In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development
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:Rcamp...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/41540 |
| _version_ | 1811181042708512768 |
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| author | Jia Zhao Weijian Zong Yiwen Zhao Dongzhou Gou Shenghui Liang Jiayu Shen Yi Wu Xuan Zheng Runlong Wu Xu Wang Fuzeng Niu Aimin Wang Yunfeng Zhang Jing-Wei Xiong Liangyi Chen Yanmei Liu |
| author_facet | Jia Zhao Weijian Zong Yiwen Zhao Dongzhou Gou Shenghui Liang Jiayu Shen Yi Wu Xuan Zheng Runlong Wu Xu Wang Fuzeng Niu Aimin Wang Yunfeng Zhang Jing-Wei Xiong Liangyi Chen Yanmei Liu |
| author_sort | Jia Zhao |
| collection | DOAJ |
| description | 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) signaling. 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. |
| first_indexed | 2024-04-11T09:12:54Z |
| format | Article |
| id | doaj.art-9e8894fee3ed44069b8ad788d33314e4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:54Z |
| publishDate | 2019-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9e8894fee3ed44069b8ad788d33314e42022-12-22T04:32:28ZengeLife Sciences Publications LtdeLife2050-084X2019-01-01810.7554/eLife.41540In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional developmentJia Zhao0https://orcid.org/0000-0002-1669-6992Weijian Zong1Yiwen Zhao2Dongzhou Gou3Shenghui Liang4Jiayu Shen5Yi Wu6Xuan Zheng7Runlong Wu8Xu Wang9Fuzeng Niu10Aimin Wang11Yunfeng Zhang12Jing-Wei Xiong13Liangyi Chen14https://orcid.org/0000-0003-1270-7321Yanmei Liu15https://orcid.org/0000-0001-9380-2560State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China; China Department of Cognitive Sciences, Institute of Basic Medical Sciences, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaSchool of Software and Microelectronics, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaSchool of Electronics Engineering and Computer Science, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaState Key Laboratory of Advanced Optical Communication System and Networks, School of Electronics Engineering and Computer Science, Peking University, Beijing, ChinaState Key Laboratory of Advanced Optical Communication System and Networks, School of Electronics Engineering and Computer Science, Peking University, Beijing, ChinaSchool of Electronics Engineering and Computer Science, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China; Institute for Brain Research and Rehabilitation (IBRR), Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, ChinaHow 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) signaling. 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.https://elifesciences.org/articles/41540functionality of β-cells in vivoins:Rcamp1.07 zebrafish2P3A-DSLMmicrocirculationglucoseCalcineurin/NFAT |
| spellingShingle | Jia Zhao Weijian Zong Yiwen Zhao Dongzhou Gou Shenghui Liang Jiayu Shen Yi Wu Xuan Zheng Runlong Wu Xu Wang Fuzeng Niu Aimin Wang Yunfeng Zhang Jing-Wei Xiong Liangyi Chen Yanmei Liu In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development eLife functionality of β-cells in vivo ins:Rcamp1.07 zebrafish 2P3A-DSLM microcirculation glucose Calcineurin/NFAT |
| title | In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development |
| title_full | In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development |
| title_fullStr | In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development |
| title_full_unstemmed | In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development |
| title_short | In vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development |
| title_sort | in vivo imaging of β cell function reveals glucose mediated heterogeneity of β cell functional development |
| topic | functionality of β-cells in vivo ins:Rcamp1.07 zebrafish 2P3A-DSLM microcirculation glucose Calcineurin/NFAT |
| url | https://elifesciences.org/articles/41540 |
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