Toggle navigation
About
What is Reactome ?
News
Team
Scientific Advisory Board
Funding
Editorial Calendar
Release Calendar
Statistics
Our Logo
License Agreement
Privacy Notice
Disclaimer
Digital Preservation
Contact us
Content
Table of Contents
DOIs
Data Schema
Reactome Research Spotlight
ORCID Integration Project
COVID-19 Disease Pathways
Docs
Userguide
Pathway Browser
How do I search ?
Details Panel
Analysis Tools
Analysis Data
Analysis Gene Expression
Species Comparison
Tissue Distribution
Diseases
Cytomics
Review Status of Reactome Events
ReactomeFIViz
Developer's Zone
Graph Database
Analysis Service
Content Service
Pathways Overview
Pathway Diagrams
Icon Info
EHLD Specs & Guidelines
Icon Library Guidelines
Data Model
Curator Guide
Release Documentation
Computationally inferred events
FAQ
Linking to Us
Citing us
Tools
Pathway Browser
Analyse gene list
Analyse gene expression
Species Comparison
Tissue Distribution
Analysis Service
Content Service
ReactomeFIViz
Advanced Data Search
Site Search
Community
Contribute Pathway Knowledge
Icon Library
Outreach
Events
Publications
Partners
Contributors
Resources Guide
Download
About
What is Reactome ?
News
Team
Scientific Advisory Board
Funding
Editorial Calendar
Release Calendar
Statistics
Our Logo
License Agreement
Privacy Notice
Disclaimer
Digital Preservation
Contact us
Content
Table of Contents
DOIs
Data Schema
Reactome Research Spotlight
ORCID Integration Project
COVID-19 Disease Pathways
Docs
Userguide
Pathway Browser
How do I search ?
Details Panel
Analysis Tools
Analysis Data
Analysis Gene Expression
Species Comparison
Tissue Distribution
Diseases
Cytomics
Review Status of Reactome Events
ReactomeFIViz
Developer's Zone
Graph Database
Analysis Service
Content Service
Pathways Overview
Pathway Diagrams
Icon Info
EHLD Specs & Guidelines
Icon Library Guidelines
Data Model
Curator Guide
Release Documentation
Computationally inferred events
FAQ
Linking to Us
Citing us
Tools
Pathway Browser
Analyse gene list
Analyse gene expression
Species Comparison
Tissue Distribution
Analysis Service
Content Service
ReactomeFIViz
Advanced Data Search
Site Search
Community
Contribute Pathway Knowledge
Icon Library
Outreach
Events
Publications
Partners
Contributors
Resources Guide
Download
Search ...
Go!
Acetylcholine regulates insulin secretion
Stable Identifier
R-HSA-399997
DOI
10.3180/R-HSA-399997.5
Type
Pathway
Species
Homo sapiens
Compartment
plasma membrane
,
cytosol
,
endoplasmic reticulum membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
Metabolism (Homo sapiens)
Integration of energy metabolism (Homo sapiens)
Regulation of insulin secretion (Homo sapiens)
Acetylcholine regulates insulin secretion (Homo sapiens)
General
SBML
|
BioPAX
Level 2
Level 3
|
PDF
SVG
|
PNG
Low
Medium
High
|
PPTX
|
SBGN
Click the image above or
here
to open this pathway in the Pathway Browser
Acetylcholine released by parasympathetic nerve endings in the pancreas causes a potentiation of insulin release when glucose is present at concentrations greater than about 7 mM. Acetylcholine binds the Muscarinic Acetylcholine Receptor M3 on pancreatic beta cells. The binding has two effects: an increase in permeability of the cell to Na+ ions through an unknown mechanism, and the activation of Phospholipase C beta-1 through a heterotrimeric G protein, G(q).
After acetylcholine binds the Muscarinic Acetycholine Receptor M3, the receptor activates the G protein Gq by causing the alpha subunit of Gq to exchange GDP for GTP. Activation of Gq in turn activates Phospholipase C beta-1. Phospholipase C beta-1 hydrolyzes the phosphodiester bond at the third position of phosphoinositol 4,5-bisphosphate, producing diacylglycerols (DAG) and inositol 1,4,5-trisphosphate.
DAG remains in the cell membrane and causes Protein Kinase C alpha (PKC alpha) to translocate from the cytosol to the membrane. This results in the activation of PKC alpha which then phosphorylates target proteins on serine and threonine residues. One known target of PKC alpha is Myristoylated Alanine-rich C Kinase Substrate (MARCKS), which is believed to affect vesicle transport and may be responsible for the increased traffic of insulin granules seen in response to acetylcholine.
Inositol trisphophate binds a receptor, the IP3 receptor, on calcium stores in the cell (probably the endoplasmic reticulum). The release of calcium into the cytosol stimulates the exocytosis of insulin granules.
Literature References
PubMed ID
Title
Journal
Year
12161432
G protein-independent activation of an inward Na(+) current by muscarinic receptors in mouse pancreatic beta-cells
Gilon, P
,
Rolland, JF
,
Henquin, JC
J Biol Chem
2002
11588141
Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function
Gilon, P
,
Henquin, JC
Endocr Rev
2001
Participants
Events
Acetylcholine binds Muscarinic Acetylcholine Receptor M3
(Homo sapiens)
Muscarinic Acetylcholine Receptor M3 activates Gq
(Homo sapiens)
Gq alpha:G beta:G gamma dissociates to Gq alpha:GTP and G beta:G gamma
(Homo sapiens)
Gq alpha activates Phospholipase C beta
(Homo sapiens)
Activated Phospholipase C beta-1 hydrolyzes 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
(Homo sapiens)
Diacylgycerol activates Protein kinase C, alpha type
(Homo sapiens)
Protein kinase C, alpha type phosphorylates MARCKS
(Homo sapiens)
Participates
as an event of
Regulation of insulin secretion (Homo sapiens)
Event Information
Go Biological Process
positive regulation of insulin secretion (0032024)
Orthologous Events
Acetylcholine regulates insulin secretion (Bos taurus)
Acetylcholine regulates insulin secretion (Caenorhabditis elegans)
Acetylcholine regulates insulin secretion (Canis familiaris)
Acetylcholine regulates insulin secretion (Dictyostelium discoideum)
Acetylcholine regulates insulin secretion (Drosophila melanogaster)
Acetylcholine regulates insulin secretion (Gallus gallus)
Acetylcholine regulates insulin secretion (Mus musculus)
Acetylcholine regulates insulin secretion (Rattus norvegicus)
Acetylcholine regulates insulin secretion (Saccharomyces cerevisiae)
Acetylcholine regulates insulin secretion (Schizosaccharomyces pombe)
Acetylcholine regulates insulin secretion (Sus scrofa)
Cross References
BioModels Database
BIOMD0000000088
Authored
May, B (2009-05-28)
Reviewed
Gillespie, ME (2009-06-02)
Created
May, B (2009-03-24)
© 2025
Reactome
Cite Us!
Cite Us!
Cite Us!
Warning!
Unable to extract citation. Please try again later.
Download As:
BibTeX
RIS
Text