Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Mass Spectrometry Resource Laboratory, University of Rochester, Rochester, NY, USA.
Commun Biol. 2021 Mar 26;4(1):421. doi: 10.1038/s42003-021-01900-0.
In pancreatic islets, catabolism of tryptophan into serotonin and serotonin receptor 2B (HTR2B) activation is crucial for β-cell proliferation and maternal glucose regulation during pregnancy. Factors that reduce serotonin synthesis and perturb HTR2B signaling are associated with decreased β-cell number, impaired insulin secretion, and gestational glucose intolerance in mice. Albeit the tryptophan-serotonin pathway is dependent on vitamin B6 bioavailability, how vitamin B6 deficiency impacts β-cell proliferation during pregnancy has not been investigated. In this study, we created a vitamin B6 deficient mouse model and investigated how gestational deficiency influences maternal glucose tolerance. Our studies show that gestational vitamin B6 deficiency decreases serotonin levels in maternal pancreatic islets and reduces β-cell proliferation in an HTR2B-dependent manner. These changes were associated with glucose intolerance and insulin resistance, however insulin secretion remained intact. Our findings suggest that vitamin B6 deficiency-induced gestational glucose intolerance involves additional mechanisms that are complex and insulin independent.
在胰岛中，色氨酸分解为血清素和血清素受体 2B（HTR2B）的激活对于β细胞增殖和妊娠期间母体葡萄糖调节至关重要。减少血清素合成和干扰 HTR2B 信号的因素与β细胞数量减少、胰岛素分泌受损和妊娠期葡萄糖耐量降低有关。尽管色氨酸-血清素途径依赖于维生素 B6 的生物利用度，但维生素 B6 缺乏如何影响妊娠期间的β细胞增殖尚未得到研究。在这项研究中，我们创建了维生素 B6 缺乏的小鼠模型，并研究了妊娠期缺乏如何影响母体葡萄糖耐量。我们的研究表明，妊娠期维生素 B6 缺乏会降低母体胰岛中的血清素水平，并以 HTR2B 依赖的方式减少β细胞增殖。这些变化与葡萄糖耐量和胰岛素抵抗有关，但胰岛素分泌保持完整。我们的研究结果表明，维生素 B6 缺乏引起的妊娠期葡萄糖耐量涉及到复杂的、与胰岛素无关的其他机制。
