Insulin regulates POMC neuronal plasticity to control glucose metabolism

作者：Garron T. Dodd, Natalie J. Michael, Robert S. Lee, Salvatore Mangiafico, Jack T. Pryor, Astrid C Munder, Stephanie E. Simonds, Jens C. Brüning, Zhong‐Yin Zhang, Michael A. Cowley, Sofianos Andrikopoulos, Tamás L. Horváth, David Spanswick, Tony Tiganis · 发表于：eLife · 年份：2018 · DOI：10.7554/elife.38704 · 被引用次数：119 · 研究领域：Regulation of Appetite and Obesity、Pancreatic function and diabetes、Adipose Tissue and Metabolism

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.