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

Joon Ho Moon, Yeong Gi Kim, Kyuho Kim, Sho Osonoi, Shuang Wang, Diane C. Saunders, Juehu Wang, Katherine Yang, Hyeongseok Kim, Junguee Lee, Ji Seon Jeong, Ronadip R. Banerjee, Seung K. Kim, Yingjie Wu, Hiroki Mizukami, Alvin C. Powers, Michael S. German, Hail Kim

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)205-214
Number of pages10
JournalDiabetes
Volume69
Issue number2
DOIs
StatePublished - 1 Feb 2020

Fingerprint

Dive into the research topics of 'Serotonin regulates adult β-cell mass by stimulating perinatal β-cell proliferation'. Together they form a unique fingerprint.

Cite this