Insulin regulates POMC neuronal plasticity to control glucose metabolism
- Monash University, Australia
- University of Melbourne, Australia
- Max Plank Institute for Metabolism Research, Germany
- Purdue University, United States
- Yale University School of Medicine, United States
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Health and Medical Research Council
- David Spanswick
- Tony Tiganis
National Health and Medical Research Council
- Michael A Cowley
National Institutes of Health
- Tamas L Horvath
National Institutes of Health
- Zhong-Yin Zhang
National Health and Medical Research Council
- Sofianos Andrikopoulos
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States
Ethics
Animal experimentation: Experiments were approved by the Monash University School of Biomedical Sciences Animal EthicsCommittee (MARP2013/137).
Version history
- Received: May 27, 2018
- Accepted: September 14, 2018
- Accepted Manuscript published: September 19, 2018 (version 1)
- Version of Record published: October 3, 2018 (version 2)
Copyright
© 2018, Dodd et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Insulin regulates POMC neuronal plasticity to control glucose metabolism
eLife 7:e38704.
https://doi.org/10.7554/eLife.38704
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