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 molecular mechanism involved in altered regulation of the rate-limiting enzyme in hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), during endotoxemia is not completely understood. We examined, therefore, the effect of a nonlethal dose of Escherichia coli endotoxin on PEPCK gene expression in fasted rats. 5 h after endotoxin treatment, the PEPCK transcription rate and the amount of mRNA(PEPCK) were significantly decreased at a time when the insulin/glucagon (I/G) molar ratio and plasma corticosterone levels were significantly increased. Similar results were observed in a time course study, in which altered cAMP induction of PEPCK gene expression paralleled changes in the I/G molar ratio. In diabetic rats treated with endotoxin, PEPCK gene expression was decreased in the absence, however, of an increased I/G molar ratio. This finding indicates that other factors, such as inflammatory mediators or cytokines, alter PEPCK gene transcription during endotoxemia. IL-6, a putative mediator of endotoxin action in the liver, had no effect on PEPCK gene expression in fasted rats, but did decrease cAMP induction of PEPCK gene expression. These results indicate that, during endotoxemia, regulation of PEPCK gene expression is influenced by inflammatory mediators in addition to the classical endocrine hormones. IL-6, however, does not appear to be involved directly in the altered regulation of the PEPCK gene during endotoxemia.
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PMID:Altered transcriptional regulation of phosphoenolpyruvate carboxykinase in rats following endotoxin treatment. 165 77

Rat hepatocytes were cultured for 24 h in the presence or absence of 100 nM dexamethasone (DX). After a medium change, phosphoenolpyruvate carboxykinase (PCK) was induced by addition of glucagon at different concentrations, from physiological 0.1 nM to hyperphysiological 10 nM, again in the presence or absence of 100 nM dexamethasone. 1. With dexamethasone addition during the culture and induction phase (DX+/+), 10 nM glucagon increased PCK mRNA abundance (Northern blot analysis) and activity (in vitro translation) synchronously to the same extent with maxima after 2 h and PCK enzyme activity after a time lag with a maximum after 6 h. The total detectable PCK mRNA amount was apparently also translationally active. 10 microM N6,2'-O-dibutyryladenosine 3',5'-(cyclic)phosphate (Bt2cAMP) as the second messenger had essentially the same effect as 10 nM glucagon. 2. In the absence of dexamethasone during the preculture and the induction phase (DX-/-), 10 nM glucagon and 10 microM Bt2cAMP could enhance PCK mRNA only about half-maximally. Glucagon or dexamethasone added alone in physiological concentrations of 0.1 nM and 100 nM, respectively, were unable to increase PCK mRNA. However, treatment of the cells with dexamethasone also enabled 0.1 nM glucagon to enhance PCK mRNA to a maximum after 2 h, independent of the presence of dexamethasone during the induction period (DX+/+ and DX+/- cells). Thus, dexamethasone was a permissive agent in that it shifted the sensitivity of the cells towards glucagon into the physiological concentration range. 3. In the presence of dexamethasone during the culture and induction phase (DX+/+) 0.1 nM glucagon maximally enhanced the transcription of the PCK gene (nuclear run on) fourfold after 30 min; in the absence of dexamethasone during both phases (DX-/-) glucagon was without any effect. The overall transcriptional rate was not significantly different in cells with and without dexamethasone during the culture and induction phase (DX+/+ vs. DX-/-). Thus, dexamethasone acted permissively mainly on the transcription of the PCK gene. 4. With culture in the presence of dexamethasone over decreasing periods of time, 1 nM glucagon could induce submaximal PCK mRNA amounts already after 1-3 h steroid culture. This restitution by dexamethasone of the PCK mRNA inducibility by glucagon was inhibited by cycloheximide. This suggested that ongoing protein synthesis was required for the permissive action of dexamethasone on the expression of the PCK gene. The results allow the following conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism of the permissive action of dexamethasone on the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in cultured rat hepatocytes. 171 Sep 84

Nuclear extracts from cultured rat hepatocytes were analyzed by gel mobility shift assay for protein binding to the cyclic AMP responsive elements CRE1 (-96/-77) and CRE2 (-152/-132) and the NF1-CTF binding site (-121/-99) of the phosphoenolpyruvate carboxykinase (PCK) promotor. Binding was very weak to the CRE2 and CRE1. The NF1-CTF site formed two complexes with nuclear protein. Protein binding was increased, when the NF1-CTF site was coupled to the CRE1, and further, when it was coupled to both the CRE1 and the CRE2. Complex formation was not altered by treatment of the hepatocytes with glucagon or with glucagon and insulin. Thus, protein binding was most efficient when all three elements were in context, which might be necessary for full transcriptional activation of the PCK gene.
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PMID:Interactions of nuclear protein from cultured rat hepatocytes with the cyclic AMP responsive elements and the NF1-CTF site in the promoter of the rat phosphoenolpyruvate carboxykinase gene. 183 77

