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Structural basis for delta cell paracrine regulation in pancreatic islets

Author

Listed:
  • Rafael Arrojo e Drigo

    (Nanyang Technological University
    Molecular and Cell Biology Laboratory)

  • 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)
    Sorbonne University, UPMC University)

  • 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)
    Sorbonne University, UPMC University)

  • 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
    The Rolf Luft Research Center for Diabetes and Endocrinology
    University of Miami)

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.

Suggested Citation

  • 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, 2019. "Structural basis for delta cell paracrine regulation in pancreatic islets," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11517-x
    DOI: 10.1038/s41467-019-11517-x
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    Cited by:

    1. Lihua Chen & Nannan Wang & Tongran Zhang & Feng Zhang & Wei Zhang & Hao Meng & Jingyi Chen & Zhiying Liao & Xiaopeng Xu & Zhuo Ma & Tao Xu & Huisheng Liu, 2024. "Directed differentiation of pancreatic δ cells from human pluripotent stem cells," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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