Structural basis for delta cell paracrine regulation in pancreatic islets

Rafael Arrojo e Drigo, Stefan Jacob, Concha F. García-Prieto, Xiaofeng Zheng, Masahiro Fukuda, Hoa Tran Thi Nhu, Olga Stelmashenko, Flavia Letícia Martins Peçanha, Rayner Rodriguez-Diaz, Eric Bushong, Thomas Deerinck, Sebastien Phan, Yusuf Ali, Ingo Leibiger, Minni Chua, Thomas Boudier, Sang-Ho Song, Martin Graf, George J. Augustine, Mark H. Ellisman and Per-Olof Berggren ()
Additional contact information
Rafael Arrojo e Drigo: Nanyang Technological University
Stefan Jacob: The Rolf Luft Research Center for Diabetes and Endocrinology
Concha F. García-Prieto: The Rolf Luft Research Center for Diabetes and Endocrinology
Xiaofeng Zheng: Nanyang Technological University
Masahiro Fukuda: Duke-NUS Medical School
Hoa Tran Thi Nhu: Bioinformatics Institute (ASTAR) and Image and Pervasive Access Lab (IPAL)
Olga Stelmashenko: Nanyang Technological University
Flavia Letícia Martins Peçanha: Universidade Federal do Rio de Janeiro (UFRJ)
Rayner Rodriguez-Diaz: University of Miami
Eric Bushong: University of California San Diego
Thomas Deerinck: University of California San Diego
Sebastien Phan: University of California San Diego
Yusuf Ali: Nanyang Technological University
Ingo Leibiger: The Rolf Luft Research Center for Diabetes and Endocrinology
Minni Chua: Nanyang Technological University
Thomas Boudier: Bioinformatics Institute (ASTAR) and Image and Pervasive Access Lab (IPAL)
Sang-Ho Song: Nanyang Technological University
Martin Graf: Nanyang Technological University
George J. Augustine: Nanyang Technological University
Mark H. Ellisman: University of California San Diego
Per-Olof Berggren: Nanyang Technological University

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11517-x

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