Insulin regulates POMC neuronal plasticity to control glucose metabolism.
Insulin regulates POMC neuronal plasticity to control glucose metabolism.
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DOI：
10.7554/elife.38704
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发表时间：
2018-09-19
期刊：
影响因子：
7.7
通讯作者：
Tiganis T
中科院分区：
文献类型：
--
作者：
Dodd GT;Michael NJ;Lee-Young RS;Mangiafico SP;Pryor JT;Munder AC;Simonds SE;Brüning JC;Zhang ZY;Cowley MA;Andrikopoulos S;Horvath TL;Spanswick D;Tiganis T
下丘脑神经元通过改变基因表达和神经元兴奋性对营养信号做出反应。控制这种适应性过程的机制仍不清楚。在这里，我们定义了小鼠中被胰岛素激活或抑制的 POMC 神经元群体，从而抑制或抑制肝葡萄糖生成 (HGP)。被胰岛素激活的 POMC 神经元的比例取决于磷酸酶 TCPTP 对胰岛素受体信号传导的调节，该磷酸酶 TCPTP 会因禁食而增加，在进食后会降解，在饮食引起的肥胖中会升高。 TCPTP 缺陷增强了胰岛素信号传导以及被胰岛素激活以抑制 HGP 的 POMC 神经元的比例。肥胖和/或禁食后 POMC 神经元中 TCPTP 升高会抑制胰岛素信号传导、胰岛素对 POMC 神经元的激活以及胰岛素诱导和 POMC 介导的 HGP 抑制。我们的研究结果定义了一种将 POMC 神经反应与进食相结合以控制葡萄糖代谢的分子机制。
Hypothalamic neurons respond to nutritional cues by altering gene expression and neuronal excitability. The mechanisms that control such adaptive processes remain unclear. Here we define populations of POMC neurons in mice that are activated or inhibited by insulin and thereby repress or inhibit hepatic glucose production (HGP). The proportion of POMC neurons activated by insulin was dependent on the regulation of insulin receptor signaling by the phosphatase TCPTP, which is increased by fasting, degraded after feeding and elevated in diet-induced obesity. TCPTP-deficiency enhanced insulin signaling and the proportion of POMC neurons activated by insulin to repress HGP. Elevated TCPTP in POMC neurons in obesity and/or after fasting repressed insulin signaling, the activation of POMC neurons by insulin and the insulin-induced and POMC-mediated repression of HGP. Our findings define a molecular mechanism for integrating POMC neural responses with feeding to control glucose metabolism.