Mechanism of the Inhibition by Insulin of the Glucagon-Dependent Activation of the Phosphoenolpyruvate Carhoxykinase Gene in Rat Hepatocyte Cultures. Action on Gene Transcription, mRNA Level and -Stability as well as Hysteresis Effect

Christ, Bruno; Nath, Annegret; Jungermann, Kurt

doi:10.1515/bchm3.1990.371.1.395

Cited by 51 publications

(57 citation statements)

References 16 publications

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“…The glucagon-induced PEPCK mRNA accumulation shown in the present work probably resulted from an increase in the rate of transcription of thc gene as shown in cultured adult rat hepatocytes [16]. In addition, the stabilisation of PEPCK mRNA by cAMP could also been involved [33].…”

Section: Cusslon Ect Of Changes In Pancreatic Hormone Level In Utevn mentioning

confidence: 70%

“…Indeed, it has been shown that demethylation of the PEPCK gene began only after day 18 of gestation in the fetal rat liver [31]. The PEPCK gene was partly hypomethylated in hepatocytes from 20-day-old fetuses and was thus capable of responding to glucagon as rapidly as hepatocytes from adult rat [16].…”

Section: Cusslon Ect Of Changes In Pancreatic Hormone Level In Utevn mentioning

confidence: 99%

“…In cultured hepatocytes from adult rat, most of the inhibitory effect of insulin on PEPCK gene expression was obtained in the presence of dexamethasonc [15,16,391. The present work provide evidence that glucocorticoids were required for insulin to be effective in the reversion of the glucagon-induced PEPCK gene expression.…”

Section: Cusslon Ect Of Changes In Pancreatic Hormone Level In Utevn mentioning

confidence: 99%

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Dominant role of glucagon in the initial induction of phosphoenolpyruvate carboxykinase mRNA in cultured hepatocytes from fetal rats

Pégorier

Salvadó

Forestier

et al. 1992

European Journal of Biochemistry

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The injection of streptozotocin to 18-day-old rat fetuses induced, 2 days later, a 50% fall in plasma insulin and a twofold increase in plasma glucagon concentrations and liver CAMP levels. Phosphoenolpyruvate carboxykinase mRNA that were undetectable in the fetal rat liver, accumulated 48 h after streptozotocin injection, their concentration being 30% of that found in the liver of l-dayold newborn rats in whom liver phosphoenolpyruvate carboxykinase gene expression is maximal. Physiological concentrations of glucagon (0.7 & 0.2 nM) induced, within 2 h, phosphoenolpyruvate carboxykinase mRNA accumulation in cultured hepatocytes from 20-day-old fetuses. The addition of insulin (0.01 -100 nM) inhibits, by no more than 30Y0, the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation. Exposure of fetal hepatocytes to insulin for 24 h did not change the glucagon doseiresponse curve and did not lead to a more efficient inhibition of the glucagoninduced phosphoenolpyruvate carboxykinase mRNA accumulation, despite a clear stimulatory effect on the rate of lipogenesis. In contrast, when hepatocytes were cutured in the presence of dexamethasone, the glucagon-induced phosphoenolpyruva te carboxykinase mRNA accumulation can be totally inhibited by pharmacological concentrations of insulin (1 0 nM).From these in-vivo and in-vitro studies, it is concluded that, under physiological conditions, the postnatal rise in plasma glucagon concentration is more important than the fall in the plasma insulin concentration for the primary induction of liver phosphoenolpyruvate carboxykinase gene expression.The development of hepatic gluconeogenesis at birth is essential to ensure glucose homeostasis in suckling newborn rats that received a high-fat/low-carbohydrate diet, the milk [l]. The appearance of hepatic gluconeogenesis at birth is due to the induction of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity. Indeed, PEPCK mRNA is undetectable in the fetal rat liver and accumulates rapidly after birth [2 -51 as the result of an increase in the rate of PEPCK gene transcription [ 5 ] . The postnatal increase of PEPCK mRNA and activity is controlled by the rapid change in pancreatic hormone concentrations that occur at birth; an increase in plasma glucagon and a decrease in plasma insulin [6]. Indeed, the injection of fetal rat in utevo with pharmacological doses of glucagon or dibutyryl cyclic AMP (But,cAMP) increases liver PEPCK activity and mRNA levels 12, 7 -91, whereas the injection of pharmacological doses of insulin has the opposite effect [9]. Similarly, the addition of glucagon or But,cAMP to cultured fetal hepatocytes induces

