Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation

Diabetes. 2020 Feb;69(2):205-214. doi: 10.2337/db19-0546. Epub 2019 Dec 5.


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 βKO) mice, perinatal β-cell proliferation was reduced along with the loss of serotonin production in β-cells. Adult Tph1 βKO 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Proliferation
  • Female
  • Glucose / metabolism*
  • Growth Hormone / metabolism
  • Humans
  • Infant
  • Insulin-Secreting Cells / physiology*
  • Mice
  • Mice, Knockout
  • Pregnancy
  • Propafenone / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Prolactin / genetics
  • Receptors, Prolactin / metabolism
  • Serotonin / metabolism*
  • Tryptophan Hydroxylase / genetics
  • Tryptophan Hydroxylase / metabolism


  • RNA, Messenger
  • Receptors, Prolactin
  • Serotonin
  • Propafenone
  • Growth Hormone
  • Tph1 protein, mouse
  • Tryptophan Hydroxylase
  • Glucose