Cited 4 time in webofscience Cited 5 time in scopus

Insulin synthesized in the paraventricular nucleus of the hypothalamus regulates pituitary growth hormone production

Title
Insulin synthesized in the paraventricular nucleus of the hypothalamus regulates pituitary growth hormone production
Authors
Lee, JaemeunKim, KyungchanCho, Jae HyeonBae, Jin YoungO'Leary, Timothy P.Johnson, James D.Bae, Yong ChulKim, Eun-Kyoung
DGIST Authors
Lee, Jaemeun; Kim, Kyungchan; Cho, Jae Hyeon; Bae, Jin Young; O'Leary, Timothy P.; Johnson, James D.; Bae, Yong Chul; Kim, Eun-Kyoung
Issue Date
2020-08
Citation
JCI insight, 5(16), e135412
Type
Article
Article Type
Article
Keywords
CORTICOTROPIN-RELEASING HORMONEMEDIAN-EMINENCEMESSENGER-RNAGENE-EXPRESSIONSTRESS-RESPONSEGH RESPONSERATSECRETIONBRAINNEURONS
ISSN
2324-7703
Abstract
Evidence has mounted that insulin can be synthesized in various brain regions, including the hypothalamus. However, the distribution and functions of insulin-expressing cells in the hypothalamus remain elusive. Herein, we show that in the mouse hypothalamus, the perikarya of insulin-positive neurons are located in the paraventricular nucleus (PVN) and their axons project to the median eminence; these findings define parvocellular neurosecretory PVN insulin neurons. Contrary to corticotropin-releasing hormone expression, insulin expression in the PVN was inhibited by restraint stress (RS) in both adult and young mice. Acute RS–induced inhibition of PVN insulin expression in adult mice decreased both pituitary growth hormone (Gh) mRNA level and serum GH concentration, which were attenuated by overexpression of PVN insulin. Notably, PVN insulin knockdown or chronic RS in young mice hindered normal growth via the downregulation of GH gene expression and secretion, whereas PVN insulin overexpression in young mice prevented chronic RS–induced growth retardation by elevating GH production. Our results suggest that in both normal and stressful conditions, insulin synthesized in the parvocellular PVN neurons plays an important role in the regulation of pituitary GH production and body length, unveiling a physiological function of brain-derived insulin. Copyright: © 2020, Lee et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
URI
http://hdl.handle.net/20.500.11750/12673
DOI
10.1172/jci.insight.135412
Publisher
The American Society for Clinical Investigation
Related Researcher
  • Author Kim, Eun-Kyoung Lab of Neuro-Metabolism & Neurometabolomic Research Center
  • Research Interests Neural functions in metabolic diseases; 뇌신경세포와 비만; 당뇨 등의 대사 질환 관련 연구
Files:
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Collection:
Department of Brain and Cognitive SciencesLab of Neuro-Metabolism & Neurometabolomic Research Center1. Journal Articles


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