1. Developmental Biology
  2. Stem Cells and Regenerative Medicine

In Vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development

  1. Jia Zhao
  2. Weijian Zong
  3. Yiwen Zhao
  4. Dongzhou Gou
  5. Shenghui Liang
  6. Jiayu Shen
  7. Yi Wu
  8. Xuan Zheng
  9. Runlong Wu
  10. Xu Wang
  11. Fuzeng Niu
  12. Aimin Wang
  13. Yunfeng Zhang
  14. Jing-Wei Xiong
  15. Liangyi Chen  Is a corresponding author
  16. Yanmei Liu  Is a corresponding author
  1. Peking University, China
https://doi.org/10.7554/eLife.41540
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Cite this article
  1. Jia Zhao
  2. Weijian Zong
  3. Yiwen Zhao
  4. Dongzhou Gou
  5. Shenghui Liang
  6. Jiayu Shen
  7. Yi Wu
  8. Xuan Zheng
  9. Runlong Wu
  10. Xu Wang
  11. Fuzeng Niu
  12. Aimin Wang
  13. Yunfeng Zhang
  14. Jing-Wei Xiong
  15. Liangyi Chen
  16. Yanmei Liu
(2019)
In Vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development
eLife 8:e41540.
https://doi.org/10.7554/eLife.41540
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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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

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).

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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  1. Jia Zhao
  2. Weijian Zong
  3. Yiwen Zhao
  4. Dongzhou Gou
  5. Shenghui Liang
  6. Jiayu Shen
  7. Yi Wu
  8. Xuan Zheng
  9. Runlong Wu
  10. Xu Wang
  11. Fuzeng Niu
  12. Aimin Wang
  13. Yunfeng Zhang
  14. Jing-Wei Xiong
  15. Liangyi Chen
  16. Yanmei Liu
(2019)
In Vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development
eLife 8:e41540.
https://doi.org/10.7554/eLife.41540

Share this article

https://doi.org/10.7554/eLife.41540

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