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Serotonin Regulates Adult ?-Cell Mass by Stimulating Perinatal ?-Cell Proliferation.

ABSTRACT: A sufficient ?-cell mass is crucial for preventing diabetes, and perinatal ?-cell proliferation is important in determining the adult ?-cell mass. However, it is not yet known how perinatal ?-cell proliferation is regulated. Here, we report that serotonin regulates ?-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/paracrine manner during the perinatal period. In ?-cell-specific Tph1 knockout (Tph1 ?KO) mice, perinatal ?-cell proliferation was reduced along with the loss of serotonin production in ?-cells. Adult Tph1 ?KO mice exhibited glucose intolerance with decreased ?-cell mass. Disruption of Htr2b in ?-cells also resulted in decreased perinatal ?-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in ?-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 ?-cell mass by regulating perinatal ?-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.

SUBMITTER: Moon JH 

PROVIDER: S-EPMC6971487 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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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 <i>Tph1</i> knockout (<i>Tph1</i> βKO) mice, perinatal β-cell proliferation was reduced along  ...[more]

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