1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
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In Vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development

Research Article
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Cite this article as: eLife 2019;8:e41540 doi: 10.7554/eLife.41540

Abstract

How pancreatic β-cells acquire function in vivo is a long-standing mystery due to the lack of technology to visualize β-cell function in living animals. Here, we applied a high-resolution two-photon light-sheet microscope for the first in vivo imaging of Ca2+ activity of every β-cell in Tg (ins:Rcamp1.07) zebrafish. We reveal that the heterogeneity of β-cell functional development in vivo occurred as two waves propagating from the islet mantle to the core, coordinated by islet vascularization. Increasing amounts of glucose induced functional acquisition and enhancement of β-cells via activating calcineurin/nuclear factor of activated T-cells (NFAT) signalling. Conserved in mammalians, calcineurin/NFAT prompted high-glucose-stimulated insulin secretion of neonatal mouse islets cultured in vitro. However, the reduction in low-glucose-stimulated insulin secretion was dependent on optimal glucose but independent of calcineurin/NFAT. Thus, combination of optimal glucose and calcineurin activation represents a previously unexplored strategy for promoting functional maturation of stem cell-derived β-like cells in vitro.

Article and author information

Author details

  1. Jia Zhao

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1669-6992
  2. Weijian Zong

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yiwen Zhao

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Dongzhou Gou

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Shenghui Liang

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jiayu Shen

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yi Wu

    School of Software and Microelectronics, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Xuan Zheng

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Runlong Wu

    School of Electronics Engineering and Computer Science, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Xu Wang

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Fuzeng Niu

    School of Electronics Engineering and Computer Science, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Aimin Wang

    School of Electronics Engineering and Computer Science, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Yunfeng Zhang

    School of Electronics Engineering and Computer Science, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Jing-Wei Xiong

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Liangyi Chen

    Institute of Molecular Medicine, Peking University, Beijing, China
    For correspondence
    lychen@pku.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1270-7321
  16. Yanmei Liu

    Institute of Molecular Medicine, Peking University, Beijing, China
    For correspondence
    yanmeiliu@pku.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9380-2560

Funding

National Science and Technology Major Project Program (2016YFA0500400)

  • Liangyi Chen

National Natural Science Foundation of China (91854112)

  • Yanmei Liu

National Natural Science Foundation of China (91750203)

  • Yanmei Liu

National Natural Science Foundation of China (31327901)

  • Liangyi Chen

National Natural Science Foundation of China (31521062)

  • Liangyi Chen

National Natural Science Foundation of China (31570839)

  • Liangyi Chen

National Natural Science Foundation of China (31301186)

  • Yanmei Liu

Beijing Natural Science Foundation (L172003)

  • Liangyi Chen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal care, generation of transgenic zebrafish lines, in vivo imaging of the live zebrafish embryos and all other experiments involving zebrafish and mouse islets were approved by the IACUC of Peking University in China (reference no. IMM-ChenLY-2).

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: August 29, 2018
  2. Accepted: January 29, 2019
  3. Accepted Manuscript published: January 29, 2019 (version 1)
  4. Version of Record published: February 28, 2019 (version 2)

Copyright

© 2019, Zhao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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