Critical metabolic roles of β-cell M3 muscarinic acetylcholine receptors

LIFE SCIENCES

卷:91

Article; Proceedings Paper

de Azua, Inigo Ruiz¹  Gautam, Dinesh¹  Jain, Shalini¹  Guettier, Jean-Marc¹  Wess, Juergen¹ 

[1] NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA

关键词: Acetylcholine;    Beta cell;    Insulin;    Muscarinic receptor;    Transgenic mice;    Type 2 diabetes;   

DOI  :  10.1016/j.lfs.2012.04.010

来源: Elsevier

【 摘 要 】

Muscarinic acetylcholine (ACh) receptors (mAChRs: M-1-M-5) regulate the activity of an extraordinarily large number of important physiological processes. We and others previously demonstrated that pancreatic beta-cells are endowed with M-3 mAChFts 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 beta-cell mAChRs is released from adjacent alpha-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 beta-cell M-3 receptors, we recently generated and analyzed various mutant mouse models. Specifically, we carded out studies with mice which overexpressed M-3 receptors or mutant M-3 receptors in pancreatic beta-cells or which selectively lacked M-3 receptors or M-3-receptor-associated proteins in pancreatic beta-cells. Our findings indicate that beta-cell M-3 receptors play a key role in maintaining proper insulin release and whole body glucose homeostasis and that strategies aimed at enhancing signaling through beta-cell M-3 receptors may prove useful to improve beta-cell function for the treatment of type 2 diabetes (T2D). Published by Elsevier Inc.

【 授权许可】

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