Premium
Role of the M 3 muscarinic acetylcholine receptor in β‐cell function and glucose homeostasis
Author(s) -
Gautam D.,
Han S.J.,
Duttaroy A.,
Mears D.,
Hamdan F. F.,
Li J. H.,
Cui Y.,
Jeon J.,
Wess J.
Publication year - 2007
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2007.00781.x
Subject(s) - medicine , endocrinology , muscarinic acetylcholine receptor , glucose homeostasis , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m4 , insulin , muscarinic acetylcholine receptor m1 , biology , beta cell , acetylcholine , receptor , chemistry , insulin resistance , islet
The release of insufficient amounts of insulin in the presence of elevated blood glucose levels is one of the key features of type 2 diabetes. Various lines of evidence indicate that acetylcholine (ACh), the major neurotransmitter of the parasympathetic nervous system, can enhance glucose‐stimulated insulin secretion from pancreatic β‐cells. Studies with isolated islets prepared from whole body M 3 muscarinic ACh receptor knockout mice showed that cholinergic amplification of glucose‐dependent insulin secretion is exclusively mediated by the M 3 muscarinic receptor subtype. To investigate the physiological relevance of this muscarinic pathway, we used Cre/loxP technology to generate mutant mice that lack M 3 receptors only in pancreatic β‐cells. These mutant mice displayed impaired glucose tolerance and significantly reduced insulin secretion. In contrast, transgenic mice overexpressing M 3 receptors in pancreatic β‐cells showed a pronounced increase in glucose tolerance and insulin secretion and were resistant to diet‐induced glucose intolerance and hyperglycaemia. These findings indicate that β‐cell M 3 muscarinic receptors are essential for maintaining proper insulin secretion and glucose homeostasis. Moreover, our data suggest that enhancing signalling through β‐cell M 3 muscarinic receptors may represent a new avenue in the treatment of glucose intolerance and type 2 diabetes.