| First Author | Ito Y | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 16180 |
| PubMed ID | 31700039 | Mgi Jnum | J:323513 |
| Mgi Id | MGI:6719761 | Doi | 10.1038/s41598-019-52691-8 |
| Citation | Ito Y, et al. (2019) The beneficial effects of a muscarinic agonist on pancreatic beta-cells. Sci Rep 9(1):16180 |
| abstractText | The brain and nervous system play an important role in pancreatic beta-cell function. This study investigated the role of muscarinic agonists or acetylcholine, which is the major neurotransmitter in the vagal nerve, in regulating pancreatic beta-cell mass and glucose homeostasis. Administration of the muscarinic agonist bethanechol increased insulin secretion and improved glucose tolerance in insulin-receptor substrate 2 (IRS2)-knockout (IRS-2(-/-)) mice and diet-induced obesity mice. Oral administration of bethanechol increased beta-cell mass and proliferation in wild-type mice, but not IRS-2(-/-) mice. The muscarinic agonist also increased the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into islets isolated from wild-type mice and pancreatic beta-cell line MIN6. The phosphorylation of protein kinase B (Akt) induced by oral administration of bethanechol was observed in wild-type mice, but not IRS-2(-/-) mice. The secretion of glucagon-like peptide-1 (GLP-1) was also stimulated by bethanechol in wild-type mice, and a GLP-1 antagonist partially inhibited the bethanechol-induced increase in beta-cell mass. These results suggest that the muscarinic agonist exerted direct and indirect effects on beta-cell proliferation that were dependent on the IRS-2/Akt pathway. The bethanechol-stimulated release of GLP-1 may be indirectly associated with beta-cell proliferation. |
