Journal article

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 Bruening, Zhong-Yin Zhang, Michael A Cowley, Sofianos Andrikopoulos, Tamas L Horvath, David Spanswick, Tony Tiganis

ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2018

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 POM..

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Grants

Awarded by National Institutes of Health


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

National Institutes of Health RO1 CA207288 Zhong-Yin ZhangNational Health and Medical Research Council Michael A Cowley Sofianos Andrikopoulos David Spanswick Tony TiganisNational Institutes of Health AG051459 Tamas L HorvathNational Institutes of Health AG052986 Tamas L HorvathNational Institutes of Health DK111178 Tamas L HorvathThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.