Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/19574
Title: Insulin regulates POMC neuronal plasticity to control glucose metabolism.
Authors: 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
Affiliation: Department of Anatomy and Histology, University of Veterinary Medicine, Hungary, Europe
Center for Endocrinology, Diabetes, and Preventive Medicine, University Hospital Cologne, Cologne, Germany
Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
National Center for Diabetes Research, Neuherberg, Germany
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, United States
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States
Metabolism, Diabetes and Obesity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia
Department of Physiology, Monash University, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Monash Metabolic Phenotyping Facility, Monash University, Victoria, Australia
Warwick Medical School, University of Warwick, Coventry, United Kingdom
Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany
Issue Date: 19-Sep-2018
EDate: 2018-09-19
Citation: eLife 2018; 7: 238704
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/19574
DOI: 10.7554/eLife.38704
ORCID: 0000-0002-8932-8592
0000-0002-7554-4876
0000-0002-9032-0862
0000-0002-7522-4602
0000-0002-8065-9942
PubMed URL: 30230471
Type: Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Subjects: POMC neurons
cellular signalling
glucose metabolism
human biology
hypothalamus
insulin
medicine
mouse
neuroscience
protein tyrosine phosphatase
Appears in Collections:Journal articles

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