1. Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation.
- Author
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Joon Ho Moon, Yeong Gi Kim, Kyuho Kim, Sho Osonoi, Shuang Wang, Saunders, Diane C., Juehu Wang, Yang, Katherine, Hyeongseok Kim, Junguee Lee, Ji-Seon Jeong, Banerjee, Ronadip R., Kim, Seung K., Yingjie Wu, Hiroki Mizukami, Powers, Alvin C., German, Michael S., Hail Kim, Moon, Joon Ho, and Kim, Yeong Gi
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SEROTONIN , *GLUCOSE intolerance , *SEROTONIN receptors , *SOMATOTROPIN , *ADULTS , *RNA metabolism , *GLUCOSE metabolism , *ANIMAL experimentation , *ANIMAL populations , *CELL physiology , *CELL receptors , *COMPARATIVE studies , *ISLANDS of Langerhans , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *OXIDOREDUCTASES , *PROPAFENONE , *RESEARCH , *RNA , *EVALUATION research , *HUMAN growth hormone - 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 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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