Insulin regulates POMC neuronal plasticity to control glucose metabolism

被引:87
|
作者
Dodd, Garron T. [1 ,2 ]
Michael, Natalie J. [1 ,3 ]
Lee-Young, Robert S. [1 ,2 ,4 ]
Mangiafico, Salvatore P. [5 ]
Pryor, Jack T. [3 ,6 ]
Munder, Astrid C. [1 ,3 ]
Simonds, Stephanie E. [1 ,3 ]
Bruening, Jens Claus [7 ,8 ,9 ,10 ,11 ]
Zhang, Zhong-Yin [12 ]
Cowley, Michael A. [1 ,3 ]
Andrikopoulos, Sofianos [5 ]
Horvath, Tamas L. [13 ,14 ]
Spanswick, David [1 ,3 ,6 ]
Tiganis, Tony [1 ,2 ,4 ]
机构
[1] Monash Univ, Monash Biomed Discovery Inst, Metab Diabet & Obes Program, Melbourne, Vic, Australia
[2] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia
[3] Monash Univ, Dept Physiol, Clayton, Vic, Australia
[4] Monash Univ, Monash Metab Phenotyping Facil, Clayton, Vic, Australia
[5] Univ Melbourne, Dept Med, Austin Hosp, Melbourne, Vic, Australia
[6] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England
[7] Max Planck Inst Metab Res, Dept Neuronal Control Metab, Cologne, Germany
[8] Univ Hosp Cologne, Ctr Endocrinol Diabet & Prevent Med, Cologne, Germany
[9] Univ Cologne, Excellence Cluster Cellular Stress Responses Agin, Cologne, Germany
[10] Univ Cologne, Ctr Mol Med Cologne, Cologne, Germany
[11] Natl Ctr Diabet Res, Neuherberg, Germany
[12] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA
[13] Yale Univ, Sch Med, Dept Comparat Med, Program Integrat Cell Signaling & Neurobiol Metab, New Haven, CT USA
[14] Univ Vet Med, Dept Anat & Histol, Budapest, Hungary
来源
ELIFE | 2018年 / 7卷
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
PROOPIOMELANOCORTIN NEURONS; HYPOTHALAMIC INSULIN; LEPTIN ACTION; AGRP NEURONS; MITOCHONDRIAL DYNAMICS; ENERGY HOMEOSTASIS; EXPRESSING NEURONS; RECEPTOR; ACTIVATION; PROTEIN;
D O I
10.7554/eLife.38704
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:30
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