RT Journal Article
SR Electronic
T1 Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabc8262
DO 10.1126/sciadv.abc8262
VO 6
IS 50
A1 White, Kate L.
A1 Singla, Jitin
A1 Loconte, Valentina
A1 Chen, Jian-Hua
A1 Ekman, Axel
A1 Sun, Liping
A1 Zhang, Xianjun
A1 Francis, John Paul
A1 Li, Angdi
A1 Lin, Wen
A1 Tseng, Kaylee
A1 McDermott, Gerry
A1 Alber, Frank
A1 Sali, Andrej
A1 Larabell, Carolyn
A1 Stevens, Raymond C.
YR 2020
UL http://advances.sciencemag.org/content/6/50/eabc8262.abstract
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.