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Section: Cusslon Ect Of Changes In Pancreatic Hormone Level In Utevn mentioning

confidence: 70%

Section: Cusslon Ect Of Changes In Pancreatic Hormone Level In Utevn mentioning

confidence: 99%

Section: Cusslon Ect Of Changes In Pancreatic Hormone Level In Utevn mentioning

confidence: 99%

See 1 more Smart Citation

Dominant role of glucagon in the initial induction of phosphoenolpyruvate carboxykinase mRNA in cultured hepatocytes from fetal rats

Pégorier

Salvadó

Forestier

et al. 1992

European Journal of Biochemistry

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“…Total RNA was prepared from the hepatocytes as described in detail elsewhere. 30,33 Fifteen micrograms of total RNA was separated on denaturing formaldehyde agarose gels. Equal lane-to-lane loading of RNA was determined by ethidium bromide staining of the gels before blotting onto nylon membranes according to standard protocols.…”

Section: Methodsmentioning

confidence: 99%

Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes

2000

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“…In vitro transcription was started by addition of 30 p1 58% glycerol, 150 mM NH4CI, 8. . The nuclei were incubated for 30 min at 25 "C and the reaction was stopped as described [32]. Labelling control was performed by precipitation of RNA from small aliquots during incubation.…”

Section: Methodsmentioning

confidence: 99%

Autoregulation of Actin Synthesis in Hepatocytes by Transcriptional and Posttranscriptional Mechanisms

Reuner¹,

Wiederhold²,

Dunker³

et al. 1995

Eur J Biochem

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Treatment of rat hepatocytes with the filamentous-actin-stabilizing toxin phalloidin decreased the amount of globular actin by 77% in the cytosol and by 80% in the nucleus within 12 h. Simultaneously, actin mRNA was specifically increased by 230%. The de-novo synthesis of actin mRNA, as measured by nuclear run-on transcription, was enhanced by 250%. Treatment of cells with actinomycin D blocked the increase of actin mRNA. The apparent half-life of actin mRNA was not significantly altered during treatment with phalloidin.In contrast, the globular-actin-stabilizing botulinum C2 toxin increased the amount of cytosolic globular actin by 50% within 12 h. Simultaneously, the actin mRNA level was decreased by 62%. However, de-novo synthesis of actin mRNA was not impaired. The apparent half-life of actin mRNA was decreased by approximately 60 % during treatment with C2 toxin.The data strongly suggest an autoregulatory control of actin synthesis on the basis of the globular/ filamentous actin ratio in rat hepatocytes at the transcriptional as well as at the posttranscriptional levels.

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Mechanism of the Inhibition by Insulin of the Glucagon-Dependent Activation of the Phosphoenolpyruvate Carhoxykinase Gene in Rat Hepatocyte Cultures. Action on Gene Transcription, mRNA Level and -Stability as well as Hysteresis Effect

Cited by 51 publications

References 16 publications

Dominant role of glucagon in the initial induction of phosphoenolpyruvate carboxykinase mRNA in cultured hepatocytes from fetal rats

Dominant role of glucagon in the initial induction of phosphoenolpyruvate carboxykinase mRNA in cultured hepatocytes from fetal rats

Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes

Autoregulation of Actin Synthesis in Hepatocytes by Transcriptional and Posttranscriptional Mechanisms

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