Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas

Alexis B. Ulrich, Jens Standop, Bruno M. Schmied, Matthias B. Schneider, Terence A. Lawson, Parviz M. Pour

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

We investigated the cellular expression of 9 cytochrome P450-isozymes (CYP1A1, CYP1A2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, CYP3A4) and 3 glutathione S-transferase-isozymes (GST-π, GST-α, GST-μ) in the pancreas of hamsters, mice, rats, rabbits, pigs, dogs and monkeys, and in comparison with the human pancreas. A wide variation was found in the cellular localization of these enzymes between the 8 species. Most enzymes were expressed in the pancreas of the hamster, mouse, monkey and human, whereas rats, pigs, rabbits and dogs were lacking several isozymes. However, in all of the species the islet cells expressed more enzymes than ductal and acinar cells. An exclusive expression of enzymes in the islet cells was found in the hamster (CYP2E1), mouse (CYP1A1, CYP1A2, GST-α, GST-μ), rat (CYP2C8,9,19), rabbit (CYP1A2, CYP2B6, GST-π), and pig (CYP1A1). Although no polymorphism was found in the pancreas of animals, in human tissue four enzymes were missing in about 50% of the cases. The results imply a greater importance of the islet cells in the metabolism of xenobiotics within the pancreas. The differences in the distribution of these drug-metabolizing enzymes in the pancreas between the species call for caution when extrapolating experimental results to humans.

Original languageEnglish (US)
Pages (from-to)247-253
Number of pages7
JournalToxicologic Pathology
Volume30
Issue number2
DOIs
StatePublished - Feb 2002

Keywords

  • Drug-metabolizing enzymes
  • cytochrome P450
  • glutathione S-transferase
  • laboratory animals

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

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    Ulrich, A. B., Standop, J., Schmied, B. M., Schneider, M. B., Lawson, T. A., & Pour, P. M. (2002). Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas. Toxicologic Pathology, 30(2), 247-253. https://doi.org/10.1080/019262302753559588