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ResearchIn-Press PreviewEndocrinologyNeuroscience Open Access | 10.1172/jci.insight.135412

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

Jaemeun Lee,1 Kyungchan Kim,1 Jae Hyun Cho,1 Jin Young Bae,2 Timothy P. O’Leary,3 James D. Johnson,3 Yong Chul Bae,2 and Eun-Kyoung Kim1

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea, Republic of

2Department of Anatomy and Neurobiology, Kyungpook National University, Daegu, Korea, Republic of

3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

4Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Deagu, Korea, Republic of

Find articles by Lee, J. in: PubMed | Google Scholar |

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea, Republic of

2Department of Anatomy and Neurobiology, Kyungpook National University, Daegu, Korea, Republic of

3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

4Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Deagu, Korea, Republic of

Find articles by Kim, K. in: PubMed | Google Scholar

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea, Republic of

2Department of Anatomy and Neurobiology, Kyungpook National University, Daegu, Korea, Republic of

3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

4Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Deagu, Korea, Republic of

Find articles by Cho, J. in: PubMed | Google Scholar

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea, Republic of

2Department of Anatomy and Neurobiology, Kyungpook National University, Daegu, Korea, Republic of

3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

4Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Deagu, Korea, Republic of

Find articles by Bae, J. in: PubMed | Google Scholar

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea, Republic of

2Department of Anatomy and Neurobiology, Kyungpook National University, Daegu, Korea, Republic of

3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

4Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Deagu, Korea, Republic of

Find articles by O’Leary, T. in: PubMed | Google Scholar

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea, Republic of

2Department of Anatomy and Neurobiology, Kyungpook National University, Daegu, Korea, Republic of

3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

4Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Deagu, Korea, Republic of

Find articles by Johnson, J. in: PubMed | Google Scholar |

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea, Republic of

2Department of Anatomy and Neurobiology, Kyungpook National University, Daegu, Korea, Republic of

3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

4Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Deagu, Korea, Republic of

Find articles by Bae, Y. in: PubMed | Google Scholar |

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea, Republic of

2Department of Anatomy and Neurobiology, Kyungpook National University, Daegu, Korea, Republic of

3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

4Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Deagu, Korea, Republic of

Find articles by Kim, E. in: PubMed | Google Scholar

Published July 9, 2020 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.135412.
Copyright © 2020, Lee et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 9, 2020 - Version history
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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 corticotrophin-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 down-regulation 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.

Graphical Abstract
graphical abstract
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Version history
  • Version 1 (July 9, 2020): In-Press Preview
  • Version 2 (August 20, 2020): Electronic publication
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