Impact of oxygen and glucose availability on the viability and connectivity of islet cells: A computational study of reconstructed avascular human islets.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238922 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7358 (Electronic) Linking ISSN: 1553734X NLM ISO Abbreviation: PLoS Comput Biol Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, [2005]-

Islets of Langerhans*/metabolism ; Islets of Langerhans*/cytology ; Islets of Langerhans*/blood supply ; Oxygen*/metabolism ; Glucose*/metabolism ; Cell Survival*/physiology ; Computer Simulation* ; Models, Biological*; Humans ; Computational Biology ; Islets of Langerhans Transplantation/methods ; Cell Hypoxia/physiology

The experimental study and transplantation of pancreatic islets requires their isolation from the surrounding tissue, and therefore, from the vasculature. Under these conditions, avascular islets rely on the diffusion of peripheral oxygen and nutrients to comply with the requirements of islet cells while responding to changes in body glucose. As a complement to the experimental work, computational models have been widely used to estimate how avascular islets would be affected by the hypoxic conditions found both in culture and transplant sites. However, previous models have been based on simplified representations of pancreatic islets which has limited the reach of the simulations performed. Aiming to contribute with a more realistic model of avascular human islets, in this work we used architectures of human islets reconstructed from experimental data to simulate the availability of oxygen for α, β and δ-cells, emulating culture and transplant conditions at different glucose concentrations. The modeling approach proposed allowed us to quantitatively estimate how the loss of cells due to severe hypoxia would impact interactions between islet cells, ultimately segregating the islet into disconnected subnetworks. According to the simulations performed, islet encapsulation, by reducing the oxygen available within the islets, could severely compromise cell viability. Moreover, our model suggests that even without encapsulation, only microislets composed of less than 100 cells would remain viable in oxygenation conditions found in transplant sites. Overall, in this article we delineate a novel modeling methodology to simulate detailed avascular islets in experimental and transplant conditions with potential applications in the field of islet encapsulation.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Félix-Martínez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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S88TT14065 (Oxygen)
IY9XDZ35W2 (Glucose)

Date Created: 20240813 Date Completed: 20240823 Latest Revision: 20240825

20240826

PMC11343470

10.1371/journal.pcbi.1012357

39137218