Critical metabolic roles of ¦Â-cell M₃ muscarinic acetylcholine receptors

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• 作者：Inigo Ruiz de Azua ; Dinesh Gautam ; Shalini Jain ; Jean-Marc Guettier ; Jü ; rgen Wess ; ^{jwess@helix.nih.gov}
• 关键词：Acetylcholine ; Beta cell ; Insulin ; Muscarinic receptor ; Transgenic mice ; Type 2 diabetes
• 刊名：Life Sciences
• 出版年：2012
• 出版时间：27 November, 2012
• 年：2012
• 卷：91
• 期：21-22
• 页码：986-991
• 全文大小：481 K

文摘

Muscarinic acetylcholine (ACh) receptors (mAChRs; M₁-M₅) regulate the activity of an extraordinarily large number of important physiological processes. We and others previously demonstrated that pancreatic ¦Â-cells are endowed with M₃ mAChRs which are linked to G proteins of the G_q family. The activation of these receptors by ACh or other muscarinic agonists leads to the augmentation of glucose-induced insulin release via multiple mechanisms. Interestingly, in humans, ACh acting on human ¦Â-cell mAChRs is released from adjacent ¦Á-cells which express both choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (vAChT), indicative of the presence of a non-neuronal cholinergic system in human pancreatic islets. In order to shed light on the physiological roles of ¦Â-cell M₃ receptors, we recently generated and analyzed various mutant mouse models. Specifically, we carried out studies with mice which overexpressed M₃ receptors or mutant M₃ receptors in pancreatic ¦Â-cells or which selectively lacked M₃ receptors or M₃-receptor-associated proteins in pancreatic ¦Â-cells. Our findings indicate that ¦Â-cell M₃ receptors play a key role in maintaining proper insulin release and whole body glucose homeostasis and that strategies aimed at enhancing signaling through ¦Â-cell M₃ receptors may prove useful to improve ¦Â-cell function for the treatment of type 2 diabetes (T2D).