Insulin regulates POMC neuronal plasticity to control glucose metabolism.

2018-09-19

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

POMC neurons

cellular signalling

glucose metabolism

human biology

hypothalamus

insulin

medicine

mouse

neuroscience

protein tyrosine phosphatase

Journal Article

0000-0002-8932-8592

0000-0002-7554-4876

0000-0002-9032-0862

0000-0002-7522-4602

0000-0002-8065-9942

10.7554/eLife.38704

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.

link

eLife 2018; 7: 238704

eLife