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- Title
Role of the M<sub>3</sub> muscarinic acetylcholine receptor in β-cell function and glucose homeostasis.
- Authors
Gautam, D.; Han, S.-J.; Duttaroy, A.; Mears, D.; Hamdan, F. F.; Li, J. H.; Cui, Y.; Jeon, J.; Wess, J.
- Abstract
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 M3 muscarinic ACh receptor knockout mice showed that cholinergic amplification of glucose-dependent insulin secretion is exclusively mediated by the M3 muscarinic receptor subtype. To investigate the physiological relevance of this muscarinic pathway, we used Cre/loxP technology to generate mutant mice that lack M3 receptors only in pancreatic β-cells. These mutant mice displayed impaired glucose tolerance and significantly reduced insulin secretion. In contrast, transgenic mice overexpressing M3 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 M3 muscarinic receptors are essential for maintaining proper insulin secretion and glucose homeostasis. Moreover, our data suggest that enhancing signalling through β-cell M3 muscarinic receptors may represent a new avenue in the treatment of glucose intolerance and type 2 diabetes.
- Subjects
ACETYLCHOLINE; PANCREATIC beta cells; CELL physiology; GLUCOSE; TRANSGENIC mice; TYPE 2 diabetes
- Publication
Diabetes, Obesity & Metabolism, 2007, Vol 9, p158
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/j.1463-1326.2007.00781.x