Abstract：
:One of the hallmarks of type 2 diabetes is that pancreatic beta 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 beta cells remains unclear at present. Here, we demonstrate that mutant mice selectively lacking the M3 muscarinic acetylcholine receptor subtype in pancreatic beta cells display impaired glucose tolerance and greatly reduced insulin release. In contrast, transgenic mice selectively overexpressing M3 receptors in pancreatic beta 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 beta cell M3 muscarinic receptors play a key role in maintaining proper insulin release and glucose homeostasis.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Gautam D,Han SJ,Hamdan FF,Jeon J,Li B,Li JH,Cui Y,Mears D,Lu H,Deng C,Heard T,Wess Jdoi
10.1016/j.cmet.2006.04.009subject
Has Abstractpub_date
2006-06-01 00:00:00pages
449-61issue
6eissn
1550-4131issn
1932-7420pii
S1550-4131(06)00128-8journal_volume
3pub_type
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