Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Yamamoto, Junpei; Imai, Junta; Izumi, Tomohito; Takahashi, Hironori; Kawana, Yohei; Takahashi, Kei; Kodama, Shinjiro; Kaneko, Keizo; Gao, Junhong; Uno, Kenji; Sawada, Shojiro; Asano, Tomoichiro; Kalinichenko, Vladimir; Susaki, Etsuo; Kanzaki, Makoto; Ueda, Hiroki; Ishigaki, Yasushi; Yamada, Tetsuya; Katagiri, Hideki
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-01869-7
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract Under insulin-resistant conditions such as obesity, pancreatic β-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 β-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 β-cell FoxM1 pathway and suppresses β-cell expansion. Inducible β-cell-specific FoxM1 deficiency also blocks compensatory β-cell proliferation. In isolated islets, carbachol and PACAP/VIP synergistically promote β-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 β-cells selectively, thereby efficiently promoting β-cell proliferation and maintaining glucose homeostasis during obesity development. This neuronal signal-mediated mechanism holds potential for developing novel approaches to regenerating pancreatic β-cells. Neuronal signals, in particular those transmitted via the vagal nerve, regulate both β-cell function and proliferation. Here, Yamamoto et al. show that the forkhead box M1 pathway is required for vagal signal-mediated induction of β-cell proliferation during obesity.