Insulin-mediated modulation of cytochrome P450 gene induction profiles in primary rat hepatocyte cultures

Jaspreet S. Sidhu, Curtis John Omiecinski

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

In this investigation, we examined the effects of insulin on gene induction responsiveness in primary rat hepatocytes. Cells were cultured for 72 hours either in the absence or presence of 1 μM insulin and then exposed to increasing concentrations of phenobarbital (PB; 0.01-3.5 mM). Culturing in the absence of insulin produced 1.5-2-fold increases in the induction magnitude of CYP2B1 and CYP2B2 mRNA expression resulting from PB exposures, without altering the bell-shaped dose-response curve characteristic of this agent. However, for the CYP3A1 gene, insulin removal led to a pronounced shift in both the PB-induction magnitude and dose-response relationships of the induction response, with higher levels of CYP3A1 expression resulting from exposures to lower concentrations of inducer. Insulin removal also reduced the time required to attain maximal induction of CYP2B1/2 and CYP3A1 gene expression. The insulin effects were not specific for PB induction, as insulin deprivation similarly enhanced both dexamethasone- and β-naphthof-lavone-inducible CYP3A1 and CYP1A1 expression profiles, respectively. In contrast, the level of albumin mRNA expression was reduced considerably in cells deprived of insulin. We conclude that insulin is an important regulator of inducible and liver-specific gene expression in primary rat hepatocytes.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Biochemical and Molecular Toxicology
Volume13
Issue number1
DOIs
StatePublished - Jan 1 1999

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Cell culture
Cytochrome P-450 Enzyme System
Rats
Hepatocytes
Genes
Modulation
Insulin
Cytochrome P-450 CYP2B1
Gene expression
Gene Expression
Messenger RNA
Cytochrome P-450 CYP1A1
Phenobarbital
Liver
Dexamethasone
Albumins
Cultured Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

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Insulin-mediated modulation of cytochrome P450 gene induction profiles in primary rat hepatocyte cultures. / Sidhu, Jaspreet S.; Omiecinski, Curtis John.

In: Journal of Biochemical and Molecular Toxicology, Vol. 13, No. 1, 01.01.1999, p. 1-9.

Research output: Contribution to journalArticle

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