PMID- 33298443 OWN - NLM STAT- In-Data-Review VI - 6 IP - 50 TI - Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography. CI - Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). LA - eng PT - Journal Article PL - United States TA - Sci Adv JT - Science advances JID - 101653440 IS - 2375-2548 (Electronic) LID - eabc8262 [pii] LID - 10.1126/sciadv.abc8262 [doi] FAU - White, Kate L AU - White KL AUID- ORCID: http://orcid.org/0000-0001-8894-9621 AD - Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. stevens@usc.edu calarabell@lbl.gov sali@salilab.org katewhit@usc.edu. AD - Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. FAU - Singla, Jitin AU - Singla J AUID- ORCID: http://orcid.org/0000-0001-6225-0783 AD - Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. AD - Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Loconte, Valentina AU - Loconte V AUID- ORCID: http://orcid.org/0000-0001-5715-9993 AD - iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. FAU - Chen, Jian-Hua AU - Chen JH AUID- ORCID: http://orcid.org/0000-0002-7998-0878 AD - Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. AD - Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Ekman, Axel AU - Ekman A AD - Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Sun, Liping AU - Sun L AD - iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. FAU - Zhang, Xianjun AU - Zhang X AUID- ORCID: http://orcid.org/0000-0003-3554-780X AD - Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. FAU - Francis, John Paul AU - Francis JP AD - Department of Computer Science, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. FAU - Li, Angdi AU - Li A AUID- ORCID: http://orcid.org/0000-0001-6143-6295 AD - iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. FAU - Lin, Wen AU - Lin W AD - Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. FAU - Tseng, Kaylee AU - Tseng K AUID- ORCID: http://orcid.org/0000-0001-7450-2247 AD - Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. FAU - McDermott, Gerry AU - McDermott G AD - Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. AD - Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Alber, Frank AU - Alber F AUID- ORCID: http://orcid.org/0000-0003-1981-8390 AD - Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. AD - Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Sali, Andrej AU - Sali A AUID- ORCID: http://orcid.org/0000-0003-0435-6197 AD - California Institute for Quantitative Biosciences, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. stevens@usc.edu calarabell@lbl.gov sali@salilab.org katewhit@usc.edu. FAU - Larabell, Carolyn AU - Larabell C AUID- ORCID: http://orcid.org/0000-0002-6262-4789 AD - Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. stevens@usc.edu calarabell@lbl.gov sali@salilab.org katewhit@usc.edu. AD - Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Stevens, Raymond C AU - Stevens RC AUID- ORCID: http://orcid.org/0000-0002-4522-8725 AD - Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. stevens@usc.edu calarabell@lbl.gov sali@salilab.org katewhit@usc.edu. AD - iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. AD - Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. IS - 2375-2548 (Linking) SB - IM PMC - PMC7725475 LR - 20210514 DP - 2020 Dec DEP - 20201209 AB - Characterizing relationships between cell structures and functions requires mesoscale mapping of intact cells showing subcellular rearrangements following stimulation; however, current approaches are limited in this regard. Here, we report a unique application of soft x-ray tomography to generate three-dimensional reconstructions of whole pancreatic β cells at different time points following glucose-stimulated insulin secretion. Reconstructions following stimulation showed distinct insulin vesicle distribution patterns reflective of altered vesicle pool sizes as they travel through the secretory pathway. Our results show that glucose stimulation caused rapid changes in biochemical composition and/or density of insulin packing, increased mitochondrial volume, and closer proximity of insulin vesicles to mitochondria. Costimulation with exendin-4 (a glucagon-like peptide-1 receptor agonist) prolonged these effects and increased insulin packaging efficiency and vesicle maturation. This study provides unique perspectives on the coordinated structural reorganization and interactions of organelles that dictate cell responses.