Impact of insulin on primary arcuate neurons culture is dependent on early-postnatal nutritional status and neuronal subpopulation

PLoS One. 2018 Feb 21;13(2):e0193196. doi: 10.1371/journal.pone.0193196. eCollection 2018.

Abstract

Nutrition plays a critical role in programming and shaping linear growth during early postnatal life through direct action on the development of the neuroendocrine somatotropic (GH/IGF-1) axis. IGF-1 is a key factor in modulating the programming of linear growth during this period. Notably, IGF-1 preferentially stimulates axonal growth of GHRH neurons in the arcuate nucleus of the hypothalamus (Arc), which is crucial for the proliferation of somatotroph progenitors in the pituitary, thus influencing later GH secretory capacity. However, other nutrition-related hormones may also be involved. Among them, insulin shares several structural and functional similarities with IGF-1, as well as downstream signaling effectors. We investigated the role of insulin in the control of Arc axonal growth using an in vitro model of arcuate explants culture and a cell-type specific approach (GHRH-eGFP mice) under both physiological conditions (normally fed pups) and those of dietary restriction (underfed pups). Our data suggest that insulin failed to directly control axonal growth of Arc neurons or influence specific IGF-1-mediated effects on GHRH neurons. Insulin may act on neuronal welfare, which appears to be dependent on neuronal sub-populations and is influenced by the nutritional status of pups in which Arc neurons develop.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Axons / metabolism*
  • Cell Culture Techniques
  • Cells, Cultured
  • Growth Hormone / metabolism
  • Growth Hormone-Releasing Hormone / metabolism
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Insulin-Like Growth Factor I / metabolism
  • Mice
  • Mice, Transgenic
  • Nutritional Status*

Substances

  • Insulin
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Growth Hormone-Releasing Hormone

Associated data

  • figshare/5545711.v1

Grants and funding

This study was supported by institutional funding from the Institut National de la Santé et de la Recherche Médicale (INSERM), l’Université Pierre et Marie Curie (Sorbonne Universités, UPMC Univ Paris 06). It benefits from funding from the Institute of Cardiometabolism and Nutrition (IHU ICAN; http://www.ican-institute.org/), Sandoz Biopharmaceuticals France (https://www.sandoz.fr/), and the Premup foundation (https://www.premup.org/fra/accueil). L.D. was supported by a PhD grant from the French Ministry for Education and Research Training and the Société Française d’Endocrinologie et Diabètologie Pédiatrique (SFEDP, the Sandoz Biopharmaceuticals grant of SFEDP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.