Structural basis for delta cell paracrine regulation in pancreatic islets
Structural basis for delta cell paracrine regulation in pancreatic islets
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DOI：
10.1038/s41467-019-11517-x
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发表时间：
2019-08-16
影响因子：
16.6
通讯作者：
Berggren, Per-Olof
中科院分区：
文献类型：
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作者：
Arrojo e Drigo, Rafael;Jacob, Stefan;Berggren, Per-Olof
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细胞分泌活性的重要旁分泌调节因子，然而这种调节的结构基础尚未确定。大多数δ细胞是细长的，具有明确的细胞索马和丝状伪足样结构。使用体内光遗传学和高速Ca 2+成像，我们表明这些丝状伪足是包含分泌机制的动态结构，使δ细胞能够到达胰岛内的大量β细胞。这提供了β细胞活性的有效调节，并通过内源性IGF-1/VEGF-A信号传导进行调节。在糖尿病前期，δ细胞经历形态学变化，这可能是维持β细胞的旁分泌调节的补偿。我们的数据提供了一个完整的图片，δ细胞如何在生理条件下调节β细胞活性。
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 Ca2+ 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.