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. EllismanPer Olof Berggren

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Article number3700
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Arrojo e Drigo, R., Jacob, S., García-Prieto, C. F., Zheng, X., Fukuda, M., Nhu, H. T. T., Stelmashenko, O., Peçanha, F. L. M., Rodriguez-Diaz, R., Bushong, E., Deerinck, T., Phan, S., Ali, Y., Leibiger, I., Chua, M., Boudier, T., Song, S. H., Graf, M., Augustine, G. J., ... Berggren, P. O. (2019). Structural basis for delta cell paracrine regulation in pancreatic islets. Nature communications, 10(1), [3700]. https://doi.org/10.1038/s41467-019-11517-x