Dodd, Garron T., Michael, Natalie J., Lee-Young, Robert S., Mangiafico, Salvatore P., Pryor, Jack T., Munder, Astrid C., Simonds, Stephanie E., Bruening, Jens Claus, Zhang, Zhong-Yin, Cowley, Michael A., Andrikopoulos, Sofianos, Horvath, Tamas L., Spanswick, David ORCID: 0000-0002-8129-8173 and Tiganis, Tony ORCID: 0000-0002-8065-9942 (2018). Insulin regulates POMC neuronal plasticity to control glucose metabolism. eLife, 7. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dodd, Garron T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michael, Natalie J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee-Young, Robert S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mangiafico, Salvatore P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pryor, Jack T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munder, Astrid C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simonds, Stephanie E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, Zhong-YinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cowley, Michael A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrikopoulos, SofianosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horvath, Tamas L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spanswick, DavidUNSPECIFIEDorcid.org/0000-0002-8129-8173UNSPECIFIED
Tiganis, TonyUNSPECIFIEDorcid.org/0000-0002-8065-9942UNSPECIFIED
URN: urn:nbn:de:hbz:38-172627
DOI: 10.7554/eLife.38704
Journal or Publication Title: eLife
Volume: 7
Date: 2018
Publisher: ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication: CAMBRIDGE
ISSN: 2050-084X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROTEIN-COUPLED RECEPTORS; PROOPIOMELANOCORTIN NEURONS; ARCUATE NUCLEUS; AGRP NEURONS; HYPOTHALAMIC INSULIN; ENERGY HOMEOSTASIS; ADIPOSE-TISSUE; LEPTIN ACTION; MITOCHONDRIAL DYNAMICS; EXPRESSING NEURONSMultiple languages
BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17262

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