Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation
| Autor: | Moon, Joon Ho, Kim, Yeong Gi, Kim, Kyuho, Osonoi, Sho, Wang, Shuang, Saunders, Diane C, Wang, Juehu, Yang, Katherine, Kim, Hyeongseok, Lee, Junguee, Jeong, Ji-Seon, Banerjee, Ronadip R, Kim, Seung K, Wu, Yingjie, Mizukami, Hiroki, Powers, Alvin C, German, Michael S, Kim, Hail |
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| Rok vydání: | 2020 |
| Předmět: |
Serotonin
Knockout 1.1 Normal biological development and functioning Messenger Tryptophan Hydroxylase Medical and Health Sciences Mice Endocrinology & Metabolism Propafenone Pregnancy Underpinning research Insulin-Secreting Cells Receptors Animals Humans Metabolic and endocrine Cell Proliferation Pediatric Diabetes Infant Newborn Prolactin Glucose Growth Hormone RNA Female |
| Zdroj: | Diabetes, vol 69, iss 2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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