PT  - JOURNAL ARTICLE
AU  - Jia Zhao
AU  - Weijian Zong
AU  - Yi Wu
AU  - Jiayu Shen
AU  - Dongzhou Gou
AU  - Yiwen Zhao
AU  - Runlong Wu
AU  - Fuzeng Niu
AU  - Xu Wang
AU  - Xuan Zheng
AU  - Aimin Wang
AU  - Yunfeng Zhang
AU  - Jing-Wei Xiong
AU  - Liangyi Chen
AU  - Yanmei Liu
TI  - <em>In vivo</em> Imaging β-cell Function Reveals Two Waves of β-cell Maturation
AID  - 10.1101/159673
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 159673
4099  - http://biorxiv.org/content/early/2017/07/05/159673.short
4100  - http://biorxiv.org/content/early/2017/07/05/159673.full
AB  - The insulin-secreting cells generated from stem cells in vitro are less glucose responsive than primary β-cells. To search for the missing ingredients that are needed for β-cell maturation, we have longitudinally monitored function of every β-cell in Tg (ins:Rcamp1.07) zebrafish embryos with a newly-invented two-photon light-sheet microscope. We have shown that β-cell maturation begins from the islet mantle and propagates to the islet core during the hatching period, coordinated by the islet vascularization. Lower concentration of glucose is optimal to initiate β-cell maturation, while increased glucose delivery to every cell through microcirculation is required for functional boosting of the β-cells. Both the initiation and the boosting of β-cell maturation demands activation of calcineurin/NFAT by glucose. Calcineurin activator combined with glucose promotes mouse neonatal β-cells cultured in vitro to mature to a functional state similar to adult β-cells, suggesting a new strategy for improving stem cell-derived β-like cell function in vitro.