Skip to main content
Home

Navigation controls

  • Search
  • Menu
September 9 – 12, 2025 | NIH Main Bethesda, Campus

Social

  • Twitter
  • Facebook
  • Email

Current Research Festival

  • 2025
  • 2024
    • General Schedule of Events
    • 2024 NIH Distinguished Scholars Program
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • National Academy of Science Mini-Symposium
    • Special Wednesday Events
    • Vendor Exhibit Information
    • Green Labs Fair
    • Research Festival Committee
  • 2023
    • General Schedule of Events
    • NIH Early–Career Investigator Lectures
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • Vendor Exhibit Information
    • Research Festival Committee
  • 2021
  • 2019
    • General Schedule of Events
    • Plenary Sessions
    • Poster Session
    • Data Blitz
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committee
  • 2018
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2017
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2016
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Tours of the National Library of Medicine and Clinical Center
    • Research Festival Committees
  • 2015
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Workshop Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • TSA Research Festival Exhibit Show
    • NIH Tours
    • Research Festival Committees
  • 2014
  • 2013
  • 2012
  • 2011
  • 2010
  • 2009
  • 2008
  • 2007
  • 2006
  • 2005
  • 2004
  • 2003
  • 2002
  • 2001
  • 2000

Main navigation

  • All Research Festivals
    • 2025
    • 2024
    • 2023
    • 2021
    • 2019
    • 2018
    • 2017
    • 2016
    • 2015
    • 2014
    • 2013
    • 2012
    • 2011
    • 2010
    • 2009
    • 2008
    • 2007
    • 2006
    • 2005
    • 2004
    • 2003
    • 2002
    • 2001
    • 2000

NIH Research Festival

September 12 – 14, 2018

A positive allosteric modulator that promotes insulin secretion in mice by selectively enhancing M3 muscarinic receptor signaling in beta-cells

Thursday, September 13, 2018 – Poster Session IV
3:30 – 5:00 p.m.

FAES Terrace

NIDDK

PHARM-7

Authors

  • Lu Zhu
  • M Rossi
  • A Cohen
  • H Zheng
  • JL Langel
  • S Hattar
  • D Apella
  • NM Doliba
  • J Wess

Abstract

The inability of pancreatic beta-cells to secrete sufficient amounts of insulin is a key feature of type 2 diabetes. We previously showed that acetylcholine (ACh)-dependent activation of beta-cell M3 muscarinic receptors (M3Rs) strongly enhances glucose-stimulated insulin release. ACh and other classical muscarinic receptor agonists bind to the so-called orthosteric site on muscarinic receptors that is highly conserved among the five muscarinic receptor subtypes (M1-M5Rs). To more selectively enhance signaling through the M3R, we studied a positive allosteric modulator (PAM) that is known to enhance ACh-mediated activation of M3Rs in vitro (VU0119498). The potential therapeutic use of allosteric modulators has the advantage that such agents preserve the temporal-spatial pattern of endogenous M3R signaling. We initially demonstrated that VU0119498 greatly enhanced ACh-induced insulin secretion in cultured MIN6 cells and isolated mouse pancreatic islets. We obtained similar findings with isolated human islets. Acute treatment of mice with VU0119498 resulted in significant increases in plasma insulin levels, associated with improved glucose tolerance. This effect was observed independent of the diet on which the mice were maintained (regular chow vs. high fat diet). Importantly, the beneficial metabolic effects caused by VU0119498 treatment were absent in mice that selectively lacked M3Rs in pancreatic beta-cells. Administration of VU0119498 had no or little effect on other M3R-mediated physiological functions including regulation of pupil size and salivary secretion. Taken together, these data strongly suggest that selective M3R-PAMs may prove useful as novel antidiabetic drugs.

Scientific Focus Area: Molecular Pharmacology

This page was last updated on Friday, March 26, 2021

  • General Schedule of Events
  • Plenary Sessions
  • Concurrent Symposia Sessions
  • Poster Sessions
  • FARE Award Ceremony
  • Special Exhibits on Resources for Intramural Research
  • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
  • Research Festival Committees

2018 program

Download the 2018 Research Festival Schedule Overview (6 pages)

  • Email
  • Print
  • Share Twitter Facebook LinkedIn

Current Research Festival

  • 2025
  • 2024
    • General Schedule of Events
    • 2024 NIH Distinguished Scholars Program
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • National Academy of Science Mini-Symposium
    • Special Wednesday Events
    • Vendor Exhibit Information
    • Green Labs Fair
    • Research Festival Committee
  • 2023
    • General Schedule of Events
    • NIH Early–Career Investigator Lectures
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • Vendor Exhibit Information
    • Research Festival Committee
  • 2021
  • 2019
    • General Schedule of Events
    • Plenary Sessions
    • Poster Session
    • Data Blitz
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committee
  • 2018
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2017
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2016
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Tours of the National Library of Medicine and Clinical Center
    • Research Festival Committees
  • 2015
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Workshop Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • TSA Research Festival Exhibit Show
    • NIH Tours
    • Research Festival Committees
  • 2014
  • 2013
  • 2012
  • 2011
  • 2010
  • 2009
  • 2008
  • 2007
  • 2006
  • 2005
  • 2004
  • 2003
  • 2002
  • 2001
  • 2000

Main navigation

  • All Research Festivals
    • 2025
    • 2024
    • 2023
    • 2021
    • 2019
    • 2018
    • 2017
    • 2016
    • 2015
    • 2014
    • 2013
    • 2012
    • 2011
    • 2010
    • 2009
    • 2008
    • 2007
    • 2006
    • 2005
    • 2004
    • 2003
    • 2002
    • 2001
    • 2000
  • Department of Health and Human Services
  • National Institutes of Health
  • USA.gov

Footer

  • Home
  • Contact Us
  • IRP
  • HHS Vulnerability Disclosure
  • Web Policies and Notices
  • Site Map
  • Search