Several hormones, including insulin, glucagon, and glucocorticoids, regulate the expression of the rate-limiting gluconeogenic enzyme, phosphoenolpyruvate carboxykinase [GTP: oxaloacetate carboxy-lyase (transphosphorylating); EC 4.1.1.32; PEPCK] in liver. In this report we demonstrate that retinoic acid (RA) also regulates PEPCK expression by inducing a 3-fold increase in the rate of transcription of the PEPCK gene. A RA response element located between -468 and -431 in the PEPCK promoter mediates a 7-fold increase in expression of a chimeric construct containing the basal PEPCK promoter ligated to the chloramphenicol acetyltransferase reporter gene. This element confers RA responsiveness through the heterologous thymidine kinase promoter and functions relatively independent of position and orientation. An 18-base-pair core sequence (-451 to -434) (i) mediates an effect of RA on PEPCK gene expression and contains motifs found in two other RA response elements; (ii) corresponds to AF1, an accessory factor element that is an integral component of the complex glucocorticoid response unit in the PEPCK gene promoter; (iii) is in a region involved in the developmental expression of the PEPCK gene; and (iv) shows homology to elements involved in the tissue-specific regulation of genes, including the hepatic apolipoprotein genes and the alpha 1-antitrypsin gene.
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PMID:A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene. 184 96

Administration of glucagon, epinephrine, or dibutyryl cAMP to chicks induced cytosol-specific phosphoenolpyruvate carboxykinase in liver. In vitro translation assay with poly(A)+RNA indicated that this induction was due to the increase in phosphoenolpyruvate carboxykinase-coding mRNA synthesis which resulted from an increased level of hepatic cAMP. Either hydrocortisone or alpha-adrenergic agonist was ineffective for the induction by itself, but showed a significant effect when administered together with one of the inducing agents given above. In particular, hydrocortisone enhanced the synthesis of phosphoenolpyruvate carboxykinase-specific mRNA without changing the profile of the time courses of the induction and of hepatic cAMP level. Those observations suggest that the fundamental machinery required for induction of cytosol-specific phosphoenolpyruvate carboxykinase in liver is shared in common between rat and chick, and that the absence of appreciable induction of cytosol-specific hepatic phosphoenolpyruvate carboxykinase in starved chicks is due to neither lack nor impairment of the hormone-mediated induction mechanism, but is due to the difference in usage of the genetic information between the two animal species.
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PMID:Regulation of hormonal induction of chick liver cytosol-specific phosphoenolpyruvate carboxykinase. 196 52

In the rat, the suckling-weaning transition is accompanied by marked changes in nutrition. During the suckling period, the pups are fed with milk which is a high-fat low-carbohydrate diet. At weaning, milk is progressively replaced by the rat chow which is a high-carbohydrate low-fat diet. This is accompanied by considerable hormonal modifications: an increase in plasma insulin and a decrease in plasma glucagon concentrations, as well as by marked changes in metabolic pathways in liver: decrease in hepatic gluconeogenesis, increase in lipogenesis, and appearance of liver glucokinase. Most of the data concerning these changes are related to maximal activity of enzymes. The recent availability of specific cDNA probes for phosphoenolpyruvate carboxykinase, acetyl-CoA carboxylase, fatty acid synthase and glucokinase has allowed study of the role of pancreatic hormones and of nutrition in the changes of the expression of these genes at weaning in the rat.
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PMID:Hormonal control of specific gene expression in the rat liver during the suckling-weaning transition. 197 92

During the suckling period, the rats are fed continuously with milk, which is a high-fat low-carbohydrate diet (HF). At weaning, milk is progressively replaced by the rat's laboratory chow which is a high-carbohydrate low-fat diet (HCHO), and this is accompanied by large hormonal modifications: an increase in plasma insulin and a decrease in plasma glucagon concentrations, and by marked changes in metabolic pathways in liver: decrease in hepatic gluconeogenesis and increase in glycolysis and lipogenesis. Most of the data concerning these changes are related to maximal activity of enzymes. The recent availability of specific cDNA probes for phosphoenolpyruvate carboxykinase (PEPCK), and glucokinase (GK) has allowed the study of the role of pancreatic hormones and nutrition in the changes of the expression of these genes at weaning in the rat. Regarding phosphoenolpyruvate carboxykinase gene transcription, the concentration of mRNA as well as the activity of PEPCK are elevated in the liver of suckling rat until the onset of weaning, 21 d after delivery. After weaning to a HCHO diet, both mRNA and activity of PEPCK rapidly decrease to a very low level. In contrast, weaning on an HF diet, which maintains high plasma glucagon and low plasma insulin levels, does not decrease in plasma glucagon concentration and a 90% decrease in PEPCK gene transcription and PEPCK mRNA concentration in 1 h. Regarding glucokinase gene transcription, the concentration of mRNA as well as the activity of GK are not detectable before 15 d after birth in the liver of the rat. They markedly increase when the newborn are weaned on an HCHO diet but not when they are weaned on an HF diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal regulation of liver phosphoenolpyruvate carboxykinase and glucokinase gene expression at weaning in the rat. 203 60

