Serotonin regulates glucose-stimulated insulin secretion from pancreatic β cells during pregnancy
Serotonin regulates glucose-stimulated insulin secretion from pancreatic β cells during pregnancy
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DOI：
10.1073/pnas.1310953110
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发表时间：
2013-11-26
影响因子：
11.1
通讯作者：
Nagamatsu, Shinya
中科院分区：
文献类型：
--
作者：
Ohara-Imaizumi, Mica;Kim, Hail;Nagamatsu, Shinya
为了准备怀孕的代谢需求，母体胰岛中的β细胞在数量和每个细胞的葡萄糖刺激胰岛素分泌（GSIS）方面都有所增加。已经提出了β细胞质量增加的机制，但没有提出GSIS增加的机制。由于血清素的产生在怀孕期间急剧增加，我们测试了通过离子型5-HT 3受体（Htr 3）的流量是否会影响怀孕期间的GSIS。妊娠的Htr 3a（-/-）小鼠表现出葡萄糖耐量受损，尽管细胞质量正常增加，并且它们的胰岛缺乏在妊娠野生型小鼠胰岛中观察到的GSIS增加。电生理学研究表明，Htr 3的激活降低了β细胞的静息膜电位，这增加了响应于葡萄糖的Ca 2+摄取和胰岛素胞吐。因此，我们的数据表明，5-羟色胺，在旁分泌/自分泌的方式通过Htr 3，降低β细胞的葡萄糖阈值，并在妊娠GSIS增加中发挥重要作用。
In preparation for the metabolic demands of pregnancy, beta cells in the maternal pancreatic islets increase both in number and in glucose-stimulated insulin secretion (GSIS) per cell. Mechanisms have been proposed for the increased beta cell mass, but not for the increased GSIS. Because serotonin production increases dramatically during pregnancy, we tested whether flux through the ionotropic 5-HT3 receptor (Htr3) affects GSIS during pregnancy. Pregnant Htr3a(-/-) mice exhibited impaired glucose tolerance despite normally increased cell mass, and their islets lacked the increase in GSIS seen in islets from pregnant wild-type mice. Electrophysiological studies showed that activation of Htr3 decreased the resting membrane potential in beta cells, which increased Ca2+ uptake and insulin exocytosis in response to glucose. Thus, our data indicate that serotonin, acting in a paracrine/autocrine manner through Htr3, lowers the beta cell threshold for glucose and plays an essential role in the increased GSIS of pregnancy.