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

10 Citations (Scopus)

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)
JournaleLife
Volume7
DOIs
StatePublished - Sep 19 2018
Externally publishedYes

Fingerprint

Pro-Opiomelanocortin
Neuronal Plasticity
Metabolism
Plasticity
Neurons
Insulin
Glucose
Liver
Fasting
Obesity
Insulin Receptor
Nutrition
Phosphoric Monoester Hydrolases
Gene expression
Cues
Chemical activation
Diet
Gene Expression
Population

Keywords

  • cellular signalling
  • glucose metabolism
  • human biology
  • hypothalamus
  • insulin
  • medicine
  • mouse
  • neuroscience
  • POMC neurons
  • protein tyrosine phosphatase

ASJC Scopus subject areas

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

Cite this

Dodd, G. T., Michael, N. J., Lee-Young, R. S., Mangiafico, S. P., Pryor, J. T., Munder, A. C., ... Tiganis, T. (2018). Insulin regulates POMC neuronal plasticity to control glucose metabolism. eLife, 7. https://doi.org/10.7554/eLife.38704

Insulin regulates POMC neuronal plasticity to control glucose metabolism. / Dodd, Garron T.; Michael, Natalie J.; Lee-Young, Robert S.; Mangiafico, Salvatore P.; Pryor, Jack T.; Munder, Astrid C.; Simonds, Stephanie E.; Brüning, Jens Claus; Zhang, Zhong-Yin; Cowley, Michael A.; Andrikopoulos, Sofianos; Horvath, Tamas L.; Spanswick, David; Tiganis, Tony.

In: eLife, Vol. 7, 19.09.2018.

Research output: Contribution to journalArticle

Dodd, GT, Michael, NJ, Lee-Young, RS, Mangiafico, SP, Pryor, JT, Munder, AC, Simonds, SE, Brüning, JC, Zhang, Z-Y, Cowley, MA, Andrikopoulos, S, Horvath, TL, Spanswick, D & Tiganis, T 2018, 'Insulin regulates POMC neuronal plasticity to control glucose metabolism', eLife, vol. 7. https://doi.org/10.7554/eLife.38704
Dodd GT, Michael NJ, Lee-Young RS, Mangiafico SP, Pryor JT, Munder AC et al. Insulin regulates POMC neuronal plasticity to control glucose metabolism. eLife. 2018 Sep 19;7. https://doi.org/10.7554/eLife.38704
Dodd, Garron T. ; Michael, Natalie J. ; Lee-Young, Robert S. ; Mangiafico, Salvatore P. ; Pryor, Jack T. ; Munder, Astrid C. ; Simonds, Stephanie E. ; Brüning, Jens Claus ; Zhang, Zhong-Yin ; Cowley, Michael A. ; Andrikopoulos, Sofianos ; Horvath, Tamas L. ; Spanswick, David ; Tiganis, Tony. / Insulin regulates POMC neuronal plasticity to control glucose metabolism. In: eLife. 2018 ; Vol. 7.
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