In liver phosphoenolpyruvate carboxykinase (PCK) activity, protein and mRNA are localized predominantly in the periportal zone. The activation of the PCK gene by glucagon was studied in primary rat hepatocyte cultures under physiological arterial and venous oxygen tensions [16% and 8% (by vol.)]. PCK gene expression was monitored on the level of transcription, mRNA abundance and enzyme activity as well as enzyme synthesis and degradation. 1. Transcription of the PCK gene was increased by 10 nM glucagon maximally after 0.5 h; it reached nearly basal levels again after 2 h. The increase in transcription was 45% lower under 8% oxygen than under 16% oxygen. 2. PCK mRNA was maximally increased after 2 h under 16% oxygen and after 4 h under 8% oxygen; it subsequently declined to twice the basal values after 8 h. The maximal increase after 2 h was 50% lower under 8% oxygen than under 16% oxygen. 3. PCK enzyme activity was maximally increased after 4-6 h. The maximal enhancement after 4 h was 50% lower under 8% oxygen than under 16% oxygen. 4. The increase in PCK enzyme activity was due to an enhanced synthesis rate of PCK protein. The rate increased after 3 h was 35% lower under 8% oxygen than under 16% oxygen. 5. The degradation of PCK protein was equal under both oxygen tensions. The results show that in cultured rat hepatocytes the induction of PCK gene expression is modulated by physiological concentrations of oxygen. The modulation occurred at the level of gene transcription, mRNA abundance, enzyme protein synthesis and enzyme activity. The periportal to perivenous oxygen gradient could be the major factor responsible for the predominant expression of the PCK gene in the periportal zone.
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PMID:Modulation by oxygen of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. 205 Jan 45

In vitro transcripts of the 3'-non-translated region of the phosphoenolpyruvate carboxykinase (PCK) gene both in "sense" and "antisense" orientation bound cytosolic protein from cultured rat hepatocytes as demonstrated by electrophoretic mobility shift assay. Binding of cytosolic protein was increased 3-fold and PCK mRNA was enhanced 10-fold by treatment of the hepatocytes with 10 nM glucagon. The similar time course of the glucagon-induced increase in protein binding to PCK mRNA 3'-end and in PCK mRNA suggests that protein binding might be involved in the stabilization of PCK mRNA.
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PMID:Binding of cytosolic protein from cultured rat hepatocytes to the 3'-end of phosphoenolpyruvate carboxykinase mRNA--significance for protein-mediated mRNA stabilization. 205 15

Food intake, plasma glucose, insulin (I) and glucagon (G), hepatic glycogen and fructose 2,6-bisphosphate (F-2, 6-P2) and liver glucokinase, glucose 6-phosphatase (G6-Pase), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6-PF-2 kinase/F-2, 6-P2ase), pyruvate kinase (PK-L) and phosphoenolpyruvate carboxykinase (PEPCK) activities were measured in 2 and 22-month-old rats before 3 d starvation and after 2, 4, 6, 24 and 48 h refeeding a high carbohydrate (HC, 74% w/w) diet. Expressed per 100 g of body weight, the food intake of old rats was 55% lower than that of young rats and the amount of carbohydrate absorbed hourly during the first 6 h of refeeding was 2.4-fold higher in young than in old rats. During the first 6 h of refeeding plasma glucose increased 2-fold and returned to normal values after 24 h in young rats, while plasma glucose did not change during refeeding in old rats. In young rats [I] fell by 85% after starvation and returned to normal values 2 h after refeeding. [I] was higher in old than in young rats; it decreased by 40% after starvation and returned to the basal value 4 h after refeeding. No marked changes were observed in plasma [G] in both groups. No difference was observed in hepatic glycogen in the two groups, while F-2, 6-P2 was higher in old than in young rats. In young rats, the opposite changes in liver glucokinase and G6-Pase activities occurring after starvation and during refeeding were
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PMID:Age-dependent glycolysis and gluconeogenesis enzyme activities in starved-refed rats. 208 82


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