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 ArticleENDOCRINE AND REPRODUCTIVE

Overexpression of Pituitary Adenylate Cyclase-Activating Polypeptide in Islets Inhibits Hyperinsulinemia and Islet Hyperplasia in Agouti Yellow Mice

Shuhei Tomimoto, Hitoshi Hashimoto, Norihito Shintani, Kyohei Yamamoto, Yuki Kawabata, Ken-Ichi Hamagami, Kazuya Yamagata, Jun-Ichiro Miyagawa and Akemichi Baba
Journal of Pharmacology and Experimental Therapeutics May 2004, 309 (2) 796-803; DOI: https://doi.org/10.1124/jpet.103.062919
Shuhei Tomimoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hitoshi Hashimoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Norihito Shintani
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyohei Yamamoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuki Kawabata
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ken-Ichi Hamagami
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuya Yamagata
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jun-Ichiro Miyagawa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akemichi Baba
  • 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

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an intraislet neuropeptide and shares insulinotropic and insulin-sensitizing properties with glucagon-like peptide-1 (GLP-1); however, the pathophysiological significance of PACAP in diabetes remains largely unknown. To assess this, we crossed our recently developed transgenic mice overexpressing PACAP in pancreatic β-cells (Tg/+), with lethal yellow agouti (KKAy) mice (Ay/+), a genetic model for obesity-diabetes, and examined the metabolic and morphological phenotypes of F1 animals. Tg/+ mice with the Ay allele (Tg/+:Ay/+) developed maturity-onset obesity and diabetes associated with hyperglycemia, hyperlipidemia, and hyperphagia, similar to those of Ay/+ mice, but hyperinsulinemia was significantly ameliorated in Tg/+:Ay/+ mice. Although Ay/+ mice exhibited a marked increase in islet mass resulting from hyperplasia and hypertrophy, this increase was significantly attenuated in Tg/+:Ay/+ mice. Size frequency distribution analysis revealed that the very large islets comprising one-fourth of islets of Ay/+ mice were selectively reduced in Tg/+:Ay/+ mice. Because functional defects have been demonstrated in the large islets of obese animal models, together these findings suggest that PACAP regulates hyperinsulinemia and the abnormal increase in islet mass that occurs during the diabetic process.

Footnotes

  • This research was supported, in part, by a Grant-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Grants-in-Aid for Scientific Research (A) and (B) from Japan Society for the Promotion of Science, and by grants from Taisho Pharmaceutical Co. Ltd., AstraZeneca, and The Naito Foundation.

  • DOI: 10.1124/jpet.103.062919.

  • ABBREVIATIONS: PACAP, pituitary adenylate cyclase-activating polypeptide; GLP-1, glucagon-like peptide-1; Tg/+ mice, transgenic mice overexpressing PACAP in pancreatic β-cells; Ay/+ mice, lethal yellow agouti (KKAy) mice; RIA, radioimmunoassay; PBS, phosphate-buffered saline; ANOVA, analysis of variance.

    • Received November 12, 2003.
    • Accepted January 21, 2004.
  • 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: 309 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 309, Issue 2
1 May 2004
  • Table of Contents
  • About the Cover
  • 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.
Overexpression of Pituitary Adenylate Cyclase-Activating Polypeptide in Islets Inhibits Hyperinsulinemia and Islet Hyperplasia in Agouti Yellow Mice
(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 ArticleENDOCRINE AND REPRODUCTIVE

Overexpression of Pituitary Adenylate Cyclase-Activating Polypeptide in Islets Inhibits Hyperinsulinemia and Islet Hyperplasia in Agouti Yellow Mice

Shuhei Tomimoto, Hitoshi Hashimoto, Norihito Shintani, Kyohei Yamamoto, Yuki Kawabata, Ken-Ichi Hamagami, Kazuya Yamagata, Jun-Ichiro Miyagawa and Akemichi Baba
Journal of Pharmacology and Experimental Therapeutics May 1, 2004, 309 (2) 796-803; DOI: https://doi.org/10.1124/jpet.103.062919

Citation Manager Formats

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

Share
Research ArticleENDOCRINE AND REPRODUCTIVE

Overexpression of Pituitary Adenylate Cyclase-Activating Polypeptide in Islets Inhibits Hyperinsulinemia and Islet Hyperplasia in Agouti Yellow Mice

Shuhei Tomimoto, Hitoshi Hashimoto, Norihito Shintani, Kyohei Yamamoto, Yuki Kawabata, Ken-Ichi Hamagami, Kazuya Yamagata, Jun-Ichiro Miyagawa and Akemichi Baba
Journal of Pharmacology and Experimental Therapeutics May 1, 2004, 309 (2) 796-803; DOI: https://doi.org/10.1124/jpet.103.062919
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

  • Role of Protein Kinase C-Ras-MAPK p44/42 in Ethanol and Transforming Growth Factor-β3-Induced Basic Fibroblast Growth Factor Release from Folliculostellate Cells
  • Therapeutic Actions of an Insulin Receptor Activator and a Novel Peroxisome Proliferator-Activated Receptor γ Agonist in the Spontaneously Hypertensive Obese Rat Model of Metabolic Syndrome X
  • Hepatic Glucocorticoid Receptor Antagonism Is Sufficient to Reduce Elevated Hepatic Glucose Output and Improve Glucose Control in Animal Models of Type 2 Diabetes
Show more ENDOCRINE AND REPRODUCTIVE

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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics