Biphasic changes in β-cell mass around parturition are accompanied by increased serotonin production
Biphasic changes in β-cell mass around parturition are accompanied by increased serotonin production
复制标题
DOI：
10.1038/s41598-020-61850-1
复制
发表时间：
2020-03-18
影响因子：
4.6
通讯作者：
Watada, Hirotaka
中科院分区：
文献类型：
--
作者：
Takahashi, Masaya;Miyatsuka, Takeshi;Watada, Hirotaka
已知啮齿类动物和人类的胰腺β细胞群在妊娠期间和分娩后发生显著变化。虽然β细胞质量在怀孕期间增加，并在分娩后开始恢复到其原始水平，但在此期间调节β细胞质量的细胞机制仍不清楚。为了解决小鼠中的这个问题，我们量化了β细胞质量，并研究了其在围产期和产后期间的调节机制。妊娠期间增加的β细胞大小和增殖在分娩后不久显著减少，而没有证据表明β细胞重编程或细胞凋亡增加。来自怀孕和产后小鼠的胰岛的直接RNA测序证明了基因表达模式的动态变化，显示分娩后1天细胞周期相关基因的稳健下调，以及产后7天5-羟色胺代谢相关基因的重新上调。5-羟色胺合成仅在哺乳期雌性中被激活，并伴有β细胞质量增加。总之，这些发现表明，由于β细胞大小和增殖减少，分娩后不久β细胞量减少，随后增加，与泌乳和5-羟色胺生物合成有关。
Pancreatic beta-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. While beta-cell mass increases during pregnancy and starts to return toward its original level after parturition, the cellular mechanisms by which beta-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified beta-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period. The increased beta-cell size and proliferation during pregnancy were significantly reduced shortly after parturition, whereas there was no evidence of beta-cell reprogramming or increased apoptosis. Direct RNA sequencing of islets from pregnant and postpartum mice demonstrated dynamic changes in gene expression patterns, showing robust downregulation of cell cycle-related genes 1 day after parturition, and the reupregulation of serotonin metabolism-related genes at postpartum day 7. Serotonin synthesis was activated only in lactating females, accompanied by increased beta-cell mass. Taken together, these findings demonstrate that beta-cell mass is decreased shortly after parturition owing to reduced beta-cell size and proliferation, and is subsequently increased, in association with lactation and serotonin biosynthesis.