期刊
LIFE SCIENCES
卷 91, 期 21-22, 页码 986-991出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2012.04.010
关键词
Acetylcholine; Beta cell; Insulin; Muscarinic receptor; Transgenic mice; Type 2 diabetes
资金
- Intramural NIH HHS [Z01 DK031132-02, Z01 DK031132-01] Funding Source: Medline
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.
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