Insulin regulates POMC neuronal plasticity to control glucose metabolism

Garron T. Dodd, Natalie J. Michael, Robert S. Lee-Young, Salvatore P. Mangiafico, Jack T. Pryor, Astrid C. Munder, Stephanie E. Simonds, Jens Claus Brüning, Zhong Yin Zhang, Michael A. Cowley, Sofianos Andrikopoulos, Tamas L. Horvath, David Spanswick, Tony Tiganis

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere38704
JournaleLife
Volume7
DOIs
StatePublished - Sep 2018
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Dodd, G. T., Michael, N. J., Lee-Young, R. S., Mangiafico, S. P., Pryor, J. T., Munder, A. C., Simonds, S. E., Brüning, J. C., Zhang, Z. Y., Cowley, M. A., Andrikopoulos, S., Horvath, T. L., Spanswick, D., & Tiganis, T. (2018). Insulin regulates POMC neuronal plasticity to control glucose metabolism. eLife, 7, [e38704]. https://doi.org/10.7554/eLife.38704