Binding of Acetylcholine by Muscarinic Acetylcholine Receptor M3 Activation of Gq by Muscarinic Acetylcholine Receptor M3 Dissociation of Gq alpha:GTP Complex from G beta:G gamma Complex Activation of Phospholipase C Beta by Gq alpha Hydrolysis of 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate by Activated Phospholipase C Beta-1 Phosphorylation of MARCKS by Protein kinase C, alpha type Activation of Protein kinase C, alpha type by Diacylglycerol PathwayStep2029 PathwayStep2028 PathwayStep2033 PathwayStep2032 PathwayStep2034 PathwayStep2031 PathwayStep2030 Regulation of Insulin Secretion by Acetylcholine 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).<br>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.<br>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.<br>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. Authored: May, B, 2009-05-28 03:44:04 Edited: May, B, 2009-05-28 03:44:04 Pubmed11588141 Pubmed12161432 Reactome Database ID Release 43399997 Reactome, http://www.reactome.org ReactomeREACT_18405 Reviewed: Gillespie, ME, 2009-06-02 00:56:21