Biphasic changes in β-cell mass around parturition are accompanied by increased serotonin production
Masaya Takahashi, Takeshi Miyatsuka, Luka Suzuki, Sho Osonoi, Miwa Himuro, Masaki Miura, Takehiro Katahira, Yuka Wakabayashi, Ayako Fukunaka, Yuya Nishida, Yoshio Fujitani, Satoru Takeda, Hiroki Mizukami, Atsuo Itakura, Hirotaka Watada
Abstract
Pancreatic β-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. While β-cell mass increases during pregnancy and starts to return toward its original level after parturition, the cellular mechanisms by which β-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified β-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period. The increased β-cell size and proliferation during pregnancy were significantly reduced shortly after parturition, whereas there was no evidence of β-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 β-cell mass. Taken together, these findings demonstrate that β-cell mass is decreased shortly after parturition owing to reduced β-cell size and proliferation, and is subsequently increased, in association with lactation and serotonin biosynthesis.