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.

中文翻译：

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血清素通过刺激围产期 β 细胞增殖来调节成人 β 细胞质量

充足的 β 细胞数量对于预防糖尿病至关重要，围产期 β 细胞增殖对于确定成人 β 细胞数量很重要。然而，目前尚不清楚围产期 β 细胞增殖是如何调节的。在这里，我们报告说，在围产期，血清素通过血清素受体 2B (HTR2B) 以自分泌/旁分泌方式调节 β 细胞增殖。在 β 细胞特异性 Tph1 敲除 (Tph1 βKO) 小鼠中，围产期 β 细胞增殖降低，同时 β 细胞中的血清素产生减少。成年 Tph1 βKO 小鼠表现出葡萄糖耐受不良，β 细胞量减少。β 细胞中 Htr2b 的破坏还导致围产期 β 细胞增殖减少和成年期葡萄糖耐受不良。发现生长激素 (GH) 在围产期通过激活 STAT5 诱导 β 细胞中血清素的产生。因此，我们的结果表明 GH-GH 受体-STAT5-5-羟色胺-HTR2B 信号传导通过调节围产期 β 细胞增殖在确定 β 细胞质量方面起着关键作用，并且该途径的缺陷会影响成人的代谢表型。