- 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
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.