Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore.
Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, San Diego, 92037, USA.
Nat Commun. 2019 Aug 16;10(1):3700. doi: 10.1038/s41467-019-11517-x.
Little is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions.
关于胰岛δ细胞在体内调节血糖稳态中的作用知之甚少。δ细胞是β细胞和α细胞分泌活动的重要旁分泌调节剂，然而，这种调节的结构基础尚未确定。大多数δ细胞呈细长状，具有明确的细胞体和类似纤毛的结构。我们利用体内光遗传学和高速 Ca 成像技术显示，这些纤毛是动态结构，包含一个分泌机制，使δ细胞能够在胰岛内到达大量的β细胞。这为β细胞活性的有效调节提供了条件，并且受到内源性 IGF-1/VEGF-A 信号的调节。在糖尿病前期，δ细胞发生形态变化，这可能是一种代偿机制，以维持对β细胞的旁分泌调节。我们的数据提供了一个综合的画面，说明δ细胞如何在生理条件下调节β细胞的活性。
