Changes in the expression of cytochromes P450 and nuclear receptors in the liver of genetically diabetic db/db mice

Kouichi Yoshinari, Shunsuke Takagi, Junko Sugatani, Masao Miwa

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Physiological and pathophysiological conditions often affect the expression of drug metabolizing enzymes such as cytochromes P450 (P450s). Diabetes is one such factor and it is of great interest to understand its effects on drug metabolism, since diabetic patients generally have increased need for pharmacotherapy. We have recently reported the coordinated reduction of CYP2B1/2 and their transcriptional regulator constitutive androstane receptor (CAR), a member of the nuclear receptor superfamily, in the liver of genetically obese/diabetic Zucker fatty rats (Xiong, H., Yoshinari, K., et al., Drug Metab. Dispos., 30, 918-923, 2002). In this study, we investigated the expression of P450s and liver-enriched nuclear receptors in the liver of genetically diabetic db/db mice. Surprisingly, both CYP2B10 and CAR levels were increased in db/db mice. CYP4A expression was also increased at both mRNA and protein levels in db/db mice, while those of peroxisome proliferator-activated receptor α, a key regulator for the transcriptional activation of CYP4As, were comparable to those in age-matched C57BL/6 mice. Our results demonstrate that db/db mice and Zucker fatty rats exhibit different expression profiles of P450s and nuclear receptors despite their similar characteristics for obesity and diabetes resulting from a defect in the leptin signaling pathway.

Original languageEnglish
Pages (from-to)1634-1638
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume29
Issue number8
DOIs
Publication statusPublished - 2006 Aug 9

Keywords

  • Constitutive androstane receptor
  • Cytochrome P450
  • Nuclear receptor
  • Peroxisome proliferator-activated receptor
  • Phenobarbital
  • db/db mouse

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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