Serotonin regulates adult β-cell mass by stimulating perinatal β-cell proliferation

Academic Article

Abstract

  • © 2019 by the American Diabetes Association. A sufficient β-cell mass is crucial for preventing diabetes, and perinatal β-cell proliferation is important in determining the adult β-cell mass. However, it is not yet known how perinatal β-cell proliferation is regulated. Here, we report that serotonin regulates β-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/ paracrine manner during the perinatal period. In β-cell-specific Tph1 knockout (Tph1 bKO) mice, perinatal β-cell proliferation was reduced along with the loss of serotonin production in β-cells. Adult Tph1 bKO mice exhibited glucose intolerance with decreased β-cell mass. Disruption of Htr2b in β-cells also resulted in decreased perinatal β-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in β-cells through activation of STAT5 during the perinatal period. Thus, our results indicate that GH-GH receptor-STAT5-serotonin-HTR2B signaling plays a critical role in determining the β-cell mass by regulating perinatal β-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.
  • Published In

  • Diabetes  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 22351107
  • Author List

  • Moon JH; Kim YG; Kim K; Osonoi S; Wang S; Saunders DC; Wang J; Yang K; Kim H; Lee J
  • Start Page

  • 205
  • End Page

  • 214
  • Volume

  • 69
  • Issue

  • 2