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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Mechanism of the Insulin-Releasing Action of α-Ketoisocaproate and Related α-Keto Acid Anions

Henrike Heissig, Karin A. Urban, Katja Hastedt, Bernd J. Zünkler and Uwe Panten
Molecular Pharmacology October 2005, 68 (4) 1097-1105; DOI: https://doi.org/10.1124/mol.105.015388
Henrike Heissig
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karin A. Urban
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katja Hastedt
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernd J. Zünkler
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Uwe Panten
  • 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

α-Ketoisocaproate directly inhibits the ATP-sensitive K+ channel (KATP channel) in pancreatic β-cells, but it is unknown whether direct KATP channel inhibition contributes to insulin release by α-ketoisocaproate and related α-keto acid anions, which are generally believed to act via β-cell metabolism. In membranes from HIT-T15 β-cells and COS-1 cells expressing sulfonylurea receptor 1, α-keto acid anions bound to the sulfonylurea receptor site of the KATP channel with affinities increasing in the order α-ketoisovalerate < α-ketovalerate < α-ketoisocaproate < α-ketocaproate < β-phenylpyruvate. Patch-clamp experiments revealed a similar order for the KATP channel-inhibitory potencies of the compounds (applied at the cytoplasmic side of inside-out patches from mouse β-cells). These findings were compared with the insulin secretion stimulated in isolated mouse islets by α-keto acid anions (10 mM). When all KATP channels were closed by the sulfonylurea glipizide, α-keto acid anions amplified the insulin release in the order β-phenylpyruvate < α-ketoisovalerate < α-ketovalerate ≈ α-ketocaproate < α-ketoisocaproate. The differences in amplification apparently reflected special features of the metabolism of the individual α-keto acid anions. In islets with active KATP channels, the first peak of insulin secretion triggered by α-keto acid anions was similar for α-ketoisocaproate, α-ketocaproate, and β-phenylpyruvate but lower for α-ketovalerate and insignificant for α-ketoisovalerate. This difference from the above orders indicates that direct KATP channel inhibition is not involved in the secretory responses to α-ketoisovalerate and α-ketovalerate, moderately contributes to initiation of insulin secretion by α-ketoisocaproate and α-ketocaproate, and is a major component of the insulin-releasing property of β-phenylpyruvate.

  • Received May 31, 2005.
  • Accepted July 12, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm 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

Molecular Pharmacology: 68 (4)
Molecular Pharmacology
Vol. 68, Issue 4
1 Oct 2005
  • 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 Molecular Pharmacology 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.
Mechanism of the Insulin-Releasing Action of α-Ketoisocaproate and Related α-Keto Acid Anions
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Mechanism of the Insulin-Releasing Action of α-Ketoisocaproate and Related α-Keto Acid Anions

Henrike Heissig, Karin A. Urban, Katja Hastedt, Bernd J. Zünkler and Uwe Panten
Molecular Pharmacology October 1, 2005, 68 (4) 1097-1105; DOI: https://doi.org/10.1124/mol.105.015388

Citation Manager Formats

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

Share
Research ArticleArticle

Mechanism of the Insulin-Releasing Action of α-Ketoisocaproate and Related α-Keto Acid Anions

Henrike Heissig, Karin A. Urban, Katja Hastedt, Bernd J. Zünkler and Uwe Panten
Molecular Pharmacology October 1, 2005, 68 (4) 1097-1105; DOI: https://doi.org/10.1124/mol.105.015388
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

  • The binding site for KCI807 in the androgen receptor
  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
Show more Article

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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

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