In Vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development
- Peking University, China
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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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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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
