Metabolic Roles of the M3 Muscarinic Acetylcholine Receptor Studied with M3 Receptor Mutant Mice: A Review

The M3 muscarinic acetylcholine (ACh) receptor (M3 mAChR) is expressed in many central and peripheral tissues. It is a prototypic member of the superfamily of G protein-coupled receptors and preferentially activates G proteins of the Gq family. Recent studies involving the use of newly generated mAChR mutant mice have revealed that the M3 mAChR plays a key role in regulating many important metabolic functions. Phenotypic analyses of mutant mice that either selectively lacked or overexpressed M3 receptors in pancreatic β -cells indicated that β -cell M3 mAChRs are essential for maintaining proper insulin release and glucose homeostasis. The experimental data also suggested that strategies aimed at enhancing signaling through β -cell M3 mAChRs might be beneficial for the treatment of type 2 diabetes. Recent studies with whole body M3 mAChR knockout mice showed that the absence of M3 receptors protected mice against various forms of experimentally or genetically induced obesity and obesity-associated metabol...