or adenosine cyclic 3:5-monophosphate caused a further but not additive increase in enzyme activity. Tryptophan given along with alphaMeTrp promoted no extra stimulation whatsoever. These data indicate that alphaMeTrp and tryptophan may act via a common pathway which in part requires RNA synthesis. Other enzymes, namely alanine and aspartate aminotransferase, ornithine aminotransferase, ornithine carbamoyltransferase, serine dehydratase, and histidine ammonialyase, were not affected by treatment of rats with alphaMeTrp.
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PMID:Stimulation of tyrosine aminotransferase activity by dl-alpha-methyltryptophan. 23 76

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 effects of corticosteroids and pancreatic hormones on two mitochondrial enzymes of ureagenesis, carbamyl phosphate synthetase-I (CPS-I) and ornithine transcarbamylase (OTC), were investigated and compared in fetal rat liver. Supplementing hydrocortisone acetate (50 micrograms) to 18.5-day-old fetuses significantly increased CPS-I activity (by 36%) and decreased OTC activity (by 23%). An actinomycin D supply (2 micrograms) to 18.5-day-old fetuses prematurely increased OTC activity and decreased fetal insulin level (by 42%). This treatment had no effect on CPS-I activity. Glucagon supply (25 micrograms) during the late fetal period increased both activities within 2 h, while dibutyryl-cAMP enhanced OTC activity 17 h later. These results suggested that the fetal development of CPS-I activity was under the control of corticosteroids and glucagon. In contrast, corticosteroid hormones produced an inhibitory effect on OTC activity. This might be explained by the permissive effect of corticosteroids on insulin action, since insulin might act as a repressor in utero of enzyme development. Thus, the paradoxical effect of actinomycin D on OTC activity was probably due to the decrease in fetal insulinemia.
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PMID:Effects of corticosteroids and pancreatic hormones on carbamyl phosphate synthetase-I and ornithine transcarbamylase activities in fetal rat liver. 299 95

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

cDNA probes were employed to measure levels of carbamoyl-phosphate synthetase I (CPS) and ornithine carbamoyltransferase (OCT) mRNAs in fetal and neonatal livers and intestines. In the fetal liver, significant levels of OCT mRNA were present at 15-days gestation while CPS mRNA could not be detected until day 17 of fetal development. Apart from a small decline just after birth, amounts of both mRNAs increased steadily to reach adult levels in postnatal life. In contrast to the situation in liver, CPS and OCT mRNA levels in the fetal intestine rose rapidly to peak at day 21 of gestation and then declined steadily in the first seven days after birth. Using the methyl-sensitive restriction isoschizomeric pair, MspI/HpaII, the 5' ends of both the CPS and OCT genes were shown to undergo demethylation during development. In the case of the OCT gene, however, the hypomethylation characteristic of the adult liver and intestinal mucosa was not observed in the 15-day-old fetal liver, where significant levels of gene expression had already been established. Levels of CPS and OCT mRNA in livers of adults responded to glucagon in normal animals (1.5-fold and 2.2-fold increases, respectively) and to dexamethasone in experimentally induced diabetic animals (3-fold increase in CPS mRNA with no change in OCT mRNA). These treatments were all without effect on the levels of CPS and OCT mRNA in intestinal mucosa.
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PMID:Rat liver and intestinal mucosa differ in the developmental pattern and hormonal regulation of carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase gene expression. 375 12

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

Hepatocyte monolayer cultures from two preruminating and two ruminating calves were used to study the effects of triglyceride accumulation on induction of ureagenesis by glucagon plus dexamethasone. Whether hepatocytes from preruminating and ruminating calves respond similarly to triglyceride accumulation and hormonal treatment was also determined. Hepatocyte monolayer cultures were incubated from 24 to 48 h with a physiological mixture of nonesterified fatty acids (NEFA, 0 or 1.5 mM) and a hormone mixture containing glucagon plus dexamethasone (0 or 100 nM of both) added as a 2 x 2 factorial (NEFA x hormones). Ureagenesis was measured at 0, .25, and 5 mM NH4Cl from 48 to 51 h and activities of ornithine transcarbamylase (OTC) and arginase were measured at 48 h. There was no significant age-related interaction for any of the measurements. Therefore, monolayer culture of hepatocytes from preruminating calves provides a reasonable model for studying the effects of glucagon, dexamethasone, and triglyceride accumulation on ureagenesis in the ruminating bovine. Intracellular triglyceride was increased by NEFA (2.3 vs 15.6 +/- 1.9 microg TG/microg DNA, P < .001). Triglyceride-engorged cells exhibited decreased ureagenesis (1.04 vs .87 +/- .135 nmol/(microg DNA x h), P < .05) but had unaltered OTC and arginase activity. Hormone addition did not affect triglyceride accumulation but increased ureagenesis (.70 vs 1.21 +/- .135 nmol/(microg DNA x h), P < .0001). There was no interaction between hormone addition and triglyceride accumulation on ureagenesis. To separate the effects of dexamethasone from that of glucagon on ureagenesis, hepatocyte monolayer cultures from one ruminating and three preruminating calves were used. Hepatocyte monolayer cultures were incubated from 24 to 48 h with glucagon (0 or 100 nM) and dexamethasone (0 or 100 nM) added as a 2 x 2 factorial. Ureagenesis was measured at 0, .25, and 5 mM NH4Cl from 48 to 51 h. Glucagon increased ureagenesis (.77 vs 1.24 +/- .11 nmol/(microg DNA x h), P < .0001). Dexamethasone did not affect ureagenesis, nor was there any interaction between glucagon and dexamethasone. Therefore, glucagon alone was responsible for the induction observed with the mixture of glucagon and dexamethasone. In conclusion, glucagon is able to increase ureagenesis in bovine hepatocytes, and triglyceride accumulation does not interfere with the induction.
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PMID:Effects of triglyceride accumulation on induction of urea synthesis by glucagon and dexamethasone in monolayer cultures of bovine hepatocytes. 1087 50

Exogenous glucagon increases hepatic glucose synthesis in part by increasing hepatic extraction of amino acids from blood for conversion to glucose. To examine the role of glucagon in orchestrating gene expression of gluconeogenic and ureagenic enzymes, we determined the mRNA concentrations of key hepatic ureagenic and gluconeogenic enzymes at d 11, 15, and 22 postpartum in multiparous Holstein cows that received 0 or 5 mg of glucagon in 60 mL of saline by subcutaneous injection every 8 h for 14 d starting on d 8 postpartum. On d 11 postpartum, glucagon increased the hepatic mRNA concentrations for all measured ureagenic enzymes (carbamoylphosphate synthetase I, ornithine transcarbamylase, and argininosuccinate synthetase) and gluconeogenic enzymes (pyruvate carboxylase and cytosolic and mitochondrial forms of phosphoenolpyruvate carboxykinase) and increased or tended to increase mRNA concentrations of gluconeogenic enzymes on d 15 postpartum but not on d 22. The effect of glucagon to increase mRNA concentrations of ureagenic and gluconeogenic enzymes was limited to times when concentrations of plasma insulin were not increased. Our results suggest that hepatic gene expression of key ureagenic and gluconeogenic enzymes in early-lactation dairy cows is responsive to hormonal regulation by glucagon.
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PMID:Glucagon increases hepatic mRNA concentrations of ureagenic and gluconeogenic enzymes in early-lactation dairy cows. 1976 27