Distinct viability and oxygen-sensing responses to hypoxia and reoxygenation in pancreatic islets
- 1Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California, United States
Abstract
Early graft hypoxia limits the efficiency and success of islet transplantation. Defining the relationships among oxygen availability, exposure duration, islet survival, and oxygen sensing is therefore critical, but these relationships remain incompletely understood. We examined adult primary rat islets under continuous exposure to 1%, 5%, or 18% O2 for 48 or 96 h and under reoxygenation conditions comprising 48 h at 1% O2 followed by 48 h at 18% O2. We assessed islet size-dependent viability, morphology, mass recovery, estimated viable mass, and targeted hypoxia-responsive gene-expression signatures. Overall, 6,699 individual islets were analyzed. At 1% O2, viability decreased significantly, with most loss occurring within the first 48 h (93.0% at 0 h, 70.8% at 48 h, and 65.0% at 96 h). Overall viability remained largely preserved at 5% and 18% O2 (92.8 and 95.0% at 96h, respectively), although larger islets showed vulnerability at 5% O2. Exposure to 1% O2 caused deformation, particularly in larger islets, and reduced estimated viable mass compared with 5% and 18% O2. Reoxygenation did not fully restore viability or estimated viable mass (76.0% at 96h). Gene-expression analyses revealed sustained hypoxia-responsive signatures at both 1% and 5% O2, distinct from those at 18% O2. Reoxygenation shifted gene-expression profiles toward a normoxia-like signature. These findings suggest divergent viability and oxygen-sensing responses to hypoxia and reoxygenation. The 5% O2 condition may represent a marginal oxygen environment that preserves short-term overall survival despite sustained molecular responses to hypoxia. These data inform the oxygen targets and timing of early graft oxygenation strategies.
Related
- Heat stress reveals divergent pollen viability responses across species and populations of monkeyflower
- Divergent cellular responses to sciatic nerve crush versus transection: bilateral MYCN induction and distinct DRG neuronal responses
- House Dust Mite Induces Distinct Cellular and Extracellular Vesicle-Associated miRNA Signatures in BEAS-2B Cells: Targeted Analysis of IL-4 Responses
- Distinct functional syndromes and responses to fire history of three Mediterranean woody resprouter species
- Multidimensional profiling of heterogeneous lateral habenula subpopulations reveals distinct responses during motivated behavior
BibTeX
@misc{kato2026distinct,
title = {{Distinct viability and oxygen-sensing responses to hypoxia and reoxygenation in pancreatic islets}},
author = {H. Kato and H. N. Zook and N. Erdem and H. Mitsugashira and H. T. Ku and H. Komatsu},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.18.759980},
url = {https://www.biorxiv.org/content/10.64898/2026.10.18.759980v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Distinct viability and oxygen-sensing responses to hypoxia and reoxygenation in pancreatic islets
AU - H. Kato
AU - H. N. Zook
AU - N. Erdem
AU - H. Mitsugashira
AU - H. T. Ku
AU - H. Komatsu
PY - 2026
DA - 2026/10/18
PB - bioRxiv
DO - 10.64898/2026.10.18.759980
UR - https://www.biorxiv.org/content/10.64898/2026.10.18.759980v1
AB - Early graft hypoxia limits the efficiency and success of islet transplantation. Defining the relationships among oxygen availability, exposure duration, islet survival, and oxygen sensing is therefore critical, but these relationships remain incompletely understood. We examined adult primary rat islets under continuous exposure to 1%, 5%, or 18% O2 for 48 or 96 h and under reoxygenation conditions comprising 48 h at 1% O2 followed by 48 h at 18% O2. We assessed islet size-dependent viability, morphology, mass recovery, estimated viable mass, and targeted hypoxia-responsive gene-expression signatures. Overall, 6,699 individual islets were analyzed. At 1% O2, viability decreased significantly, with most loss occurring within the first 48 h (93.0% at 0 h, 70.8% at 48 h, and 65.0% at 96 h). Overall viability remained largely preserved at 5% and 18% O2 (92.8 and 95.0% at 96h, respectively), although larger islets showed vulnerability at 5% O2. Exposure to 1% O2 caused deformation, particularly in larger islets, and reduced estimated viable mass compared with 5% and 18% O2. Reoxygenation did not fully restore viability or estimated viable mass (76.0% at 96h). Gene-expression analyses revealed sustained hypoxia-responsive signatures at both 1% and 5% O2, distinct from those at 18% O2. Reoxygenation shifted gene-expression profiles toward a normoxia-like signature. These findings suggest divergent viability and oxygen-sensing responses to hypoxia and reoxygenation. The 5% O2 condition may represent a marginal oxygen environment that preserves short-term overall survival despite sustained molecular responses to hypoxia. These data inform the oxygen targets and timing of early graft oxygenation strategies.
ER -