Regulation of the expression of the phosphoenolpyruvate carboxykinase gene in cultured rat hepatocytes by glucagon and insulin
Open Access
- 1 December 1988
- journal article
- research article
- Published by Wiley in European Journal of Biochemistry
- Vol. 178 (2) , 373-379
- https://doi.org/10.1111/j.1432-1033.1988.tb14460.x
Abstract
The induction of phosphoenolpyruvate carboxykinase (PEPCK) by glucagon was studied in primary rat hepatocyte cultures by determining the time course of the sequential events, increases in the enzyme's mRNA abundance, synthesis rate, amount and activity, and by investigating the antagonistic action of insulin on the induction by glucagon. 1 The mRNA of PEPCK was induced maximally 2–3 h after addition of 10 nM glucagon, as detected by Northern‐blot analysis after hybridization with a biotinylated antisense RNA of PEPCK. 2 The synthesis rate of PEPCK increased maximally 2–3 h after application of glucagon as revealed by pansorbin‐linked immunoprecipitation of [35S]methionine‐labelled PEPCK. 3 The enzyme amount and activity was maximally induced 4 h after glucagon application. 4 The mRNA of PEPCK was half‐maximally induced by 0.1 nM and maximally by 1 nM and 10 nM glucagon. The half‐maximal induction by 0.1 nM glucagon was antagonized almost totally, and the maximal induction by 1 nM glucagon partially, while the maximal induction by 10 nM glucagon remained unaffected by 10 nM insulin. The results show that in cultured rat hepatocytes physiological concentrations of glucagon stimulated the induction of PEPCK by an increase in mRNA, that the glucagon‐dependent increase in mRNA and enzyme‐synthesis rate occurred in parallel and preceded the increase of enzyme amount and activity by 1–1.5 h, and that physiological levels of insulin antagonized the induction by glucagon in the physiological concentration range with glucagon being the dominant hormone.This publication has 46 references indexed in Scilit:
- Modulation of the Glucagon-dependent Induction of Phosphoenolpyruvate Carboxykinase by Adenosine, but not Ketone Bodies or Animonia in Rat Hepatocyte Cultures. Possible significance for the zonal heterogeneity of liver parenchymaBiological Chemistry Hoppe-Seyler, 1987
- Primary activation of cytosolic phosphoenolpyruvate carboxykinase gene in fetal rat liver and the biogenesis of its mRNAEuropean Journal of Biochemistry, 1984
- Inhibition of transcription of the phosphoenolpyruvate carboxykinase gene by insulinNature, 1983
- Coordinate regulation of gluconeogenesis by the glucocorticoids and glucagon: Evidence for acute and chronic regulation by glucagonJournal of Cellular Physiology, 1981
- Induction of phosphoenolpyruvate carboxykinase by sympathetic agents in primary cultures of adult rat hepatocytesBiochemical and Biophysical Research Communications, 1981
- Regulation of phosphoenolpyruvate carboxykinase by glucagon and glucocorticoids in primary cultures of rat hepatocytesBiochimica et Biophysica Acta (BBA) - General Subjects, 1980
- Autoregulatory Shift from Fructolysis to Lactate Gluconeogenesis in Rat Hepatocyte Suspensions. The Problem of Metabolic Zonation of Liver ParenchymaHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1976
- Control of Enzyme Levels in Mammalian TissuesPublished by Wiley ,1973
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970
- A convenient, rapid and sensitive method for measuring the incorporation of radioactive amino acids into proteinBiochemical and Biophysical Research Communications, 1960