Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Effect of Hyperinsulinemia and Type 2 Diabetes-Like Hyperglycemia on Expression of Hepatic Cytochrome P450 and GlutathioneS-Transferase Isoforms in a New Zealand Obese-Derived Mouse Backcross Population

Georgia J. Pass, Walter Becker, Reinhart Kluge, Katharina Linnartz, Leona Plum, Kirsten Giesen and Hans-Georg Joost
Journal of Pharmacology and Experimental Therapeutics August 2002, 302 (2) 442-450; DOI: https://doi.org/10.1124/jpet.102.033553
Georgia J. Pass
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Walter Becker
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Reinhart Kluge
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katharina Linnartz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leona Plum
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kirsten Giesen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hans-Georg Joost
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

In subgroups of a New Zealand obese mouse-derived backcross population with defined aberrations of glucose homeostasis, a comprehensive study of the hepatic expression of cytochrome P450 and glutathioneS-transferase was performed. Three patterns of alterations in response to insulin resistance (normoglycemia/hyperinsulinemia) or diabetes (hyperglycemia/hypoinsulinemia) were observed: mRNA levels ofCyp2b9, Cyp3a16, Cyp4a14, and Gstt2 as assessed by Northern- and dot-blot analysis were increased markedly in liver from diabetic mice with no or only a slight increase in insulin resistant mice. Western-blot analysis detected the corresponding changes of the CYP2B and CYP4A proteins. In contrast, expression of Cyp2c22, Cyp2c29, and Cyp2c40 was reduced in diabetic, but normal in insulin resistant mice. These alterations were correlated with changes in serum free fatty acid levels and, therefore, seem to be mediated by the peroxisome proliferator activated receptor-α. Furthermore, expression of Cyp1a2, Cyp7b1,Gstm3, and Gstm6 was reduced in both diabetic and insulin resistant mice. Because this third pattern was not correlated with the alterations of serum free fatty acid levels, it seems to reflect an early alteration in the course of the disease, and may be related to the progression of the syndrome from insulin resistance to the type 2-like diabetes.

Footnotes

  • ↵1 Current address: Merck, Sharp and Dohme, Terlings Park, Harlow, Essex, UK.

  • ↵2 Current address: Institute of Laboratory Animal Research, Medical Faculty of the Technical University of Aachen, Aachen, Germany.

  • ↵3 Current address: German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany.

  • This project was supported by the Deutsche Forschungsgemeinschaft Grant FOR 441, Jo117/11-2.

  • DOI: 10.1124/jpet.102.033553

  • Abbreviations:
    NZO
    New Zealand obese
    NSZO
    NZO × F1 (SJL × NZO) backcross population
    P450
    cytochrome P450
    FFA
    free fatty acids
    GST
    glutathione S-transferase
    PPAR
    peroxisome proliferator activated receptor
    BG
    blood glucose
    PI
    plasma insulin
    SSC
    standard saline citrate
    EST
    expressed sequence tags
    SJL
    Swiss Jackson Laboratory
    • Received January 22, 2002.
    • Accepted April 5, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 302 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 302, Issue 2
1 Aug 2002
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Effect of Hyperinsulinemia and Type 2 Diabetes-Like Hyperglycemia on Expression of Hepatic Cytochrome P450 and GlutathioneS-Transferase Isoforms in a New Zealand Obese-Derived Mouse Backcross Population
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Effect of Hyperinsulinemia and Type 2 Diabetes-Like Hyperglycemia on Expression of Hepatic Cytochrome P450 and GlutathioneS-Transferase Isoforms in a New Zealand Obese-Derived Mouse Backcross Population

Georgia J. Pass, Walter Becker, Reinhart Kluge, Katharina Linnartz, Leona Plum, Kirsten Giesen and Hans-Georg Joost
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 442-450; DOI: https://doi.org/10.1124/jpet.102.033553

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Effect of Hyperinsulinemia and Type 2 Diabetes-Like Hyperglycemia on Expression of Hepatic Cytochrome P450 and GlutathioneS-Transferase Isoforms in a New Zealand Obese-Derived Mouse Backcross Population

Georgia J. Pass, Walter Becker, Reinhart Kluge, Katharina Linnartz, Leona Plum, Kirsten Giesen and Hans-Georg Joost
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 442-450; DOI: https://doi.org/10.1124/jpet.102.033553
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Transport Is Not Rate-Limiting in Morphine Glucuronidation in the Single-Pass Perfused Rat Liver Preparation
  • Enhanced Hepatic Uptake and Bioactivity of Type α1(I) Collagen Gene Promoter-Specific Triplex-Forming Oligonucleotides after Conjugation with Cholesterol
  • Characterization of P-glycoprotein Inhibition by Major Cannabinoids from Marijuana
Show more ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics