Insulin suppresses the induction of CYP2B1 and CYP2B2 gene expression by phenobarbital in adult rat cultured hepatocytes

Biochem Biophys Res Commun. 1996 Dec 4;229(1):182-8. doi: 10.1006/bbrc.1996.1777.


The effect of insulin on the phenobarbital (PB)-induced gene expression of CYP2B1 and CYP2B2 (CYP2B1/2B2) in adult rat hepatocytes was investigated. Insulin, which has been regarded as an essential hormone for primary hepatocytes, was found to strongly suppress the induction of CYP2B1/2B2 gene expression in hepatocytes cultured on EHS-gel. Although the induction by PB was not seen in monolayer hepatocytes cultured on type I collagen under standard culture conditions, the induced expression of the CYP2B1/2B2 gene was observed in monolayer hepatocytes by removing insulin from the medium. Further, we succeeded in maintaining the prolonged induction of CYP2B1/2B2 by PB in monolayer hepatocytes by using a medium containing dexamethasone but not insulin. Since the PB-induced UDP-glucuronosyltransferase gene expression was not reduced by insulin, the suppressive effect of insulin was considered to be specific to the CYP2B1/2B2 gene. These results demonstrate that insulin in media masks the PB-induced expression of the CYP2B1/2B2 gene in conventional monolayer hepatocytes and that the use of insulin-free media with primary hepatocytes provides a useful tool for investigating the molecular mechanism of CYP2B1/2B2 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Cells, Cultured
  • Culture Techniques / methods
  • Cytochrome P-450 CYP2B1 / drug effects*
  • Cytochrome P-450 Enzyme System / drug effects*
  • Diabetes Mellitus, Experimental
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Gene Expression Regulation, Enzymologic*
  • Insulin / pharmacology*
  • Liver / cytology
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Phenobarbital / pharmacology*
  • Rats
  • Rats, Wistar
  • Steroid Hydroxylases / drug effects*
  • Streptozocin / pharmacology
  • Time Factors


  • Insulin
  • Streptozocin
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2B1
  • steroid 16-beta-hydroxylase
  • Phenobarbital