| First Author | Yamamoto J | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 1930 |
| PubMed ID | 29208957 | Mgi Jnum | J:257771 |
| Mgi Id | MGI:6112555 | Doi | 10.1038/s41467-017-01869-7 |
| Citation | Yamamoto J, et al. (2017) Neuronal signals regulate obesity induced beta-cell proliferation by FoxM1 dependent mechanism. Nat Commun 8(1):1930 |
| abstractText | Under insulin-resistant conditions such as obesity, pancreatic beta-cells proliferate to prevent blood glucose elevations. A liver-brain-pancreas neuronal relay plays an important role in this process. Here, we show the molecular mechanism underlying this compensatory beta-cell proliferation. We identify FoxM1 activation in islets from neuronal relay-stimulated mice. Blockade of this relay, including vagotomy, inhibits obesity-induced activation of the beta-cell FoxM1 pathway and suppresses beta-cell expansion. Inducible beta-cell-specific FoxM1 deficiency also blocks compensatory beta-cell proliferation. In isolated islets, carbachol and PACAP/VIP synergistically promote beta-cell proliferation through a FoxM1-dependent mechanism. These findings indicate that vagal nerves that release several neurotransmitters may allow simultaneous activation of multiple pathways in beta-cells selectively, thereby efficiently promoting beta-cell proliferation and maintaining glucose homeostasis during obesity development. This neuronal signal-mediated mechanism holds potential for developing novel approaches to regenerating pancreatic beta-cells. |
