Regulation of the expression of the phospho enol pyruvate carboxykinase gene in cultured rat hepatocytes by glucagon and insulin

CHRIST, Bruno; NATH, Annegret; BASTIAN, Helge; JUNGERMANN, Kurt

doi:10.1111/j.1432-1033.1988.tb14460.x

Cited by 58Metabolism, Diabetes, and CancerPancreatic function and diabetesGlycogen Storage Diseases and Myoclonus

Regulation of the expression of the phospho enol pyruvate carboxykinase gene in cultured rat hepatocytes by glucagon and insulin

CHRIST, Bruno, NATH, Annegret, BASTIAN, Helge, JUNGERMANN, Kurt·1988·European Journal of Biochemistry

DOI 10.1111/j.1432-1033.1988.tb14460.x

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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.

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Authors: CHRIST, B., NATH, A., BASTIAN, H., & JUNGERMANN, K.
Affiliations: University of Göttingen (DE)
Corresponding author: CHRIST, Bruno
ORCID: CHRIST, Bruno
Venue: European Journal of Biochemistry
Publisher: Wiley
Published: 1988-12
Volume: 178
Issue: 2
Pages: 373-379
ISSN: 0014-2956 (ISSN-L)
1432-1033
DOI: 10.1111/j.1432-1033.1988.tb14460.x
OpenAlex: W2086604833
Cited by: 58
References: 55
Citations by year: 2025: 1 · 2022: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2012: 1
FWCI: 1.19
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5936 d)
Locations: European Journal of Biochemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
Keywords: phosphoenolpyruvate carboxykinase, gene expression regulation, glucagon, insulin, hepatocytes, mRNA induction, enzyme synthesis rate, gluconeogenesis
MeSH terms: Animals, Cells, Cultured, Enzyme Induction, Gene Expression Regulation, Glucagon, Insulin, Liver, Male, Phosphoenolpyruvate Carboxykinase (GTP), Rats, Inbred Strains, RNA, Messenger, Transcription, Genetic, Rats

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Regulation of the expression of the phospho enol pyruvate carboxykinase gene in cultured rat hepatocytes by glucagon and insulin

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