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

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.

营养在调节和塑造早期生后生命中的线性生长过程中起着至关重要的作用，其作用机理是通过直接影响神经内分泌生长轴（GH/IGF-1）的发育。IGF-1是该时期线性生长编程的关键因素。值得注意的是，IGF-1优先刺激下丘脑弓状核（Arc）中GHRH神经元的轴突生长，这对于垂体中体细胞祖细胞的增殖至关重要，从而影响后续的生长激素分泌能力。然而，其他与营养相关的激素也可能参与其中。其中，胰岛素与IGF-1在结构和功能上具有相似之处，以及下游信号传导效应。我们通过体外弓状核移植培养模型和细胞特异性方法（GHRH-eGFP小鼠）研究胰岛素在控制Arc神经元轴突生长中的作用，分别在生理条件（正常喂养的幼鼠）和饮食限制条件（饥饿的幼鼠）下进行研究。我们的数据表明，胰岛素未能直接控制Arc神经元的轴突生长或影响IGF-1介导的GHRH神经元的具体效应。胰岛素可能作用于神经元福利，这似乎依赖于神经元亚群，并受Arc神经元发育中的幼鼠营养状态的影响。