Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, South Korea.
Department of Oral Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, South Korea.
JCI Insight. 2020 Aug 20;5(16):135412. doi: 10.1172/jci.insight.135412.
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.
有越来越多的证据表明胰岛素可以在包括下丘脑在内的各种脑区中合成。然而，下丘脑内表达胰岛素的细胞的分布和功能仍不清楚。本文中，我们发现，在小鼠的下丘脑，胰岛素阳性神经元的胞体位于室旁核（PVN），其轴突投射到正中隆起；这些发现定义了小细胞神经分泌的 PVN 胰岛素神经元。与促肾上腺皮质激素释放激素的表达相反，束缚应激（RS）抑制成年和幼年小鼠 PVN 中的胰岛素表达。急性 RS 诱导的成年小鼠 PVN 胰岛素表达抑制降低了垂体生长激素（Gh）mRNA 水平和血清 GH 浓度，而 PVN 胰岛素的过表达可减轻这种抑制。值得注意的是，幼年小鼠的 PVN 胰岛素敲低或慢性 RS 抑制了 GH 基因表达和分泌，从而阻碍了正常生长，而幼年小鼠的 PVN 胰岛素过表达通过提高 GH 的产生，防止了慢性 RS 诱导的生长迟缓。我们的结果表明，在正常和应激条件下，由小细胞 PVN 神经元合成的胰岛素在调节垂体 GH 产生和体长方面发挥着重要作用，揭示了脑源性胰岛素的一种生理功能。
