Structural basis for delta cell paracrine regulation in pancreatic islets

AUTHORS

Arrojo e Drigo Rafael , Jacob Stefan , Garcia-Pietro Concha , Zheng Xiaofeng , Fukuda Masahiro , Thi Nhu Hoa Tran , Stelmashenko Olga , Martins Pecanha Flavia Leticia , Rodriguez-Diaz Rayner , Bushong Eric , Deerinck Thomas , Phan Sebastien , Ali Yusuf , Leibiger Ingo , Chua Minni , Boudier Thomas , Song Sang-Ho , Graf Martin , Augustine Geroge , Ellisman Mark , Berggren Per-Olof . Nature Communications. 2019 8 ; 10().

ABSTRACT

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.