Cell Metabolism
Volume 3, Issue 6, June 2006, Pages 449-461
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Article
A critical role for β cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo

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Summary

One of the hallmarks of type 2 diabetes is that pancreatic β cells fail to release sufficient amounts of insulin in the presence of elevated blood glucose levels. Insulin secretion is modulated by many hormones and neurotransmitters including acetylcholine, the major neurotransmitter of the peripheral parasympathetic nervous system. The physiological role of muscarinic acetylcholine receptors expressed by pancreatic β cells remains unclear at present. Here, we demonstrate that mutant mice selectively lacking the M3 muscarinic acetylcholine receptor subtype in pancreatic β cells display impaired glucose tolerance and greatly reduced insulin release. In contrast, transgenic mice selectively overexpressing M3 receptors in pancreatic β cells show a profound increase in glucose tolerance and insulin release. Moreover, these mutant mice are resistant to diet-induced glucose intolerance and hyperglycemia. These findings indicate that β cell M3 muscarinic receptors play a key role in maintaining proper insulin release and glucose homeostasis.

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5

Present address: Innate Immunology Laboratory, Institut Pasteur Korea, Seoul 136-791, Korea

6

Present address: Département de Biochimie, Université de Montréal, Montréal, QC, H3T 1J4, Canada

7

Present address: Instituto de Ciencias Biomédicas, Faculty of Medicine, University of Chile, Santiago, Chile