Simulating the Loss of $$\beta $$-cell Mass in a Human Pancreatic Islet: Structural and Functional Implications

Ruiz-Santiago, Sergio; Godínez‐Fernández, J. Rafael; Félix‐Martínez, Gerardo J.

doi:10.1007/978-3-031-18256-3_22

Cited by 2 publications

(1 citation statement)

References 19 publications

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“…These models can also be used to analyze the effects of different interventions, such as drug treatments, on islet function. Applying this type of mathematical modeling [37,47,48,74] to simulated islet cell distributions with similar network characteristics but distinct topological characteristics or vice versa would be an interesting future direction to determine the relevance of nonlocal topological features to islet function.…”

Section: Discussionmentioning

confidence: 99%

Geometric and topological characterization of the cytoarchitecture of islets of Langerhans

Aggarwal,

Striegel,

Hara

et al. 2023

PLoS Comput Biol

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The islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta and alpha cells, respectively, are responsible for metabolic switching between fat and glucose utilization. Dysfunction in their secretion and/or counter-regulatory influence leads to diabetes. Debate in the field centers on the cytoarchitecture of islets, as the signaling that governs hormonal secretion depends on structural and functional factors, including electrical connectivity, innervation, vascularization, and physical proximity. Much effort has therefore been devoted to elucidating which architectural features are significant for function and how derangements in these features are correlated or causative for dysfunction, especially using quantitative network science or graph theory characterizations. Here, we ask if there are non-local features in islet cytoarchitecture, going beyond standard network statistics, that are relevant to islet function. An example is ring structures, or cycles, of α and δ cells surrounding β cell clusters or the opposite, β cells surrounding α and δ cells. These could appear in two-dimensional islet section images if a sphere consisting of one cell type surrounds a cluster of another cell type. To address these issues, we developed two independent computational approaches, geometric and topological, for such characterizations. For the latter, we introduce an application of topological data analysis to determine locations of topological features that are biologically significant. We show that both approaches, applied to a large collection of islet sections, are in complete agreement in the context both of developmental and diabetes-related changes in islet characteristics. The topological approach can be applied to three-dimensional imaging data for islets as well.

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Section: Discussionmentioning

confidence: 99%

Geometric and topological characterization of the cytoarchitecture of islets of Langerhans

Aggarwal,

Striegel,

Hara

et al. 2023

PLoS Comput Biol

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The simplified Kirchhoff network model (SKNM): a cell-based reaction–diffusion model of excitable tissue

Jæger,

Tveito

2023

Sci Rep

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Cell-based models of excitable tissues offer the advantage of cell-level precision, which cannot be achieved using traditional homogenized electrophysiological models. However, this enhanced accuracy comes at the cost of increased computational demands, necessitating the development of efficient cell-based models. The widely-accepted bidomain model serves as the standard in computational cardiac electrophysiology, and under certain anisotropy ratio conditions, it is well known that it can be reduced to the simpler monodomain model. Recently, the Kirchhoff Network Model (KNM) was developed as a cell-based counterpart to the bidomain model. In this paper, we aim to demonstrate that KNM can be simplified using the same steps employed to derive the monodomain model from the bidomain model. We present the cell-based Simplified Kirchhoff Network Model (SKNM), which produces results closely aligned with those of KNM while requiring significantly less computational resources.

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Simulating the Loss of $$\beta $$-cell Mass in a Human Pancreatic Islet: Structural and Functional Implications

Cited by 2 publications

References 19 publications

Geometric and topological characterization of the cytoarchitecture of islets of Langerhans

Geometric and topological characterization of the cytoarchitecture of islets of Langerhans

The simplified Kirchhoff network model (SKNM): a cell-based reaction–diffusion model of excitable tissue

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