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
  • Log out
  • 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
  • Log out
  • 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 Diabetes

Ranolazine Increases β-Cell Survival and Improves Glucose Homeostasis in Low-Dose Streptozotocin-Induced Diabetes in Mice

Yun Ning, Wei Zhen, Zhuo Fu, Jenny Jiang, Dongmin Liu, Luiz Belardinelli and Arvinder K. Dhalla
Journal of Pharmacology and Experimental Therapeutics April 2011, 337 (1) 50-58; DOI: https://doi.org/10.1124/jpet.110.176396
Yun Ning
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Zhen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhuo Fu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jenny Jiang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dongmin Liu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luiz Belardinelli
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arvinder K. Dhalla
  • 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 addition to its anti-ischemic and antianginal effects, ranolazine has been shown to lower hemoglobin A1c (HbA1c) in patients with coronary artery disease and diabetes. The present study was undertaken to test the hypothesis that ranolazine lowers HbA1c because of improved glucose homeostasis in an animal model. Diabetes in mice was induced by giving multiple low doses of streptozotocin. Ranolazine was given twice daily via an oral gavage (20 mg/kg) for 8 weeks. Fasting plasma glucose levels were significantly lower in the ranolazine-treated group (187 ± 19 mg/dl) compared with the vehicle group (273 ± 23 mg/dl) at 8 weeks. HbA1c was 5.8 ± 0.4% in the vehicle group and 4.5 ± 0.2% in the ranolazine-treated group (p < 0.05). Glucose disposal during the oral glucose tolerance test (OGTT) and insulin tolerance test were not different between the two groups; however, during OGTT, peak insulin levels were significantly (p < 0.05) higher in ranolazine-treated mice. Mice treated with ranolazine had healthier islet morphology and significantly (p < 0.01) higher β-cell mass (69 ± 2% per islet) than the vehicle group (50 ± 5% per islet) as determined from hematoxylin and eosin staining. The number of apoptotic cells was significantly (p < 0.05) less in the pancreas of the ranolazine-treated group (14 ± 2% per islet) compared with the vehicle group (24 ± 4% per islet). In addition, ranolazine increased glucose-stimulated insulin secretion in rat and human islets in a glucose-dependent manner. These data suggest that ranolazine may be a novel antidiabetic agent that causes β-cell preservation and enhances insulin secretion in a glucose-dependent manner in diabetic mice.

Footnotes

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.110.176396.

  • ABBREVIATIONS:

    CAD
    coronary artery disease
    HbA1c
    hemoglobin A1c
    FPG
    fasting plasma glucose
    OGTT
    oral glucose tolerance test
    PBS
    phosphate-buffered saline
    H&E
    hematoxylin and eosin
    GSIS
    glucose-stimulated insulin secretion
    FITC
    fluorescein isothiocyanate
    KRB
    Krebs-Ringer-bicarbonate
    GLP-1
    glucagon-like peptide-1.

  • Received October 22, 2010.
  • Accepted January 10, 2011.
  • Copyright © 2011 by 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 387 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 387, Issue 1
1 Oct 2023
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
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.
Ranolazine Increases β-Cell Survival and Improves Glucose Homeostasis in Low-Dose Streptozotocin-Induced Diabetes in 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 Diabetes

Ranolazine Increases β-Cell Survival and Improves Glucose Homeostasis in Low-Dose Streptozotocin-Induced Diabetes in Mice

Yun Ning, Wei Zhen, Zhuo Fu, Jenny Jiang, Dongmin Liu, Luiz Belardinelli and Arvinder K. Dhalla
Journal of Pharmacology and Experimental Therapeutics April 1, 2011, 337 (1) 50-58; DOI: https://doi.org/10.1124/jpet.110.176396

Citation Manager Formats

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

Share
Research ArticleEndocrine and Diabetes

Ranolazine Increases β-Cell Survival and Improves Glucose Homeostasis in Low-Dose Streptozotocin-Induced Diabetes in Mice

Yun Ning, Wei Zhen, Zhuo Fu, Jenny Jiang, Dongmin Liu, Luiz Belardinelli and Arvinder K. Dhalla
Journal of Pharmacology and Experimental Therapeutics April 1, 2011, 337 (1) 50-58; DOI: https://doi.org/10.1124/jpet.110.176396
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Nrp-1 Antagonist Enhances Revascularization in OIR Mice
  • Insulin Inhibits Ubiquitination via USP14
  • Characterization of a Novel Weekly Basal Insulin
Show more Endocrine and Diabetes

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