Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism.
Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism.
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DOI：
10.1038/s41467-017-01869-7
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发表时间：
2017-12-05
影响因子：
16.6
通讯作者：
Katagiri H
中科院分区：
文献类型：
--
作者：
Yamamoto J;Imai J;Izumi T;Takahashi H;Kawana Y;Takahashi K;Kodama S;Kaneko K;Gao J;Uno K;Sawada S;Asano T;Kalinichenko VV;Susaki EA;Kanzaki M;Ueda HR;Ishigaki Y;Yamada T;Katagiri H
在胰岛素抵抗的情况下，如肥胖症，胰腺β细胞增殖以防止血糖升高。肝-脑-胰腺神经元中继在这一过程中起着重要作用。在这里，我们展示了这种代偿性β细胞增殖的分子机制。我们确定FoxM 1激活胰岛神经元继电器刺激小鼠。阻断这一传递（包括迷走神经切断术）可抑制肥胖诱导的β细胞FoxM 1通路活化并抑制β细胞扩增。可诱导的β细胞特异性FoxM 1缺陷也会阻断代偿性β细胞增殖。在分离的胰岛中，卡巴胆碱和PACAP/VIP通过FoxM 1依赖性机制协同促进β细胞增殖。这些发现表明，释放多种神经递质的迷走神经可能允许选择性地同时激活β细胞中的多种途径，从而有效地促进β细胞增殖并维持肥胖发展期间的葡萄糖稳态。这种神经元信号介导的机制具有开发再生胰腺β细胞的新方法的潜力。神经元信号，特别是通过迷走神经传递的那些，调节β细胞功能和增殖。在此，Yamamoto等人表明，肥胖期间迷走神经信号介导的β细胞增殖诱导需要叉头盒M1通路。
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.
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影响因子：
7.7
作者：
Kulkarni RN;Mizrachi EB;Ocana AG;Stewart AF
通讯作者：
Stewart AF
影响因子：
21.3
作者：
Laoukili, J;Kooistra, MRH;Medema, RH
通讯作者：
Medema, RH
影响因子：
3
作者：
Kim, SY;Volsky, DJ
通讯作者：
Volsky, DJ
影响因子：
--
作者：
Filipsson, K;Sundler, F;Ahren, B
通讯作者：
Ahren, B
DOI：
10.1152/ajpendo.00321.2002
发表时间：
2003-01-01
影响因子：
5.1
作者：
Hara, M;Wang, XY;Bell, GI
通讯作者：
Bell, GI